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Our Technology: How it Works

It all began in 2003 with the launch of the Port-a-Patch: the World's smallest patch clamp rig. Since then we have expanded our product portfolio, building on the success and experience of the Port-a-Patch to increase throughput and assay flexibility. We now offer medium and high throughput automated patch clamp devices, instruments for automated bilayer recordings, SSM-based electrophysiology, impedance and EFP recordings. We continue to listen to our customers and develop our technology to meet their needs in research and drug development.


Automated Patch Clamp

Automated Patch Clamp based on Planar Patch Clamp

The patch clamp technique is the gold standard for real-time investigation of ion channels. With its exceptional signal resolution, complex biophysical properties and effectors of ion channels can be studied.

The automation of the patch clamp method was made possible with the development of the chip-based planar patch clamp technology. Automated patch clamp increases throughput and ease of use compared to the conventional patch clamp technique making it accessible to a wider audience.

Planar Patch Clamp

Nanion has been the 'first on the market' with the launch of the semi-automated planar patch clamp device, the Port-a-Patch, in 2003. Since then, we have developed further instruments which are all "true Giga-seal" devices and offer a wide variety of experimental possibilities based on the planar patch clamp technology, expanding on the capabilities of conventional patch clamp.


Nanion's planar patch clamp devices

icon pap   The Port-a-Patch is a semi-automated device with a small footprint for the analysis of ion channels in cells and lipid bilayers.

icon pl   The Patchliner is an automated patch clamp robot for medium thoughput with ultimate flexibility for assay design.

icon sp96   The SyncroPatch 384PE is a high-throughput patch clamp instrument which can be upgraded to the SyncroPatch 768PE with a throughput of 20,000 and 40,000 datapoints per day, respectively.


patch clamp instrument comparison


Recommended publications on Planar Patch Clamp

2017 - Automated Patch Clamp Recordings of Human Stem Cell- Derived Cardiomyocytes.

icon pl  Patchliner and   icon sp96   SyncroPatch 384PE book chapter in Stem Cell-Derived Models in Toxicology (2017)

2016 - Automated Patch Clamp Meets High-Throughput Screening: 384 Cells Recorded in Parallel on a Planar Patch Clamp Module

icon sp96  SyncroPatch 384PE publication in Journal of Lab Automation (2016)

2015 - Novel screening techniques for ion channel targeting drugs

icon pl  Patchliner,   icon sp96   SyncroPatch 384PE and   Icon CE   CardioExcyte 96 publication in Channels (2015)

2014 - Ultra-stable glass microcraters for on-chip patch clamping

icon pap  Port-a-Patch publication in Joyal Society of Chemistry Advances (2014)

2014 - New strategies in ion channel screening for drug discovery: are there ways to improve its productivity?

icon sp96  SyncroPatch 384PE publication in Journal of Laboratory Automation (2014)

2014 - Early identification of hERG liability in drug discovery programs by automated patch clamp

icon pl  Patchliner and   icon sp96   SyncroPatch 384PE publication in Frontiers in Pharmacology (2014)

2014 - Automated Patch Clamp Analysis of nAChα7 and NaV1.7 Channels

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Current Protocols in Pharmacology (2014)

2013 - Minimized cell usage for stem cell-derived and primary cells on an automated patchclamp system

icon pl  Patchliner publication in Journal of Pharmacological and Toxicological Methods (2013)

2013 - Automated Planar Patch Clamp

icon pl   Patchliner book chapter in Ion Channels (2013)

2012 - Toward a new gold standard for early safety: automated temperature-controlled hERG test on the Patchliner

icon pl   Patchliner publication in Frontiers in Pharmacology (2012)

2012 - Natural and artificial ion channels for biosensing platforms

icon pap   Port-a-Patch,   icon pl   Patchliner,   icon sp96   SyncroPatch 96 ((a predecessor model of SyncroPatch 384PE) and   icon vpp   Vesicle Prep Pro publication in Analytical and Bioanalytical Chemistry (2012)

2012 - HTS techniques for patch clamp-based ion channel screening - economy and advances

icon pap   Port-a-Patch,   icon pl   Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Expert Opinion on Drug Discovery (2012)

2011 - State-of-the-art automated patch clamp devices: heat activation, action potentials, and high throughput in ion channel screening

icon pap   Port-a-Patch,   icon pl  Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)

2011 - Automated electrophysiology makes the pace for cardiac ion channel safety screening

icon pl  Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)

2010 - Renaissance of ion channel research and drug discovery by patch clamp automation

icon pap  Port-a-Patch,   icon pl   Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE)  publication in Future Medical Chemistry (2010)

2009 - Robotic multiwell planar patch-clamp for native and primary mammalian cells

icon pl  Patchliner publication in Nature Protocols (2009)

