Stochastic sensing of single molecules in a nanofluidic electrochemical device.

We report the electrochemical detection of individual redox-active molecules as they freely diffuse in solution. Our approach is based on microfabricated nanofluidic devices, wherein repeated reduction and oxidation at two closely spaced electrodes yields a giant sensitivity gain. Single molecules entering and leaving the cavity are revealed as anticorrelated steps in the faradaic current measured simultaneously through the two electrodes. Cross-correlation analysis provides unequivocal evidence of single molecule sensitivity. We further find agreement with numerical simulations of the stochastic signals and analytical results for the distribution of residence times. This new detection capability can serve as a powerful alternative when fluorescent labeling is invasive or impossible. It further enables new fundamental (bio)electrochemical experiments, for example, localized detection of neurotransmitter release, studies of enzymes with redox-active products, and single-cell electrochemical assays. Finally, our lithography-based approach renders the devices suitable for integration in highly parallelized, all-electrical analysis systems.

Electrochemical sensing of ethylene employing a thin ionic-liquid layer.

We introduce an electrochemical ethylene sensor that employs a thin layer of ionic liquid as electrolyte. Ethylene is oxidized in a potential window starting ∼600 mV before the onset of the gold working electrode oxidation, which inhibits the ethylene oxidation at high applied potential. The current amplitude and sensor response time depend on the ionic-liquid film thickness, relative humidity, and applied potential, in agreement with a theoretical model based on diffusion. A detection limit of 760 ppb and a linear response up to 10 ppm were achieved. As illustrated by the detection of ethylene, ionic liquids could serve as an alternative electrolyte for many electrochemical gas sensors that heretofore relied on a strongly acidic electrolyte.

Charge noise in graphene transistors.

We report an experimental study of 1/f noise in liquid-gated graphene transistors. We show that the gate dependence of the noise is well described by a charge-noise model, whereas Hooge's empirical relation fails to describe the data. At low carrier density, the noise can be attributed to fluctuating charges in close proximity to the graphene, while at high carrier density it is consistent with noise due to scattering in the channel. The charge noise power scales inversely with the device area, and bilayer devices exhibit lower noise than single-layer devices. In air, the observed noise is also consistent with the charge-noise model.

Influence of electrolyte composition on liquid-gated carbon nanotube and graphene transistors.

Field-effect transistors based on single-walled carbon nanotubes (SWNTs) and graphene can function as highly sensitive nanoscale (bio)sensors in solution. Here, we compare experimentally how SWNT and graphene transistors respond to changes in the composition of the aqueous electrolyte in which they are immersed. We show that the conductance of SWNTs and graphene is strongly affected by changes in the ionic strength, the pH, and the type of ions present, in a manner that can be qualitatively different for graphene and SWNT devices. We show that this sensitivity to electrolyte composition results from a combination of different mechanisms including electrostatic gating, Schottky-barrier modifications, and changes in gate capacitance. Interestingly, we find strong evidence that the sensor response to changes in electrolyte composition is affected by a high density of ionizable groups on both the underlying substrate and the carbon surfaces. We present a model based on the (regulated) surface charge associated with these ionizable groups that explains the majority of our data. Our findings have significant implications for interpreting and optimizing sensing experiments with nanocarbon transistors. This is particularly true for complex biological samples such as cell extracts, growth media, or bodily fluids, for which the complete composition of the solution needs to be considered.

Nanocavity redox cycling sensors for the detection of dopamine fluctuations in microfluidic gradients.

Electrochemical mapping of neurotransmitter concentrations on a chip promises to be an interesting technique for investigating synaptic release in cellular networks. In here, we present a novel chip-based device for the detection of neurotransmitter fluctuations in real-time. The chip features an array of plane-parallel nanocavity sensors, which strongly amplify the electrochemical signal. This amplification is based on efficient redox cycling via confined diffusion between two electrodes inside the nanocavity sensors. We demonstrate the capability of resolving concentration fluctuations of redox-active species in a microfluidic mixing gradient on the chip. The results are explained by a simulated concentration profile that was calculated on the basis of the coupled Navier-Stokes and convection-diffusion equations using a finite element approach.

Fast electron-transfer kinetics probed in nanofluidic channels.

We demonstrate that a 50 nm high solution-filled cavity bounded by two parallel electrodes in which electrochemically active molecules undergo rapid redox cycling can be used to determine very fast electron-transfer kinetics. We illustrate this capability by showing that the heterogeneous rate constant of Fc(MeOH)(2) sensitively depends on the type and concentration of the supporting electrolyte. These solid-state devices are mechanically robust and stable over time and therefore have the potential to become a widespread and versatile tool for electrochemical measurements.

Electrochemical correlation spectroscopy in nanofluidic cavities.

We introduce both theoretically and experimentally a new electrochemical technique based on measuring the fluctuations of the faradaic current during redox cycling. By analogy with fluorescence correlation spectroscopy (FCS), we refer to this technique as electrochemical correlation spectroscopy (ECS). We first derive an analytical expression of the power spectral density for the fluctuations in a thin-layer-cell geometry. We then show agreement with measurements using ferrocenedimethanol, Fc(MeOH)2, in water and in acetonitrile in microfabricated thin-layer cells with a approximately 70 nm electrode spacing. The fluctuation spectra provide detailed information about the adsorption dynamics of Fc(MeOH)2, which cause an apparent slowing of Brownian motion. We furthermore observe high-frequency fluctuations from which we estimate the rates of adsorption and desorption.

Redox cycling in nanofluidic channels using interdigitated electrodes.

Amperometric detection is ideally suited for integration into micro- and nanofluidic systems as it directly yields an electrical signal and does not necessitate optical components. However, the range of systems to which it can be applied is constrained by the limited sensitivity and specificity of the method. These limitations can be partially alleviated through the use of redox cycling, in which multiple electrodes are employed to repeatedly reduce and oxidize analyte molecules and thereby amplify the detected signal. We have developed an interdigitated electrode device that is encased in a nanofluidic channel to provide a hundred-fold amplification of the amperometric signal from paracetamol. Due to the nanochannel design, the sensor is resistant to interference from molecules undergoing irreversible redox reactions. We demonstrate this selectivity by detecting paracetamol in the presence of excess ascorbic acid.

Mesoscopic concentration fluctuations in a fluidic nanocavity detected by redox cycling.

We show that a nanofluidic device consisting of a solution-filled cavity bounded by two closely spaced parallel electrodes can amplify the electrical current from redox molecules inside the cavity by a factor of approximately 400 through redox cycling. The noise spectral density of this signal agrees quantitatively with the calculated fluctuations in the number of molecules inside the cavity due to their diffusive motion. We demonstrate sensitivity to fluctuations of as few as approximately 70 molecules.