Microfabricated tuneable and transferable porous PDMS membranes for Organs-on-Chips

Abstract

We present a novel and highly reproducible process to fabricate transferable porous PDMS membranes for PDMS-based Organs-on-Chips (OOCs) using microelectromechanical systems (MEMS) fabrication technologies. Porous PDMS membranes with pore sizes down to 2.0 μm in diameter and a wide porosity range (2–65%) can be fabricated. To overcome issues normally faced when using replica moulding and extend the applicability to most OOCs and improve their scalability and reproducibility, the process includes a sacrificial layer to easily transfer the membranes from a silicon carrier to any PDMS-based OOC. The highly reliable fabrication and transfer method does not need of manual handling to define the pore features (size, distribution), allowing very thin (<10 μm) functional membranes to be transferred at chip level with a high success rate (85%). The viability of cell culturing on the porous membranes was assessed by culturing two different cell types on transferred membranes in two different OOCs. Human umbilical endothelial cells (HUVEC) and MDA-MB-231 (MDA) cells were successfully cultured confirming the viability of cell culturing and the biocompatibility of the membranes. The results demonstrate the potential of controlling the porous membrane features to study cell mechanisms such as transmigrations, monolayer formation, and barrier function. The high control over the membrane characteristics might consequently allow to intentionally trigger or prevent certain cellular responses or mechanisms when studying human physiology and pathology using OOCs.

Engineering New Microvascular Networks On‐Chip: Ingredients, Assembly, and Best Practices

“…However, another method of including an endothelium published regularly is to situate a tissue monolayer or 3D assembly across from a monolayer of ECs, separated by a thin membrane. [105][106][107][108] The membrane, usually made of PDMS but sometimes fibers of ECM proteins, [109,110] is typically less than 10 µm thick and has pores of diameters on the scale of single micrometers. Like the reviewed devices herein, these setups allow for shear-induced factor release by ECs, paracrine signaling between the two compartments, and a direct endothelium-cell or endothelium-tissue communication.…”

Engineered Tools to Study Intercellular Communication

“…For instance, altering pore diameter on PDMS membranes can either permit or exclude certain molecules from participating in intercellular signaling, providing a way to examine systematically the combinatorial effects of secretory determinants. [ 49 ] Moreover, several 3D culture systems of multiple organs have been assembled together in tandem to monitor organ–organ crosstalk and drug metabolism through their secretory outputs. [ 50 ] The ability to study tissue‐tissue interactions with precise control is a rich and emerging endeavor to investigate critical tissue‐tissue interfaces across a diverse range of biological systems.…”

Double-Framed Thin Elastomer Devices

“… 2 However, low thickness ( e.g. , below 100 μm) is a crucial requirement for several applications, including epidermal electronics, 3 , 4 organs on chips, 5 artificial skin models, 6 microfluidic chips, 7 molds for soft lithography, 8 cell studies, 9 tissue engineering, 10 and membranes. 11 Such very thin and soft films are extremely difficult to manufacture and to handle.…”