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Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices
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Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices
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Journal Article
Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices
2017
Overview
Key Points
There has been a renaissance in single-cell biology, facilitated in part by the rise of microfluidic devices that can facilitate easy capture, processing and profiling of single cells and their components, reducing labour and costs relative to conventional plate-based methods while also improving consistency.
The three most common classes of microfluidic device are defined by their fundamental elements: valves, droplets or nanowells. Valve-based microfluidic devices afford control but have limited scale; droplet-based devices have high throughput but limited control; and nanowell-based methods have intermediate scale and control, but greater simplicity in operation. These factors influence the costs and benefits of porting any existing assay to each microfluidic device.
Each of these three classes has been used to profile several cellular 'omics' — including the genome, epigenome, transcriptome and proteome — achieving different levels of throughput and efficiency, while leaving opportunities for future development.
Emerging efforts are beginning to focus on measuring multiple cellular properties at once, such as the transcriptome and the proteome or the transcriptome and the epigenome, to obtain a more comprehensive picture of cellular phenotype and its drivers.
Such comprehensive profiling is especially important when studying single cells owing to technical and biological noise sources, which limit the utility of any given measurement from any given cell.
Sequencing is increasingly becoming the
de facto
method for profiling information from single cells given its bandwidth relative to the information content of a single cell and the growing ease of mapping information in a nucleic acid readout. Yet, given fixed sequencing bandwidth and the often limited utility of any one measurement, it is important to carefully consider how to most judiciously allocate reads over cells and their variables.
As the genetic and phenotypic heterogeneities among cells become more appreciated, there is increasing demand for technologies that facilitate high-throughput and high-efficiency single-cell 'omic' analyses in miniaturized and automated formats. This Review discusses the diverse microfluidic methodologies — with a primary focus on valve-, droplet- and nanowell-based platforms — for characterization of the genomes, epigenomes, transcriptomes and proteomes of single cells, and addresses technical considerations and future opportunities.
Recent advances in cellular profiling have demonstrated substantial heterogeneity in the behaviour of cells once deemed 'identical', challenging fundamental notions of cell 'type' and 'state'. Not surprisingly, these findings have elicited substantial interest in deeply characterizing the diversity, interrelationships and plasticity among cellular phenotypes. To explore these questions, experimental platforms are needed that can extensively and controllably profile many individual cells. Here, microfluidic structures — whether valve-, droplet- or nanowell-based — have an important role because they can facilitate easy capture and processing of single cells and their components, reducing labour and costs relative to conventional plate-based methods while also improving consistency. In this article, we review the current state-of-the-art methodologies with respect to microfluidics for mammalian single-cell 'omics' and discuss challenges and future opportunities.
Publisher
Nature Publishing Group UK,Nature Publishing Group
