Microfluidic cell sorting

Particle and 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 peripheral blood, enrichment of Algae cells, and fractionation of mesenchymal stem cells (MSCs) as well as blood cells.  In our group, we are using advanced modelling and experimental tools to investigate the inertial migration of particles in microchannels within a wide parameter space. The knowledge and models we are developing can be utilised to build new devices with better separation efficiency for new applications such as water treatment, haemodialysis, Algae dewatering, etc.

References:
1. Majid E. Warkiani, Bee L. Khoo, Lidan Wu, Andy Tay, Ali Asgar S. Bhagat, Jongyoon Han and Chwee Teck Lim “Ultra-fast, label-free isolation of circulating tumor cells from blood using spiral microfluidics”, Nature Protocols, 11,134-148, 2016. [PDF]
2. 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]
3. 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]
4. 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. [PDF]
5. 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. [PDF]
6. Maira Shakeel Syed, Mehdi Rafeie, Rita Henderson, Dries Vandamme, Rob Taylor, Mohsen Asadnia, and Majid E. Warkiani, “Selective Separation of microalge cells using inertial microfluidics”, Bioresource Technology, 2017. [PDF]

Organ-on-a-chips

Microfluidic platforms are creating powerful tools for cell biologists to control the complete cellular microenvironment, leading to new questions and new discoveries. In our group, we are using advanced microfabrication techniques to build simple to use microfluidics devices to mimic live organ physiology. We recently developed a temporarily sealed microfluidic stamping device (2D) which utilizes a novel valve design for patterning various cell types to study cell-cell interactions in a multitude of applications. Using the same concept, we developed a new platform to generate hundreds of uniform stationary droplets for single cell culture and analysis. Our method offers a new approach to easily capture, image and culture single (or multiple) cells in a chemically isolated microenvironment for high-throughput single-cell assays. We are also developing novel 3D microfluidic devices (organ-on-a-chips) 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.

References:
1. Amin Hassanzadeh, J. Shemesh, Nona Farbehi, Mohsen Asadnia, Guan Heng Yeoh, Richard Harvey, Robert Nordon, and  Majid E. Warkiani “A rapid co-culture stamping device for studying intercellular communication” Scientific Reports (Nature Publishing Group), 2016. [PDF]
2. Andrea Pavesi, Giulia Adriani, Andy Tay, Majid E. Warkiani, Yeap Wei Hseun, Siew Cheng Wong and Roger D. Kamm "Engineering a 3D microfluidic culture platform for tumor-treating field application", Scientific Reports (Nature Publishing Group), 6, 26584, 2016. [PDF]
3. Jonathan Shemesh, Iman Jalilian, Anthony She, Guan Yeo, Melissa Knothe and Majid E. Warkiani “Flow induced stress on adherent cells in microfluidic devices”, Lab on a chip, 15, 4114-4127, 2015. [PDF]

3D printing

The advent of microfluidic systems with integrated functions such as valving, metering and mixing has allowed for an unprecedented expansion in both basic and applied research. Yet the production of such systems using standard microfabrication techniques is proven to be tedious and have cumbersome user interfaces, which all render commercialization difficult. Recently, 3D printing approaches have emerged as an alternative solution for rapid production of complex microfluidic structures. In our group, we are developing novel approaches to produce microfluidic componenets by combining direct/wax printing and softlithography, creating the possibility of low-cost manufacturing of microchannels and structures with desired lengths, cross-sections and directions. We are using this approach to build a wide range of functional microfluidic components such as valves and micromixers for future development of integrated lab-on-a chip-systems.

References:
1. Mehdi Rafeie, Marcel Welleweerd, Amin Hassanzadeh-Barforoushi, Mohsen Asadnia, Wouter Olthuis, Majid E. Warkiani “An easily fabricated three-dimensional threaded lemniscate-shaped micromixer for a wide range of flow rates”, accepted, Biomicrofluidics, 2017. [PDF]
2. M. Raoufi, A. Mashhadian, H. Niazmand, M. Asadnia, A. Razmjou, Majid E. Warkiani, “Experimental and numerical study of elasto-inertial focusing in straight channels”, Biomicrofluidics, 2019.