Flagship Project 3

Integrated PAT

PAT for cell proliferation and recovery, including inline and intermittent monitoring to promote efficacy and safety attributes for timely cell product release

What ?

Integrated process analytic technologies (PAT) for cell proliferation and recovery, including in-line and intermittent monitoring to promote efficacy and safety attributes for timely cell product release

Why ?

Approaches to monitor and test the CQA – for example identity (phenotype), potency, efficacy, and purity of cells in real-time remains slow and cumbersome. Advancing this requires the development of new chemical, physical, microbiological, mathematical, and risk analysis tools collectively known as integrated process analytics technologies (PAT) so that the very cells that are expanded in vitro and intended to deliver to the patient can be analyzed prior to packaging and delivery.

What we do ?

FP3 develops and demonstrates process analytics technologies (PAT) and feedback control systems to monitor and modulate the appropriate release, recovery, and quantification of proliferating, adherent and suspended cells.

Highlights

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Publications

Ri Lu (NUS), Yan Shan Ang (NUS), Ka-Wai Cheung (SMART), Kai Yun Quek (SMART), Wei-Xiang Sin (SMART), Elizabeth Lee (SMART), Shir Lynn Lim (NUS), Lin-Yue Lanry Yung (NUS), Michael E. Birnbaum (MIT/SMART), Jongyoon Han (MIT/SMART), Lih Feng Cheow (NUS), Kerwin Kwek Zeming (SMART)

iSECRETE: Integrating Microfluidics and DNA Proximity Amplification for Synchronous Single-Cell Activation and IFN-𝜸 Secretion Profiling

Adv. Sci. 2024, 2309920; Aug 22, 2024
2024

SMART CAMP Authors

Hyungkook Jeon (MIT), Caleb R. Perez (MIT/SMART), Taeyoon Kyung (MIT), Michael E. Birnbaum (MIT/SMART), and Jongyoon Han (MIT/SMART)

Separation of Activated T Cells Using Multidimensional Double Spiral (MDDS) Inertial Microfluidics for High-Efficiency CAR T Cell Manufacturing

Analytical Chemistry; Jun 18, 2024
2024

SMART CAMP Authors

Nicholas Tan Kwan Zen (SMART), Kerwin Kwek Zeming (SMART), Teo Kim Leng (A*STAR-BTI), Mavis Loberas (NUS), Jialing Lee (NUS), Goh Chin Ren (SMART), Yang Dahou (SMART), Steve Oh (A*STAR-BTI), James Hui Hoi Po (NUS), Simon M. Cool (A*STAR-IMCB), Han Wei Hou (NTU), Jongyoon Han (MIT/SMART)

Scalable Mesenchymal Stem Cells Enrichment from Bone Marrow Aspirate View Article Online using Deterministic Lateral Displacement (DLD) Microfluidics Sorting

Lab on a Chip (Published online); Sep 01, 2023
2023

SMART CAMP Authors

Zheng Li (MIT), Jin Xue (MIT), Marc de Cea (MIT), Jaehwan Kim (MIT/SMART), Hao Nong (GF, Singapore), Daniel Chong (GF, Singapore), Khee Yong Lim (GF, Singapore), Elgin Quek (GF, Singapore) & Rajeev J. Ram (MIT/SMART)

A sub-wavelength Si LED integrated in a CMOS platform

Nature Communications, 14, Article number: 882; Feb 16, 2023
2023

SMART CAMP Authors

Iksung Kang, Marc de Cea, Jin Xue, Zheng Li, George Barbastathis, and Rajeev J. Ram

Simultaneous spectral recovery and CMOS micro-LED holography with an untrained deep neural network

Optica, 9 (10), pp. 1149-1155; Oct 01, 2022
2022

SMART CAMP Authors

Sharvaj Kubal, Elizabeth Lee, Chor Yong Tay, Derrick Yong

Multitrack Compressed Sensing for Faster Hyperspectral Imaging, Sensors

Sensors, 21 (15), 5034; Jul 24, 2021
2021

SMART CAMP Authors

Chayakorn Petchakupa, Paul Edward Hutchinson, Hui Min Tay, Sheng Yuan Leong, King Ho Holden Li, Han Wei Hou

Label-free quantitative lymphocyte activation profiling using microfluidic impedance cytometry

Sensors and Actuators B: Chemical, 339, 129864; Jul 15, 2021
2021

SMART CAMP Authors

Lingyan Gong, Chayakorn Petchakup, Pujiang Shi, Pei Leng Tan, Lay Poh Tan, Chor Yong Tay, and Han Wei Hou

Direct and Label-Free Cell Status Monitoring of Spheroids and Microcarriers Using Microfluidic Impedance Cytometry

Small, 17 (21), 2007500; Mar 24, 2021
2021

SMART CAMP Authors

Kerwin Kwek Zeming, Ri Lu, Kai Lee Woo, Guoyun Sun, Kai Yun Quek, Lih Feng Cheow, Chia-Hung Chen, Jongyoon Han, and Shir Lynn Lim

Multiplexed Single-Cell Leukocyte Enzymatic Secretion Profiling from Whole Blood Reveals Patient-Specific Immune Signature

