New software release for QPatch II available

Take full advantage of your QPatch II system(s) by upgrading to QPatch II Mars, the newest software upgrade for this platform.

QPatch ll Mars includes a variety of new features developed with great input from our users and in-house scientists. Highlights of the QPatch II Mars software features include:

Adaptive Current Clamp

Current clamp (CC) allows you to record how the ion channels set the cell’s membrane potential and how they generate e.g. action potentials in neurons and cardiomyocytes. To investigate such physiological responses on automated patch clamp, it is desirable to be able to handle each cell individually, which is now possible on QPatch II. Adaptive CC is built on the “V_xx” functionality and automatically measures and applies a unique current value for each cell. Each cell can be interrogated independently, analyzed online, and automatically exposed to individual current injections. Such individual current injection can be used to obtain a proper resting membrane potential and to evoke action potentials, that are more uniform across the QPlate.

If you are familiar with the adaptive voltage protocols, “V_xx”, then this is the current clamp ditto, and it is named “I_adapt” in the Sophion Analyzer user interface.

XY-plot of any property from your experiments

On QPatch II you can now plot any property from your experiment and from the analysis of your experiment against each other. Thereby, you have more efficient data evaluation, and it helps you find correlations.

It can be useful to visualize and detect, which properties correlate to unwanted experiments and hence should be removed from the analysis. You can use this knowledge to optimize the unbiased filtering of the data. Rather than guessing and turning on and off filters, this is much more user-friendly.

Live IT-plot on screening station during assay execution

With the live IT-plot functionality on QPatch II, you can now follow the progress of your experiment in real-time. The live IT-plots (current vs. time) shows how the ion channel current responds to compounds or voltage protocols over time. In addition, the plot shows compound name and concentration with compound info on the screening station based on the online cursor set in the voltage protocol. The same information is visible in the live sweep plot.

Additional new functionalities

There are several additional new features included in the QPatch II Mars software suite:

• Sweep subtraction has been expanded and now you can subtract all the sweeps of a step protocol from a baseline or several compound conditions.
• You can make an average of sweeps in an IV-protocol or in repeated liquid periods.
• Automatically combine slightly different experiment protocols with the same compound with liquid period groupin
• Assign any value to the baseline and full response of group Hill fi
• More current clamp analysis methods and all methods have been moved out to standard results for easier access
• Pipetting noise filter can be applied in ligand gated experiments to clean up sweep appearance
• .xls export upgraded to .xlsx which gives > 1 million rows
• E-mail to notify if a backup has failed
• Both front and back side, of the QPlate, pressure data, with 10x increased resolution

In addition to adding features to the software, we have performed software maintenance and improved the user interface for Sophion Analyzer. For example, you can now get automatic scale bars for publication grade graphs. Also, QPatch II comes with the newest Festo VTEP system and supports Oracle 19.

With the enhancements to QPatch II, you can increase the output of your ion channel research even more. Learn more about QPatch II and the new Mars software suite here: https://sophion.com/products/qpatch-ll-automated-patch-clamp/

You are also very welcome to book one of our application scientists for an online demo at: info@sophion.com or visit our labs in Copenhagen, Denmark, Boston, United States, Tokyo, Japan or Shanghai, China.

QPatch II secured the best infrastructure for Linköping University’s new academic core facility

Our high-throughput QPatch II automated patch clamp instrument enabled Linköping University to accelerate its research into a new epilepsy drug – and get the green light to build a national core facility for ion channel research.

Linköping University’s Division of Neurobiology immediately saw the full potential of its new QPatch II patch clamp instrument. The team had been accustomed to testing one compound on one ion channel per day using conventional manual equipment in their electrophysiology laboratory. The arrival of the automated QPatch II from Sophion Bioscience changed that at a stroke.

For Linköping University, the focus now is on using the QPatch II to make further progress towards a drug for epilepsy. At the same time, the team has high hopes for their new core facility to attract clinicians, electrophysicists, and pharmacologists from all over Sweden, who want to expand their range of automated patch clamp experiments.

