Sophion PNAS paper on nanomaterials & the blood brain barrier

Whilst Sophion are known for our expertise in ion channel recordings, our scientists are also leading the way in understanding the physiological effects of nanomaterials crossing the blood brain barrier (BBB).

Nanomaterials hold great promise for future technologies & applications. But as we enter this brave new nanoworld, so we must determine the safety of these new materials.

Funded by the Marie Curie charity this seminal study was an academic-industry collaboration crossing four countries & two continents, in which Sophion’s head of innovation & technology development Dr. Sandra Wilson was a co-author. The study authors also created the cover image & was published in the prestigious journal Proceedings of the National Academy of Sciences (PNAS).

The study investigated the effects of metallic nanomaterials crossing the BBB, leading to better understanding of these materials in the body & their potential for neurotoxicity in the brain. This invaluable study will allow us to make safer nanomaterials with a range of uses including drug delivery & nanomedicines.

Congratulations to first author Zhiling Guo, Sandra & all authors on this groundbreaking research. You can follow this link to read more.

Ion channel talks for graduate and undergraduate students

Sophion’s Daniel Sauter recently gave a talk on ‘Ion Channel Drug Discovery’ at Universidad De La Salle Bajio, Mexico. The talk was live on Facebook and covered how automated patch clamp plays a key role in discovering new medicines in this critical target class…….. the what, why & how we study ion channels, including a typical drug screening cascade.

Fear not if you missed this excellent talk, the video recording can be found here on Facebook

Thanks to Dr. Miriam Sanchez of the Centro de Neurociencias at Universidad De La Salle Bajio, Mexico, for hosting Daniel & producing & sharing such a professional lecture video.

If you are interested in one of our application scientists give a similar talk on ‘Ion Channels and Automated Patch Clamping’ for your graduate or undergraduate students please contact us (info@sophion.com) or use the contact box on the homepage.

Interested in Optogenetics?

Optogenetics uses light to activate (depolarize) or inhibit (hyperpolarize) cells genetically engineered to express light-gated ion channels. In this way, control of a cell’s membrane potential can be controlled by light, allowing fast & precise control only in the cells expressing the light-gated ion channels. Channelrhodopsins (e.g. ChR2) are cation channels that when gated by light will depolarize the cell membrane; halorhodopsin (e.g. NpHR) is a chloride ion pump that can be used to hyperpolarize the cell membrane.

By combining these optogenetic actuators with cell-type specific gene promotors & using viral delivery (e.g. adenovirus), very specific neurons within a neural circuit can be targeted in vivo to define roles & mechanisms in behaviours in live, active animals.

Unsurprisingly this very powerful technique has many applications & would not be hyperbole to say it’s revolutionized neuroscience. Indeed, Nature made it their method of the year for 2010. Barring the Nobel Prize, which is sure to follow, all the main scientific prizes & plaudits have been awarded to Georg Nagel, Peter Hegemann, Ernst Bamberg & Karl Deisseroth, the scientists who invented & developed this technique.

The ability to control membrane voltage by both voltage-clamp & optogenetics on an automated patch clamp platform with the flexibility & potential this may afford researchers was not lost on Sophion. By 2018 we had developed a functional Qube with LED arrays to perform simultaneous voltage-clamp & optogenetic light control of membrane voltage. Using ‘Qube Opto’ we have now produced a book chapter, application reports & presentations.

For more info on how Qube Opto might be used in your research see the links below or contact us at info@sophion.com.

