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Presentasi Kimia Bahan Makanan : Precision Fermentation



Kelompok 1 Pendidikan Kimia 1. Maradistha Cheva 2. M Ilham Luqmanoel H 3. Naura Ismatina 4. Sinta Nurrohim 5. Sulistya …

Bismillahirrahmanirrahim asalamualaikum warahmatullahi wabarakatuh Kami dari kelompok 1 eh dari mata kuliah kimia bahan makanan kelas 5A Pendidikan Kimia akan mempresentasikan mengenai precision fermentation atau fermentasi presisi di mana Eh terdiri dari Saya sendiri maradis sebatriawan sebagai moderator dan juga teman-teman saya rekan-rekan saya itu ada M Ilham lmanul Hakim Naura ismatina sintanurahim dan juga su Setia Munawarah Nah untuk materi yang pertama yaitu mengenai pengertian dan juga prinsip kerja atau cara kerjanya yang akan dibahas langsung oleh Naura ismatina kepadanya disilakan Baik terima kasih kepada moderator untuk yang pertama yaitu mengenai pengertian dan prinsip kerja dari fermentasi presisi pengertian fermentasi presisi sendiri adalah istilah yang dijelaskan oleh eh dua asosiasi perdagangan yaitu precision fermentation Alliance atau yang singkat pfa dan food fermentation Europe atau FF yang tujuannya adalah membantu pelaku industri regulator dan konsumen memahami konsep ini terutama Bagaimana fermentasi presisi yang berbeda dari metode Fermentasi yang lainnya nah menurut definisi sendiri fermentasi presisi merupakan kombinasi fermentasiad tradisional dengan teknologi bioteknologi modern untuk menghasilkan senyawa tertentu secara efisien senyawa ini bisa berupa protein molekul perasa vitamin pigmen ataupun lemak Nah untuk cara kerjanya sendiri dari fermentasi presisi yaitu dalam fermentasi presisi mikroorganisme dimodifikasi dengan memasukkan urutan molekul tertentu yang berfungsi sebagai instruksi untuk memproduksi senyawa yang diinginkan selama fermentasi urutan molekul ini berasal dari basis data digital yang bukan dari sumber alami seperti hewan dan atau tumbuhan setelah proses fermentasi selesai senyawa yang dihasilkan dipisakan dari mikroorganisme melalui penyaringan teknologi ini sebenarnya telah dilakukan selama lebih dari 30 tahun untuk memproduksi obat-obatan contohnya insulin dan bahan pangan umum seperti renet atau oligosakarida susu manusia meskipun istilah fermentasi presisi baru muncul pada9 menalui ratings X penggunaannya sudah lama diterapkan misalnya dalam produksi simosin enzim yang sebelumnya diperoleh dari perut anak sapi namun kini dihasilkan oleh mikroorganisme hasil rekayasa genetik kemajuan dalam biologi sintestis terutama dalam pengurutan dan sintetis DNA telah mendorong banyak perusahaan startup untuk memproduksi berbagai senyawa bernilai tinggi produk ini meliputi pemanis pewarna perasa protein susu kolagen hingga komponen dalam Asim manusia yang ditunjukkan untuk meningkatkan nutrisi susu pada formula baik baik mungkin e Cukup sekian penjelasan dari saya saya kembalikan kepadaar Baik terima kasih naur atas penyampaiannya selanjutnya ituu mengenai aplikasinya yang akan dijelaskan oleh Sinta kepada Sinta disilakan Baik terima kasih kepada moderator jadi fermentasiis memiki yang luas dalam industri pangan terutama dalam menciptakan produk yang lebih berkelanjutan efisien dan bernutrisi terus di sini tu ada beberapa aspek penting dari aplikasi fermentasi presisi dalam industri pangan nah yang pertama itu ada eh produksi protein alternatif nah fermentasi presis Ini itu memungkinkan produksi protein alternatif yang identik dengan produk hewani mikroorganisme yang direkayasa dapat menghasilkan protein susu dan daging tanpa memerlukan eh hewan yang mengurangi dampak lingkungan dari peternakan tradisional contohnya tuh perusahaan seperti formo yang memproduksi protein susu bebas hewani dan eh nouris ingredien yang menciptakan lemak nabati untuk meningkatkan rasa dan tekstur produk berbasis tanaman Kemudian yang kedua ada peningkatan nilai gizi nah proses fermentasi Ini tuh dapat meningkatkan eh ketersediaan gizi dalam produk pangan misalnya eh fermentasi pada tempe dapat memperkayaan dengan vitamin B12 sedangkan produk seperti yogur dan kevir mengandung probiotik yang yang mendukung kesehatan pencernaan nah fermentasi presisi juga memungkinkan pembuatan protein dengan sifat E hipoalergenik dan stabilitas yang lebih baik sesuai dengan eh permintaan konsumen akan produk sehat Nah kemudian yang ketiga ada inovasi dalam rasa dan tekstur fermentasi presisi ini tuh mampu menciptakan cita rasa dan tekstur unik ee yang dapat tercapai dengan metode pengolahan lainnya produk seperti keju dan roti sodog merupakan contoh hasil perermentasi yang sangat diminti karena eh karakteristik rasanya yang khas nah teknologi ini tuh e memberikan peluang bagi eh pelaku usaha untuk menciptakan diferensiasi produk di pasaran gitu kemudian yang keempat eh slide selanjutnya yang keempat ada keberlanjutan dan efisiensi nah fermentasi bersih ini itu berkontribusi pada keberlanjutan dengan mengurangi penggunaan lahan air dan emisi gas rumah kaca yang terkait dengan peternakan konvensional Nah dengan memproduksi makanan secara lokal menggunakan mikroorganisme si jejak karbon dari transportasi juga dapatimalkan kemudian yang kelima ada penggunaan teknologi modern nah teknologi fermentasi modern termasuk eh bioreaktor otomatis memungkinkan kontrol yang lebih baik terhadap ee proses fermentasinya nah hal ini itu memastikan konsistensi kualitas produk eh dan efisiensi produksi Nah dengan pengawasan otomatis terhadap parameter seperti suhu dan PH proses fermentasi juga menjadi lebih terstandarisasi mungkin Sekian dari saya saya kembalikan kepada moderator Baik terima kasih kepada Sinta atas penyampaiannya selanjutnya itu mengenai manfaat dari permentasi presisi yang akan dijelaskan oleh kepada disilakan Baik terima kasih kepada moderator di sini saya akan menjelaskan sedikit manfaat dari permentasi presisi Yang di mana Yang pertama ada meningkatkan kualitas produkmentasi presisi ini dapat menghasilkan senyawa yang bernilai tinggi dengan kistensi danisih dapat meningkatkan kualitas produk lalu yang kedua ada mengurangi dampak lingkungan yang di mana fermentasi presisi dapat mengurangi dampak lingkungan dari produksi pangan dan biofarmasi karena memerlukan lebih sedikit sumber daya lalu yang ketiga itu memproduksi protein alternatif yang di mana fermentasi presisi dapat digunakan untuk memproduksi protein enzim molekul rasa vitamin pigmen dan lemak tertentu secara efisien lalu untuk keempat yaitu memproduksi terapi baru memproduksi terapi baru yang di mana fermentasi presisi ini dapat digunakan untuk menghasilkan terapi baru seperti biologi vaksin dan trapigigen lalu yang kelima ini ada memproduksi makanan secara lokal yang di mana fermentasi presisi memungkinkan negara-negara kecil dan daerah perkotaan untuk memproduksi makanan yang lebih padat nutrisi secara lokal lalu yang keenam memproduksi makanan tanpa hewan yang di mana maksud dari sini adalah fermentasi presisi menyediakan cara untuk menciptakan protein hewani tanpa hewan lalu yang ketujuh Ini meningkatkan efisiensi dan produksi nah perasi presisi dapat membantu meningkatkan efisiensi dan juga produksi lalu yang kedelap yaitu memilihin yang menghasilkan metabolit spesifik nah fermentasi presisi ini dapat membantu memilih strain yang menghasilkan metabolit spesifik untuk profil rasa atau tekstur yang lebih kompleksitu yang dapat sikan saya kembalikan kepada moderator Baik terima terima kasih Sulis atas penyampaiannya selanjutnya itu mengenai dampak dari fermentasi presisi Adapun dampak positif dan juga negatifnya akan dijelaskan oleh Ilham kepada Ilham disilakan oke eh di sini ada dampaknya dari fermentasi presisi ada dua ada dampak negatif dan juga ada eh dampak positifnya nah dampak positif dari fermentasi presisi Ini pertama itu produk yang dihasilkan akan lebih efisien gitu yang kedua pengurangan jejak karbon yang ketiga keberlanjutan sumber daya yang keempat produksi bahan langka secara mal yang kelima Kean pangan lebih tinggi nah Adapun dampak negatifnya itu isu etika terkait rekayasa genetika dari fermentasi itu sendiri lalu adanya potensi dampak negatif pada petani dan peternak tradisional Lal ada biaya awal yang tinggi dan yang keempat itu risiko homogenitas biologis yangagan berkangit yang tantangan reguli dan jangka mungkinupkiak sampan Terima kasih saya ke mod Baik terima kasih pen nah eh dapat kita jadi ada beberapa perusahaan teknologi itu yang mengola makanan besar yang menggunakan eh dengan fermentasi presisi jadi ada tiga ada perfect Dayar dan juga Impossible foods nah di mana pada Perfect Day ini perusahaan teknologi pangan ini tuh memproduksi eh protein susu bebas hewani menggunakan fermentasi presisi di mana perusahaan ini tuh menggunakan proses fermentasi untuk memproduksi Wei dan juga kasinnya nah dua protein yang ditemukan dalam susu protein yang diproduksi oleh perfekd ini diproduksi tanpa menggunakan hewan Teknik ini lebih berkelanjutan daripada peternakan hewan tradisional dan juga menghilangkan Riko penyakit bawaan makanan yang terkait dengan produk hewani ini keterkaitannya juga ada sama yang tadi disebutkan oleh manfaatnya dari fermentasi presisi itu Nah yang kedua itu ada kelarakur Di mana perusahaan ini tuh memproduksi putih telur bebas hewan menggunakan fermentasi presisi nah perusahaan ini tuh menggunakan proses fermentasi untuk menghasilkan protein yang identik ee dengan protein yang ditemukan dalam telur ayam nah protein ini juga dapat digunakan dalam berbagai produk makanan termasuk makanan panggang dan juga mayones nah yang terakhir yaitu ada Impossible foods Di mana perusahaan ini itu memproduksi alternatif daging berbahan dasar tumbuhan nah mereka ini tuh menggunakan fermentasi persisi ini untuk menghasilkan Hema atau molekul yang ditemukan dalam darah hewan yang memberikan rasa khas pada daging nah perusahaan ini juga menggunakan eh ragi yang dimodifikasi secara genetik untuk menghasilkan hem yang mereka gunakan dalam burger berbahan dasar tumbuhan dan juga produk-produk lainnya ee Mungkin cukup dari studi kasus yang saya sampaikan selanjutnya yaitu mengenai perbandingan dengan teknologi lainnya antara fermentasi presisi dan juga teknologi lainnya yang akan dijelaskan oleh Sulis kepada Sulis disilakan Baik terima kasih kepada moderator di sini saya akan sedikit menyampaikan mengenai perbandingan fermentasipresisi teknologi lainnya nah yang pertama di sini ada fermentasi presisi terlebih dahulu yang di mana fermentasi presisi adalah penggunaan mikroorganisme yang direkayasa secara genetik sebagai starter untuk produk molekul target melalui fermentasi nah fermentasi presisi ini semakin banyak digunakan untuk pembuatan berbagai bahan makanan yang secara konvensional bersumber dari hewan dan tuumbuhan contoh produk tersebut meliputi protein way oleh per produksi gatin vanili kunyit dan glikosida teviol oleh evolvgel dan laktoferin ASI oleh konag Nah yang kedua di sini ada fermentasi tradisional yang di mana meningkatnya minat terhadap makanan fermentasi setelah menyebabkan popularisasi dan komersialisasi produk fermentasi tradisional seperti kevir dan kombuca di luar daerah asal mereka dengan perluasan pasar yang cepat fermentasi tradisional adalah proses fermentasi yang dilakukan secara manual dan tidak terkendali selanjutnya eh selanjutnya di sini ada fermentasi bat yang di mana fermentasi bat adalah proses fermentasi yang dilakukan dalam jumlah besar dan tidak kontinu seperti produksi bir pembuatan keju produksi yogur dan pembuatan tempe yang di mana produksi bir dengan fermentasi gandum ber dan hop selama 7 sampai 14 hari terus pembuatan keju dengan fermentasi susu selama 30 sampai 60 hari produksi yogurt dengan fermentasi susu selama 4 sampai 8 jam dan pembuatan tempe dengan fermentasi kedelai selama 24 sampai 48 jam lalu di sini yang terakhir ada fermentasi semi kontinu yang di mana fermentasi semiontinu adalah proses fermentasi yang dilakukan secara dengan penambahan substrat dan pengambilan produk secara berkala contohnya di sini pada produksi yogurt yang di mana asi susu selama 4 sampai 8 jam kemudian sebagian produk diambil dan digantikan oleh susu baru baik sekian yang dapat saya sampaikan saya kembalikan kepada moderator terima Oke terima kasih kepadais atas penyampaiannya kurang lebih e yang dapat kami sampaikan dari kelompok s e Cukup sekian terima kasih atas perhatiannya kurang lebihnya mau dimafkan asalamualaikum warahmatullahi wabarakatuh

Cellular agriculture and advanced biotechnology for food production | Ensuring safety and quality in food systems | United Nations Food and Agriculture Organization

The Food and Agriculture Organization (FAO) is exploring cell-based food production and precision fermentation to address growing global demand for proteins and nutrients. Cell-based food production involves using animal, plant, or microbial cells to create food products, while precision fermentation uses microorganisms to produce specific target products. The FAO is working with stakeholders to advance knowledge and develop regulatory frameworks to ensure food safety. A stakeholder meeting in Canada and an informal technical working group (TWG) with 34 countries and the EU are discussing food safety aspects of cell-based food production and precision fermentation.

The FAO has published reports on precision fermentation and cell-based food, including a literature synthesis and a guide for food safety authorities. The reports examine nomenclature, production principles, and regulatory frameworks, and provide good practices and lessons learned. The FAO and WHO have also launched a publication on food safety aspects of cell-based food, which includes a comprehensive hazard identification and case studies from various countries. The FAO is continuing to facilitate discussions and knowledge sharing to support the development of safe and sustainable food production systems.

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Day4-PRECISION FERMENTATION FOR SUSTAINABLE MANUFACTURING OF BIO-ACTIVES AND INDUSTRIAL BIOCHEMICALS