2009 - Port-a-Patch and Patchliner: High fidelity electrophysiology for secondary screening and safety pharmacology

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Combinatorial Chemistry & High Throughput Screening (2009)

2008 - Planar patch clamp: Advances in electrophysiology

icon pap  Port-a-Patch book chapter in "Potassium Channels" (2008)

2008 - Ion channel screening – automated patch clamp on the rise

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Drug Discovery Today (2008)

2008 - High-throughput electrophysiology: an emerging paradigm for ion-channel screening and physiology

icon pap  Port-a-Patch publication in Nature Reviews Drug Discovery (2008)

2007 - Planar Patch Clamping

icon pap  Port-a-Patch and   icon pl   Patchliner book chapter in "Patch Clamp Analysis – Advanced Techniques", Series: Neuromethods (2007)

2006 - Microchip technology for automated and parallel patch clamp recording

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Small Journal (2006)

2005 - The Port-a-Patch: The smallest patch clamp set up for high quality electrophysiology

icon pap  Port-a-Patch publication in HEKA Impulse (2005)

2004 - Ion channel drug discovery and research: The automated Nano-Patch-Clamp technology

icon pap  Port-a-Patch publication in Current Drug Discovery Technologies (2004)

2003 - Simultaneous optical and electrical recording of single gramicidin channels

icon pap  Port-a-Patch publication in Biophysical Journal (2003)

2003 - Lighting up single ion channels

icon pap  Port-a-Patch publication in Biophysical Journal (2003)

2003 - High quality ion channel analysis on a chip with the NPC-technology

icon pap  Port-a-Patch publication in Assay and Drug Development Technologies (2003)

2002 - Whole cell patch clamp recording performed on a planar glass chip

icon pap  Port-a-Patch publication in Biophysical Journal (2002)

2002 - Patch clamp on a chip

icon pap  Port-a-Patch publication in Biophysical Journal (2002)

2002 - Activity of single ion channel proteins detected with a planar microstructure

icon pap  Port-a-Patch publication in Applied Physics Letters (2002)

2001 - Microstructured glass chip for ion channel electrophysiology

icon pap  Port-a-Patch publication in Physical review. E, Statistical, nonlinear, and soft matter physics (2001)

2000 - Stable integration of isolated cell membrane patches in a nanomachined aperture

icon pap  Port-a-Patch publication in Applied Physics Letters (2000)

Lipid Bilayer Recordings

Artificial Bilayer Recordings:
Analysis of Channels and Pores free from other Proteins

One way to monitor ion channel activity is to use the artificial lipid bilayer recording method, in which many types of reconstituted ion channels and pores can be measured. In contrast to experiments on whole living cells, artificial bilayers provide a different approach for the investigation of ion channels and other integral membrane proteins. The main advantage lies in the complete absence of any unwanted interfering species as well as the convenient and reproducible investigation of target molecules down to a single channel level. This is achieved by the introduction of purified proteins or fusion of proteo-liposomes with precisely controlled composition to the otherwise highly insulating model membrane devoid of any contaminants. Further advantages of this technology are an excellent electrical sealing which provides an extremely sensitive monitoring (down to the single-molecule level), while the compositions of membrane and incorporated proteins can be precisely controlled. In addition, only a small fraction of membrane extract from cells expressing target ion channels is necessary.

Bilayer Recordings


Nanion's Chip-based Planar Bilayer Devices

icon pap   The Port-a-Patch is a semi-automated device with a small footprint for the analysis of ion channels in cells and lipid bilayers.

icon orbit mini   The Orbit Mini combines state of the art amplifier technology with the easy and reproducible investigation of four planar lipid bilayers in parallel. The optional automated temperature control enables experiments at physiological temperatures or on temperature-sensitive species such as TRP channels.

icon orbit   The Orbit 16 has a higher throughput than the Orbit Mini and comprises automated membrane generation which maximizes the system's ease of use and the reproducibility of the experiments.

icon vpp   A helpful device to generate giant unilamellar vesicles (GUVs) for your bilayer recordings is the Vesicle Prep Pro.


bilayer instrument comparison


Recommended publications on Chip-based Bilayer Recordings

SSM-based Electrophysiology

The Solid Supported Membrane (SSM): Measuring transporter currents

Solid supported membrane (SSM)-based electrophysiology differs from conventional electrophysiology such as patch-clamp, since no living cells are required, but rather diverse native or artificial membrane vesicles. The samples used range from reconstituted protein in proteoliposomes to membrane preparations from organelles or plasma membrane. For the sample preparation bacterial cells, eukaryotic cell culture or native tissue can be used. The membrane sample is added to an SSM in advance of the experiment. This leads to the stable adsorption of the membranes to the SSM and the formation of a capacitively coupled compound membrane. The SSM itself consists of a lipid monolayer on top of a thiolated gold coated sensor chip. One important advantage compared to patch-clamp is the large sensor size of up to 3 mm. This allows the measurement of about 10^9 transporters at the same time and yields a significant improvement of signal to noise ratio. Therefore low-turnover targets become accessible to electrophysiological characterization.


