Controlling biomicrofluidic device surface chemistry using smart surface-segregating zwitterionic polymers

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Abstract The use of microfluidic devices in biomedical research through tissue culture experiments (tissues/organs-on-chips) and biological separations is growing rapidly. Polydimethylsiloxane (PDMS) has been the most popular material for microfluidics due to its feature replication down to the nanoscale, flexibility, gas permeability for oxygenation, and low cost. Yet, the hydrophobicity of PDMS leads to the adsorption of macromolecules (e.g. proteins) and hydrophobic compounds (e.g. Class II & IV drugs) on device surfaces. This curtails its use for drug screening in “organs-on-chips”, and other applications. Current technologies to improve PDMS surface hydrophilicity involve added processing steps and/or do not create surfaces that remain hydrophilic for long periods. They also cannot simultaneously incorporate functional groups to promote binding of specific biomolecules and create bioactive surfaces. This hampers their large-scale implementation and adoption. Our long-term goal is to develop smart materials to improve the precision, robustness, and functionality of biomicrofluidics while keeping their large-scale fabrication simple, facile, and efficient. In this application, we detail a novel, simple technology to modify PDMS via rationally designed smart polymers that, when blended with PDMS during device manufacture, spontaneously segregate to surfaces and create a <1 nm layer when in contact with aqueous solutions that prevents non-specific adsorption of organic and biomolecules, yet can be functionalized to control specific binding for a given application. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. To achieve this immediate goal, we aim to develop novel CP additives for “Smart Copolymer Addition for Modification of PDMS Surfaces” (SCAMPS), specifically highly branched CPs of PDMS with zwitterionic (ZI) groups (Aim 1), with the addition of functional groups that mediate specific binding (Aim 2). We will design and synthesize several members of each smart copolymer class, prepare samples from their blends with PDMS, and characterize them in terms of their mechanical properties, optical clarity, surface chemistry, and tendency to adsorb proteins and small molecule drugs. For functionalized samples, we will also measure the selective adhesion of desired solutes (e.g. avidin on biotin-functional surfaces) and cell types. We will also test the stability and chemistry of the surface upon long-term storage in air and water. We will prepare microfluidic devices from most promising candidates and validate their performance in long-term cell culture experiments. We expect the technologies we develop to improve the accessibility of microfluidics to end users (patients, researchers, drug industry) by providing a low-cost and user-friendly approach to the fabrication of reliable biomicrofluidics.