IonWorks Barracuda Plus Automated Patch Clamp System. Unmatched performance for automated electrophysiology.

Transcription

1 IonWorks Barracuda Plus Automated Patch Clamp System Unmatched performance for automated electrophysiology

2 A new era in electrophysiology IonWorks Systems are used in more electrophysiology laboratories worldwide than any other automated electrophysiology platform. The next generation, IonWorks Barracuda Plus System has bridged the gap between low cost screening and the accuracy of direct electrophysiological analysis. Now a single platform provides an affordable, rapid solution for voltage- and ligandgated ion channel research for drug discovery screening and safety assessment. Direct screening earlier Introduce the accuracy of direct electrophysiological screening earlier in the drug discovery process fail compounds early to save time and money downstream. Replace manual methods IonWorks Barracuda Plus System is easy to use eliminates the need for labor intensive conventional patch clamp Precise voltage control and high temporal resolution produces results similar to manual patch clamp methods Long assay windows, up to 30 minutes, support the study of use-dependent blockers Afford the speed and benefits of automated electrophysiology Lowest running costs make primary screening affordable compared to GigaSeal instruments Peer reviewed publications show IonWorks Barracuda Plus System system recordings yield comparable results to GigaSeal recordings (1-8) Reliable, proven consumables with no requirement for non-physiologic sealing solutions 1 / IonWorks Barracuda Plus System

3 Replace slow, expensive methods IonWorks Barracuda Plus System GigaSeal system Screens 25,000 compounds for $20,000 in 3 days Screens 25,000 compounds for $312,000 in 81 days Cost Cost 0 $80,000 0 $80,000 $160,000 $240,000 $320,000 Days Days IonWorks Barracuda Plus System / 2

4 Innovations that yield unmatched performance Rapid fluidic additions during data acquisition yield highly resolved measurements of voltage- or ligand-gated ion channels Flexible voltage- and fluidic- recording parameters combined with long assay windows The ultimate drug discovery tool for the discovery of use-dependent compounds True 384-parallel acquisition Fluidic pipettor provides solution exchange simultaneously in all 384 wells 384 discrete amplifiers and digitizers allow voltage-clamp recordings simultaneously in all wells Highly parallel recording rates of > 1,100 data points per hour for single point assays Rapid individual offset correction for each of the 384 electrodes Patented flow through well design for rapid solution exchange Provides the fastest solution exchange of any automated electrophysiology platform 9 Unique fluidic protocols to achieve very long assay windows User-defined aspirate and dispense speed and height Disposable tips which can be reused if desired after ultrasonic washing 3 / IonWorks Barracuda Plus System

5 Patented Population Patch Clamp (PPC) recording True PPC recording has 64 holes per well for better well-to-well consistency over all other automated systems Produces robust and reproducible recordings with near 100% data success rates Averaging data from a population of cells mitigates biological variability and eliminates lost data points from non-expressing cells IonWorks PatchPlate consumable: proven in drug discovery labs for over a decade High-quality, low-cost plates keep running costs down Dose response curves can be performed as cross-well comparisons or within single wells Multiple compound additions support within-well dose response curves greatly reducing running costs Constant fluid level maintained when using multiple compound additions Working deck designed for ease of use Ultrasonic pipette tip washer with two wash solutions eliminates the potential of cross contamination Unique cell delivery system minimizes cell usage < 5 ml/run Easy access to plates and consumables IonWorks Barracuda Plus System / 4

6 Software that s advanced yet simple Built on Axon Instruments-inspired software For over 25 years, Axon Instruments has been providing world-class data acquisition software for electrophysiology. The software for the IonWorks Barracuda Plus System was developed using the expertise and knowledge used in Axon Systems to build an interface that is simple to use yet offers all the flexibility needed to develop complex assays. Assay development and screening modes of operation 600,000 data points per sweep Unlimited number of sweeps can be acquired Digitizer sample rates from 100 Hz to 20 KHz 1. Build sophisticated voltage protocols in assay development mode Voltagedependence of activation Voltagedependence of inactivation Recovery from inactivation Pulse trains 2. Combine protocols and run in Screening Mode 5 / IonWorks Barracuda Plus System

