arXiv subjects

Aydogan Ozcan

Publications and source records attributed to Aydogan Ozcan.

At least 55 records · Page 3Linked to original sources

arXiv2024

Deep learning-enhanced chemiluminescence vertical flow assay for high-sensitivity cardiac troponin I testing

Democratizing biomarker testing at the point-of-care requires innovations that match laboratory-grade sensitivity and precision in an accessible format. Here, we demonstrate high-sensitivity detection of cardiac troponin I (cTnI) through innovations in chemiluminescence-based sensing, imaging, and deep learning-driven analysis. This chemiluminescence vertical flow assay (CL-VFA) enables rapid, low-cost, and precise quantification of cTnI, a key cardiac protein for assessing heart muscle damage and myocardial infarction. The CL-VFA integrates a user-friendly chemiluminescent paper-based sensor, a polymerized enzyme-based conjugate, a portable high-performance CL reader, and a neural network-based cTnI concentration inference algorithm. The CL-VFA measures cTnI over a broad dynamic range covering six orders of magnitude and operates with 50 uL of serum per test, delivering results in 25 min. This system achieves a detection limit of 0.16 pg/mL with an average coefficient of variation under 15%, surpassing traditional benchtop analyzers in sensitivity by an order of magnitude. In blinded validation, the computational CL-VFA accurately measured cTnI concentrations in patient samples, demonstrating a robust correlation against a clinical-grade FDA-cleared analyzer. These results highlight the potential of CL-VFA as a robust diagnostic tool for accessible, rapid cardiac biomarker testing that meets the needs of diverse healthcare settings, from emergency care to underserved regions.

physics.med-ph↗

arXiv2024

Unidirectional focusing of light using structured diffractive surfaces

Unidirectional optical systems enable selective control of light through asymmetric processing of radiation, effectively transmitting light in one direction while blocking unwanted propagation in the opposite direction. Here, we introduce a reciprocal diffractive unidirectional focusing design based on linear and isotropic diffractive layers that are structured. Using deep learning-based optimization, a cascaded set of diffractive layers are spatially engineered at the wavelength scale to focus light efficiently in the forward direction while blocking it in the opposite direction. The forward energy focusing efficiency and the backward energy suppression capabilities of this unidirectional architecture were demonstrated under various illumination angles and wavelengths, illustrating the versatility of our polarization-insensitive design. Furthermore, we demonstrated that these designs are resilient to adversarial attacks that utilize wavefront engineering from outside. Experimental validation using terahertz radiation confirmed the feasibility of this diffractive unidirectional focusing framework. Diffractive unidirectional designs can operate across different parts of the electromagnetic spectrum by scaling the resulting diffractive features proportional to the wavelength of light and will find applications in security, defense, and optical communication, among others.

physics.optics↗

arXiv2024

Virtual Staining of Label-Free Tissue in Imaging Mass Spectrometry

Imaging mass spectrometry (IMS) is a powerful tool for untargeted, highly multiplexed molecular mapping of tissue in biomedical research. IMS offers a means of mapping the spatial distributions of molecular species in biological tissue with unparalleled chemical specificity and sensitivity. However, most IMS platforms are not able to achieve microscopy-level spatial resolution and lack cellular morphological contrast, necessitating subsequent histochemical staining, microscopic imaging and advanced image registration steps to enable molecular distributions to be linked to specific tissue features and cell types. Here, we present a virtual histological staining approach that enhances spatial resolution and digitally introduces cellular morphological contrast into mass spectrometry images of label-free human tissue using a diffusion model. Blind testing on human kidney tissue demonstrated that the virtually stained images of label-free samples closely match their histochemically stained counterparts (with Periodic Acid-Schiff staining), showing high concordance in identifying key renal pathology structures despite utilizing IMS data with 10-fold larger pixel size. Additionally, our approach employs an optimized noise sampling technique during the diffusion model's inference process to reduce variance in the generated images, yielding reliable and repeatable virtual staining. We believe this virtual staining method will significantly expand the applicability of IMS in life sciences and open new avenues for mass spectrometry-based biomedical research.

cs.CV↗

arXiv2024

Leveraging Computational Pathology AI for Noninvasive Optical Imaging Analysis Without Retraining

Noninvasive optical imaging modalities can probe patient's tissue in 3D and over time generate gigabytes of clinically relevant data per sample. There is a need for AI models to analyze this data and assist clinical workflow. The lack of expert labelers and the large dataset required (>100,000 images) for model training and tuning are the main hurdles in creating foundation models. In this paper we introduce FoundationShift, a method to apply any AI model from computational pathology without retraining. We show our method is more accurate than state of the art models (SAM, MedSAM, SAM-Med2D, CellProfiler, Hover-Net, PLIP, UNI and ChatGPT), with multiple imaging modalities (OCT and RCM). This is achieved without the need for model retraining or fine-tuning. Applying our method to noninvasive in vivo images could enable physicians to readily incorporate optical imaging modalities into their clinical practice, providing real time tissue analysis and improving patient care.