Day 4 | GIAN Course on “PRECISION FERMENTATION FOR SUSTAINABLE MANUFACTURING OF BIO-ACTIVES AND …

good morning everyone so yesterday we did discuss about the batch design and the FED batch design do you have any questions with respect to that no okay so in today’s session we are going to discuss about the Heat and mass transfer in a bioreactor and we are also going to discuss about the scale up of Biore reactors because you always start small at lab scale then you increase the volume and then slowly you move it on to your large scale for Mentor or the industrial skill for Mentor so we’ll start our conversation today with uh Mass transfer in bi reactors but before that I wanted to set up the base with respect to some of the basics of heat and mass transfer okay now let’s start with heat transfer I’m hoping all of you have had courses in heat transfer how many modes of heat transfer exist there are three modes so you have your conduction convection and radiation radiation is do you think sorry so do you think radiation would be applicable in bi reactors not to a greater extent the most important would be the conductions and the convection so conduction we do have the equation which is your fixed law where your K is your conductivity the a is your cross sectional area right so this is your cross sectional area and then you have your temperature gradient DT by DX in in case of your convection it is h a delta T where your H is your convective heat transfer coefficient the notation might change from textbook to textbook but H is the most common notification that I have always seen so H is your convective heat transfer coefficient the area in case of convection is cross-sectional or the surface it’s a surface area and again the temperature will be the temperature difference now keeping these These are the the most basic right and after this we get into the governing equation where you have your Inus out plus generation is equal to accumulation right so the accumulation term for the uh is always given as DT by DX is it accumulation is with respect to time right so that’s why when a steady state scenario you don’t consider the accumulation because there is no change in temperature with respect to time in practical sense do we use steady state scenarios or non-steady state scenarios or unsteady State scenarios it’s mostly unsteady State because the temperature is going to change with respect to time even in bioreactors when you’re going to work with the bioreactors what are the source of heat in the bioreactor the organisms are one source of heat right because as they are multiplying as they are going to grow their metabolic engineering sorry metabolic mechanism is working that is going to generate some amount of heat right so that is your generation that gets added in the Govern equation if you remember for your heat transfer what else is there with respect to your heat what adds the heat mixing right vegitation that will add a little bit of heat do you think the amount the amount of heat that is added through the biochemical process that mean the growth of the microorganism or through agitation is it very significant the delta T is that very significant in uh in case of a bi reactor it’s not very significant you’re right it’s not very very significant but it is still it still exist even a small variation in temperature can ruin your whole by reaction so it is very very important to understand how the reaction uh is moving forward how much of heat is generated from the biochemical process that means from the cell growth how much heat is being added through the agitation and how much heat you are adding to the system heat from external sources is most mostly used to maintain the temperature the optimum temperature that is required for the cell growth or for the fermentation process and it’s also used for sterilization so you can use the steam sterilization to clean your bi reactor at one point of time right so even that’s one way of transferring the heat but that is not when you have your material inside you don’t put the steam because otherwise you’re going to kill all your microbes so that’s the basics of heat transfer sorry before I move on to the mass transfer which of the mode of heat transfer is prominent in a bioreactor convection or conduction convection right so You’ be dealing with surface area majority of the times you’ll be dealing with surface area you’re going to see equations such as u a DT where your U is universal heat transfer coefficient a is your surface area of the inside of your Biore reactor and the DT would be the temperature gradient similarly you have mass transfer so what are the different modes of mass transfer diffusion and have you heard of the term dispersion dispersion is when you have I call it forced diffusion and then you have your convection so you have your diffusion which is your d d is the alphabet which is used to denote diffusivity so da a DC by DX but it’s always like D A to B DC by DX where your X is the distance that it has diffused the DC is a change in the concentration or the concentration difference a is your area but generally when we are working with mass we always work with flux so when we say flux is per unit area we go for that so that’s why you will see D DC by DX because a would have gone onto side of the flow to give you the flux so in case of heat let’s say it’s minus k a DT by DX Q by a Q dot is your flux heat flow per unit area is going to be your flux so mass flow per unit area is going to give you your flux so when we are working with Biore reactors we are working with flux the dispersion is given as e even that equation looks the same so e a DC by DX or E DC by DX this would be for your dispersion this would be for your diffusion the negative sign is going to say from higher concentration to the lower concentration for the heat the negative sign is from higher temperature to the lower temperature the other is h m a DC or Delta C where your hm is your convective mass transfer coefficient now for this h on your conduct on your heat transfer side that is your convective heat transfer coefficient the the HM which is convective mass transfer coefficient if I do provide you that information if I provide you with the HM value or the H value you’re okay to solve any type of scenario with respect to convection if you are not provided with the H value how do you estimate it you use equations for nles number right which is a function of renold’s number and panal number same thing in Mass transfer nles number is called as sharewood number which is a function of renold’s number and Schmid number this is the most important concept that you would be applying in heat and mass transfer in by reactor your ral’s number the ral’s number is given as U which is your velocity D that would be the distance right Row the density divided by the viscosity right now U the velocity of what use the velocity of what of the fluid right so U is the velocity of the fluid D is a distance at which you are trying to estimate your mass transfer or heat transfer so or the sorry the type of flow that you have whether it is going to be what sort of flows can R number tell you whether it is laminar or turbulent what what sort of float do you assume will be existing inside a Biore reactor you have your agitator moving so you’re going to have mostly turbulent the regular standing fan that we keep in summer in front of our face it’s like sturing air right is basically generating turbulence and it’s trying to push that turbulence towards you you have so that’s why it’s a because a turbulent flow you will feel Air at one point of time and then suddenly it goes away and then again you feel a gust of air on your face that’s a turbulency because it’s coming in bursts to you D sorry the road the density is also very important that’s also of the fluid the V is also of the fluid so fluid properties are important the fluid properties are very very important if you are trying to estimate your renals number now the renal number are required to estimate your sharewood number or your nles number which are part of your heat and mass transfer respectively sorry sharewood number is mass transfer nles number is heat transfer you have to have an understanding of the fluid properties so when we talk about the fluid properties what are those properties the viscosity the density you need to know all of those parameters before you go and start doing the calculations right so estimating those is also an important parameter in terms of assessing the values for your heat and mass transfer the other part is your planet number and Schmid number your planet number depends on what if you have the mic if you can answer in that that would be great the panel number would be dependent on is it is it for the fluid is it based for on the geometry okay do you remember a term called as Alpha which is your diffusivity what is the equation for Alpha I’m so sorry for putting you at the spot but do you remember you have your k k over row CP so your density of the material the CP is your heat capacity of the material K is your conductivity of the material does this Alpha has to do anything with PR the planet number you have your phone you can check what is the equation for Planet number if I remember correctly is p r a n D LT parel number V row VY row that is ktic is kemetic viscosity by density where is Alpha now where in the numerator or denominator what about number so your parate number is Chic viscosity divided by diffusivity heat what it spint number okay so what’s the value for spint number see I learned while teaching my students undergrads there that the best way because you all are so inclined towards your own technology to make you do the work that I’m supposed to do that is finding it so give me the value of of speci number V by D so V by dtic viscosity by diffusivity diffusivity diffusivity right is the density term there at all if Will convert it is the density if you will convert mu upon r r d okay kynetic viscosity will be converted to Dynamic this m upon Row D right so that’s your Smith number now the row the D the D is the diffusivity is a property of the fluid of the material through which your mass so whatever material sorry if a is diffusing right it is diffusing through with it is a fluid or any material is a property of the material right we talk about the diffusivity of a membrane it’s a property of the of the material so the material property comes into picture when we are working with SMI number and Planet number renal number provides you the fluid properties that’s why these two are very very important and we are going to use them when we get into the Heat and mass transfer proper discussion about of the Heat and mass transfer in the bi reactor so I hope this basic refresh of your heat and mass transfer concept are helpful later on okay so Mass transfer in bioreactor so mass is transferred under the influence of concentration gradient Mass can only move from a higher concentration region to a lower concentration region in case of a bioreactor gas liquid mass transfer is extremely important because in a bioreactor you’re looking at Mass transfer specifically the one that you are mostly interested about is your oxygen which you are sparging so when you’re sparging Air at the bottom of the bio reactor it is going to throw bubbles in the bioreactor in the medium and the mass transfer that means oxygen coming out from the gas molecule where it is in higher concentration into the medium where it is in lower concentration and then to the cells that transfers that’s it’s a two- stage transfer so you have your gas bubble so let’s say these are your cells here so your oxygen is going to come out of the gas bubble into the medium and then from The Medium it is going to go to your cells now if it is a small single cell the mass transfer would be different if it is a cluster of cells the mass transfer is going to be different so the type of host that you use the way they grow or the way you are mixing it how homogeneous your medium is inside is going to determine how much of mass transfer of oxygen is going to take place so this oxygen coming out of the gas bubble if you remember there were two terms that we came across yesterday one was OTR and O Ur OTR was oxygen transfer rate right and this was oxygen uptake so OTR is basically your this stage o are is this stage where the oxygen is being uptick by the cells to grow clear okay so in an anerobic process oxygen must first be transferred from gas bulk through a series sorry in an aerobic process not an aerobic an aerobic process you don’t transfer in oxygen you should have stopped me if I made a mistake in an aerobic process oxygen must first be transferred from gas bulk through a series of steps onto the surface of the cell this is your step so you have spared the oxygen so you have your reactor you have your Sparger it’s giving out the bubbles here as the bubbles are moving up in the medium medium they’re going to release their oxygen into the medium the solubility of oxygen within broth is actually very very poor we did talk about that because you’re trying to dissolve oxygen in the liquid that’s where the concept of Henry’s constant comes into picture now temperature plays a very important role in determining how much of gas is dissolved within a liquid the pressure also plays a very important control in determining how much of gas is dissolved in a liquid correct now let’s have a very quick conversation about this Henry’s constant what would be the best example in your day-to-day life of hen’s constant soda can you have carbon dioxide dissolve D in the soda or like in the liquid right so when you open it you hear that noise right so that’s like it’s under pressure within that pressure the the carbon dioxide is dissolved but the moment you open you will see that FY bubbles coming up so that means that your carbon dioxide is coming up the other would be uh we call it diverse Bend so if you do a deep sea diving you go pretty quick inside the pressure of the water is pretty high on you the nitrogen gets dissolved in your blood and if you come up very very quickly that nitrogen the pressure has been released on the body that nitrogen will become bubble and will stop the blood flow it can kill you okay so this is what happens the other part would be when you are moving from uh let’s say from an it you’re going all the way to Himalayas when you go up the mountain you feel that oxygen is less in the air is it that the concentration of oxygen in the air is Al itself less or less oxygen is dissolving in your blood it’s less oxygen which is dissolving the blood will the concentration of oxygen change from ground surface onto the mountain top or the air will have constant concentration of oxygen throughout that’s the question that I ask my undergraduate students every time it’s a homework think about it it it’s a pretty good uh it’s an interesting topic is basically the amount of oxygen that is dissolving in your blood is less when you go on a higher altitude because of the pressure difference so enhancement of gas liquid mass transfer during aerobic fermentation is priority if you’re working on aerobic fermentation because oxygen is required for your cells to grow and to flourish you have to make sure that you are able to transfer the oxygen in appropriate amount that is required by the micro orms for their growth if you’re not able to provide that you’re going to see sell that okay so you’re going to see sell that if there is the oxygen is not about sorry so whenever the light goes off it breaks the continuity of the thought oxygen transfer is very very important in BIO process you have to make sure that you are providing appropriate amount of oxygen so that means the am the OU cannot be less than OTR can it be oh sorry o cannot be more than OT so oxygen uptake rate is higher OTR is less you won’t have any Oxygen for the uptake anymore right it’s the other way around I will say things which will be other way around just to check whether you’re listening to me or not and if you not saying yes that means you are just agreeing to everything I am saying think use your brain okay now mode of mass transfer which is common in a bio reactor is molecular diffusion so movement of molecules under the influence of concentration gradient is what is used for with respect to the diffusion now continuous diffusion that means supplying material to the high concentration region and removing it from the low concentration region is possible right if you continuously provide the if you maintain that concentration gradient you can maintain continuous diffusion process so if you maintain that OTR at a very high level your Ur will remain if you don’t have that OTR you cannot have your o you won’t have any Oxygen for to be taken by the by the microbes now continuous diffusion is exploited for Mass transfer operations in bioreactor the fixed law of diffusion which we already discussed is basically used in terms of estimating the amount of mass that has been transferred so you do need to know the diffusivity the concentration gradient and the distance through which it is diffusing through now mixing as we have already discussed in the very first slide when we were having conversation about the mass transfer is a very very important uh unit operation you can say in a bi reactor so mixing that means turbulence INF fluids produce bulk mixing to a Max up to the smallest edies formation so when you are having your agitation taking place you’re going to have small edies which will get generated you know what the edies are Ed is like a Vortex right they are very small vortexes which will form and those vortexes allow a very nice mixing ground it’s like have you ever seen a movie called twister no if you get a chance there is an new movie called twister watch it it’s really interesting or have you seen a tornado on TV it’s moving very very fast so it’s actually mixing everything just think about that at a very microscopic scale taking place inside the Biore reactor in an Eddie if you are in that particular Eddie what is going to happen your mixing is pretty quick so oxygen and the cell if the if you have the gas bubble up there and you have the cell also up there the oxygen transfer would be faster so within the small cies flow is largely streamline so that the further mixing must occur for diffusion of fluid components mixing on a molecular scale therefore completely relies on diffusion as the final step in the mixing process yes edes are there but diffusion is the main parameter through which the mass is transferred now Mass transfer between phases occurs often in biopress so in the case of your your gas bubble moving through let’s say a liquid media if I give you a column and I’m sparging oxygen from the bottom let’s say so the bubbles will move up right and this particular column is filled with water the bubble is going to move up from bottom it is going to move up what will happen to the size of the bubble will it increase decrease if decrease y if increase y if you have a fish tank at home or or an aquarium close your eyes remember how how the the bubble is moving up in the aquarium it remains in the same size or it increases in size or decreases in size it increases in size as it goes up right why because of pressure keeps on decreasing right from the depth and by the moment it has touched up it has become bigger now oxygen transform from gas bubbles to the fermentation broth will also follow the same principle that’s why when you’re sparging oxygen the design of the Sparger plays a very very important role you don’t want smaller or bigger bubble like you don’t want bigger bubbles to go through the medium you want very small bubbles because very small bubbles can be uniformly distributed and homogeneously mixed so you have to make sure that when it is moving up it is in a very small shape like the size of the B is very very small so design of the sparer itself is a very important parameter in the design of a bioreactor the other part would be what are the Restriction what would what are the phases that the oxygen has to go through so oxygen inside the bubble is in the gas phase now when you have a bubble it is inside a liquid media you have a film that generates at the surface right so the oxygen has to come out from the gas bubble go through this particular film into the and this film is because of the liquid media surface tension right the bubbles is going through the liquid medium so it’s going to be have a sort of like a restrictive film across it which will get generated and that particular film has to be crossed before the oxygen goes into the medium it’s a very important parameter to look at similar type of film does exist on the cell structure itself so you have now two films through which the oxygen has to go through the movement of oxygen in a bio reactor is also called as a two film Theory because of these two films that exist we’ll be discussing that in detail but I’m just giving you a bit of a basic idea to it so oxygen transfer from gas bubbles to the fermentation broth takes place uh goes through the the two phases so it is going from the gas bubbles to the fermentation broth Now product recovery from the Aquas to organic liquid the nutrient transfer from liquid medium into the cell is also going through phases right there are two phases from liquid to to the solid the cell is considered as a solid medium not as a liquid medium the fluid velocity near the phase interface is significantly decreased diff Fusion becomes crucial for Mass transfer across the phase interface why here comes the concept of convection so let’s say if I’m going back to convection ction for a moment if you have a flat plate now I’m going to talk about convection from the heat transfer perspective first then we’ll talk about the mass transfer perspec perspective so you have a flat plate the air is going to flow over the surface of this flat plate it is going to flow in layers right that will lead to formation of a velocity boundary layer right and a thermal boundary layer depending upon which particular whether the plate or the fluid has a higher temperature so the thermal boundary layer will exist and a velocity boundary layer will exist now what is this boundary layer if you remember correctly it used to be the 99.9% of the distance at which the fluid will have the same temperature as the surrounding fluid or the so if this is at higher temperature let’s say 100° C this one is at 20 C what is the temperature at the surface the plate is at 100° C the fluid which is moving over the surface of the plate is at 20° C what is the temperature at the surface 100 20 60 50 40 80 what is the temperature at the surface I given you so many options now we call it a film temperature at the surface the velocity of the layer of the air at the surface is zero what is the mode of heat transfer at the surface of that layer with the surface of this or of the heated surface what is the mode of heat transfer then conduction same concept in convection the fluid is flowing over the surface at the surface the velocity of the fluid is zero what would be the mode of convection then sorry what would be the mode of mass transfer diffusion as the bubble is moving up it’s moving up at the surface there is that layer through which the diffusion is going to take place the mode of is convective mass transfer but it has diffus diffusion at the interface the transfer is called convective Mass transfer it has diffusion at the interface just the way you have conduction at the interface now to answer that question what would be the temperature is the film temperature the film temperature is an average of your surface temperature and the fluid temperature so that means 60 so from 60 50° C you’re going to reach all the way to 20° C so with the distance at which the fluid temperature at the surface which is 60 it will keep on lowering down and it will reach the fluid temperature of 20° C that distance is called your thermal boundary layer the velocity of the fluid is at 1 m/s at the surface it is 0 m/s the distance at which the fluid layer goes back to 1 m/s is your velocity boundary layer same concept is followed in Mass transfer at the surface it’s always a surface phenomena it’s the most interesting thing generally you you have studied this uh concept of boundary conditions have you studied boundary conditions so let’s say I give you a membrane or like a a thick slab of membranes you have diffusion taking place right so it’s minus D DC by DX inside at the surface you have air blowing so here you’ll have hm a DC right or Delta C the flux Remains the Same Mass conservation so your minus D DC by DX is equal to h a Delta C or H ma a Delta C at the surface what is the boundary condition at xal to 0 minus D DC by DX is equal to hm a Delta C that’s what your boundary condition is so now coming back into your bio Reactor with the same concept what would be the boundary condition at the surface of the gas bubble is diffusion and if it is moving with a velocity it would be convection you’re getting my point if it is stationary diffusion only the flux has to be conserved Mass has to be conserved right the mass flux has to be conserved now the theories of interfase mass transfer there is a two film Theory and a penetration Theory the two film Theory the entire resistance to transfer is contained in two fous fous films on either side of the interface in which transfer occurs by molecular diffusion we will look at what that film Theory looks like later on so the KL which is your diffusivity constant or parameter would be given by D by Z where D is the diffusivity and the Z is the film thickness the mass transfer coefficient is the KL you would see there is a term called as KL a which is used in estimating your oxygen uptake in a bi reactor the a is your area D is your diffusivity the Z is a distance that it has moved it requires for the diffusion that combined gives you the KL and the a gives you the area the penetration theory on the other hand assumes turbulent edes travel from the bulk of the phase to the interface where they remain for a constant exposure time T the solute is assumed to penetrate into the Eddie during its stay at the interface by diffusion so the k for that particular case is given by this equation don’t get bothered by the equations that much but understand the conceptual part at the interface what is your boundary condition that matters the most if there is a thick layer at the interface the diffusion of the gas has has to come from inside which is at highest concentration it is going to diffuse through that thick layer and into the medium and then from The Medium it is going to go into the cells that thick layer will have its own resistance similar to resistances that you see in your mass transfer you remember right minus da a DC by DX the resistance is given by D is DX by minus da l/ da this is your resistance R diffusion resistance to diffusion remember this we also use a term called as K which is your distribution coefficient when we are working with mass transfer which has to be multiplied to your diffusivity for a specific product or a specific uh component which is diffusing through the membrane or anything like that this is mostly used when we are working with the membrane now the film Theory so this is your phase boundary you have your gas phase and then you have your liquid phase so the gas phase film resistance and then you have your liquid phase film resistance so the rate of mass transfer is direct ly proportional to the driving force for transfer which would be the concentration gradient because that’s the only driving force if the concentration gradient does not exist mass does not move and the available area for the transfer process to take place transfer rate is directly proportional to transfer area the transfer rate is also directly proportional to the driving force so d force is the concentration gradient and the a the area this K is your proportionality coefficient in case of heat transfer we generally use the K as conductivity but in this case we are not going to use it as conductivity we are going to call it as a mass transfer coefficient I have used the same as hm before but I said it is convective Mass Mass transfer coefficient but here we are using it as a k because diffusive values it the K is already estimating d by Z right so it already has the parameter of diffusivity in it so I’m not representing it as D I’m representing it as K this is because of the film Theory the K depends on the boundary layer the geometry the flow and the fluid properties why ral’s number Schmid number are involved right so number is going to give you the require all the fluid properties if the material is very viscous what would be the mass transfer will it be less will it be more it would be less diffusion would be less right if it is yeah flu viscosity is the most important fluid property other would be the speed at which the fluid is Flowing that will determine the rate of mass transfer the value of K what else can be taken into account the temperature the density density will Define not the temperature the density will Define change in temperature will change the density but density is the the parameter that will defin so density viscosity right all of these will come into the fluid properties that we are looking at so the gas liquid mass transfer the rate of mass transfer of a component a through the gas boundary layer for that means your gas B B layer is kga a c a minus C AI that this layer the distance the the concentration gradient similarly for the liquid side it would be KL c a i minus Cal so the thing is there’s always a resistance at the boundary at the phas right so when you have your concentration coming in it is at a lower concentration at the surface then the concentration that was there in the bulk then from there when it goes into another phase there’s a drop let’s say if I use a membrane there will be a drop in the concentration within the membrane if the the