Photoreceptors initiate vision by converting photons to electrical activity. The onset of the phototransduction cascade is marked by the isomerization of photopigments upon light capture. We revealed that the onset of phototransduction is accompanied by a rapid (<5 ms), nanometer-scale electromechanical deformation in individual human cone photoreceptors. Characterizing this biophysical phenomenon associated with phototransduction in vivo was enabled by high-speed phase-resolved optical coherence tomography in a line-field configuration that allowed sufficient spatiotemporal resolution to visualize the nanometer/millisecond-scale light-induced shape change in photoreceptors. The deformation was explained as the optical manifestation of electrical activity, caused due to rapid charge displacement following isomerization, resulting in changes of electrical potential and surface tension within the photoreceptor disc membranes. These all-optical recordings of light-induced activity in the human retina constitute an optoretinogram and hold remarkable potential to reveal the biophysical correlates of neural activity in health and disease.

Currently, cellular action potentials are detected using either electrical recordings or exogenous fluorescent probes that sense the calcium concentration or transmembrane voltage. Ca imaging has a low temporal resolution, while voltage indicators are vulnerable to phototoxicity, photobleaching, and heating. Here, we report full-field interferometric imaging of individual action potentials by detecting movement across the entire cell membrane. Using spike-triggered averaging of movies synchronized with electrical recordings, we demonstrate deformations up to 3 nm (0.9 mrad) during the action potential in spiking HEK-293 cells, with a rise time of 4 ms. The time course of the optically recorded spikes matches the electrical waveforms. Since the shot noise limit of the camera (~2 mrad/pix) precludes detection of the action potential in a single frame, for all-optical spike detection, images are acquired at 50 kHz, and 50 frames are binned into 1 ms steps to achieve a sensitivity of 0.3 mrad in a single pixel. Using a self-reinforcing sensitivity enhancement algorithm based on iteratively expanding the region of interest for spatial averaging, individual spikes can be detected by matching the previously extracted template of the action potential with the optical recording. This allows all-optical full-field imaging of the propagating action potentials without exogeneous labels or electrodes.

Neurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear. Here we report full-field imaging of cellular deformations accompanying the action potential in mammalian neuron somas (−1.8 to 1.4 nm) and neurites (−0.7 to 0.9 nm), using high-speed quantitative phase imaging with a temporal resolution of 0.1 ms and an optical path length sensitivity of <4 pm per pixel. The spike-triggered average, synchronized to electrical recording, demonstrates that the time course of the optical phase changes closely matches the dynamics of the electrical signal. Utilizing the spatial and temporal correlations of the phase signals across the cell, we enhance the detection and segmentation of spiking cells compared to the shot-noise–limited performance of single pixels. Using three-dimensional (3D) cellular morphology extracted via confocal microscopy, we demonstrate that the voltage-dependent changes in the membrane tension induced by ionic repulsion can explain the magnitude, time course, and spatial features of the phase imaging. Our full-field observations of the spike-induced deformations shed light upon the electromechanical coupling mechanism in electrogenic cells and open the door to noninvasive label-free imaging of neural signaling.