7 One platform does it all Primary screen The lowest running costs of any automated electrophysiology system makes screening directed compound libraries of hundreds of thousands of compounds affordable. Primary screen using 384-well plates. Secondary screen Long assay windows, the ability to run multiple compound additions and generate cumulative concentration-response data makes hit validation and safety assessment of even challenging ion channels possible. Population Patch Clamp (PPC) technology yields high well-to-well reproducibility by allowing cross-well comparisons. Results Software gives rapid visualization clearly showing whether active compounds were detected. Filter analysis view provides a visual readout of the half inhibition values for different compounds. IonWorks Barracuda Plus System / 6

8 Perform advanced kinetic profiling on hit compounds The IonWorks Barracuda Plus System's unique features allow user to perform use-dependent experiments with very high reproducibility and throughput. Plots of peak ionic currents displayed show use-dependency of various Na V 1.5 channel blockers. Current (na) Na V 1.5 (Control) Data shows blockade of ionic currents at each compound's approximate IC 20 concentrations at the first pulse. Subsequent use-dependent blockade with strikingly different behavior is shown for tetracaine, lidocaine, and tetrodotoxin Time (minutes) Na V 1.5 (50 um Tetracaine) Current (na) Time (minutes) Na V 1.5 (948 um Lidocaine) Current (na) Time (minutes) Na V 1.5 (0.2 um TTX) Current (na) Time (minutes) / IonWorks Barracuda Plus System

9 Capable of very long assay time-windows Start Time Pulse Train 2 / Train 1-1.0% 10.1 Train 3 / Train 2-3.5% 11.6 Train 4 / Train 3 0.4% 13.7 Train 5 / Train 4 1.1% 14.7 Train 6 / Train 5 2.0% 16.3 Train 7 / Train 6-2.2% 17.8 Train 8 / Train 7-0.7% 19.9 Train 9 / Train 8-0.3% 20.9 Train 10 / Train 9 5.1% 22.5 Train 11 / Train % 24.0 Train 12 / Train % 26.1 Train 13 / Train % 27.1 Train 14 / Train % 28.7 Train 15 / Train % 30.2 Train 16 / Train % Mean 0.28% S.D Start Time Pulse Train 2 / Train 1-1.9% 10.1 Train 3 / Train 2-2.0% 11.6 Train 4 / Train 3 0.3% 13.7 Train 5 / Train 4 1.0% 14.7 Train 6 / Train 5 1.7% 16.3 Train 7 / Train 6-1.7% 17.8 Train 8 / Train 7-1.1% 19.9 Train 9 / Train 8-0.2% 20.9 Train 10 / Train 9 4.7% 22.5 Train 11 / Train % 24.0 Train 12 / Train % 26.1 Train 13 / Train % 27.1 Train 14 / Train % 28.7 Train 15 / Train % 30.2 Train 16 / Train % Mean 0.31% S.D The IonWorks Barracuda Plus System is capable of providing very wide assay windows even with difficult ion channel targets. Plots of peak ionic currents are displayed in wells where mock compound (buffer) additions were made at the arrows. A very wide assay window for Na V 1.5 ion channel currents is shown. 30-pulse trains are displayed with the starting time of each train plotted below the ionic current plots. Tables display the percent change in peak ionic currents (Pulse 1 and Pulse 30) from one train to the next. Very stable peak currents are seen at both Pulse 1 and Pulse 30. Current (na) Na V 1.5 (control) Train start time (min.) IonWorks Barracuda Plus System / 8