The Difference to Conventional Electrophysiology

An important difference between SSM-based electrophysiology and conventional electrophysiology is the principle of measurement. In patch-clamp electrophysiology, stationary currents can be obtained due to the fact that the voltage and, therefore, the driving force is clamped during the measurement. In SSM-based electrophysiology a substrate gradient established by a fast solution exchange is the main driving force. The transport of charged substrates or ions into the liposomes or vesicles generates a membrane potential. This potential can be detected via capacitive coupling between the membrane and the SSM on the gold layer of the sensor. In short: The change in membrane potential due to electrogenic transport is measured. At some point the membrane potential equals the chemical driving force and the transport process comes to a halt. This is why any current measured with SSM-based electrophysiology is transient. The peak current amplitude reflects the transporter activity under steady-state conditions.

Since the current decay is fast, one measurement takes only one second. Due to the high stability of the SSM, multiple measurements can be performed using the same sensor and different buffer conditions to determine kinetic parameters such as EC50, IC50 or even rate constants.


Nanion's Chip-based Solid Supported Membrane Devices

icon n1   The SURFE²R N1 is a medium throughput device, designed for basic research and Universities.

icon 96se   The SURFE²R 96SE is a high throughput device, integrated into the CyBio Felix liquid handling platform.

SSM Instrument Comparison


Recommended Readings

2017 - SSM-Based Electrophysiology for Transporter Research

Icon N1   SURFE²R N1 and   Icon 96SE   SURFE²R 96SE book chapter in Methody in Enzymology

2017 - An emerging technique for the characterization of transport proteins: SSM-based electrophysiology

Icon N1   SURFE²R N1 and    Icon 96SE   SURFE²R SE96 poster, 19th IUPAB / 11th EBSA congress 2017  logo pdf   (3.3 MB)

2016 - Functional analysis of Torpedo californica nicotinic acetylcholine receptors in multiple activation states by SSM-based electrophysiology

Icon 96SE   SURFE²R N96 (predesessor model of SURFE²R 96SE) publication in Toxicological Letters (2016)

Extracellular Recording Techniques

Impedance and Extracellular Field Potential Recordings (EFP)

Impedance and Extracellular Field Potential recordings are non-invasive "label-free" methods and ideally suited to analyze cell motility and action potentials of excitable, intact cultured cells, e. g. cardiomyocytes and neurons.

The extracellular field potential is the electrical potential produced by cells, e.g. nerve or muscle cells, outside of the cell. Electrophysiological studies investigate these potentials using extracellular microelectrodes. In these experiments the extracellular field potential is detected as an electrical potential. For individual cells, the time course of the extracellular potential theoretically is inversely proportional to the transmembrane current.

The electrical impedance is the measurement of the resistance to a current when a voltage is applied and possesses both magnitude and phase. In other words, it is the voltage–current ratio for a single complex exponential at a particular frequency ω. The impedance may be measured or displayed directly in ohms.
Practically: Cells seeded onto an electrical impedance chip or plate cover the electrodes inducing a higher resistance which can be detected. Impedance assays may be carried out at one frequency or over a range of frequencies. Depending on the applied frequency ω, the electrons cross through or in between the cells and thus different parameters of cell morphology and cover rate can be detected. Electrical impedance measurements are suitable to detect the contraction motion of cardiomyocytes, cell growth and motility as well as changes in cell morphology upon application of toxicological substances or substances effecting the cell-cell and cell-matrix contacts in long-term studies.


Nanion's Plate-based Impedance and EFP device

icon CE   The CardioExcyte 96 records action potentials (EFP) and contraction motility (impedance) of cardiomyocytes in parallel.


Recommended publications

2017 - Combined Impedance and Extracellular Field Potential Recordings from Human Stem Cell-Derived Cardiomyocytes 

Icon CE  CardioExcyte 96 book chapter in Stem Cell-Derived Models in Toxicology (2017)

2016 - Safety pharmacology studies using EFP and impedance

Icon CE  CardioExcyte 96 publication in Journal of Pharmacological and Toxicological Methods (2016)

2015 - New Easy-to-Use Hybrid System for Extracellular Potential and Impedance Recordings.

Icon CE  CardioExcyte 96 publication in Journal of Laboratory Automation (2015)

Optogenetics

Optogenetics: Optical Triggering of Action Potentials in Excitable Cells

Optogenetics is a novel technology which can be used to control excitable cells: The expression of specific light-sensitive ion channels makes it possible to depolarize cells with light pulses with millisecond-scale temporal precision and thus accurately triggering action potentials.

