Wavelength-multiplexed massively parallel diffractive optical information storage and image projection

We introduce a wavelength-multiplexed massively parallel diffractive information storage platform composed of dielectric surfaces that are structurally optimized at the wavelength scale using deep learning to store and project thousands of distinct image patterns, each assigned to a unique wavelength. Through numerical simulations in the visible spectrum, we demonstrated that our wavelength-multiplexed diffractive system can store and project over 4,000 independent desired images/patterns within its output field-of-view, with high image quality and minimal crosstalk between spectral channels. Furthermore, in a proof-of-concept experiment, we demonstrated a two-layer diffractive design that stored six distinct patterns and projected them onto the same output field of view at six different wavelengths (500, 548, 596, 644, 692, and 740 nm). This diffractive architecture is scalable and can operate at various parts of the electromagnetic spectrum without the need for material dispersion engineering or redesigning its optimized diffractive layers. The demonstrated storage capacity, reconstruction image fidelity, and wavelength-encoded massively parallel read-out of our diffractive platform offer a compact and fast-access solution for large-scale optical information storage, image projection applications.

Large-scale nonlinear optical computing with incoherent light via linear diffractive systems

Nonlinear computation is essential for various information processing tasks. Optical implementations are attractive because passive light propagation can manipulate high-dimensional signals with extreme throughput and parallelism; yet realizing nonlinear mappings in optical hardware remains challenging due to the weak nonlinearity of optical materials and the large intensities required to induce nonlinear interactions. This challenge is further amplified in many systems that operate with incoherent illumination, motivating a coherence-aware framework for scalable optical nonlinear processing. Here, we show that linear optical systems, in particular, optimized diffractive processors comprising passive surfaces, can perform large-scale nonlinear function approximation under spatially incoherent or partially coherent illumination, when preceded by intensity-only input encoding. We quantify how the accuracy of the nonlinear function approximation varies with the degree of parallelism, the number of diffractive layers, and the number of trainable diffractive features. Numerical results demonstrate snapshot computation of up to one million distinct nonlinear functions in a single forward pass through a diffractive processor, with the function outputs spatially multiplexed and read out using densely packed detectors at the output. We further provide a proof-of-concept experimental demonstration under incoherent illumination from a liquid crystal display (LCD), enabled by a model-free in situ learning strategy that jointly optimizes the diffractive profile and detector readout geometry in the presence of hardware imperfections and misalignments. Our findings establish diffractive processors as a massively parallel universal function approximator for both spatially incoherent and partially coherent illumination.

Compressive single-pixel imaging via a wavelength-multiplexed spatially incoherent diffractive optical processor

Despite offering high sensitivity, a high signal-to-noise ratio, and a broad spectral range, single-pixel imaging (SPI) is limited by low measurement efficiency and long data-acquisition times. To address this, we propose a wavelength-multiplexed, spatially incoherent diffractive optical processor combined with a compact/shallow digital artificial neural network (ANN) to implement compressive SPI. Specifically, we model the bucket detection process in conventional SPI as a linear intensity transformation with spatially and spectrally varying point-spread functions. This transformation matrix is treated as a learnable parameter and jointly optimized with a shallow digital ANN composed of 2 hidden nonlinear layers. The wavelength-multiplexed diffractive processor is then configured via data-free optimization to approximate this pre-trained transformation matrix; after this optimization, the diffractive processor remains static/fixed. Upon multi-wavelength illumination and diffractive modulation, the target spatial information of the input object is spectrally encoded. A single-pixel detector captures the output spectral power at each illumination band, which is then rapidly decoded by the jointly trained digital ANN to reconstruct the input image. In addition to our numerical analyses demonstrating the feasibility of this approach, we experimentally validated its proof-of-concept using an array of light-emitting diodes (LEDs). Overall, this work demonstrates a computational imaging framework for compressive SPI that can be useful in applications such as biomedical imaging, autonomous devices, and remote sensing.

