Direct label-free electrical immunodetection in human serum using a flow-through-apparatus approach with integrated field-effect transistors

In order to identify changes in the levels of key proteins in response to the onset or development of a disease, the research fields of proteomics and genomics seek to develop new biomarkers. Specifically, simple and fast biomarker screens have a central role in many areas of healthcare, including disease diagnosis and drug discovery. Biologically modified field-effect transistor (BioFET) is one of the most attractive approaches because of the on-chip integration of the sensor array, fast response, high reliability and low-cost mass production. However, the BioFETs used to detect macromolecules have been operated only in buffer solution with low salt concentrations because of the Debye screening length of blood or serum. Here we report a novel detection technique for direct label-free immunodetection of cancer markers in human serum using a Si-FET that was fabricated by conventional photolithographic processes. The proposed sensing method shows no dissociation of antigen–antibody binding as in general immunoassays, unlike the previous reports on Si-FET sensors. This method therefore overcomes the Debye length problem of immunodetection in human fluids, such as serum, that are generally encountered by FET-based biosensors. Our results demonstrate specific label-free and real-time immunodetection of a cancer marker at a concentration of 0.2 ng/mL in human serum, quantitative detection of the marker from 0.2 to 114 ng/mL, and successful multiplexed sensing of three different cancer markers. We believe that connecting our simple electrical detection method, which does not require pretreatment of serum, with well-established whole blood filter technology will contribute to the development of new point-of-care testing (POCT) sensors.