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Current methods for the accurate diagnosis of osteoarthritis (OA) based on magnetic resonance imaging and enzyme-linked immunosorbent assay method are highly sensitive and specific but require specialised laboratory facilities and highly trained operators to obtain a definitive result. A quartz crystal microbalance (QCM) immunosensor has been developed to detect cartilage oligomeric matrix protein (COMP) in this work. This QCM immunosensor was fabricated to immobilize COMP antibodies in orientation. Its potential dynamically monitored the processes of immunoreaction and could evaluate for the rapid and sensitive detection of COMP in laboratory-cultured preparations and clinical samples. The frequency response of the QCM immunosensor changed 10 kHz to 100 ng/ml COMP. The linear regression equation of frequency shift and COMP concentration is y = 0.0872 x + 1.2138 (R2 =0.9957).