The IonWorks family of instruments targets the unmet need for a low cost, high throughput, direct electrophysiological assay for ion channel targets. Unlike indirect assays, such as fluorescent or ion flux assays, that are surrogate measure of ion channel activity, IonWorks instrumentation measures ionic currents directly and controls the membrane voltage inside a cell. The IonWorks® Barracuda? System builds on the capabilities demonstrated by the IonWorks Quattro system while adding the capability to measure rapidly desensitizing ligand-gated channels. With the IonWorks Barracuda System a throughput of over 10,000 data points per day can be achieved with both voltage- and ligand-gated ion channels (VGICs and LGICs). The system features Population Patch Clamp (PPC) technology1 which improves data consistency and success rates by mitigating the biological variability seen when measuring from single cells. PPC has enabled the primary screening of large directed libraries2 as well as novel assays including channel opener assays and multiplexing multiple ion channel targets in a single assay3. The IonWorks Barracuda System supports both PPC and single hole (SH) recording modes. SH recording mode is important where information must be obtained from individual cells during ion channel assay optimization and in applications such as the selection of individual clones for cell line optimization.
The IonWorks Barracuda System features a 384-well assay plate (our PatchPlate? consumable) with a uniquely designed recording chamber that is optimized for rapid fluid exchange. This is especially important when measuring fast LGICs in order to resolve the rapid activation and desensitization kinetics of their ionic currents. The system combines 384 discreet amplifiers and a 384-channel pipettor head for the recording of ionic currents in all wells simultaneously. The parallel recording and fluidics configuration allow for the generation of over 10,000 data points per day. A typical ion channel assay with one compound addition per well can be completed in as little as 20 minutes. The system also allows up to eight compound additions per well further increasing the throughput and reducing the cost per data point. The IonWorks Barracuda System is ideal for primary screening of large directed compound libraries.  Further, with the capability to add multiple compound additions per well, for example increasing concentrations on a dose response curve, the system is also well suited for compound profiling and safety assessment.
The IonWorks Barracuda System comes in two configurations: a base system and a fully automated system which includes cell management capabilities and plate-handling. Both systems come with an automated pipettor for the transfer of cell suspension to a cell boat designed to minimize cell usage (<5mls/run) to cut down on the operating costs of cell culture. To load cells on the base system, the user simply provides a tube of cell suspension to a position on the assay deck. The automated system adds a plate handler that shuttles PatchPlates, pipette tips, and compound plates from the external landing pad to each deck position and removes them back to the landing pad as needed. Onboard cell storage and cell suspension preparation is provided on  the assay deck of the automated system. Cells are removed from the cell storage vessel, followed by solution exchange and cell concentration utilizing the on-board centrifuge. The fully automated configuration provides unattended operation for up to 6 hours.
 
Feature
·               Simultaneous compound addition and data acquisition allows the measurement of both voltage- and rapidly activating and desensitizing ligand-gated channels
·               Unique flow through recording chamber design enables rapid solution exchange
·               384 discrete amplifiers combined with a 384 channel pipettor head for parallel acquisition of an entire 384 well PatchPlate? in as little as 20 minutes
·               Optional on-board cell management and plate handling for unattended operation up to six hours and >10,000 data points per day
·               CellPettor delivery of cell suspension minimizes on board cell usage when operating with or without optional cell management
·               Proven low-cost IonWorks PatchPlate consumable to keep running costs down
·               Eight compound additions per well further increases throughput and decreases the cost per data point over previous IonWorks systems
·               Population Patch Clamp? (PPC) technology which reduces well-to-well variability to deliver consistent, reproducable results
·               Flexible software with two modes of operation, Assay Development and Screening streamlines assay optimization and simplifies ion channel screening
·               Rapid analysis of ionic currents using simple metrics similar to the IonWorks Quattro
·               Ultrasonic pipette tip washer with two wash solutions eliminates the potential of cross contamination across experimental runs
 Application
Voltage-gated ion channels:  Many voltage-gated ion channels (VGIC) including Na+, K+, Cl-, and Ca2+ channels have been measured on IonWorks systems. The same VGIC targets measured on the IonWorks® HT and Quattro systems can be measured on the IonWorks Barracuda system.
Ligand-gated ion channels: The measurement of ligand-gated ion channels (LGIC) including ASIC1a, GABA, and nACh channels have been validated on the IonWorks Barracuda system.
Directed library screening: The introduction of the Population Patch Clamp (PPC) technique allowed the screening of large directed libraries in the 10's-100's of thousands of compounds against ion channel targets.
Clonal selection: The IonWorks family of instruments has been shown to be an excellent way of identifying and optimizing cell lines for use with IonWorks systems and other electrophysiological assays.   
Lead identification: Ion channel targets are implicated in many diseases. Once researchers determine that a particular ion channel is involved in a particular disease state, a screening assay can be established against which large numbers of compounds can be screened to identify "hits" or "leads" that could ultimately become drug candidates.
Lead optimization: After "hits" or "leads" have been identified, drug discovery researchers optimize their chemical structure in order to get the best possible drug candidates-the compounds that are most likely to have the desired effect on ion channels with the fewest possible side effects.
Safety assessments: A critical part of lead optimization involves early safety assessments, such as hERG testing, in order to eliminate any compounds with potential safety concerns as early as possible. This allows researchers to focus their resources on the most promising drug candidates to streamline the drug discovery process.  Safety assessment assays including hERG, HCN, KCNQ, and Nav 1.5 channels have been published.