Specific and Label-Free bioFET Sensing of the Interaction Between the Electrically Neutral Small Estriol Molecule and Its Antibody in a Microliter Drop of Diluted Plasma

The sensing of small molecules is important to a variety of fields and particularly to clinical diagnostics. Estriol is an important small chemical molecule, as it is one of three markers measured during mid-gestation for the Down syndrome. Point-of-care testing of estriol will increase maternal compliance for aneuploidy mid-gestation screening. A bioFET technology is a promising point-of-care platform. The meta-nano-channel (MNC) bioFET is employed with its tunable channel configuration to optimize the coupling between the electrostatics of the estriol-receptor interactions and the electrodynamics of the conducting readout current. Also, the MNC bioFET receptor layer is composed of anti-estriol antibodies to address the high structural similarity of estriol to other estrogens. Despite the small size and the electrical neutrality of estriol, real-time is demonstrated, specific, and label-free sensing of estriol in 0.5 µL of 1:100 diluted plasma with excellent linearity, sensitivity, dynamic range extending to ten orders of magnitude in estriol concentration and limit-of-detection of 1 fg mL⁻¹. Extensive control and non-specific measurements are reported including the response to other neutral members of the estrogen family.