Graphene Electric Field Sensor Enables Single Shot Label-Free Imaging of Bioelectric Potentials

Abstract

The measurement of electrical activity across systems of excitable cells underlies current progress in neuroscience, cardiac pharmacology, and neurotechnology. However, bioelectricity spans orders of magnitude in intensity, space, and time, posing substantial technological challenges. The development of methods permitting network-scale recordings with high spatial resolution remains key to studies of electrogenic cells, emergent networks, and bioelectric computation. Here, we demonstrate single-shot and label-free imaging of extracellular potentials with high resolution across a wide field-of-view. The critically coupled waveguide-amplified graphene electric field (CAGE) sensor leverages the field-sensitive optical transitions in graphene to convert electric potentials into the optical regime. As a proof-ofconcept, we use the CAGE sensor to detect native electrical activity from cardiac action potentials with tens-of-microns resolution, simultaneously map the propagation of these potentials at tissue-scale, and monitor their modification by pharmacological agents. This platform is robust, scalable, and compatible with existing microscopy techniques for multimodal correlative imaging.

Voltage Modulation of Nanoplasmonic Metal Luminescence from Nano-Optoelectrodes in Electrolytes

“…Significantly, our measurements in Figure C and Figure C demonstrate that biocompatible Au-based NLNOEs can produce PE-ERS signals with a substantial voltage modulation rate normalΔ I PE ‐ ERS ( Δ U ) normalΔ U · I PE ‐ ERS ( U 0 ) of ≈15% V –1 to ≈30% V –1 in physiological electrolytes (e.g., 1× PBS); thus, they can potentially serve as label-free nonlinear voltage nanosensors. Although the PE-ERS voltage modulation rate from NLNOEs is still lower than label-based voltage-sensitive fluorophores (80% to 200% V –1 ) and recently reported label-free linear scattering-based voltage nanotransducers (≈100% V –1 ), , they may enjoy advantage by combining label-free operations, low phototoxicity, excellent photostability, and nonlinear NIR deep-tissue sensing/imaging modalities by filtering elastic scattering background. Furthermore, our analytical model in eqs and reveals that there is room to improve the PE-ERS voltage modulation performance in signal brightness and voltage sensitivity.…”

Dual-Color Optical Recording of Bioelectric Potentials by Polymer Electrochromism

“…A zoomed-in view of the signal shows a highly complex shape (Figure d). In cardiomyocytes, an electrical signal is immediately followed by a mechanical contraction through excitation-contraction coupling. ,, The mechanical contraction at the cell–substrate interface perturbs the light reflection and results in the complex ECORE signal. As shown in Figure d, the extracellular electrical signals appear as fast spikes typically on the order of 5 ms, which can be easily distinguished by the opposite changes in the two channels (red and green arrows).…”

“…For example, nitrogen-vacancy color centers of a thin diamond layer were used to detect the nuanced magnetic field accompanied by the electrical signals of excited worm and squid giant axons . Field-sensitive optical transitions in graphene have been used to convert electrical signals into reflectance changes to detect spontaneous action potentials from whole chicken hearts . Intrinsic optical properties of cells such as light scattering or membrane deformations can be modulated by membrane potentials, although these properties are indirect readouts and can be modulated by cellular mechanisms other than action potentials. , Recently, we demonstrated that ElectroChromic Optical REcording (ECORE) converts bioelectrical signals into optical readout by harnessing the electrochromic property of π-conjugated polymer poly­(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) thin films .…”

Engineering optical tools for remotely controlled brain stimulation and regeneration

“…149 This issue can be alleviated by chemical doping of graphene or by introducing an electric current to the electrode, in order to modulate the Fermi energy. 150 Alternatively, efficient electron cooling after light exposure can be ensured by minimising the presence of defects in graphene's crystal structure, which are responsible for heat-generating acoustic phonon emission. 151 An attractive strategy consists of incorporating these conductive nanomaterials with photoactive compounds efficiently absorbing light, such as poly-3-hexylthiophene (P3HT), 127 carbon nitride, 152 and other organic dye molecules, [153][154][155] as well as semiconducting quantum dots and nanorods.…”