Biomanufacturing Technology

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Biomanufacturing Technology

Driving the future of biomanufacturing through novel devices, systems, biomaterials and products

The Biomanufacturing Technology Group has two focuses: (1) biomanufacturing devices and systems innovation and (2) biomaterials biomanufacturing and tissue product innovation. We specialize in developing efficient and scalable biomanufacturing systems, focusing on bioreactor aseptic fluid transfer and management, and sample preparation and monitoring. We develop innovative manufacturing platforms and lean processes to extract precious natural biomaterials from various cells and tissues. We convert these biomaterials to amenable forms for different application needs. We also innovate key biofabrication approaches and work on lab-based manufacturing of various novel biomimetic tissue products. Together, we provide end-to-end solutions, encompassing biomaterials transformation to bioprocessing device fabrication, applicable to cell therapy, biologics, regenerative medicine, cellular agriculture including cultivated meat, synthetic biology and drug development.

Focus Areas

• Novel biomanufacturing devices and systems (e.g., single-use technologies, bioreactors, automated bioprocessing system, Organ-on-Chips, fluid control and management, sterile connectors, automated sterile sampler, closed cartridges and manifolds, process integration) for advancing manufacturing of cell therapy, biologics, and future food.
• Innovative platforms and lean processes to extract precious natural biomaterials from various cells and tissues including from various species of animals, plants, bacteria, algae, and fungi.
• Conversion of biomaterials to various amenable forms (micro/macro beads, fibres, sheets) and configurations - scaffolds, hydrogels, substrates, bioinks and coatings etc.
• Biomanufacturing of novel biomimetic cell and tissue products for cultivated meat, regenerative medicine, and cell therapy.

Our Capabilities

Cell Processing

Investigate different cell processing technologies from 2D/3D cell expansion to cell stimulation by using both single-use technologies and automated systems.

ASEPTIC FLUID HANDLING & MANAGEMENT

Sterile and effective fluid handling steps with customised closed manifolds to accommodate diverse biomanufacturing requirements and applications.

AUTOMATED SAMPLE PREPARATION & MONITORING

Sample preparation with real-time product monitoring and integration of automated modules for dilution, dispensing, and protein measurement. Implementing advanced Process Analytical Technologies (PAT) in bioprocessing.

TISSUE BIOMANUFACTURING & CHARACTERIZATION

Developing biomimetic functional tissue products starts from material selection to fabrication, followed by detailed biomaterial/scaffold physical-chemical characterisations and rigorous in vitro/in vivo validations.

BIOFABRICATION PLATFORMS

Customise biomaterials to create desired shapes and configurations at scale. Biofabrication methods like bioprinting, electrospinning, stereolithography, roll-to-roll (R2R) printing, and freeze-drying enable applications in cell therapy, cellular agriculture, regenerative medicine and synthetic biology.

TUNABLE NATURAL HYDROGEL FORMULATIONS

Transform naturally sourced biomaterials into versatile forms of hydrogel for diverse applications, including regenerative medicine, cell therapy, drug screening and cultivated meat. These hydrogels can be shaped into coatings, microbeads, fibres and sheets of varying sizes from a few millimetres to a few centimetres.

DEVELOPMENT OF MICROTISSUE MODELS

Developing cost-effective microtissue models like spheroids/organoids and organ-on-chip platforms. These models mimic organ function using 3D microtissues/organ constructs, benefiting drug testing, disease modelling, alternative proteins and biological studies.

Our Technologies

“cGMP-IN-A-BOX” - AUTOMATED AND FUNCTIONALLY CLOSED BIOREACTOR SYSTEM FOR DECENTRALIZED CELL THERAPY MANUFACTURING

• Automated: Automated cell and medium inoculation, medium change, sampling and harvesting
• Functionally closed: Minimum contamination risk in room condition
• Scalable: Direct process transfer from process development to manufacturing

AUTOMATED ASEPTIC SAMPLER SYSTEM FOR ONLINE SMALL-VOLUME CULTURE SAMPLING

• Automated and Aseptic: Programmable tubing and and valve system tested for aseptic culture sampling during cell therapy manufacturing
• Small volume sampling with zero dead-volume: Sample volume as low as 20µl
• Integrable: Able to be integrated with different culture vessels or bioreactor systems

DECELLULARIZED EXTRACELLULAR MATRIX (DECM) REACTOR

• Scalable, Clean and Compact: Able to decellularize animal, human, plant and fungi samples (50-400 g)
• Process Monitoring: Process controls employed to regulate the progress and optimize yield
• Application Focus: Cultivated meat and regenerative medicine applications

