Sequentially addressable dielectrophoretic array for high-throughput sorting of large-volume biological compartments.

Isozaki, A; Nakagawa, Y; Loo, M H; Shibata, Y; Tanaka, N; Setyaningrum, D L; Park, J-W; Shirasaki, Y; Mikami, H; Huang, D; Tsoi, H; Riche, C T; Ota, T; Miwa, H; Kanda, Y; Ito, T; Yamada, K; Iwata, O; Suzuki, K; Ohnuki, S; Ohya, Y; Kato, Y; Hasunuma, T; Matsusaka, S; Yamagishi, M; Yazawa, M; Uemura, S; Nagasawa, K; Watarai, H; Di Carlo, D; Goda, K

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate.