Kv1.3 current clamp assay developed on Qube 384 with Metrion Biosciences

Automated patch clamp experts: Stefano Stabilini, Senior Scientist from Metrion Biosciences, and our Sophion Application Scientist Beatrice Badone have collaborated to develop a novel current clamp assay on the Qube 384. By screening compounds against the Kv1.3 ion channel in current clamp mode, the assay allows the direct effects of the potassium channel’s modulation to be measured in terms of the changes in membrane voltage.

Dr. Eddy Stevens, Director of Drug Discovery at Metrion Biosciences posits that this membrane voltage measure, e.g. Resting Membrane Potential, RMP, is the direct translation of the channel current activity and a definition of how excitable the compound has made the cell membrane.

Thus, for Kv1.3 modulating compounds, this Qube current clamp assay will allow the drug discovery of Kv1.3 inhibitors. The inhibitor activity will functionally translate into a hyperpolarized, less excitable cell membrane in effector memory T-cells (TEM), which have been identified as driving over-activity in autoimmune diseases (such as psoriasis).

Read the full application report on the new Kv1.3 assay here

Snake bite antidotes using engineered human antibodies discovered

Snakebite envenoming continues to claim many lives across the globe, necessitating the development of improved therapies. Recent research discovers and optimizes a broadly-neutralizing human monoclonal antibody to possess advantages over current plasma-derived antivenoms by offering superior safety and high neutralization capacity.

Approximately 60.000 people die from snakebites every year. The World Health Organization (WHO) has set a goal to halve snakebite mortality by 2030. A recent study aims at developing broadly neutralizing human monoclonal antibodies and demonstrates a potential of a range of IgGs to neutralize toxins from several snake species. Such discovery is a critically important next step towards enabling the design of novel, broadly-neutralizing recombinant antivenoms against snakebite envenoming.

A new paper entitled ‘Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes’ is now published in ‘Nature Communications’ and can be read here

Both the QPatch and Qube 384 systems have been used for data generation for the paper. Our Senior Research Scientist, Kim Boddum, summarizes the research conducted on our platforms very well in a poster video here

Great collaboration was achieved between IONTAS, DTU (Technical University of Denmark), Universidad de Costa Rica UCR, ETH Zürich, and Sophion Bioscience.

Would you like to learn more about Large Molecules and Biologicals?

Currently, more than 90% of approved drugs are small molecules, but large molecules (>1.000 Da, also known as biologics) are rapidly rising in prominence and importance in drug discovery. Today, they constitute the lion’s share of the top 10 selling drugs worldwide.

Large molecules have gained attention due to their mode of action, often achieving greater target specificity and potency than small molecule drugs. This, however, comes at a cost as they are usually expensive, scarce, and can have unwanted polyreactivity (“stickiness”). In addition, they are more sensitive to their environment, as their three-dimensional structure is key to their function, and they rely on other, weaker interactions than covalent bonds.

Learn more about Large Molecules and Automated Patch Clamp here

How can we encourage more women to take leading positions in science?

Meet Sandra Wilson, Head of Innovation & New Technology Development at Sophion Bioscience. We asked her; How can we encourage more women to take leading positions in science? We asked her to give us her story of when she became interested in science and how she has made it all the way to a leading position at Sophion Bioscience.

First, can you tell us a little about yourself, Sandra?

I’m Scottish and Canadian and I have lived internationally since I was 11, so I would say I have a pretty global context for life. I’m an extremely curious person and always learning, poking away at things, and trying new things out. This includes a lot of travel and meeting people.

When did you first know you wanted to work in science? 

In high school, I did an O-level in Design & Technology and one of my favorite things was to work with metal, especially casting – I found it mesmerizing, and I have always been curious about processes and how things have been made. It wasn’t clear that I wanted a scientific career until I was considering what to study and realized that I wanted something practical that also involved languages because I already spoke fluent French. I was accepted to study IT, French & Spanish but took a gap year and returned to Canada to work and watch the Winter Olympics in Calgary, loved the mountains and decided to stay. It was during that time I pivoted direction to study materials because it includes a lot of the core sciences, physics, chemistry, mechanics, and maths, and its endlessly complex, especially when I added biology at a later stage.

How has your journey been to where you are today?

When I look back on my career so far what stands out are the variety of companies, projects, and teams I have worked with internationally. Each country has had its own distinct flavor and way of approaching challenges and there are plenty of gifts in that. I’m also really proud that I studied and worked simultaneously. Work experience really helped me to get clear on what kind of impact I wanted to have next and my ongoing studies have helped support me to focus on achieving that impact. Further education doesn’t have to be done all in one continuous shot and I certainly highly recommend getting work experience along the way. Having an international career also builds a certain kind of resilience and most definitely a great network. I’m really pleased that my ongoing development as an engineer, then scientist then scientific manager has allowed me the opportunity for working in such a huge range of sectors from telecom, space to health.

