Center for Biosystems

Center for sensing technologies

Project aim: Project aims are focused on development of plant-based edible microcarriers and scaffolds for use in cellular agriculture i.e. cultivated meat tissue engineering. The project is jointly implemented by the Serbian partners Biosense Institute and Faculty of Technology University of Novi Sad, and German Fraunhofer Institute for Process Engineering and Packaging (Fraunhofer IVV).
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About the project: Cultivated meat &#8211; CM (meat produced in cultures of animal cells) promises enormous benefits for the animal welfare and the environment, and offers tremendous potential for feeding the growing world population (projected to reach 9.7 billion by 2050 which will require food production to increase by 70%). Culturing of skeletal muscle cells for CM production is complex process and it can be divided into 2 stages with distinct goals: Stage 1 (S1) proliferation phase &#8211; with the goal to obtain maximum number of cells from the starting batch of cells (whether myoblasts and skeletal muscle resident stem cells i.e. satellite cells); Stage 2 (S2) differentiation and maturation stage where cells are seeded onto scaffolds, allowed to mature into the skeletal muscle cells and coerced into maximum protein production (hypertrophy stage). Each of these phases has specific requirements for the design of media, scaffolds, and bioreactors.
Since the microcarriers (MC)/scaffold constitute a main component of the final product (MCs in minced meat, 3D scaffold in “steak-like” products), these structural components should be edible and resemble the composition and properties of meat. Plant-based materials are ideal components for this use, since they can be porous, food-grade, inexpensive and can offer good anchor points for cell adherence. n addition, the combination of different plant-based materials improves the structure, better imitating the fibrous and juicy texture of meat. Such “hybrid” products using both plant- and animal-sourced components are estimated to be the first of cellular agriculture products to enter the commercial arena.
For all the above reasons, the focus of this project is on the plant-based scaffold elements that will be used in both phases of the KM bioprocess.

Senior research associate in the field of natural/mathematical sciences - biology

Ivana Gađanski

Nejra Omerović is a Research Assistant at the BioSense Institute. She received her BSc and MSc degree in 2015 and 2017, respectively, from the Faculty of Technology, University of Novi Sad, Serbia, where she is currently a PhD student at the Department of Materials engineering. From October 2015 to September 2016 she did an internship at AGFA-Gevaert NV, Mortsel, Belgium, where she worked at the Inkjet Ink Development Department. Her current research activities are focused on biopolymers and their nanocomposites.

Nejra Omerović

Jovana Stanojev is a research assistant and a PhD student at the Faculty of Technology, University of Novi Sad. She studied materials engineering. She is working towards finishing her PhD thesis. Topic of her PhD thesis is "Development of uncooled infrared detector based on lead selenide". Her current research focuses are development of new materials for sensors, nanomaterials and nanomembranes, microfluidics, development of organ-on-a-chip platforms, cell culturing.

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Jovana Stanojev

Teodora Knežić joined BioSense Institute as Junior Researcher in the Center for Biosystems. Teodora has a bachelor's and master's degrees in Molecular Biology and she is currently a Ph.D. student of Molecular Biology at the Faculty of Sciences, University of Novi Sad, Serbia, with Dr Ivana Gađanski as the mentor. During her studies she volunteered in the Laboratory for Biochemistry and Molecular Biology at the Faculty of Sciences where was involved in the analyses of gene expression of the European corn borer using techniques for RNA isolation, gel electrophoresis, cDNA synthesis, end-point and qPCR analysis. Also, at the Institute for Nuclear Sciences Vinča she was trained to work with human cancer cell cultures, perform viability assays and flow cytometry. Teodora has just completed a 3 month specialization practice in BioSense as well. Her main research interests are biosensor development and molecular techniques for pathogen detection, cellular agriculture and development of lab-on-a-chip platforms.

Teodora Knežić

Mila Djisalov has a BSc in Biochemistry and a Master’s degree in Molecular Biology. She is currently a Ph.D. Student of Biochemistry at the Faculty of Sciences in Novi Sad and a Junior Researcher in BioSense Institute. Her main research interests are biosensor development and molecular tools for pathogen detection, cellular agriculture, and the development of lab-on-a-chip platforms. Mila is also one of the co-founders of the student group The BioSense Alt. Protein Project formed at the BioSense Institute.

