Search Results (26)

Lensless on-chip microscopy enables high-throughput, wide-FOV imaging; however, the Bayer color filter array (CFA) in standard color sensors spatially multiplexes spectral channels, introducing sub-sampling and spectral crosstalk that degrade phase retrieval. We propose a Wirtinger Poly-Gradient Solver (WPGS) for quantitative phase reconstruction with Bayer-filtered color sensors under sequential Red–Green–Blue Light-Emitting Diode (RGB-LED) illumination. The method combines Transport of Intensity Equation (TIE)-based initialization with polychromatic Wirtinger optimization to suppress CFA-induced artifacts and enable pixel super-resolution (PSR). Experiments resolve a $2.76 \mu \mathrm{m}$ linewidth using a $1.85 \mu \mathrm{m}$ pixel-pitch sensor, exceeding the nominal Nyquist limit imposed by pixel sampling. We further demonstrate label-free imaging of HeLa cells and unstained tissue sections, supporting high-throughput digital pathology and offering potential for longitudinal biological observation. Full article

Multi-wavelength lensless microscopy enables high-speed, wide-field, and high-throughput imaging, making it highly attractive for modern biomedical applications. However, its practical performance is often limited by unreliable autofocusing and wavelength-dependent phase inconsistencies, which together degrade reconstruction fidelity in complex environments. To explicitly address these two limitations, we present a fully scanning-free computational microscopy framework using a static four-wavelength Light-Emitting Diode (LED) illumination module that sequentially switches between wavelengths to provide strong spectral constraints. For robust geometric parameter estimation, we develop an Adaptive-Weighted Multi-wavelength Autofocus (A-WMAF) scheme that exploits the differential defocus sensitivities of multiple wavelengths to yield a single, sharply peaked autofocus curve and thereby reliably determines the sample–sensor distance. To mitigate chromatic phase inconsistencies, we further introduce an iterative optical-path-difference (OPD)–domain adaptive fusion strategy that fuses multi-wavelength phase estimates in a physically consistent OPD space, suppressing wavelength-dependent artifacts and reconstruction noise. With only four raw holograms acquired within seconds, the proposed method achieves high-fidelity quantitative phase reconstruction with a Phase Structural Similarity Index Measure (SSIM) of 0.9942 and a quantitative OPD accuracy of 95.0%, as well as a measured lateral resolution of 1.23 µm, surpassing the Nyquist–Shannon sampling limit. Experimental demonstrations on fixed biological samples and long-term live-cell monitoring validate that the proposed framework simultaneously achieves reliable autofocusing and chromaticity-robust phase fusion, highlighting its potential for high-throughput biomedical imaging and clinical diagnostics. Full article

Lensless microscopy is a well-established imaging approach that replaces traditional lenses with phase modulators, enabling compact, low-cost, and computationally driven analysis of biological samples. In this work, we show how ray tracing simulations can be used to optimize lensless imaging systems for automated classification, particularly for detecting red blood cell (RBC) disease. Rather than improving the machine learning classification algorithm, our focus is on refining optical parameters such as element spacing and modulator type to maximize classification performance. We modeled a lensless microscope in Zemax OpticStudio (ray tracing) and compared the results against Fourier optics simulations. Despite not explicitly modeling diffraction, ray tracing produced classification results largely consistent with wave optics simulations, confirming its effectiveness for parameter optimization in lensless imaging setups used for classification tasks. Furthermore, to show the flexibility of the ray tracing model, we introduced a microlens array (MLA) as the phase modulator and performed the classification task on the generated patterns. These results establish ray tracing as an efficient tool for the optical design of lensless microscopy systems intended for machine learning based biomedical applications. The developed lensless microscopy model enables the generation of datasets for training neural networks. Full article

