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A high frequency thickness shear mode (TSM) sensor was developed for detection of tumor-associated serum autoantibody biomarkers to diagnose prostate cancer early and to monitor effectiveness of treatment and recurrence of disease. The sensor response to three different proteins present in the cell lysate to their antibodies (W632, anti-plakoglobin and anti-EDDR1) were investigated using an array of TSM sensors operating at 100 MHz. The sensor exhibited the detection of all three biomarkers and detected differences in the concentration of the proteins in the lysate. The acoustic data was corroborated with a standard clinical test data (Western Blot). The obtained results clearly indicate that the proposed 100 MHz TSM sensor detection system is suitable for sensitive and selective multi-antigen assay platform for an autoantibody biomarker-based diagnostic screen for the early detection of prostate cancer.