Facile Macrocyclic Polyphenol Barrier Coatings for PDMS Microfluidic Devices

Abstract

Soft lithography techniques using polydimethylsiloxane (PDMS) are a cornerstone of microfluidic microdevices and emerging technologies such as microphysiological systems (MPS). Most of these systems employ hydrophobic small molecules during either stem cell differentiation, drug screening, or organoid development. However, due to PDMS's structure and hydrophobicity, lipophilic molecules are strongly absorbed creating unpredictable concentrations of mitogens, drugs, differentiation factors, and analytes, which is a major limitation in its use for biological applications. In this study, several catechol-functionalized calix[4]arene based macrocyclic polyphenols (MPPs) are synthesized and coated on PDMS through a dip-coating or flow through process. One molecule, MPP-5 cone , synthesized from catechol and resorcinol in its cone isomer form, increases the hydrophilicity of PDMS and drastically reduces the absorption of a number of hydrophobic drug surrogates, while preserving high oxygen permeability, good cell viability and function. However, simple rules of molecular absorption based on Log P are not observed, suggesting screening barrier coatings for PDMS with single probes is not sufficient. The coating procedure is easily translated to microfluidic devices by infusion through channels with a pump, and therefore should find use in applications where molecular absorption into PDMS is a significant problem.

Facile Patterning of Thermoplastic Elastomers and Robust Bonding to Glass and Thermoplastics for Microfluidic Cell Culture and Organ-on-Chip

“…To assess the absorption of small molecules into TPE, a comparative study against PDMS was performed. Three different rhodamine dye molecules, with similar molecular weights (479–491 g/mol), were used to account for the effect of different hydrophobicity (2.13 ≤ Log P ≤ 7.8) [ 48 ]. Dye solutions were injected into the microchannels, and the fluorescence profiles in the microchannels were monitored at different time points ( Figure 3 ).…”

Versatile polyphenolic platforms in regulating cell biology

“…3.2.2 Covalent interactions. Covalent chemical modifications of polyphenols could be achieved by different kinds of reactions, such as esterification, 58 etherification, 59 condensation, 60 oxidation, 61 radical coupling, 62,63 polyphenol-metal coordination complexation, 64 polyphenol-boronate complexation, 65 and Michael addition/Schiff base reactions, 66,67 which could modulate the physicochemical properties of the as-fabricated polyphenolic platform. The active phenol groups could react with carboxylic acid groups by esterification, or with alkyl halides by etherification under a basic environment.…”

Stem cell-based vascularization of microphysiological systems

“…This microfluidic device strategy has been used to model multiple tissue interfaces such as the BBB ( Park et al., 2019 ), lung alveoli ( Benam et al., 2016 ), the kidney glomerulus ( Musah et al., 2017 ), and the intestinal villi ( Vatine et al., 2019 ). Establishment of reliable tissue MPS models, which account for drug absorption losses into the external casing of the MPS, have led to obtaining more detailed and physiological pharmacokinetics of drugs compared with in vivo models ( Herland et al., 2020 ; Lee-Montiel et al., 2020 ; Reese et al., 2020 ; Yu et al., 2015 ).…”