• Optogenetics and Optical Tools in Automated Patch Clamping (Book chapter), Boddum, K., Skafte-Pedersen, P., Rolland, J. F., & Wilson, S 2021. Sophion Bioscience, Axxam S.p.A.
• Qube Opto 384 – Optical modulation of ion channels (Application Report). Kim Boddum 2019, Sophion Bioscience.
• Optical modulation of ion channels using Qube Opto (Poster). Kim Boddum, Peder Skafte-Pedersen, Jens Henneke, Daniel Sauter, Jean Francois Rolland, Jiaye Zhang, Sandra Wilson 2019. Sophion Bioscience, Cranfield University, Axxam S.p.A.
• Ligand-activation of GABAA receptors on the automated patch clamp platforms QPatch and Qube 384 using conventional electrophysiology and optopharmacology (Poster). Melanie Schupp, Kim Boddum, Daniel R. Sauter, Peder Skafte-Pedersen, Linda Blomster, Hervør L. Olsen, Rasmus. B. Jacobsen 2018. Sophion Bioscience, Saniona.
• Super-short ligand exposure time on Qube Opto 384. News piece 2018
• Light activated rubi-GABA on Qube Opto 384. News piece 2018
• Qube Opto 384 – for optical stimulation of ion channels or compounds. News piece 2018

If you are interested in developing new assays, set up collaborations on optogenetics/optopharmacology or have ideas for future work lets talk.

Visit our lab from the comfort of your home

We are excited to invite you to our 3D virtual lab.

In this lab, you don’t need hand sanitizer, lab coat or face mask. You can wear your oldest trainers or sit on your sofa while casually strolling through the lab, and for once a cup of coffee can be brought along.

Have a walk through our lab – we are excited to hear how you like it

Visit the Sophion Virtual Showroom

Yale School of Medicine and Veterans Administration Acquire Automated Patch-Clamp

The ‘Center for Neuroscience and Regeneration Research’ at Yale School of Medicine and Veterans Affairs West Haven Medical Center has evaluated multiple Automated Patch Clamp (APC) solutions on the market in order to support and enhance their research, predominantly focused on chronic pain. We are happy to announce that the Waxman lab has acquired both Qube 384 and QPatch II 48 robotic patch clamp systems, making Yale and Veterans Affairs West Haven Medical Center one of the few academic institutions to house this powerful new technology.

The choice of both Qube and QPatch II was driven by a desire to both run larger screens and to run more focused assays in physiological solutions. Qube can run larger screens with the ability to run unattended overnight operation and the QPatch family of systems provides the only available medium-throughput APC instruments that can achieve gigaohm seals without the use of seal enhancers. Each of these robotic devices provide high throughput screening capability equivalent to that of half a dozen human electrophysiologists.

A core group of electrophysiologists including Dr. Mark Estacion, Dr. Brian Tanaka and Dr. Sulayman Dib-Hajj, as well as multiple postdoctoral fellows and Yale MD-PhD students, will carry out initial studies using this high throughput instrumentation.

About Center for Neuroscience and Regeneration Research at Yale School of Medicine and Veterans Administration. The goal of the Center for Neuroscience and Regeneration research is to harness the “molecular revolution” in order to restore function in the injured nervous system and to promote functional recovery following spinal cord injury, multiple sclerosis, stroke, traumatic brain injury and neuropathic pain. Read more here

About Director Stephen Waxman MD, PhD, (Bridget M. Flaherty Professor of Neurology and of Neuroscience) founded the Center for Neuroscience and Regeneration Research in 1988 at the Veterans Administration campus in West Haven, Connecticut. He served as the Chairman of Neurology at Yale from 1986 until 2009. Dr. Waxman’s research uses molecular, genetic, biophysical, stem-cell based and pharmacological techniques, together with sophisticated molecular imaging and computer simulations, to study the molecular basis for neurological diseases, especially spinal cord injury, multiple sclerosis, and neuropathic pain, and to search for new treatments that will alleviate suffering in these disorders. Dr. Waxman has published more than 700 scientific papers and his papers have been cited more than 40,000 times. Dr. Waxman has served on the editorial boards of many journals and has trained more than 200 academic neurologists and neuroscientists who lead research teams around the world.  Read more about Dr. Waxman here

We are staffing up in North America

Daniel Sauter, previous Sophion laboratory manager in Boston, have relocated to California where he will support the western part of USA and Canada. We will be looking for a new application scientist in Boston.

