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

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.

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 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

BPS2021 65th Biophysical Annual Meeting

Biophysics 2021 will be virtual. Sophion will be attending as usual but with a virtual booth.

Read more about the meeting here. More information about the annual satellite meeting: Drug Discovery in Ion Channels will follow shortly, so stay posted.

Sophion – Empowering innovation in drug discovery

An increasing number of patents using QPatch data are published worldwide. More than 350 patent families have been published with the support of QPatch high-quality electrophysiology data since 2005. Last year alone 60 patent families were published supported with QPatch data and the rate of patents filed per year is increasing.

The majority of the patents are filed in the US (46%), with Japan and the UK as follow-ups (11% each) and Switzerland in close pursuit (10%). The remaining 22% comes from a variety of countries with China as the prominent with 5% of the patent filings and then Germany, Italy, Denmark, Sweden etc.
Not surprisingly the majority of patent applications come from big pharma like Shionogi, Dainippon, Novartis, AstraZeneca, J&J and Gilead, but surprisingly, many smaller pharmaceutical companies use the QPatch data as a part of their patent filing.

We are of course happy that QPatch is used actively, not only for drug discovery, compound characterization and cardiac safety studies, but are also that QPatch data is used in the patent filings worldwide.

Source: https://worldwide.espacenet.com/

Biophysical Society 63rd Annual Meeting 2019

As always at Biophysics we have a lot of activities going on. Please see below.

Friday, 1st March

Ion Channel Satellite Meeting

Sophion will be co-hosting the recurring satellite meeting, Drug Discovery for Ion Channels. Read more about the meeting here.

Saturday, 2nd March

Customer outing

Monday, 4th March

01:45 PM – Poster presentation:

Title: IPSC-derived motor neurons on the automated patch clamp platforms Qube and QPatch

Poster presenter: Application scientist Kadla Rosholm

Location: Exhibit Hall A-E – Poster board No.: B332

Abstract:

Human induced pluripotent stem cells (hiPSCs) can be differentiated into multiple cell types, including neurons and cardiomyocytes. This gives rise to a novel way of establishing human disease models, which in turn can be used for drug development in vitro. Ion channels represent highly attractive therapeutic targets in the nervous and the cardiovascular system, rendering electrophysiological studies of hiPSCs important for their usage in drug discovery. However, such studies have traditionally been limited by the labor-intensive and low-throughput nature of patch-clamp electrophysiology. Here we use our automated patch clamp systems Qube 384 and QPatch 48 in order to increase throughput and reduce timelines.
Our observations include channel expression versus time in culture, the pharmacological dissection of endogenous ion channels (e.g. Nav and Kv), identification of ligand-gated receptors, and recordings of action potentials using the current clamp feature. Also, we show the electrophysiology of a spinal muscular atrophy (SMA) and an amyotrophic lateral sclerosis (ALS) model. The disease model for SMA was derived by mutations in the SMN1 gene and shows enhanced sodium channel activity but no shift in the normalized current-voltage relationship. ALS was here mimicked by a single point mutation in the superoxide dismutase 1 protein (SOD1), D90A, which had previously been identified in recessive, dominant and seemingly sporadic pedigrees. Cells carrying this point mutation displayed larger sodium currents, which eventually led to neurofilament aggregation, neurite degeneration and other phenotypes. We could confirm that the electrophysiological effect could be reversed by point mutation to D90D.

Our measurements validate the feasibility of measuring hiPSC ion channel currents using the APC platforms Qube and QPatch. Altogether, these results can facilitate evaluating the use of hiPSC for early drug development and in extension personal medicine.

Tuesday, 5th March

Sophion Seminar

9:30-11:00 AM – Sophion will be hosting a mini ion channel symposium in Room A at Baltimore conference center titled:

Electrophysiological characterization using automated patch clamp (QPatch and Qube) of hiPSC-derived neurological disease models, new automated patch clamp ion channel assays for CiPA cardiac safety testing (dynamic hERG and LQT3 late Na_V1.5) and Na_V1.7 drug discovery.