Analytical Chemistry, 93 (10), pp. 4374–4382; Feb 18, 2021
2021

SMART CAMP Authors

Ng Ee Xien, Wang Ming, Neo Shu Hui, Tee Ching Ann, Chen Chia-Hung, Van Vliet Krystyn

Dissolvable gelatin-based microcarriers generated through droplet microfluidics for expansion and culture of mesenchymal stromal cells

Biotechnology Journal, 16 (3), 2000048; Oct 13, 2020
2020

SMART CAMP Authors

Taehong Kwon, Sung Hee Ko, Jean-François P. Hamel, and Jongyoon Han

Continuous Online Protein Quality Monitoring during Perfusion Culture Production Using an Integrated Micro/Nanofluidic System

Analytical Chemistry, 2020, 92 (7), pp. 5267-5275; Mar 13, 2020
2020

SMART CAMP Authors

Conference Presentations

Haoran Zhao, Xuanhe Zhao

"Mass-produce microcarrier for MSCs efficient expansion", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

Nicholas Ng Zhi Heng, Kerwin Kwek Zeming, Kai Yun Quek, Francesca Loraine Lim, Yunxin Chen, Chin Ren Goh, Faye Cheung Ka Wai, Sin Wei Xiang, Michael E. Birnbaum, Jongyoon Han

"Rapid Label-Free Profiling and CAR-T Biophysical Morphologies for Continuous Monitoring", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

Nicholas Tan Kwan Zen, Kerwin Kwek Zeming, Kai Yun Quek, Francesca Loraine Lim, Yunxin Chen, Chin Ren Goh, Nicholas Ng Zhi Heng, Michael E. Birnbaum, Jongyoon Han

"Rapid Assessment of immunological response in post-infusion CAR-T patients using biophysical WBC analysis", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

Kerwin Kwek Zeming, Kai Yun Quek, Wei-Xiang Sin, Ka-Wai Cheung, Michael E. Birnbaum, Jongyoon Han

"Rapid Label-free Microfluidic Assay for Profiling Functional Phenotypes of CAR T Cells: Towards Enhanced Manufacturing Control", Singapore Cell & Gene Therapy Conference 2023, Aug 04, 2023-Aug 05, 2023, Singapore

SMART CAMP Authors

2023

Zhi Xian Chan, Linxin Hou, Elizabeth Lee, Ching Ann Tee, and Derrick Yong

"Feature Analysis on Label-Free Multimodal Images of Mesenchymal Stromal Cells with Different Metabolic States", Microscopy Histopathology and Analytics 2022, Apr 24, 2022-Apr 27, 2022, Fort Lauderdale, Florida United States

SMART CAMP Authors

2022

N. Persits (MIT), C.C. Farruggio (MIT), Rajeev Ram (MIT), and K. Van Vliet (MIT)

"Metabolite Monitoring of Mesenchymal Stromal Cell Cultures by Spontaneous Raman Spectroscopy", Annual meeting of the American Institute of Chemical Engineers (AIChe), Nov 07, 2021-Nov 19, 2021, Virtual

SMART CAMP Authors

2021

Elizabeth Lee (SMART), Maciej Baranski (SMART), Marvin Chew (SMART), Wei Xiang Sin (SMART), Ka-Wai Cheung (SMART), Lisa Tucker-Kellogg (Duke-NUS), Derrick Yong (A*STAR-SIMTech), Michael Birnbaum (MIT), and George Barbastathis (MIT)

"Supervised Dimensionality Reduction of Single-cell Features from Label-free Multimodal Images for T Cell Subtype Classification", Frontiers in Optics/Laser Science 2021, Nov 01, 2021-Nov 04, 2021, Virtual, Washington, DC United States

SMART CAMP Authors

2021

J. Kim (MIT), N. Persits (MIT), and R. J. Ram (MIT)

"Automated microfluidic Raman spectroscopy system", 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS), Oct 10, 2021-Oct 14, 2021, Palm Springs, California, USA & Virtual

SMART CAMP Authors

2021

Yong, Zixin (SMART), Elizabeth Lee (SMART), Maciej Baranski (SMART), Lisa Tucker-Kellogg (Duke-NUS), and George Barbastathis (MIT)

"CycleGAN for Reflection and Aberration Artifact Removal in Quantitative Phase Images of Mesenchymal Stromal Cells", Novel Techniques in Microscopy, Optical Society of America, April 2021., Apr 12, 2021-Apr 16, 2021, Virtual

SMART CAMP Authors

2021

Kubal Sharvaj (NTU), Elizabeth Lee (SMART), Chor Yong Tay (NTU), and Derrick Yong (A*STAR-SIMTech)

"Multitrack Adaptive Compressive Hyperspectral Imaging for Cell Monitoring Applications", Frontiers in Optics 2020, Optical Society of America, Sep 14, 2020-Sep 17, 2020, Virtual, Washington, DC, United States

SMART CAMP Authors

2020

Lee, Elizabeth (SMART), Maciej Baranski (SMART), Zixin Yong (SMART), Lakshmi Venkatraman (SMART), Derrick Yong (A*STAR-SIMTech), and George Barbastathis (MIT)

"Multimodal Microscopy for Label-free Monitoring of Mesenchymal Stromal Cells", Frontiers in Optics 2020, Optical Society of America, Sep 14, 2020-Sep 17, 2020, Virtual, Washington, DC, United States

SMART CAMP Authors

2020