The Cytopatch Instrument: the New Automated Patch Clamp Standard in a Comparative Study to the Manual Patch Clamp Technique Regarding the High Data Quality and Flexibility in Assay Design

Abstract

Manual patch clamp is known as the gold standard for investigating ion channel modulation. The high data quality is achieved at the expense of very low throughput, a low standardization feasibility and the need of an experienced operator. Here, it is shown that with the fully automated patch clamp platform CytoPatch Instrument the high data quality known from the manual patch clamp can be achieved, combined with a complete process and assay automation, resulting in the increased throughput needed for screening purposes. Based on the unique design of the Cytocentrics Chip with its dedicated micro fabricated glass pipette, the patch clamp process of the manual patch clamp is resembled. With the advanced microfluidic system various defined and precisely triggered perfusion protocols can be executed. This results in the same flexibility, giga seals, data quality and stability of recordings as it is known for manual patch clamp.It is shown that the CytoPatch Instrument can be used for electrophysiological characterisation of different ion channels. Dose-response relationships of typical hERG blocking compounds were generated using the CytoPatch Instrument. These are in excellent accordance with the data generated using the manual patch clamp technique. Furthermore, it is shown that the CytoPatch Instrument can be used for more advanced electrophysiological studies, e. g. the discrimination of different blocking mechanisms of compounds acting on the hERG ion channel. This study demonstrates that patch clamp automation with the CytoPatch Instrument can extend the standard screening process by more advanced studies. Furthermore, the CytoPatch Instrument is highly standardized and can be utilized in GLP studies.