  We show that simple, commercially sourced n-channel silicon field-effect
transistors (nFETs) operating under closed loop control exhibit an ~3-fold
improvement in pH readout resolution to (7.2+/-0.3)x10^-3 at a bandwidth of 10
Hz when compared with the open loop operation commonly employed by integrated
ion-sensitive field-effect transistors (ISFETs). We leveraged the improved nFET
performance to measure the change in solution pH arising from the activity of a
pathological form of the kinase Cdk5, an enzyme implicated in Alzheimer's
disease, and showed quantitative agreement with previous measurements. The
improved pH resolution was realized while the devices were operated in a remote
sensing configuration with the pH sensing element off-chip and connected
electrically to the FET gate terminal. We compared these results with those
measured by using a custom-built dual-gate 2D field-effect transistor (dg2DFET)
fabricated with 2D semi-conducting MoS2 channels and a moderate device gain,
alpha=8. Under identical solution conditions the pH resolution of the nFETs was
only 2-fold worse than the dg2DFETs pH resolution of (3.9+/-0.7)x10^-3.
Finally, using the nFETs, we demonstrated the effectiveness of a custom
polypeptide, p5, as a therapeutic agent in restoring the function of Cdk5. We
expect that the straight-forward modifications to commercially sourced nFETs
demonstrated here will lower the barrier to widespread adoption of these
remote-gate devices and enable sensitive bioanalytical measurements for high
throughput screening in drug discovery and precision medicine applications.
