Swelling via Impedimetry Using Specifically Adhered Hydrogels on Co-Planar Microfabricated Electrodes

Abstract

Responsive hydrogels adhered to microfabricated electrodes find applicability as chemical or biological sensors and in electro-stimulated drug delivery. A well-defined method of cleaning, surface modification, and surface functionalization of microlithographically-fabricated biochips composed of heterogeneous, abio surfaces (gold and glass) is presented for the reproducible adhesion of responsive hydrogels. The method uses cleaning approaches adapted from the semiconductor electronics industry and combines these with reactive organosilane chemistry to achieve the specific (covalent) attachment of UV cross-linked, poly(HEMA-co-PEGMA-co-HMMA)-based hydrogels. Specific attachment of hydrogels via acryloyl-poly(ethylene glycol)-3500 n-hydroxysuccinimide (APNHS)-functionalized surfaces and subsequent hydrogel hydration resulted in the strongest adhesive force as determined by centrifugal adhesion testing. Comparison with substrates functionalized via hydroxyl-poly(ethylene glycol)-3500 n-hydroxysuccinimide (PNHS) confirmed the superiority of adhesion involving covalent bonding (APNHS) (4.48 kPa) versus hydrogen bonding (PNHS) (1.29 kPa). Adhered, fully hydrated and dehydrated hydrogels are characterized by Electrochemical Impedance Spectroscopy (EIS) and their hydration kinetics determined using impedimetry at a rationalized frequency. Impedimetry confirmed that p(HEMA-co-PEGMA-co-HMMA) hydrogels have an equilibration time of ≈30 min, a diffusion-dependent rate coefficient k₁ = 0.311 s^−0.5 and relaxation-dependent coefficient k₂ = −0.022 s⁻¹. Hydrogel swelling may be studied by impedimetry to fashion biomedical devices for co-joined, real-time biosensing with electro-stimulated drug delivery.