cs.CV↗

arXiv2024

Optical Generative Models

Generative models cover various application areas, including image, video and music synthesis, natural language processing, and molecular design, among many others. As digital generative models become larger, scalable inference in a fast and energy-efficient manner becomes a challenge. Here, we present optical generative models inspired by diffusion models, where a shallow and fast digital encoder first maps random noise into phase patterns that serve as optical generative seeds for a desired data distribution; a jointly-trained free-space-based reconfigurable decoder all-optically processes these generative seeds to create novel images (never seen before) following the target data distribution. Except for the illumination power and the random seed generation through a shallow encoder, these optical generative models do not consume computing power during the synthesis of novel images. We report the optical generation of monochrome and multi-color novel images of handwritten digits, fashion products, butterflies, and human faces, following the data distributions of MNIST, Fashion MNIST, Butterflies-100, and Celeb-A datasets, respectively, achieving an overall performance comparable to digital neural network-based generative models. To experimentally demonstrate optical generative models, we used visible light to generate, in a snapshot, novel images of handwritten digits and fashion products. These optical generative models might pave the way for energy-efficient, scalable and rapid inference tasks, further exploiting the potentials of optics and photonics for artificial intelligence-generated content.

cs.NE↗

arXiv2024

Deep Learning-based Detection of Bacterial Swarm Motion Using a Single Image

Distinguishing between swarming and swimming, the two principal forms of bacterial movement, holds significant conceptual and clinical relevance. This is because bacteria that exhibit swarming capabilities often possess unique properties crucial to the pathogenesis of infectious diseases and may also have therapeutic potential. Here, we report a deep learning-based swarming classifier that rapidly and autonomously predicts swarming probability using a single blurry image. Compared with traditional video-based, manually-processed approaches, our method is particularly suited for high-throughput environments and provides objective, quantitative assessments of swarming probability. The swarming classifier demonstrated in our work was trained on Enterobacter sp. SM3 and showed good performance when blindly tested on new swarming (positive) and swimming (negative) test images of SM3, achieving a sensitivity of 97.44% and a specificity of 100%. Furthermore, this classifier demonstrated robust external generalization capabilities when applied to unseen bacterial species, such as Serratia marcescens DB10 and Citrobacter koseri H6. It blindly achieved a sensitivity of 97.92% and a specificity of 96.77% for DB10, and a sensitivity of 100% and a specificity of 97.22% for H6. This competitive performance indicates the potential to adapt our approach for diagnostic applications through portable devices or even smartphones. This adaptation would facilitate rapid, objective, on-site screening for bacterial swarming motility, potentially enhancing the early detection and treatment assessment of various diseases, including inflammatory bowel diseases (IBD) and urinary tract infections (UTI).

cs.CV↗

arXiv2024

Unidirectional imaging with partially coherent light

Unidirectional imagers form images of input objects only in one direction, e.g., from field-of-view (FOV) A to FOV B, while blocking the image formation in the reverse direction, from FOV B to FOV A. Here, we report unidirectional imaging under spatially partially coherent light and demonstrate high-quality imaging only in the forward direction (A->B) with high power efficiency while distorting the image formation in the backward direction (B->A) along with low power efficiency. Our reciprocal design features a set of spatially engineered linear diffractive layers that are statistically optimized for partially coherent illumination with a given phase correlation length. Our analyses reveal that when illuminated by a partially coherent beam with a correlation length of ~1.5 w or larger, where w is the wavelength of light, diffractive unidirectional imagers achieve robust performance, exhibiting asymmetric imaging performance between the forward and backward directions - as desired. A partially coherent unidirectional imager designed with a smaller correlation length of less than 1.5 w still supports unidirectional image transmission, but with a reduced figure of merit. These partially coherent diffractive unidirectional imagers are compact (axially spanning less than 75 w), polarization-independent, and compatible with various types of illumination sources, making them well-suited for applications in asymmetric visual information processing and communication.

physics.optics↗

arXiv2024

Pyramid diffractive optical networks for unidirectional image magnification and demagnification

