From sensing interactions to controlling the interactions: a novel approach to obtain biological transistors for specific and label-free immunosensing.

Antibody-antigen interactions are shaped by the solution pH level, ionic strength, and electric fields, if present. In biological field-effect transistors (BioFETs), the interactions take place at the sensing area in which the pH level, ionic strength and electric fields are determined by the Poisson-Boltzmann equation and the boundary conditions at the solid-solution interface and the potential applied at the solution electrode. The present study demonstrates how a BioFET solution electrode potential affects the sensing area double layer pH level, ionic strength, and electric fields and in this way shapes the biological interactions at the sensing area. We refer to this as 'active sensing'. To this end, we employed the meta-nano-channel (MNC) BioFET and demonstrate how the solution electrode can determine the antibody-antigen equilibrium constant and allows the control and tuning of the sensing performance in terms of the dynamic range and limit-of-detection. In the current work, we employed this method to demonstrate the specific and label-free sensing of Alpha-Fetoprotein (AFP) molecules from 0.5 µL drops of 1 : 100 diluted serum. AFP was measured during pregnancy as part of the prenatal screening program for fetal anomalies, chromosomal abnormalities, and abnormal placentation. We demonstrate AFP sensing with a limit-of-detection of 10.5 aM and a dynamic range of 6 orders of magnitude in concentration. Extensive control measurements are reported.

A new approach towards the Debye length challenge for specific and label-free biological sensing based on field-effect transistors.

Biologically-modified field-effect transistors (BioFETs) are promising platforms for specific and label-free biosensing due to their sub-micron footprint suitable for multiplexing in ultra-small samples, low noise levels, inherent amplification, etc. Debye screening length is a well-recognized challenge for any BioFET-based technology. The screening length is the smallest at the double layer, where the solution ion population is higher than the bulk population. One way to address the small double layer screening length is to electrostatically modify the potential drop across the solution such as to minimize the potential drop over the double layer. This will decrease the population of the double layer ions and increase the screening length. However, this is not possible with BioFETs as voltage application to the reference electrode simultaneously affects both the double layer and the BioFET conducting channel. The current study addresses the screening length challenge with the novel Meta-Nano-Channel (MNC) BioFET. The MNC BioFET, which is fabricated in a complementary-metal-oxide-silicon (CMOS) process, allows decoupling of the electrostatics of the double layer from the electrodynamics of the conducting channel. The study explores the mechanism of sensing with the MNC BioFET, and demonstrates how the double layer can be electrostatically tuned in order to optimize the screening length without affecting the conducting channel. Finally, specific and label-free sensing of 10 ng ml-1 prostate specific antigen (PSA) is demonstrated. It is shown that by electrostatically increasing the double layer screening length, the sensing signal increases from 70 mV to 133 mV.