Abstract
Stimuli-responsive hydrogels have a wide range of potential applications in microfluidics, which has drawn great attention. Double cross-linked hydrogels are very well suited for this application as they offer both stability and the required responsive behavior. Here, we report the integration of poly(N-isopropylacrylamide) (PNiPAAm) hydrogel with a permanent cross-linker (N,N′-methylenebisacrylamide, BIS) and a redox responsive reversible cross-linker (N,N′-bis(acryloyl)cystamine, BAC) into a microfluidic device through photopolymerization. Cleavage and re-formation of disulfide bonds introduced by BAC changed the cross-linking densities of the hydrogel dots, making them swell or shrink. Rheological measurements allowed for selecting hydrogels that withstand long-term shear forces present in microfluidic devices under continuous flow. Once implemented, the thiol-disulfide exchange allowed the hydrogel dots to successfully capture and release the protein bovine serum albumin (BSA). BSA was labeled with rhodamine B and functionalized with 2-(2-pyridyldithio)-ethylamine (PDA) to introduce disulfide bonds. The reversible capture and release of the protein reached an efficiency of 83.6% in release rate and could be repeated over 3 cycles within the microfluidic device. These results demonstrate that our redox-responsive hydrogel dots enable the dynamic capture and release of various different functionalized (macro)molecules (e.g., proteins and drugs) and have a great potential to be integrated into a lab-on-a-chip device for detection and/or delivery.
Highlights
Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany; Organische Chemie der Polymere, Technische Universität Dresden, Mommsenstraße 4, 01062 Dresden, Germany
The re-oxidation of disulfide bonds in the double cross-linked hydrogel dots was based on a protocol for BAC/BIS double crosslinked macrogels [54]. 0.01 M tris(2-carboxyethyl)phosphine hydrochloride (TCEP) aqueous solution has been reported to sufficiently reduce the disulfide bonds into thiol groups, and 0.1 M FeCl3 aqueous solution was proven to oxidize thiol groups into disulfide bonds
The PNiPAAm hydrogel dot arrays were successfully integrated into the PDMS-on-glass microfluidic device through photopolymerization
Summary
Synthesis of 2-(2-pyridyldithio)-ethylamine (PDA)sulfoxide (DMSO), cystamine hydrochloride (≥98%), 2,2′-dipyridyl disulfide (98%), iron(III) chloride hexahydrate (≥99%), boPDA was produced following a published procedure [60]. 2 eq.) was dissolved in 10 mL of methanol in a round bottom flask and 400 μL acetic acid saline tablet (PBS), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride was added. The cysteamine hydrochloride (0.28 g, 2.5 mmol, 1 eq.) dissolved in 5 mL (EDAC, ≥99%), 2-(N-morpholino)ethanesulfonic acid (MES, ≥99%), sodium peroxodisulof methanol was added dropwise in 30 min. The reaction was performed under argon atmofate (99%), N,N,N′,N′-tetramethylethylenediamine (TMEDA, 99%) were purchased from sphere. N,N′-Bis(acryloyl)cystamine (BAC, 98%) was purresidue was purified by precipitation in cold diethyl ether overnight followed by filtration chased from Alfa Aesar (Kandel, Germany). Sodium bicarbonate (99.5%) was purchased (2 times).
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