Microchip Technology for Automated and Parallel Patch‐Clamp Recording

Brüggemann, Andrea; Stoelzle, Sonja; George, Michael; Behrends, Jan C.; Fertig, Niels

doi:10.1002/smll.200600083

Cited by 83 publications

(51 citation statements)

References 14 publications

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“…Such an expansion in the number of membrane proteins is due to the fact that technological advances have allowed structural biology to reach a position where the elucidation of the three-dimensional structure of relevant proteins on a large scale appears possible. At the same time high-throughput approaches are emerging [8][9][10] to characterize membrane proteins and analyze their topology, issues of significant interest for drug discovery. Unfortunately, the expression and crystallization of integral membrane proteins, such as ion channels, is still fraught with difficulties.…”

Section: Membrane Proteinsmentioning

confidence: 99%

Molecular dynamics simulations of potassium channels

Domene

2007

Open Chemistry

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Despite the complexity of ion-channels, MD simulations based on realistic all-atom models have become a powerful technique for providing accurate descriptions of the structure and dynamics of these systems, complementing and reinforcing experimental work. Successful multidisciplinary collaborations, progress in the experimental determination of three-dimensional structures of membrane proteins together with new algorithms for molecular simulations and the increasing speed and availability of supercomputers, have made possible a considerable progress in this area of biophysics. This review aims at highlighting some of the work in the area of potassium channels and molecular dynamics simulations where numerous fundamental questions about the structure, function, folding and dynamics of these systems remain as yet unresolved challenges.

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Section: Membrane Proteinsmentioning

confidence: 99%

Molecular dynamics simulations of potassium channels

Domene

2007

Open Chemistry

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“…Various substrate materials and chip configurations were demonstrated to measure different types of cells and ion channel functions (Fertig et al, 2002;Lau et al, 2006;Lehnert et al, 2007;Li et al, 2006;Milligan et al, 2009;Py et al, 2010). Microscope, micromanipulator, and skilled operator is essentially not required; hence, automated and parallel-executed ion channel recording were further developed to enhance the throughput for drug discovery and side effect screening (e.g., human ether-a-go-go-related gene) (Bruggemann et al, 2006;Finkel et al, 2006;Mathes, 2006). Ion channel assays require a variety of solution exchanges for investigating channel behaviors.…”

Section: Introductionmentioning

confidence: 99%

Ion channel electrophysiology via integrated planar patch‐clamp chip with on‐demand drug exchange

Chen

Jong

et al. 2011

Biotech & Bioengineering

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Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays.

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“…Planar Patch-clamp Technology-To examine the kinetics of HCN channel activation by intracellular cCMP, the planar patch-clamp technology combined with a fast internal perfusion system (Port-a-Patch, Nanion Technologies, Munich, Germany) was used (26). Currents were recorded using an EPC-10 patch-clamp amplifier (HEKA, Lambrecht, Germany) and PatchMaster acquisition software (HEKA).…”

Section: Methodsmentioning

confidence: 99%