With an increase in installs and activities the last years, it was time to again get some people on the ground on the west coast. We are happy that Daniel has accepted to relocate to San Diego with his wife and two kids. In his new position Daniel will continue to support our users scientifically with his vast knowledge on electrophysiology and expertise on QPatch and Qube 384. Also, Daniel will take on new responsibilities within business development and sales. Over the next month when Daniel gets settled, he will contact users in the area, but you are welcome to take contact to him, if you have questions or just want to welcome him to the golden state (DRS@sophion.com)

Daniel will surely be missed in Boston. We aim to cover Daniels vacancy as soon as possible. Job posting can be found here. It will be big shoes to fill after Daniel, but we are sure that there are still many talented and passionate electrophysiologists out there, so let us know.

Posters from SPS2019 in Barcelona now live

As always we spend some good days at the SPS meeting, getting new acquaintances and meeting old friends and partners.

Steve Jenkinson (Pfizer, San Diego) did a well-received talk:

“The use of High-Throughput Multi Ion Channel profiling [on Qube 384 ed.] and in silico modelling in assessing arrhythmia risk: One Pharma’s experience and perspective”.

A very interesting presentation that addressed the Pfizer’s approach to early de-risking in cardiac safety. However, as an oral presentation, we cannot post it here, but watch out for similar talks in the future.

Five posters using QPatch was presented, emphasizing QPatch as the benchmark automated patch clamp solution for cardiac safety

“Electrophysiological characterization of human dopaminergic neurons derived from LUHMES cells”, Udo Kraushaar, Dominik Loser, Timm Danker, Clemens Möller, Marcel Leist. NMI (LINK)

“Functional Assessment of hNav1.x Ion Channels Using State- Dependent Protocols on the QPatch HT Automated Patch Clamp System”, Bryan Koci, Jennifer Wesley, Muthukrishnan Renganathan, Haiyang Wei, Diane Werth, Eurofins (LINK)

“Predicting Cardiac Proarrhythmic Risk Exclusively Using Automated Patch Clamp Data”, Edward SA Humphries, John Ridley, Robert Kirby and Marc Rogers, Metrion Biosciences, UK (LINK)

“Automatic estimation of hNaV1.5 channel inactivation improves pharmacological evaluation using the new adaptive protocol feature on Qube”, Anders Lindqvist, Sophion Biosciences (LINK)

“Activities for optimizing CiPA recommended protocols in patch clamp assays”, Katayama Y, Matsukawa H, Kanehisa T, Abe A, Yoshinaga T, Asakura K, Yoshikawa K, Tsurudome K, Tsukamoto T, Nissan Chemical, Japan Tobacco Inc., Eisai Co., Nippon Shinyaku, LSI Medience corp.and Sophion Bioscience (LINK)

Posters from ICMS2019 in Cambridge UK now online

Nine posters from ICMS 2019 in Cambridge UK are online. Thank you to the authors for the contribution to make this years meeting another success

• Cole BA et al 2019. Structure-based identification of novel KNa1.1 inhibitors (Uni of Leeds)
• Chakrabarti et A l 2019. In vitro inflammatory knee pain: Of Mice and Men (Uni of Cambridge)
• McCoull et Al 2018. Development of a novel screening system to identify activators of Two-pore domain potassium channels (K2Ps) (LifeArc)
• Moreels L et al 2019. Generating potent and selective inhibitors of Kv1.3 ion channels by fusing venom derived mini proteins into peripheral CDR loops of antibodies (Iontas)
• Marklew A et al 2019. Development and validation of NMDA ligand-gated ion channel assays using the Qube 384 automated electrophysiology platform (Charles River Laboratories)
• Rosholm et al 2019. Characterization of hiPSC-derived neurological disease models using automated patch clamp (Qube and QPatch) (Sophion)
• Sauter D et al 2019. Biophysical and pharmacological profiling of multiple voltage-gated sodium channel subtypes on QPatch II (Sophion)
• Williams S and Kammonen J 2019. Adaptive voltage protocols increase precision of voltage-gated ion channel measurements on highthroughput automated patch clamp platforms (Charles River Laboratories)
• Schombert B et al 2019. A pharmacological synopsis of small molecules, toxins and CiPA compounds targeting human cardiac Kv4.3 channels (Sanofi)

Find them here 

New application report: Perforated patch recordings on Qube 384

Would you like to fight run-down but think perforated whole-cell is not possible on a 384-instrument? We have made a new application report with a thorough description of how to make perforated patch experiments on Qube using either of four different perforating agents.

