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Review
. 2014 Feb;25:114-23.
doi: 10.1016/j.copbio.2013.09.005. Epub 2013 Dec 18.

Advances in High-Throughput Single-Cell Microtechnologies

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Free PMC article
Review

Advances in High-Throughput Single-Cell Microtechnologies

Westbrook M Weaver et al. Curr Opin Biotechnol. .
Free PMC article

Abstract

Micro-scale biological tools that have allowed probing of individual cells--from the genetic, to proteomic, to phenotypic level--have revealed important contributions of single cells to direct normal and diseased body processes. In analyzing single cells, sample heterogeneity between and within specific cell types drives the need for high-throughput and quantitative measurement of cellular parameters. In recent years, high-throughput single-cell analysis platforms have revealed rare genetic subpopulations in growing tumors, begun to uncover the mechanisms of antibiotic resistance in bacteria, and described the cell-to-cell variations in stem cell differentiation and immune cell response to activation by pathogens. This review surveys these recent technologies, presenting their strengths and contributions to the field, and identifies needs still unmet toward the development of high-throughput single-cell analysis tools to benefit life science research and clinical diagnostics.

Figures

Figure 1
Figure 1
High throughput, single cell analysis tools grouped by the cellular property which they quantify. Single cell techniques range from phenotypic characterization of antibiotic resistance in plug-based systems (bottom left) to proteome, genome, and transcriptome analysis using bar-codes and integrated valving microfluidics. Continuous flow microfluidic systems are currently being developed to measure whole cell deformability in high throughput, towards real-time patient diagnosis and new regenerative medicine tools. Massively parallel cellular surface patterns are used to probe cell-matrix interactions, as well as force generation within cells when coupled with magnetic nanoparticles.
Figure 2
Figure 2
(A) Important cell population subsets and dynamics can be easily masked by conventional bulk analysis. (B) Confinement of single cells into two-phase plug systems has allowed for direct observation of the ‘founder’ phenomenon in bacterial antibiotic resistance. When cells are pre-incubated then segmented, all plugs have a low baseline fluorescence, but when each cell is segmented individually and exposed to antibiotic only in the plug, cells either die (dark), or proliferate because they are resistant (red). (C) siRNA knockdown of a housekeeping gene GAPDH shows high variability cell to cell, where in some cases knockdown is ~100%, and in others is only ~50% effective, giving the typical 25% activity bulk measurement of an ‘effective’ knockdown. (D) Single cell analysis of differentiating stem cells shows a distinct difference between differentiated and pluripotent cells.

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