Optimal Signal Transduction with Silicon Transistors Enable Therapeutic Enzyme Regulation

We used commercially sourced n-channel silicon field-effect transistors (nFETs) operating under PID control to demonstrate pH measurements with a resolution of (7.2+/-0.3)x10^-3 at 10 Hz. The results represent a 3-fold improvement over open loop operation of the nFETs and over ion sensitive field-effective transistors (ISFETs). The improved performance was realized when the pH sensing membrane was separated from the nFETs and connected electrically to the transistor gate. The technique leverages key operating procedures from our previous work with dual-gate 2D field-effect transistors (dg2DFET) fabricated with 2D semi-conducting MoS₂ channels. The devices were used to measure the function of the enzyme Cdk5, which facilitates signaling within cells by modifying proteins via the hydrolysis of adenosine triphosphate (ATP), and thereby changing the pH of the surrounding solution by a very small amount. By measuring this subtle change in pH, we quantified the activity of Cdk5, which has been previously implicated in Alzheimer’s disease, under physiological conditions. Finally, we demonstrated the effectiveness of a custom polypeptide, p5, as a therapeutic agent in restoring the function of the pathological form of Cdk5.