For the full report please click here 

Congratulations to our latest Ph.D student Jiaye Zhang

Big congrats to Jiaye Zhang who successfully received his Ph.D. degree for his thesis entitled “Development of an Optogenetic System for Ion Channel Studies” from Cranfield University.

Great that Ph.D. students can come to Sophion and start up new exciting work. In this case Jiaye’s project was prework and inspiration for the Qube Opto solution.

We are also very happy that Jiaye is well underway, currently working at the Chinese Academy of Sciences as a Post Doc within neuronal stem cells.

Diseased and control hIPSC motor neurons measured on Qube and QPatch

Motor neurons control essential voluntary muscle activity such as speaking, walking, breathing, and swallowing. Motor neuron diseases (MND) are a group of progressive neurological disorders that destroy motor neurons. Some MNDs are inherited, but the causes of most MNDs are not known.

Being able to measure and screen on diseased and wildtype hIPS motor neurons have long been requested from many of our users.

In this new poster just presented at “Neuroscience 2018” we show that measurements on normal and diseased motor neurons are possible with good success rates on both Qube and QPatch

• Electrophysiological properties of hiPSCs from Spinal Muscular Atrophy (SMA) or Amyotrophic Lateral Sclerosis (ALS) patients was measured and compared to their control cell lines
• ALS disease cells exhibit a significantly increased NaV current as compared to the control, which could be rescued by a single point mutation.

Find it here

31 new Publications and Reports from Q3

We have been informed that we missed a few publications from the Q3 list we posted some weeks ago. Thanks for letting us know…thats what friends are for.

Here is the (hopefully) complete list of publications from Q3 (and a part of Q2).

Learn more about how cannabis inhibits Na_v currents at therapeutically relevant concentrations or venom from the giant red bull ant published by, among others, Xenon Pharmaceuticals, GSK, AstraZeneca, Sanofi, Eisai, Uni Queensland and more

Peer reviewed publications

• Sokolov et Al 2018. Co-expression of β Subunits with the Voltage-Gated Sodium Channel NaV1.7: the Importance of Subunit Association and Phosphorylation and Their Effects on Channel Pharmacology and Biophysics. Journal of Molecular Neuroscience (LINK)
• Kanase et Al 2018. 4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties. Bioorganic & Medicinal Chemistry, Volume 26, Issue 9 (LINK)
• Gonçalves et Al. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology, Volume 133, 404-414 (LINK)
• Zha et Al. 2018. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, Volume 148, Pages 140-153 (LINK)
• Israel et Al. 2018. The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6. J. Med. Chem., 2018, 61 (4), pp 1730–1736 (LINK)
• Loucif et Al. 2018. GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. British Journal of Pharmacology (LINK)
• Xu et Al. 2018. Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. European Journal of Medicinal Chemistry, Volume 145, Pages 74-85 (LINK)
• Agwa et Al 2018. Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel Na_V7. Bioconjug Chem. 2018 Sep 12. (LINK)
• Colley et Al 2018. Screening strategies for the discovery of ion channel monoclonal antibodies. Current Protocols in Pharmacology, 82, e44. (LINK)
• Robinson et Al 2018. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 12 Sep 2018:Vol. 4, no. 9 (LINK)
• Procopiou et Al 2018. Discovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. Med. Chem (LINK)
• Ghovanloo et Al 2018. Inhibitory effects of cannabidiol on voltage-dependent sodium currents. Journal of Biological Chemistry (LINK)
• Bankar et Al 2018. Selective Nav1.7 Antagonists with Long Residence Time Show Improved Efficacy against Inflammatory and Neuropathic Pain. (LINK)

