Rare cell capture in microfluidic devices

Abstract

This article reviews existing methods for the isolation, fractionation, or capture of rare cells in microfluidic devices. Rare cell capture devices face the challenge of maintaining the efficiency standard of traditional bulk separation methods such as flow cytometers and immunomagnetic separators while requiring very high purity of the target cell population, which is typically already at very low starting concentrations. Two major classifications of rare cell capture approaches are covered: (1) non-electrokinetic methods (e.g., immobilization via antibody or aptamer chemistry, size-based sorting, and sheath flow and streamline sorting) are discussed for applications using blood cells, cancer cells, and other mammalian cells, and (2) electrokinetic (primarily dielectrophoretic) methods using both electrode-based and insulative geometries are presented with a view towards pathogen detection, blood fractionation, and cancer cell isolation. The included methods were evaluated based on performance criteria including cell type modeled and used, number of steps/stages, cell viability, and enrichment, efficiency, and/or purity. Major areas for improvement are increasing viability and capture efficiency/purity of directly processed biological samples, as a majority of current studies only process spiked cell lines or pre-diluted/lysed samples. Despite these current challenges, multiple advances have been made in the development of devices for rare cell capture and the subsequent elucidation of new biological phenomena; this article serves to highlight this progress as well as the electrokinetic and non-electrokinetic methods that can potentially be combined to improve performance in future studies.

Enhanced contactless dielectrophoresis enrichment and isolation platform via cell-scale microstructures

“…Of special interest are cells typically found in small concentrations such as white blood cells, circulating tumor cells and tumor-initiating cells. 1,[11][12][13][14] To separate similar cells, the device must be sensitive enough to distinguish small differences in electrical properties between cells. An example of such separation is the isolation of tumor-initiating cells (TICs), also known as cancer stem cells.…”

Magnetophoretic-based microfluidic device for DNA isolation

“…13 Other separation techniques include, but are not limited to biochemical interactions, sheath flow and streamline sorting, dielectrophoresis, fluorescence activated cell sorting (FACS), and deterministic lateral displacement. 15,16 The end goal of the microfluidic magnetophoresis separators is to incorporate them into a complete lTAS. 17 Magnetophoretic microfluidic platforms when compared to centralized lab based separation techniques have the potential to increase the ability for point-of-care diagnosis, reduce the required sample size, and provide faster sample processing.…”

Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis

“…To address these limitations, lab-on-a-chip (LOC) devices have been widely developed over the last 10-15 y (9, 10); these devices integrate and automate multiple laboratory protocols into a miniature device that employs microfluidic technology to handle small sample volumes on the order of microliters to nanoliters (11). The majority of LOC devices can therefore be used for clinical assays (9) to perform a variety of tasks, including single-cell analysis (12), rare-cell isolation (13), sample preparation, pretreatment or preconcentration (14,15,16), purification (17), fractionation (18), drug screening (19,20), enrichment of rare cells and molecules (21,22), target cells of interest manipulation (23)(24)(25)(26), positioning (27), counting and characterizing (28)(29)(30), DNA analysis (14), protein detection (31), environmental monitoring (32), and the detection of biohazards (33). Among different techniques, the family of electrokinetic phenomena (e.g., electrophoresis, electroosmosis, diffusiophoresis, and capillary osmosis) (34), is perfectly suitable and the most widely used concept in LOC devices for the applications mentioned above.…”