The IonWorks Quattro system employs a new PatchPlate Population Patch Clamp (PPC) substrate, a 384-well planar array that is designed to allow ion channel recordings to be simultaneously collected from multiple cells within each well.
The patch clamping method is commonly used for measuring currents flowing through ion channels in cell membranes. Patch clamping, which looks at the entry or exit of ions through these channels, is used for testing compounds and side effects of pharmaceuticals.
Ion channels are an important therapeutic target class for diseases of the cardiovascular and central nervous systems. IonWorks Quattro is ideal for these applications, from primary screening of directed compound libraries, to hit confirmation, selectivity testing and lead optimisation.
Ion channels are also important in early safety testing. The IonWorks Quattro system is designed to be used for early screening of lead candidates for unintentional activity on ion channels, such as the cardiac potassium channel or human ether related gene (hERG).
Ion channels play an important role in cell signalling, electrical excitability and fluid transport, and are drug targets themselves in a number of indications, including heart disease, diabetes, autoimmune diseases and migraine. Small molecules that block or open ion channels are considered to be promising drug candidates.
In addition, some ion channels on heart muscle cells are associated with toxicology problems, and candidate's drugs are routinely screened against them.
The IonWorks Quattro system has shown success rates of 95 per cent plus, a figure that is deemed so high that it is not necessary to apply test compounds to four wells. This enables a four-fold throughput improvement and up to 50 per cent reduction in cost per data point over the IonWorks HT system.
The PPC technology utilised by the IonWorks Quattro system extends the multi-cell technology inherent in Molecular Devices' existing fluorescence screening instruments, such as FLIPR, to electrophysiology.
Alan Finkel, chief technology officer at Molecular Devices said: "All previous electrophysiological recording systems are limited by the success rate that is achievable with a single cell in a well, which is unlikely to exceed 70 per cent consistently, even under the best of circumstances."
He added: "The PPC technique is designed to remove the dependence on the expression levels or viability of individual cells, thereby enabling each well to measure the response to a population of cells."
The throughput and reduced cost-per-data-point of this system makes it affordable to conduct primary screening campaigns of directed library sets. In addition, the IonWorks Quattro is fully compatible with IonWorks HT technology, supporting both the original PatchPlate and new PatchPlate PPC substrates.