Posters

• Bettini et Al 2018. NMDA Receptor Modulators in QPatch. Evotech Gmbh (LINK)
• Boddum et Al 2018. Optical modulation of ion channels. Sophion Bioscience. (LINK)
• Boddum et Al 2018. GABAA receptor pharmacology evaluted in overexpressing HEK cells and primary astrocytes on QPatch. Sophion Bioscience. (LINK)
• Standing et Al 2018. Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384. GlaxoSmithKline (LINK)
• Klint et Al 2018. HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384. Lundbeck A/S (LINK).
• Bouyer and Hebeisen 2018. Na_V5 big late : An inactivation deficient mutant of Na_V1.5 as screening tool for late sodium currents of the cardiac action potential. B’SYS (LINK)
• Douglin Guo et Al. 2018 Simultaneous measurement of cardiac Na_v5 peak and late current in an automated QPatch platform. Pfizer. SPS 2018
• Koci et Al 2018. Optimization of Cardiac CiPA targets (Ca_v2 and KCNQ1/MinK) on the QPatch HT automated system. Eurofins. SPS 2018
• Huphries et Al 2018. New CiPA ion channel cell lines and assays for in vitro proarythmia risk assessment. Metrion Biosciences. SPS 2018. (Will be uploaded soon)
• Donglin Guo et Al 2018. Simultaneous measurement of cardiac hERG and Na_v5 currents using an automated Qube patch clamp platform. Pfizer. SPS 2018. (Will be uploaded soon)
• Renganathan et Al 2018. Automated High Throughput Na+ Late current Assay on QPatch HT platform for CiPA28. Eurofins. SPS 2018 (Will be uploaded soon)
• Lindqvist and Christensen 2018. Estimating hERGdrug binding using temperature-controlled high throughput automated patch clamp. Sophion Bioscience. SPS 2018 (Will be uploaded soon)

Application Reports

• Humphries and Binzer 2018. CiPA hERG Milnes kinetic assay on Qpatch (LINK)
• Sauter D 2018. Voltage and current clamp recordings of Cor.4U® human iPS cell-derived cardiomyocytes using Sophion’s QPatch (LINK)
• Boddum K 2018. Ligand gated ion channels: GABAA receptor pharmacology on QPatch (LINK)
• Sauter D 2018. Human iPS cell-derived cardiomyocytes (Cor.4U®) on Sophion’s Qube 384: voltage and current clamp recordings (LINK)
• Rosholm & Schupp 2018.2 recordings using QPatch (LINK)
• Schupp 2018. 8 hours unattended hERG run with ≥97% success rate and consistent pharmacology results (LINK)

QPatch II attracts a full house in Washington DC

QPatch II has it’s first public show at the Safety Pharmacology Society annual meeting in Washington DC the last few days.

It has been very well received by the many current and future users that have passed by the booth for a demonstration. Most are excited by the new icon-based operator software, that makes operation even easier, but also the speed, the reduced cell consumption and the preloaded standard protocols. And the looks off course. Isn’t she a beauty? Besides that, we have had excellent feedback on the new online V½ estimation…. The first QPatch II has been sold and we are we are currently producing more so you all can have something cool under your Christmas tree this year.

Read more here

New papers, posters and reports (Q3 2018)

Papers:

