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Label-free optical detection of bioelectric potentials using electrochromic thin films

Significance Optical recording is highly desirable to detect bioelectric activities, as it can flexibly record a variety of user-selected locations. Here, we present ECORE, a label-free optical recording method that uses different principles than fluorescence-based voltage recording and offers independent advantages. ECORE utilizes voltage-dependent absorption of an electrochromic thin film and thus is not affected by photobleaching. ECORE offers spatial flexible and long-term optical recording without genetic or molecular perturbation. Understanding how a network of interconnected neurons receives, stores, and processes information in the human brain is one of the outstanding scientific challenges of our time. The ability to reliably detect neuroelectric activities is essential to addressing this challenge. Optical recording using voltage-sensitive fluorescent probes has provided unprecedented flexibility for choosing regions of interest in recording neuronal activities. However, when recording at a high frame rate such as 500 to 1,000 Hz, fluorescence-based voltage sensors often suffer from photobleaching and phototoxicity, which limit the recording duration. Here, we report an approach called electrochromic optical recording (ECORE) that achieves label-free optical recording of spontaneous neuroelectrical activities. ECORE utilizes the electrochromism of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) thin films, whose optical absorption can be modulated by an applied voltage. Being based on optical reflection instead of fluorescence, ECORE offers the flexibility of an optical probe without suffering from photobleaching or phototoxicity. Using ECORE, we optically recorded spontaneous action potentials in cardiomyocytes, cultured hippocampal and dorsal root ganglion neurons, and brain slices. With minimal perturbation to cells, ECORE allows long-term optical recording over multiple days.