10 Technical specifications Amplifiers Number of amplifiers 384 Amplifier bandwidth 30 KHz (Max) Current range (SH*) ± 100 na Current range (PPC**) actual ± 4,700 na Current range (PPC) scaled per hole (screen display) ± 70 na Digitizer Number of channels 384 Sample rate 100 Hz 20 KHz Bit resolution noise (VGICs) 3 pav Bit resolution noise (LGICs) 6 pa Fluidics Simultaneous transfer 384 Pipettor range 5 20 µl 5 µl 4% CV Pipetting increments 1.0 µl Wash station Ultrasonic capability with two-solution inputs General specifications Dimensions (door closed) 1.2 m (48 ) W x 0.8 m (33 ) D x 1.8 m (72 ) H Dimensions (door open) 1.2 m (48 ) W x 0.8 m (33 ) D x 2.14 m (84 ) H Weight 499 kg (1,100 lbs.) *SH = Single Hole (1 hole per well) **PPC = Population Patch Clamp (64 holes per well) 9 / IonWorks Barracuda Plus System

11 Ordering information IonWorks Barracuda System item Part number IonWorks Barracuda System Box, 48 Barracuda PatchPlates, SH Box, 48 Barracuda PatchPlates, PPC Standard Cell Boat (24-trough) for the IonWorks Barracuda System Supplemental Electrode Plate for the IonWorks Barracuda System Supplemental Model Cell Plate for the IonWorks Barracuda System IonWorks Barracuda Software Package, Version Clear Pipette Tips for the IonwWorks Barracuda System Black Pipette Tips for the IonWorks Barracuda System Buffer Boat for the IonWorks Barracuda System (25 Boats/Case) CellPettor Pipettes for the IonWorks Barracuda System (200 CellPettor Pipettes/case) References 1. Bridgland-Taylor, M. H., A. C. Hargreaves, et al. (2006). "Optimisation and validation of a medium-throughput electrophysiology-based herg assay using IonWorks HT." J Pharmacol Toxicol Methods 54(2): Cao, X., Y. T. Lee, et al. (2010). "Cardiac ion channel safety profiling on the IonWorks Quattro Automated Patch Clamp System." Assay Drug Dev Technol 8(6): Castle, N., D. Printzenhoff, et al. (2009). "Sodium channel inhibitor drug discovery using automated high throughput electrophysiology platforms." Comb Chem High Throughput Screen 12(1): Felix, J. P., B. T. Priest, et al. (2012). "The inwardly rectifying potassium channel Kir1.1: development of functional assays to identify and characterize channel inhibitors." Assay Drug Dev Technol 10(5): Gillie, D. J., S. J. Novick, et al. (2013). "Development of a high-throughput electrophysiological assay for the human ether-a-go-go related potassium channel herg." J Pharmacol Toxicol Methods 67(1): Graef, J. D., L. C. Benson, et al. (2013). "Validation of a high-throughput, automated electrophysiology platform for the screening of nicotinic agonists and antagonists." J Biomol Screen 18(1): Harmer, A. R., N. Abi-Gerges, et al. (2008). "Optimisation and validation of a medium-throughput electrophysiology-based hna V 1.5 assay using IonWorks." J Pharmacol Toxicol Methods 57(1): Jow, F., R. Shen, et al. (2007). "Validation of a medium-throughput electrophysiological assay for KCNQ2/3 channel enhancers using IonWorks HT." J Biomol Screen 12(8): Excluding the PatchXpress 7000A System IonWorks Barracuda Plus System / 10

12 Contact Us Phone: Web: Check our web site for a current listing of worldwide distributors. Regional Offices USA and Canada Brazil China (Beijing China (Shanghai) Germany / Japan (Tokyo) Japan (Osaka) South Korea United Kingdom FOR RESEARCH USE ONLY. NOT FOR USE IN DIAGNOSTIC PROCEDURES. The trademarks used herein are the property of Molecular Devices, LLC or their respective owners Molecular Devices, LLC 10/13 Printed in USA PN: A2