Case study

Two years of the SyncroPatch 384
in the City of ScienceTools:
SyncroPatch 384

The University of Göttingenfeatured by Nanion Technologies
The University of Göttingen celebrates theIn the years since the patch clamp technique was invented,

second anniversary of the installation ofthe method has been expanded and automated in a way

the SyncroPatch 384, a high throughput

that enables the recording from multiple cells simultaneously,automated patch clamp device. Funded

vastly improving ease-of-use and increasing the throughput

by the Multiscale Bioimaging Cluster ofof data acquisition. The SyncroPatch 384 is a high throughput

Excellence (MBExC) at the University Medical

automated patch clamp instrument for recording from up toCenter Göttingen (UMG), the instrument is384 cells in parallel. The system is highly flexible and is ideal

under continuous use by researchers at thefor drug screening in the pharma industry, and for complex

forefront of cardiac and neuronal cellularbiophysical studies in academic research.1

electrophysiology.

The city of Göttingen, dubbed the City of Science for its
In excitable cells such as cardiomyocytes and neurons, ion
channels embedded within cellular membranes conduct
minuscule currents into or out of the cell. This maintains
cellular homeostasis and facilitates action potential
propagation, transferring electrical signals across cardiac
muscle or throughout the nerves of the brain. Ion channels,
encoded by specific genes, are prone to mutations that
can alter their protein structure and function. At the systemlevel such alterations can lead to severe medical conditions,
including cardiac arrhythmias or neurological disorders.
By understanding the underlying functional pathologies,
medical researchers can identify molecular drug targets forpharmacological treatment and clinical management ofthese diseases.
The patch clamp technique is of profound methodologicalimportance to biomedical research because it allows for
precise quantification of the microscopic currents thatflow through the ion channels of living cells. This technique
was established in the 1970’s by Dr Erwin Neher and Dr Bert
Sakmann in Göttingen, Germany. They would go on to win
the Nobel Prize in Physiology or Medicine in 1991 for theirimmense body of work which still allows researchers in thepresent day to understand how cells of the body function.

Nanion’s SyncroPatch 384 platform
is a high throughput automated patch-clamp
device capable of patching and recording up to384 cells in parallel. It is highly flexible, making it ideal
for complex biophysical studies in academic labs.

many contributions to scientific research over centuries, hascontinued to be a hub for biophysical research. Realizing
the need for high throughput patch clamp measurements toaccelerate their electrophysiological research, the Multiscale
Bioimaging Cluster of Excellence (MBExC) at the University
Medical Center Göttingen (UMG) installed a SyncroPatch 384
at their research campus in July 2022. As an initiative fundedby the German Federal and State Governments, the MBExC
aims to unravel the structure and function of heart and brain

“Together with Nanion’s dedicated researchers, we performed
novel experiments on primary cardiomyocytes using theSyncroPatch. These experiments laid the foundation for our exciting
future collaboration with Nanion and multiple new projects.”
Professor Niels Voigt, University Medical Center Göttingencells specifically to understand how to treat cardiac andsamples indicate that less animals need to be used in future

neurological diseases. Under the umbrella of the MBExC,

for scientific purposes while still obtaining large data sets.

the SyncroPatch 384 is curated by Prof. Dr. Niels Voigt, an

Popular functional models such as human cardiomyocytes

expert in cellular mechanisms of cardiac arrhythmias, andderived from induced pluripotent stem cells (iPSC-CM) also

Dr. Thomas Mager, a neuroscientist with extensive expertis

acknowledge the ethical responsibility of reducing animale in optogenetics. This case study, written on the two-year

use by providing theoretically infinite amounts of patientanniversary of the Göttingen SyncroPatch 384 acquisition,

specific cells in vitro. In Göttingen, the SyncroPatch 384 acts

will summarize the combined projects, collaborations,as both a primary biophysical tool to investigate ion channel

publications and career opportunities that have been madefunction in health and disease, and as a screening platform

possible over the last two years.

to determine iPSC-CM batch quality and purity. iPSC-CM
differentiation often results in heterogeneous cell populations

In the cardiac field, a wide variety of academic projectsof nodal, atrial or ventricular subtypes.3 In studies of chamber-in Göttingen have made use of the SyncroPatch 384,

specific diseases such as atrial fibrillation, it is necessary toincluding the first ever successful measurements of primary

ensure the cellular substrate is indeed of the desired subtype.

cardiomyocytes using high throughput automated patch

Compounds such as the M2 receptor agonist carbachol canclamp.2 The vast amounts of voltage clamp and current

be applied to unmask the atrial-specific current IK,ACh and giveclamp data obtained from a small batch of mammaliana readout of atrial purity within a cellular cohort.4,5 This is an

