A Microfluidic Chip for Analysis of Mechanical Forces Generated During Cell Migration

Abstract

AbstractVascular smooth muscle cell migration is a microscopic in vivo process where specific cells crawl in order to partake in crucial physiological functions relating to embryonic development, wound healing, and tissue development. Abnormalities of cell migration result in pathologies such as tumor metastasis, angiogenesis, chronic inflammation, and various immune response dysfunctions. The mechanism behind cellular migration and the role of intracellular proteins in the instigation of cell directionality remains poorly understood without effective biomedical device available. The development of microfluidic biochips technologies enable detection, sample preparation and treatment on one single chip. We are reporting the design and fabrication of a novel microfluidic trip for guiding and quantifying cell migrations. The chip featured micropillar arrays imbedded in a multichannel microfluidic chip, where cell migration can be guided by utilizing the characteristics of laminar flow. Non-blending layers of fluid injected through the multi-channel device simulated a wounded edge across a monolayer of cells by limiting flow of trypsin, a serine protease, to half of the main channel, promoting cell migration in a desired direction. Control over cell directionality allows for the measurement and analysis of mechanical forces generated during cell migration in relation to migratory responses from intracellular protein inhibition. The micro-fluidic chip template was designed and manufactured using photolithography techniques. Polydimethylsiloxane (PDMS) served as the bulk material of the two compromising chip layers (channels and pillars), which were subsequently aligned and adhered to form the device. It was confirmed through both computer simulation and experimentation that the through optimized arrangement of the chip design, this device can effectively hold laminar flows of trypsin and cell media. Thus, this microfluidic device allows the user to simultaneously acquire force data during cell migration and observe migratory patterns to ultimately gain a better understanding of the underlying mechanisms of cell migration and directionality.