Vivek Boominathan

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm ² FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging the oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1 to 3 cm ² ) coregistered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point of care.

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep-learning-enabled endomicroscope that breaks these constrains and achieves 20 mm ² FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep-learning optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1-3 cm ² ) co-registered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point-of-care.

Wearable photoacoustic imaging devices hold great promise for continuous health monitoring and point-of-care diagnostics. However, the large data volume generated by high-density transducer arrays presents a major challenge for realizing compact and power-efficient wearable systems. This article presents a photoacoustic imaging receiver (RX) that embeds compressive sensing directly into the hardware to address this bottleneck. The RX integrates 16 AFEs and four matrix-vector-multiplication (MVM) SAR ADCs that perform energy- and area-efficient analog-domain compression. The architecture achieves a $4\times $ – $8\times $ reduction in output data rate while preserving low-loss full-array information. The MVM SAR ADC executes passive and accurate MVM using user-defined programmable ternary weights. Two signal reconstruction methods are implemented: 1) an optimization approach using the fast iterative shrinkage-thresholding algorithm and 2) a learning-based approach employing implicit neural representation. Fabricated in 65-nm CMOS, the chip achieves an ADC’s signal-to-noise-distortion ratio (SNDR) of 57.5 dB at 20.41 MS/s, with an analog front-end (AFE) input-referred noise of 3.5 nV/ $\mathbf {(\text {Hz})^{1/2}}$ . MVM linearity measurements show $R^{2} \gt 0.999$ across a wide range of weights and input amplitudes. The system is validated through phantom imaging experiments, demonstrating high-fidelity image reconstruction under up to $8\times $ compression. The RX consumes 5.83 mW/channel and supports a general ternary-weighted measurement matrix, offering a compelling solution for next-generation miniaturized, wearable PA imaging systems.

Evaluating the heterogeneity of extracellular vesicles (EVs) is crucial for unraveling their complex actions and biodistribution. Here, we identify consistent architectural heterogeneity of EVs using cryogenic transmission electron microscopy (cryo-TEM), which has an inherent ability to image biological samples without harsh labeling methods while preserving their native conformation. Imaging EVs isolated using different methodologies from distinct sources, such as cancer cells, normal cells, immortalized cells, and body fluids, we identify a structural atlas of their dominantly consistent shapes. We identify EV architectural attributes by utilizing a segmentation neural network model. In total, 7,576 individual EVs were imaged and quantified by our computational pipeline. Across all 7,576 independent EVs, the average eccentricity was 0.5366 ± 0.2, and the average equivalent diameter was 132.43 ± 67 nm. The architectural heterogeneity was consistent across all sources of EVs, independent of purification techniques, and compromised of single spherical, rod-like or tubular, and double shapes. This study will serve as a reference foundation for high-resolution images of EVs and offer insights into their potential biological impact.

Foveated imaging provides a better tradeoff between situational awareness (field of view) and resolution, and is critical in long wavelength infrared regimes because of the size, weight, power, and cost of thermal sensors. We demonstrate computational foveated imaging by exploiting the ability of a meta-optical frontend to discriminate between different polarization states and a computational backend to reconstruct the captured image/video. The frontend is a three-element optic: the first element, which we call the “foveal” element, is a metalens that focuses s-polarized light at a distance of f₁ without affecting the p-polarized light; the second element, which we call the “perifovea” element, is another metalens that focuses p-polarized light at a distance of f₂ without affecting the s-polarized light. The third element is a freely rotating polarizer that dynamically changes the mixing ratios between the two polarization states. Both the foveal element (focal length=150mm; diameter=75mm) and the perifoveal element (focal length=25mm; diameter=25mm) were fabricated as polarization-sensitive, all-silicon, meta surfaces resulting in a large-aperture, 1:6 foveal expansion, thermal imaging capability. A computational backend then utilizes a deep image prior to separate the resultant multiplexed image or video into a foveated image consisting of a high resolution center and a lower-resolution large field of view context. We build a prototype system and demonstrate 12 frames per second real-time, thermal, foveated image and video capture..