Jonatan Kutchinsky

Characterization of potassium channel modulators with QPatch automated patch-clamp technology: system characteristics and performance.

Planar silicon chips with 1-2-microm etched holes (average resistance: 2.04 +/- 0.02 MOmega in physiological buffer, n = 274) have been developed for patch-clamp recordings of whole-cell currents from cells in suspension. An automated 16-channel parallel screening system, QPatch 16, has been developed using this technology. A single-channel prototype of the QPatch system was used for validation of the patch-clamp chip technology. We present here data on the quality of patch-clamp recordings and from actual drug screening studies of human potassium channels expressed in cultured cell lines. Using Chinese hamster ovary (CHO) and human embryonic kidney cells (HEK), gigaseals of 4.1 +/- 0.4 GOmega (n = 146) and high-quality whole-cell current recordings were obtained from hERG and KCNQ4 potassium channels. Success rates for gigaseal recordings varied from 40 to 95%, and 67% of the whole-cell configurations lasted for >20 min. Cells were maintained in suspension up to 4 h in a cell storage facility that is integrated in the QPatch 16. No decline in patchability was observed during this time course. A series of screens was conducted with known inhibitors of the hERG and KCNQ4 potassium channels. Dose-response relationship characterizations of verapamil and rBeKm-1 blockage of hERG currents provided IC(50) values similar to values reported in the literature.

Observation of Supercurrent Enhancement in SNS Junctions by Nonequilibrium Injection into Supercurrent Carrying Bound Andreev States

We report for the first time enhancement of the supercurrent by means of injection in a mesoscopic three terminal planar SNSNS device made of Al on GaAs. When a current is injected from one of the superconducting Al electrodes at an injection bias

Andreev reflections at interfaces between δ‐doped GaAs and superconducting Al films

V=\Delta(T)/e

An electrophysiological lab on a chip

, the DC Josephson current between the other two superconducting electrodes has a maximum, giving evidence for an enhancement due to a non-equilibrium injection into bound Andreev states of the underlying semiconductor. The effect persists to temperatures where the equilibrium supercurrent has vanished.

Electro-Osmotic Flow Micro Pumps for Cell Positioning in Biochips

By placing several Si δ‐doped layers close to the surface of a GaAs molecular beam epitaxy–grown crystal, we achieve a compensation of the Schottky barrier and obtain a good Ohmic contact between an in situ deposited (without breaking the vacuum) Al metallization layer and a highly modulation doped (n++) conduction layer embedded below the δ‐doped layers in the GaAs crystal. When cooled to below the critical temperature (≊1.2 K) of Al, superconductivity is induced in the conductive layer of the semiconductor. We have studied the current voltage (I–V) characteristics in a planar geometry where the Al has been removed in a thin stripe. We find a manifestation of the superconducting energy gap and a rich fine structure at injection energies both below and above the gap.

Experimental investigation of supercurrent enhancement in S-N-S junctions by non-equilibrium injection into supercurrent-carrying bound Andreev states

We present the successful integration of an electroosmotic flow pump and a patch-clamp orifice in the same package. When experiments are performed the electroosmotic pump is used both to position e.g. a single HEK293 cell on a micron-sized orifice and later to rupture the cell membrane, to bring the cell in the whole-cell configuration. In this configuration we are able to perform high quality electrophysiological ion-channel measurements. In the experiments we have used a sieve geometry for the pump. This design is a particularly promising candidate for such an integration scheme. The sieve pumps have relatively low volumetric flow rats, but are able to supply relatively high stall pressures (>200 mbar), which make the sieve pumps well suited to work on a load with high flow resistance e.g. a patch-clamp orifice. In the following we present a characterisation of such electroosmotic sieve pumps. For our system we were able to determine the zeta-potential of the glass/electrolyte interface of to be well above 10 mV. Furthermore we also present ion-channel measurements performed on this integrated platform.

Photon-assisted Andreev transport and sub-gap structures

A feasible scheme for positioning of cells in a patch clamp biochip for high throughput drug screening comprises the application of suction by means of on-chip micro-pumps. A practical realization of such micro-pumps is based on Electro-Osmotic Flow (EOF). The principle of operation, and the design considerations for such pumps is described. Specific EOF pump geometries are demonstrated.

Enhancement of superconducting critical current by injection of quasiparticles in superconductor semiconductor devices

Abstract We report measurements on three-terminal superconductor–semiconductor–superconductor injection devices demonstrating enhancement of the supercurrent by injection from a superconducting injector electrode. Two other electrodes were used to form the detector junction. Applying a small voltage to the injector electrode reduced the maximum supercurrent (the critical current) between the detector electrodes. When the injector voltage was increased further (upto the gap voltage Δ / e ), the critical current between the detector electrodes increased and approached a new maximum. This is evidence of enhancement of the supercurrent by non-equilibrium injection into bound supercurrent-carrying Andreev states. The effect persists to temperatures where the equilibrium supercurrent has vanished.

Superconductor-semiconductor-superconductor planar junctions of aluminium on /spl delta/-doped gallium-arsenide

Abstract We report new measurements of microwave-induced perturbations of the sub-harmonic energy gap structures in the current–voltage characteristics of superconductor–semiconductor-superconductor junctions. Around the sub-gap bias voltages associated with the enhanced quasi-particle transfer mediated by multiple Andreev reflection processes we observe microwave induced satellites, shifted in voltage by multiples of hf / en , where hf is the photon energy and n is the number of quasi-particle traversals as determined by the Andreev processes. The observed behavior is the analogue of the so-called photon-assisted tunneling but here associated with the multiple Andreev reflections.

Electro Osmotic Flow Pump Based on the Corbino Disc Geometry

Abstract We report new measurements on 3-terminal superconductor semiconductor injection devices, demonstrating enhancement of the supercurrent by injection from a superconducting injector electrode. Two other electrodes were used as detectors. Applying a small voltage to the injector, reduced the maximum supercurrent between the detector electrodes. When further increasing the injection voltage to Δ / e , the critical current approached a new maximum.