Using Full Factorial Design of Experiments on an Automated Patch Clamp Instrument: A Case Study on the Ionworks Quattro and Nav1.5 Channel

Abstract

In the past decade, technological advancements have enabled automation of patch clamp recordings. Instruments like the Ionworks Quattro produces electrophysiological data from a 384 well plate in about an hour. However, they also require proprietary and expensive one-use consumables like the PatchPlate. Conversely, the large amount of data produced from these instruments also allows more than the “one factor at a time” experiments. Here we present an example of a full factorial experiment on the Nav1.5 channel using the Ionworks Quattro. A full factorial experimental design provides more information about the instrument by having a more precise estimation of each factor alone and by estimating the interactions between factors.We tested the potencies of several known blockers on the cardiac sodium channel (Nav1.5) and varied 3 factors: incubation time, mixing cycles, and cell density. From the experiment, we find that the IC50s of most compounds are affected by incubation time and cell density. We also observed interactions with the factors of incubation time/cell density and the number of mixing cycles/cell density. From this case study, we propose that a factorial design of experiments can be done effectively with an automated patch clamp instrument to optimize assay conditions with enriched information to the effect of reduction of consumables and shortened time of assay development.