Towards nanometer-spaced silicon contacts to proteins.

A vertical nanogap device (VND) structure comprising all-silicon contacts as electrodes for the investigation of electronic transport processes in bioelectronic systems is reported. Devices were fabricated from silicon-on-insulator substrates whose buried oxide (SiO2) layer of a few nanometers in thickness is embedded within two highly doped single crystalline silicon layers. Individual VNDs were fabricated by standard photolithography and a combination of anisotropic and selective wet etching techniques, resulting in p(+) silicon contacts, vertically separated by 4 or 8 nm, depending on the chosen buried oxide thickness.

Simultaneous Scanning Ion Conductance Microscopy and Atomic Force Microscopy with Microchanneled Cantilevers.

We combined scanning ion conductance microscopy (SICM) and atomic force microscopy (AFM) into a single tool using AFM cantilevers with an embedded microchannel flowing into the nanosized aperture at the apex of the hollow pyramid. An electrode was positioned in the AFM fluidic circuit connected to a second electrode in the bath. We could thus simultaneously measure the ionic current and the cantilever bending (in optical beam deflection mode).

Force-controlled patch clamp of beating cardiac cells.

From its invention in the 1970s, the patch clamp technique is the gold standard in electrophysiology research and drug screening because it is the only tool enabling accurate investigation of voltage-gated ion channels, which are responsible for action potentials. Because of its key role in drug screening, innovation efforts are being made to reduce its complexity toward more automated systems. While some of these new approaches are being adopted in pharmaceutical companies, conventional patch-clamp remains unmatched in fundamental research due to its versatility.

Cooperative vaccinia infection demonstrated at the single-cell level using FluidFM.

The mechanisms used by viruses to enter and replicate within host cells are subjects of intense investigation. These studies are ultimately aimed at development of new drugs that interfere with these processes. Virus entry and infection are generally monitored by dispensing bulk virus suspensions on layers of cells without accounting for the fate of each virion.

FluidFM: combining atomic force microscopy and nanofluidics in a universal liquid delivery system for single cell applications and beyond.

We describe the fluidFM, an atomic force microscope (AFM) based on hollow cantilevers for local liquid dispensing and stimulation of single living cells under physiological conditions. A nanofluidic channel in the cantilever allows soluble molecules to be dispensed through a submicrometer aperture in the AFM tip. The sensitive AFM force feedback allows controlled approach of the tip to a sample for extremely local modification of surfaces in liquid environments.