Click to download the full story here

Sophion technology helped Metrion Biosciences meet higher customer demands and growing assay complexity

Metrion Biosciences successfully met the challenge of growing complexity in ion channel research by adopting Sophion Bioscience’s automated QPatch II and Qube 384 patch clamp platforms. The move transformed Metrion’s research output, enabling it to take on more – and larger – projects and grow its customer base.

Together, Metrion and Sophion have forged a close relationship over the years. Sophion’s input on assay optimization, application, and technical instrument support and instrument service has helped Metrion maximize the in-laboratory benefits of automated patch clamping.

Click to download the full story here

Challenging CRAC channel assays recorded on Sophion’s platforms and without any use of seal enhancers

Calcium release-activated calcium (CRAC) channels play prominent roles, among others, in autoimmune diseases, metastatic breast cancer, diabetes, inflammatory bowel disease, as well as having the potential to prevent transplant rejection. Consequently, molecules that modulate the activity of the CRAC channel current (I_CRAC) are of much interest.

Fluoride is a no-go in assays investigating CRAC channels. To achieve good, high resistance (giga-Ohm) membrane seals, some APC manufacturers rely heavily on seal enhancers like fluoride. Therefore, it has been considered difficult to conduct CRAC channel assays on automated patch clamp systems. With Sophion Bioscience’s platforms, we ensure true gigaseal formation in your experiments without the need for fluoride.

If you would like to learn more about performing CRAC channel assays using Sophion’s QPatch or Qube 384 automated patch clamp systems, read more here

Sophion-authored paper addresses the challenge of safety pharmacology in the elderly

Despite the looming problems that a growing elderly population causes drug discovery, limited, concrete solutions have been offered to address medicinal developments for the elderly. This threatens to engulf societies across the world.

In a thought-provoking review, ex-Pfizer safety pharmacology expert Bernard Fermini and Sophion scientist Damian Bell have called on the drug discovery community to open discussions and act to develop and implement adequate, robust, and safe testing of medicines for the ageing demographic.

We have made the review open access (no paywall); read the paper here.

Latest advances in stem cell recordings on APC reviewed

A Sophion authored pluripotent stem cells and APC review paper shows the much-vaunted use of hiPSC in biomedical research is drawing closer to the promise they hold for safety pharmacology, drug discovery, and personalized medicine.

Research scientist Kadla Røskva Rosholm, Ph.D., and colleagues at Sophion Bioscience, in conjunction with co-authors Prof. Niels Voigt and scientist Fitzwilliam Seibertz of the University of Göttingen have written a wide-ranging review of techniques and applications of hiPSC, developments driven by high-throughput APC.

This figure illustrates paced action potentials in 10 individual hiPSC-cardiomyocyte current clamp recordings from a single measurement QPlate. The expanded action potential shows typical AP characterization measurements: threshold potential (Vt), peak potential (Vp), hyperpolarization potential (Vh), and action potential duration at 90% repolarization (APD90).

View the full, open access paper here

Successful hERG recordings at 22°C and 35°C on QPatch II

When conducting your ion channel experiments a key environmental factor to consider is temperature. In this latest application report, the conductance, kinetics and pharmacology of the hERG ion channel current, a critical component of the cardiac action potential, were recorded at 22°C and 35°C.

Like nearly all physiological processes, the activity and pharmacology of ion channels are highly dependent on temperature. Whether making ion channel recordings at mammalian body temperature (~35°C) or simply a consistent room temperature (RT), it is imperative to accurately control the temperature of your recordings. Even ‘simply’ ensuring all your recordings are not subject to the particular vagaries of the lab’s diurnal/seasonal micro-climate can be challenging. With temperature control, by setting the recording site to RT means accurately recording and reporting at 22°C, not the 18-27°C that we all know can be the real world lab RT.

If you want to learn more about temperature control on Sophion’s platforms, read more here

Collaborative paper on antibodies neutralizing cobratoxin published by the University of Toronto, Technical University of Denmark and Sophion Bioscience

Snakebite affects some of the poorest populations across the globe and was designated a neglected tropical disease (World Health Organisation, 2017).

