Recent advances in microfluidic cell separations

Abstract

The isolation and sorting of cells has become an increasingly important step in chemical and biological analyses. As a unit operation in more complex analyses, isolating a phenotypically pure cell population from a heterogeneous sample presents unique challenges. Microfluidic systems are ideal platforms for performing cell separations, enabling integration with other techniques and enhancing traditional separation modalities. In recent years there have been several techniques that use surface antigen affinity, physical interactions, or a combination of the two to achieve high separation purity and efficiency. This review discusses methods including magnetophoretic, acoustophoretic, sedimentation, electric, and hydrodynamic methods for physical separations. We also discuss affinity methods, including magnetic sorting, flow sorting, and affinity capture.

Enrichment of circulating tumor cells in tumor-bearing mouse blood by a deterministic lateral displacement microfluidic device

“…To separate CTCs from benign cells in blood, two major approaches can be used: biochemical approaches and biophysical approaches. In biochemical approaches, affinity capture of cell surface antigens (Gao et al 2013;Nagrath et al 2007;Ariyasu et al 2012;Ohnaga et al 2013;Liu et al 2013a;Sheng et al 2013) and fluorescent labeling are generally used to identify CTCs. These examples include the Veridex Cellsearch® system (Raritan, NJ, USA), which has been approved by the U.S. FDA (Food and Drug Administration) for clinical enumeration of CTCs.…”

Non-linear optical measurements using a scanned, Bessel beam

“…3 After analysis, cells are separated from complex mixtures into pure populations using a variety of techniques. 1,4,5,10 In order to perform efficient sorting, current systems typically utilize fluorescent labels in a process called fluorescence activated cell sorting or FACS. This requires conjugation of an external fluorescent label to the cells using antibodies specific to receptors on the cells which are representative of a particular cell type.…”

“…[1][2][3][4][5] The use of both optical and microfluidic technologies allows these tasks to be performed by efficiently analyzing single cells at a high throughput (>10,000 cells/second). [6][7][8][9] Cells of interest are suspended within a stream of liquid and hydrodynamically focused allowing the sample to pass through a small optical excitation region where they are analyzed individually.…”

3D Pulsed Laser Triggered High Speed Microfluidic Fluorescence Activated Cell Sorter

“…Besides solving the aerosolization issue and offering downstream integration capabilities, microfluidic FACS systems also has strong advantages in handling structures or flows at a scale commensurate with that of single cells. This offers greater control over single cell analysis in realizing true point-of-care (POC) labon-a-chip (LOC) systems [5][6][7][8][9][10][11]. Moreover, from the economic perspective, miniaturizing the device reduces both device cost and reagent consumption.…”

“…However, aerosols accompanying high-speed droplet generation and sorting in conventional FACS are always concerns for both sample contamination and operating personnel safety when sorting infectious samples [4]. To address this problem, various closed-form microfluidic FACS systems [5][6][7][8][9][10][11] have been developed over the past decade to provide sterile (contamination and infectious agent-free) sorting and improved downstream device integration for additional molecular analysis following sorting. Besides solving the aerosolization issue and offering downstream integration capabilities, microfluidic FACS systems also has strong advantages in handling structures or flows at a scale commensurate with that of single cells.…”