Microfluidic Single-Cell Manipulation and Analysis: Methods and Applications

Abstract

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.

Advances in Label-Free Detections for Nanofluidic Analytical Devices

“…Single-cell analysis, and single-cell omics in particular, increasingly gained attention due to the recognition of cell heterogeneity in cell biology [ 126 , 127 ]. Nanofluidic devices offer fascinating platforms to analyze complex biological systems at the single-cell level, because they allow the processing of sample volumes at the scale from attoliters to femtoliters, which is much smaller than the volume of a single cell (picoliters).…”

Coupling between electrokinetics and electrode kinetics by bipolar faradaic depolarisation processes in microfluidic channels

“…Indeed, we could argue that a proper evaluation of electrokinetics of metals requires combination with independent monopolar electrochemical measurements from which the bipolar electrodic determinants of the electron transfer reaction rates can be derived under given electrokinetic measurement conditions, such as the strength of the DC field across the bulk liquid medium. Subsequently, it can be decided whether or not these faradaic reactions interfere with streaming potential generation and [65][66][67], and for the spatially-resolved detection of electroactive analytes in sensor devices whose functioning calls for bipolar electrochemistry principles.…”

Magnetic Actuation Systems for Miniature Robots: A Review

“…The external magnetic field offers wireless manipulation, and the microfluidics reduces the number of samples and enables high throughput. One of the significant applications is the droplet‐based microfluidic device, where ferrofluid and magnetic beads are often adopted, which is versatile in single‐cell manipulation and biological macromolecule characterization . Common microfluidic functions, such as pumping and mixing, are also performable through magnetic methods…”