concentration on the left hand side of the material is pretty high than on the right hand side so there’s a drop because that would be determined by the diffusivity parameter permeability of that membrane how much of the material can be diffused through at a given time if it can only give let’s say if 10 molecule comes on the one side of the membrane so if this is a membrane 10 molecules have come from the bulk and they’re like hey I I need to go through I need to go through but this particular membrane can only allow two at a time or three at a time it will only allow three so there would be dip in the concentration from the surface within it at this surface you’ll have three now this three is still higher than what is present on the right hand side so that that dip is what you are seeing here got the concept in the most Len way I’m trying to explain there is a dip because of how much can go through at a given time that’s the resistance of the film that will determine now assume equilibrium exist at the interfaces cagi and CLI can be related equilibrium concentration in the gas phase is a linear function of the liquid concentration the steady state at interface there is no accumulation of component a so there is the K Star Distribution coefficient is not existing there the component a transported through Phase 1 must be transported through Phase 2 these are the assumptions that you have to make so your n a is equal to n l is equal to n a the total flux the mass is conserved or the flux is conser conserved at all times now oxygen Mass transfer so when you multiply equation 2 by m so your equation two is here on the liquid side and rearrange you get this particular equation here now dividing the equation by m we’ll provide you further so the overall the most important equation that you have to look into would be this or sorry this where the KL is overall Mass transfer coefficient so KL is c l star minus c a l this is the equation that determines the mass transfer you have your flux isal sorry you have your uh mass flow on one side you have your KL which is your overall Mass transfer coefficient a and the CL star minus CL where exactly will you have the Cal star at the interface now this this particular uh concept that is there so liquid phase Mass transfer resistant dominates and the kga is much larger than the klaa so liquid side Mass transfer resistance is more as compared to the gas side resistance which is an obvious thing liquid side will have a higher resistance as compared to the gas side so the kga would be higher in terms of the to maintain the flow so the rate of oxygen transfer from gas to liquid is of prime importance in an aerobic fermentation process because without oxygen the micros are not going to grow but understanding how much oxygen is required the oxygen demand of the microbes will be able you will provide you with the information which will be which will make you capable to estimate the flow rate that you will set up so that your oxygen transfer rate is always higher than the O oxygen uptake rate can you so let’s say if if I give you a bi reactor you are purging oxygen into it I ask you to stop it what will happen what is the worst case that will happen eventually the cells will die right but what if you reduce it only for a certain period of time and then again increase it will that impact the metabolic pathway of the the cells or how what type of product is being formed by the cells because for survival the cells will change their Machinery immediately and then again when they get it they are going to go into a different mode so that switching of the mode takes a bit of time so there is always some uh products which gets generated during that period so it’s always make you have to always make sure for an aerobic fermentation system you’re maintaining the oxygen demand that is required by the fermentation system other otherwise what the product that you are expecting the quality of the product that you’re expecting might not be there at high cell densities oxygen is quickly consumed in an aerobic culture and must be constantly replaced by sparging the low solubility of oxygen which is Max of 7 to 8 PPM at ambient condition now if you ask me what an ambient condition would be I will say 25° C that’s what an ambient condition is for us what would would the ambient condition in a bi reactor 25° C the ambient condition is ambient condition you don’t change it so the low solubility of oxygen limits the concentration difference the CL R by minus cl to very small value at all times what it means is like once the oxygen has come out of the bubble so now once the oxygen has come out of the gas bubble it has to be in the liquid medium but if it does not dissolve if it does not solubilize in the liquid medium it cannot be transported now the the the solubility is less the concentration in the liquid medium available of concentration of oxygen in the liquid medium is less as compared to that present in the gas that might be available for the cells to obtain so that means your oxygen concentration in the liquid medium is lower that’s an obvious thing as compared to what is there in the gas but because of lower solubility it goes even lower the then what is present like you have added let’s say 10 but only five or six would be available for the cells because the solubility is less now solubility is uh depends on the temperature solubility depends on the pressure solubility depends on the fluid properties so all of those parameters has to be taken into account when you’re trying to Define how much oxygen would get solubilized what can you do in that case if you want to improve the solubility of your fermentation system what will you do you can change the type of medium that you’re using that might be able to dissolve more oxygen in it or you can provide some sort of uh let’s say additives that will help dissolve oxygen but all of that will impact your fermentation process so you have to be very careful in choosing what you can do to maintain this oxygen demand so designing of the fermentors for aerobic operation takes these factors into account to provide Optimum Mass transfer conditions now factors affecting cellular oxygen demand now the rate of oxygen consumptions by cell determines the rate of oxygen from transfer from the gas to broth the OTR is dependent on o how much oxygen is being taken away that will determine what the OTR would be that means oxygen coming from the uh from the gas bubbles into the liquid medium now factors that influence this oxygen demand are the type of microbes the host the type of microb that you have chosen for the fermentation process the species some uh microbes require higher oxygen they have higher oxygen demand some don’t have that high as compared to the others the culture growth phase whether it is in the lack phase whether it is in the log phase early log phase or later log phase like in the de acceleration stage or in the stage phase the oxygen demand will change will it not when do you think in the case of the cell growth the oxygen demand is the highest the early growth phase to the the exponential phase as it being the constant phase where you have the constant growth going up your oxygen demand is high you need as it is doubling right at this particular stage when it is starting to e climatize you might not have a very high oxygen demand but the moment it will start dividing the oxygen demand will shoot up and you have to make sure during that period you’re providing appropriate amount of oxygen into your bi reactor and the nature of the carbon Source in the medium the type of source of carbon that you choose will also Define how much oxygen is there is is available because if the if the if the source itself interacts with the oxygen then less oxygen is available okay you have to be very cautious about the choice of your source now factors affecting cellular oxygen demand so in a batch culture the rate of oxygen uptake varies as the concentration of cells increases during the ctiv cultivation period this means that the rate of oxygen uptake is proportional to the number of cell present so as the number of cells will increase the rate of uptake of oxygen will INE increase so in a batch culture the rate of oxygen uptake varies as the concentration of cells increases during the cultivation period so as you are growing the bulk of the cell Mass keeps on increasing your oxygen demand will also keep on increasing now the specific oxygen uptake which is your Q2 or the specific oxygen uptake rate increases to a Max maximum value at early log phase and then it decreases gradually at early log phase it will start it increases and then it decreases gradually so you you can see that early loog phase it has increased for a certain period of time and then it has decreased gradually as the cell concentration has increase this is your X this is your Q2 okay and now this is where we were talking about the film theories type right so you have the gas liquid interface and the liquid cell interface so your OTR is basically the oxygen that is coming out from the gas into the liquid that is your oxygen transfer rate and then your o is from the liquid whatever oxygen is being taken away by the cell again the question would be single cells in a cluster things will change because this size of this interface will change question is this so let’s say you have a cluster of cells right now there is this let’s say a thin layer of interface over please excuse my drawing okay please excuse my drawing now this particular cell requires oxygen now the oxygen which is coming in has to pass through the other cells to reach that last cell right that’s why clusters are not good for your bi reactor because the cells will die they cannot get enough oxygen for their survival and that might lead to production of uh products that are of not your interest that is something that you don’t want so you always try to reduce the cluster what is the way that you can reduce the cluster agitation right not this type of agitation a single one you have an agitation rotating at a particular speed question here if I may so let’s say if I give you a bio reactor I have a sparer that is pumping I have set the flate of oxygen or the flow rate of the gas through the sparer let’s say okay volumetric fluorate would be like let’s say 50 ml per liter like 50 mL of oxygen per liter I’m just throwing it in will the speed of the agitate impact how much oxygen will get dissolved in the water if just the water is here if I take a dissolve oxygen probe at one end and put it inside of my in the in the fermentor or in the by reactor and I change the speed of my agitator do you think that will change the amount of oxygen that would be present in the water because it is going to break the bubbles into smaller bubbles diffusion changes smaller bubbles will have smaller interface layer thinner not smaller thinner interface layer so your mass transfer is higher larger the surface area more the catalysis we call it more smaller the bubbles is much better it is the easiest example to that would be um the the Taps that you see these days the old tabs were like just the liquid coming out this uh current time the tabs it gives you that sound sh and it comes out in like bubbles like in streamlines right it’s less water but it’s very stream line so that’s why it reduces the amount of water that you’re using same way you if you streamline if you basically break all the bubbles into very small bubbles it will diffuse very EAS easily in the medium so agitation does impact the OTR oxygen transfer rate it’s a very important parameter in that case and that’s why when you’re trying to think about scale up from a small scale to a larger scale you have to maintain that OTR depending upon because larger the fermentor more the OU are so you have to increase your OTR so what all you have to increase you have to increase your agitation system also and the amount of flow of oxygen the sparer design Everything Will Change that’s why scale up is not an easy process when we looking at the fermentation we think about it’s a small bottle I can go to a bigger bottle it doesn’t it does not replicate just by comparing okay in this small bottle I have 2 L for 2 L I used uh this much of oxygen so how much will I use for 4 L you don’t do that calculation anymore because if you do that your OTR is less you have to now think about what are the other parameters that were impacting my whole thing now the viscosity will change the density will change because I’m going into bigger system you have to take into account all the other parameters to estimate the scale up that’s why understanding Mass transfer is very very important before you understand scaleup any questions no excuse me now now if the qo which is your specific oxygen uptake rate is the oxygen sorry if the qo is oxygen uptake small qo is your specific oxygen uptake rate if the qo is oxygen uptake rate per volume of the broth and qo is your specific oxygen uptake rate the equation is your qo divided by X it has to be with respect to the X to give you your specific oxygen uptake rate so total of oxygen upt rate divided by per unit volume divided by the cell biomass so inherent demand of oxygen depends primary primarily on the biochemical nature of the cell and its nutritional environment now this is also another parameter that has to be taken into account when you’re trying to design a particular bioprocess what it means is that many of times when you’re designing a bioprocess the type of uh sources you use as your medium Source or the uh nutrient Source how is the bacteria going to utilize it it’s like how much water you’re going to drink if you’re eating something very very spicy it will change the amount of water intake for you depending on the type of food that you’re eating right same thing happens with the cells there’s not much of a difference in that sort of concept but the cells biochemical pathway will change and the amount of water demand or sorry oxygen demand will also change depending upon the type of carbon source that they are working with the other aspect would be the environment depending on the temperature outside the the temperature of the medium the cell metabolism might reduce the cell metabolism might increase right because if the temperature is at its Optimum the cell growth was Optimum the moment we cross that Optimum temperature threshold you remember from yesterday’s lecture the moment we cross this Optimum temperature threshold the cell starts to die but it will keep on increasing as I’m increasing the temperature so that means more and more metabolism is taking place more and more cell mass is growing my oxygen demand is higher so the surrounding environmental parameters also impact the amount of oxygen that would be required for the cell to grow you have to take into that take that into account when you’re trying to design your bi reactor again as the level of dissolved oxygen in the BR Falls below a certain point which is your critical oxygen level the specific rate of oxygen uptake is also dependent on the oxygen concentration in the broth so you have to make sure that you have provided enough oxygen beyond the threshold not less than the threshold beyond the Threshold at all times to maintain enough oxygen in the broth the broth that we keep on talking about is the medium you need to maintain enough oxygen in the broth for the cells to grow it’s the same concept again and again you have to maintain the oxygen you have to maintain the oxygen but that maintenance of oxyen depends on the broth parameters like the type of sugar that you are taking the species the cell species that you have inside the what else the properties of the fluid that you are using so to eliminate dissolved oxygen just give me one second oh yeah so to eliminate dissolved oxygen limitations and allow cell metabolism to function at its Optimum the dissolved oxygen concentration at every point in the fermentor must be above the C critical so you don’t want to be below the C critical at any given point as the fermentor is running estimation of the C critical is very very important how will you estimate this C critical just give me an idea on that how will you estimate the C critical value through experimentation you’ll try to see the optimum growth right you’re going to you never go to the fermentor directly you always go to the seed culture you have a small scale fermentation unit first that is what you’re trying to optimize first and then only then you go into the industrial scale fermenter so you try everything there understanding the relationship between all the process parameters with your cell growth and only then you replicate that in a large scale formentor you can estimate through that through experiment ation that’s the only way you can do it the exact value of C critical depends on the organism but under average condition operating conditions usually Falls between 5 to 10% of air saturation so other way to circumvent the circumvent the C critical is pump as much as you can just pump as much as you can but that is going to add to the cost that’s why understanding the SEC iCal is important because when you are working with Precision fermentation you are always giving every parameter at the precise value at the specific value nothing more nothing less you’re trying to optimize your productivity right improve your productivity with the least amount of resources oxygen is not a cheap substrate that is added to your fermentation system so you have have to be very careful in estimating the C critical for cells with relatively high C critical level the task of transferring sufficient oxygen to maintain the concentration on the liquid side the Cal greater than the C critical now what is this C critical C critical is the concentration of oxygen that should be there available for the cells to take right so that means I’m not bothered about how much oxygen is there in the bubble I’m more bothered about how much oxygen is dissolved in the liquid medium at all times so when you are putting your dissolved oxygen probe you’re estimating how much oxygen dissolved in the medium that gives you the idea so you’re trying to maintain that Cal that me the concentration in the liquid medium over the C critical value it’s always more challenging than for the cultures with a low C critical so for cells with relatively high C critical level the task of transferring sufficient oxygen to maintain Cal is always more challenging than for cultures with low cal or C critical why if I have cells which have a very high Ur oxygen uptake rate or the demand is pretty high you have to maintain a pretty high concentration of Cal right why it is a challenging thing fluid properties like how much oxygen can you dissolve there’s a limitation to it right you cannot increase the temperature you cannot change the pressure what do you change you change your agitation you Chang how much oxygen you are pumping in those are the very few parameters that you can actually handle and control you cannot play with the temperature and pressure that much because the moment you change the temperature you’re going to change the growth rate you don’t want to go into the thermal rate uh thermal death rate for uh for your micros right you want to maintain it below that but there are only few parameters that are manageable or can be maintained by you so maintaining any so choosing the right host which will require less and less oxygen and still give you your product might be an ideal choice to reduce the overall cost of production if you’re choosing something which is of higher oxygen demand you have to provide more oxygen at all times and that is going to increase your production cost so a lot of parameters gets affected by this the choice of substrate for the fermentation can also significantly affect your oxygen demand as glucose is generally consumed more rapidly than other sugars or carbon containing substrates rate of oxygen demands are higher when glucose is used now you see the relationship between the substrate and oxygen demand I’m hungry or I get to see gulab jamun I love gulab Jam I’ll eat a lot of it but I need to drink water too you all depends on your choice right when you’re when they are basically consuming glucose that means your metabolic pathway is consuming glucose continuously it is going to need because it it cells don’t say to themselves you know what my tummy is full I’m going to sit now I W I don’t want that extra glucose right now I’m good I’m good no they they will continue dividing they’ll continue consuming it they don’t stop like us they continue consuming it that creates the situation in which your oxygen is being continuously utilized for the growth of your microbes so for that you have to maintain it depending on the choice of the substrate that you have used you might want to change glucose to galactose or fructose something which the micros might not like that much or the the demand of oxygen for the processing of that uh sugar would be less so you have to choose the right carbon source for the growth of your microbes now the step of Transport for the gas uh for of oxygen from the gas bubble to the cell I have already discussed this a little bit let’s look at it so let’s say this is your gas bubble inside this is your gas liquid interface so at the gas liquid interface I said that this is an imaginary or line or imaginary thickness or layer which is present and that oxygen has to cross through this layer and only then it will reach the cells so oxygen molecules must overcome a series of Transport resistances before being utilized by the cell what about this cell or the cell here it might get the oxygen from the other sides but I’m just saying that there are other cells around it’s a cluster it will has to go through now other barriers so you will keep on increasing the resistance for the oxygen transport you’re going to reduce the amount of oxygen that is going to be transported the stagnant medium or the stagnant region is the uh the the the film that we have talked about the two films on the liquid side and on the gas side you you should have heard about this in certain biomaterials porous biomaterials which are used uh to immobilize cell for cell growth or they can be used for as uh as a scaffold for the cells to grow properly and they poor in nature for the nutrients to get transported for the oxygen to get transported quite easily to the microbes those are also utilized these days in the fermentation process to improve the amount of oxygen that is transported into the system it’s like uh it’s a very porous media and the cells are growing on the surface of these pores or on the surface and then because it’s Hollow and porous the liquid medium with the nutrient and the oxygen can go through the distance that they have to now move for the oxygen transport is less so that reduces the amount of resistance it’s it’s like imagine this as a pen this has a hollow cylinder but it’s a very small section of it so there is a small hole in the center okay and this whole structure the cylinder part is porous in nature the cells will be growing or immobilized on on the surface am I correct now the nutrient can flow through the hole in the center on the like axially and the transport of nutrients can happen through the pores inside so it’s a porous media the cells are growing on the surface that is sometimes used for cell culture basically we use that for cell culture but those type of materials are or the beads we call them are generally used in the fermentation system even nanomaterials are also being used in the fermentation system okay this is just to improve the overall fermentation efficiency I want more cell Mass but I want to reduce the overall cost so if I can do that why not okay so steps for the oxygen transport from gas bubble to the cell so transfer through the bulk gas phase in the bubble is relatively fast the gas liquid interface itself contr attributes negligible resistance the gas liquid interface is negligible resistance the liquid film around is a major resistance for the transport so you have your gas bubble it has released the oxygen into the liquid and then it goes towards the cell that’s the major hindrance or the resistance in a well mixed fermentor concentration gradients in the bulk liquid are minimized and the mass transfer resistance in this region is small so if you are well mixed the distance imagine it this way the cell cluster is here the distance of the bubble is not too far it might be available that the distance the resistance is less that it has to go through single cells are much smaller than the gas bubbles hence the liquid film surrounding each cell is much thinner than the around the bubbles and it effects on mass transfer can be neglected completely if the cells from large clums if they form large clums liquid film resistance can be significant now the other steps for oxygen transport from gas bubble to the cell is resistance at the cell liquid interface is generally neglected resistance at the cell liquid interface is generally neglected not the liquid so the resistance at at the cell and the liquid interface if this is your cell the cell and the liquid interface is generally neglected so when the cells are in clumps intra particle resistance is likely to be significant as oxygen has to diffuse through solid pellets like one cell to another cell to reach the interior cells the magnitude of this resistance depends on the size of the clumps larger the size more the resistance smaller the size less the resistance intercellular oxygen transfer resistance is negligible because of small distance involved we don’t consider the resistance at that time when we are trying to estimate the the movement of oxygen because it’s not too like what is the size of a micro microns so it’s not too much of a distance that the oxygen has to get transferred that’s the reason so the mass balance for oxygen at a steady state will involve the k that means CL star minus CL the CL is a concentration at the liquid side CL star is on the interface where your A a is a by V A is your interfacial area interfacial transfer area and the V is the broth volume the K is your volumetric mass uh transfer coefficient this equation above can be used to predict the effect of cl to changes in the mass trans transfer operating conditions for example if K is increased by raising the stir speed to reduce the thickness of the boundary layer around the bubbles the dissolved oxygen concentration that is clal will rise for equilibrium if you can reduce the film resistance thickness you will have more CL more oxygen in the liquid similarly if the rate of oxygen consumption by the cell accelerates while K is unaffected the Cal will decrease that means the concentration of oxygen on the liquid side will decrease because now uptake has increased so you have to maintain CL whatever you do maintain CL at all cost above the C critical now the maximum cell concentration that can be supported by by the fermentate uh fermented oxygen transfer system is an important parameter to look at so the way we estimate that is for a given set of operating condition the maximum rate of oxygen transfer occurs when the concentration difference driving force that is C star CL star minus CL is highest so higher the concentration gradient more the transfer that is when the concentration of dissolved CL is zero that means the the concentration gradient would be highest when the CL is zero under what condition will the CL be zero when your OT R is equal to O so whatever oxygen comes out from the gas is consumed comes out consumed comes out consumed there is no oxygen in the medium so your C concentration gradient will always be maximum so because of that your mass transfer would be maximum so maximum cell concentration can be supported by the mass transfer function of the reactor and this is the equation that is used so your x max that means the amount of cell the maximum amount of cell that can be generated you if you know the K you know the Cal divide it with Q which is your specific oxygen uptake rate another important parameter is the max is the minimum k a required to maintain Cal over C critical in the fermentor this can be determined as CLA critical is equal to QX / CL star minus C critical this is like to maintain the cells that I have right now what is the minimum K value that I have to have this is the equation that I’m trying to use at that time to maintain what I have like what is required above or how much I can get with the respective Kaa would be the xmax value if I know what my xmax value is and I want to know how much Kaa I need to have to maintain that x max is what I will use the second equations this is to get what xmax I want I can get second is to what K I should have to maintain it now determining the mass transfer coefficient the KL the k and a can be calculated using empirical correlations and experimental me measurements experimental measurements are the most common way of estimating the K value separate determination of KL and a is tedious it is convenient to directly evaluate the product Kaa The combined term Kaa is referred as a volumetric mass transfer coefficient the objective of the ferment design is to maximize oxygen transfer rate with minimum power consumptions necessary to agitate the fluid and also minimum air flow rate you got the drift least amount of air flow least amount of agitation but I still want growth right it sounds like Industries I’ll give you least amount of money but I want the product right the boss will come and give you the work and they’ll say like okay I’m not giving going to give you enough salary but you have to do it it’s exactly like that so you the reasoning for that is because all of these agitation requires power power means energy is consumed energy is consumed means what amount of money that is we are going to spend on energy it becomes an energy intensive process you don’t want it to be if you’re purging in a lot of uh air inside you’re