MIla Đisalov

Ivana Gadjanski PhD is Research Associate Professor at BioSense Institute, University of Novi Sad, Serbia. She graduated from the Faculty of Biology, University of Belgrade as the 1st in the class (2003). She obtained PhD in Neuroscience (summa cum laude -oral presentation) from Georg-August University &amp; Max Planck Institute for Biophysical Chemistry, Goettingen, Germany (2007) and worked as a postdoctorate researcher at Ludwig-Maximillian University, Munich, Germany. Ivana then turned to the bioengineering field and spent a year as a Fulbright Visiting Scholar at Columbia University, USA - Lab for Stem cells and Tissue Engineering (Head: prof. Gordana Vunjak-Novakovic). In BioSense, she is moving further into the cellular agriculture field - developing solutions for cultivated meat. She also works on biosensing for agrifood, biomedicine and environmental monitoring. Ivana is a grantee of the Good Food Institute and coordinator of Horizon2020 projects DRAGON GA 810755 and IPANEMA GA 872662.

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BILATERAL

Cellular agriculture refers to production of agricultural products using cell cultures. Cellular agriculture products are part of the larger group called Alternative proteins (alt.pro). Alt.pro are proteins that can act as substitutes for traditional animal‐based food. Generally, alt.pro are classified based on the source into: Plant-based, Insect-based and Cultured meat that is produced by cellular agriculture methods. Majority of the methods for cellular agriculture stem from the tissue engineering and biomedical field, while the application of the products generated by cellular agriculture falls predominantly into the food science.

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Cultured meat is the main type of alternative proteins BioSense addresses. One of the main challenges for scaling up the cultured meat production to the industry levels is concerning the overall costs of production. The highest portion of costs (up to 80%) for cultured meat production is for the cell culture medium and fetal calf or bovine serum. The challenge to decrease expenses is not only in designing low-cost cell culture medium formulations, but also in developing methods to optimize the bioreactor design, instrumentation and to include monitoring features via sensors for the maximum cell production capacity per unit medium volume.

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In that sense, we focus our research on optimizing procedures for generating cellular products, and we closely collaborate with the Center for sensing technologies regarding development of sensors for monitoring of key parameters in cultured meat bioprocess: Biomass concentration, a key variable in cell cultures and Concentration of key nutrients – glucose and glutamine and their main metabolites, lactate and ammonia, that can inhibit the cell growth. Sensors are tested using "miniaturized" bioreactors i.e. microfluidic model and Lab-on-a-chip (LOC) principle, which will be scaled up to the bioreactors of larger volumes.

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Projects:

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REALSENSE1 - Monitoring of cell culture parameters using sensors for biomass and nutrients/metabolites in media: Lab-on-a-Chip (LOC) approach, 2019-2021; Good Food Institute Inaugural Competitive Grant Program.

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REALSENSE2 - From lab-on-a-chip to custom bioreactor: scale up modeling study, 2020-2022 Good Food Institute Competitive Grant Program

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<img class="alignnone wp-image-1459 size-large" src="https://api.biosens.rs/wp-content/uploads/2021/06/31-1024x644.png" alt="" width="1024" height="644" />

Cellular agriculture

Development of plant-based edible microcarriers and scaffolds for use in cellular agriculture i.e. cultivated meat tissue engineering

Centar za Biosisteme

Centar za senzorske tehnologije

Cilj projekta: Ciljevi ovog projekta fokusirani su na razvoj jestivih mikronosača tj. 3D nosača za ćelije u cilju primene u ćelijskoj poljoprivredi tj. proizvodnji kultivisanog mesa putem tkivnog inženjerstva, na čemu zajednički rade srpski Institut Biosens i nemački Fraunhofer institut za procesno inženjerstvo i pakovanje (Fraunhofer IVV).
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O projektu: Kultivisano meso &#8211; KM (meso proizvedeno u kulturama životinjskih ćelija) obećava ogromne koristi za dobrobit životinja i životnu sredinu, i nudi neizmerne mogućnosti za ishranu rastuće svetske populacije (za koju se predviđa da će dostići 9,7 milijardi do 2050. godine, što će zahtevati da se proizvodnja hrane poveća bar za 70%). Kultivisanje ćelija skeletnih mišića za proizvodnju KM predstavlja kompleksan proces koji se sastoji iz dve faze sa različitim ciljevima: Faza 1 (F1) faza proliferacije &#8211; sa ciljem da se dobije maksimalan broj ćelija iz početne serije ćelija (bilo da su to mioblasti i matične ćelije rezidualnih skeletnih mišića, tj. satelitske ćelije); Faza 2 (F2) faza diferencijacije i maturacije u kojoj se ćelije seju na skafolde, maturiraju u ćelije skeletnog mišića i u kojoj je indukovana maksimalna proizvodnja proteina (hipertrofijska faza). Svaka od ovih faza ima specifične zahteve za dizajn medijuma, skafolda i bioreaktira. 
S obzirom da mikronosači (MN) i skafoldi predstavljaju glavnu komponentu konačnog proizvoda (MN u mlevenom mesu, 3D skafoldi u „steak-like“ products), ove strukturne komponente trebalo bi da budu jestive i po sastavu i svojstvima slične mesu. Biljni materijali su idealne komponente za ovu upotrebu, jer mogu biti porozni, jestivi, jeftini i sa mogućnošću adhezije ćelija. Pored toga, kombinacija različitih biljnih materijala poboljšava strukturu, bolje imitirajući vlaknastu i sočnu strukturu mesa. Procenjuje se da će takvi „hibridni“ proizvodi, koji koriste komponente i biljnog i životinjskog porekla, biti prvi proizvodi ćelijske poljoprivrede koji će ući u komercijalnu upotrebu. 
Iz svih gore navedenih razloga, fokus ovog projekta je na elementima skafolda od biljnih proteina koji će se koristiti u obe faze bioprocesa kojim se dobija KM.