Portable and easy-to-use imaging systems are in high demand for medical, security screening, nondestructive testing, and sensing applications. We present a new microwave-induced thermoacoustic imaging system with noncontact, airborne ultrasound (US) detection. In this system, a 2.7 GHz microwave excitation causes differential heating at interfaces with dielectric contrast, and the resulting US signal via the thermoacoustic effect travels out of the sample to the detector in air at a standoff. The 65 dB interface loss due to the impedance mismatch at the air-sample boundary is overcome with high-sensitivity capacitive micromachined ultrasonic transducers with minimum detectable pressures (MDPs) as low as 278 µPa rms and we explore two different designs-one operating at a center frequency of 71 kHz and another at a center frequency of 910 kHz. We further demonstrate that the air-sample interface presents a tradeoff with the advantage of improved resolution, as the change in wave velocity at the interface creates a strong focusing effect alongside the attenuation, resulting in axial resolutions more than 10× smaller than that predicted by the traditional speed/bandwidth limit. A piecewise synthetic aperture radar (SAR) algorithm modified for US imaging and enhanced with signal processing techniques is used for image reconstruction, resulting in mm-scale lateral and axial image resolution. Finally, measurements are conducted to verify simulations and demonstrate successful system performance. Index Terms-Capacitive micromachined ultrasonic transducer (CMUT), non-contact microwave-induced thermoacoustics, piecewise synthetic aperture, ultrasound (US) imaging. I. INTRODUCTION P ORTABLE imaging systems are in demand for a variety of applications, from nondestructive testing and sensing to security screening and point-of-care diagnostic imaging [1]-[3]. Such systems must also be low-cost, safe, Manuscript

A radio frequency (RF)/ultrasound hybrid imaging system using airborne capacitive micromachined ultrasonic transducers (CMUTs) is proposed for the remote detection of embedded objects in highly dispersive media (e.g., water, soil, and tissue). RF excitation provides permittivity contrast, and ultrasensitive airborne-ultrasound detection measures thermoacoustic-generated acoustic waves that initiate at the boundaries of the embedded target, go through the medium-air interface, and finally reach the transducer. Vented wideband CMUTs interface to 0.18 lm CMOS low-noise amplifiers to provide displacement detection sensitivity of 1.3 pm at the transducer surface. The carefully designed vented CMUT structure provides a fractional bandwidth of 3.5% utilizing the squeeze-film damping of the air in the cavity. V

Neurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear.We report full-field imaging of cellular deformations accompanying the action potential in mammalian neuron somas (-1.8nm~1.3nm) and neurites (-0.7nm~0.9nm), using fast quantitative phase imaging with a temporal resolution of 0.1ms and an optical pathlength sensitivity of <4pm per pixel. Spike-triggered average, synchronized to electrical recording, demonstrates that the time course of the optical phase changes matches the dynamics of the electrical signal, with the optical signal revealing the intracellular potential rather than its time derivative detected via extracellular electrodes. Using 3D cellular morphology extracted via confocal microscopy, we demonstrate that the voltage-dependent changes in the membrane tension induced by ionic repulsion can explain the magnitude, time course and spatial features of the phase imaging. Our full-field observations of the spike-induced deformations in mammalian neurons opens the door to non-invasive label-free imaging of neural signaling.

Photoreceptors in the retina convert light into electrical signals through a phototransduction cycle that consists of multiple electrical and biochemical events. Phase-resolved optical coherence tomography (pOCT) measurements of the optical path length (OPL) change in the cone photoreceptor outer segments after a light stimulus (optoretinogram) reveal a fast, ms-scale contraction by tens of nm, followed by a slow (hundreds of ms) elongation reaching hundreds of nm. Ultrafast measurements with a line-scan pOCT system show that the contractile response amplitude increases logarithmically with the number of incident photons, and its peak shifts earlier at higher stimulus intensities.We present a model that accounts for these features of the contractile response. Conformational changes in opsins after photoisomerization result in the fractional shift of charge across the disk membrane, leading to a transmembrane voltage change, known as the early receptor potential (ERP). Lateral repulsion of the ions on both sides of the membrane affects its surface tension and leads to its lateral expansion. Since the volume of the disks does not change much on a ms time scale, their lateral expansion leads to an axial contraction of the outer segment. With increasing stimulus intensity and resulting tension, the area expansion coefficient of the disk membrane also increases as thermally-induced fluctuations are pulled flat, resisting further expansion. This results in a logarithmic saturation of the deformation and a peak shift to earlier with brighter stimuli. Slow expansion of the photoreceptors is explained by the influx of water due to osmotic changes during phototransduction. Both effects closely match measurements in healthy human volunteers.

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