• Sokolov et Al 2018. Co-expression of β Subunits with the Voltage-Gated Sodium Channel NaV1.7: the Importance of Subunit Association and Phosphorylation and Their Effects on Channel Pharmacology and Biophysics. Journal of Molecular Neuroscience (LINK)
• Kanase et Al 2018. 4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties. Bioorganic & Medicinal Chemistry, Volume 26, Issue 9 (LINK)
• Gonçalves et Al. 2018. Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches. Neuropharmacology, Volume 133, 404-414 (LINK)
• Zha et Al. 2018. Design, synthesis and biological evaluation of tetrahydronaphthyridine derivatives as bioavailable CDK4/6 inhibitors for cancer therapy. European Journal of Medicinal Chemistry, Volume 148, Pages 140-153 (LINK)
• Israel et Al. 2018. The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and Excitatory Activities on Human NaV1.6. J. Med. Chem., 2018, 61 (4), pp 1730–1736 (LINK)
• Loucif et Al. 2018. GI‐530159, a novel, selective, mechanosensitive two‐pore‐domain potassium (K2P) channel opener, reduces rat dorsal root ganglion neuron excitability. British Journal of Pharmacology (LINK)
• Xu et Al. 2018. Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. European Journal of Medicinal Chemistry, Volume 145, Pages 74-85 (LINK)
• Agwa et Al 2018. Efficient Enzymatic Ligation of Inhibitor Cystine Knot Spider Venom Peptides: Using Sortase A To Form Double-Knottins That Probe Voltage-Gated Sodium Channel Na_V7. Bioconjug Chem. 2018 Sep 12. (LINK)
• Colley et Al 2018. Screening strategies for the discovery of ion channel monoclonal antibodies. Current Protocols in Pharmacology, 82, e44. (LINK)
• Robinson et Al 2018. A comprehensive portrait of the venom of the giant red bull ant, Myrmecia gulosa, reveals a hyperdiverse hymenopteran toxin gene family. Science Advances 12 Sep 2018:Vol. 4, no. 9 (LINK)
• Procopiou et Al 2018. Discovery of (S)-3-(3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenyl)-4-((R)-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)butanoic Acid, a Nonpeptidic αvβ6 Integrin Inhibitor for the Inhaled Treatment of Idiopathic Pulmonary Fibrosis. Med. Chem (LINK)

Posters:

• Bettini et Al 2018. NMDA Receptor Modulators in QPatch (LINK)
• Boddum et Al 2018. Optical modulation of ion channels (LINK)
• Boddum et Al 2018. GABAA receptor pharmacology evaluted in overexpressing HEK cells and primary astrocytes on QPatch (LINK)
• McCoull et Al 2018. Development of a novel screening system to identify activators of Two-pore domain potassium channels (K2Ps)(LINK)
• Standing et Al 2018. Development of high-throughput electrophysiological assay for the screening of hERG ion channel modulators using Sophion Qube 384 (LINK)
• Klint et Al 2018. HT Automation for patch clamp based primary screen for Nav1.1 using Qube 384. (LINK)
• Bouyer and Hebeisen 2018. Na_V5 big late : An inactivation deficient mutant of Na_V1.5 as screening tool for late sodium currents of the cardiac action potential (LINK)

Application reports:

• Sauter D 2018. Voltage and current clamp recordings of Cor.4U® human iPS cell-derived cardiomyocytes using Sophion’s QPatch (LINK)
• Boddum K 2018. Ligand gated ion channels: GABAA receptor pharmacology on QPatch (LINK)
• Sauter D 2018. Human iPS cell-derived cardiomyocytes (Cor.4U®) on Sophion’s Qube 384: voltage and current clamp recordings (LINK)
• Rosholm & Schupp 2018. Cav1.2 recordings using QPatch (LINK)
• Schupp & Korsgaard 2018. 8 hours unattended hERG run with ≥97% success rate and consistent pharmacology results (LINK)

Introducing QPatch II

QPatch has been the benchmark automatic patch clamp solution for cardiac safety and advanced electrophysiology since the early 00’s.

With the new QPatch II we raise the bar for efficiency and usability, while maintaining the proven data quality from QPatch.

If you want to find out how QPatch II can increase the efficiency in your ion channel lab, come visit our booth #113 at SPS in Washington or send a mail to info@sophion.com to book a private demo

Sophion co-organized channelopathy symposium in China

In mid-July Sophion Bioscience co-organized a meeting at the University of Peking entitled

“International Symposium on channelopathy and drug discovery – Ion channels as drug targets”

The meeting was hosted by the State Key Laboratory of Natural and Biomimetic Drugs, Health Science Center of Peking University.

