Continuous trapping, elasticity measuring and deterministic printing of single cells using arrayed microfluidic traps

Abstract

Analysis of single cells after elasticity measurement may construct a linkage between biophysics and other cellular properties, e.g., cell signaling and genetics. This paper reports a microfluidic technology integrating trapping, elasticity measurement, and printing of single cells based on the precise regulation of pressure across an array of U-shaped traps. Both numerical and theoretical analyses revealed that the positive and negative pressure drop across each trap correspondingly contributed to the capture and release of single cells. Afterward, microbeads were employed to demonstrate the capabilities in rapid capturing of single beads. As the printing pressure increased from 0.64 to 3.03 kPa, all beads were released from traps one by one and dispensed into individual wells with an efficiency of 96%. Cell experiments demonstrated that all traps captured K562 cells within 15.25 ± 7.63 seconds. The single-cell trapping efficiency (75.86–95.31%) was proportional to the sample flow rate. Based on the protrusion of each trapped cell and the relevant pressure drop, the stiffness of passages 8 and 46 K562 cells was respectively determined as 171.15 ± 73.35 Pa and 13 959 ± 6328 Pa. The former was consistent with previous studies and the latter was extremely elevated, owing to the cell property variation during a long culture period. Finally, the single cells with known elasticity were deterministically printed into well plates with an efficiency of 92.62%. This technology is a powerful tool for both continuous single cell dispensing and innovatively enabling the relation of cell mechanics to biophysical properties using traditional equipment.