EXTRACELLULAR MATRIX (ECM) SPONGE

• Biofabrication: Enables biofabrication of natural biomaterial into a porous sponge-like scaffold for tissue manufacturing applications
• Controllable: Range of pore size and the degradation rate of the cell culture scaffolds adjustable to match structure and regenerative speed of the different tissues

EDIBLE SCAFFOLDS FOR CULTIVATED MEAT

• Microarchitecture: Access and exploit microarchitecture and morphologies in plants
• Applicable: To various species, including plants, fungi, and fruits, highly versatile
• Configurable: Readily shaped into various forms and sizes to fit to culture configurations

Our Track Record

Featured publications:

• Wee Swan Yap, Deepak Choudhury and Ratima Suntornnond (2023) Towards biomanufacturing of cultured meat. Trends in Biotechnology 41(3):292-294
• Sixun Chen, Ahmad Amirul Bin Abdul Rahim, Who‑Whong Wang, Rachael Cheong, Akshaya V. Prabhu, Jerome Zu Yao Tan, May Win Naing, Han Chong Toh & Dan Liu (2022) In-Situ Scalable Manufacturing of Epstein–Barr Virus-Specific T-Cells Using Bioreactor with an Expandable Culture Area (BECA). Scientific Reports 12: 7045
• Ying Ying Wu, Jia Sheng Zach Lee, Sixun Chen and Dan Liu (2022) Sterile Fluid Transfer for Cell Therapy Manufacturing-The Value of Multiple-Use Aseptic Connector. Frontiers in Bioengineering and Biotechnology-Biomaterials 9: 806677
• Weng Wan Chan, Fang Yu, Quang Bach Le, Sixun Chen, Marcus Yee and Deepak Choudhury (2021) Towards Biomanufacturing of Cell-Derived Matrices International Journal of Molecular Sciences 22(21): 11929
• Ying Y Wu, Dan Liu and May W Naing (2021) Development of A Closed and Automated Bioreactor Technology for Cell Therapy Manufacturing - A Sharing of Our Journey Regenerative Medicine 15(12) Commentary
• Harish K. Handral , Shi Hua Tay, Weng Wan Chan and Deepak Choudhury (2020) 3D Printing of cultured meat products. Critical Reviews in Food Science and Nutrition 1-10
• Liu Dan, Chen Sixun and May Win Naing (2020) A Review of Manufacturing Capabilities of Cell Spheroid Generation Technologies and Future Development. Biotechnology and Bioengineering 118(2): 542-554
• Deepak Choudhury, Marcus Yee, Zach Lee Jia Sheng, Ahmad Amirul and May Win Naing (2020) Decellularization systems and devices: State-of-the-art. Acta Biomaterialia 115: 51–59

Landmark Patent & IP:

• Connector Component And Connector System (2022)
• Liquid Sampling Device (2022)
• Methods and apparatus for decellularization of biological tissues and organs (2022)
• Device for cell culture and method for culturing cells (2018)
• Method And System For Monitoring Activity Of An Animal (2015)

The Team

Dr Deepak Choudhury

[email protected] Principal Scientist I

PhD in Bioengineering (2012), National University of Singapore, Singapore

Research Focus / Interest

• Biomanufacturing process/platform development for biomaterials extraction from animals, plants, bacteria, algae, and fungi
• Development of scaffolds/substrates/inks for regenerative medicine and cultivated meat manufacturing
• Scale-up spinning, patterning, and printing of biomaterials
• Development of tissue manufacturing devices and platforms including Organ-on-Chips

Dr Liu Dan

[email protected] Senior Scientist II

PhD in Tissue Engineering (2012), Nanyang Technological University, Singapore

Research Focus / Interest

• Single-use technologies
• Devices for scaling-up and –out of cell therapy and cell-derived product manufacturing,
• Devices for biological, bioprocessing and biomedical applications

Dr Chen Sixun

[email protected] Senior Scientist I

PhD in Chemical Biology (2017), Harvard University, United States of America

Research Focus / Interest

• Process optimization and validation in bio-manufacturing
• Scaling of bioprocess for manufacturing

Dr Le Quang Bach

[email protected] Senior Scientist I

PhD in Biomedical Engineering (2018), University of Maastricht, The Netherlands

Research Focus / Interest

• Developing cell-derived matrix platforms for tissue manufacturing
• Development of biomaterial formulations/hydrogels/bioinks
• Medical devices for orthopaedic applications

Dr Ratima Suntornnond

[email protected] Scientist

PhD in Tissue engineering (2018), Nanyang Technological University, Singapore

Research Focus / Interest

• Development of natural and synthetic biomaterial formulations, hydrogels and bioinks
• Development of scaffolds, substrates and hydrogels for cultured meat
• Bioprinting/biofabrication processes for cellular agriculture and tissue engineering

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