Rare cell isolation and analysis in microfluidics

Abstract

Rare cells are low-abundance cells in a much larger population of background cells. Conventional benchtop techniques have limited capabilities to isolate and analyze rare cells because of their generally low selectivity and significant sample loss. Recent rapid advances in microfluidics have been providing robust solutions to the challenges in the isolation and analysis of rare cells. In addition to the apparent performance enhancements resulting in higher efficiencies and sensitivity levels, microfluidics provides other advanced features such as simpler handling of small sample volumes and multiplexing capabilities for high-throughput processing. All of these advantages make microfluidics an excellent platform to deal with the transport, isolation, and analysis of rare cells. Various cellular biomarkers, including physical properties, dielectric properties, as well as immunoaffinities, have been explored for isolating rare cells. In this Focus article, we discuss the design considerations of representative microfluidic devices for rare cell isolation and analysis. Examples from recently published works are discussed to highlight the advantages and limitations of the different techniques. Various applications of these techniques are then introduced. Finally, a perspective on the development trends and promising research directions in this field are proposed.

Whole-blood sorting, enrichment and in situ immunolabeling of cellular subsets using acoustic microstreaming

“…These functions allow one to identify target cells based on two important characteristics-size and surface biomarkers in a single device. Here we are utilizing enrichment ratio (ER, materials and methods) as a metric to analyze the device performance 14,35,36 . It is defined as the enhancement of target cell to background cell ratio from the device input to the output sample 36 .…”

“…Here we are utilizing enrichment ratio (ER, materials and methods) as a metric to analyze the device performance 14,35,36 . It is defined as the enhancement of target cell to background cell ratio from the device input to the output sample 36 . ER in the order of~100 × to 1000 × is clinically significant for subsequent gene profiling by RT-PCR as discussed by Tong et al 14,37 In our device, we enhanced the ER to 170 × for particle mixture (15 and 10 μm at initial ratio 1:1 00 000).…”

Isolation and enrichment of low abundant particles with insulator-based dielectrophoresis

“…[1][2][3] Excellent reviews on the potential of microfluidics for rare cell separation and enrichment are available in the literature. 4,5 Microfluidics has revolutionized the way many analytical assessments are performed; working on the microscale level has inherent advantages such as portability, quick processing times, and low cost. Electric field driven techniques such as electrophoresis (EP), electrorotation, and dielectrophoresis (DEP) have proven to be robust and reliable options for the assessment of a wide range of macromolecules, cells, and inert particles.…”

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.…”