pH Sensing Properties of Flexible, Bias‐Free Graphene Microelectrodes in Complex Fluids: From Phosphate Buffer Solution to Human Serum

Abstract

Advances in techniques for monitoring pH in complex fluids could have significant impact on analytical and biomedical applications ranging from water quality assessment to in vivo diagnostics. We developed flexible graphene microelectrodes (GEs) for rapid (< 5 seconds), very low power (femtowatt) detection of the pH of complex biofluids. The method is based on real-time measurement of Faradaic charge transfer between the GE and a solution at zero electrical bias. For an idealized sample of phosphate buffer solution (PBS), the Faradaic current varied monotonically and systematically with the pH with resolution of ~0.2 pH unit. The current-pH dependence was well described by a hybrid analytical-computational model where the electric double layer derives from an intrinsic, pH-independent (positive) charge associated with the graphene-water interface and ionizable (negative) charged groups described by the Langmuir-Freundlich adsorption isotherm. We also tested the GEs in more complex bio-solutions. In the case of a ferritin solution, the relative Faradaic current, defined as the difference between the measured current response and a baseline response due to PBS, showed a strong signal associated with the disassembly of the ferritin and the release of ferric ions at pH ~ 2.0. For samples of human serum, the Faradaic current showed a reproducible rapid (<20s) response to pH. By combining the Faradaic current and real time current variation, the methodology is potentially suitable for use to detect tumor-induced changes in extracellular pH.

All-Electronic Quantification of Neuropeptide–Receptor Interaction Using a Bias-Free Functionalized Graphene Microelectrode

“…From Figure 2b, we see that the Faradaic current for 0.2 pM enkephalin decreased gradually over tens of minutes and saturated after more than 30 min, which is ascribed to an increase in R ct caused by enkephalin binding to wsMOR on the graphene microelectrode so that charge transfer sites were physically blocked. 16 In contrast, for a target concentration of 22 nM, the current decreased much more quickly and saturated after about 6 min. To quantify the binding kinetics, we fit the current i ( t ) with a single-time relaxation model 33 describing ligand−receptor binding: i(t)=iA(c)−iB(c)(1−e−t/τ) where i A (c) is an offset current at t = 0, τ is the saturation time constant, and i A ( c ) − i B ( c ) is the saturation current for long times as the system reaches equilibrium (for practical purposes, this requires t ≥ 3τ).…”

“…22 The charge transfer rate, ∼pC/s, was thus primarily determined by the charge transfer resistance R ct , which is independent of ionic strength. 16 Charge transferred from the solution to graphene accumulated on the feedback capacitor, C f , of the electrometer to produce the readout voltage. For graphene microelectrodes, the effective potential that drives the spontaneous Faradaic current decays logarithmically with increasing ionic strength, 15 instead of the much faster exponential decrease that is characteristic of transistor-based devices.…”

“…20 To overcome this limitation, our approach is to monitor the spontaneous, zero-bias Faradaic charge transfer from the solution into the microelectrode (∼pC/s). 15,16 We show that this current varies systematically with the analyte concentration, providing picomolar sensitivity in a solution with physiological salt content. We used this approach to quantify the association rate constant, 2.8 ± 0.1 × 10 7 M −1 min −1 , and the dissociation rate constant, 0.089 ± 0.001 min −1 , for binding between the engineered wsMOR and enkephalin.…”

Flow-sensory contact electrification of graphene

“…The PBS solution was prepared before the experiment. Since the graphene charge-transfer current is associated with the hydrolysable groups at graphene defects and the pH of the liquid through the Langmuir–Freundlich isotherm 32 , the pH for the blood/PBS was precisely measured and well-controlled in our experiment.…”

Recent Advances in Flexible Field‐Effect Transistors toward Wearable Sensors

“…[11,160,[208][209][210] F-FET-based biochemical sensors could provide in situ monitoring of the sweat compositions in a noninvasive way. [211] Considering the complexity of sweat compositions, numerous sensors have been reported toward different ingredients, including pH sensors, [47,147,210,[212][213][214][215][216][217] ion sensors, [47,147,[218][219][220][221][222][223] glucose sensors, [21,45,48,159,[224][225][226] lactate sensors, [227] etc. Based on WO 3 NP, Santos et al [212] reported a representative F-FET-based pH sensor for in vivo applications (Figure 12e).…”