Women are underrepresented in leading positions in science. Do you think that is a problem?

I think women are still underrepresented in leadership positions in science, and I see the need for focus to improve it. For example, through programs such as the WiLD program (Women in Life Science Denmark, www.womeninlifescience.dk) and mentoring programs such as CyberMentor (www.cybermentor.ca).

In general, in science, whether academic or commercial – women bring a huge amount of value and knowledge to the table and the kind of collaborative skills that pull teams together and help generate results in a very efficient way. Science can be a tough field to work in. Wins are by no means guaranteed and there are always unknowns that you are figuring out.  I think there still exists this misperception that aggression and confidence is equated with brilliance in the science world. I don’t believe it’s sustainable. It can alienate some exceptional scientists that are more shy or less confident – good science can be done with kindness and inclusion.

Can you describe your role in Sophion Bioscience?

I really enjoy my role at Sophion. It’s such a great team of people to work with and a diverse range of skills from the software development team to hardware, consumables, production, technical support, and of course the extensive range of biology knowledge the team has. Plus all of the fantastic collaborations with academia and research institutions and companies. I can’t really speak a lot about the work I do, because it’s future-focused, but Sophion is growing a lot and that tells you we have some exciting things happening and new products coming. Essentially, I focus on technology development and scientific collaborations that support the strategic goals of Sophion Bioscience as a company and everything that entails.

You collaborate with external institutions like universities and research centers. Why?

Collaborations with Danish and international universities and research institutions are key, not only because they are customers but because academics are really the experts in their fields. They ask important questions, are developing really cool and exciting methods, and bring ideas and skills. They are targeting extremely complex health science issues, so there are some great synergies for us here at Sophion. These collaborations bring excitement to the team, and they challenge us to make better and new products – making great science tools that ultimately help understand and treat disease. I think that’s a fantastic focus for a career.

You find it important to mentor women and men in their early careers. Why?

It’s been important to me to mentor throughout my career, whether it be leadership with the scouts, through Cybermentor, a Canadian program to mentor girls in high school interested in careers in engineering and science or informally with people that I cross paths with. It’s also important to be mentored, and that has also been a part of my journey – feedback, mirroring, and gentle challenging from trusted advisors have really helped me get clear about what I want to achieve and to help me map out pathways to get there.

Most recently I joined the Spark program, which started at Stanford but is a new program in Denmark (https://sparkdenmark.ku.dk/) that provides some funding and more importantly tailored mentoring to support academic scientists to take their brilliant inventions further toward commercialization. So, giving and receiving mentoring, in whatever form, I think is a crucial part of living up to your potential and it can be deeply enjoyable.

How do you explain the lack of women pursuing leading science positions?

I see many more women in STEAM careers now than when my career started, so that’s a good thing, but there is still a gap to getting to those leadership positions, and we need to elevate that focus and be active about resolving it. I don’t think that women are not pursuing leadership positions, I think they would jump given the chance and proper support – but leadership also has the responsibility to actively create opportunities for women to have a voice and seat at the table.

Sandra, thank you for sharing your story and helping us bring gender equality in science to the forefront today.

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.

World first: High throughput ion channel recordings of isolated primary dorsal root ganglion (DRG) neurons on Yale University’s Qube 384

Researchers at Yale University have published groundbreaking work. Dr Reza Ghovanloo and colleagues in Prof. Stephen Waxman’s lab have taken highly prized DRG nociceptive neuronal recordings from the very low throughput manual patch clamp technique onto the Qube high-throughput automated patch clamp.

Their methods will revolutionize the quantity and quality of the data obtainable from these pain pathway neurons, providing invaluable insights into the physiology of pain sensation.

The authors sum it up better than we can:

“In this proof-of-concept study, we applied adaptations to an automated high-throughput electrophysiological platform to the study of DRG neurons, which provides a model of neuronal cell types that manifests a high degree of diversity, and is relevant to pain, a global unmet medical need. However, this approach is applicable for the study of other excitable cell types”.

“Our results demonstrate the feasibility of patch clamp analysis of freshly isolated neurons on a high-throughput platform [Qube 384 eds]. This approach allows a blinded, unbiased, simultaneous, high-throughput, and comprehensive VC [voltage clamp] investigation of freshly isolated neurons, immediately after tissue dissociation. Moreover, CC [current clamp] analysis can be carried out following VC study, on the same neuron, in a high-throughput mode. This approach provides a basis for the high-throughput physiological and pharmacological study of a variety of types of channels and receptors within multiple types of freshly isolated neurons”.

