Key features

384 or 768 cells in parallel (384 or 768 amplifier)

384 pipettor head

85 % success rates routinely obtained

Excellent results with voltage-gated & ligand-

gated ion channels

Modular approach – easy upgrade & integration

Single- and multi-hole recording substrates

Nanion Technologies

SyncroPatch 384PE - Patch Clamp gone HTS!

Dr. Markus Rapedius, Application Scientist

Measure More

Membrane

The Port-a-Patch. The world’s smallest patch clamp rig.

• Fast access to high quality patch

clamp data

• Quick evaluation of cells and

compounds

• Novel experimental possibilities

The Patchliner. Because quality does matter.

• Unlimited experimental freedom

• Best of all worlds: throughput,

performance and versatility

• Press one button and walk away:

- 48 cells in one run

The SyncroPatch 96. Get more throughput.

• Cost-efficient ion channel

screening

• Ligand- and voltage-gated

channels

• High throughput and high data

quality

The Vesicle Prep Pro. Liposomes made easy.

• Quick and easy formation of

GUVs

• Temperature control

• Stable bilayers for ephys

recordings

The Orbit 16. Instant bilayer – just add protein.

• 16 parallel bilayers

• Low noise, high bandwidth

recordings

• Compatible with your existing

amplifier

The SURFE2R. Catch the wave for transporters.

• In-depth analysis of transporter

protein activity and function

• Compatible with diverse

membrane sources

• Multiple targets investigated with

one sensor

Smart tools for ion channel and transporter research and screening

12 years of patch clamping - and more to come

The CardioExcyte 96. Bump up your safety screening.

• Ultra-precise impedance

measurements

• Real time access to beating

parameters

• Quick experiments and long term

observations

Nanion:

Stand alone machines

Higher throughput

Patch Clamping

Integration in HTS?

48

8

96

384

16

The PatchEngine – modular, compact and accessible

The PatchEngine –

the core of the SyncroPatch 384PE

Components:

Biomek FX with a 384 pipetting head

including gripper

1-2 SyncroPatch 384PE Modules

1 - 2 x 384 channel amplifier

SyncroPatch 384 software

NPC-384 borosilicate chip

Temperature controlled cell hotel

Integrated Barcode scanner

Optional 8 channel pipetting head

(Screen 100% of all compounds)

SyncroPatch 384PE – Set-up overview using the Biomek FX robot

Open design allows for seamless integration into robotic HTS-highways

Available as single and multi-hole borosilicate plates:

Single-hole substrate: Four-hole

substrate:

SyncroPatch 384 PE – Consumables NPC-384

84 % > 500 Mohm

Wellplate overview Close up

selectable traces

Experiment

statistics

One well highlighted

Current-Voltage (I/V) Relationship of hERG (CHO)

84 % > 500 Mohm

Current-Voltage (I/V) Relationship of hERG (CHO)

0

50

100

150

200

250

<5 5-10 10-15 15-20 20-25 >25

co

un

ts

C slow [pF]

0

50

100

150

200

250

300

<5 5-10 10-15 15-20 20-25

co

un

ts

R series [MΩ]

0

20

40

60

80

100

disabled (no

catch)

<100 100 - 500 >500c

ells

[%]

R seal [MΩ]

Start of experiment

End of experiment

Success rates of hERG expressed in CHO cells

Chip load &

priming

1-2 Control washes +

3 cmpd concentrations

8 – 12 minutes 5 minutes 2 minutes

Exp end &

Chip unload

Total experiment length for 4 – 5 additions: 15 – 20 minutes

Experiment length is exposure time dependent.

Experiment overview

SyncroPatch 384 PE – quick priming and short experiments

The SyncroPatch 384 PE has been validated with:

• cell lines: CHO, HEK, LTK, 1321 N1, NCL-SG3, Jurkat and RBL-1

• Cor.4U® iPSC Derived Human Cardiomyocytes

• ion channels:

• voltage-gated: hERG, Nav1.1, 1.5, 1.7, Kv1.3, Cav3.2

• ligand-gated: GABAA (α1,β2,γ2), Glycine (α1), GluA2,

P2X3, TRPA1, ASIC3, GluN1/N2B

• other: TMEM16a, Kir6.2-SUR2A, Kir2.1

SyncroPatch 384 PE – Assay compatibility examples

Voltage-gated channels (e.g. hNav 1.7)

hNav1.7 block by Tetracaine (5 µM, 50 µM and 500 µM )

CHO-hNav1.7 cells were kindly provided by Anaxon

Success rate: 92.4 %

SyncroPatch 384PE Solution Application: Mix and Read

for Voltage gated channels

cu

rre

nt

time

0

-

+

Exp length: 15 minutes

Success rate: 86.2 %

Tetracaine IC50: 49.6µM

hNav1.7 block by Tetracaine (5 µM, 50 µM and 500 µM)

