On 5th July 2000, Sophion Bioscience was founded as a spin-off from the Danish pharmaceutical company NeuroSearch. It is hard to believe that 20 years have passed.
From the annals on our servers and a carefully written diary by Sophion’s first CEO Torsten Freltoft, it is fascinating to follow the first years after the founding. As with all start-ups chasing capital was a part of everyday life to secure the development of what ended up being QPatch. Also, longer entries about Fussball-tournaments and fun nights out at conferences take up a lot of space and of course the inauguration of the new facilities that were opened in 2001.
With the launch of the QPatch in 2005, Sophion started manufacturing, and focus changed from securing capital for development to securing global growth. Around that time someone wrote in one of those vision statements, that were very popular in the ’00s, that potential users of the APC systems not only needed the system and measurement plates but that strong support from application scientists and field service engineers was needed by users and lacking from other vendors. Today, 16 years later we operate from the same principles, ensuring that our users are always supported by a dedicated team of Application Scientists and Field Service Engineers.
In the years from 2005-2010 new installs were booming and Sophion was on the list of fastest-growing companies in Denmark for four consecutive years. While production was busy ensuring supply for new users, R&D continued new developments on the QPatch introducing, among others, the worlds-first automated Rs compensation, ligand applications, QPatch HT (48), multi-hole QPlates and current clamp. All features that are now standard on all Sophion products and most commercially available platforms.
In 2011 a major transformation occurred when Sophion was integrated with Biolin Scientific. Although ‘only’ 11 years old at that point it forced Sophion to grow-up quickly as a company and we still benefit today from the professionalism and structure that was introduced in the Biolin years. A more efficient supply chain and financial reporting system, as well as our ISO 9001 certification, are all processes that we enjoy today and that made us better equipped for the future.
When Qube 384 was introduced in 2014 it changed the way ion channel drug discovery could be done. With 384 individual channels, patch-clamp experiments running primary screening could suddenly be performed. With the introduction of the stacker solution in 2015, it became possible to perform overnight unattended screens of up to 15 QChips, something which is performed routinely by leading CROs and pharma companies on Qube 384 today.
However, the integration into a larger corporation was not a commercial success, and in 2017 a management buyout resulted in Sophion again being “masters in our own house”. After that, things have speeded up again, as many of our current and new partners have noticed. With the introduction of QPatch II 48, QPatch II 16, Qube Opto, online V½ estimation, and the new improved temperature controller, our APC systems are now easier than ever to use, with more advanced features. Double-digit growth, year on year, for the past 4 years has put us in an interesting new situation where we are running more EU projects, more industry partnerships, and more academic collaborations than ever.
In 2020 Sophion Bioscience is stronger than ever, and despite a challenging “Corona-quarter” in Q2-2020”, the future looks bright and promising. While parts of the world are still in lockdown, the crates shipped from Copenhagen in the past few weeks are a sure sign that other parts of the world are opening up again.
With Qube and QPatch installs in all major pharmaceutical companies we are proud to have left our mark on the ion channel field for the past 20 years and plan to continue doing just that for the next 20 years as well.
“Good habits formed at youth make all the difference”
We do not know what the future holds. In the first twenty years, we have managed not only to bring the world’s best APC platforms to market, combining high performance and data quality with a design that makes them so easy to use that patch clamping is accessible to everybody. We promised back then to “take the voodoo out of patch clamping”, and we believe we have achieved just that.
What we can promise you for the future; We will continue to be inquisitive and innovative. We will continue to push the boundaries, enabling ion channel drug discovery and adjacent fields by combining ease-of-use with performance. We will do that while honouring the vision from 2004 because we ‘choose to focus on customer support’.
— hIPSC, QPatch, Qube
hiPSC motor neurons on Qube and QPatch
Neurological diseases like Amyotrophic Lateral Sclerosis are detrimental in their nature and not easy to treat. In the search for new interventions it is necessary with model systems to test molecules, genetic modifiers etc. We can record both healthy, diseased and rescued hiPSC on our instruments. Read more here.
— APC, cav1.2, high throughput screening, Qube
Cav1.2 on Qube, no rundown
High success rates and minimal rundown with pharmacology according to literature values. The third CaV1.2 cell line, this time kindly provided by Charles River, helps demonstrate how Ca-currents can be recorded stably on automated patch clamp. So, whether you want to investigate the CiPA protocol, interrogate for state dependent mode of action or biophysical characteristics, Qube is the enabling technology. See the full report here.