still spending a lot of money you don’t want that you want to reduce the overall cost so the idea is always you want to design a fermentor you want to make sure that you are going to use least amount of vegetation and the least amount of air flow so you have to be careful so what will you do if I want this like minimum air flow is required least amount of agitation is required what what what will you do how will you take care of it use the mic so when whenever we are selecting the media so the media which having the higher water sorry oxygen uh dis dissolving property so you will select a media that already has oxygen no no which which have the higher oxygen dissolving property because the viscosity matter the higher oxygen dissolving property that means it is able to dissolve enough oxygen in it okay got the idea but uh what media will that be it should be less viscous first of it has to be less vus okay what is the best media that we use in the ferment system what do you think is the liquid media that generally we use in the fermenter water water water right water is the only one thing that we use what other parameter can you change lower lower temperature the dissolution of carbon dioxide is higher definitely hopefully carbon oxin also higher so we can control the metabolism of the organism which can produce maximum yield at a lower temperature or we can modify the metabolism according to genetically modify the organism according to okay now let me put forward a question to you so let’s say if your intent for your fermentor is to get the maximum cell density and the cell mass that means you want to grow and grow and grow and grow and grow as much as you can okay what will happen to your Ur and O OT are even uh the oxygen uptake will be more than the oxygen transfer rate right that means you have to continuously increase your agitation yes yes so then again it is going to increase your cost what will you do at that time your intent is still to get the maximum yield but your intent is to use the least amount of agitation so you might want to go for a different type of fermentation system right yes rather than going for let’s say AIC uh a Fed batch or a batch where you have a stir you don’t want to use a stir you can go for a fluidized system in the fluidized system the cell is mixed because of the movement of the medium itself okay and mixing is taking place you might be able to get more oxygen transfer there has to be a solution I’m just trying to throw ideas I might be wrong in my idea but I’m just trying to throw to give you some type of solution you have to find me instead of agitation we can supply the oxygen as even for example uh sparge this noil can be the size of the noil can be reduced in order to reduce the size of a gas bubbling okay so that means you want spares with smaller holes like atomizer okay atomizers very good that can be used that is actually used what else you have some stabilizers can use stabilizers for what like uh even for example in certain industry uh for example in ice cream industry and all they are using certain stabilizer which will stabilize the dissolution of oxygen but I don’t know you’re comparing an Emulsion with uh with fermentation a stabilizer for an imulsion I can understand because you want to maintain them into their ulive state like dispersed State I I don’t know whether it’s work this no I I I really appreciate your effort that at least you’re you’re thinking out of the box I really appreciate that but think again it would be so funny using a stabilizer what are what are the most common stabilizer that you use like alides and if you add you’ll get clumps so the even the media uh which is used like whatever the substrate we are used for the fermentation uh which also should improve the oxygen dissolution see we we are we are we are having the same conversation again and again we are we are coming back to the media property we more or less something has to be done neither you are aware of it neither I aware of it it has to be done experimentally you have to choose right you have to go through that whole rigorous experimental process that’s the reason if you go back to my very first presentation on the fermentation when I started I showed you that diagram and I said like it has so many pipes it looks very dangerous it’s a very simple process fermentation is a very simple process but it’s very complex when you go deep into it it’s very very complex because but once you have optimized it you come you switch it on you forget about it you go back home you have your product ready that’s the way it works for this yes there there are solutions the beads I talked about that’s one of the solution where you might be able to keep your cells suspended without them clumping together they might you might give them extra surfaces so you’re increasing the surface area area but you’re also helping to improve the nutrient delivery so you’re not going to have like a thick cell mass in which you have let’s say an agitator trying the fan blade trying to move if if if your cell M was filamentous you you cannot have an agitation if you’re growing a filamental like a like a fungi you cannot have agitation it will break right the filaments so there are things that can be done there are a lot of research that keeps on going in the fermentation area even if it is the century old technique you will still find people doing research in this area just because of this it is such an interesting area okay let’s get into the final few slides of the oxygen supply sorry oxygen Mass transfer uh the factors that affect oxygen supply rate we have already discussed a few of them temperature is one of those pressure is another diffusivity now the diffusivity of what diffusivity of oxygen in the medium or diffusivity in the cell side it’s all about the CLA right in the medium the diffusivity of oxygen in the medium the viscosity of the medium density of the medium surface tension for the air bubbles surface tension will Define if I am correct the thickness of the of the film presence of surfectants surfectants can impact oxygen transfer the ionic strength can impact the oxygen transfer the concentration of solids can impact oxygen transfer power input less power input that means less agitation more power input higher agitation Iration rate higher the Iration rate you’ll be maintaining more OTR geomet of the Biore reactor you will never like to use a Biore reactor of this geometry where only you have a small like impeller in the center the mass is everywhere else you’re not going to have enough mixing so your design of the bi reactor has to be optimized based on mixing homogeneity has to be maintained homogeneous mixing of your nutrients homogeneous mixing of oxygen and it should also be capable of maintaining your cell growth and it ease of operation ease of cleaning all of those things come into picture anyway but your design has to be maintained that way now the variables that can be manipulated majority of the times are your pressure so if you increase the pressure you’re basically going to increase your OT R your Shear rate and power input that means more agitation you are increasing the OT we have already discussed this idea eration velocity will increase your OTR so there is a relationship between Iration rate and your uh agitation rate that can be studied for different mediums before I put the cell if I can study how that will change then I can provide my my cell growth into it even that will lead to changes into it but it will allow me to start with a certain SEC critical and then I can increase it depending upon how the cell is growing I know how much oxygen is required for the cells to grow I’ll keep on increasing it depending upon the demand so other parameters are for given geometry of the bioreactor depends on the nature of the fermentation process I will take a break of 15 minutes and then we’ll start the session on heat transfer operations in the Biore reactor okay e welcome back so now that we have gone through the mass transfer operations for a bioreactor we are going to go through the heat transfer operations in a bioreactor similar to mass transfer we did go through the concept of heat transfer at the very beginning of the lecture so similar to mass transfer heat transfers is also a very important parameter when you’re looking at the cell growth we have already discussed about this a little bit in detail yesterday when we were talking about the thermal depth or the growth of microbes or how the cell growth is related to the temperature so if you increase the temperature the cell growth will increase to a level which is your Optimum temperature value and below this particular temperature value the cell growth will reduce or they will die but heat transfer application is not just for the cell growth in terms of application of heat transfer in uh let’s say in molecular biology or cellular biology what do you use uh heat transer or heat for auto caving like sterilization so any time you are working with microbes let’s say any in any utensil if whether it is be a fermentor a batch fermentor or fed batch fermentor or cstr or even if you are uh let’s say curling milk any container if you have to clean it you will be applying heat to kill the microbes so that is part of the heat transport or heat application in case of uh fermentation system we need to have a sterile medium it should be free of any other micro but not free of sucrose or the nutrients that it has it has to have but it has to be free of any micro so what do you do when you’re growing uh let’s say micros on an agar plate what is the very first thing that you do with your agar gel thear you Auto cleave it heat it and then you pour you let it set then you streak your organism into it you see all the growth and everything and then when you have to get rid of it auto cleave again right so in C2 bath sterilization of liquid medium is one of the applications of uh heat transfer in by reaction or in by reactor in fermentation so in this process the fermenter vessel containing medium is heated using steam and held at sterilization temperature for a period of time it’s just like pasturization cooling water is then used to bring the temperature back to normal operating condition so you put in everything you use the steam to heat the ster up to the sterilization temperature you bring it back to an Optimum temperature that would be appropriate for your cells to grow that’s when you add your seed culture into it and then you let it ferment okay so temperature control during reactor operation is very very important to manage a few things that would be the metabolic activity of the cells generate heat because we have to have a temperature control because as the cells are growing they are also going to generate heat the metabolic activity within the cell is generating heat we have already had this discussion at the very beginning of the lecture today or the session today so some microorganisms need extreme temperature conditions example would be cyrilic thermophilic microorganisms for those we have to have we have to maintain a very high temperature now when you’re maintaining these type of organisms how will you work with your oxygen transport that will also change depending on the temperature of the medium the oxygen transport rates will also change so depending on the organism we are looking at the OTR so you study the organism you find out what OTR they require and only then you build the rest of the system on that but the generation of heat because of the metabolic or the microbial biochemical Pathways is an important parameter that you you have to take into account understanding what microbes you’re going to use for your process how they grow and how much heat do they produce is an important parameter now the heat transfer configuration for bu reactors include jacketed vessels external coils internal coils and external heat exchangers so you you will have like a jacket around the vessel that will add the heat to the vessel or you can have external coil into it and then you have your internal coils which are inside not on the outside of the fermentation system but on the inside of the fermentation system have you seen a ferment I think in today’s uh in the afternoon you’re going to see uh a bi reactor in the lab not today we don’t have the lab today okay sorry you if if you do get an opportunity go to the bio bio technology department here you should be able to see a bioreactor if you have had a course in bioprocessing if you have had a lab in that you should have seen a bio reactor so if you’re using a glass bioreactor the only way you can provide the temperature is by using a jacket around it and then that particular jacket has heating elements into it and then you pass on the heat to the fermentation system so you only jacket it to the level that you put in your fluid so that you’re not not providing excessive heat just to the fluid that is of your interest and then you have your external heat exchanger I always like these external heat exchanges they remind me of the old way of heating your water in the morning of winter you switch on and there is a probe that you put in the bucket and then you let the water heat take it out but that can also be used to murder people so don’t use that anyways so external heat exchangers are also used to maintain the temperature within a fermentation system so heat exchanger configurations so I will go with each and every one of them so external jackets and coil give low heat transfer area they are rarely used at industrial scale they are widely used at lab scale depending upon how how much money you have spent on buying your bioreactor or how much money you have for your B reactor in my research group we have this jacket ones to heat our fermentation system then you have your internal coils which are frequently used in the production vessels the coils give relatively large heat transfer area because you need more surface area for the transfer of the heat the coil interfere with the mixing in the vessel and make cleaning of the reactor difficult so if you have internal coils because they’re inside it everything is going to go over the coil have you heard about uh the term fowling right or plaque generation over the surface so if your if the heating elements are not cleaned properly or the fermentor is not cleaned properly heat exchange would be impacted so design of the heat exchanger where you have a cross flow parallel flow heat exchangers when we go into those type of design even there you have to take into account the fing process right the other would be the coil interfer sorry another problem is the growth of cells as film on the heat transfer surfaces again fing so those biofilms that get generated on the heat transfer surfaces so you have to make sure that you clean these heat transfer surfaces these heat transfer surfaces to maintain an appropriate heat transfer level external heat exchanger unit is independent of the reactor easy to scale up and provides the best heat transfer capability sterility must be maintained the cells must be able to withstand the sheer forces imposed during pumping during aerobic fermentation the residence time in the heat exchanger must be small enough to ensure that Medium does not become depleted of oxygen if you’re using an external Heat exchanger you want to make sure that the medium does not get depleted of oxygen if you’re passing the heat from another source sterility has to be maintained because sterility is the most important parameter in a fermentation process because if it was internal I know everything is inside whatever is there inside is what I’m working with if I’m using something from another location I have to make sure the sterility is maintained let’s say even if uh if I’m using some sort of like steam to heat my uh system if the steam is being produced at different location and the steam is going to be passed through the pipes right when it is going to be passed through the pipes those pipes have to be clean enough that they don’t contain anything the steam before it enters in my fermentation system I have to check that is free of any microbes right so all that uh controls have to be in place if you’re working with an external heat exchanger excuse me so common heat transfer operations uh removing heat generated during the fermentation process so the operations that invol are involved in the fermentation process would be removing the heat generated during fermentation removing heat generated due to mixing almost 90% of the time the Heat generated due to mixing is higher than the heat of reaction now this heat of reaction is not with respect to the chemical reactors I’m talking about this heat of reaction from the microbes perspective how much energy is being produced by the microbes during the growth okay so that heat is less compared to the heat generated by mixing sterilization operation is a major heat transfer operation in a fermentation system sterilization is a major heat transfer operation in a fermented system coming back to this uh what sort of mode of heat transfer is this is it convection or we are looking at convection but we looking at mostly Heat exchangers if it is internal coils we are looking at heat exchangers it’s like a heat exchanger the the heat transfer the lmtd has to be included you remember that so you have to take that into account if it is just from the outside surface and the heat is being provided by the surface of the fermentor it would be conduction but if the fluid is moving over the surface it’s conduction at the interface but there is a flow of the fluid so convection has to be taken into account then again it will depend on the fluid properties the viscosity you have to take uh you have to look into the table get the values at a specific temperature what’s the viscosity of the medium the density of the medium and then you’re going to use your nles sorry nles number equations to estimate the value so microwave growth involves complex Network for metabolic reactions now I’m talking about the heat generation because of the microbes during cell growth cell derive energy from catabolic reaction and use them to drive anabolic reactions some energy is lost to the surrounding as heat if the bioreactor temperature is to be maintained then this heat must be removed hence the first objective is to quantify the heat released due to the growth so when you are going into designing a bi reactor if you have your growth of microbes being if you’re if you’re estimating the growth rate you can also estimate the amount of heat that would be generated by that particular microbes once you estimate that value it becomes easier for you to identify what sources will you choose to remove that heat from the peration system this part is mostly numerical there are equations that are available to you to do that I’ll give you some of the examples like what would be the heat of combustion for a biomass like KJ per kg if you’re looking at an eoli you’re looking at 23.03.2013 on different biomasses you’re going to have different heat of combustions once you know your heat of communions if you do your in minus out plus generation is equal to accumulation where will this particular value go the heat generated by the micros will that be an in or will that be considered as a generation in would be anything that you’re providing out is whatever you’re taking away generation can be from the microbes that will lead to the change in the temperature with respect to time so when you do that particular balance you can take into account all the heat sources which are going to add to the system now because it generation is adding to the system is positive if it was removal of the heat there it would have been a negative value right that’s how simple it is now the model equation for the batch system for heat transfer if you remember Q is minus k a DT by DX now DX is the distance DT is the time or sorry DT is the temperature difference DX is the distance you have to have that gradient minus K is your conductivity sorry K is your conductivity is your cross-sectional area but here you’re going to look at the QR value with respect to the microbial growth so this is the equation which is used with respect to microbial growth this QR is for the microbial growth VL is the volume okay change in biomass concentration with respect to time DX by DT is your biomass con uh concentration with respect to time so the I take that into account the yield you’ll be able to estimate how much would be the heat of combustion coming out so if you know the heat of combustion you know the biomass concentration you can estimate the amount of heat that is coming out for that particular biomass in a given period of time so the total heat that has to be removed would be this QR the heat of combustion or the heat generated by the biomass and the heat added by mixing so Q mixing is a heat generated due to agitation where we are converting the mechanical energy to the heat energy assuming no heat loss to the surrounding this amount of heat must be removed from the system to maintain constant temperature in the bioreactor so if you have a bioreactor this agitation as it is going around you it is going to generate heat because of the sheer stress like there’s a friction as is moving through you that heat which is generated my major concerns this is my own personal opinion to this my major concern with respect to the agitation has been that it does not generate a very huge amount of heat even if you keep on rotating your hand inside of water you won’t be generating a lot of heat yes you’ll warm it up a little bit maybe by a degree or two but even that small degree or two can impact your fermentation process because it’s a very controlled precise system so heat transfer area should be designated sorry designed accordingly so you’re what you’re looking for from the Q mixing is the UA delta T U is your overall heat transfer coefficient a is your surface area delta T is the temperature difference so the heat accumulation now would be the heat generation minus the heat removed so your DT by DT is the term with respect to your accumulation the CP is your heat capacity density and the volume then you’re looking at the Q and you’re looking at the UA delta T the QR is your for the biomass you have it for your mixing you add both of them you get the value for the total amount of heat that is going to be generated that needs to be removed how do you remove heat in uh fermentation system if you’re using that internal coil those are not heated coils let’s say those coils are hollow tubes and you’re passing steam through them if you pass cold water you’re going to reduce the temperature right if you have a jacket you pass cold water you’re going to reduce the temperature so you always use a medium that is able to extract the heat from the medium of the fermentation medium fairly quickly because you don’t want to have uh spend too much time in that right longer the medium will remain at a higher temperature it might lose its viability so you want to reduce amount of time that is required for the removal of the Heat and reach the optimum temperature that is required for your cells to grow that balance is very very important okay is there any other idea that you can actually use for removal of heat you have have your uh you can use some condensation column like you circulate it the circulation can be done the media can be circulated the media can be so you’re taking the media out of the fermentation system no like when there is a for example in pools and all there is a water purification the same way you’ll be like one time it’s circulating like there’s a pipe should be there from the side and it’s circulating like see you forgetting two things so yes there is a heat which is being generated by the cell uhhuh right yes there is a heat which is generated by the mixing now from where are you actually taking away from this heat from the surface right you’re not taking the heat from inside the broth or the medium you’re taking the heat away from the surface from the surface so if you increase the surface area reduce you are able to remove more heat heat that’s one way of doing it by increasing the surface area so baffles sometimes are not only used to get rid of the edies but they are also used to increase the overall heat transfer surface area question for you in this case this is just from the conceptual perspective so you have your medium so heat is going to pass from your medium to your surface right that is conduction so you do you remember the unsteady State heat transfer in unsteady State heat transfer we have something called as uh High SL char charts High SL charts you don’t remember that for different types of geometry if you have like a slab you have a cylinder or a hollow fiber or a sphere you can use these charts to estimate what would be the heat transfer specifically for cylinder slab and uh Sphere not for the hollow fibers I haven’t seen that but cylinder slab sphere you can use this high but the condition for those ISO chart was the surface the condition at the surface the B at the surface is maintained throughout the process it is not changing but here the things are changing so that mean what I’m what it means is like let’s say if this is a slab we’ll always look at the Symmetry and then if this is your x equal to 0 this becomes your x equal to l the length of least resistance right the length of least resistance that the least amount of distance that the heat has to travel to get out so if you’re looking at the Burger let’s say a burger patty the Alo Patty or potato Patty that you get the heat transfer if you’re doing conduction what would be the the L value in this case it would be the thickness not the length because this is the least resistance the heat is going to transfer this way why why I’m bringing this is I’m trying to imagine in our conversation with each other the medium in a cylindrical in a cylindrical uh fermentor system can be considered as a cylinder of uniform conductivity it can be considered as a cylinder of a uniform conductivity if it is homogeneously mixed if it is homogeneously mixed can I consider it to be a uniform distributed conductive material a cylindrical now the heat is going from inside to outside if the heat is being removed from the surface right heat is going from inside to outside now as you increase the size of the fermentor you’re increasing the surface area right as in the cylinder like in a slab the heat transfer is linear in a cylinder the Heat transfer is not linear it’s parabolic because of an increase in the area in the radius the surface area keeps on increasing the heat transfer the Q will keep on increasing in this case how will that impact if I consider that removal of the heat from the surface do you think that will have any impact if the material is stationary and if the material is moving homogeneous nature is maintained I have my material heated at a specific value I have to remove the heat so then it becomes if I am passing cold water on the surface of the jacket I’m basically doing convection convective heat transfer removal right but that would be from a cylindrical surface it would will it be considered as a force convection over a cylindrical surface there is an equation for force convection over a cylindrical surface right which can be used that nles number equations so those nles number equations can be used if you def if you have a defined geometry of your bio reactor when you’re trying to cool it down heat it up you’re using those defined nusle number equations to estimate the amount of heat transferred yes you’re getting my idea of the drift because I’m considering the whole bi reactor only the medium part as a cylinder of homogeneous constant conductivity there is water flowing over the surface that means through convection the water jacket is Flowing so will that be considered as a convective heat trans transer that is what my question is will that be considered as a convective heat transfer will that be considered as a heat exchanger will you consider it to be like a uh like a conduction a basic conduction because water is Flowing so convection is there how will you take it how will you take it like can you take it as convection can you take it as basic so convection within the uh media and then from the film the film which is at the boundary layer from there to the uh like jacket as conduction if the medium is moving then convection yeah right I’m considering the medium as stationary it’s like a solid cylinder of uniform conductivity because of the homogenity being maintained can I consider the heat that is coming out of that Medium because I’m trying to remove it from the surface and if I’m passing the water in tubes will that be considered as a convection or will that be considered as a heat exchanger as a heat exchanger as a heat exchanger so we generally end up using heat exchanger equations to solve the amount of heat that is being removed from the peration system but we use convective equations to estimate the amount of heat that we are generating within the fermentation system okay so don’t get confused in those two now design equation for a continuous system so the heat accumulation is equal to the heat input due to flow heat out due to flow heat generated and the heat removed by cooling so your accumulation is this ter so you have your VL row CP DT by DT you know what is v why VL row volumetric flate or the mCP delta T V is what is mass volume into density right so you have your volume into density CP delta T So mCP delta T is the amount of heat which is there accumulated within the system clear so this term is your mCP delta T similarly break it down for yourself first thing is heat input due to flow f is your flow row CP now this becomes volumetric flow f is your volumetric flow so that becomes your mass flow rate this is your heat generated because of biomass this is the heat added because of mixing this is the heat being removed this TC is the cold