The SyncroPatch 384 can be used as a functional subtype screening platform to determine the purity of atrial or ventricular induced
pluripotent stem-cell derived cardiomyocytes (iPSC-CM). Flexible distribution of different cell lines or types across the 384 well recording
plate allows for simultanous measurement and characterization. M2 receptor agonist carbachol (CCh) can be applied to unmask
acetylcholine-activated inward rectifiers (IK,ACh) that are only present in atrial cells.4,5

economical method to test each batch “on the side” after
crucial measurements to avoid difficult and time-consuming

delayed rectifier current (IKr) in iPSC-CM using equimolar

Cs+ concentrations,8 and through long term tracking of ion

molecular techniques to test for atrial or ventricular-specificchannel development in iPSC-CM to identify the optimal timegenes.

window for measurement as cells get older in culture.3

Collaborations involving the Göttingen SyncroPatch 384

In the field of optogenetics, the SyncroPatch 384 in Göttingen

have unveiled new potential roles for existing drugs such as

has been instrumental in the development of new red-shifted

the SGLT2 inhibitor Dapagliflozin. Usually prescribed to treat

light sensitive ion channels, known as opsins. Derived fromdiabetes and kidney failure, recent research has revealed

microbial organisms, these light sensitive ion channels canthat this drug imparts atrial-specific regulation of cardiac

be virally inserted into the target organ system and could beexcitability through modulation of the cardiac sodium

used in future for arrhythmia control in the heart and even thecurrent.6 This is particularly important because effective

clinical restoration of vision or hearing. Much work has been

atrial-specific therapies for rhythm control in the absence ofconducted with the Göttingen SyncroPatch 384 combined

proarrhythmic ventricular side effects are severely needed towith the optical stimulation tool to screen immense libraries oftreat patients with atrial fibrillation. Other major collaborations

new opsins to develop new constructs with a sustained highhave identified that gene therapy to restore Plakophilin

single channel conductance under continuous illumination

2 function in Knock-Out iPSC-CM models reverses theconditions. Researchers at the Göttingen campus have beenarrhythmic phenotype commonly displayed by patients withable to show that their new construct, named ChReef (ChRmutations in the Plakophilin gene.7[channel rhodopsin] that excites efficiently), was successful inpartially restoring vision in blind mice following viral insertion of

The SyncroPatch 384 has also driven important descriptive

the opsin into retinal ganglion cells.9 Not only limited to visionwork optimizing experimental procedures in the iPSC-restoration, application of ChReef into the spiral ganglion

CM field. For example, through the development of aneurons of the inner ear was followed by sustained activationnovel protocol to measure the rapid component of theof the auditory pathway under low illumination conditions.

Prof. Niels Voigt (left), Aistė Liutkutė, Dr. Fitzwilliam Seibertz and Dr. Funsho Fakuade with the SyncroPatch 384 at theUMG. The SyncroPatch 384 is routinely used in the lab to record hiPSC-derived cardiomyocytes to investigate thephysiology and pathophysiology of cardiac arrhythmias.

“The SyncroPatch 384 expands our ability to screen natural variants
and follow previously impossible protein engineering approaches
for the purpose of advancing optogenetic tools for basic sciences
and future medical therapies.”
Dr. Thomas Mager, University Medical Center Göttingen

These developments are particularly exciting from a clinical

References

standpoint, as lowering the energy threshold for cochlea

1.

Seibertz F, Voigt N. High-throughput methods for cardiac cellularelectrophysiology studies: the road to personalized medicine. American Journalof Physiology-Heart and Circulatory Physiology. 2024. 326:H938–H949.

2.

Seibertz F, Rapedius M, Fakuade FE, Tomsits P, Liutkute A, Cyganek L, Becker
N, Majumder R, Clauß S, Fertig N, Voigt N. A modern automated patchclamp approach for high throughput electrophysiology recordings in native
cardiomyocytes. Commun Biol. 2022. 5:969.

3.

Seibertz F, Sutanto H, Dülk R, Pronto JRD, Springer R, Rapedius M, Liutkute A,Ritter M, Jung P, Stelzer L, Hüsgen LM, Klopp M, Rubio T, Fakuade FE, Mason FE,Hartmann N, Pabel S, Streckfuss-Bömeke K, Cyganek L, Sossalla S, Heijman J,Voigt N. Electrophysiological and calcium-handling development during longterm culture of human-induced pluripotent stem cell-derived cardiomyocytes.
Basic Res Cardiol. 2023;118:14.

4.

Seibertz F, Rubio T, Springer R, Popp F, Ritter M, Liutkute A, Bartelt L, Stelzer L,Haghighi F, Pietras J, Windel H, Díaz I Pedrosa N, Rapedius M, Döring Y, SolanoR, Hindmarsh R, Shi R, Tiburcy M, Brügmann T, Kutschka I, Streckfuss-Bömeke K,
Kensah G, Cyganek L, Zimmermann WH, Voigt N. Atrial fibrillation-associatedelectrical remodelling in human induced pluripotent stem cell-derived atrial
cardiomyocytes: a novel pathway for antiarrhythmic therapy development.
Cardiovasc Res. 2023. 119(16):2623-2637.