Two papers were recently published mechanistic studies; in Inhibitory effects of cannabidiol on voltage-dependent sodium currents Xenon together with Simon Frasier University used temperature control on Qube to describe the potency and mechanism of cannabidiol binding to voltage-gated sodium channels. Interestingly the potency is higher at lower temperatures. In Selective Nav1.7 Antagonists with Long ResidenceXenon together with Genentech describe the mechanism of several of their compounds in selectively inhibiting Nav1.7, which is relevant in relation to inflammatory and neuropathic pain. These compounds act very slowly, but Qube allows more than one hour long experiments with very good voltage control during the whole experiment or as the authors state:
“Appropriate filters for minimum seal resistance and minimum current size were applied, and series resistance was compensated >80% to yield high- quality sodium channel recordings on par with manual voltage clamp techniques”
— high throughput screening, Qube, Qube 384
Qube is designed for drug discovery
We asked one of our customers how they screen several hundred thousands of compounds with high fidelity electrophysiology?
“We let the Qube run our large screening campaigns unattended during the night so we can run and develop other assays on the same instruments during the day”
Juha Kammonen, Principal Scientist, Charles River Laboratories
1 - 6 March
— automated patch clamp, ion channels, ipsc-derived motor neurons, QPatch, Qube, Sophion
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
Monday, 4th March
01:45 PM – Poster presentation:
Title: IPSC-derived motor neurons on the automated patch clamp platforms Qube and QPatch
Location: Exhibit Hall A-E – Poster board No.: B332
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
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,
Sarah Williams (Charles River): Adaptive online V½ estimation.
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
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.
2 - 6 February
— QPatch, Qube
Make sure to come and see us at booth #1703 at SLAS2019 in Washington DC. The conference will take place at the Walter E. Washington Convention Center.
To reflect our growing customer base in Japan we are happy to introduce our new Japanese version of www.sophion.com. The new Japanese website ensures that also our Japanese customers and partners have access to our publication database with posters, publications and application reports, as well as our application database where you can browse content grouped by ion channel type or disease area.
5 - 6 September
— automated patch clamp, Drug Discover, ion channels, QPatch, Qube, User Meeting
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.
— Qube, Qube 384
How easy is it to use Qube?
At Sophion we believe that ease of use is important. When a customer spontaneously express clear appreciation of how easy it is to use our systems, we know we got it right:
“It was true that it’s really up and running after two days training. We are very pleased”
Maija Ivaska, Research Assistant, Orion Pharma
Ease of use does not come by itself with sophisticated electrophysiological recordings in automated patch clamp, but is embedded in the Sophion DNA.
Ask for a demo anywhere in the world to experience this yourself. We are so confident that you will be allowed to run your own experiments at the end of the first day….and that is not always the case with APC instruments.
With our instruments you can perform experiments with a very low risk of human error and large degree standardization, enabling easy learning, many operators and high laboratory efficiency.
Qube Opto 384 – for optical stimulation of ion channels or compounds.
Optical stimulation combined with Automated Patch Clamp allows for precise control of e.g. channelrhodopsins, caged compounds and pacing studies. To allow for even better control than with our standard APC solutions, we have now integrated 384 adjustable LEDs to allow for optical stimulation of ion channels, ligands or compounds.
To compensate for heating due to the large amount of energy released, we have adapted our on-site temperature control, so temperature effects are reduced to a minimum.
To avoid desensitization from ambient light we have darkened the cabinet so Qube looks even cooler, having a distant resemblance to a well-known character from a movie happening in a galaxy far, far away.
384 LEDs to ensure consistent and even light distribution throughout all 384 sites
Light ramps and other waveforms through adjustment of timing, duration and intensity of light
Integrated temperature control to avoid unwanted temperature effect
Full LED control integrated in Qube software
Dark cabinet allows for automated handling of light sensitive compounds and cells
During the coming months we will be playing with this new setup ourselves together with a few select partners. If you are also interested to discover the full potential of this setup and would like to come play with us, you are welcome to contact Sandra Wilson (firstname.lastname@example.org) or visit booth #518 at Biophysics for more information.
— high throughput screening, HTS, Nav1.1, Qube
High throughput screening on Nav1.1 using Qube
The voltage-gated sodium channel NaV1.1 is highly expressed in fast spiking interneurons (FSIs), which are important for memory encoding and other cognitive functions. An impaired function of FSIs is associated with disorders like autism, schizophrenia, Alzheimer’s and others. Potentiators of NaV1.1 have been shown to minimize cognitive dysfunction in transgenic mice with decreased levels of NaV1.1 in parvalbumin-positive neurons and this target thus lend itself to therapeutic intervention. The challenge is to identify the molecule with the desired mode-of-action which inherently requires electrophysiology. In summary we show that Qube 384 provides:
hCav1.2 recordings on Qube 384 using step, train and CiPA protocols
Some ion channels have a tendency to exhibit reducing current level in the course of an experiment. A notable member of this class is the CaV1.2 channel, a very important ion channel expressed in nervous tissue, the heart and smooth muscle and thus a target for a range of therapeutics as well as a liability target for other groups of medications. Therefore it is important to be able to record reliably, stably and with a high success rate in the pursue of novel compounds with the desired profile on CaV1.2 modulation. Qube 384 provides a stable assay with the CaV1.2 channel generated by SB Drug Discovery with these characteristics:
Pharmacology and current-voltage relationship in accordance with literature values
Success rates up to 94%
Stable currents with rundown as low as (1.2 ± 0.9)% per minute
The CiPA protocol yields stable currents with rundown as low as (1 ± 1)% per minute
— BPS18, ion channels, QPatch, Qube
Biophysics 2018 – here we come!