Diffractive deep neural networks (D2NNs) are composed of successive transmissive layers optimized using supervised deep learning to all-optically implement various computational tasks between an input and output field-of-view (FOV). Here, we present a pyramid-structured diffractive optical network design (which we term P-D2NN), optimized specifically for unidirectional image magnification and demagnification. In this design, the diffractive layers are pyramidally scaled in alignment with the direction of the image magnification or demagnification. This P-D2NN design creates high-fidelity magnified or demagnified images in only one direction, while inhibiting the image formation in the opposite direction - achieving the desired unidirectional imaging operation using a much smaller number of diffractive degrees of freedom within the optical processor volume. Furthermore, P-D2NN design maintains its unidirectional image magnification/demagnification functionality across a large band of illumination wavelengths despite being trained with a single wavelength. We also designed a wavelength-multiplexed P-D2NN, where a unidirectional magnifier and a unidirectional demagnifier operate simultaneously in opposite directions, at two distinct illumination wavelengths. Furthermore, we demonstrate that by cascading multiple unidirectional P-D2NN modules, we can achieve higher magnification factors. The efficacy of the P-D2NN architecture was also validated experimentally using terahertz illumination, successfully matching our numerical simulations. P-D2NN offers a physics-inspired strategy for designing task-specific visual processors.

physics.optics↗

arXiv2024

Virtual Gram staining of label-free bacteria using darkfield microscopy and deep learning

Gram staining has been one of the most frequently used staining protocols in microbiology for over a century, utilized across various fields, including diagnostics, food safety, and environmental monitoring. Its manual procedures make it vulnerable to staining errors and artifacts due to, e.g., operator inexperience and chemical variations. Here, we introduce virtual Gram staining of label-free bacteria using a trained deep neural network that digitally transforms darkfield images of unstained bacteria into their Gram-stained equivalents matching brightfield image contrast. After a one-time training effort, the virtual Gram staining model processes an axial stack of darkfield microscopy images of label-free bacteria (never seen before) to rapidly generate Gram staining, bypassing several chemical steps involved in the conventional staining process. We demonstrated the success of the virtual Gram staining workflow on label-free bacteria samples containing Escherichia coli and Listeria innocua by quantifying the staining accuracy of the virtual Gram staining model and comparing the chromatic and morphological features of the virtually stained bacteria against their chemically stained counterparts. This virtual bacteria staining framework effectively bypasses the traditional Gram staining protocol and its challenges, including stain standardization, operator errors, and sensitivity to chemical variations.

q-bio.QM↗

arXiv2024

Multi-scale Conditional Generative Modeling for Microscopic Image Restoration

The advance of diffusion-based generative models in recent years has revolutionized state-of-the-art (SOTA) techniques in a wide variety of image analysis and synthesis tasks, whereas their adaptation on image restoration, particularly within computational microscopy remains theoretically and empirically underexplored. In this research, we introduce a multi-scale generative model that enhances conditional image restoration through a novel exploitation of the Brownian Bridge process within wavelet domain. By initiating the Brownian Bridge diffusion process specifically at the lowest-frequency subband and applying generative adversarial networks at subsequent multi-scale high-frequency subbands in the wavelet domain, our method provides significant acceleration during training and sampling while sustaining a high image generation quality and diversity on par with SOTA diffusion models. Experimental results on various computational microscopy and imaging tasks confirm our method's robust performance and its considerable reduction in its sampling steps and time. This pioneering technique offers an efficient image restoration framework that harmonizes efficiency with quality, signifying a major stride in incorporating cutting-edge generative models into computational microscopy workflows.

eess.IV↗

arXiv2024

Integration of Programmable Diffraction with Digital Neural Networks

Optical imaging and sensing systems based on diffractive elements have seen massive advances over the last several decades. Earlier generations of diffractive optical processors were, in general, designed to deliver information to an independent system that was separately optimized, primarily driven by human vision or perception. With the recent advances in deep learning and digital neural networks, there have been efforts to establish diffractive processors that are jointly optimized with digital neural networks serving as their back-end. These jointly optimized hybrid (optical+digital) processors establish a new "diffractive language" between input electromagnetic waves that carry analog information and neural networks that process the digitized information at the back-end, providing the best of both worlds. Such hybrid designs can process spatially and temporally coherent, partially coherent, or incoherent input waves, providing universal coverage for any spatially varying set of point spread functions that can be optimized for a given task, executed in collaboration with digital neural networks. In this article, we highlight the utility of this exciting collaboration between engineered and programmed diffraction and digital neural networks for a diverse range of applications. We survey some of the major innovations enabled by the push-pull relationship between analog wave processing and digital neural networks, also covering the significant benefits that could be reaped through the synergy between these two complementary paradigms.

physics.optics↗

arXiv2024

An insertable glucose sensor using a compact and cost-effective phosphorescence lifetime imager and machine learning