Congratulations to Reza Ghovanloo, Sidharth Tyagi, Peng Zhao, Emre Kiziltug, Mark Estacion, Sulayman D. Dib-Hajj and Stephen G. Waxman on this seminal publication.

Read the full paper here

Early career scientists can apply for research and travel grants from Sophion Bioscience

Scientists in the early stages of their careers are eligible for grants offered by Sophion Bioscience. Don’t miss the February opportunity to apply for our research and travels grants!

We are looking for students (MSc or PhD) or early career scientists (within 5 years of BSc/MSc/PhD award). You are working in ion channels or related fields, and you would like to present your work at Sophion’s Ion Channel Modulation Symposium. You could also have QPatch II or Qube384 data and want to tell your story at any international conference. Take this opportunity to make an application for our travel grant.

Alternatively, your postgraduate studies or early career lab research could be rocketed into the stratosphere by applying for our research grant. This will give you access to our platforms and experts in our labs across the world. Sophion’s research grant might be your ticket to completing a key finding for your thesis or strengthening your lab’s latest funding application.

For more info & application forms click here.

Developing iPSC ion channel recordings with automated patch clamp

Induced pluripotent stem cell (iPSC) techniques have been developing over the last few years, improving cell differentiation and maturation. In combination with improved culturing and handling, iPSC ion channel recordings via automated patch clamp (APC) have made these model ‘adult’ differentiated cells extremely useful in biomedical research, more translatable in defining human physiology and disease, whilst reducing the need and use of animal tissue.

Over 2022, Sophion scientists, collaborators, and users of our platforms have been at the forefront of this iPSC and APC revolution. Our collaborative research is captured here:

Webinars

Mike Hendrickson (BrainXell) & Daniel Sauter on iPSC-motor neurons:

Liz Buttermore (Human Neuron Core, Boston Children’s Hospital) & Kadla Rosholm on iPSC-cortical neurons:

Will Seibertz (University Medical Center Göttingen) & Kadla Rosholm on iPSC-cardiomyocytes:

Review paper

Adventures and Advances in Time Travel With Induced Pluripotent Stem Cells and Automated Patch Clamp. Rosholm et al., Frontiers Mol. Neurosci., 2022: view

Are you interested in learning more about the research performed on Sophion automated patch clamp platforms and stem cells? We have gathered a list of relevant publications here

Bruce Bean and Clifford Woolf Labs at Harvard Medical School Acquire QPatch Compact

After a beta testing period of Sophion’s new semi-automated patch-clamp system, QPatch Compact, the Bruce Bean and Clifford Woolf Labs at Harvard Medical School’s Blavatnik Institute and the F.M. Kirby Neurobiology Center at Boston Children’s Hospital have decided to acquire the technology.

The decision to acquire QPatch Compact was driven by two key factors: the need to “scale up” patch-clamp assays previously done manually and the power of the QPatch Compact for fast, highly-flexible application of multiple pharmacological agents to a single cell. QPatch Compact utilizes technology proven by use for over 20 years in QPatch I and QPatch II.

Bean commented, “The QPatch Compact is amazing in that you can apply a solution almost instantly just by pipetting a few microliters of solution, so that you can make any sequence of solution changes you like on-the-fly during an experiment. The flexible solution handling capability is perfect for doing quick dose-response determinations and the fact that you get complete solution exchange with just a few microliters of solution is especially useful for experiments with expensive toxins.”

The group is using QPatch Compact to investigate the pharmacology of a variety of voltage-gated ion channels with a focus on generating novel non-opioid compounds for the treatment of pain.

The instrument will be run by a core group of experienced electrophysiologists including Bruce Bean, Patric Vaelli, Akie Fujita, Bear Zhang, Sooyeon Jo, Tomás Osorno, and Rasheen Powell.

About the Blavatnik Institute: Led by HMS Dean George Q. Daley, the Blavatnik Institute at Harvard Medical School is home to world-class faculty who aim to solve the greatest problems of human health through fundamental and translational biomedical research. The institute reflects the unique identity of the scientific enterprise housed on the HMS Quadrangle, encompassing the School’s 11 basic and social science departments, including the departments of Biological Chemistry and Molecular Pharmacology, Biomedical Informatics, Cell Biology, Genetics, Global Health and Social Medicine, Health Care Policy, Immunology, Microbiology, Neurobiology, Stem Cell and Regenerative Biology, and Systems Biology. The institute was named in November 2018 in recognition of a momentous commitment from the Blavatnik Family Foundation to benefit Harvard Medical School.

