The Precise Modulation of Probe Effective Charges by Debye Length for Enhancing Performance of Aptamer-FET Biosensors

Field-effect transistor (FET) biosensors have garnered significant interests in disease diagnosis. The electrostatic interaction between channel materials and probes/targets is important to the performance. However, the modulation of electrostatic interaction is difficult because it was severely attenuated in real environment, which is common in practical bioanalytical detection. With small size, aptamer possesses programmable base composition, which is unlimited by the binding sites. Herein, we systematically investigate the precise modulation of Debye length (λ_D) on the effective charge quantity of aptamer probe to regulate electrostatic interaction. We discovered that the performance achieves the optimum due to the largest quantity difference of aptamer probe effective charges when λ_D approaches the minimum between aptamer probe lengths before and after binding with targets. This precise modulation is highly effective for both signal-on and signal-off detection of biomolecules such as serotonin and dopamine, exhibiting a wide linear detection range, spanning from 10 fM to 1.0 nM (10⁵), and an ultra-low limit of detection (<10 fM). Importantly, this precise modulation exhibits practical detection improvement of dopamine secretion from living PC12 cells. Our findings provide a pioneering guideline for enhancing performance of aptamer-FET biosensors and offer in-depth understanding of probe molecular structure.