Automated HER2 scoring with uncertainty quantification using lensfree holography and deep learning

Accurate assessment of human epidermal growth factor receptor 2 (HER2) expression is critical for breast cancer diagnosis, prognosis, and therapy selection; yet, most existing digital HER2 scoring methods rely on bulky and expensive optical systems. Here, we present a compact and cost-effective lensfree holography platform integrated with deep learning for automated HER2 scoring of immunohistochemically stained breast tissue sections. The system captures lensfree diffraction patterns of stained HER2 tissue sections under RGB laser illumination and acquires complex field information over a sample area of ~1,250 mm^2 at an effective throughput of ~84 mm^2 per minute. To enhance diagnostic reliability, we incorporated an uncertainty quantification strategy based on Bayesian Monte Carlo dropout, which provides autonomous uncertainty estimates for each prediction and supports reliable, robust HER2 scoring, with an overall correction rate of 30.4%. Using a blinded test set of 412 unique tissue samples, our approach achieved a testing accuracy of 84.9% for 4-class (0, 1+, 2+, 3+) HER2 classification and 94.8% for binary (0/1+ vs. 2+/3+) HER2 scoring with uncertainty quantification. Overall, this lensfree holography approach provides a practical pathway toward portable, high-throughput, and cost-effective HER2 scoring, particularly suited for resource-limited settings, where traditional digital pathology infrastructure is unavailable.

Autonomous Uncertainty Quantification for Computational Point-of-care Sensors

Computational point-of-care (POC) sensors enable rapid, low-cost, and accessible diagnostics in emergency, remote and resource-limited areas that lack access to centralized medical facilities. These systems can utilize neural network-based algorithms to accurately infer a diagnosis from the signals generated by rapid diagnostic tests or sensors. However, neural network-based diagnostic models are subject to hallucinations and can produce erroneous predictions, posing a risk of misdiagnosis and inaccurate clinical decisions. To address this challenge, here we present an autonomous uncertainty quantification technique developed for POC diagnostics. As our testbed, we used a paper-based, computational vertical flow assay (xVFA) platform developed for rapid POC diagnosis of Lyme disease, the most prevalent tick-borne disease globally. The xVFA platform integrates a disposable paper-based assay, a handheld optical reader and a neural network-based inference algorithm, providing rapid and cost-effective Lyme disease diagnostics in under 20 min using only 20 uL of patient serum. By incorporating a Monte Carlo dropout (MCDO)-based uncertainty quantification approach into the diagnostics pipeline, we identified and excluded erroneous predictions with high uncertainty, significantly improving the sensitivity and reliability of the xVFA in an autonomous manner, without access to the ground truth diagnostic information of patients. Blinded testing using new patient samples demonstrated an increase in diagnostic sensitivity from 88.2% to 95.7%, indicating the effectiveness of MCDO-based uncertainty quantification in enhancing the robustness of neural network-driven computational POC sensing systems.

Deep learning-enhanced dual-mode multiplexed optical sensor for point-of-care diagnostics of cardiovascular diseases

Rapid and accessible cardiac biomarker testing is essential for the timely diagnosis and risk assessment of myocardial infarction (MI) and heart failure (HF), two interrelated conditions that frequently coexist and drive recurrent hospitalizations with high mortality. However, current laboratory and point-of-care testing systems are limited by long turnaround times, narrow dynamic ranges for the tested biomarkers, and single-analyte formats that fail to capture the complexity of cardiovascular disease. Here, we present a deep learning-enhanced dual-mode multiplexed vertical flow assay (xVFA) with a portable optical reader and a neural network-based quantification pipeline. This optical sensor integrates colorimetric and chemiluminescent detection within a single paper-based cartridge to complementarily cover a large dynamic range (spanning ~6 orders of magnitude) for both low- and high-abundance biomarkers, while maintaining quantitative accuracy. Using 50 uL of serum, the optical sensor simultaneously quantifies cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) within 23 min. The xVFA achieves sub-pg/mL sensitivity for cTnI and sub-ng/mL sensitivity for CK-MB and NT-proBNP, spanning the clinically relevant ranges for these biomarkers. Neural network models trained and blindly tested on 92 patient serum samples yielded a robust quantification performance (Pearson's r > 0.96 vs. reference assays). By combining high sensitivity, multiplexing, and automation in a compact and cost-effective optical sensor format, the dual-mode xVFA enables rapid and quantitative cardiovascular diagnostics at the point of care.

