Case study

Advancing cardiac research:
32 wells at a timeTools:
SyncroPatch 384
32-well mode

Professor Niels Voigt and Dr. Fitzwilliam Seibertz at UMG
featured by Nanion Technologies
Professor Niels Voigt is Professor of Molecular

ideally be employed that accurately represent the structure

Pharmacology at the University Medical

and function of endogenous organ-specific cells. In contrast

Center Göttingen. His research focuses onto heterologous expression systems which may not completely

investigating the pathophysiology of cardiac

reflect cardiomyocyte or neuron physiology, primary cells fromarrhythmias. Using the SyncroPatch 384,

humans or large animal models are desirable. In addition,

Professor Voigt’s lab has used a variety of

induced pluripotent stem cell (iPSC) technology has emerged

cells including stem-cell derived atrial andover the last decade to provide wider access to cardiac andventricular cardiomyocytes and adult primaryneuronal material directly derived from human patients.

cardiomyocytes.

Traditional methods for the acquisition of ion currents, action
potentials and analysis of ion channel biophysics involve
The study of cellular electrophysiology involves in-depth
functional characterization of ion channels and transporters
bound within cellular membranes. In excitable cells, suchas cardiomyocytes and neurons, physiological ion channel
function is crucial for the formation of action potentials, which
serve as an elegant means of organized electrical signal
propagation across cardiac muscle or throughout the brain.
Encoded by specific genes, ion channels are susceptible tomutations which can alter their protein structure and function.
On a system level, this may translate into severe medical
conditions such as cardiac arrhythmias or neurologicaldisorders. It is therefore of vital importance to study thefunctional abnormalities of these channels and the resultant
modifications of action potential morphology at a cellularlevel. Understanding the underlying functional pathologies
then allow medical researchers to identify molecular drug
targets that could be utilized for pharmacological treatment
and clinical management of these diseases.
In order to accurately understand the impact of ion channel
mutations on human organ function, cellular models should

Nanion's SyncroPatch 384 platform
is highly flexible, making it ideal for academic
research labs. The 32-well mode optimizes assay
development and maximizes NPC-384 economy.
Alternatively, the SyncroPatch 384 can be run in fully
automated, unattended mode making it both ahigh and medium throughput instrument in one.

the patch-clamp technique. This approach is complex,
requires extensive user expertise and is highly laborious. It is,
by definition, a low-throughput method. New developments
in automated patch-clamp (APC) instrumentation haveremoved this limitation, with high throughput devices such as
the new SyncroPatch 384 which can measure up to 384 cells
simultaneously during single experiment. This is achieved
by depositing cells in suspension via robotic liquid handler
across a precision engineered 384-well measurement chip.

“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, Principle Investigator, UMG

Originally designed for drug discovery, APC systems areNewly launched in 2021, the SyncroPatch 384 equipped

amenable to a huge range of measurements from different

with 32-well mode has been invaluable in recent studies

cellular substrates. Such scalability in the methodologicalfrom basic science research groups such as the groupdomain has been invaluable, however sometimes mayof Professor Niels Voigt at the University of Göttingen. His

surpass the requirements of those in academia working

lab primarily aims to unravel the molecular mechanisms

with highly limited and valuable cellular models. In orderthat contribute to atrial fibrillation and other cardiac

to introduce more flexibility and cost economy into thearrhythmias in human patients. The 32-well mode played

academic workflow of high throughput measurements, thea pivotal role in the successful first-time measurements ofSyncroPatch 384 offers a reduced means of measurement,

primary cardiomyocytes using APC1. Here, cost-effective

the 32-well mode. This new feature allows the experimenter

measurements of action potentials and ionic currents wereto use only a fraction of the chip per experiment throughsuccessful even when cellular isolation yielded very low

customizable constellations of wells in multiples of 32.

numbers of viable cellular material (~7000 cells per 5 ml). ForAfterwards, the chip can then be stored and used again

these sparsely populated isolates, it was vital to concentrateat later time points with no impact on future measurement

cellular numbers with low solution volumes. The 32-wellquality or success rate.

mode of operation accommodated this requirement withease while still delivering high throughput results. The 32-well

The SyncroPatch can be used in 32-well mode for assay development, smaller screening
projects and where the number of cells is limited. The amplifier and pipettes can be used incolumns of 32-wells at a time and the rest of the chip can be used at a later time point without
any reduction in success rate.

