Screening
experiment is straightforward using a graphical user interface. Data analysis is finished within sec- onds, also with new cursors and analysis settings, yielding a data output format so flexible that it can be transferred to any existing database (Figure 25).
Sophion Bioscience’s (
www.sophion.com) entry into the APC market with the QPatch 16 in 2004 gave a major boost to the field of ion channel research. In 2009 Sophion launched the multi-hole technology for the QPatch. The multi-hole technology makes experiments with low-conductance or transiently transfected ion channels more efficient. It provides nearly 100% success rate and hence the highest pos- sible throughput and the lowest possible price per data point. Sophion provides three QPatch models, QPatch 8, QPatch 16 and QPatch HT which main- ly differ in their number of channels. The systems are applicable in all phases of drug discovery and on all types of ion channels. Sophion’s strategic focus is data quality. Therefore all QPatch systems provide high-quality data based on true giga-seals and glass- coated compound pathways. A novel and patented 100% R-series compensation makes experiments on fast voltage-gated ion channels very accurate and adds to the quality focus. Sophion provides an upgrade pathway from lower to higher throughput systems. A focus area for QPatch has been to avoid the potential bottleneck of data analysis. The QPatch Assay Software provides automated data analysis. The software is very comprehensive and is updated one to two times per year based on input from Sophion’s customers. In the very near future Sophion will launch an upgrade package to the QPatch that facilitates experiments based on stem cells and primary cells. This includes current clamp, different patch clamp hole sizes and ability to use fewer cells for the experiments. A 384-channel high throughput automated patch clamp system provid- ing very high-quality data based on true giga-seals is also around the corner (Figure 26).
Discussion
The products and services offered by the vendors reported in this review are detailed in Table 2. The new developments presented in the vendor snap- shots can be broadly summarised under the fol- lowing categories:
Cells: Most service providers cited (BioFocus, B’SYS, ChanTest, Cytocentrics, Essen, EMD- Millipore) have access to all major voltage- and lig- and-gated ion channels at high expression in a vari- ety of cell lines or can offer custom cell line devel- opment. In addition, several instrument developers
Drug Discovery World Fall 2011
Figure 26: Sophion’s QPatch has been installed globally at pharmaceutical companies, CROs and academic research centres contributing to a major boost to the field of ion channel research
also offer cells and cell line development matched to their specific APC technology (Cytocentrics, fly- ion, Molecular Devices, Nanion and Sophion). Few currently offer primary or stems cells (eg human cardiomyocytes); although their usefulness in drug discovery and safety is under investigation by label-free (Corning) and with APC instruments and protocols being modified by system developers (Nanion, Sophion) and service providers to sup- port them (B’SYS, ChanTest). Oscillating car- diomyocytes derived from human ESCs/iPSCs were reported to have been investigated for Ca2+ and membrane potential in a 96-well plate fluorescent dispense and read assay format (Hamamatsu).
Megaohm and gigaohm patch clamping: Increas- ingly service offerings are combining fluorescence imaging with both manual patch clamping and sev- eral different APC platforms from multiple vendors. These support both megaohm (population patch clamp or multi-hole devices) and gigaohm patch clamping (single cell recordings), at varying through- puts (BioFocus, B’SYS, ChanTest, EMD-Millipore, Essen). There appears to be an increasing demand for high quality ion channel screening, particularly for detailed follow-up/mechanistic studies. In addition to first-generation APC systems such as the PatchExpress (Molecular Devices), this is now being addressed by new third-generation platforms that offer true giga-seal recordings against single cells at drastically increased throughputs with 96 records
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