Optical continuous glucose monitoring (CGM) systems are emerging for personalized glucose management owing to their lower cost and prolonged durability compared to conventional electrochemical CGMs. Here, we report a computational CGM system, which integrates a biocompatible phosphorescence-based insertable biosensor and a custom-designed phosphorescence lifetime imager (PLI). This compact and cost-effective PLI is designed to capture phosphorescence lifetime images of an insertable sensor through the skin, where the lifetime of the emitted phosphorescence signal is modulated by the local concentration of glucose. Because this phosphorescence signal has a very long lifetime compared to tissue autofluorescence or excitation leakage processes, it completely bypasses these noise sources by measuring the sensor emission over several tens of microseconds after the excitation light is turned off. The lifetime images acquired through the skin are processed by neural network-based models for misalignment-tolerant inference of glucose levels, accurately revealing normal, low (hypoglycemia) and high (hyperglycemia) concentration ranges. Using a 1-mm thick skin phantom mimicking the optical properties of human skin, we performed in vitro testing of the PLI using glucose-spiked samples, yielding 88.8% inference accuracy, also showing resilience to random and unknown misalignments within a lateral distance of ~4.7 mm with respect to the position of the insertable sensor underneath the skin phantom. Furthermore, the PLI accurately identified larger lateral misalignments beyond 5 mm, prompting user intervention for re-alignment. The misalignment-resilient glucose concentration inference capability of this compact and cost-effective phosphorescence lifetime imager makes it an appealing wearable diagnostics tool for real-time tracking of glucose and other biomarkers.

physics.med-ph↗

arXiv2024

Training of Physical Neural Networks

Physical neural networks (PNNs) are a class of neural-like networks that leverage the properties of physical systems to perform computation. While PNNs are so far a niche research area with small-scale laboratory demonstrations, they are arguably one of the most underappreciated important opportunities in modern AI. Could we train AI models 1000x larger than current ones? Could we do this and also have them perform inference locally and privately on edge devices, such as smartphones or sensors? Research over the past few years has shown that the answer to all these questions is likely "yes, with enough research": PNNs could one day radically change what is possible and practical for AI systems. To do this will however require rethinking both how AI models work, and how they are trained - primarily by considering the problems through the constraints of the underlying hardware physics. To train PNNs at large scale, many methods including backpropagation-based and backpropagation-free approaches are now being explored. These methods have various trade-offs, and so far no method has been shown to scale to the same scale and performance as the backpropagation algorithm widely used in deep learning today. However, this is rapidly changing, and a diverse ecosystem of training techniques provides clues for how PNNs may one day be utilized to create both more efficient realizations of current-scale AI models, and to enable unprecedented-scale models.

physics.app-ph↗

arXiv2024

Automated HER2 Scoring in Breast Cancer Images Using Deep Learning and Pyramid Sampling

Human epidermal growth factor receptor 2 (HER2) is a critical protein in cancer cell growth that signifies the aggressiveness of breast cancer (BC) and helps predict its prognosis. Accurate assessment of immunohistochemically (IHC) stained tissue slides for HER2 expression levels is essential for both treatment guidance and understanding of cancer mechanisms. Nevertheless, the traditional workflow of manual examination by board-certified pathologists encounters challenges, including inter- and intra-observer inconsistency and extended turnaround times. Here, we introduce a deep learning-based approach utilizing pyramid sampling for the automated classification of HER2 status in IHC-stained BC tissue images. Our approach analyzes morphological features at various spatial scales, efficiently managing the computational load and facilitating a detailed examination of cellular and larger-scale tissue-level details. This method addresses the tissue heterogeneity of HER2 expression by providing a comprehensive view, leading to a blind testing classification accuracy of 84.70%, on a dataset of 523 core images from tissue microarrays. Our automated system, proving reliable as an adjunct pathology tool, has the potential to enhance diagnostic precision and evaluation speed, and might significantly impact cancer treatment planning.

eess.IV↗

arXiv2024

Neural Network-Based Processing and Reconstruction of Compromised Biophotonic Image Data