CHO-hNav1.7 cells were kindly provided by Anaxon

read-out at 3 different pulses

Fast and easy analysis – more complex protocols

control 5 µM 15 µM 50 µM Tetracaine

control

5 µM

15 µM

50 µM

Effect of 0, 5, 15 and 50 mM Tetracaine

on 1st, 2nd and 10th pulse

DataControl 384: A fast and easy way of data analysis

Effect of 0, 5, 15 and 50 mM Tetracaine

on 1st, 2nd and 10th pulse

DataControl 384: A fast and easy way of data analysis

Tetracaine

1st pulse IC50 = 41.8 µM

2nd pulse IC50 = 9.9 µM

10th pulse IC50 = 3.0 µM

Current amplitude stability Seal stability

SyncroPatch 384 PE – High Quality Measurements

Inactivation stability (C1/C2)

TRPA1

TRPA1 expressed in HEKcells

The cells were kindly provided by Millipore

TRPA1 currents were initially activated by Supercinnamaldehyde (SCMA; 5 μM) and then blocked by the specific inhibitor A-967079. 242 of 283 cell were used for the IC50 analyses

TRPA1 expressed in HEKcells

74,2 % > 500 Mohm

The cells were kindly provided by Millipore

Ligand gated channels (e.g. hGABAA)

Stacked Application of solutions

for ligand-gated channels

cu

rre

nt

time

0

-

+

Repeated exposure of GABA

3x application of 2µM GABA -> stable and reproducable responses

Fast ligand gated channels (e.g. hGluA2)

Time course of stacked application

Repeated activation of HEK-hGluA2 by 300 µM Glutamate

Activation by 100 µM, 300 µM and 1 mM Glutamate

Zooming in shows an activation below 10 ms

Potassium currents through endogenous Kir 2.1-channels in RBL cells

Exp length: 15 minutes

Success rate: 90.1 %

Exchange rate: <50 ms

Fluidic Properties tested on RBL cells

Allosteric Modulation

1 µM GABA + 100 µM Pentobarbital

Allosteric Modulation of HEK-GABA by Pentobarbital

1 µM GABA

The amplitude of the allosteric modulation can be normalized to the original

amplitude of the agonist (GABA) within every individual cell.

1 µM GABA

1 µM GABA + 1 µM Pentobarbital

1 µM GABA + 10 µM Pentobarbital

1 µM GABA + 100 µM Pentobarbital

1 µM GABA + 1mM Pentobarbital

1 µM GABA + 30 µ M GABA

1 µM GABA

1 µM GABA

1 µM GABA

1 µM GABA

1 µM GABA

1 µM GABA

SyncroPatch 384 PE – Allosteric Modulation, fast and easy

HEK Gaba, 2µM GABA + 10 µ M

Ongoing project: HTS screening of Cor.4U cells!

384 scd cardiomyocytes (Cor.4U) in parallel!

Ongoing project: HTS screening of Cor.4U cells!

Ongoing project: HTS screening of Cor.4U cells!

384 scd cardiomyocytes (Cor.4U) in parallel!

The SyncroPatch PE (PatchEngine) a Revolutionary Instrument for APC-based Ion Channel Drug Screening

Key features

384 or even 768 cells in truly parallel & modular approach

Giga-seal recordings of individually clamped cells

Up to 25,000 data points per day

85 % success rates routinely obtained

Extremely low cost per data point

Validated for diverse ion channels targets

Integrates easily into an HTS environment

Already installed in pharma, biotech, CRO + academia!

Foreign Branches: USA China Japan

Nanion Customer Reference

- a global customer base distributed between industrial and academic laboratories

Companies:

• Abbott

• Almirall Prodesfarma

• AstraZeneca

• Amgen

• Aurigene Discovery Technologies,

Ltd.

• Axiogenesis

• Bayer

• Bionomics

• Boehringer Ingelheim

• Bristol-Myers Squibb

• Center for New Drug Safety

Evaluation and Research (NCDSER),

• Chromocell

• conoGenetix biosciences GmbH

• Evotec

• Genionics

• GlaxoSmithKline

• Grünenthal

• Hofman La Roche

• Hydra Biosciences

• Japanese Tobacco

• Lupin Limited

• Merck

• Merch Serano

• Novartis

• Novo Nordisk

• Nycomed

• Ono Pharmaceutical

• Orion Pharma

• Pfizer

• Pierre Fabre

• Regeneron Pharmaceuticals

• Rytmion

• Sanofi-Aventis

• Shinogi

• Siena Biotech

• SK Holding, Co Ltd

• Sundia MediTech Company, Ltd.

• Suven Life Sciences Ltd, Hyderabad,

India

• Syngenta

• UCB Pharma

• Vertex Pharmaceuticals

• Vimta Labs Life Sciences,

Hyderabad, India

• Wyeth

• Xention

Research institues and universites:

