Microfluidic Devices in the Fast‐Growing Domain of Single‐Cell Analysis

Abstract

Recent advances in cellular analysis revealed that the seemingly identical cells are heterogeneous in term of functionality, compositions, and genetic performance. These differences cause difficulty in the diagnostic for a specific model of disease. Detection of biomolecules such as DNA, RNA, and protein or analysis of cell(s), detection of cell surface molecules, and secreted protein, can help us to improve the understanding of a targeted disease and development of new diagnostic and therapeutic approaches. A single-cell includes the minute quantity of these target molecules. Microfluidic devices have the ability to capture a single-cell and its lysate into a pico or femtoliter volumes droplet, or micro-well thus preventing dilution and limiting diffusion. In this review we described the advancement and limitations in microfluidic techniques used toward single-cells analysis.

Selective cell encapsulation, lysis, pico-injection and size-controlled droplet generation using traveling surface acoustic waves in a microfluidic device

“…In some cases, where cell viability is desired, this is a drawback; in other cases, this can be a feature: lysing a single cell and then immediately capturing its contents in a single droplet would facilitate single-cell resolution for a host of techniques, including single-cell sequencing, transcriptomics, and proteomics. [37][38][39] At present, these single-cell techniques, both in bulk and in droplets, rely on chemicals to break down the cell membrane or cell wall, lysing the cells and exposing their internal contents; 38,[40][41][42] how these chemical lysing agents affect genetic and protein materials is not in general known, 38 and at least in principle, a purely mechanical way to lyse cells and encapsulate their contents could be desirable.…”

A step towards enzyme-free tissue dissociation

“…In this paper, we present a novel enzyme-free approach for mechanically dissociating of tissue samples into viable single-cell suspensions. Liver is generally considered to be among the easiest tissues to dissociate, but hepatocytes are well known to be fragile [5]. Therefore this method is suitable, in particular as a model system, to prove the gentle tissue dissociation of an enzyme-free approach.…”

“…Single cell analysis requires effective, sensitive, and quantitative techniques for separation and detection [5]. Therefore, a desired tissue dissociation system is robust enough to effectively singularise the tissue while maintaining cell viability and cell yield.…”

“…Tissue is typically disintegrated by proteolytic digestion and various mechanical treatments. These conventional methods of tissue dissociation include titration, manual cutting with scalpel, micro-scissors, tissue choppers and micro fabricated filters, expose the sample at high risk of contamination [5]. However, success has been limited by long processing times, low yield and high manual workload leading to a significant increase in the overall analysis time [6].…”

Single-cell Analysis with Microfluidic Devices

“…In concerning chip-MS system, Lin's group has designed an on-chip intestine-liver model for multiple drug absorption and metabolism behavior simulation. 56 In addition, Lin et al [57][58][59] have reported some other work on single-cell analysis, and have written a number of reviews in this field. In the past few years, various new chemical entities (NCEs) and screenable drug targets emerged quickly.…”