Abstract

Nanomaterial-based optical techniques for biomarker detection have garnered tremendous attention from the nanofabrication community due to their high precision and enhanced limit of detection (LoD) features. These nanomaterials are highly responsive to local refractive index (RI) fluctuations, and their RI unit sensitivity can be tuned by varying the chemical composition, geometry, and dimensions of the utilized nanostructures. To improve the sensitivity and LoD values of these nanomaterials, it is common to increase both dimensions and aspect ratios of the fabricated nanostructures. However, limited by the complexity, prolonged duration, and elevated costs of the available nanofabrication techniques, mass production of these nanostructures remains challenging. To address not only high accuracy, but also speed and production effectiveness in these nanostructures' fabrication, our work reports, for the first time, a fast, high-throughput, and cost-effective nanofabrication protocol for routine manufacturing of polymer-based nanostructures with high sensitivity and calculated LoD in the pM range by utilizing anodized aluminum oxide (AAO) membranes as templates. Specifically, our developed platform consists of arrays of nearly uniform polystyrene nanopillars with an average diameter of ∼185 nm and aspect ratio of ∼11. We demonstrate that these nanostructures can be produced at a high speed and a notably low price, and that they can be efficiently applied for biosensing purposes after being coated with aluminum-doped silver (Ag/Al) thin films. Our platform successfully detected very low concentrations of human C-reactive protein (hCRP) and SARS-CoV-2 spike protein biomarkers in human plasma samples with LoDs of 11 and 5 pM, respectively. These results open new opportunities for day-to-day fabrication of high aspect ratio arrays of nanopillars that can be used as a base for nanoplasmonic sensors with competitive LoD values. This, in turn, contributes to the development of point-of-care devices and further improvement of the existing nanofabrication techniques, thereby enriching the fields of pharmacology, clinical analysis, and diagnostics.

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