Optopatch: high-throughput all-optical electrophysiology.

C. A. Werley, O. M. McManus, G. T. Dempsey
Q-State Biosciences, United States

Keywords: neuroscience, disease modeling, drug screening, stem cell, electrophysiology

Compromised neurological function is a major unmet medical need in both military and civilian contexts, impacting nearly 1 billion people globally. The inability to develop treatments has been attributed to a lack of translatable model systems and screening technologies with outputs predicting a primary therapeutic endpoint. To address these challenges, Q-State has developed a robust, industrial-scale platform for derivation and functional assessment of human induced pluripotent stem cell (hiPSC)-derived neurons. Neuronal misfunction can be modeled with neurons derived either from an adult patient or by inducing a genetic mutation in healthy control cells using CRISPR/Cas9 gene editing technology. Neuronal function is assayed with Q-State’s proprietary all-optical electrophysiology platform “Optopatch.” Optopatch allows simultaneous optical stimulation and recording of neuronal action potentials (APs) using genetically encoded proteins: the engineered channelrhodopsin CheRiff enables AP stimulation with blue light and the engineered voltage-sensitive fluorescent protein QuasAr enables high-speed electrical recordings with red light. The custom-designed Firefly microscope can stimulate individual neurons using patterned blue light and record from 100s of neurons in parallel, enabling incisive measurements of neuronal excitability and synaptic transmission. Optopatch maintains the rich information content of manual patch clamp, but with 20,000x higher throughput.