Biosensors support biological and clinical diagnostic applications, offering high accuracy, precision, and functionality. Viable reusable biosensors for enclosed microfluidics are challenging because regeneration methods must ensure precision and sensitivity after recycle. Self-Assembled Monolayers (SAMs) and electrochemical processes show promise; intermediate and long chain SAMs are commonly used, but during desorption, re-adsorption and non-specific adsorption degrades biosensors, limiting reusability. Overcoming these limits is the focus of this work. We tested a prototype and regeneration method using densely packed, short-chain SAMs. Used in conjunction with controlled surface roughness, they reduced re-adsorption and non-specific molecule adsorption. Results confirmed short-chain SAM formation in enclosed microfluidic devices, and desorption promoted “clean” surface recycling for up to 50 cycles. Sensor reusability was evaluated in situ and in real time by Surface Plasmon Resonance (SPR), with a Relative Standard Deviation (RSD) of less than 0.82%, suggesting reusable microfluidics biosensors are finally within reach.
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