Beyond Polydimethylsiloxane: Alternative Materials for Fabrication of Organ-on-a-Chip Devices and Microphysiological Systems

Abstract

Polydimethylsiloxane (PDMS) is the predominant material used for organ-on-a-chip devices and microphysiological systems (MPSs) due to its ease-of-use, elasticity, optical transparency, and inexpensive microfabrication. However, the absorption of small hydrophobic molecules by PDMS and the limited capacity for high-throughput manufacturing of PDMS-laden devices severely limit the application of these systems in personalized medicine, drug discovery, in vitro pharmacokinetic/pharmacodynamic (PK/PD) modeling, and the investigation of cellular responses to drugs. Consequently, the relatively young field of organ-on-a-chip devices and MPSs is gradually beginning to make the transition to alternative, nonabsorptive materials for these crucial applications. This review examines some of the first steps that have been made in the development of organ-on-a-chip devices and MPSs composed of such alternative materials, including elastomers, hydrogels, thermoplastic polymers, and inorganic materials. It also provides an outlook on where PDMS-alternative devices are trending and the obstacles that must be overcome in the development of versatile devices based on alternative materials to PDMS.

Fabrication and Applications of Microfluidic Devices: A Review

“…The most evident limitation is the opacity of silicon, which renders it incompatible for optical detection in the visible and ultraviolet regions [ 2 , 10 , 25 , 28 ]. If in situ imaging is required, at least a portion of the device must be non-silicon [ 29 ]. Moreover, being quite fragile and having a high elastic modulus, incorporating active components, i.e., valves and pumps, in the silicon platform is complicated [ 17 , 28 ].…”

“…However, microfabrication difficulties arise, limiting the applications of glass microfluidic devices. Despite being cheap, glass is expensive to be manufactured into chips, requires time-consuming labor, and preparation in cleanrooms is sometimes implied [ 10 , 28 , 29 ].…”

“…Another widely used material that is suitable for the manufacturing of microchips is PMMA [ 29 , 35 ]. PMMA is an amorphous thermoplastic [ 25 , 35 ] with slightly better solvent compatibility than PDMS [ 2 ] and no small-molecule absorption [ 29 ].…”

“…Another widely used material that is suitable for the manufacturing of microchips is PMMA [ 29 , 35 ]. PMMA is an amorphous thermoplastic [ 25 , 35 ] with slightly better solvent compatibility than PDMS [ 2 ] and no small-molecule absorption [ 29 ]. PMMA is optically transparent [ 17 ], has good mechanical properties [ 29 ], and allows surface modification [ 2 ] and prototyping at a small scale of production [ 17 , 35 ].…”

Advances in Engineering Human Tissue Models

“…In addition, current OOC and MPS systems are fabricated predominantly with polydimethylsiloxane (PDMS), due to its ease-of-use, elasticity, optical transparency, and low-cost microfabrication. But issues related to the absorption of small hydrophobic molecules by this material severely compromise the validity of such systems in drug screening studies, pushing for transition to alternative, non-absorptive materials (Campbell et al, 2020 ). Also, 3D tissue equivalents and OOCs, as more sophisticated and multi-parametric models, require close control and synchronism of these different parameters to achieve the necessary functionality, particularly when long-term viability is the case (Sontheimer-Phelps et al, 2019 ).…”