Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro‐Hydrodynamic Surface Molecular Lithography

Abstract Micro‐ and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab‐on‐a‐chip diagnostics. Herein, a micro‐ and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro‐hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro‐ and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high‐precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro‐ and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano‐plasmonic lab‐on‐a‐chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point‐of‐care detection of disease‐indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost‐effective micro‐ and nanoplatforms for accurate detection.