automated patch clamp Archives - Sophion
Safety pharmacology with aging population Sophion paper

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 aging demographic.

We have made the review open access (no paywall), read the paper in full here

Sophion-hiPSC-derived-cell-lines

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.

Sophion read more

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.

Sophion-hiPSC-CM-current-clamp

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

Sophion-hERG-current-traces-22-35C

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.

Sophion read more

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

 

Sophion-Webinar-APC-and-hiPSC

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:

Sophion-alpha-cobratoxin

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

Collaborative paper on antibodies neutralizing cobratoxin

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).

Sophion-automated-patch-clamp-and-large-molecules

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.

Sophion read more

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 NaV1.5) and NaV1.7 drug discovery.

  • Marc Rogers (Metrion Bioscience): Milnes and late Nav1.5 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 (NaV1.1–1.9) 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 (NaV1.1-8). A first step was to determine the half-inactivation potential V½(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 NaV1.1 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

High throughput screening

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