The aim was to provide a platform for communication and knowledge exchange in channelopathy area for basic researchers, doctors, and pharmaceutical companies in China. Chinese and international speakers was invited to give presentations on novel scientific ideas, cutting‐edge technologies and latest research achievements on ion channels as well as the relevant diseases. Our own Application Scientist Melanie Schupp also gave a talk on “Nav1.1 in high throughput screening”.

It was a great pleasure for us at Sophion to co-organize this event in China and we were happy to see the large attendance from engaged researchers.

For full program and speaker biographies see here (It takes a while to load)

Super-short ligand exposure time on Qube Opto 384

With the new optical capability of Qube Opto in combination with the microfluidic system of the QChip, the exposure time of a ligand can be drastically reduced. Here we use rubi-GABA, a caged GABA compound, and demonstrate two strategies to obtain short ligand exposure.

RuBi-GABA activation followed by wash-out

When 1mM RuBi-GABA is washed in, no response is seen, as the caged GABA does not activate the GABA receptors. Upon stimulation with light for 100 ms, GABA is uncaged and activates the GABA_A receptor. 500 ms after the stimulus, the microfluidic channel is flushed, the response terminated, and the channels are completely deactivated.

RuBi-GABA activation during perfusion

To further decrease the ligand exposure time, the light stimulation was executed during perfusion with RuBi-GABA. The uncaged GABA was instantaneously washed out, and in combination with a shortening of the light stimulus to 20ms, a sharp, ultrashort GABA response was recorded with an exposure time approaching that of a synaptic response.

Updated privacy policy

We have also updated our privacy policy in relation to the new requirements (GDPR).

In short:

• We only collect personal information to facilitate commercial engagements with you or to provide you with the world class service that is expected from us.
• You can always ask us to correct, change or delete personal data, and unsubscribe to news by clicking the “unsubscribe button” in the footer of all our communication.

So all in all…. no changes on our side. We will continue to handle your personal information with integrity and respect

You can read the full privacy policy here

Light activated rubi-GABA on Qube Opto 384

The new optical capability of Qube Opto introduces the possibility of employing optopharmacology in combination with patch clamp in a 384 format. As we continue to challenge our system we will present some of the results here. Recently we have been playing with experiments employing rubi-GABA, a caged GABA compound activated by visual wavelengths.

GABA_AR mediated currents was elicited by optical uncaging of GABA in both a concentration and light dependant fashion.

Stay tuned for more news on Qube Opto 384 in the coming weeks

Concentration-response relationship

• HEK 293 / GABA_A (α₅β₃γ₂)
• Caged GABA (Rubi-GABA – Tocris)
• Light: 475 nm for 200 ms @ 100% light output intensity
• Rubi-GABA: 3-fold dilution series
• EC50: 10,6 uM +/- 0,5 uM

Optical dose-response relationship

• HEK 293 / GABA_A (α₅β₃γ₂)
• Caged GABA (Rubi-GABA – Tocris)
• Light: 475 nm for 200 ms @ 10-100% light output intensities

See application report here.

For more information on Optogenetic capabilities on Qube Opto 384 contact SWI@sophion.com

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 (swi@sophion.com) or visit booth #518 at Biophysics for more information.

2017 in brief

What a year!

For Sophion it has been a year with many changes, a lot of news and countless achievements. It has also, by far, been the best year in the history of Sophion Bioscience and on behalf of the whole Sophion Bioscience team we would like to thank all our partners and customers for their continued support. Read more about 2017 seen from our perspective here “Sophion 2017 in brief”

Eight new QPatch publications, two of them in Nature.com

A lot of new peer reviewed publications have seen the light over the summer. Here is some selected new publications. For more interesting publilcations on QPatch and Qube you can always search our publication database here

Huang et Al 2017 Synthesis and biological evaluation of novel 6,11-dihydro-5H-benzo[e]pyrimido- [5,4-b][1,4]diazepine derivatives as potential c-Met inhibitors