• Cambridge University, Cambridge, UK

• Charité - Universitätsmedizin Berlin,

Germany

• Consiglio Nazionale delle Ricerche,

Povo (Trento), Italy

• Copenhagen University, Denmark

• Cornell University, Geneva, NY, USA

• Eberhard Karls Universität Tübingen,

Germany

• FMP, Berlin, Germany

• Forschungszentrum Caesar, Bonn,

Germany

• Forschungszentrum Jülich GmbH, Jülich,

Germany

• Friedrich-Schiller-Universität Jena,

Germany

• Georg-August-Universität Göttingen,

Germany

• Griffith University, Nathan, Australia

• GSF - Forschungszentrum für Umwelt

und Gesundheit, GmbH, Neuherberg,

Germany

• Hasselt University, Diepenbeek ,Belgium

• Hertie Institute for Clinical Brain

Research, Germany

• Howard Florey Institute, USA

• Howard Hughes Medical Institute,

Ashburn, VA, USA

• Institute of Genomics and Integrative

Biology, Delhi, India

• IPBS-CNRS, Tolouse, France

• Istituto Italiano di Tecnologia, Genova,

Italy

• Jacobs University, Bremen, Germany

• JNCASR, Bangalore, India

• Julius von Sachs Institut, Würzburg,

Germany

• Karolinska Institute, Stockholm, Sweden

• Kiserleti Orvostudomanyi Kutatointezet,

Budapest, Hungary

• Korea Institute of Science and

Technology (KIST), Seoul, South Korea

• Laboratorio Especial de Toxinologia

Aplicada CAT-CEPID, Sao Paolo, Brazil

• Ludwig Maximillian Universität,

München, Germany

• Lund University, Lund, Sweden

• Max Planck Institut, Göttingen,

Germany

• Medizinische Hochschule Hannover,

Germany

Research institues and universites: (cont.)

• University of Michigan, Ann Arbor, MI,

USA

• Università degli Studi di Napoli -

Federico II, Napoli, Italy

• University of North Carolina, Wilmington,

NC, USA

• University of Queensland, Brisbane,

Australia

• University of Rochester, NY, USA

• University of Tennessee Health Science

Center, USA

• University of Valladolid and Spanish

National Research Council (CSIC),

Valladolid, Spain

• University of Washington, USA

• University of Wisconsin, Madison, WI,

USA

• Universität Zürich, Switzerland

• Universitatea Lucian Blaga din Sibiu,

Romania

• Universität Augsburg, Germany

• Universität Freiburg, Germany

• Universität für Bodenkultur, Wien, Austria

• Universität Heidelberg, Germany

• Universität Hohenheim, Germany

• Universität Osnabrück, Germany

• Vanderbilt Medical School, Nashwille,

TN, USA

• Virginia State University, Blacksburg, VA,

USA

• X-Lab, Göttingen, Germany

• Yale University, New Haven, CT, USA

• Inje University, Busan, South Korea

Research institues and universites: (cont.)

• Nanjing University, Nanjing, China

• Nanyang Technological University,

Singapore

• National University of Singapore,

Singapore

• National Center for New Drug Safety

Evaluation and Research (NCDSER),

Shanghai, China

• National Heart Center, Singapore

• National Jewish Medical and Research

Center, Denver, CO, USA

• NIH/NINDS, Bethesda, MD, USA

• NIST, Gaithersburg, MD, USA

• New York University, NY, USA

• RMIT University, Bundoora, Australia

• Ruhr-Universität Bochum, Germany

• Shanghai Institute of Materia Medica,

Shanghai, China

• Simon Fraser University, Burnaby,

Canada

• Southampton General Hospital,

Southampton, UK

• Stiftung Alfred-Wegener-Institut für

Polar- und Meeresforschung,

Bremerhaven, Germany

• Syracuse Univerity, NY, USA

• Technische Universität Ilmenau,

Germany

• Technische Universität Darmstadt,

Germany

• Technische Universiät München,

Germany

• Uppsala University, Uppsala, Sweden

• UNESCO, Bahía Blanca, Argentina

• Universidade Federal de Sao Paulo,

Brazil

• Università degli Studi di Genova, Italy

• Universitatea Lucian Blaga Din Sibiu,

Romania

• University of California, Los Angeles,

CA, USA

• University of California, San Diego, CA,

USA

• University of Cambridge, UK

• University of Cincinnati, OH, USA

• University of Groningen, the

Netherlands

• University of Leeds, UK

• Universidade de Lisboa, Portugal

Companies:

• Abbott

• Almirall Prodesfarma

• AstraZeneca

• Amgen

• Aurigene Discovery Technologies,

Ltd.

• Axiogenesis

• Bayer

• Bionomics

• Boehringer Ingelheim

• Bristol-Myers Squibb

• Center for New Drug Safety

Evaluation and Research (NCDSER),

• Chromocell

• conoGenetix biosciences GmbH

• Evotec

• Genionics

• GlaxoSmithKline

• Grünenthal

• Hofman La Roche

• Hydra Biosciences

• Japanese Tobacco

• Lupin Limited

• Merck

• Merch Serano

• Novartis

• Novo Nordisk

• Nycomed

• Ono Pharmaceutical

• Orion Pharma

• Pfizer

• Pierre Fabre

• Regeneron Pharmaceuticals

• Rytmion

• Sanofi-Aventis

• Shinogi

• Siena Biotech

• SK Holding, Co Ltd

• Sundia MediTech Company, Ltd.

• Suven Life Sciences Ltd, Hyderabad,

India

• Syngenta

• UCB Pharma

• Vertex Pharmaceuticals

• Vimta Labs Life Sciences,

Hyderabad, India

• Wyeth

• Xention