Gigaohm seals (‘gigaseals’) are essential for patch clamp electrophysiology, enabling high-quality recordings by ensuring strong electrical access to cells. In manual patch clamp, seals form between the cell membrane and glass pipette, while in planar patch clamp, they form on a chip substrate. Planar patch clamp often uses seal enhancers like CaF2, which is believed to promote sealing through CaF2 precipitate formation at the solution interface. However, F- can interfere with intracellular components and affect ion channel properties. To address these issues, Sophion developed new seal-enhancing solutions in 2017 (Patent: WO2018100206A1). Metrion and Sophion later collaborated to explore alternative insoluble salts and their impact on ion channels' biophysics and pharmacology.
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Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.
The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.