• Marc Rogers (Metrion Bioscience): Milnes and late Na_v1.5 for cardiac safety,
• Bryan Moyer (Amgen): HTS drug discovery,
• Kadla Rosholm (Sophion): hIPS neuronal disease models
• Sarah Williams (Charles River): Adaptive online V½ estimation.

Poster presentation

01:45 PM – Poster presentation:

Title: Biophysical and pharmacological profiling of multiple voltage-gated sodium channel subtypes on QPatch II

Poster presenter: Application scientist Daniel Sauter

Location: Exhibit Hall A-E – Poster board No.: B285

Abstract:

Voltage-gated sodium channels (VGSC) are responsible for the initiation and propagation of action potentials in excitable cells. VGSC have been identified as excellent drug targets for treatment of pain, epilepsy and to other neurological disorders. Early compounds, however, were developed using empirical approaches. The identification of the molecular identity of VGSC in combination with technological advances, such as the automated patch clamp technique, provide the basis for a rational design of subtype-selective compounds.

To date, 9 functional mammalian isoforms (Na_V1.1–1.9) have been described in the literature. The various subtypes differ in their expression pattern and exhibit distinct biophysical and pharmacological profiles. All have in common that they produce a transient inward current in response to membrane depolarization. During this process, the VGSC transitions from a closed to an open into an inactivated state. Interestingly, inhibitor compounds often exhibit different pharmacological profiles dependent upon the ion channel conformational state.

In the present study, the second generation QPatch (QPatch II; Sophion Bioscience) was used in combination with adaptive voltage protocols to investigate state-dependent inhibition of tetrodotoxin (TTX) and tetracaine on 8 different VGSC subtypes (Na_V1.1-8). A first step was to determine the half-inactivation potential V_½(inactivation) for each individual cell. This value was then used during the next steps as preconditioning pulse. Such an adaptive protocol allowed to determine IC₅₀ values for both the closed and the inactivated state and reduce heterogeneity of the cells. Both IC₅₀ values and biophysical parameters of the different subtypes align well with literature values.

Sophion User Meeting 2018 – Europe

Join us for a couple of days of great QPatch and Qube talks and good company

We are happy to invite you to our European Sophion User Meeting on 5th and 6th September 2018 and we are very pleased to announce that GSK in Stevenage kindly has offered to host the meeting this year.

We are preparing an interesting programme starting at noon on 5th September giving everyone a chance to travel to Stevenage in the morning. Wrap-up on 6th September just around lunchtime.

More information about the meeting will follow shortly.

Make sure to register for the meeting now as there are a limited number of seats.

SLAS2018

This year you can meet the following Sophion people:

• Richard Kondo, sales manager, North America
• Weifeng Yu, director of customer support, North America
• Daniel Sauter, applications scientist, North America
• Thomas Binzer, vice president – R&d & Marketing

On Wednesday, February 7, 2018, 11:30 AM – 12:30 PM Daniel Sauter will be presenting a poster titled (Poster Number 1319-E-):

HT Automation for patch clamp based primary screen for Na_V1.1 using Qube384

Read more about SLAS2018 here.

Sophion user meeting in our new facilities in Japan

To accommodate the needs of a growing customer base in Japan, we have expanded our laboratory and demo space in our Japanese facilities in Honjo-Waseda. This was celebrated with a three day user meeting; two days with work shop and one day with seminar with great talks on science. Both the demo room with QPatch and Qube side by side as well as the conference room were in use to accommodate the approx. 30 users that wanted to learn about the latest tips, tricks and software for QPatch and Qube 384. A great success with active interaction and continuing into the evenings with delicious Japanese foods.

Tecan publishing article about QPatch

We are proud to share with you an article published in Tecans latest journal about Sophion and our work with the QPatch. You can read the article here.

Sophion Bioscience is acquired by Sophion CEO, management and investors

Sophion Bioscience has been acquired by Sophion CEO Thais T. Johansen, its management and a group of experienced investors.

