LAB ON A CHIP PERFUSION DEVICE FOR CONSTRUCTING MICRO-PHYSIOLOGICAL IN VITRO MODEL OF HUMAN ORGANS

Micro-physiological in vitro models providing in vivo like environment has abundant prospects in the field of drug discovery and monitoring the physiological events. These models are currently achieved in setups like dual compartment cell culture Transwell system in which cells are grown in an insert with a porous membrane. Such in vitro tools are static in nature and therefore cannot simulate fully the in vivo conditions inside body [1]. Using these techniques needs a large amount of cells, reagents and culture media, which makes this a rather expensive approach. These models are also limited with number of simulated parameters, and are dedicated to a particular application [2-3]. In our previous work [4], we have tested an intestinal model using porous silicon membrane with pores of well controlled dimensions.

In this study, we are developing a microfluidic-based lab-on-chip platform for studying the interaction of various types of cells by co-culturing them and to use this platform for in vitro modeling of human organs. Here, the processes used in typical cell culture experiments are incorporated in an independent microfluidic platform. We report the characterization and optimization of device designs accomplished by means of in-depth FEA simulations (Fig. 1). The chip is made from silicon substrate, which allows us to create features with well controlled dimensions and the critical structures are realized by Deep reactive-ion etching (DRIE) process. The silicon chip itself is 15 mm wide and 40 mm long, capped with glass by means of anodic bonding which provides a leak proof fluidic system and the fluidic channels are accessed through a polymethyl methacrylate (PMMA) jig (Fig. 3). We have developed different chip designs suitable for diverse applications. The major component of the microfluidic device is a perfusion-based microflouidic structure (Fig. 2) which allows the communication between different cell types as well as facilitates the fluid flow. The cell co-culture (Fig. 4b) is achieved by growing them in discrete chambers separated by porous barriers which forms the perfusion structure. The perfusion channels provide opening ranging from 4 to 30 µm² optimized based on the function of each chamber.

This platform provides dynamic environment by precisely controlling the flow rate, spatiotemporal gradients, mechanical stress by fluid flow etc. which enable us to mimic the tissue structure and functions with better physiological relevance. This Organ-on-a-chip design can offer several cell culture chambers with either identical or different cellular structures to study the role of each cell type as well as to compare the cell response to various chemical exposures in parallel experiments.