temperature right it is the heat being removed u a delta T U is your overall Heat transfer coefficient but we are looking it as from conduction perspective or convective perspective convection UA delta T okay we’re looking from the convection perspective so understand like mCP delta T is the key here so don’t get confused by the overall uh these big equations mCP delta T is what the VL row CP is the volume into density will give you the mass the CP then the delta T So model equation should be able to predict what heat transfer area is needed to achieve the required temperature time profile so if you are able to identify these equations once you solve this equation you’ll be able to predict what heat transfer area is required or is needed to achieve the required temperature time profile okay so if you’re designing your Biore reactor if you know how much heat is being generated by the biomass what would be the removal of the heat you can design inside again the area so you can add baffles just in case if you want to improve the overall removal of heat you can add baffles if you don’t need you can change the number of coils that you’ll have so you can do a lot of those modifications to your design of the bioreactor depending upon what heat requirement is or what heat removal requirement is then comes the topic of scaleup okay so Mass transfer done heat transfer is mostly for sterilization purposes heat transfer application is mostly for sterilization purposes I’m not going to teach you that log 10 deductions okay that is not part of this or it’s not in the scope of our conversation today you can check when you’re working on the calization pasturization purposes for your own courses the idea of heat transfer in the Forma system is because of the sterilization of the media because everything has to be sterile to start with once you add your culture to it or the seed culture to it that’s when it will start growing the other aspect of the heat transfer was to maintain the heat for the optimal growth of your microbes that is by your mixing the heat that is being added the generation of the biomass the heat that is being added and how much you can remove UA delta T right so that’s was what was involved now look at the scale up now you have understand you have now you have understood your mass transfer and the heat transfer now keep those Concepts in mind and then think about your scaleup all of those parameters have to be transferred if you’re moving from a small fermentor to a larger fermentor your OTR Ur has to be maintained your removal of heat has to be maintained the agitation speed that you were using in a smaller fermentor might not be the same as a larger fermentor the amount of power input for that small that agitation will differ if you’re working on a larger fermentor so all of that power ratio has to be maintained when you’re looking at scaleup so what is the scaleup in practice scaleup it is the study of problems associated with the transfer of experimental data from Laboratories and pilot plants equipments to a large scale industrial equipment so you’re starting from a test tube to a 5 ml flask 35 ml flask to 200 mL flask then you go to a 5 lit bioreactor move to a 30 L bioreactor 220 L bioreactor I personally have seen up to 1,000 L bioreactors then you go to 10,000 L bi reactors we have already scaled up these bio reactors up to 600,000 L now there are bi reactors of capabilities of 600,000 L think about it now it’s a very scaling it’s a process that can be scaled up quickly but it has to be done in a proper way because there are so many parameters that depends on the scale of process itself your heat transfer Mass transfer Mass transfer specifically your oxygen whenever you think about Mass transfer in a fermentation system it’s all about oxygen when you think about heat transfering for itation system the heat generated by the biomass plus the stiring is not that significant it’s all about sterilization the most important part will be the sterilization that’s the most important heat transfer application in the fermentation process what else will you take into account if you’re thinking about the scaleup the geometry of your bioreactor that has to be taken into account right the diameter the height all of that has to be taken into account the third most important the nature of your organism has to be taken into account the fourth so nature of the organism heat and mass what else was there this agitation is going to impact Mass it’s going to impact heat what else Iration agitation is going to impact Iration aration is going to impact mass aration is also going to impact heat can I now Iration is mostly for the mass transfer applications okay what else will you take into account when you’re looking at scale up you have taken your bioprocess course come on thinky thinky I can see people’s mouth moving but I cannot hear anything honestly give it a try there is no wrong answer let her answer first just three parameters we mainly consider about one is uh K okay that is your a m sir and imp tip speed tip speed that is your agitation yes sir you written everything sir then what else is there and the geometry right these are the three we take care because power power conception power conception is also agitation yes sir py yeah but then it is used for what power is used for what again comes to the and agitation but these are the three things mainly but you have written already yes but I’m seeing it from a different perspective right as a faculty my intent is that you just don’t give me the bookish example of the tips paid and all those things you give me from the conceptual whatever you have understood till now we have discussed batch reactors we have discussed fed batch reactor we have discussed how to design a batch reactor we have discussed how to design a Fed batch reactor you know none of you have talked to me about when you’re changing the geometry you’re also going to change the flow of your feed your feed rates will change there are so many parameters change the moment you change the design of your bioreactor or even when you scale it up there are a lot of things that come into picture the most important that are used to take if I have to take this pen make a bigger pen I will will take the things that I can control the first thing is the geometry that I can actually control and pass it on that’s why you were taking about talking about that now tip speed and all those things affect your agitation affect your K values how many let’s say for a small fermentor oh yeah see for a small fermentor I will can use only one impeller but what was the design of the pill that I was using for a small fermentor might not work if I move it to a bigger fermentor what will you do then the heat the agitation will change right so it requires some consistency but there are also certain parameters where variability exist that variability is what matters the most but for fermentation is a very forgiving unit operation that’s why I said it’s a very simple system it’s like it’s like one of the nicest unit operation that you can work with it’s also very forgiving you add everything you will get something at least but if you are able to put a little bit of effort in understanding each and every intricacies and then design it it will give you the best of it that’s what the intent is in our conversation I can understand what you told me the tips paid I have all of that in my slides next but I just wanted to get a bit more from you what else will you change if you are moving from one smaller fermentor to a larger fermentor what else will you change are we just focusing on the batch if we are only focusing on the batch I will not care about the feed will I care about the feed I won’t what if I’m trying to scale up on a Fed batch level I have to think about my feed rates my flow rates so that has to be scaled up depending upon how much I want to grow but that would also come with a different set of calculation but that has nothing to do with the design of the fermentor you’re getting my point that has to do with my working but it has nothing to do with my design of the ferment that’s the reason why feeds and all those things are not taken into account that will only depend on the growth productivity that you want productivity has nothing to do with the respect to the design in terms like in our conversation I’m just saying it’s just physical conversion of a small thing into bigger thing that is what we are talking about so we’ll get more into this so what is the exact aim of scaling up the objective is to keep the cellular environment constant your cellular environment has to be constant across scales to achieve comparable growth I’m not using the term exact I wish I can use the term exact but I’m using a comparable you might not get an exact growth but you’ll get a comparable growth relatively comparable growth metabolism productivity and product quality sometimes like people make fun of these things where they’ll say it’s like a onetime Wonder right your thing worked at the lab skill the moment you scaled it up it didn’t there is something wrong in the input for your large skill that’s what the problem is there’s nothing wrong at a small skill but there is something which is missing at the large scale understanding that from the biochemical perspective everything will remain the same it’s mostly the physical that thing has changed from a small fermentor I became a bigger fermentor that’s it I used to be a thin guy now I’m a big guy it changes but inside I remain the same I used to be the same person 10 years back I’m the same person 10 years now or I will be the same person 10 10 years after except I would be much more older but my body will change that’s what the scale up is all about is you’re changing the physical aspect but internal has to be constant you’re trying to maintain it as much as possible so which are the most important criteria similarity criteria now we talked about that and thank you for bringing all of that answers so similarity criteria that you have to maintain would be your mass transport which is your O2 and the CO2 the CO2 which is being generated has to be removed larger the fermentor more the biomass more the CO2 more the removal larger the fermentor more the biomass more the O2 mode is required mechanical stress on the cells larger the biomas bigger the agitators and the impellers the design of the impellers more the stress sheer stress larger the population too many people right it’s just like going in an autoa or you’re going in a crowded bus scaled up stress right from the sales perspective mixing time that would have been required at a small scale would be very different than the mixing time that would be required at a larger scale so how quickly can you reach the homogeneous or homogeneity is very very important when you’re trying to do scaleup now these are the most important parameters from the industrial perspective think about I’m so proud that you all are aware of the basics of scaleup I’m really really proud of that think it from a completely I said you keep an open mind think it from your own project your own uh experiences how are you going to do the scale of what are the parameters that will get impacted the most that has to be taken into account oh sorry okay yeah so the scale of principles uh involv ensuring circulation of nutrients dissolved gases and removing metabolites is an important in B reactor agitation and Iration allows for the bulk liquid mixing and sheer stress agitation adds to that oxygen transport and pco2 removal is through the areation aspect mixing is more difficult as scales increases mixing does become an issue as the scale increases so on the right hand side you can see the process definitions uh I would like you all to look at this particular link to get the same uh graph that I’m using here so temperature control so temperature is directly related to cell growth and viability okay then temperature control also regulates the O2 and the CO2 solubilities then you have your pressure control pressure control basically impacts your CO2 and O2 solubilities and that impact imps your cellular environment nutrient addition your glucose glutamine and the feed addition nutrient concentration that will impact your cellular uh environment if you’re looking at the pH you have your base addition now why do you add a base to maintain the pH right so now the base if the base and the substrate will interact or some other combinations get generated that is going to impact your cellular environment the one comes here is the focus the dissolve oxygen control so dissolve oxygen control is through agitation gas flow rates and the Sparger type the type of sparer that you’re going to use at a small scale I could have had a ring Sparger at a large scale what will I do if I have a larger like as big as this if I have a larger Sparger here the bubbles are going only in the quter nothing is going to come in the center so I have to Define I have to design a sparer which is multi-layer right so you have to think about the design from that perspective nobody talks about increase scaling up of a spon people are talking about the scaling up of Iration the O2 but that will lead to the change in the design of the Sparger so as an engineer I understand the O2 that what biochemical guys or biochemical engineer is interested in the O2 he or she will come and say hey bro I need this I say okay fine I have to redesign the sparer as an engineer I would love to do that that’s my area of Interest how to redesign the sparer to make sure that you able to maintain the O2 that you require now if the cellular environment is maintained that will impact your cell growth viabilities nutrient uptake and waste accumulation that will also look into your product concentration and the product quality maintaining all of this is your primary motor with respect to scale up now determining the derived parameters in reference to those would be your calculate your agitation regime so you have to look at your Ed size the power density the tip speed the mixing time the K and the turbulent Shear Force then you calculate so you once you have estimated you again calculate at your Iration regime you have your porosity spargers air flow spargers oxygen flow spargers then you have another second round of perity spargers or air flow spargers you have if you need more and a eration sorry agitation Iration regime for a targeted scale determination has to be determined depending upon O2 CO2 removal mixing time tip speed these are the main ones this is an example so if you are scaling up a 1 lit bioreactor to 100 lit volume based bioreactor so the volume is pi T1 2 by 4 so T1 is your diameter for the smaller one so Pi d by 4 right d ² by 4 H1 H1 is your height for a small one so you’re looking at s this s is the parameter that we use for scale up this is also called a scale up parameter from the geometry perspective so you’re looking at scale up from uh from the diameters of the spargers sorry of the SP for the impeller you’re looking at the the diameter of the vessel you’re also looking at the distance of the impeller the tip of the impeller and the base does that impact the speed of the impeller the distance at which it is placed that will impact your mixing that will impact your mixing so a single scale ratio s this is called your single scale ratio s defines the relative magnitude of all linear Dimensions between the large and the small scale okay so volume one is given as this volume two is for the larger one if you take a ratio of volume two and volume 1 the S value for your case should be 100 to^ 1X 3 if you make it a 10 lit let’s say every place where you have 100 will become a 10 so this will become 10 1×3 10 are easier to work for one you go to 10 10 to to 100 100,000 an increment of 10 makes your life much more easier let good any questions no question now the scale of strategies deep speed so tip speed is defined as the tangential velocity of an impeller at a point on its tip the tip speed is a function of the RPM revolutions per minute and the DI diameter of the impeller so diameter of the impeller or the size of the impeller will Define the tip speed so the tip speed is pi DN the D is your impellar diameter and N is the impellar agitation rate so the RPM that you’re talking about the criteria is you ensure the L by D the length by diameter to be the same in both cases so L by D in a small scale L by D in the large scale the agitators should be identical should be identical they might not be identical depending upon the how big an agitation system you go to or what type of design you all had before it doesn’t take into account the impeller design at all this one doesn’t take into account the impeller design so if you have a specific impeller with a twisted hook at one end you might want to have the same in the other one sometimes it’s possible sometimes it’s not possible so when that happens you have to redesign your smaller one with a different impeller and then see if that can be used or you have to compare again so you take that Twisted one you still think that it’s a flat and then you use the flat one on the other side and then compare the performance the productivity if it is comparable you’re good to go if it is is not comparable don’t go with it now the other scaleup strategy involves the power per unit volume the W per meter cube the power per unit volume sometimes referred to as power density is a power output for a given volume of culture so impeller design fluid density and the agitation rates are considered in the power per unit volume so your NP is the impellar power in number row is your fluid density N3 or n to^ 3 n is your impeller agitation rate the D is your impeller diameter the V is a liquid working volume and the P not is a ungassed power input this power input is just with respect to ration or agitation it’s just agitation okay there’s no irration yet it’s just agitation so larger the fermentor larger the agitation system that you use larger the amount of power that you’re going to consume redesign it you might be able to make it cheaper questions now shall I continue the other scale of strategy comes for the K so she was right you have K tip speed power density I’m going to put you on place don’t worry about that so tip speed power density k k is for the areation now tip speed power density is mostly for the agitation or the design of the geometry tip speed for with respect to Geometry also power density is with the impeller the agitation purpose K is with respect to oxygen Mass transfer coefficient so this is a parameter that controls the rate of how oxygen transitions from the gas phase into the liquid phase the intent is sufficient o or air delivery is required to support cell growth the metabolic pathways or cell metabolism itself the protein Productions protein Productions requires oxygen if you’re using the host that requires oxygen it is also to prevent excessive CO2 in the media which can impact critical performance end points So Physical K are determined by various Power by volume uh ratios you can use and the gas flow rates the vbms using the static gasing out method you know what the static gasing out method is what is it you have the mic wait somebody give the mic uh first of all we Supply the gas then we allow the bacteria to or microb to utilize the complete amount of gas and then we sparge again then we know how much gas was utilized okay now there are different way methods to measure the K one method I remember is you estimate the amount of oxygen that is there at the beginning of the fermenter as you passing in and then you measure how much is coming out so that will give you the difference of how much oxygen is required another one is where you pass in the oxygen you let the uh the growth and then you pass mer the nitrogen to remove all that oxygen and then you estimate then you pass the oxygen again that’s the static Dynamic guessing that’s the one right the static and dynamic one okay and also there is sodium sulfite oxidation method that I’m not aware of I know about these two that’s what I have read in my undergrad I have not used them yet but those are the ones we oh no for the K we have used the static one anyways so so the K is defined as oxygen transfer rate divided by the do which is your dissolve oxygen dissolve oxygen saturation concentration so OTR divided by the C star biological Kaa depends on the Clone and maximum viable cell concentration so you remember that x value that we have looked at how we estimate how much biomass we can generate with respect to the oxygen concentration that we have and if we have a specific biomass concentration how to estimate how much oxygen we require we did that back equation it was also there so K bio specifically for biological purposes would be your oxygen uptake rate divided by the dissolve oxygen saturation concentration o Max divided by the C star the oxygen uptake rate is not not known at all times sometimes it’s not known what will you do in that case you run the system is is learned by experience so you have to estimate it experimentally that’s why fermentation is not successful in the very first go that you go through it takes time for the fermentation to build up once you are set with all the parameters for your fermentation system you’re in the best condition possible so to prevent oxygen limitation available k for a bioreactor design should be superior to the biological K demand of the cell lines in culture that means your OTR should always be higher than your Ur as simple as that your OTR has to be greater than Ur clear up to here now what are the difficulties with respect to your scaleup if I’m looking from the geometric similarity large bio reactors are physically different from small ones they are physically different from the small world so it’s there’s nothing else I can talk about in that they are just physically different so sometimes it’s not that viable when you’re trying to do the the the scale up it’s not easy mixing time the fluid dynamics V vary in large scale bi reactors causing differences in mixing times due to size and geometry variations the power input per volume difficult to maintain consistent power input per unit volume due to the equipment constraints and the fluid property differences it changes the fluid properties will change depending on the volume oxygen Mass transfer coefficient larger bi reactors can have reduced oxygen Mass transfer coefficients why limitation in gas liquid interaction impacting cell growth and product yield so finding the appropriate size it’s not like that hey I have been successful in this 10 lit bi reactor in my lab let’s go and make 100,000 lit by reactor it doesn’t work like that you go from 10 L Max you go up to 200 L you try in that if it works perfect if you can scale that up then you go for 600 L you don’t go 100,000 immediately you have to be very cautious because as you scale up the difficulties will increase so you only go up to the extent where you know that you’re going to get the maximum productivity okay the tip speed the larger bio reactors require larger impellers resulting in variations in tip speed compared to small vessels affecting the sheer stress and the cell Behavior it will not mix properly cell clusters might appear homogeneity cannot be maintained all of this comes into picture when you’re looking at from the difficulty for the scale of purpose now this is an example where you’re looking at scaleup strategies for let’s say if you’re doing antibi antibodies uh production or the viral proteins or the cell production so if you’re looking at antibodies so production of monoclonal or polyclonal antibodies for therapy diagnosis or research you use Mamon cells example would be the CH cells which are your Mamon cells the process involves cell growth antibody expression and purification the emphasis for this type of fermentation is on the mass transfer for nutrient and oxygen supply so that’s our core focus when we are looking at mumon cells sheer force management to protect fragile antibody producing cells so your agitation you have to be very careful about it because it might break the cells which are going to produce your antibodies so depending on the type of product you’re going to make your scaleup practices will also change clear or the choice of design of B reactor will also change let’s go on the virus side so virus production involves the manufacturing of viral vectors which are used in gene therapy to deliver genetic materials into the target cells production of viral vectors often using aderant or suspension cell cultures example is given to you here the process involves involves transection viral replication and purification steps crucial focus is on controlling Mass transfer for efficient nutrient Supply sheer force management is essential to preserve the integrity and productivity of the viral vectors again agitation has to be very controlled in this case but you do need the mass transfer right so agitation has to be there to make sure the mixing is there is mix exist for the oxygen to get your OTR to be higher than your Ur similarly on the cell side so cell production for therapies like K cells or the stem cells involves cell expansion and differentiation to generate sufficient numbers of theraputic cells if you looking from the cellular agriculture if I’m looking at stem cells stem cells get differentiated into different types of cells that’s where this type of situation will come if you’re looking from cellular agriculture so during cell production is Cru is critical to optimize Mass transfer for adequate nutrients and oxygen delivery to maintain cell health and function throughout the expansion process additionally managing sheer forces is vital to prevent damage to the cultured cells ensuring they remain viable and functional so for almost all of them O2 agitation is important if you go from small scale to large scale you have to make sure the O2 and the agitation can be maintained you maintain the agitation you maintain your O2 but O2 also involves the sparer right it also involves uh putting in the oxygen in the system mixing will allow to better the OTR right it will also help for the viable growth of the cells so you have to make sure the agitation is proper so that mixing takes place now there are also regulatory aspects to bioprocess design this is the I think the last slide for us today so the regulatory aspects for the bioprocess design involved our product quality and Purity the sterility Assurance the validation and qualification and the scaleup validation these are the three that are the most important so what is about the product quality and Purity consistent bioprocess design is required to achieve rigorous control over the quality and purity of the therapeutic products the core focus of the fermentation industry is not only on food but fermentation is also widely utilized for therapeutic drugs from that perspective the Purity and the quality is primary requirement okay because that’s where the regulatory people will come into picture because the Purity and the quality has to be maintained if it is being used for therapeutic purposes for medicinal purposes the sterility Assurance the maintaining sterility to prevent contamination you have to maintain stability to prevent contamination you cannot expect any contamination anywhere traceability documentation and traceability of each steps in the bio process for product safety and Regulatory Compliance if you’re making any changes to the process parameters those have to be documented because that will lead to changes to the product quality If the product quality changes you have a written documentation to know why you would be able to trace the reasoning for it okay validation and qualification validating and qualifying the bioprocess in producing safe and effective therapies consistently so whenever you’re doing any sort of these bioprocessing they have to be consistent and you can validate them scale of validation requires the scale of procedures are validated and meet quality and safety standards so it’s not like I have one bottle in my room and I go and buy a drum and put everything inside and start doing fermentation in it you have to take into account the safety regulations because if you’re working with microbes some of the microbes that you would be working on let’s say if you’re doing fermentation they’re recombinantly uh generated right so they are genetically modified so if those microbes if God forbid if they are pathogenic in nature what will happen things can go wrong so you have to very careful when you’re trying to do the design of these Z cool I hope you have learned something with respect to your bioreactor design and Analysis till now with respect to scaleup the batch design the FED batch design the mass transfer the heat transfer we also had an amazing time discussing About Cellular agriculture the Precision fermentation and not so amazing time thinking about synthetic biology systems biology and enzyme engineering why I said not so wonderful because I felt that I would have given you more information I should have been more prepared for it but I felt that that way that I should have been more prepared but I hope you enjoyed okay I wish that you can work on your case studies case study one and case study two and please try to submit it today in the evening so that we can assemble all the presentations and that would be so we we have to assemble it with respect to the case study one and the case study 2 when you come tomorrow you’ll be presenting all the case study one in one of the sessions and all the case study two in the other session and then we’ll have this type of conversation where we’ll have back and forth why you chose this particular host what was the requirement of this particular host with this is necessary that is necessary we’ll be looking at all of that any questions for me before we end the session today you all look hungry so thank you that will be the end for today’s session

