Automated Electrophysiology: Enhancing Research Capability in Oxford

Lead Research Organisation: University of Oxford
Department Name: Oxford Physics

Abstract

Ion channels are tiny ion-permeable pores that contribute to the electrical currents found in nearly every human cell and are required for their healthy function. Their properties can be regulated by many factors within the body, and they represent important therapeutic targets for treatment of many different diseases.

The University of Oxford is world-leading centre of excellence in the area of ion channel research and hosts a network consisting of over fifty scientists and clinicians working in this area from 'bench to bedside'. The applicants are all members of this network and their labs are interested in problems such as stroke, heart disease, degenerative brain disorders including Parkinson's Disease, and Alzheimers, depression, sleep apnea and pain, including how our bodies are more sensitive to pain at different times of the day.

Assessing the function of ion channels, including how they can be controlled by new drugs, typically involves the 'gold-standard' but painstaking manual 'patch clamp' technique that require high-level manual skills and excellent hand-eye coordination combined with many months of training to acquire. The quality of data and experimental insight that can be generated is unsurpassed, but the technique is extremely low throughput with often only a few data points being generated each day even by highly skilled users.

Automated multi-channel devices based upon planar patch-clamp technology that are capable of processing multiple samples have therefore been developed. Compared to manual patch-clamp they are restricted in some types of experiments that can be undertaken, but for many of the more standard & routine electrophysiology experiments they can increase productivity many-fold, with some instruments capable of processing 384 samples in parallel. However, their cost, complexity and high levels of maintenance mean they are typically only found in industrial environments where high-throughput screening approaches are more common.
The proposed instrument (Nanion Patchliner) is a fully automated 8-channel device meaning that medium throughput standard electrophysiological screens that might take several months to complete using manual methods can be completed within just 1-2 days. The instrument also offers wide-ranging experimental flexibility that is either difficult or impossible to achieve with conventional patch clamp electrophysiology. The Nanion Patchliner is therefore an ideal solution to enhance the capacity and experimental capabilities of a consortium of academic laboratories, who already have unparalleled skills in the more labour-intensive manual patch clamp technique. Its relative ease of use also means that it is likely to attract other non-expert users who may not have considered certain electrophysiology-based projects due to a lack of available equipment and/or experience. Purchase of the instrument therefore represents an excellent investment.

Technical Summary

The acquisition of an automated patch clamp device for multiple channel electrophysiology will dramatically expand the research capability and increase the competitiveness of an internationally recognised consortium of MRC-funded ion channel and membrane transport research groups at the University of Oxford. Such instruments are used for a variety of applications ranging from basic research into channelopathies and biophysical characteristics of ion channels in many cell types, through to routine screening of drug effects and different mutations. No equivalent devices exist within the University or nearby.

We propose to purchase an 8-channel Patchliner with current clamp and full temperature control (Nanion, GmbH, Germany). This is the only robotic, fully automated planar and parallel 8-channel patch clamp device that offers the option of current clamp. It also offers full access to a broad range of other experimental protocols including voltage clamp, standard whole cell, cell-attached, and perforated patch configurations plus the ability for exchange of internal solutions - something not possible with most conventional approaches. It is therefore highly versatile and adaptable for many different ion channel systems and is based upon the manufacturers proven planar patch clamp technology. When combined with its ability to record not just from cultured mammalian cells, but also both native and primary mammalian cells this instrument will enhance the experimental capacity and overall capabilities of all the groups involved.

The Patchliner therefore represents a highly attractive option for this consortium of academic labs and also enables those without formal training in patch clamp techniques to generate high-quality data with relative ease. We therefore expect to attract other local users who have not considered certain electrophysiology-based projects due to a lack of available equipment and/or experience.

Publications

10 25 50