Fabrication of a microporous PDMS membrane for an Organ-on-Chip device

Abstract

Organs on chips are a novel set of devices whose aim is to mimic cellular in-vivo conditions of the human physiology within a microchip. The need of reliable disease models, particularly for the development of pharmaceutical drugs, has drawn increased attention as the current widespread models; static cell cultures and animal tests, have proven poor predictability, are costly and are increasingly ethically problematic. By providing physiologically relevant bio-chemical, mechanical and other relevant cues to the cells cultured, these in-vitro 'organs' develop similar characteristics to those observed in their in-vivo counterparts. To achieve this, these chips are carefully designed and fabricated with various micro-fabrication technologies, in particular soft-lithography, due to its extensive use for microfluidic devices and materials' proven biological compatibility. However, standard soft-lithography presents major drawbacks as a platform for mass-scale fabrication of complex devices, in particular the extensive use of manual processing which makes it un-reliable and promotes break of thin substrates. At the Eindhoven University of Technology, an Organ-on-chip is being developed to study cancer cell dissemination; cancer metastasis, and several design features have been identified. In particular, the need of a thin micro-porous substrate that allows multiple-cells to be cultured in close contact, bio-chemical and mechanical stimuli, and migration of cells through this layer. Though several soft-lithographic techniques have been reported for the fabrication of similar thin porous films, the manual handling problem has been assessed to be the major technical bottle-neck. In this thesis, a fabrication method based on soft-lithography was designed to make thin micro-porous elastomeric membranes and a brief evaluation of their characteristics to be used for a Cancer-on-Chip was done. By integrating a selective sacrificial layer approach in the soft-lithographic molding process of the membrane, we have addressed the manual handling problem. This enabled us to fabricate large area thin PDMS membranes with micro-pores of 7 to 10 micrometer diameter. The membranes were successfully integrated in micro-fluidic devices and tested for reliability, robustness and porosity by mass transport experiments. Validation for its compatibility for cancer cell culturing was done by seeding breast cancer cells and observing their adhesion on and migration through the membrane.