Microfluidic parallel patterning and cellular delivery of molecules with a nanofountain probe.

This brief report describes a novel tool for microfluidic patterning of biomolecules and delivery of molecules into cells. The microdevice is based on integration of nanofountain probe (NFP) chips with packaging that creates a closed system and enables operation in liquid. The packaged NFP can be easily coupled to a micro/nano manipulator or atomic force microscope for precise position and force control. We demonstrate here the functionality of the device for continuous direct-write parallel patterning on a surface in air and in liquid. Because of the small volume of the probes (~3 pL), we can achieve flow rates as low as 1 fL/s and have dispensed liquid drops with submicron to 10 µm diameters in a liquid environment. Furthermore, we demonstrate that this microdevice can be used for delivery of molecules into single cells by transient permeabilization of the cell membrane (i.e., electroporation). The significant advantage of NFP-based electroporation compared with bulk electroporation and other transfection techniques is that it allows for precise and targeted delivery while minimizing stress to the cell. We discuss the ongoing development of the tool toward automated operation and its potential as a multifunctional device for microarray applications and time-dependent single-cell studies.