Microscopy is a fundamental tool in biological research. However, conventional microscopes require manual operation and depend on user and equipment availability, limiting their suitability for continuous observation. Moreover, their size and complexity make them impractical for in situ experimentation. In this work, we present a novel, compact, affordable, and portable microscope that enables continuous in situ monitoring by being placed directly on biological samples. This chip-sized lensless holographic microscope (CLHM) is specifically designed to overcome the limitations of traditional microscopy. The device consists solely of an ultra-compact, state-of-the-art micro-LED display and a CMOS sensor, all enclosed within a 3D-printed housing. This unique light source enables a size that is markedly smaller than any comparable technology, allowing a resolution of 2.19 μm within a 7 mm distance between the light source and the camera. This paper demonstrates the CLHM’s versatility by monitoring in vitro models and performing whole-organism morphological analyses of small specimens. These experiments underscore its potential as an on-platform sensing device for continuous, in situ biological monitoring across diverse models. Full article

There is a growing field that is devoted to developing inexpensive microscopes and measurement devices by leveraging low-cost commercial parts that can be controlled using smartphones or embedded devices, such as Arduino and Raspbery Pi. Examples include the use of Blu-ray optical heads like the PHR-803T to perform cytometry, spinning disc microscopy, and lensless holographic microscopy. The modular or disposable nature of these devices means that they can also be used in contaminating and degrading environments, including radioactive environments, where replacement of device elements can be expensive. This paper presents the development and operation of a confocal microscope that uses the PHR-803T optical device in a Blu-ray reader for both imaging and detection of temperature variations with between 1.5 and 15 µm resolution. The benefits of using a PHR-803T confocal system include its relatively inexpensive design and the accessibility of the components that are used in its construction. The design of this scanning confocal thermal microscope (SCoT) was optimized based on cost, modularity, portability, spatial resolution, and ease of manufacturability using common tools (e.g., drill press, 3D printer). This paper demonstrated the ability to resolve microscale features such as synthetic spider silk and measure thermal waves in stainless steel using a system requiring <USD 1000 in material costs. Full article

The need for faster and more accessible alternatives to laboratory microscopy is driving many innovations throughout the image and data acquisition chain in the biomedical field. Benchtop microscopes are bulky, lack communications capabilities, and require trained personnel for analysis. New technologies, such as compact 3D-printed devices integrated with the Internet of Things (IoT) for data sharing and cloud computing, as well as automated image processing using deep learning algorithms, can address these limitations and enhance the conventional imaging workflow. This review reports on recent advancements in microscope miniaturization, with a focus on emerging technologies such as photoacoustic microscopy and more established approaches like smartphone-based microscopy. The potential applications of IoT in microscopy are examined in detail. Furthermore, this review discusses the evolution of image processing in microscopy, transitioning from traditional to deep learning methods that facilitate image enhancement and data interpretation. Despite numerous advancements in the field, there is a noticeable lack of studies that holistically address the entire microscopy acquisition chain. This review aims to highlight the potential of IoT and artificial intelligence (AI) in combination with portable microscopy, emphasizing the importance of a comprehensive approach to the microscopy acquisition chain, from portability to image analysis. Full article

Background: Sudden volcanic eruptions can lead to volcanic ash entering the eyes, causing severe discomfort and complicating evacuation efforts. The specific effects of volcanic ash on ocular tissues, especially when wearing soft contact lenses (SCLs), are not well documented, prompting this experimental investigation. Methods: White rabbits with normal eyes were randomly divided into three groups: (1) a bare eye group: bare eye + volcanic ash exposure + eye washing, (2) an SCL group: SCL-wearing eye + volcanic ash exposure + eye washing, and (3) a control group: eye washing only. In groups 1 and 2, volcanic ash was applied to one eye under topical anesthesia, followed by immediate saline rinsing. Slit-lamp microscopy and histopathological analysis were conducted after euthanasia. Results: Slit-lamp and histopathological examinations revealed more significant corneal and conjunctival erosion in the bare eye group compared to the SCL group, which showed limited damage. The control group displayed no ocular damage. Conclusions: Guidelines from the “Volcanic Ash Health Effects: A Guide for the Public” by the National Research Institute for Earth Science and Disaster Resilience recommend removing SCLs during ashfall. Our findings suggest that the damage to the corneal and conjunctival epithelium is less severe in SCL-wearing eyes than in bare eyes, recommending that SCL wearers prioritize evacuation over lens removal during sudden ashfall. Full article

