Synthesis and Characterization of High-Throughput Nanofabricated Poly(4-Hydroxy Styrene) Membranes for In Vitro Models of Barrier Tissue

Abstract

Commercially available permeable supports with microporous membranes have led to significant improvements in the culture of polarized cells because they permit them to feed basolaterally and thus carry out metabolism in a more in vivo-like setting. The porous nature of these membranes enables permeability measurements of drugs or biomolecules across the cellular barrier. However, current porous membranes have a high flow resistance due to great thickness (20-40 μm), low porosity, and a wide pore size distribution with tortuous diffusion paths, which make them low-throughput for permeability studies. Here we describe an alternate platform that is more flexible, allows for more control over physical parameters of the membranes, and is high-throughput. This study reports on the synthesis, nanofabrication, and surface characterization of a 3-μm-thick transparent membrane based on poly(4-hydroxy styrene) (PHOST). The membranes are nanofabricated using electron beam lithography and deep ion plasma etching to achieve an organized array of straight pores from 50 to 800 nm in diameter, with at least 23 times less flow resistance. It also shows for the first time the potential utility of PHOST as a cell culture substrate without cytotoxicity, and suitability for nanofabrication processes due to temperature stability.

Electrospun fibro-porous polyurethane coatings for implantable glucose biosensors

“…The decrease was usually statistically insignificant for both ESC and EPU, when the coating was applied in a single step. However, when EPU was applied as two separate coats, the sensitivity reduced drastically, which reiterated that the surface to surface interconnectivity of the pore network is essential for higher flux of trans-membrane analyte transport [51]. Thus, any decrease in sensitivity can be attributed to the increasing trans-membrane distance the analyte needs to diffuse through, which is clear from the decrease in diffusion coefficients with increasing thickness of electrospun membranes spun on flat-plate collector (Table 1) [26].…”

Reductive nanometric patterning of graphene oxide paper using electron beam lithography

“…In the context of biomedical applications, EBL has been explored as an attractive technique for the fabrication of submicron (down to the nanoscale) topographies on a diverse palette of materials, including protein patterns for multiplexed cytokine detection, [46] substrates with grooved topographies to modulate cell differentiation, [47] and membranes for in vitro models of barrier tissue [48]. However, its application to graphene-based materials has been scarcely investigated, despite the tremendous biological interest of these materials due to their attractive physico-chemical properties and versatile nature for functionalization.…”

Microfabricated mammalian organ systems and their integration into models of whole animals and humans

“…Microfabricated membranes can address these issues by reducing the global thickness and create high porosity with regular distribution of pores. Shayan et al have developed a nanofabricated membrane with controlled pore size and low thickness (3 μm) allowing cell culture 57 . They demonstrated significant reduction of the flow resistance across the synthetized membrane and maintenance of metabolic activity and viability for at least three days.…”