Ultrasensitive FET biosensor chip based on self-assembled organic nanoporous membrane for femtomolar detection of Amyloid-β

Early diagnosis of Alzheimer’s disease (AD) is critical for preventing disease progression, however, the diagnosis of AD remains challenging for most patients due to limitations of current sensing technologies. A common pathological feature found in AD-affected brains is the accumulation of Amyloid-β (Aβ) polypeptides, which lead to neurofibrillary tangles and neuroinflammatory plaques. Here, we developed a portable ultrasensitive FET biosensor chip based on a self-assembled nanoporous membrane for ultrasensitive detection of Aβ protein in complex environments. The microscale semiconductor channel was covered with a self-assembled organic nanoporous membrane modified by antibody molecules to pick up and amplify the Aβ protein signal. The nanoporous structure helps protect the sensitive channel from non-target proteins and improves its stability since no chemical functionalization process involved, largely reduces background noise of the sensing platform. When a bio-gated target is captured, the doping state of the polymer bulk could be tuned and amplified the strength of the weak signal, achieving ultrasensitive detecting performance (enabling the device to detect target protein less than 1 fg/ml in 1 µl sample). Moreover, the device simplifies the circuit connection by integrating all the connections on a 2 cm × 2 cm chip, avoiding expensive and complex manufacturing processes, and makes it usable for portable prognosis. We believe that this ultrasensitive, portable, low-cost Aβ sensor chip shows the great potential in the early diagnosis of AD and large-scale population screening applications.