 Viši naučni saradnik u oblasti prirodno-matematičke nauke - biologija

Nejra Omerović je zaposlena na Institutu BioSens kao istraživač saradnik. Osnovne i master studije završila je 2015., odnosno 2017. godine na Tehnološkom fakultetu, Univerzitet u Novom Sadu, Srbija, gde je trenutno sudent doktorskih studija na Katedri za Inženjerstvo materijala. Od oktobra 2015. do septembra 2016. godine obavljala je stručnu praksu u kompaniji AGFA-Gevaert NV, Mortsel, Belgija, gde je radila na Departmanu za razvoj inkdžet mastila. Njene trenutne istraživačke aktivnosti usmerene su na biopolimere i njihove nanokompozite.

Jovana Stanojev je istraživač saradnik i student doktorskih studija na Tehnološkom fakultetu u Novom Sadu, na Univerzitetu u Novom Sadu. Studirala je inženjerstvo materijala i trenutno završava svoju doktorsku disertaciju. Tema njene doktorske disertacije je "Razvoj nehlađenog infracrvenog detektora na bazi olovo selenida". Njeno istraživanje se fokusira na razvoj novih materijala za senzore, nanomaterijala i nanomembrana, mikrofluidiku, uzgajanje ćelijskih kultura i razvoj platformi organ-na-čipu.

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Teodora Knežić je zaposlena kao istraživač-pripravnik na Institutu BioSens, u Centru za biosisteme. Teodora je završila osnovne i master akademske studije molekularne biologije i trenutno pohađa doktorske akademske studije molekularne biologije na Prirodno-matematičkom fakultetu Univerziteta u Novom Sadu, pod mentorstvom dr Ivane Gađanski. Tokom svojih studija volontirala je u Laboratoriji za biohemiju i molekularnu biologiju na Prirodno-matematičkom fakultetu gde je vršila analizu genske ekspresije kukuruznog plamenca koristeći metode za izolaciju RNK, gel elektroforezu, sintezu cDNK, end-point i qPCR analizu. Takođe, na Institutu za nuklearne nauke Vinča obučena je za rad sa humanim ćelijskim linijama, izvođenje eseja vijabilnosti i protočnu citometriju. Teodora je završila i tromesečno fakultativno stručno usavršavanje na Institutu BioSens. Njen glavni fokus istraživanja je razvoj biosenzora i molekularnih tehnika za detekciju patogena, ćelijska poljoprivreda i razvoj lab-on-a-chip platformi.

Mila Đisalov je diplomirani biohemičar i master molekularne biologije. Trenutno je student doktorskih studija biohemije na Prirodno-matematičkom fakultetu u Novom Sadu i istraživač-pripravnik na Institutu BioSens. Njena glavna istraživačka interesovanja vezana su za razvoj biosenzora i molekularnih alata za detekciju patogena, ćelijska poljoprivreda i razvoj laboratorija na čipu. Mila je takođe jedan od osnivača studentske grupe The BioSense Alt. Protein Project, osnovane na Institutu BioSens.

