Nanoscale electrochemical charge transfer kinetics investigated by electrochemical scanning microwave microscopy.

We show how microwave microscopy can be used to probe local charge transfer reactions with unprecedented sensitivity, visualizing surface reactions with only a few hundred molecules involved. While microwaves are too fast under classical conditions to interact and sense electrochemical processes, this is different at the nanoscale, where our heterodyne microwave sensing method allows for highly sensitive local cyclic voltammetry (LCV) and local electrochemical impedance spectroscopy (LEIS). LCV and LEIS allow for precise measurement of the localized charge transfer kinetics, as illustrated in this study for a ferrocene self-assembled monolayer immersed in an electrolyte. The theoretical analysis presented here enables a consistent mapping of the faradaic kinetics and the parasitic contributions (nonfaradaic) to be spectrally resolved and subtracted. In particular, this methodology reveals an undistorted assessment of accessible redox site density of states associated with faradaic capacitance, fractional surface coverage and electron transfer kinetics at the nanoscale. The developed methodology opens a new perspective on comprehending electrochemical reactivity at the nanoscale.

Attoampere Nanoelectrochemistry.

Electrochemical microscopy techniques have extended the understanding of surface chemistry to the micrometer and even sub-micrometer level. However, fundamental questions related to charge transport at the solid-electrolyte interface, such as catalytic reactions or operation of individual ion channels, require improved spatial resolutions down to the nanoscale. A prerequisite for single-molecule electrochemical sensitivity is the reliable detection of a few electrons per second, that is, currents in the atto-Ampere (10-18 A) range, 1000 times below today's electrochemical microscopes. This work reports local cyclic voltammetry (CV) measurements at the solid-liquid interface on ferrocene self-assembled monolayer (SAM) with sub-atto-Ampere sensitivity and simultaneous spatial resolution < 80 nm. Such sensitivity is obtained through measurements of the charging of the local faradaic interface capacitance at GHz frequencies. Nanometer-scale details of different molecular organizations with a 19% packing density difference are resolved, with an extremely small dispersion of the molecular electrical properties. This is predicted previously based on weak electrostatic interactions between neighboring redox molecules in a SAM configuration. These results open new perspectives for nano-electrochemistry like the study of quantum mechanical resonance in complex molecules and a wide range of applications from electrochemical catalysis to biophysics.

High-Sensitivity Dual Electrochemical QCM for Reliable Three-Electrode Measurements.

An electrochemical quartz crystal microbalance (EC-QCM) is a versatile gravimetric technique that allows for parallel characterization of mass deposition and electrochemical properties. Despite its broad applicability, simultaneous characterization of two electrodes remains challenging due to practical difficulties posed by the dampening from fixture parasitics and the dissipative medium. In this study, we present a dual electrochemical QCM (dual EC-QCM) that is employed in a three-electrode configuration to enable consequent monitoring of mass deposition and viscous loading on two crystals, the working electrode (WE) and the counter electrode (CE). A novel correction approach, along with a three standard complex impedance calibration, is employed to overcome the effect of dampening while keeping high spectral sensitivity. Separation of viscous loading and rigid mass deposition is achieved by robust characterization of the complex impedance at the resonance frequency. Validation of the presented system is done by cyclic voltammetry characterization of Ag underpotential deposition on gold. The results indicate mass deposition of 412.2 ng for the WE and 345.6 ng for the CE, reflecting a difference of the initially-present Ag adhered to the surface. We also performed higher harmonic measurements that further corroborate the sensitivity and reproducibility of the dual EC-QCM. The demonstrated approach is especially intriguing for electrochemical energy storage applications where mass detection with multiple electrodes is desired.

Evaluation of the inhibitory effect of antisense oligodeoxynucleotides on the growth of hepatitis C-associated hepatocellular carcinoma cells in vitro.

OBJECTIVE: Hepatitis C virus (HCV) RNA is invariably detected in the serum and tumor tissue of anti-HCV-positive patients with hepatocellular carcinoma (HCC). The inflammation and cirrhosis caused by HCV could be the promoter for development of HCC or HCC could be the consequence of HCV infection independent of the effect of cirrhosis. The ability of the core protein of HCV to modulate gene transcription, cell proliferation and cell death by interacting with cellular genes that regulate cell growth and differentiation is involved in the pathogenesis of HCC. HCV NS3 protease is an attractive target for antiviral agent development because it is required for viral replication. Recent studies that constructed an in vitro model of HCC demonstrated that antisense oligodeoxynucleotides (AS-ODN) interfered with NS3 translation in a dose-dependent fashion and significantly inhibited protease activity. We studied the in vitro effect of AS-ODN on the rate of growth of the HCC cells grown in culture associated with HCV. METHODS: Core biopsy was taken from 20 patients with HCC associated with HCV and each one was divided into two parts: group I to which antisense was added and group II which served as a control group. Comparison of cell viability between tubes with and without AS-ODN was done using MTT assay, LDH assay, cell cycle analysis, trypan blue exclusion test and colony formation in soft agar. RESULTS: Colony formation in soft agar was inhibited in group I compared with the control group and the inhibition was highly significant (P < 0.01). The LDH concentration in culture supernatant and the trypan blue exclusion test, both reflecting cellular death, was higher in group I than group II and the difference was highly significant (P < 0.01). MTT assay showed a highly significant decrease in cell activation in group I than in group II (P < 0.01). The percentage of cells in the G(0)/G(1) phase was higher in group I than in group II and the difference was significant (P = 0.04). There was an insignificant difference between both groups in the percentage of cells in S phase (P = 0.378). The inhibitory effect of AS-ODNs on tumor cells in G(2)/M phase was highly significant compared with the control group (P < 0.01). CONCLUSIONS: AS-ODN has a significant inhibitory effect on the growth of HCV-associated HCC cells grown in fluid culture, and there is potential for the use of AS-ODN as oncotherapy.