Microfluidics: A Better Approach For Sequencing Single Cells

“Microfluidics: a better approach for sequencing single cells”

Single cell sequencing, including the whole genome amplification-sequencing and the whole transcriptome sequencing, has been achieved recently. However, there are various technical challenges which may still hinder single-cell studies in many applications. I am going to talk about the technologies we recently developed, using microfluidic devices to achieve single cell whole genome sequencing and whole transcriptome sequencing with better performance. We have developed a microfluidics-facilitated method to enable simultaneous detection of copy number variations (CNVs) and single nucleotide variations (SNVs) in an individual cell, offering much finer resolution of CNV detection and significantly improved accuracy of SNV detection than existing single cell WGA methods. We also developed a microfluidic platform to perform single cell RNA-Seq sample prep. We adapted a previously developed strategy for single-cell RNA-Seq that has shown promise for superior sensitivity and implemented the chemistry in a microfluidic platform for single-cell whole transcriptome analysis. Microfluidic implementation increased mRNA detection sensitivity as well as improved measurement precision compared with tube-based protocols. We also quantified variation between and within different types of mouse embryonic cells and found that enhanced measurement precision, detection sensitivity, and experimental throughput aided the distinction between biological variability and technical noise. With this work, we validated the advantages of an early approach to single-cell RNA-Seq and showed that the benefits of combining microfluidic technology with high-throughput sequencing will be valuable for large-scale efforts in single-cell transcriptome analysis.