NEOM makes significant investment in biomanufacturing, marking a new chapter in its innovative green economy initiatives – Arabian Business: Latest news on the Middle East, real estate, finance, and more.

The NEOM Investment Fund (NIF) has invested in Liberation Labs, a global leader in precision-fermentation biomanufacturing, to support Topian, NEOM’s food company, in designing and developing an advanced precision-fermentation facility in Saudi Arabia. Liberation Labs develops and operates purpose-built biomanufacturing facilities that use precision fermentation to produce basic food ingredients. This investment marks a significant step in NEOM’s journey to become a global hub for sustainable food production. The partnership will enable Topian to produce high-quality alternative proteins efficiently and sustainably, reducing food imports and improving food security, while also creating new economic opportunities and high-skilled jobs. The investment embodies NIF’s role as a strategic investor and ecosystem developer, laying the groundwork for scalable solutions that will benefit Topian’s business and advance Saudi Arabia’s position as a leader in advanced food biomanufacturing. The collaboration will redefine the future of food production, offering a scalable and sustainable solution to traditional food production methods.

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Here is one possible rewritten version of the line: Korean Startup Secures $9 Million Investment for Precision-Fermented Grape Yeast Proteins

Intake, a South Korean food tech company, has secured ₩13.5 billion ($9.2 million) in Series C funding to commercialize its precision-fermented dairy, meat, and egg proteins. The company, backed by CJ Investment, HB Investment, and other investors, has developed a yeast strain from locally grown grapes that can produce proteins with 1.5 times the protein of traditional yeast. This strain will be used to create “first-generation protein powders” for “second-generation alternative proteins” like dairy, meat, and egg alternatives.

The company is working on several protein suites, including heme protein, which gives beef its red color and flavor, and albumen, or egg white protein. Intake plans to commercialize its products in the US market by 2026, starting with its whey protein replacer, which is currently in its early commercialization phase. The company’s B2B business will continue to focus on providing protein ingredients to manufacturers.

With the new funding, Intake aims to accelerate its R&D and global infrastructure expansion. The company’s existing businesses, including hydration brand Vital Water and plant-based meat brand Innocent, generated ₩22.4 billion ($15.2 million) in revenue last year. Intake is also involved in a government-backed project to develop plant-based and cultivated fish products.

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Intake secures $9.2 million to accelerate precision fermentation breakthroughs

Here is a summarized version of the content in 200 words:

Intake, a South Korean company specializing in precision fermentation food technology, has secured $9.2 million in Series C funding from seven institutional investors, led by CJ Investment. This brings the company’s total funding to $20 million. Founded in 2013, Intake has developed yeast-based solutions for sustainable protein sources, with revenue increasing 30% to $15.2 million in 2024. The funding will be used for R&D, global infrastructure expansion, and commercialization of microbial-based alternative proteins. Intake’s patented yeast strain boasts 1.5 times the protein content of conventional yeast, positioning it to tap into the $35 trillion global protein market. The company is also developing Hemeprotein, a flavor component traditionally derived from meat and egg albumin, through precision fermentation. Intake is committed to advancing microbial-based alternative food technologies to provide consumers with healthy and environmentally-friendly options. With this funding, the company aims to finalize its core microbial-based alternative food technologies and establish itself as a leader in the alternative food sector.

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Partnership announced between Nourish Ingredients and CABIO Biotech to bring precision fermentation fats to the global market at commercial scale.

Nourish Ingredients, an Australian startup, has successfully completed its first commercial production of Tastilux, a potent meaty fat, in partnership with Chinese biotech company CABIO Biotech. This achievement marks a significant breakthrough in precision fermentation, demonstrating the commercial viability of producing animal-free fats at a low cost. Nourish Ingredients has increased its production capacity by 1700% and meets 170,000 tons of end-product demand. This milestone validates the company’s fermentation process and solidifies its partnership with CABIO Biotech.

Tastilux is a game-changer in the plant-based industry, offering rich, meaty flavors and textures that are unmatched by traditional alternatives. The product has been tested and proven to deliver exceptional flavor stability, satisfying customers with its deep, meaty richness from the first bite to the last.

Nourish Ingredients plans to ship the first batch to customers across three continents, marking the beginning of a future where sustainable food is accessible to everyone. This partnership with CABIO Biotech has enabled the company to deliver its innovative ingredients at scale, paving the way for a new industry standard in precision-fermented fats.

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Sustainable food production: cell-based innovations and precision fermentation for safe and high-quality food, as implemented by the Food and Agriculture Organization of the United Nations.

Cell-based food production involves using cells from animals, plants, or microorganisms to produce food products, ingredients, or additives. Precision fermentation is a process that uses microorganisms to produce specific products through controlled systems. The global demand for proteins and nutrients is driving innovation in food production, and food safety authorities are working to address the potential implications. The Food and Agriculture Organization (FAO) is collaborating with stakeholders to advance knowledge and develop regulatory frameworks.

The FAO has published several reports and held stakeholder meetings on cell-based food safety, including a publication on food safety aspects of cell-based food and a webinar report. The organization is also facilitating an informal technical working group for government sector regulatory experts to exchange information.

The FAO is also developing a literature synthesis on precision fermentation and has published reports on stakeholder meetings in Canada, Israel, and China. The organization is working to advance knowledge and develop regulatory frameworks for cell-based food production and precision fermentation.

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FAO forecasts significant potential for precision fermentation to unlock a safer and more sustainable food future.

Here is a summary of the text in 200 words:

The Food and Agriculture Organization of the United Nations (FAO) has released a report on “Precision Fermentation – With a Focus on Food Safety” by Drs. Sturme, van der Berg, and Kleter from Wageningen Food Safety Research. The report examines the intricacies of precision fermentation, a new method of food production that uses microorganisms to create traditional food compounds in a controlled environment. Fermentation processes are performed in bioreactors, similar to big beer-brewing tanks, using microorganisms such as bacteria, yeasts, or algae.

The report covers the three phases of precision fermentation (technology development, upstream fermentation, and downstream processing), and includes three case studies highlighting the practical applications of this technology. The report also summarizes the outcomes of two online regulatory consultations with over 100 experts, collecting information on food safety frameworks from 35 jurisdictions.

The document serves as a guide for food safety competent authorities worldwide to understand and ensure the safety of food products derived from precision fermentation. It provides a valuable reference point for countries to learn from good practices and lessons learned, and lays the groundwork for future regulatory actions. The report can be downloaded on the FAO website.

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Protein-Rich Dairy Formulations: precision-crafted, high-performance dairy protein solutions

The Verley functional dairy protein range is a series of precision-fermented solutions designed to overcome the limitations of traditional dairy and plant-based products. The range includes three varieties: FermWhey Native, FermWhey MicroStab, and FermWhey Gel, each suited for different applications. FermWhey Native is targeted towards sports nutrition, while MicroStab is suitable for UHT beverages and fresh dairy products, and Gel is designed for spoonable dairy and cheese products. According to CEO Stéphane Mac Millan, precision fermentation has the potential to revolutionize the food industry, and Verley’s patented functionalization technologies allow for the development of proteins with improved functionality, including 11% more leucine than native WPI and 50% more than soy alternatives. This innovation has the potential to significantly impact the health and wellness industry, particularly in sports nutrition.

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Next year, our business operations will generate a sustainable profit.

The EVERY Co, a company that produces egg proteins through precision fermentation, aims to have “profitable unit economics” next year as it increases its manufacturing capacity to meet growing demand. The company’s technology uses yeast to express proteins found in eggs, and it has received “no questions” letters from the FDA for its products. The EVERY Co has developed two main products: OvoPro, which replaces the functionality of egg whites, and OvoBoost, a highly soluble protein that is bio-identical to a glycoprotein found in egg white. The company’s pricing model is based on the functionality of ovalbumin, which is responsible for most of the binding, emulsification, foaming, and gelation properties of egg whites. This means that customers are not paying a premium for OvoPro, as they can use less of it to achieve the same results as egg whites. The company offers labeling options such as “animal-free egg white protein” and “egg white from yeast,” and it expects to produce in the hundreds of tons next year.

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At the Food and Agriculture Organization of the United Nations, we focus on the safety and quality of cell-based food and precision fermentation.

The article discusses cell-based food production, which involves using cells from animals, plants, or microorganisms to produce food products, ingredients, or additives. The article also mentions precision fermentation, which uses microorganisms to produce specific target products. As the global demand for proteins and specific nutrients grows, many in the agrifood sector are looking into opportunities to expand the scope of diverse food production systems. To address the potential food safety implications, food safety authorities are working to develop regulatory frameworks that protect consumers. The Food and Agriculture Organization (FAO) has been working to advance knowledge in this area, collaborating with stakeholders and organizing meetings and publications. The article mentions various reports, including a literature synthesis on precision fermentation, a factsheet on food safety aspects of cell-based food, and reports on stakeholder meetings and side events.

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Plant-based dairy alternative company launches US debut of protein-rich whey products

French precision fermentation startup Bon Vivant has rebranded to Verley and launched a range of functional animal-free whey proteins. The company’s new portfolio, FermWhey, is based on recombinant beta-lactoglobulin protein, which is produced through precision fermentation. The FermWhey line includes three products: Native, MicroStab, and Gel, each with unique properties for different applications. The products are designed to offer superior nutrition, stability, and functionality, making them suitable for a range of food and beverage applications.

Verley’s technology allows for the production of whey protein with enhanced protein stability, gelling properties, and foaming properties. The company claims that its products require 81% less water, 99% less land, and 72% fewer greenhouse gas emissions to produce, making it a more sustainable option.

The company has already secured contract manufacturing partnerships to scale up production and is working with dairy and ingredient companies to bring its solutions to market. Verley is also seeking FDA approval for its FermWhey ingredients, with an expected approval letter this year.

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The UK government has committed £1.4 million to bolster its precision fermentation capabilities, marking a significant investment in cutting-edge technology.

The UK government has invested £1.4m in a new innovation hub to support the Food Standards Agency (FSA) in advancing its expertise in new technologies like precision fermentation. This technology uses microorganisms to produce ingredients such as dairy proteins, allowing for the creation of plant-based products that mimic the taste and texture of animal-based foods. The global precision fermentation market is expected to reach $34.2bn by 2031. The UK government’s investment will enhance the FSA’s risk assessment capabilities and provide regulatory clarity for start-ups seeking to sell precision-fermented products in the UK. The Good Food Institute (GFI) Europe welcomed the funding, citing its potential to make the UK a world leader in food innovation while maintaining safety regulations. This initiative is separate from the FSA’s regulatory sandbox for cultivated meat, which aims to expand knowledge about this product.

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Marble Invests in Capacity Building to Enhance Accuracy in Fermentation-Based Fatty Acid Production

Melt&Marble, a company that specializes in precision-fermented fats, has announced the addition of two new leaders to its team. Tue Hodal, a veteran of industrial biotech and pharma, has joined as Chief Technology Officer (CTO). Prior to this, he held high-level positions at companies such as Chr. Hansen, Novo Nordisk, and Lundbeck. As CTO, Hodal will optimize bioprocesses and downstream operations to support large-scale commercial production. Paulo Teixeira, previously the Chief Innovation Officer at Mycorena, has been appointed as Product Manager. He will focus on shaping the company’s product development strategy, including enhancing the taste and mouthfeel of alternative food products. Melt&Marble’s technology uses precision fermentation to create tailored fats, which are designed for various industries, including food and personal care. The company has already demonstrated the scalability of its production process, with plans to expand to thousands of liters per batch this year. The new hires are expected to support the company’s growth and partnerships, including a €2.76 million grant from the European Union and a partnership with Finnish food company Valio.

