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

Abstract

Abstract 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.

Keywords

• antibody‐small molecule interactions
• bioFET
• biosensing
• estriol
• field‐effect sensing