About Bruce Bean, PhD: Dr. Bean is the Robert Winthrop Professor of Neurobiology at Harvard Medical School. He is a physiologist recognized for his work on how ion channels control the excitability of neurons and cardiac muscle. Bean received a PhD in Biophysics from the University of Rochester in 1979 and further training as a postdoctoral fellow at the Yale School of Medicine, working with Richard W. Tsien on cardiac electrophysiology. In addition to his current position at Harvard Medical School, he has worked at the University of Iowa and at the Vollum Institute of Oregon Health Sciences University.

About Clifford Woolf, MD, PhD: Dr. Woolf is Director of the F.M. Kirby Neurobiology Center and the Neurobiology Program at Boston Children’s Hospital. He trained for his M.D. and Ph.D. at the University of the Witwatersrand in Johannesburg South Africa before joining University College London, where he was a professor of neurobiology. Woolf moved to Boston as the first incumbent of the Richard J Kitz Chair of Anesthesia Research at Harvard Medical School and established the Neural Plasticity Research Group, based in the Department of Anesthesia and Critical Care at the Massachusetts General Hospital. He is a faculty member of the Harvard Stem Cell Institute and the Department of Neurobiology at Harvard Medical School.

New video tutorials to help you get the best start with QPatch Compact

For our new users of QPatch Compact, we have produced five new video tutorials to help you get started with planar patch clamp experiments on QPatch Compact. Besides the new video tutorials, on the new QPatch Compact Support Site, you have access to safety instructions, user manual incl. test protocols, and troubleshooting guides.

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

Sussex Drug Discovery Centre and Sophion Bioscience announce new strategic partnership

Sophion Bioscience has partnered closely with Sussex Drug Discovery Centre (SDDC), based at the University of Sussex, for many years. We are now looking forward to extending our partnership, providing SDDC with wider access to our automated patch clamp technology and knowledge.

For SDDC, this partnership will strengthen their potential for research collaborations with both academic and industrial partners. Their existing structural biology, drug discovery and ion channel expertise, together with core facilities such as Cryo-EM also available at the University, mean SDDC is now ideally placed to become a centre of excellence for ion channel research.

We want to support SDDC in training, education, and inspiring the next generation of ion channel drug discovery experts. Additionally, for Sophion Bioscience, the strategic partnership will allow us to expand our field support operations in the UK by welcoming our customers to the SDDC laboratory for application development and demonstrations.

We look forward to providing even better and faster customer service to our UK automated patch clamp users, working dedicated to accelerating and pioneering ion channel research.

Would you like to book a meeting with our application specialist at SDDC?

Please contact Sarah Lilley directly or you can book a demonstration in one of our laboratories in Copenhagen, Denmark, Boston, US, and Tokyo, Japan here: https://sophion.com/about/contact-info/

Sophions third webinar on APC and iPSC. Did you miss it?

The discovery that it is possible to restore pluripotency to adult somatic human cells has revolutionized the field of biological science and regenerative medicine.

With Sophion’s automated patch technology, we have been able to record cardiac voltage-gated ion channel currents (INa, ICa, IKr, IK1) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), with up to 50% success rates and paced action potentials in up to 20% of recorded cells.

Last week, guest speaker Fitzwilliam Seibertz from University Medical Center Göttingen and Kadla Røskva Rosholm from Sophion Bioscience gave a joint presentation on their latest research in manual and automated patch clamp measurements of IK1 currents in hiPSC-CM, a current that is often lacking in ‘immature’ hiPSC-CM.

You find the recording here:

Sign up for our next webinar

You can now sign up for our next webinar on Automated Patch Clamp and iPSC. In this webinar, we will be focusing on manual and automated patch clamp measurements of IK1 currents in human induced pluripotent stem cell-derived cardiomyocytes.

Guest speaker Fitzwilliam Seibertz from the University Center Göttingen will join us to give a presentation on ‘Differentiation of induced pluripotent stem cells into cardiomyocytes with a focus on maturity-induced IK1 development’.

This is followed by Sophion’s iPSC expert, Kadla Røskva Rosholm, who will take us through recent Sophion data on the electrophysiological characterization of hiPSC-derived CMs, including voltage-gated IK1 currents and action potential measurements, using automated patch clamp.

Read more and register for the webinar here

Sophion Bioscience offers research and travel grants for early career scientists

Don’t miss the September opportunity to apply!

