Smith, Christopher W.Hızır, Mustafa SalihNandu, NidhiYigit, Mehmet, V2022-08-052022-08-0520210003-27001520-6882https://hdl.handle.net/20.500.12885/2019Here, we report a biomarker-free detection of various biological targets through a programmed machine learning algorithm and an automated computational selection process termed algorithmically guided optical nanosensor selector (AGONS). The optical data processed/used by algorithms are obtained through a nanosensor array selected from a library of nanosensors through AGONS. The nanosensors are assembled using two-dimensional nanoparticles (2D-nps) and fluorescently labeled single-stranded DNAs (F-ssDNAs) with random sequences. Both 2D-np and F-ssDNA components are cost-efficient and easy to synthesize, allowing for scaled-up data collection essential for machine learning modeling. The nanosensor library was subjected to various target groups, including proteins, breast cancer cells, and lethal-7 (let-7) miRNA mimics. We have demonstrated that AGONS could select the most essential nanosensors while achieving 100% predictive accuracy in all cases. With this approach, we demonstrate that machine learning can guide the design of nanosensor arrays with greater predictive accuracy while minimizing manpower, material cost, computational resources, instrumentation usage, and time. The biomarker-free detection attribute makes this approach readily available for biological targets without any detectable biomarker. We believe that AGONS can guide optical nanosensor array setups, opening broader opportunities through a biomarker-free detection approach for most challenging biological targets.eninfo:eu-repo/semantics/openAccessChemistryArticle10.1021/acs.analchem.1c0437994211951202N/AQ1