From single-cell analysis towards a digital microfluidic point-of-care platform: a capillary journey

For the past years, my laboratory has been working on microfluidic devices to enable the analysis of single cells. Our technology of choice has been droplet microfluidics that encapsulates samples in small (pL-nL range) independent reactors that can be generated and manipulated at rates of 1000’s per second. However, such high throughput loses relevance when analyzing small size samples that contain 100’s to a few 1000’s cells. In addition, there is still a discrepancy between the single-cell manipulation throughput and the capacity of sequencing platforms. To address this unexplored territory, we decided to trade the throughput of droplet microfluidics for higher precision in single cell manipulation and designed a new strategy called trapping and encapsulation. In this approach, we trap almost all the cells (>99%) we inject in our device before encapsulating them. In practice, we came up with different methods to perform the encapsulation. This led us to one particular mode, the capillary-mode, that allows us not only to encapsulate single particles but also to perform controlled and deterministic particle pairs (cells, beads or cell-bead), which has been a long-standing limitation due to the Poisson’s statistics nature of particle encapsulation. Finally, this capillary mode opened new opportunities to perform sample partitioning in plastic material that can be readily manufactured and deployed.

Learning Objectives:

1. Identify various challenges in designing microfluidic devices

2. Explain physical principles harnessed in designing microfluidic devices

3. Review fundamental limitations of current approaches for single particle encapsulation and microfluidic manufacturing