A 3D hydrodynamic flow-focusing device for cell sorting

Xiaofei Yuan,Andrew Glidle,Hitoshi Furusho,Huabing Yin

doi:10.1007/s10404-021-02425-y

Abstract

Optical-based microfluidic cell sorting has become increasingly attractive for applications in life and environmental sciences due to its ability of sophisticated cell handling in flow. The majority of these microfluidic cell sorting devices employ two-dimensional fluid flow control strategies, which lack the ability to manipulate the position of cells arbitrarily for precise optical detection, therefore resulting in reduced sorting accuracy and purity. Although three-dimensional (3D) hydrodynamic devices have better flow-focusing characteristics, most lack the flexibility to arbitrarily position the sample flow in each direction. Thus, there have been very few studies using 3D hydrodynamic flow focusing for sorting. Herein, we designed a 3D hydrodynamic focusing sorting platform based on independent sheath flow-focusing and pressure-actuated switching. This design offers many advantages in terms of reliable acquisition of weak Raman signals due to the ability to precisely control the speed and position of samples in 3D. With a proof-of-concept demonstration, we show this 3D hydrodynamic focusing-based sorting device has the potential to reach a high degree of accuracy for Raman activated sorting.

Highlights

With the capability of high throughput screening in cell sorting, traditional flow cytometer and fluorescence activated cell sorting (FACS) systems have become powerful tools for routine clinical and laboratory use (Bonner et al 1972; Nolan et al 1988)
These show that position of the focus could be moved by distances of up to 10′s microns by adjusting the sheath flows using pressures that are all comfortably within those that can be stably generated by simple hydrostatic pressure, good quality microfluidic pressure systems, or good quality syringe pumps
Additional insights gained from the modelling included an examination of the sheath flow streamlines that showed that after passing through the detection chamber, each of the sheath flow streams is directed to corresponding outlets with the focused sample flow being directed into the central outlet for cell sorting and that scaling the inlet and outlet pressures is all that is required to get flow focused cross sections of the order of 10 μm or less with low linear sample flow rates of ~ 0.01 mm/s in the detection chamber

Summary

Introduction

With the capability of high throughput screening in cell sorting, traditional flow cytometer and fluorescence activated cell sorting (FACS) systems have become powerful tools for routine clinical and laboratory use (Bonner et al 1972; Nolan et al 1988). These techniques usually require target cells to be labelled and are not universally applicable. This is true when label-free methods are desirable due to the time required to label the sample, the difficult to label efficiency and specificity, or adverse effects of the label on cell metabolism and viability. This leads to platforms that enable sophisticated cellular analyses and/or the isolation of target cells for post-processing (Skommer et al 2013; Wolff et al 2003)

Methods

Results

Conclusion