Mila Đisalov

Dr Ivana Gađanski je viši naučni saradnik na Institutu Biosens, Univerzitet u Novom Sadu, Srbija. Diplomirala je na Biološkom fakultetu Univerziteta u Beogradu kao prva u klasi (2003). Doktorirala je iz neuronauka (ocena summa cum laude – usmena odbrana) na Georg-August Univerzitetu i Institutu za biofizičku hemiju Maks Plank, Getingen, Nemačka (2007) i radila na posledoktorskim studijama na Univerzitetu Ludvig-Maksimilijian, Minhen, Nemačka. Ivana se zatim posvetila oblasti bioinženjerstva i provela godinu dana kao Fulbrajt stipendista – gostujući istraživač na Univerzitetu Kolumbija, Njujork, SAD u Laboratoriji za matične ćelije i tkivno inženjerstvo (rukovodilac: prof. Gordana Vunjak-Novaković). U BioSensu radi na bioinženjerstvu u oblasti ćelijske poljoprivrede - razvija rešenja za kultivisano meso. Takođe radi na razvoju biosenzora za monitoring u oblasti poljoprivrede, biomedicine i zaštite životne sredine. Ivana je stipendista Instituta za dobru hranu i koordinator Horizont2020 projekata DRAGON GA 810755 i IPANEMA GA 872662.

BILATERALNI

Ćelijska poljoprivreda se bavi proizvodnjom poljoprivrednih proizvoda pomoću kultura ćelija i ulazi u oblast tzv. alternativnih proteina (alt.pro). Alt. pro su proteini koji se mogu koristiti kao zamena za uobičajene životinjske proteine. Alt.pro mogu biti biljnog porekla, mogu biti i od insekata, a posebna grupa proteina označena kao kultivisano meso se dobija pomoću metoda ćelijske poljoprivrede. Većina metoda ćelijske poljoprivrede potiče iz biomedicine i tkivnog inženjerstva, dok primene i upotreba proizvoda dobijenih ćelijskom poljoprivredom pretežno pripadaju oblasti tehnologije hrane.

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Kultivisano meso je osnovni tip alternativnih proteina kojim se bavi Institut BioSens. Jedan od glavnih izazova za skaliranje tj. industrijsku proizvodnju kultivisanog mesa su ukupni troškovi proizvodnje. Najveći deo troškova (čak do 80%) za kultivaciju mesa potiče od cene hranljivog medijuma i fetalnog goveđeg seruma, neophodnih za gajenje ćelija u kulturi. Troškovi se mogu smanjiti ne samo jeftinijim formulacijama hranljivog seruma, već i putem metoda optimizacije dizajna bioreaktora i instrumenata i naročito upotrebom senzorskog sistema praćenja ključnih parametara, da bi se postigla maksimalna produkcija ćelija po jedinici zapremine medijuma.

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U tom smislu se fokusiramo na optimizaciju procedura za dobijanje ćelijskih produkata, a u bliskoj saradnji sa Centrom za senzorske tehnologije razvijamo i senzore za praćenje ključnih parametara u bioprocesu kultivacije mesa: koncentracija biomase, što je osnovni parametar ćelijske kulture i koncentracija osnovnih hranljivih materija – glukoze i glutamina i njihovih glavnih metabolita, laktata i amonijaka, koji mogu inhibirati rast ćelija. Senzori se testiraju na „minijaturizovanim“ bioreaktorima tj. mikrofluidnim modelima uz primenu „Laboratorija na čipu“ principa, koji će se zatim skalirati na bioreaktore većih zapremina.

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Projekti:

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REALSENSE1 - Monitoring of cell culture parameters using sensors for biomass and nutrients/metabolites in media: Lab-on-a-Chip (LOC) approach, 2019-2021; Good Food Institute Inaugural Competitive Grant Program.

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REALSENSE2 - From lab-on-a-chip to custom bioreactor: scale up modeling study, 2020-2022 Good Food Institute Competitive Grant Program

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<img class="alignnone wp-image-1459 size-large" src="https://api.biosens.rs/wp-content/uploads/2021/06/31-1024x644.png" alt="" width="1024" height="644" />

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Ćelijska poljoprivreda

Razvoj biljnih jestivih mikronosača i skafolda tj. 3D nosača za ćelije u cilju primene u ćelijskoj poljoprivredi tj. proizvodnji kultivisanog mesa putem tkivnog inženjerstva

Razvoj biljnih jestivih mikronosača i skafolda tj. 3D nosača za ćelije u cilju primene u ćelijskoj poljoprivredi tj. proizvodnji kultivisanog mesa putem tkivnog inženjerstva

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CBS

CST