The integration of deep learning techniques with biophotonic setups has opened new horizons in bioimaging. A compelling trend in this field involves deliberately compromising certain measurement metrics to engineer better bioimaging tools in terms of cost, speed, and form-factor, followed by compensating for the resulting defects through the utilization of deep learning models trained on a large amount of ideal, superior or alternative data. This strategic approach has found increasing popularity due to its potential to enhance various aspects of biophotonic imaging. One of the primary motivations for employing this strategy is the pursuit of higher temporal resolution or increased imaging speed, critical for capturing fine dynamic biological processes. This approach also offers the prospect of simplifying hardware requirements/complexities, thereby making advanced imaging standards more accessible in terms of cost and/or size. This article provides an in-depth review of the diverse measurement aspects that researchers intentionally impair in their biophotonic setups, including the point spread function, signal-to-noise ratio, sampling density, and pixel resolution. By deliberately compromising these metrics, researchers aim to not only recuperate them through the application of deep learning networks, but also bolster in return other crucial parameters, such as the field-of-view, depth-of-field, and space-bandwidth product. Here, we discuss various biophotonic methods that have successfully employed this strategic approach. These techniques span broad applications and showcase the versatility and effectiveness of deep learning in the context of compromised biophotonic data. Finally, by offering our perspectives on the future possibilities of this rapidly evolving concept, we hope to motivate our readers to explore novel ways of balancing hardware compromises with compensation via AI.

physics.optics↗

arXiv2024

Multiplane Quantitative Phase Imaging Using a Wavelength-Multiplexed Diffractive Optical Processor

Quantitative phase imaging (QPI) is a label-free technique that provides optical path length information for transparent specimens, finding utility in biology, materials science, and engineering. Here, we present quantitative phase imaging of a 3D stack of phase-only objects using a wavelength-multiplexed diffractive optical processor. Utilizing multiple spatially engineered diffractive layers trained through deep learning, this diffractive processor can transform the phase distributions of multiple 2D objects at various axial positions into intensity patterns, each encoded at a unique wavelength channel. These wavelength-multiplexed patterns are projected onto a single field-of-view (FOV) at the output plane of the diffractive processor, enabling the capture of quantitative phase distributions of input objects located at different axial planes using an intensity-only image sensor. Based on numerical simulations, we show that our diffractive processor could simultaneously achieve all-optical quantitative phase imaging across several distinct axial planes at the input by scanning the illumination wavelength. A proof-of-concept experiment with a 3D-fabricated diffractive processor further validated our approach, showcasing successful imaging of two distinct phase objects at different axial positions by scanning the illumination wavelength in the terahertz spectrum. Diffractive network-based multiplane QPI designs can open up new avenues for compact on-chip phase imaging and sensing devices.

physics.optics↗

arXiv2024

Virtual birefringence imaging and histological staining of amyloid deposits in label-free tissue using autofluorescence microscopy and deep learning

Systemic amyloidosis is a group of diseases characterized by the deposition of misfolded proteins in various organs and tissues, leading to progressive organ dysfunction and failure. Congo red stain is the gold standard chemical stain for the visualization of amyloid deposits in tissue sections, as it forms complexes with the misfolded proteins and shows a birefringence pattern under polarized light microscopy. However, Congo red staining is tedious and costly to perform, and prone to false diagnoses due to variations in the amount of amyloid, staining quality and expert interpretation through manual examination of tissue under a polarization microscope. Here, we report the first demonstration of virtual birefringence imaging and virtual Congo red staining of label-free human tissue to show that a single trained neural network can rapidly transform autofluorescence images of label-free tissue sections into brightfield and polarized light microscopy equivalent images, matching the histochemically stained versions of the same samples. We demonstrate the efficacy of our method with blind testing and pathologist evaluations on cardiac tissue where the virtually stained images agreed well with the histochemically stained ground truth images. Our virtually stained polarization and brightfield images highlight amyloid birefringence patterns in a consistent, reproducible manner while mitigating diagnostic challenges due to variations in the quality of chemical staining and manual imaging processes as part of the clinical workflow.

physics.med-ph↗

arXiv2024

Deep Learning-based Kinetic Analysis in Paper-based Analytical Cartridges Integrated with Field-effect Transistors

This study explores the fusion of a field-effect transistor (FET), a paper-based analytical cartridge, and the computational power of deep learning (DL) for quantitative biosensing via kinetic analyses. The FET sensors address the low sensitivity challenge observed in paper analytical devices, enabling electrical measurements with kinetic data. The paper-based cartridge eliminates the need for surface chemistry required in FET sensors, ensuring economical operation (cost < $0.15/test). The DL analysis mitigates chronic challenges of FET biosensors such as sample matrix interference, by leveraging kinetic data from target-specific bioreactions. In our proof-of-concept demonstration, our DL-based analyses showcased a coefficient of variation of < 6.46% and a decent concentration measurement correlation with an r2 value of > 0.976 for cholesterol testing when blindly compared to results obtained from a CLIA-certified clinical laboratory. These integrated technologies can create a new generation of FET-based biosensors, potentially transforming point-of-care diagnostics and at-home testing through enhanced accessibility, ease-of-use, and accuracy.

q-bio.QM↗