Kristof et Al 2017 An Official American Thoracic Society Workshop Report: Translational Research in Rare Respiratory Diseases. Official workshop report of the American Thoracic Society

Lazewska et Al 2017 Biphenyloxy-alkyl-piperidine and azepane derivatives as histamine H3 receptor ligands

Menegon et Al 2017 A new electro-optical approach for conductance measurement: an assay for the study of drugs acting on ligand-gated ion channels

Prashanth et Al 2017 Pharmacological screening technologies for venom peptide discovery

Sousa et Al 2017 Discovery and mode of action of a novel analgesic β-toxin from the African spider Ceratogyrus darlingi

Zhou et Al 2017 Design, synthesis and biological evaluation of 4,7,12,12a-tetrahydro-5Hthieno [3′,2’:3,4]pyrido[1,2-b]isoquinolines as novel adenosine 5′-monophosphate-activated protein kinase (AMPK) indirect activators for the treatment of type 2 diabetes

Zidar et Al 2017 Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels

New faces at Sophion

To meet the increasing demand of new application development and customer support, we have hired two new application specialists.

Kim Boddum has a PhD in neuropharmacology and comes from a post doc at the Department of Biomedical Sciences at the Uni of CPH. Kim has for the past 7-8 years worked on membrane receptors and ion channels function and pharmacology.

Kadla Røskva Rosholm has a PhD in Nanoscience working on high-throughput fluorescence-based cell assays. Also she been done two post docs working on electrophysiological and fluorescence methodologies to investigate the molecular mechanism of ion-channel signaling.

You can meet Dr. Kadla Røskva Rosholm and Dr. Kim Boddum at customer sites, demos or conferences.

Ph.D. course at Sophion Denmark

Sophion was hosting a PhD summer school on cardiac electrophysiology Wednesday the 7th of June.
The course consists of 30 students from many different institutions all around Europe and will be in conjunction with a European Marie Sklodowska Curie training network.
The students will be introduced to our company and the spirit of Sophion Bioscience but will also learn about patch clamp technique and even get some hands-on experience with our high throughput devices.

New paper on KCa2.X (SK) on QPatch

Small conductance calcium-activated K+ channels (KCa2.X, SK channels) are promising new targets for the treatment of Atrial fibrillation (AF), the most common type of arrhythmia. In a collaboration with Acesion Pharma, Bo Bentzen and his group revealed an inhibitory effect of some established AF drugs on SK channels using Sophion`s QPatch.   The paper benefits from QPatch`s capability to gain gigaohm seal resistances without relying on the presence of seal enhancing fluoride in the internal solution.

Read more here

Interested in CFTR? ….or traditional Chinese/Japanese medicine?

Another paper has just been published using QPatch, showing that the Kampo medicine Mashiningan (MNG) improves opioid-induced constipation in rats by activating cystic fibrosis transmembrane conductance regulator. The effects were determined using QPatch.

To our knowledge this is one of the first papers on traditional Japanese/Chinese medicine-based on studies with a QPatch, which we find rather exciting.

For those of you who are not acquainted with Japanese Kampo, it is based on traditional Chinese medicine but adapted to Japanese culture. Kampo is widely practiced in Japan, and is fully integrated into the modern healthcare system.

You can read more about Kampo here and read more from the paper here

Ion channel blocking antibodies

Exciting work from Iontas. Concentration-dependent inhibition of Kv1.3 and ASIC1a currents were demonstrated using QPatch automated patch clamp.

Read more here

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

New Nature paper on QPatch and neuronal stem cells

A group from University of Rostock has together with Sophion proved the feasibility of automated electrophysiological characterization of neuronal cells. The automated electrophysiology was done on a Sophion QPatch. With the QPatch’ unique ability to create gigaseals in physiological solutions the QPatch has again has shown its worth for advanced ephys measurements.

The QPatch data was done during a 6 weeks stay at Sophion as a part of Denise Franz Pd.D project. Congrats on the publication Denise, hope to see you again soon.

Read more here

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.