Engineering and Validation of Open Microfluidic Platform for Organ on a Chip

Abstract

Open microfluidic device was developed using the open-access microfluidic device with through-hole membrane for the regenerative medicine of Peripheral arterial disease (PAD). PAD is commonly defined as narrowing of blood vessels in the lower part of arteries or arterioles. Major risk factors of occurrence of PAD include smoking, hypertension, hypercholesterolemia, atherosclerosis, and complications of diabetes. To develop safe and effective procedures for vascularized tissue injection, we focused on open microfluidic device using through-hole membrane and open-access microfluidic device system. For the transplantable tissue culture, simple fabrication method of through-hole membrane was developed for the media supply to the tissue. Due to the small scale of the fabricated pores, the construction of through-hole membranes on a large scale and with relatively large areas faces many difficulties. Novel fabrication methods for a large-area, freestanding micro/nano through-hole membrane constructed from versatile membrane materials using through-hole membranes on a microfluidic chip (THMMC) for the reconstitution of 3D tissue. The through-hole site was easily customizable from the micro to the nanoscale, with a low or high aspect ratio giving rise to reliable membranes. Also, the rigidity and biocompatibility of the through-hole membrane are easily tunable by simple injection of versatile membrane materials to obtain a large area (up to 3600 mm2). And we describe a simple, versatile method of generating open-access microfluidic device (OAMD) with possible non-destructive tissue sampling for TEM imaging. Generally, the analysis of organ-on-a-chip usually applied by optical microscope, fluorescence microscope and confocal microscopy. Although optical imaging technologies are widespread and effective observational tools, they possess functional and resolution limitations. The myelination by Schwann cells is critically important in restoring neuromuscular motor function after injury or peripheral neuropathy, and in the case of quantifying myelination, transmission electron microscope (TEM) analysis is a requisite. The proposed OAMD platform incorporated a novel biocompatible self-detachable photopolymer (BSP) substrate to provide a viable closed microphysiological system culture environment while also allowing for controllable and nondestructive tissue sampling for TEM analysis. Furthermore, We herein thesis a novel transplantable tissue engineering technique that yields functional and vascularized tissue that can be successfully transplanted into the Balb C Nu nude mouse using THMMC and OAMD technology.