Lensless fluorescence microscopy (LLFM) has emerged as a promising approach for biological imaging, offering a simplified, high-throughput, portable, and cost-effective substitute for conventional microscopy techniques by removing lenses in favor of directly recording fluorescent light on a digital sensor. However, there are several obstacles that this novel approach must overcome, such as restrictions on the resolution, field-of-view (FOV), signal-to-noise ratio (SNR), and multicolor-imaging capabilities. This review looks at the most current developments aimed at addressing these challenges and enhancing the performance of LLFM systems. To address these issues, computational techniques, such as deconvolution and compressive sensing, hardware modifications and structured illumination, customized filters, and the utilization of fiber-optic plates, have been implemented. Finally, this review emphasizes the numerous applications of LLFM in tissue analysis, pathogen detection, and cellular imaging, highlighting its adaptability and potential influence in a range of biomedical research and clinical diagnostic areas. Full article

Lensless imaging allows for designing imaging systems that are free from the constraints of traditional imaging architectures. As a broadly investigated technique, mask-modulated lensless imaging encodes light signals via a mask plate integrated with the image sensor, which is more compacted, with scalability and compressive imaging abilities. Here, we review the latest advancements in mask-modulated lensless imaging, lensless image reconstruction algorithms, related techniques, and future directions and applications. Full article

Cholesterol (Chol) is an essential component of animal cell membranes and is most abundant in plasma membranes (PMs) where its concentration typically ranges from 10 to 30 mol%. However, in red blood cells and Schwann cells, PMs Chol content is as high as 50 mol%, and in the PMs of the eye lens fiber cells, it can reach up to 66 mol%. Being amphiphilic, Chol molecules are easily incorporated into the lipid bilayer where they affect the membrane lateral organization and transmembrane physical properties. In the aqueous phase, Chol cannot form free bilayers by itself. However, pure Chol bilayer domains (CBDs) can form in lipid bilayer membranes with the Chol content exceeding 50 mol%. The range of Chol concentrations surpassing 50 mol% is less frequent in biological membranes and is consequently less investigated. Nevertheless, it is significant for the normal functioning of the eye lens and understanding how Chol plaques form in atherosclerosis. The most commonly used membrane models are unilamellar and multilamellar vesicles (MLVs) and supported lipid bilayers (SLBs). CBDs have been observed directly using confocal microscopy, X-ray reflectometry and saturation recovery electron paramagnetic resonance (SR EPR). Indirect evidence of CBDs has also been reported by using atomic force microscopy (AFM) and fluorescence recovery after photobleaching (FRAP) experiments. The overall goal of this review is to demonstrate the advantages and limitations of the various membrane models and experimental techniques suitable for the detection and investigation of the lateral organization, function and physical properties of CBDs. Full article

Lensless holographic microscopy (LHM) comes out as a promising label-free technique since it supplies high-quality imaging and adaptive magnification in a lens-free, compact and cost-effective way. Compact sizes and reduced prices of LHMs make them a perfect instrument for point-of-care diagnosis and increase their usability in limited-resource laboratories, remote areas, and poor countries. LHM can provide excellent intensity and phase imaging when the twin image is removed. In that sense, multi-illumination single-holographic-exposure lensless Fresnel (MISHELF) microscopy appears as a single-shot and phase-retrieved imaging technique employing multiple illumination/detection channels and a fast-iterative phase-retrieval algorithm. In this contribution, we review MISHELF microscopy through the description of the principles, the analysis of the performance, the presentation of the microscope prototypes and the inclusion of the main biomedical applications reported so far. Full article

