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Micromachines (Basel). 2019 Feb 1;10(2). pii: E104. doi: 10.3390/mi10020104.

Microfluidic Single-Cell Manipulation and Analysis: Methods and Applications.

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Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China.
Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China.
Shenzhen Research Institute of City University of Hong Kong, Shenzhen 518057, China.


In a forest of a hundred thousand trees, no two leaves are alike. Similarly, no two cells in a genetically identical group are the same. This heterogeneity at the single-cell level has been recognized to be vital for the correct interpretation of diagnostic and therapeutic results of diseases, but has been masked for a long time by studying average responses from a population. To comprehensively understand cell heterogeneity, diverse manipulation and comprehensive analysis of cells at the single-cell level are demanded. However, using traditional biological tools, such as petri-dishes and well-plates, is technically challengeable for manipulating and analyzing single-cells with small size and low concentration of target biomolecules. With the development of microfluidics, which is a technology of manipulating and controlling fluids in the range of micro- to pico-liters in networks of channels with dimensions from tens to hundreds of microns, single-cell study has been blooming for almost two decades. Comparing to conventional petri-dish or well-plate experiments, microfluidic single-cell analysis offers advantages of higher throughput, smaller sample volume, automatic sample processing, and lower contamination risk, etc., which made microfluidics an ideal technology for conducting statically meaningful single-cell research. In this review, we will summarize the advances of microfluidics for single-cell manipulation and analysis from the aspects of methods and applications. First, various methods, such as hydrodynamic and electrical approaches, for microfluidic single-cell manipulation will be summarized. Second, single-cell analysis ranging from cellular to genetic level by using microfluidic technology is summarized. Last, we will also discuss the advantages and disadvantages of various microfluidic methods for single-cell manipulation, and then outlook the trend of microfluidic single-cell analysis.


microfluidics; single-cell analysis; single-cell manipulation

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