5.

Fakuade FE, Hubricht D, Möller V, Sobitov I, Liutkute A, Döring Y, Seibertz F,
Gerloff M, Pronto JRD, Haghighi F, Brandenburg S, Alhussini K, Ignatyeva N,Bonhoff Y, Kestel S, El-Essawi A, Jebran AF, Großmann M, Danner BC, Baraki
H, Schmidt C, Sossalla S, Kutschka I, Bening C, Maack C, Linke WA, Heijman J,Lehnart SE, Kensah G, Ebert A, Mason FE, Voigt N. Impaired Intracellular Calcium
Buffering Contributes to the Arrhythmogenic Substrate in Atrial Myocytes From
Patients With Atrial Fibrillation. Circulation. 2024. Jun 24. Epub ahead of print. doi:
10.1161/CIRCULATIONAHA.123.066577.

6.

Paasche A, Wiedmann F, Kraft M, Seibertz F, Herlt V, Blochberger PL, Jávorszky N,Beck M, Weirauch L, Seeger T, Blank A, Haefeli WE, Arif R, Meyer AL, Warnecke
G, Karck M, Voigt N, Frey N, Schmidt C. Acute antiarrhythmic effects of SGLT2
inhibitors-dapagliflozin lowers the excitability of atrial cardiomyocytes. Basic ResCardiol. 2024. 119, 93–112.

7.

Kyriakopoulou E, Versteeg D, de Ruiter H, Perini I, Seibertz F, Döring Y, Zentilin L,Tsui H, van Kampen SJ, Tiburcy M, Meyer T, Voigt N, Tintelen van JP, Zimmermann
WH, Giacca M, van Rooij E. Therapeutic efficacy of AAV-mediated restorationof PKP2 in arrhythmogenic cardiomyopathy. Nature Cardiovascular Research.
2023. 2, 1262–1276.

8.

Bloothooft M, Verbruggen B, Seibertz F, van der Heyden MAG, Voigt N, de Boer
TP. Recording ten-fold larger IKr conductances with automated patch clamping
using equimolar Cs(+) solutions. Front Physiol. 2024.15:1298340.

9.

Zerche M, Hunniford V, Alekseev A, May F El, Vavakou A, Siegenthaler D, Hüser
MA, Kiehn SM, Garrido-Charles A, Alvanos T, Witzke I, Trenholm S, Macé E, KuschK, Bruegmann T, Wolf BJ, Mager T, Moser T. Efficient and sustained optogenetic
control of nervous and cardiac systems. bioRxiv. 2023.

activation represents a realistic step closer to wearable
optogenetic devices for effective hearing restoration.9
In the last two years, the Göttingen SyncroPatch 384 has
assayed hundreds of thousands of cells. However, it is not
only a platform for scientific discovery. It has also kick-started
a teaching programme at the university. Regular seminars
and methods courses are offered to masters- and PhD-level
students by the Hertha Sponer College within the MBExC.
These courses aim to teach students about the automatedpatch clamp technique and encourage collaborations
throughout the university. Within the last two years, key usersof the Göttingen device have graduated PhD and medical
thesis study programmes, started post-doctoral fellowships,
and have joined high level industry positions.
The MBExC has remained on the global frontier of biomedical
research into heart and brain function. It is high throughput
techniques such as automated patch clamp that add tothe growth of this immense program within a historicallysignificant university. At Nanion, we look forward to
supporting the ongoing work of the MBExC and following theirjourney with the SyncroPatch 384.

Contact Information
Professor Niels Voigt
Cluster of Excellence (Multiscale Bioimaging: From
Molecular Machines to Networks of Excitable Cells)
Institute of Pharmacology and Toxicology
University Medical Göttingen
Robert-Koch-Str. 40
37075 Göttingen
Germany
https://pharmacology.umg.eu/research/voigt-lab/

Dr. Thomas Mager
Cluster of Excellence (Multiscale Bioimaging: From
Molecular Machines to Networks of Excitable Cells)
Institute for Auditory Neuroscience
University Medical Göttingen
Robert-Koch-Str. 4037075 Göttingen
Germany

Acknowledgments
We thank the MBExC, along with Niels and Thomas
for sharing their views on the use of the SyncroPatch
384. We are grateful for their valuable insights andwonderful collaboration.

Nanion Technologies GmbH I Ganghoferstr. 70a, 80339 Munich, Germany+49 89 2190 95-0 I info@nanion.de I www.nanion.de