For decades, terahertz (THz) microscopic imaging has been limited by the resolution of the system due to the larger wavelength, the power of the source, and the equivalent noise power of the detector, so a lot of research has focused on single-point scanning imaging. With the development of hardware, full-field THz imaging based on high-power continuous-wave THz sources have been developed such as the direct intensity imaging method and lensless coherent imaging. In particular, the THz direct intensity imaging method requires no complicated computational reconstruction, while the high resolution, as a key issue, still needs to be improved. In this paper, the rotating coherent scattering microscopy was applied to THz imaging for the first time. Here, we designed and fabricated a hemisphere lens with high-resistance silicon. The tilted hemisphere lens transformed the incident divergent beam into a plane wave, and the total internal reflection occurred in the planar surface within the hemispherical lens, and generated evanescent waves in the rare medium. At the same time, the sample was placed very close to the plane of the hemispherical lens, so that the sample was illuminated by the evanescent waves. The scattered waves carried high frequency information to the far field, and thus through an objective, the super-resolution imaging was achieved along a single direction. Then, the hemispherical lens was rotated to obtain coherent scattering microscopic images under different evanescent wave illumination angles. Finally, the full-field super-resolution imaging results were obtained through incoherent superposition. Full article

X-ray diffraction microscopy (XDM) is an established lens-less imaging method extensively practiced at synchrotrons and X-ray free-electron lasers (XFELs). XDM is broadly operated in two different modes: scanning and non-scanning. The non-scanning mode of operation in XDM is commonly called coherent diffraction imaging (CDI) and has been the key research direction of many XFEL facilities. This method typically images objects smaller than the size of the illumination, which precludes the imaging of a large group of samples physically larger than the illumination. Furthermore, satisfying this requirement at X-ray free-electron lasers tremendously reduces the volume of practically useful data, leading the experimental scheme to be less efficient. Such a limitation can be circumvented by using a uniform illumination probe rather than the traditional Gaussian-focused probe from the X-ray focusing optics. Here in this article, we report a numerical study on the design of an optical element to generate uniform X-ray illumination and its application to the CDI. We demonstrate the benefits of such illumination in imaging objects that are larger than the illumination size and in improving the efficiency of the experimental scheme overall. Full article

Empowered by pixel super-resolution (PSR) and phase retrieval techniques, lensless on-chip microscopy opens up new possibilities for high-throughput biomedical imaging. However, the current PSR phase retrieval approaches are time consuming in terms of both the measurement and reconstruction procedures. In this work, we present a novel computational framework for PSR phase retrieval to address these concerns. Specifically, a sparsity-promoting regularizer is introduced to enhance the well posedness of the nonconvex problem under limited measurements, and Nesterov’s momentum is used to accelerate the iterations. The resulting algorithm, termed accelerated Wirtinger flow (AWF), achieves at least an order of magnitude faster rate of convergence and allows a twofold reduction in the measurement number while maintaining competitive reconstruction quality. Furthermore, we provide general guidance for step size selection based on theoretical analyses, facilitating simple implementation without the need for complicated parameter tuning. The proposed AWF algorithm is compatible with most of the existing lensless on-chip microscopes and could help achieve label-free rapid whole slide imaging of dynamic biological activities at subpixel resolution. Full article

An important imaging technique in biomedicine, the conventional optical microscopy relies on relatively complicated and bulky lens and alignment mechanics. Based on the Gabor holography, the lensless digital holographic microscopy has the advantages of light weight and low cost. It has developed rapidly and received attention in many fields. However, the finite pixel size at the sensor plane limits the spatial resolution. In this study, we first review the principle of lensless digital holography, then go over some methods to improve image contrast and discuss the methods to enhance the image resolution of the lensless holographic image. Moreover, the applications of lensless digital holographic microscopy in biomedicine are reviewed. Finally, we look forward to the future development and prospect of lensless digital holographic technology. Full article