A Microfluidic Microprocessor: Controlling Biomemetic Containers and Cells using Hybrid Integrated Circuit / Microfluidic Chips

Abstract

We present an integrated platform for performing biological and chemical experiments on a chip based on CMOS (complementary metal–oxide–semiconductor) technology. We have developed a hybrid integrated circuit (IC) / microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety 25 of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picoliter containers for reagents on the chip. The hybrid chip can be programmed to trap, move, porate, fuse, and deform individual living cells and vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber 30 using 128 x 256 (32,768) 11 x 11 μm2 metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chip’s basic functions can be combined in series to perform complex biological and chemical tasks and performed in parallel on the chip’s many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz 35 frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research into automated and inexpensive chips.