Transistor-based immunosensing in human serum samples without on-site calibration

Health monitoring and disease diagnostics are increasingly moving away from central laboratories towards the point of need. Despite tremendous progress in transducer research, the general need for sample preparation and calibration has impeded wide-spread adoption of new biosensor technologies. In this work, we realize an on-site calibration-free biosensor by using “differential” readout of pairs of differently functionalized field-effect transistors (FET). Specifically, biosensor 1 carries capture antibodies for the target of interest while biosensor 2 is passivated with a blocking agent. We found that their real-time signal difference is largely unaffected by non-specific binding, drift or device-to-device variations. Using this system, highly sensitive detection of a clinically relevant model antigen, thyroid-stimulating hormone, is demonstrated. The sensors are validated in human serum samples vs. a state-of-the-art central laboratory analyzer. The FET-based platform reaches over 4 orders of magnitude dynamic range with a sub-picomolar lower detection limit and an upper detection limit superior to the state-of-the-art system (>10 nM vs. ˜0.1 nM). In contrast to existing technology, the FET sensors do not require any expensive optical components, labelled detection antibodies, sample pre-treatment or washing steps, and remove the need for sensor calibration. These results represent a critical step towards clinical testing outside the centralized lab.