Snapshot 3D image projection using a diffractive decoder

3D image display is essential for next-generation volumetric imaging; however, dense depth multiplexing for 3D image projection remains challenging because diffraction-induced cross-talk rapidly increases as the axial image planes get closer. Here, we introduce a 3D display system comprising a digital encoder and a diffractive optical decoder, which simultaneously projects different images onto multiple target axial planes with high axial resolution. By leveraging multi-layer diffractive wavefront decoding and deep learning-based end-to-end optimization, the system achieves high-fidelity depth-resolved 3D image projection in a snapshot, enabling axial plane separations on the order of a wavelength. The digital encoder leverages a Fourier encoder network to capture multi-scale spatial and frequency-domain features from input images, integrates axial position encoding, and generates a unified phase representation that simultaneously encodes all images to be axially projected in a single snapshot through a jointly-optimized diffractive decoder. We characterized the impact of diffractive decoder depth, output diffraction efficiency, spatial light modulator resolution, and axial encoding density, revealing trade-offs that govern axial separation and 3D image projection quality. We further demonstrated the capability to display volumetric images containing 28 axial slices, as well as the ability to dynamically reconfigure the axial locations of the image planes, performed on demand. Finally, we experimentally validated the presented approach, demonstrating close agreement between the measured results and the target images. These results establish the diffractive 3D display system as a compact and scalable framework for depth-resolved snapshot 3D image projection, with potential applications in holographic displays, AR/VR interfaces, and volumetric optical computing.

Pixel Super-Resolved Fluorescence Lifetime Imaging Using Deep Learning

Fluorescence lifetime imaging microscopy (FLIM) is a powerful quantitative technique that provides metabolic and molecular contrast, offering strong translational potential for label-free, real-time diagnostics. However, its clinical adoption remains limited by long pixel dwell times and low signal-to-noise ratio (SNR), which impose a stricter resolution-speed trade-off than conventional optical imaging approaches. Here, we introduce FLIM_PSR_k, a deep learning-based multi-channel pixel super-resolution (PSR) framework that reconstructs high-resolution FLIM images from data acquired with up to a 5-fold increased pixel size. The model is trained using the conditional generative adversarial network (cGAN) framework, which, compared to diffusion model-based alternatives, delivers a more robust PSR reconstruction with substantially shorter inference times, a crucial advantage for practical deployment. FLIM_PSR_k not only enables faster image acquisition but can also alleviate SNR limitations in autofluorescence-based FLIM. Blind testing on held-out patient-derived tumor tissue samples demonstrates that FLIM_PSR_k reliably achieves a super-resolution factor of k = 5, resulting in a 25-fold increase in the space-bandwidth product of the output images and revealing fine architectural features lost in lower-resolution inputs, with statistically significant improvements across various image quality metrics. By increasing FLIM's effective spatial resolution, FLIM_PSR_k advances lifetime imaging toward faster, higher-resolution, and hardware-flexible implementations compatible with low-numerical-aperture and miniaturized platforms, better positioning FLIM for translational applications.

Universal point spread function engineering for 3D optical information processing

Point spread function (PSF) engineering has been pivotal in the remarkable progress made in high-resolution imaging in the last decades. However, the diversity in PSF structures attainable through existing engineering methods is limited. Here, we report universal PSF engineering, demonstrating a method to synthesize an arbitrary set of spatially varying 3D PSFs between the input and output volumes of a spatially incoherent diffractive processor composed of cascaded transmissive surfaces. We rigorously analyze the PSF engineering capabilities of such diffractive processors within the diffraction limit of light and provide numerical demonstrations of unique imaging capabilities, such as snapshot 3D multispectral imaging without involving any spectral filters, axial scanning or digital reconstruction steps, which is enabled by the spatial and spectral engineering of 3D PSFs. Our framework and analysis would be important for future advancements in computational imaging, sensing and diffractive processing of 3D optical information.

Snapshot multi-spectral imaging through defocusing and a Fourier imager network

Multi-spectral imaging, which simultaneously captures the spatial and spectral information of a scene, is widely used across diverse fields, including remote sensing, biomedical imaging, and agricultural monitoring. Here, we introduce a snapshot multi-spectral imaging approach employing a standard monochrome image sensor with no additional spectral filters or customized components. Our system leverages the inherent chromatic aberration of wavelength-dependent defocusing as a natural source of physical encoding of multi-spectral information; this encoded image information is rapidly decoded via a deep learning-based multi-spectral Fourier Imager Network (mFIN). We experimentally tested our method with six illumination bands and demonstrated an overall accuracy of 92.98% for predicting the illumination channels at the input and achieved a robust multi-spectral image reconstruction on various test objects. This deep learning-powered framework achieves high-quality multi-spectral image reconstruction using snapshot image acquisition with a monochrome image sensor and could be useful for applications in biomedicine, industrial quality control, and agriculture, among others.