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Animal Cell Bioprocessing

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Transforming animal cell manufacturing processes

The Animal Cell Bioprocessing group enables research translations by facilitating scalable manufacturing and commercialisation of products made using animal cell culture. The products include recombinant proteins, viral vectors, vaccines and cultivated meats. We develop and innovate cell cultivation technologies that is part of the upstream biomanufacturing process. Our team has the expertise and technology platforms to enable cell culture media and bioreactor process development. With access to the expertise of other groups within BTI, the team is well-positioned to transform animal cell manufacturing processes, to meet the growing demands of the biomanufacturing industry.

Focus Areas

  • Continuous/ perfusion bioreactor cultures
  • Innovations in viral vector production and process development
  • Media and bioreactor process development for cultivated meats


Our Capabilities

Process Design

CULTURE MEDIA DEVELOPMENT

In-house serum free basal and feed media formulations
Batch, Fed-batch, Continuous and Perfusion Bioreactor Culture

BATCH, FED-BATCH, CONTINUOUS AND PERFUSION BIOREACTOR PROCESS DESIGN

Efficient, high-titer and scalable animal cell cultivation processes from 10 mL to 50 L
Multi-omics Analytics-based Media Development

MEDIA AND PROCESS OPTIMISATION USING MULTI-OMICS ANALYSIS

In partnership with BTI’s Analytical Science & Technology (AS&T) research groups
Control And Feed Strategies

Control & Feed Strategies

Optimized process parameter and feeding strategies to improve product yield and quality
Sampling and Monitoring

Sampling & Monitoring

Automated/Manual sampling of bioreactor cultures for monitoring of critical process parameters
Aseptic Handling and Bioreactor Operation

Aseptic Handling & Bioreactor Operation

Aseptic manipulation throughout seed-train and bioreactor process

These capabilities enable research translation by facilitating scalable manufacturing and commercialization of products made using animal cell culture, such as recombinant proteins, viral vectors, vaccines and cultivated meats.

Our Technologies

ACB Main Capability

Our team develops technologies to enable the use of animal cells for different applications. Our in-house media component screening platform has enabled us to develop several serum-free cell culture media formulations for various cultivation modes.

Examples of our Technologies

Some technologies we have developed are listed below:

  • Suspension bioreactor process for adeno-associated viral vector production
  • GLUL-KO HEK293 bioproduction system
  • Proprietary serum-free media formulations for CHO, HEK, NS0, chicken and fish cell lines
  • Media component screening and optimization platform and know-hows
  • Optimised transient gene expression processes
  • Animal virus propagation processes
  • Bioreactor set-up and process control strategies for fed-batch and perfusion cultures
  • Method of increasing protein yield of a serum free mammalian cell culture using maltose as a carbohydrate supplement
  • Production of Alpha-1-antitrypsin, Alkaline phosphatase and Erythropoietin

Illustration of GLUL-KO HEK293 bioproduction system
GLUL-KO HEK293 bioproduction system that enables the production of recombinant proteins with decent 1 g/L titer in a human cell line.

Illustration of rAAV expression technology
Optimised process for rAAV production using Triple plasmid transfection with PEI, that does not require media replacement after transfection, and is validated in 2L stirred tank bioreactors.

OUR TRACK RECORD

Featured Publications

  • Evan Tan, Cara Sze Hui Chin, Zhi Feng Sherman Lim, Say Kong Ng (2021) HEK293 Cell Line as a Platform to Produce Recombinant Proteins and Viral Vectors. Frontiers in Bioengineering and Biotechnology 9: 796991
  • Yin Ying Ho, Hao Kim Lu, Zhi Feng Sherman Lim, Hao Wei Lim, Ying Swan Ho, Say Kong Ng (2021) Applications and Analysis of Hydrolysates in Animal Cell Culture. Bioresources and Bioprocessing 8(1): 93
  • Alison P. Lee, Yee Jiun Kok, Meiyappan Lakshmanan, Dawn Leong, Lu Zheng, Hsueh Lee Lim, Shuwen Chen, Shi Ya Mak, Kok Siong Ang, Neil Templeton, Taha Salim, Xiaona Wei, Eric Gifford, Andy Hee‐Meng Tan, Xuezhi Bi, Say Kong Ng, Dong‐Yup Lee, Wai Lam W. Ling and Ying Swan Ho (2021) Multi‐omics profiling of a CHO cell culture system unravels the effect of culture pH on cell growth, antibody titer, and product quality. Biotechnology and Bioengineering 118(11): 4305-4316
  • Christine Lin Chin, Justin Bryan Goh, Harini Srinivasan, Kaiwen Ivy Liu, Ali Gowher, Raghuvaran Shanmugam, Hsueh Lee Lim, Matthew Choo, Wen Qin Tang, Andy Hee-Meng Tan, Terry Nguyen-Khuong, Meng How Tan and Say Kong Ng (2019) A human expression system based on HEK293 for the stable production of recombinant erythropoietin. Scientific Reports 9: 16768
  • Dawn Sow Zong Leong, Brian Kah Hui Teo, Janice Gek Ling Tan, Hayati Kamari, Yuan Sheng Yang, Peiqing Zhang and Say Kong Ng (2018) Application of maltose as energy source in protein-free CHO-K1 culture to improve the production of recombinant monoclonal antibody. Scientific Reports 8: 4037

The Team

Ng Say Kong

Dr Ng Say Kong

ng_say_kong@bti.a-star.edu.sg
Senior Principal Scientist I

PhD in Molecular Engineering of Biological and Chemical Systems (2006) National University of Singapore, Singapore

Research Focus / Interest

  • Culture medium and bioreactor process developments to improve the bioproduction using animal cells
  • Development of perfusion culture processes
  • Recombinant protein expression in mammalian cells
  • Production of viral vaccines and viral vectors
  • Reducing upstream production costs for cultivated meats

Eunice Leong

Dr Eunice Jiayu Leong

eunice_leong@bti.a-star.edu.sg
Senior Scientist I

PhD in Chemical Engineering (2018), University of Illinois at Urbana-Champaign, USA

Research Focus / Interest

  • Bioreactor process development for producing biologics from animal cell cultures
  • Recombinant protein expression in mammalian cells

Evan Tan

Dr Evan Tan

evan_tan@bti.a-star.edu.sg
Senior Scientist I

PhD in Molecular and Cell Biology (2017), National University of Singapore, Singapore

Research Focus / Interest

  • Recombinant adeno-associated virus (rAAV) production
  • Engineering of mammalian cells for rAAV production

Quek Jun Ping

Dr Quek Jun Ping

quek_jun_ping@bti.a-star.edu.sg
Scientist

PhD in Molecular and Structural Biology (2022), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Research Focus / Interest

  • Culture medium and bioreactor process developments for cultivated meats
  • Production of viral vaccines

Tan Yu Xuan

Dr Tan Yu Xuan

tan_yu_xuan@bti.a-star.edu.sg
Scientist

PhD in Developmental Neuroscience (2023), Francis Crick Institute, King’s College London, UK

Research Focus / Interest

  • Cell-type differentiation and bioreactor process development for cultivated meats

Viknesvaran Selvarajan

Dr Viknesvaran Selvarajan

viknesvaran_selvarajan@bti.a-star.edu.sg
Scientist

PhD in Cancer Biology (2016), National University of Singapore, Singapore

Research Focus / Interest

  • Viral vector production and purification
  • Allogeneic NK cell production process development

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