I-Corps: Three-dimensional nanoelectrodes for non-invasive intracellular electrophysiology

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The drug development pipeline requires that potential drugs pass through a gamut of tests which demonstrate the drugs' efficacy and safety. The drug safety test starts from cellular studies before moving into animals and finally humans. As a drug moves from cellular measurements to animal measurements, the time and money involved increase dramatically. Therefore, it is essential to detect potential drug toxicity early on, preferably at the cellular level. The drug toxicity manifests mostly as non-specific binding to ion channels and therefore affecting cardiac action potentials. The current golden standard technique to detect action potential changes is patch clamps. However, the patch clamp has very low throughput and is challenging to implement, which limit the number of drug trials or drug candidates that can be screened. The proposed nanoelectrode device allows these companies to expedite testing and reduce the cost of cellular tests. In particular, nanoelectrodes can measure electrophysiology in high throughput and low toxicity and therefore allowing testers to measure more drugs with greater ease.Current drug toxicology screens inevitably involve patch clamp electrophysiology to test off-target cardiac activity. Patch clamp is technically challenging to use and has limited multiplexing capability. Over the last six years, this group has worked to develop a new nanotechnology tool for electrophysiology. The proposed tool measures intracellular recordings of mammalian cells with high throughput and low requirements on technical capability in the experimenter. Signals recorded by these nanoelectrodes are carried out from the culture under test on metal leads and amplified at an external multi-electrode array (MEA) amplifier. This team expects to have customers in both pharmaceutical toxicology and academic laboratories who are interested in pursuing electrophysiological questions. This team also believes that anyone interested in the initial screening of new drugs for their toxicological side effects would be interested in the proposed technology that could be integrated into automated cell culture systems and offers simple handling and experimentation.