Membrane displacement traps for deterministic droplet and cell manipulation

M. Yeh, J. Harriot, D.L. DeVoe
University of Maryland,
United States

Keywords: droplet microfluidics, cell culture


Microfluidics technology offers powerful capabilities for discretizing and manipulating small aqueous sample volumes. By enabling the compartmentalization of nanoliter or picoliter scale sample volumes, droplet microfluidics has been successfully harnessed for diverse biological assays including digital PCR, whole genome amplification, single-cell RNA sequencing, and a variety of high throughput screening assays. However, technologies for droplet microfluidics cannot yet match the flexibility of robotic liquid handling stations using conventional well plates for sample discretization and manipulation in support of complex multistep assays. Here we describe a membrane displacement trap (MDT) technology that enables software-defined control over arbitrary sequences of complex droplet operations. The MDT platform allows direct modulation of trap volumes to capture, split, merge, and eject selected droplets within the traps, together with an H-bridge valve topology enabling bidirectional flow control for arbitrary droplet positioning within the system. Using this simple chip design, fabricated devices can be coupled with a vision system capable of automated droplet tracking and closed-loop control of the on-chip valves for fully automated operation of the system. Furthermore, the system can be applied to single-phase flows for the selective capture and long-term culture of cells, opening new opportunities for deterministic control over multi-stage chemical and biological assays utilizing sample and reagent volumes orders of magnitude smaller than accessible through robotic microwell plate handlers. This talk will describe several implementations of the MDT technology, including droplet-based control of chemical assays and single-phase co-cultures of lymphocytes and tumor cells to study the dynamics of immune response.