Time flies and soon BPS2018 will kick-off in San Francisco. We look forward to see you in San Francisco and hope that you will join us for the below events:
Satellite meeting – Friday, February 16th
Beer tasting and dining – Saturday, February 17th
Sophion Ion Channel meeting – Tuesday, February 20th
Poster presentation – Wednesday, February 21st
Read much more about each event here and make sure to sign up as the seats fill up quickly.
— ion channels, QPatch, Qube, User Meeting
Sophion User Meeting, Boston – Save the date!
We are still working with the agenda but can, at this point, reveal that we have the pleasure of having Julie Klint, Lundbeck as one of several speakers. Julie will give a talk titled: Finding NaV1.1 activators – development and validation of a HTS suitable assay on the Qube. Also Noah Shuart from Xenon will be giving a talk.
Hilton Boston/Woburn, 2 Forbes Rd. Woburn, MA 01801
11.30 AM Registration and lunch buffet
01.00 PM Dr Kelly Gatfield, GSK: Tools for drug discovery: Early safety profiling and electrophysiology platforms for reducing attrition
01.30 PM Dr Julie Klint, Lundbeck: Finding NaV1.1 activators – development and validation of a HTS suitable assay for the Qube 384
02.00 PM Dr Noah Shuart, Xenon: Using Qube to assess IPSC neuronal sodium currents and studying mechanism of VSD4 binding ligands in heterologous expression systems
02.30 PM Coffee break
03.00 PM Bryan Koci, Eurofins: Optimization of cardiac safety pharmacology assay on the QPatch HT
03.30 PM Dr Kris Kahlig, Praxis Precision Medicines: Benchmarking Eleclazine: Biophysical characterization of a cardiac late INa inhibitor
04.00 PM Dr Mads P G Korsgaard, Sophion Bioscience A/S: Update on Qube 384
04.30 PM Dr Daniel Sauter, Sophion Bioscience, Inc.: Light stimulated electrophysiology on Qube: applications for ligand-gated ion channels
05.30 PM Wine tasting and tapas
08.30 AM Registration and coffee
09.00 AM Dr Kathryn Henckels, Amgen: Development of a TMEM16A QPatch assay for assessing small molecule antagonists
09.30 AM Dr Robert Petroski, Dart: Using the QPatch HTX for lead optimization of ligand-gated ion channels
10.00 AM Coffee break
10.30 AM Dr Haoyu Zeng, Merck: Systematic Performance Comparison between QPatch and PatchXpress for Cardiac Ion Channel Assays, and GLP-readiness Evaluation of QPatch for the CiPA Paradigm
11.00 AM Dr Rasmus B Jacobsen, Sophion Bioscience A/S: QPatch, Past, Present and Future
— ICMS2018, ion channel modulation symposium, QPatch, Qube
Registration for ICMS2018 is now open
Wednesday and Thursday 20th and 21st June, 2018 Sophion will be arranging and hosting the third Ion Channel Modulation Symposium at Clare College in Cambridge (UK) and it is now possible to register for the event.
We look forward to seeing you in Cambridge next June.
— Fast desensitizing, Fast desensitizing ion channels, Qube, Qube 384
Fast desensitizing ion channels recorded on Qube 384
Some ligand gated ion channels have a tendency to desensitize over time, making it difficult to establish a stable assay baseline. Rapid compound washout can counteract desensitization by reducing ligand exposure time to a minimum.
On Qube 384 the minimum washout is now less than 1 second (0.8 s), enabling stable assay for fast desensitizing ion channels.