Optogenetics offers great potential in regard to cardiac safety studies: Compounds affecting the contraction of cardiomyocytes may affect ion channels and receptors in a use-dependent way which results in different effects for different beat rates. With this technology, its is possible to pace cardiomyocytes in a large beat frequency range simply with light pulses to discover the use-dependent effects of toxins. In iPSC-derived cardiomyocytes, the optogenetic actuator Channelrhodopsin has been proven to be well suited and accepted as a model. A transient transfection Kit for Channelrhodposin is available from iPSC cell providers, e.g. NCardia, for the use of optogenetics in cardiac safety studies.


Nanion's Optogenetics-Compatible Device

icon CE   The CardioExcyte 96 is a device for the investigation of impedance and extracellular field potentials of iPSC-derived cardiomyocytes. A specifically developed lid "SOL" enables the optogenetic pacing of the cells.


Recommended Readings on Optogenetics for Cardiac Safety Studies

CardioExcyte 96 Flyer - SOL

Icon CE   CardioExcyte 96 Product flyer  logo pdf   (2.0 MB)

Cardiomyocytes - Channelrhodopsin 2 (ChR2) transfected Cor.4U cells and optical pacing

Icon CE   CardioExcyte Optogenetics 2CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

ChR2 transfected Cor.4U cells are following the optical pace rate.

Raw data traces upon a 1 Hz, 1.5 Hz, 2 Hz., 2.5 Hz and 3 Hz stimulation rate, extracellular field potentials (top) and impedance (bottom).

 

 

 

Cardiomyocytes - Myocyte phase II study: CiPA conform analysis and arrhythmia detection

Icon CE   CardioExcyte CiPAII 1CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

Nanion developed a CiPA conform analysis for the Myocyte phase II study. The feature comes along is included in our CiPA analysis routine. Automated arrhythmia detection is just one highlight out of many when it comes to the CardioExcyte 96 software.

Cardiomyocytes - Optogenetics meets cardiac safety

Icon CE   CardioExcyte Optogenetics 1CardioExcyte data and applications:
Cells were kindly provided by Axiogenesis.

The stimulating optical lid, CardioExcyte 96 SOL, uses LEDs for spatially uniform stimulation of cells transfected with light-gated ion channels such as Channelrhodopsin2 (ChR2).

Right graph: LPM – Light pulse per minute plotted against the recorded beat rate (average of 96 wells). ChR2 transfected Cor.4U cells are following the optical pace rate.

Giant Unilamellar Vesicles (GUV's)

GUVs: Vesicles for Multiple Applications

A vesicle is a lipid bilayer rolled up into a spherical shell, enclosing a small amount of water and separating it from the water outside the vesicle. Because of this fundamental similarity to the cell membrane, vesicles have been used extensively to study the properties of lipid bilayers. Another reason vesicles have been used so frequently is that they are relatively easy to make. If a sample of dehydrated lipid is exposed to water it will spontaneously form vesicles. These initial vesicles are typically multilamellar (many-walled) and range in size from tens of nanometers to several micrometers.

Further methods are required to break these initial vesicles into smaller, single-walled vesicles of uniform diameter known as small unilamellar vesicles (SUVs) with diameters of 50 nm to 200 nm. Since artificial SUVs can be made in large quantities they are suitable for bulk material studies such as x-ray diffraction to determine lattice spacing and differential scanning calorimetry to determine phase transitions. Dual polarisation interferometry can measure unilamellar and multilamellar structures and insertion into and disruption of the vesicles in a label-free assay format. Vesicles can also be labelled with fluorescent dyes to allow sensitive FRET-based fusion assays.

In spite of this fluorescent labeling it is often difficult to perform detailed imaging on SUVs simply because they are so small. To combat this problem researchers have developed the giant unilamellar vesicle (GUV). GUVs are large enough (several tens of micrometres) to study with traditional fluorescence microscopy. Many of the studies of lipid rafts in artificial lipid systems have been performed with GUVs for this reason. Compared to supported bilayers, GUVs present a more “natural” environment since there is no nearby solid surface to induce defects or denature proteins.

Products Vesicles bea 330


Nanion's Giant Unilamellar Vesicles Device

icon vpp   The Vesicle Prep Pro is a device for the fomration of GUVs by means of electro-swelling.


GUVs can be used for the following devices:

icon pap   Port-a-Patch: Bilayer Recordings

Icon N1   SURFE²R: SSM-based Electrophysiology

Icon 96SE   SURFE²R: SSM-based Electrophysiology

 


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Nanion Technologies GmbH

Ganghoferstr. 70A
D-80339 Munich - Germany
info@nanion.de