Microfluidics cell sorting
Cell sorting is critical for many applications ranging from stem cell research to cancer therapy. Isolation and fractionation of cells using microfluidic platforms have been flourishing areas of development in recent years. The need for efficient and high-throughput cell enrichment, which is an essential preparatory step in many chemical and biological assays, has led to the recent development of numerous microscale separation techniques. We have pioneered some inertial microfluidic platforms for various applications, including separation of circulating tumor cells (CTCs) from blood, enrichment of malaria parasite and fractionation of mesenchymal stem cells (MSCs).
Majid E. Warkiani, Guofeng Guan, Khoo Bee Luan, Wong
Cheng Lee, Ali Asgar S. Bhagat, Daniel Shao-Weng Tan, Soo Chin Lee, Wan Teck
Lim, Peter C Y Chen, Chwee Teck Lim, Jongyoon Han. "Slanted spiral
microfluidics for ultra-fast, label-free circulating tumor cells
isolation", Lab on a chip, 2014. [PDF]
Hanwei Hou, Majid E. Warkiani, Khoo Bee Luan, Zi Rui
Li, Daniel Shao-Weng Tan, Wan-Teck Lim, Jongyoon Han, Ali Agar S. Bhagat and
Chwee Teck Lim. “isolation and retrieval of circulating tumor cells using
centrifugal forces", Scientific Reports (Nature Publishing Group)
3,1259, 2013. [PDF]
- Bee Luan Khoo, Majid E. Warkiani, Daniel Shao-Weng Tan, Ali Asgar S. Bhagat, Darryl Irwin, Alvin S.T. Lim, Kiat Hon Lim, Wan-Teck Lim, Yoon Sim Yap, Soo Chin Lee, Ross A. Soo, Priscilla Hunt, Jongyoon Han, Chwee Teck Lim" Clinical validation of an ultra high-throughput microfluidic device for detection and enrichment of viable rare circulating tumor cells in blood", PlosOne, 2014, Accepted.
- Majid E. Warkiani, Bee Luan Khoo, Daniel Shao-Weng Tan, Ali Asgar S Bhagat, Wan-Teck Lim, Yoon Sim Yap, Soo Chin Lee, Ross A Soo, Jongyoon Han, Chwee Teck Lim. " An ultra-high-throughput spiral microfluidic biochip for the enrichment of circulating tumor cells ", Analyst, 2014.
Isopore membranes are versatile structures with numerous potential and realized applications in various fields of science, such as micro/nano-filtration, cell separation and harvesting, controlled drug delivery, optics, gas separation and HPLC. Recent advances in micro/nano fabrication techniques and material synthesis provide novel methods towards controlling the detailed microstructure of membrane materials, allowing fabrication of membranes with well defined pore size and shape. We have pioneered new methods for fabrication of polymeric/metallic isopore filters for various applications such as pathogen removal from drinking water, bacteria separation and blood fractionation.
- Majid E. Warkiani, Ali Agar S. Bhagat, Khoo Bee Luan, Jongyoon Han, Chwee Teck Lim, Tony Fane, Thomas Gong. “Isoporous micro/nanoengineered membranes", ACS Nano, 7 (3), pp 1882–1904, 2013. [PDF]
- Majid E. Warkiani, Liu-Hoabing, Chao-Ping Lou, and Hai-Qing Gong "A high-flux isopore micro-fabricated membrane with integrated back-support for isolation of waterborne pathogens", J. of Biomedical Microdevices, pp.1-9, 2012. [PDF]
- Majid E. Warkiani, Chao-Ping Lou, and Hai-Qing Gong "Fabrication of multi-layer polymeric micro-sieve having narrow slot pores with conventional ultraviolet-lithography and micro-fabrication techniques", J. of Biomicrofluidics 5 (3), art. no. 036504, 2011. [PDF]
- Majid E. Warkiani, Longqing Chen, Hao-Bing Liu, Chao-Ping Lou, Zhang Rui, and Hai-Qing Gong, "Capturing and recovery of Cryptosporidium oocysts with polymeric micro-fabricated filter", J. of Membrane Science 369, pp.560-568, 2011. [PDF]
- Majid E. Warkiani, Chao-Ping Lou, and Hai-Qing Gong, "Fabrication and characterization of microporous polymeric micro-filter for isolation of Cryptosporidium parvum oocysts", J. of Micromechanics and Microengineering, 21(3), art. no. 035002, 2011. [PDF]
High-throughput droplet microfluidics
Most cell biology experiments are performed in bulk cell suspensions where cell secretions become diluted and mixed in a contiguous sample. Confinement of single cells into small, picoliter-sized droplets within a continuous phase of oil provides a great opportunity for analysis of the cells at the single-cell level using various chemical and biological assays. We have pioneered novel integrated microfluidic devices combining a droplet jetting generator and a deterministic lateral displacement (DLD) size-sorting channel, which is capable of encapsulating individual cancer cells inside picoliter droplets at 5 kHz, while instantaneously sorting out empty droplets from cell encapsulated ones, to enhance single cell encapsulation rate (up to 80%) regardless of the cell density in sample solutions.
- Tengyang Jing, Ramesh Ramji, Majid Ebrahimi Warkiani, Chwee Teck Lim, Jongyoon Han, Chia-Hung Chen. "High throughput single cancer cell encapsulation and self sorting for protease assay by using jetting microfluidics", MicroTAS 2013 Proceeding, Freiburg, Germany, 2013.
Integrated microfluidic cells systems
Microfluidic platforms provide 3D cell culture environments that better imitate physiological environment compared to 2D planar surface. The 3D system facilitates examination of temporal and spatial changes to cells under electrical stimulations. Furthermore, microfluidic cell culture system enables co-culture to be established. This is crucial to understand cellular interactions especially because cancer cells can interact with other cell types in vivo during process such as intra and extravasation. Lastly, by allowing chemical, mechanical and electromagnetic stimulations to be applied, microfluidic cell culture allows the biological effects of TTF to be investigated at the cellular and molecular level. We develop platforms and methods to quantify behavior of cells within mixed, structurally complex populations and systems. Such devices, methods, and associated computational analysis of timelapsed responses can aid in creating in vitro assays that more accurately mimic conditions in vivo.
- Amir R. Aref, Ruby Yun-Ju Huang, Wei-miao Yu, Kian-Ngiap Chua, Wei Sun, Ting-Yuan Tu, Jing Ba, Wen-Jing Sim, Ioannis K Zervantonakis, Jean Paul Thiery and Roger D. Kamm, "Screening therapeutic EMT blocking agents in a three dimensional microenvironment" Integrative Biology, 2012.
- Yoojin Shin, Sewoon Han, Jessie S Jeon, Kyoko Yamamoto, Ioannis K Zervantonakis, Ryo Sudo, Roger D Kamm & Seok Chung," Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels", Nature protocol, 2012.