Flow Homogenization Enables a Massively Parallel Fluidic Design for High-throughput and Multiplexed Cell Isolation

Chinchun Ooi; Christopher M Earhart; Casey E Hughes; Jung-Rok Lee; Dawson J Wong; Robert J Wilson; Rajat Rohatgi; Shan X Wang

doi:10.1002/admt.201900960

Flow Homogenization Enables a Massively Parallel Fluidic Design for High-throughput and Multiplexed Cell Isolation

Adv Mater Technol. 2020 May;5(5):1900960. doi: 10.1002/admt.201900960. Epub 2020 Mar 18.

Authors

Chinchun Ooi¹, Christopher M Earhart², Casey E Hughes³, Jung-Rok Lee⁴, Dawson J Wong⁵, Robert J Wilson², Rajat Rohatgi⁶, Shan X Wang⁷

Affiliations

¹ Department of Chemical Engineering, Stanford University, Stanford, California, USA; Department of Fluid Dynamics, Institute of High Performance Computing, Singapore.
² Department of Materials Science and Engineering, Stanford University, Stanford, California, USA.
³ Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah, USA.
⁴ Division of Mechanical and Biomechanical Engineering, Ewha Womans University, Seoul, South Korea.
⁵ Department of Electrical Engineering, Stanford University, Stanford, California, USA.
⁶ Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
⁷ Department of Materials Science and Engineering, Stanford University, Stanford, California, USA; Department of Electrical Engineering, Stanford University, Stanford, California, USA.

Abstract

Microfluidic devices are widely used for applications such as cell isolation. Currently, the most common method to improve throughput for microfluidic devices involves fabrication of multiple, identical channels in parallel. However, this 'numbering up' only occurs in one dimension, thereby limiting gains in volumetric throughput. In contrast, macro-fluidic devices permit high volumetric flow-rates but lack the finer control of microfluidics. Here, we demonstrate how a micro-pore array design enables flow homogenization across a magnetic cell capture device, thus creating a massively parallel series of micro-scale flow channels with consistent fluidic and magnetic properties, regardless of spatial location. This design enables scaling in 2-dimensions, allowing flow-rates exceeding 100 mL/hr while maintaining >90% capture efficiencies of spiked lung cancer cells from blood in a simulated circulating tumor cell system. Additionally, this design facilitates modularity in operation, which we demonstrate by combining two different devices in tandem for multiplexed cell separation in a single pass with no additional cell losses from processing.

Keywords: flow homogenization; magnetic separation; microfluidics; multiplexed cell separation; rare cell isolation.

Abstract

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