Title: Phase‐Regulated Sensing Mechanism of MoS₂ Based Nanohybrids toward Point‐of‐Care Prostate Cancer Diagnosis

Abstract: Alpha‐methylacyl‐CoA racemase (AMACR) has been proven to be consistently overexpressed in prostate cancer epitheliums, and is expected to act as a positive biomarker for the diagnosis of prostate carcinoma in clinical practice. Here, a strategy for specific determination of AMACR in real human serum by using an electrochemical microsensor system is presented. In order to implement the protocol, a self‐organized nanohybrid consisting of metal nanopillars in a 2D MoS₂ matrix is developed as material for the sensing interface. The testing signal outputs are strongly enhanced with the presence of the nanohybrids owing to that the metal pillars provide an efficient mass difussion and electron transfer path to the MoS₂ film surface. Furthermore, the phase‐regulated sensing mechanism over MoS₂ is noticed and demonstrated by density functional theory calculation and experiments. The explored MoS₂ based nanohybrids are employed for the fabrication of an electrochemical microsensor, presenting good linear relationship in both ng µL⁻¹ and pg µL⁻¹ ranges for AMACR quantification. The sampling analysis of human serum indicates that this microsensor has good diagnostic specificity and sensitivity toward AMACR. The proposed electrochemical microsensor system also demonstrates the advantages of convenience, cost‐effectiveness, and disposability, resulting in a potential integrated microsystem for point‐of‐care prostate cancer diagnosis.