Personalized Cancer-Specific Protein-Aptamer Corona for Orthogonal Multiplex Cancer Diagnosis
Aptamers are powerful synthetic recognition elements for biosensing, yet their application in complex biofluids, such as human serum, is critically limited by enzymatic degradation. To overcome this fundamental challenge, we introduce a novel analytical platform centered on the concept of a personalized protein-aptamer corona (PAC). This strategy leverages the spontaneous formation of a disease-specific protein corona on magnetic nanoparticles, which not only enriches low-abundance biomarkers but also creates a stabilized, nuclease-free nanobio interface for subsequent aptamer recognition. The integration of this PAC concept with an 8-channel orthogonal multiplexed electrochemical (OMEC) chip enables sensitive, amplification-free (PCR-free) signal transduction via alternating current voltammetry. By coupling this platform with machine learning algorithms, we translate complex, multiplexed aptamer binding signatures into a robust diagnostic output. Clinical validation on two independent cancer cohorts demonstrated outstanding performance, achieving an area under the curve of 99.50% for ovarian cancer (
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National Key Research and Development Program of China Grant 2022YFB3205600National Key Research and Development Program of China Grant 2022YFC3401000Key Research and Development Program of Zhejiang Province Grant 2023SDYXS0001Natural Science Foundation of Zhejiang Province Grant YXD24B0402Zhejiang Weijianwei Key Program Grant WKJ-ZJ-2513Zhejiang Leading Innovation and Entrepreneurship Team Grant 2022R01006Hangzhou Key Program Grant 20241203A20