Pocket-sized drug discovery: An AI-empowered smartphone platform coupled with single-atom nanozymes for on-site inhibitor screening.

Abstract

The point-of-care (POC) quantification of α-glucosidase (α-Glu) activity and the high-throughput screening of its inhibitors are pivotal for antidiabetic drug discovery, yet they are frequently hindered by the reliance on bulky optical instruments and unstable colorimetric systems. Herein, this work reported an integrated "pocket-sized" analytical platform synergizing an ionic liquid (IL)-regulated Co-N-C single-atom nanozyme (SAzyme) with artificial intelligence (AI)-empowered smartphone analytics. Synthesized via IL-mediated cobalt anchoring and pyrolysis, the engineered SAzyme featured an optimized coordination microenvironment that exhibits robust, H2O2-free oxidase-like activity. This catalyzed the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB), driving a highly specific target-triggered cascade: α-Glu hydrolyzes α-arbutin to yield hydroquinone, triggering a naked-eye visible "signal-off" reductive fading (limit of detection [LOD] = 0.106 U/L). Conversely, inhibitors block this cascade, preserving the blue signal to elegantly translate the inhibition into a distinct "signal-on" readout. To bridge the gap between benchtop precision and on-site deployment, a smartphone-assisted RGB chromaticity analysis was implemented, achieving a reliable instrument-free LOD of 0.645 U/L. Building upon this, a custom-built smartphone application was constructed to autonomously extract multidimensional color features. By embedding a multilayer perceptron (MLP) algorithm, the platform accurately interpreted these optical signals to predict α-Glu activity (validation R2 = 0.927). Utilizing this all-in-one system, the high-throughput POC screening of natural compounds was successfully executed, identifying ursolic acid (IC50 = 3.43 μM) and glycyrrhetinic acid (IC50 = 13.01 μM) as potent inhibitors. Ultimately, this work delivered a versatile, highly integrated approach that liberates enzymatic assays from laboratory constraints, offering a robust strategy for advanced biomedical sensing and drug discovery.

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