mode also opens the door for direct assessment of humanprecious cells based on their availability, or as a means

cardiomyocyte electrophysiology from small biopsies thatto test and optimize voltage protocols and solution

can be acquired from human patients undergoing open

components without wasting cellular material, reagents andheart surgery. Operating under reduced tissue requirements

consumables. A recent study from the Voigt lab made use

is also particularly important for decreasing the amount ofof the 32-well mode to optimize a novel protocol to measure

animals needed for scientific use. In the aforementioned

IKr in iPSC-derived cardiomyocytes using equimolar caesium

study, the 32-well mode allowed for a massive amount ofconcentrations7. The findings of this study provide deepfunctional data to be collected from very few animals,

insights into the maturation of distinct ion currents in iPSC-indicating that APC paired with this approach may

derived cardiomyocytes over long-term culture to address

represent a desirable step towards reducing the number of

their often controversial applicability and usefulness as aanimals sacrificed for disease modeling purposes.

model of human cardiomyocyte function.

Advents such as induced pluripotent stem cell technology

In a recent symposium (Nanion Cardiac Safety Symposium

also acknowledge the ethical responsibility of reducing2023), Fitzwilliam Seibertz described his use of the 32-wellanimal use by providing a theoretically infinite amount ofmode as an alternative screening platform for a rapid

patient specific cellular material. iPSC-derived cells pair very

determination of batch-based purity of iPSC constructs.

well with APC and a number of modeling, screening and

iPSC-derived cardiomyocytes often display heterogeneous

methodological studies have been released over recent

subtype specificity ranging from nodal, to atrial or

years1–6. However, it is clear that regular cell differentiation

ventricular characteristics. In the study of cardiac chamber-and maintenance of iPSC lines is an expensive exercisespecific diseases such as atrial fibrillation, it is necessary

requiring large amounts of reagents and personnel. Theto verify the cells under investigation are of the desired

32-well mode can be used to screen a limited number ofsubtype. Following the deployment of a depolarizing ramp
protocol to measure inward rectifier activity, compounds
such as the M2 receptor agonist carbachol can be applied

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.

“If I’m experimenting with new protocols on cardiomyocytes,
the 32 well mode really puts my mind at ease knowing that I canstill optimise my recordings and save most cells for later when
everything is ready to go.”Dr. Fitzwilliam Seibertz, Postdoctoral Scientist, UMG

to unmask acetylcholine-activated inward rectifiers that are
only present in atrial-specific cells8. 32-well mode can beused to easily and economically test each batch “on theReferences
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clamp approach for high throughput electrophysiology recordings in native

and time consuming molecular techniques to test for atrial

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APC instruments. A smooth gear change from high-to-in APC: using physiological fluoride-free solutions for high throughput automatedmedium throughput (or vice versa) on the same device

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Becker N, Stoelzle S, Göpel S, Guinot D, Mumm P, Haarmann C, Malan D, Bohlen

Principal Investigator

H, Kossolov E, Kettenhofen R, George M, Fertig N, Brüggemann A. Minimized cell

Department of Pharmacology and Toxicology

usage for stem cell-derived and primary cells on an automated patch clamp

University Medical Center, Göttingensystem. J Pharmacol Toxicol Methods 2013; 68:82–87.

Robert-Koch-Straße 40
37075 Göttingen

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Ritter M, Jung P, Stelzer L, Hüsgen LM, Klopp M, Rubio T, Fakuade FE, Mason FE,

Germany

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https://pharmacology.umg.eu/research/voigt-lab/

Voigt N. Electrophysiological and calcium-handling development during longterm culture of human-induced pluripotent stem cell-derived cardiomyocytes.

Dr. Fitzwilliam Seibertz

Basic Res Cardiol 2023; 118:14.

Postdoctoral Scientist
Department of Pharmacology and Toxicology

Seibertz F, Sutanto H, Dülk R, Pronto JRD, Springer R, Rapedius M, Liutkute A,

8.

Seibertz F, Rubio T, Springer R, Popp F, Ritter M, Liutkute A, Bartelt L, Stelzer L,

University Medical Center, Göttingen

Haghighi F, Pietras J, Windel H, Díaz I Pedrosa N, Rapedius M, Döring Y, Solano

Robert-Koch-Straße 40

R, Hindmarsh R, Shi R, Tiburcy M, Brügmann T, Kutschka I, Streckfuss-Bömeke K,37075 Göttingen

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electrical remodelling in human induced pluripotent stem cell-derived atrial
cardiomyocytes: a novel pathway for antiarrhythmic therapy development.

Acknowledgments

Cardiovasc Res 2023; cvad143. doi: 10.1093/cvr/cvad143.

We thank Niels and Will for sharing their views on theimportance of the 32-well mode for their researchon primary cardiomyocytes and stem cell-derived
cardiomyocytes. We are grateful for your valuable
insights and wonderful collaboration.

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