With nAChRa1 as model, acetyl choline as agonist and tetracaine as test compound, a stable and high performance assay was established with:
Ligand exposure time 0.8 s
Whole-cell resistance of average 1.2 GΩ
Overall success rate of 89%
Very tight data – CV of ≤ 9% for control rows and columns
High throughput screening for mode-of-action on Nav1.7
A high-fidelity patch clamp set up is necessary to discover use-dependent mode of action. Qube is a second-generation automated patch clamp system that fulfils this requirement and allows for testing of many thousands of compounds per day in an unattended fashion. Using Qube in a drug development cascade allows asking the right questions during the primary screen, making a follow-up validation study obsolete. Some key points for a Qube screening like this are:
— biophysics, ion channels, QPatch, Qube
Biophysical Society 62nd Annual Meeting
We look forward to Biophysics 2018 where we will be doing a lot of activities:
First of all you can meet with our ion channel experts at our booth #518 at the Moscone Center.
Friday, 16th February Sophion will be hosting the annually recurring satellite meeting, Drug Discovery for Ion Channels.
See the agenda for the meeting here and make sure to sign up as the spaces are limited.
Beer Tasting & Dinner
Saturday, 17th February we have the pleasure of inviting you to an informal evening of beer tasting, good food and great networking at the Bartlett Hall in San Francisco.
Make sure to sign up for this event here. Limited number of seats so be quick.
Ion Channel Mini Symposium
Tuesday, 20th February we will be having a short meeting at the conference center with the presentation title: Drug discovery and electrophysiological characterization using automated patch clamp (QPatch).
Venue: Room 6, Moscone Center, San Francisco – sign up here for the meeting:
10:30 – 11:00
Dr Damian Bell, Iontas Ltd. Efficient ion channel cell line generation using MaxCyte electroporation and QPatch validation
11:00 – 11:30
Dr Daniel Sauter, Application Scientist, Sophion Bioscience A/S Induced pluripotent stem cell-derived cardiomyocytes (Cor.4U) characterized on an automated planar patch clamp set up (QPatch HT)
11:30 – 12:00
Dr Alan Wickenden, Scientific Director & Fellow, Molecular & Cellular Pharmacology, Janssen R&D, L.L.C NaViGATING the long and winding road to new analgesics: Discovery of potent, selective, closed-state peptide Nav1.7 blockers
Refreshments will be served.
Wednesday, 21st February between 10.30 AM and 11.30 AM, Dr Daniel Sauter will present a poster titled:
Induced pluripotent stem cell-derived cardiomyocytes (Cor.4U) characterized on an automated planar patch clamp setup (QPatch HT)
Poster board no. B301
18 - 20 October
— CiPA, Patch Clamping, QPatch, Qube, User Meeting
Sophion Seminar & Workshop – Japan
You are invited to the Sophion Seminar & Workshop in Japan at Sophion Bioscience K.K.’s premises:
Waseda Research Park
1011 Nishitomida, Honjo, Saitama 367-0035, Japan
10:30 Welcome remarks and safety briefing Dr. Yuji Tsurubuchi, Country Manager, Sophion Bioscience K.K., Japan
10:40 New ownership and future strategy at Sophion (tentative) Mr. Thais Johansen, CEO, Sophion Bioscience A/S, Denmark
11:00 Educational lecture: Redox Physiology of TRP channels Prof. Yasuo Mori, Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Japan
12:00 Lunch break and new Sophion K.K. lab tour
Each participant is assigned to either group A or B at the time of registration. The tour starts at 12:00 and 12:45 for group A and B, respectively. Lunch is served for group A after the tour.
13:30 Potency of ReproNeuro “Human iPS derived neurons” in the drug discovery support Dr. Makoto Honda, ReproCELL, Inc., Japan
13:50 iPS derived human cells; iCel®, MyCell® DDP/ “disease in a dish” and ideas of application for drug discovery Dr. Ko Zushida, Cellular Dynamics International Japan Co., Ltd.
14:20 Using the QPatch HTX to drive drug discovery: ligand-gated ion channels Dr. Robert E. Petroski, Scientist IV/Manager Neurophysiology, Dart Neuroscience LLC, USA
15:00 Coffee break
15:30 Targeting T-type calcium channel for anti-pain drug discovery Dr. Norio Hashimoto, Nissan Chemical Industries, Ltd., Japan
16:10 Exemplar of optical recording from neural and cardiac activities Mr. Kenji Tsubokura, Brain Vision Co., Ltd., Japan
Voltage- and current clamp on induced pluripotent cardiomyocytes with Qube 384
Action potentials are induced in both HL-1 mouse atrial cardiomyocytes and Axiogenesis Cor.4U iPS cell-derived cardiomyocytes.
Voltage- and current clamp on induced pluripotent cardiomyocytes with Qube 384. Action potentials are induced in both HL-1 mouse atrial cardiomyocytes and Axiogenesis Cor.4U iPS cell-derived cardiomyocytes. Qube can combine voltage clamp and current clamp in the same sweep for added experimental control. Click here to read more.