We are looking for students (MSc or PhD) or early career scientists (within 5 years of BSc/MSc/PhD award). You are working in ion channels or related fields and you would like to present your work at Sophion’s Ion Channel Modulation Symposium. You could also have QPatch II or Qube384 data and want to tell your story at any international conference. Take this opportunity to make an application for our travel grant.

Alternatively, your postgraduate studies or early career lab research could be rocketed into the stratosphere by applying for our research grant. This will give you access to our platforms and experts in our labs across the world. Sophion’s research grant might be your ticket to completing a key finding for your thesis or strengthening your lab’s latest funding application.

For more info & application forms click 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

Did you miss our second webinar on APC and iPSC from last week?

Research in iPSC holds huge promise for drug discovery. With Sophion’s automated patch technology, we can begin to understand the functional changes taking place in neurons with loss of CDKL5 function.

Last week, guest speaker Elizabeth Buttermore, from Boston Children’s Hospital and Kadla Røskva Rosholm, from Sophion Bioscience presented in collaboration their latest research on cellular, molecular and electrophysiological characterization of CDKL5 deficiency disorder iPSC-derived neurons.

From all over the world, we were happy to see so many engaged and interested participants.

You can see the recorded webinar below:

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

Two papers published by Nanyang Technological University Singapore on QPatch

Profs. Seow Theng Ong, George Chandy and colleagues at A*STAR and Nanyang Technological University, Singapore, have recently published two papers to share their research on ion channels and immunology using our QPatch solution.

In a multi-disciplinary collaboration spanning four continents, they published a Nature Microbiology paper contributing QPatch recordings of KCNJ15/Kir4.2 ion channels in monocyte immune cells. This work furthers our understanding of tuberculosis infection and clearance. The paper can be read here

The second paper generated cryo-EM structures of Kv1.3 ion channels with and without the Kv1.3 toxin peptide analogue dalazatide (ShK-186) bound. Kv1.3 ion channels are a key element in the activation of immune T-cells: by blocking them with dalazatide the over-activity seen in autoimmune diseases (e.g. psoriasis) can be reduced. Find the paper published in PNAS here

Big steps in cardiomyocyte action potential recordings on QPatch II

In a fruitful collaboration between Prof. Niels Voigt and scientist Fitzwilliam Seibertz of The University of Göttingen and our research scientist Kadla Røskva Rosholm, PhD, we have made great strides in overcoming the maturation and recording hurdles in the research of human induced pluripotent and stem cell (hiPSCs).

With improved culturing and induction techniques, the Voigt lab have generated consistently ‘matured’ hiPSC-derived CMs. These maturation developments married with significant advances in QPatch II current clamp recordings have led to high quality recordings and success rates.

Action potential recordings were made in physiological Ringer’s solutions on our QPatch II instrument without using fluoride or calcium ‘seal enhancing’ solutions. Our developments on automated patch clamping provides techniques for fast, efficient data generation allowing accurate biophysical and pharmacological characterisation of hiPSC-CMs.

This collaborative data was recently presented at the Biophysical Society meeting. See the poster here

Sophion Travel & Research Grants for students and early career researchers

Sophion are pleased to announce two new grants supporting young scientists: travel & research grants.

We are looking for students (MSc or PhD) or early career scientists (within 5 years of BSc/MSc/PhD award). You are working in ion channels or related fields and you would like to present your work at Sophion’s Ion Channel Modulation Symposium. You could also have QPatch II or Qube384 data and want to tell your story at any international conference. Take this opportunity to make an application for our travel grant.

Alternatively, your postgraduate studies or early career lab research could be rocketed into the stratosphere by applying for our research grant. This will give you access to our platforms and experts in our labs across the world. Sophion’s research grant might be your ticket to completing a key finding for your thesis or strengthening your lab’s latest funding application.

For more info & application forms click here.

Introducing QPatch Compact – semi-automated patch clamping

With QPatch Compact, anyone can learn to patch-clamp in less than half an hour. The ready-to-use system offers the flexibility of manual patch clamp with the robustness and ease of use known from the QPatch and Qube automated patch clamping solutions.

QPatch Compact is a semi-automated patch-clamp solution enabling you to conduct up to 8 experiments at the same time, either synchronized to increase replicates or independent to increase information content in a short time.

The software helps you set up and analyze your experiments. All you must do is prepare the cells and handle the pipetting. QPatch Compact does the rest.

Imagine a benchtop instrument that you simply plug in and conduct your experiments without needing an antivibration table, micromanipulator, faraday cage, etc.

QPatch Compact gives you:

• Stable recordings
• Integrated system
• Small footprint
• Giga-seal on demand

Read more.