Sophion was founded in 2000 as a spinoff from Neurosearch and have since the beginning been pioneering ion channel research and drug discovery. In 2004 Sophion launched the QPatch automated patch clamp solution, which still today is benchmark for advanced electrophysiology and cardiac safety in drug discovery. In 2013 Sophion Qube was launched taking automated patch clamp to the HTS space and taking automated patch clamping to a whole new level of usability. In between Sophion has continuously improved performance and capabilities and launched pioneering new features such as automated Rs compensation, automated current clamp, integrated cell preparation, etc.

Sophion was in 2011 acquired by Biolin Scientific Holding AB, a company owned by Swedish private equity firm Ratos AB.

Sophion CEO Thais Johansen states “Our new ownership structure and financial partners bring a long-term orientation and expertise in building a high-growth life science business. With this involvement, we are well-positioned to continue investing in innovation, technologies and people”.

Thais also said, “we will continue to build on the Sophion legacy with focus on quality, innovation and customer satisfaction” and continues “I am looking forward to talk to our partners over the next weeks to discuss these changes as well as discuss the many great news we have in pipeline”.

Sophion Bioscience employs approximately 60 people worldwide. It is headquartered in Copenhagen, Denmark and has subsidiaries in Boston, Tokyo and Shanghai, as well as distributors in Japan, India and Korea. Sophion has an install base of 100+ automated patch clamp systems and presence in more than 75% of the TOP20 largest Pharma companies in the world.

Sophion Bioscience, Inc. is in the building

Internal solution exchange on Qube 384 – New application report

Internal addition of compounds targeting the chloride channel CIC-1.

We demonstrate a robust ClC-1 assay on Qube with internal addition of compounds. The assay shows biophysical characteristics as expected for ClC-1 with good pharmacology and high Z-score. We further introduce Sophion`s Analyzer software that allows rapid analysis of large data sets to answer advanced electrophysiological questions, in the present case: What is the mode of action of a novel, unknown compound?

See the full application report here

Sophion User Meeting – Paris

We are happy to invite you to our European Sophion User Meeting on 7th and 8th September and we are very pleased to announce that Sanofi in Paris kindly has offered to host the meeting this year.

We are preparing an interesting programme starting at noon on 7th September giving everyone a chance to travel to Paris in the morning. Wrap-up on 8th September just around lunchtime.

À bientôt

Sponsors:

Safety Pharmacology Society annual meeting

Hope to see you at the annual Safety Pharmacology Meeting 2017 in Berlin. Meet us at booth #113 and speak with our ion channel experts on site.

When:  24th to 27th September

Venue: Maritim Hotel Berlin

Poster presentation (Poster #022)
Temperature effect on hERG channel pharmacology measured by using the Qube automated patch clamp system.

Abstract:

The human ether-à-go-go related gene (hERG) function is important for cardiac repolarization and inhibition of the channel can prolong the cardiac action potential, which give increased risk for ventricular arrhythmias including torsade des points (TdP). Therefore, In vitro evaluations of the compound effects is performed on the hERG channel routinely in drug development projects to detect potential arrhythmic side-effects.

Usually these compound measurements are carried out at ambient temperatures. Previously it has been shown that the potency for many compounds have been underestimated when compared to near physiological temperature tests. Therefore, a temperature controlled measuring environment is beneficial when testing compounds for the aims as mentioned here.

Until recently, the only possibility to test compound potency under voltage control conditions has been the manual patch clamp technique. Now automated patch clamp instruments with temperature control have come available making it possible to perform up to 384 parallel recordings at controlled temperatures ranging from 18°C and above.

Here we used an automated patch clamp system, Qube, to study the effect of temperature on concentration response relationships on a panel of compounds known to block the hERG channel. Qube has a temperature controlled test environment and in these studies, we show that temperature merits being taken into consideration when evaluating for hERG potency.

Neuroscience

See you at Neuroscience 2017, the world’s largest neuroscience conference for scientists and physicians devoted to understanding the brain and nervous system. You can find us at booth #823 where we look forward to meet you for an ion channel talk.

Venue:  Walter E. Washington Convention Center, Washington, DC