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The announcement is made: Americas Finalists and Winners Revealed

Hydrosome Labs, a Chicago-based start-up, has won the first heat of the Global Food Tech Awards 2025, using a natural, chemical-free microbubble process to enhance fermentation performance. The company’s technology uses ultrafine bubbles and nanobubbles to improve precision fermentation capacity and accelerate cell growth. The Global Food Tech Awards aims to recognize innovative food technology and drive innovation in the industry. The competition attracted a strong field of entries, which were evaluated by a panel of five expert judges. Hydrosome Labs’ win was praised for its simplicity, scalability, and potential applications. Two runners-up, Careit and Marine Biologics, were also recognized for their innovative approaches to reducing food waste and transforming seaweed into a programmable biomass. The awards will continue with the EMEA and APAC heats, with the overall winner to be announced in December.

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The precision fermentation market is expected to surge to a value of USD 48.16 by [year]. Note: I added the year to provide more context and clarity, but you can adjust this if you need a different format. Let me know if you have any further requests!

The Precision Fermentation Market is expected to grow at a CAGR of 40.56% from 2024 to 2031, reaching a market size of $48.16 billion by 2031. The market focuses on the use of microbial hosts to produce specific ingredients like proteins, enzymes, and fats through controlled fermentation. Growing demand for alternative proteins, advancements in biotechnology, and increasing investments in sustainable food solutions are driving market expansion.

The report highlights key players in the market, such as Geltor, Perfect Day, and Impossible Foods, among others. Recent industry developments include Nestle’s launch of its first-ever dairy protein powder produced through precision fermentation and Vivici’s plans to manufacture industrial-scale whey protein using precision fermentation.

The report also provides information on the market’s regional analysis, covering North America, Europe, Asia-Pacific, Middle East and Africa, and South America. The report is beneficial for businesses seeking to understand the global precision fermentation market, its trends, and growth opportunities. By purchasing this report, companies can gain insights to navigate the market and make informed decisions.

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At the Global Food Tech Awards Americas, Hydrosome Labs’ innovative ultrafine bubbles made a splash, winning top honors.

Hydrosome Labs, a nanotechnology company, has won the first round of the Global Food Tech Awards with its innovative ultrafine bubbles. These bubbles, which are smaller than a champagne bubble, are capable of delivering nutrients and gasses to cells, boosting production of precision fermentation and improving nutritionals. The technology has the potential to alter the texture of food, speed up production, and reduce the need for expensive or less desirable ingredients. The company is exploring the use of different gases, such as those that could enhance taste and sensory experiences, and has found that the addition of ultrafine bubbles in water can help modulate the gut microbiome in a positive way, reducing inflammation. The technology also has potential applications in the cosmetics industry to improve the feel and permeability of topical products. The company is partnering with celebrity Cindy Crawford to launch a line of Meaningful Beauty products using its technology. The Global Food Tech Awards will continue with the EMEA heat in March 2025 and the APAC heat in August, with the global champion to be announced at the end of the year.

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The fermentation ingredients market is expanding at a 44% Compound Annual Growth Rate (CAGR), fueling high demand for precision fermentation solutions.

The global precision fermentation ingredients market is growing rapidly, with a value of $2.8 billion in 2023 and projected to reach $36.3 billion by 2030, at a CAGR of 44.0%. The market is driven by shifting consumer preferences towards veganism, increased protein consumption, and investments in cutting-edge innovations. Companies like Geltor, Perfect Day, and Impossible Foods are leveraging technological advancements to develop specialized food protein constituents through precision fermentation. The North American market is expected to maintain its dominance, driven by increasing consumer awareness, preference for healthier food ingredients, and the growing trend of veganism. The cosmetics & others segment is projected to have the highest CAGR, driven by the demand for fermented cosmetic products that offer nutrient absorption and skincare benefits. The meat & seafood alternatives segment is also experiencing significant growth, driven by the increasing demand for plant-based proteins and fats that replicate the taste, texture, and nutritional profile of meat products.

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From plant-based dairy alternatives to lab-grown proteins, fermentation gets a new stamp of approval

Swiss organization V-Label has launched a new certification label, F-Label, for fermentation-derived proteins. The label is designed to address confusion about vegan-friendly labels on these products. F-Label is the world’s first certification mark for products made through precision, biomass, and gaseous fermentation, as well as cell-free synthesis. The label verifies that the production process is animal-free, without antibiotics, and the final product is free from genetically modified organisms (GMOs).

The first recipient of the F-Label is Chilean food tech startup Luyef Biotechnologies, which makes precision-fermented nutrients to enhance cultivated meat. Marketed as TAMEE, this is a heme protein that enhances the color, aroma, and flavor of meat analogues.

V-Label’s founder, Renato Pichler, emphasized that the label aims to provide transparency and build trust with consumers and industry partners. He noted that regulatory approval varies by region and application, and the F-Label does not replace regulatory oversight.

Pichler also highlighted that the self-affirmed GRAS (Generally Recognized as Safe) rule in the US, which allows companies to self-affirm their ingredients as safe without formal FDA notification, may be eliminated. This could have significant implications for fermentation startups, which may have to adapt to more rigorous oversight and slower approvals.

Overall, the F-Label aims to clarify the differences between vegan and animal-free labels and provide consumers with more accurate information about the production process and ingredients.

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Marking a new frontier in precision fermentation, the launch of the F-Label reaches a crucial milestone.

V-Label, a labeling certification, has introduced the F-Label, the world’s first certification for precision fermentation and other innovative animal-free production technologies. This comes after the success of C-Label, a certification for cultivated meat. The F-Label aims to enhance consumer transparency and trust in food products made using advanced fermentation techniques such as biomass fermentation, syngas fermentation, and cell-free synthesis. The certification ensures that products meet strict criteria, including animal-free production, non-GMO status, and antibiotic-free processes. The F-Label is designed to give consumers confidence in their food choices and support ethically and sustainably produced products. The certification is particularly relevant in the alternative protein sector, where clarity on definitions such as “vegan” can vary. The launch of F-Label marks a significant moment for the food industry, with potential to transform food production through precision fermentation. The certification aims to reshape consumer perceptions and support innovations that prioritize ethical and sustainable practices.

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Here’s a rewritten version of the headline: Vivici Clears FDA Pathway for Cow-Free Whey with Unconditional Approval

Vivici, a company specializing in animal-free dairy alternatives, has received a “no questions” letter from the US Food and Drug Administration (FDA) for its cow-free whey product. This milestone comes amidst the FDA’s overhaul of its Generally Recognized as Safe (GRAS) notification process. A “no questions” letter is a favorable designation from the FDA, indicating that the agency has reviewed Vivici’s submission and has no further questions or concerns regarding the safety of their product.

The FDA’s GRAS reform aims to modernize the notification process, making it more efficient and transparent. Vivici’s success in securing a “no questions” letter demonstrates the company’s compliance with the FDA’s rigorous guidelines. The achievement enables Vivici to market its animal-free whey product in the US, offering a sustainable and dairy-free alternative for the food industry. This development has significant implications for the dairy-free and plant-based food sector, as well as for consumers seeking to reduce their environmental impact and adapt to changing consumer preferences.

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Sennos, formerly Precision Fermentation, launches new chapter with strategic restructuring and appointment of a team of industry experts to fuel global expansion and success.

Sennos, a leading company in sensing, analytics, and automation for the fermentation and fluidics industries, is rebranding to further expand its impact beyond the brewing and beverage industry. The company’s platform is designed to help businesses in various sectors, including alternative food production, biopharmaceuticals, and alternative fuel development, achieve consistency, quality, and control in their manufacturing processes. Sennos has assembled a world-class leadership team to drive innovation and success, including its Founder and CEO, Jared Resnick, and other experienced professionals. The company will be demonstrating its next-generation solutions at the Craft Brewers Conference in April 2025. Sennos’ flagship product, BrewIQ, provides real-time fermentation telemetry and actionable insights, enabling businesses to operate at peak efficiency and avoid product loss. Founded in 2017, Sennos has revolutionized fermentation monitoring with its patented remote sensor platform and AI-driven data analytics. By transforming raw data into a powerful tool for quality control and operational excellence, Sennos is bridging the art of brewing with state-of-the-art technology to meet the high expectations of discerning consumers.

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Unlocking Opportunities in the Fermented Ingredients Market from 2024 to 2030: Precision Fermentation Advancements Unlock New Possibilities for Customized Fermented Compounds and Functional Additives I made the following changes: * Simplified the language to make it more concise and clear * Rephrased the sentence to make it more engaging and concise * Used more dynamic verbs like Unlocking to convey a sense of excitement and possibility * Emphasized the benefits of precision fermentation by highlighting New Possibilities for customized fermented compounds and functional additives.

The “Fermented Ingredients – Global Strategic Business Report” report provides an in-depth analysis of the global fermented ingredients market, which is expected to reach $79.3 billion by 2030, growing at a CAGR of 8.8% from 2024 to 2030. The market is driven by rising consumer demand for functional foods, advancements in fermentation technology, a shift towards clean-label and natural products, and sustainability goals. Fermented ingredients are used in various applications, including food, beverages, animal feed, and nutraceuticals, and are expected to play a key role in the future of the food and beverage industry.

Technological advancements have improved the efficiency, quality, and application range of fermented ingredients. Probiotics, kombucha, and fermented soy products are popular choices for individuals seeking dietary solutions that promote digestive health and wellness. The report highlights the role of health trends and sustainability concerns in shaping the fermented ingredients market, with consumers prioritizing natural, nutritious, and environmentally friendly ingredients.

The report provides comprehensive market data, regional analysis, and company profiles, with a focus on major players such as Ajinomoto Corporation Inc., Allied Bakeries, Angelyeast Co., Ltd., and more. The report also provides insights into the amino acids, organic acids, industrial enzymes, antibiotics, polymers, and other types of fermented ingredients, as well as their applications in food and beverages, feed, pharmaceuticals, personal care, and paper.

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The world of precision fermentation is making headlines with the latest news in the field.

The global precision fermentation market is expected to grow at a CAGR of 33.01% from 2023 to 2029, driven by increasing demand for sustainable and alternative protein sources. Precision fermentation is the process of using microorganisms to create various products, such as food ingredients, drugs, and biofuels. The method uses genetically modified microorganisms to maximum production processes and product quality, unlike traditional fermentation which uses natural organisms. The growing use of alternative protein sources, such as plant-based and lab-grown products, is a major driver of the market. Precision fermentation allows for the production of plant-based proteins, dairy alternatives, and cultured meat, which are sustainable and can meet the growing demand for protein without the need for animal husbandry. The market is also expected to expand into new applications, including cosmetics, textiles, and agriculture, where precision fermentation can provide sustainable and eco-friendly alternatives to traditional methods. Overall, precision fermentation is expected to play a key role in the development of sustainable and alternative products that meet the growing demand for healthy, personalized, and sustainable food and other products.

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Pow.Bio officially opens its state-of-the-art continuous fermentation demo facility on the West Coast, in California.

Pow.Bio, a startup that is revolutionizing the field of precision fermentation, has opened a new 25,000 sq ft facility in Alameda, California. The facility is equipped with a fleet of dual-chamber continuous fermentation systems and proprietary software, allowing for the production of hundreds of kilos of ingredients. CEO Shannon Hall believes that the new facility will help companies overcome the high costs and prolonged development timelines associated with traditional batch precision fermentation processes.

Pow.Bio’s continuous fermentation process decouples the growth of microorganisms from the production of target ingredients, solving problems such as contamination and genetic drift. The company’s technology enables the production of large quantities of ingredients without the need for traditional batch processing, resulting in significant cost savings and increased efficiency.

The facility is designed to be capex-light, allowing customers to integrate the technology into their existing infrastructure with minimal modifications. This makes it possible for companies to shift from batch or fed-batch to continuous operation without significant capital expenditures, resulting in faster and lower-cost production.

Pow.Bio works with customers of all sizes, from startups to publicly traded multinationals, and has a proven track record of delivering results quickly and deploying its solution within existing systems. The company’s technology has the potential to revolutionize the biomanufacturing industry by enabling the production of high-quality ingredients at a lower cost and faster rate.

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Unlocking the power of precision fermentation to sustainably feed a growing world.

In the science fiction world, the idea of eating synthetic food grown in vats is a common theme. However, what if I told you that this technology is already here and has been around for decades? Precision fermentation, a process that uses microorganisms to produce food and other products, has been used to make foods like cheese, wine, and beer. This technology has the potential to revolutionize the way we produce food.

With the rise of CRISPR, genetic engineering is now easier and more accessible, allowing for a wide range of new products to be created. Companies like Impossible Foods and Perfect Day are already producing plant-based meat and dairy products, such as vegan milk and cheese, using precision fermentation. Other companies are working on creating egg substitutes and even protein-rich flour made from hydrogen-eating bacteria.

The benefits of precision fermentation are numerous. It’s a cruelty-free and environmentally friendly way to produce food, reducing the need for animal agriculture, which is a significant contributor to climate change. It’s estimated that 1/3 of the world’s arable land is used to grow feed for animals, and that livestock production is responsible for 14.5% of global greenhouse gas emissions.

However, there are concerns about the lack of transparency and control over these new technologies. With companies keeping their methods and production processes secret, it’s difficult to assess the true environmental impact of precision fermentation. Dr. Julie Guthman, a professor of social sciences, notes that Silicon Valley food tech entrepreneurs are more concerned with making a profit than with being transparent and accountable to the public.

Ultimately, the future of food production is likely to be a combination of conventional and advanced technologies. As we move forward, it’s essential to balance the need for innovation with the need for transparency and regulation to ensure that this technology is used responsibly and sustainably.

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Unlocking the Secrets of the Microbial World: A Leap Forward in Fermentation Technology

Companies like Creamilux are using precision fermentation to create dairy-like products, including alternatives to milk, cheese, and butter. These products, such as Tastilux and Creamilux, can help simplify food manufacturers’ formulas by providing potent ingredients at low inclusion rates. The technology can also reduce the need for hydrogenation, chemical additives, and artificial flavors. Other companies, like Oobli and TurtleTree, are using precision fermentation to create products like chocolate and lactoferrin, a milk protein with potential health benefits. The development of these products has led to the formation of the Precision Fermentation Alliance, a group of nine companies working together to ensure that regulators use a science-based approach in regulating the technology. However, there are challenges to scaling up production, particularly for ingredients that require large quantities, such as bulk alternative proteins. Despite these challenges, precision fermentation holds great promise for creating sustainable and animal-free food options.

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From proteins to AI, February sees investments in cutting-edge cleanrooms and advanced factories.

Vivici, a Dutch protein startup, has raised €32.5 million in funding to produce high-quality proteins without using animals through precision fermentation. The investment will enable the company to expand internationally, launch a second dairy protein ingredient, and build long-term production capacity. The Eindhoven University of Technology (TU/e) has also announced a €200 million investment to construct a new lab building and cleanroom, which will be used for semiconductor research and education. The European Union has unveiled a €200 billion investment in AI gigafactories, with the aim of establishing four facilities to train highly complex AI models. Finally, Sirius Medical, a spin-off of the Netherlands Cancer Institute, has secured €10 million in funding to advance its surgical marker navigation portfolio and expand its global presence. The funding will improve the company’s system and software, making it more user-friendly and expanding its uses, and strengthen sales and support in new markets. Overall, these investments highlight the significant potential for growth and innovation in various industries, including technology, healthcare, and sustainability.

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Introducing the Allbiotech Bioreactor, a cutting-edge tool for precision fermentation research at an affordable price point.

Spanish biotech startup Allbiotech Biotechnologies has launched its Genesys V1 bioreactor, a lower-cost alternative for precision fermentation research. The bioreactor is designed for early-stage testing, process optimization, and scale-up research in food production and is priced at one-third of traditional pharmaceutical bioreactors. The company aims to make bioreactor technology more accessible to food tech startups, research institutions, and universities. The Genesys V1 bioreactor features a 1-liter glass vessel, integrated sensors, and five peristaltic pumps, making it ideal for precision fermentation applications. Allbiotech was founded in 2024 with the goal of reducing the cost barrier associated with precision fermentation equipment. The company plans to scale its operations through a direct-to-consumer sales model, bypassing traditional distributors and reaching customers through digital channels. This innovation has the potential to democratize access to bioreactor technology, promoting the development of sustainable and sustainable food production methods.

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Precision fermentation is poised to revolutionize the development of game-changing functional foods.

Precision fermentation, a technology that produces protein products, was previously seen as a mid-term alternative to plant-based and lab-grown meat. However, only a few companies, such as Perfect Day, have successfully moved from the tech stage to commercial products. As a result, companies are now focusing on developing high-value products, such as nutrients. One key nutrient that has emerged is lactoferrin, which has antibacterial, antiviral, and anti-inflammatory properties. TurtleTree, a company that uses precision fermentation, has pivoted from developing alternative milk and dairy products to focusing on lactoferrin as its star product. The company aims to use lactoferrin in sports nutrition and target vegan and vegetarian athletes who lack access to dairy-based proteins. Other companies, such as FrieslandCampina and All G Foods, are also working on developing lactoferrin made via precision fermentation. TurtleTree has successfully completed self-GRAS application in the US and partnered with brands like Cadence Cold Brew and Strive to launch products. The company is also set to launch a lactoferrin-containing coffee in Singapore in 2025.

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Vivici secures €32.5 million in its Series A funding to fuel the growth of its precision fermentation capabilities.

Dutch ingredients start-up Vivici has raised €32.5 million in Series A funding to expand its precision fermentation dairy protein business. The funding was led by APG on behalf of pension fund ABP and Invest-NL, with additional support from InnovationQuarter and existing shareholders DSM-Firmenich and Fonterra. Vivici plans to use the investment to enter new international markets, launch its second dairy protein ingredient, and build long-term manufacturing capabilities. The company’s first commercial product, Vivitein BLG, is an isolated whey protein designed to supplement dairy industry protein production, offering significant environmental benefits, including 86% lower water usage and a 68% reduction in carbon footprint. The company aims to expand its product portfolio, with the launch of lactoferrin (Vivitein LF) expected later this year. Vivici’s CEO says the funding demonstrates investors’ confidence in the company’s mission and capabilities, and paves the way for the company to turn precision fermentation into a commercial reality. The company’s product is expected to become a mainstay of consumer protein products, offering a new standard of protein with sustainability, consumer, and commercial benefits.

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Wageningen University prepares next generation of food technology leaders.

Wageningen University & Research (WUR) is launching a master’s course on precision fermentation, starting on March 10, 2025. The course aims to provide students with hands-on experience in precision fermentation, a technology that combines precision biology with traditional fermentation methods to produce specific proteins and compounds identical to those found in animal-based products without the need for traditional agricultural methods. The 8-week course has attracted over 50 students from diverse backgrounds and will cover topics such as bioprocess engineering, food quality design, and food process engineering. The course is well-timed, as the precision fermentation market is projected to grow from $1.6 billion in 2022 to $36.3 billion by 2030. The Netherlands, which has a strong background in biotechnology and food production, has launched two open-access scale-up facilities focused on precision fermentation, positioning it for strong growth in the industry. The course is part of the National Growth Fund project on Cellular Agriculture, which aims to develop the skills needed to contribute to the rapidly evolving sustainable food production landscape.

