Measurement of Alzheimer’s Enzymes at Physiological Concentrations with Solid-State Dual-Gate 2D-MoS2 Transistors

We have developed sensors based on ionic liquid gated field-effect transistors (FETs) operating at the quantum capacitance limit that allow ultrasensitive pH measurements for biophysics applications [1]. To improve the durability and accessibility of the devices for the broader biological research community, we have recently developed a solid-state version of these high-performance devices and applied it to measure the activity of enzymes relevant to Alzheimer’s disease. The FETs are fabricated with a single-monolayer of the 2D transition metal dichalcogenide MoS₂ and are top-gated with a high-k dielectric gate oxide. The asymmetric capacitive coupling between the high- k top-gate and the back-gate dielectric (substrate oxide) enables amplification of a voltage applied to the top gate by up to a factor of 8. We leveraged the high performance of the devices to enable pH measurements with sensitivities that exceed the Nernst value of 59 mV/pH at room temperature. The improved sensitivity allows the detection of pH changes as small as 0.004. We demonstrate that this enhanced sensitivity facilitates the measurement of activity and kinetics of enzyme-catalyzed phosphorylation of substrate proteins at physiological concentrations.
[1]: S. T. Le et. al, Nanoscale, 2019, 11, 15622–15632.