Addressing the challenge of solution gating in biosensors based on field-effect transistors

Transistor-based biosensing (BioFET) is a long-enduring vision for next generation medical diagnostics. The study addresses a challenge associated with the BioFET solution gating. The standard BioFET sensing measurement involves sweeping of the solution gate (V_sol) with a concurrent measurement of the source-drain current (I_DS). This I_DS-V_sol sweep poses a great challenge, as V_sol does not only determine I_DS, but also determines the pH levels, ion concentrations, and electric fields at the sensing area double layer accommodating the biomolecules. Therefore, inevitably, an I_DS-V_sol sweep implies that the sensing area double layer is not in an electrochemical equilibrium, but rather in a continuous transient state as electrochemical potential gradients induce transient ion currents continuously affecting double layer hosting the biomolecules and the biological interactions. This challenge calls for a BioFET design which permits I_DS sweeping from an off-state to an on-state while keeping V_sol constant and the double layer sensing area in electrochemical equilibrium. The study explores a BioFET design addressing this challenge by decoupling the solution potential from I_DS gating. Specific and label-free sensing of ferritin in 0.5 μL drops of 1:100 diluted plasma is pursued. We show an excellent sensing performance once the solution potential and I_DS gating are decoupled, with a limit-of-detection of 10 fg/ml, a dynamic range of 10 orders of magnitude in ferritin concentration and excellent linearity and sensitivity. In contrast, a poor sensing performance is recorded for the conventional V_sol sweep performed in parallel to the above. Extensive control measurements quantifying the non-specific signals are reported.