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A new player in the lactoferrin market is building a precision fermentation facility in the US.

A new company, PFerrinX26, is planning to enter the lactoferrin market by building a precision fermentation facility in the Midwest. Lactoferrin is an iron-binding protein found in mammalian milk, with benefits for human health, but has historically been costly to isolate from milk. The company is backed by Earth First Food Ventures Ltd (EFFV), which has assembled a consortium of players from the big dairy, dextrose providers, off-takers, CPG, and ingredient companies to fund a facility capable of producing 200 tons of bovine lactoferrin in the coming years. The facility will utilize genetically engineered microbes to produce lactoferrin, which can be used in various applications such as cosmetics, adult nutrition, and infant formula. The company aims to reduce costs by using continuous fermentation technology and novel approaches. The market demand for lactoferrin is expected to grow, driven by the increasing popularity of dairy alternatives, the aging population, and the growing demand for protein-enriched foods and supplements.

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Innovative fermented proteins: A novel class of high-quality feed for pets Let me know if you’d like me to make any changes!

The pet food industry is facing increasing pressure to find alternative protein sources due to a constricting supply chain and growing concerns about sustainability. Companies like Bond Pet Foods are using precision fermentation to create nature-identical animal proteins without the use of animals. Rich Kelleman, CEO of Bond Pet Foods, discussed their process at the 2025 Pet Food Conference. They create their proteins by isolating a protein strain responsible for producing skeletal muscle protein, combining it with brewer’s yeast, and fermentation. The resulting protein is flexible and can be incorporated into various pet food formats. Bonde has developed two protein products, a brewed chicken protein and a protein specifically designed for Hill’s Pet Nutrition, which have shown promising nutritional efficacy and environmental benefits. The company is planning to bring its products to market within the next couple of years and is refining its products to create customized solutions for dogs and cats. Bond’s novel approach to protein production has the potential to alleviate the pressure on the protein supply chain and provide pet owners with more sustainable and nutritious options.

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Liberation Labs secures $50.5 million in funding to establish precision fermentation facilities in the US and Saudi Arabia.

Liberation Labs, a US-based biotech manufacturing company, has raised $50.5 million in funding for its precision-fermented foods, with a focus on building large-scale facilities in Richmond, Indiana, and Saudi Arabia. The company aims to commercialize precision-fermented ingredients through a global network of dedicated production plants, which will feature a fit-for-purpose design to enable cost-effective solutions.

The funding round was led by the state-owned NEOM Investment Fund, which provided part of the $31.5 million raised, along with other investors such as Galloway Limited, Meach Cove Capital, and existing investors Agronomics, New Agrarian Capital, and Siddhi Capital. The remaining $19 million comes from insider bridge notes raised last year.

Liberation Labs plans to build a first commercial-scale biomanufacturing plant in Richmond, Indiana, which will have a fermentation capacity of 600,000 liters and will produce between 600 to 1,200 tons of protein annually. The company also intends to build factories in six geographies, starting with a 600,000-liter launch facility and eventually opening a plant with a capacity of four million liters in each market.

The precision fermentation company is also in the late stages of constructing a facility in Saudi Arabia, which will produce “building block ingredients” for food, chemicals, and other industrial products. The company has raised a total of $71.5 million in private capital since its founding in 2022, in addition to $55 million in non-dilutive funding commitments.

The company’s focus on precision fermentation, also known as a biomanufacturing platform, has gained interest from investors and policymakers, with the US Department of Defense providing funding for its projects. The company’s goal is to build a future where precision fermentation proteins can reach industrial scale to meet growing global demand.

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Start-up Precision Fermentation Firm Liberation Labs Raises $50.5 Million to Boost Production Capacity

Liberation Labs, a biotech company, has raised $50.5 million in a convertible note round, bringing its total funding to $75 million. The investment was led by new investors NEOM Investment Fund, Galloway Limited, and Meach Cove Capital, while existing investors Agronomics, New Agrarian Capital, and Siddhi Capital also participated. The funding will be used to complete the company’s first commercial-scale precision fermentation biomanufacturing facility in Richmond, Indiana, which is expected to be operational in 2025. The 600,000-liter facility will produce bio-based materials for food, chemicals, and industrial applications, addressing a supply gap in the US market. The funding will also support the development of a second facility, which could be built with an additional 4-million-liter capacity. The company’s founder and CEO, Mark Warner, sees this as validation of their technology and strategy, while Jim Mellon, director of Agronomics, believes it will help build a future where precision fermentation proteins can meet growing demand globally.

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Nova Scotia Bolsters Precision Fermentation Ecosystem with $1 Million Injection

The Government of Nova Scotia is investing $1,055,000 to expand the capabilities of the Verschuren Centre’s fermentation plant in Cape Breton. The funding will enhance automation, support additional clients, and create skilled jobs in the biomanufacturing sector. The expansion will increase the plant’s client capacity from 40 to 50, allowing it to accommodate more advanced projects and drive further direct investment and job creation. The initiative will also support the development of an in-house training program, focusing on skills development in electronics, digitization, process engineering, and fermentation technology. The Verschuren Centre is a key player in Canada’s biomanufacturing sector, housing a pilot-scale bioreactor and utilizing living systems to produce commercial materials. The investment will help the centre address the demand for sustainable products in the supply chain for Canadian manufacturing, matching assets only available in Europe and Mexico.

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UK start-up Better Dairy leads the charge in precision fermentation, revolutionizing the dairy industry with innovative, cow-free cheese alternatives.

Better Dairy, a UK-based start-up, is developing a cheese and yogurt alternative that is animal-free, healthier, and better for the environment. The company uses precision fermentation to produce animal-free casein, a key milk protein, which allows them to make a variety of dairy products without the need for cows. This technology can produce cheese that tastes, melts, and stretches just like traditional dairy cheese, but with a lower environmental impact. The company plans to sell its proteins to existing manufacturers, enabling them to produce an animal-free cheese that is identical to traditional dairy cheese. Better Dairy’s goal is to reduce the environmental impact of dairy production, which is a significant contributor to greenhouse gas emissions and resource consumption. The company is currently producing its products at a lab scale and plans to increase production capacity and navigate regulatory approval in target markets, including the US. With approval expected by 2027 and 2028, Better Dairy aims to revolutionize the dairy industry and provide a more sustainable alternative for consumers.

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Pioneering a New Era in Cellular Agriculture – Cavendish

Agronomics Limited, a UK-based investment company, is a leading player in the burgeoning cellular agriculture sector. In 2024, the company made significant strides, investing £13.5 million in precision fermentation technologies and cultivated meat innovations. One notable achievement was Meatly’s development of a protein-free culture medium, which reduces the cost of cultivated meat production. The company also secured regulatory approval for its cultivated chicken for pet food, a crucial step towards commercialization. Despite reporting a net unrealised loss of £8.3 million, Agronomics’ portfolio saw positive revaluations of £6.9 million. The company’s diversified portfolio, comprising 30% precision fermentation, 30% cultivated meat, and 16% Liberation Labs, allows it to tap into different market segments and leverage the faster commercialization timeline of precision fermentation technologies. With its focus on sustainability and innovation, Agronomics is well-positioned to capitalize on the growing demand for sustainable food solutions and alternative proteins, making it a compelling investment opportunity for those seeking exposure to this transformative industry.

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Vegan dairy company Those Vegan Cowboys partners with Hochland to pioneer a plant-based casein alternative.

Those Vegan Cowboys (TVC), a Belgian precision fermentation start-up, has partnered with Hochland, a European cheese major, to test its dairy-identical, animal-free casein. Casein is a key component in cheese that makes it stretch and melt. TVC’s casein is produced through precision fermentation, a method that utilizes genetically-modified microbes to produce milk proteins. The partnership builds on TVC’s previous collaborations with other cheese producers, including Dutch cheese maker Westland Cheese. The companies claim that TVC’s casein can stretch better than animal-derived casein and plans to use it in new products. To bring the product to market, TVC needs to obtain regulatory approval, which may take several years. The company expects to file for approval in the US later this year and target the Asian market next. The partnership with Hochland is a significant step towards commercialization and a key milestone in reducing the cost and environmental impact of dairy production.

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New Culture, a pioneering animal-free casein startup, unveils the ingredients behind its innovative Mozzarella alternative.

New Culture, a US-based startup, has revealed the ingredients of its animal-free mozzarella cheese ahead of its launch. The company has developed a method to produce casein, a protein found in milk, using microflora fermentation. This process allows for the creation of a cheese that is identical in taste and texture to traditional mozzarella, but is free from animal products. The ingredients list includes:

* Microflora fermentation broth
* Plant-based starter culture
* Vegetable-based rennet
* Salt
* Water

The company claims that its animal-free mozzarella has a rich, creamy taste and a smooth texture, making it suitable for pizzas, lasagnas, and other dishes. New Culture’s innovative production method has the potential to revolutionize the dairy industry, offering a sustainable and cruelty-free alternative to traditional cheese. The company plans to launch its product in the near future, with the goal of making it widely available in stores and restaurants.

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Natural Colour Enhancers: Fungal Protein Derivatives

Michroma, an Argentine company, is revolutionizing the food colorant industry with its innovative, multifunctional ingredients. Through a precision fermentation process, the company cultivates specialized fungi strains that produce vibrant pigments when fed with affordable feedstocks. With backing from major industry players like General Mills and Dr. Oetker, Michroma has secured $6.4 million in funding to advance its approach to food ingredients. Its flagship product, Red+, offers a game-changing solution for plant-based meat products by incorporating essential amino acids, fiber content, and exceptional stability across various pH and high-temperature conditions. This premium ingredient has broad application potential in beverages, confectionery, and baked goods, making it an attractive option for food manufacturers seeking healthier, trend-setting products.

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Unlocking the Future of Food: Global Insights into the Precision Fermentation Market

The global Precision Fermentation market was valued at $3.16 billion in 2023 and is expected to reach $48.16 billion by 2031, growing at a CAGR of 40.56% during the forecast period. The market focuses on market trends, historical growth rates, technologies, and the changing investment structure. The report highlights the latest market insights, increasing growth opportunities, business strategies, and growth plans adopted by major players. Precision fermentation is an advanced biotechnological process that uses microorganisms to produce specific substances or ingredients with high precision. The market is divided into six major regions: North America, South America, Europe, Asia Pacific, the Middle East, and Africa.

The report provides an analysis of current market dynamics, future developments, and Porter’s Five Forces Analysis. It also lists key players, including Geltor, Perfect Day, Inc., The Every Co., Impossible Foods Inc., and others. The report includes a chapter on industry development, highlighting recent developments and partnerships, such as Nestlé’s launch of precision-fermented dairy protein powder and Perfect Day’s partnership with Unilever’s Breyers to produce lactose-free chocolate. Regional breakdowns are also provided, with a focus on North America, Europe, Asia Pacific, and other regions.

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Pioneering Developments in High-Performance Fermentation Ingredients

The Precision Fermentation Ingredients Market Report 2025-2032 by CoherentMI is a comprehensive analysis of the market, including key trends, upcoming technologies, industry drivers, challenges, regulatory policies, and company profiles. The report provides an in-depth assessment of the market, covering future trends, current growth factors, opinions, facts, and industry-validated market data forecast until 2032.

The report notes that the precision fermentation ingredients market is expected to grow from USD 4.65 billion in 2024 to USD 58.3 billion by 2031, with a compound annual growth rate (CAGR) of 35.6%. The report also provides insights on market segmentations, including product type, ingredient source, and application. Additionally, the report includes information on leading players, such as Perfect Day Inc., Motif Foodworks, Impossible Foods Inc., and The EVERY Company (Clara Foods), and provides a detailed analysis of their strategies and growth prospects.

The report also includes information on market trends, drivers, and challenges, as well as SWOT analysis, PEST analysis, and Porter’s five force analysis. The report is designed to help businesses make informed decisions and stay ahead of the competition.

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Euro-Investment Bank (EIB) injects €35 million into Formo, enabling the company to scale up its innovative animal-free cheese production.

German food-tech start-up Formo has secured a €35 million loan from the European Investment Bank (EIB) to accelerate the production of its animal-free cheese products. Formo, founded in 2019, uses micro-fermentation and precision fermentation technologies to create its products, including alt-dairy and egg-based products. The loan will enable Formo to further develop and scale its fermentation processes. Formo is currently undergoing regulatory approval for its products in the US and Europe. The company has already launched its micro-fermentation product line, with several flavors of its Frischhain product available in Germany and Austria. Raffael Wohlgensinger, founder of Formo, stated that the EIB’s support is a strong signal for European innovation and confirms the company’s strategy. The EIB loan is part of the InvestEU program, expected to unlock €372 billion in additional investment in new technologies by 2027. This follows Formo’s successful €61 million Series B funding round in September 2024, bringing the company’s total funding to over €135 million.

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Formo secures $36m in venture debt to accelerate the growth of its animal-free fermentation technology.

Formo, a Berlin-based startup, has received a €35 million venture debt loan from the European Investment Bank to scale its fermentation technologies. The company uses microbiology to express dairy proteins like casein via precision fermentation. However, they are using different technology in their first range of cheeses, where they grow natural occurring Aspergillus Oryzae (koji) to make cheese alternatives like Frischhain and Camembritz.

The company produces triple-digit tons of cheese alternatives monthly and plans to triple capacity in the next year. While koji does not offer the same stretchability and meltability performance as traditional casein or whey proteins, Formo plans to launch own consumer products with casein proteins this year.

Formo focuses on partnerships that leverage existing facilities rather than building its own manufacturing setup. On the regulatory front, the company is working on securing self-GRAS status for its casein proteins and plans to add harder cheese features like traditional cheese within its brand range in the near future. The cash injection follows a $61 million series B round and brings total funding to $139 million.

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A novel dairy company, Free French Cow, poised to scale up production at Ajinomoto’s state-of-the-art facility.

A French start-up, called Alt Dairy, is set to expand its animal-free dairy products production at the Ajinomoto plant, a Japanese healthcare and biopharmaceutical firm. Alt Dairy, which specialized in creating free dairy products free from cows milk, will establish a manufacturing center at Ajinomoto to scale up the production of plant-based casein, a whey protein analogue. This protein is commonly found in milk from cows and provides a similar flavor and texture experience in dairy-alternative milk and yogurt drinks.

The startup will use amino acids from genetically modified yeast at the Ajinomoto facilities to produce animal-free casein, allowing mass production and reaching a wider distribution network.

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French brand Bon Vivant secures US clearance for its animal-free whey protein products.

French startup Bon Vivant has received clearance to sell its animal-free whey protein in the US market. The company uses microorganisms to produce a whey protein that is identical to traditional whey protein, but without the need for animal milk. This innovation makes it possible to produce a vegan-friendly alternative to traditional whey protein, which is commonly used in sports nutrition and food products.

Bon Vivant’s product has been recognized by the US authorities, and the company has obtained the necessary approvals to launch its product in the US market. This marks a significant milestone for the company, which has been working to develop a sustainable and animal-friendly alternative to traditional whey protein.

The use of microorganisms to produce whey protein offers several benefits, including reduced environmental impact, lower carbon footprint, and a more sustainable production process. Bon Vivant’s animal-free whey protein is also suitable for individuals with dairy allergies or intolerances, making it a more inclusive option for the food industry. With its US clearance, Bon Vivant is poised to make a significant impact in the global protein market.

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The US lactoferrin market is also a prominent player Let me know if you’d like me to make any further changes!

Lactoferrin is a bioactive protein found in bovine and human milk, used in infant nutrition as well as human and animal nutrition. However, its production process is complex and requires a multi-stage process of extraction, purification, and drying, making it a high-value product. To address this, companies have turned to precision fermentation, using genetically programmed microorganisms to produce proteins without the need for livestock. All G, an Australian company, is one of the pioneers in this space and has achieved self-affirmed GRAS status for animal-free lactoferrin. Their product is designed to mimic the molecular structure and functional properties of bovine lactoferrin, allowing it to align with established consumer acceptance and regulatory pathways. The company plans to commercialize their product, with a production cost lower than that of dairy-derived lactoferrin. However, the challenges to commercialization include education and differentiating the product in a competitive space. The precision fermentation industry is expected to grow in 2025, with premium PF-derived ingredients expanding into mainstream applications driven by consumer demand for transparency, quality, and sustainability.

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The European Union is injecting €5 million into a pioneering fermentation project to revolutionize the production of plant-based cheese alternatives.

The European Union has invested €5 million in a fermentation project to develop better-tasting vegan cheese and kefir alternatives. The project aims to create plant-based products that are indistinguishable from their dairy counterparts in terms of taste, texture, and nutritional value. The funding will support research and development of novel fermentation technologies and microbial strains to improve the production process. The goal is to create a more sustainable and environmentally friendly alternative to traditional dairy products.

The project will focus on developing vegan cheese and kefir products that are not only more sustainable but also more appealing to consumers. The funding will also support the scaling up of production and commercialization of the new products. The project has the potential to revolutionize the dairy industry and provide a more sustainable and environmentally friendly option for consumers.

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OneGo submits GRAS notice to FDA for animal-free egg protein.

Finnish food tech startup Onego Bio has submitted a formal notice to the US Food and Drug Administration (FDA) regarding the safety of its precision-fermented egg protein, Bioalbumen. This protein is made using a fungal strain called Trichoderma reesei and is designed to be a more sustainable and environmentally friendly alternative to traditional eggs. Onego Bio plans to target the US market first, with plans to produce 2 million liters of protein per year, equivalent to the output of 6 million hens. The company has received $15.2 million in funding and has plans to submit dossiers for novel food approval in the EU, South America, and Asia. With its production process, the company claims to use 95% less land, 97% less water, and 89% fewer greenhouse gas emissions compared to traditional egg production. The company hopes to offer a competitive price point to chicken eggs and provide a sustainable solution to the food industry.

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Indian company Sterling Biotech is poised to launch construction of a cutting-edge dairy protein facility in Gujarat, leveraging fermentation technology.

Sterling Biotech, a joint venture between Perfect Day and Zydus, has started constructing the world’s first precision fermentation-based dairy protein manufacturing facility in Bharuch, Gujarat. The 27-acre facility is expected to be operational by the first quarter of 2026 and has already received substantial bookings for its capacity. The facility is designed to meet the growing global demand for sustainable food ingredients and will produce dairy proteins using precision fermentation technology, which is considered better for the environment and can meet diverse customer needs worldwide. Perfect Day CEO TM Narayan stated that this facility marks a significant milestone in transforming the global food industry. The company’s precision-fermented proteins have already gained recognition in various applications, and this new facility will enable it to scale its offerings, contributing to a more resilient and sustainable global food ecosystem.

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