In further seminal developments, Sophion has helped to develop and characterize the next generation of monoclonal antibodies to neutralize a key alpha-cobratoxin in the venom of the monocled cobra. The antibodies were discovered and developed via phage display by collaborators at the University of Toronto and the Technical University of Denmark. Their in vitro functional, neutralizing effect on the nicotinic acetyl choline receptor (nAChR) ion channel was determined on QPatch II.

Find the paper published in Protein Science here

Assessment of the in vitro neutralization potency of the top two IgGs was performed via electrophysiological measurements using whole cell patch-clamp. The blockade of ACh-dependent currents by purified α-CTx was reversed by pre-incubation of the toxin with serial dilutions of blocking IgG. Signals were normalized to full response (in the absence of α-CTx and IgG).

Large Molecules: New application report focus on Wnt signaling pathway activation

In a new application report, written together with Dr. Aamir Ahmed from Kings College London, UK, we obtained automated patch clamp (APC) recordings using the fragile and scarce Wnt proteins. Wnt 9B, 5A and 10B, were all shown to activate ion channel currents in PC3 cells.

Wingless-related integration site (Wnt) comprises a diverse family of secreted signaling proteins (350–400 amino acids, 35-45 kDa), which act as close-range signaling molecules. Wnt signal activation initiates a complex downstream signal cascade in eukaryotic cells and is critical in the development of many diseases, including cancer.

It was possible to obtain both manual and automated patch clamp recordings of fragile and scarce Wnt proteins after a thorough optimization of the protein handling.

We highlight aspects of the handling of Wnt proteins optimized for APC testing, which could also be applied to other large molecules (e.g. peptide toxins, nanobodies, antibodies).

You can find all relevant Wnt signaling (and other large molecules) publications and posters here

Large molecule characterization using automated patch clamp

Automated patch clamp solutions have been used for years to routinely research ion channels on large molecules. Being able to screen and characterizing large molecules on automated patch clamp is the key to ensure an efficient drug discovery process.

Today, more than 90% of all approved drugs are coming from research on small molecules, but large molecules research is rapidly rising in prominence. The importance of drug discovery already constitute the lion’s share of the top 10 selling drugs worldwide.

Large molecules have gained more attention due to their mode of action, often achieving greater target specificity and potency than small molecule drugs.

Learn more about the various classes of large molecules and ion channel research on our Qube and QPatch solutions here

QPatch II 48 at University of Zürich

If you are in the vicinity of the University of Zürich and interested in conducting automated electrophysiology on a brand new QPatch II 48, then you have a great opportunity now. Just contact ephac@mls.uzh.ch at the university. Click here if you’d like to learn more.

QPatch ll Temperature Control

Laboratory temperatures can change from winter to summer or during the day and affect the reproducibility and repeatability of your assay results. With QPatch II temperature control you can ensure that assays are always performed at a constant and controlled temperature (between 10-42°C) with high accuracy (+/-0.5°C).

Consider the temperature control add-on module if you want to:

• keep a constant controlled temperature to increase repeatability
• perform assays at physiological temperatures 35-37°C
• Log assay temperature for GLP and tracking purposes

The new QPatch ll temperature control and regulate temperature at the Bed-of-Nails directly beneath the measurement sites and also the manifold is thermostated to ensure rapid equilibration.

The recorded temperature data is transferred automatically to the analyzer software where further analysis can be made.

Click here to read more about design, accuracy, precision and validation work. Click here to visit the product page.

CiPA recommended Milnes kinetic hERG assay on QPatch

Up to now, only high-fidelity manual patch clamp recordings have been used to reliably measure hERG channel binding kinetics and drug trapping, both important aspects of drug action and potency as well as cardiac liability.

We have together with Metrion Biosciences implemented the challenging Milnes hERG cardiac safety assay on QPatch.

The Milnes assay meets the FDA’s CiPA requirements for improved arrhythmia prediction and data has a very good correlation with FDA’s manual patch clamp data.

• High fidelity QPatch hERG kinetic data closely mimics FDA’s manual patch clamp Milnes protocol data
• Stable hERG current profile during repetitive long depolarizing test pulses
• The assay can detect changes in hERG amplitude and decay kinetics due to drug binding and trapping
• Pharmacologically validated with clinical drugs showing a wide range of drug trapping activity

Download the application report here