Development of a Low-cost Smartphone-connected Digital Microscope.
ABSTRACT: Introduction:Modern light microscopes are available with built-in illuminator and facility of photomicrography. This enables the microscopy to be ready for telemedicine. However, resource-limited settings still find difficulty in procuring those microscopes. Aim:The aim of this study was to upgrade a light microscope to a smartphone-connected digital microscope with minimal cost to make it ready for telemedicine. Materials and Methods:A commercially available (price: ?389) Universal Serial Bus (USB) web camera was set on the eyepiece and fixed with the help of an aluminum sheet. Light emitting diodes (LEDs), covered with an optical diffuser, were set below the condenser. The camera was connected to an Android smartphone with an application for capturing image and video. Sixteen faculty members provided their opinion about the new device. Results:The smartphone-connected microscope was successfully used to focus and capture image and video of various slides. The images and videos were stored in the smartphone and shared via E-mail and other channels (e.g., WhatsApp and Telegram). This camera was also successfully connected to a laptop for projecting the real-time microscopic field on a screen. According to faculty members, focusing an object and capturing the image are the best features of the device; however, development of the device received lowest score. Conclusion:A light microscope was upgraded to telemedicine ready microscope with nominal cost and moderate effort. It can also be used in medical teachings as it can project real-time images of a slide under the microscope. As it is equipped with LEDs, powered by the same smartphone, it can be operated without daylight or during a power outage.
Project description:In this article, we demonstrated a handheld smartphone fluorescence microscope (HSFM) that integrates dual-functional polymer lenses with a smartphone. The HSFM consists of a smartphone, a field-portable illumination source, and a dual-functional polymer lens that performs both optical imaging and filtering. Therefore, compared with the existing smartphone fluorescence microscope, the HSFM does not need any additional optical filters. Although fluorescence imaging has traditionally played an indispensable role in biomedical and clinical applications due to its high specificity and sensitivity for detecting cells, proteins, DNAs/RNAs, etc., the bulky elements of conventional fluorescence microscopes make them inconvenient for use in point-of-care diagnosis. The HSFM demonstrated in this article solves this problem by providing a multifunctional, miniature, small-form-factor fluorescence module. This multifunctional fluorescence module can be seamlessly attached to any smartphone camera for both bright-field and fluorescence imaging at cellular-scale resolutions without the use of additional bulky lenses/filters; in fact, the HSFM achieves magnification and light filtration using a single lens. Cell and tissue observation, cell counting, plasmid transfection evaluation, and superoxide production analysis were performed using this device. Notably, this lens system has the unique capability of functioning with numerous smartphones, irrespective of the smartphone model and the camera technology housed within each device. As such, this HSFM has the potential to pave the way for real-time point-of-care diagnosis and opens up countless possibilities for personalized medicine.
Project description:Smartphone-based fluorescence microscopy has been rapidly developing over the last few years, enabling point-of-need detection of cells, bacteria, viruses, and biomarkers. These mobile microscopy devices are cost-effective, field-portable, and easy to use, and benefit from economies of scale. Recent developments in smartphone camera technology have improved their performance, getting closer to that of lab microscopes. Here, we report the use of DNA origami nanobeads with predefined numbers of fluorophores to quantify the sensitivity of a smartphone-based fluorescence microscope in terms of the minimum number of detectable molecules per diffraction-limited spot. With the brightness of a single dye molecule as a reference, we compare the performance of color and monochrome sensors embedded in state-of-the-art smartphones. Our results show that the monochrome sensor of a smartphone can achieve better sensitivity, with a detection limit of ?10 fluorophores per spot. The use of DNA origami nanobeads to quantify the minimum number of detectable molecules of a sensor is broadly applicable to evaluate the sensitivity of various optical instruments.
Project description:Through their computational power and connectivity, smartphones are poised to rapidly expand telemedicine and transform healthcare by enabling better personal health monitoring and rapid diagnostics. Recently, a variety of platforms have been developed to enable smartphone-based point-of-care testing using imaging-based readout with the smartphone camera as the detector. Fluorescent reporters have been shown to improve the sensitivity of assays over colorimetric labels, but fluorescence readout necessitates incorporating optical hardware into the detection system, adding to the cost and complexity of the device. Here we present a simple, low-cost smartphone-based detection platform for highly sensitive luminescence imaging readout of point-of-care tests run with persistent luminescent phosphors as reporters. The extremely bright and long-lived emission of persistent phosphors allows sensitive analyte detection with a smartphone by a facile time-gated imaging strategy. Phosphors are first briefly excited with the phone's camera flash, followed by switching off the flash, and subsequent imaging of phosphor luminescence with the camera. Using this approach, we demonstrate detection of human chorionic gonadotropin using a lateral flow assay and the smartphone platform with strontium aluminate nanoparticles as reporters, giving a detection limit of ?45 pg mL-1 (1.2 pM) in buffer. Time-gated imaging on a smartphone can be readily adapted for sensitive and potentially quantitative testing using other point-of-care formats, and is workable with a variety of persistent luminescent materials.
Project description:Portable chip-scale microscopy devices can potentially address various imaging needs in mobile healthcare and environmental monitoring. Here, we demonstrate the adaptation of a smartphone's camera to function as a compact lensless microscope. Unlike other chip-scale microscopy schemes, this method uses ambient illumination as its light source and does not require the incorporation of a dedicated light source. The method is based on the shadow imaging technique where the sample is placed on the surface of the image sensor, which captures direct shadow images under illumination. To improve the image resolution beyond the pixel size, we perform pixel super-resolution reconstruction with multiple images at different angles of illumination, which are captured while the user is manually tilting the device around any ambient light source, such as the sun or a lamp. The lensless imaging scheme allows for sub-micron resolution imaging over an ultra-wide field-of-view (FOV). Image acquisition and reconstruction are performed on the device using a custom-built Android application, constructing a stand-alone imaging device for field applications. We discuss the construction of the device using a commercial smartphone and demonstrate the imaging capabilities of our system.
Project description:Electron microscopists are increasingly turning to intermediate voltage electron microscopes (IVEMs) operating at 300-400 kV for a wide range of studies. They are also increasingly taking advantage of slow-scan charge coupled device (CCD) cameras, which have become widely used on electron microscopes. Under some conditions, CCDs provide an improvement in data quality over photographic film, as well as the many advantages of direct digital readout. However, CCD performance is seriously degraded on IVEMs compared to the more conventional 100 kV microscopes. In order to increase the efficiency and quality of data recording on IVEMs, we have developed a CCD camera system in which the electrons are decelerated to below 100 kV before impacting the camera, resulting in greatly improved performance in both signal quality and resolution compared to other CCDs used in electron microscopy. These improvements will allow high-quality image and diffraction data to be collected directly with the CCD, enabling improvements in data collection for applications including high-resolution electron crystallography, single particle reconstruction of protein structures, tomographic studies of cell ultrastructure, and remote microscope operation. This approach will enable us to use even larger format CCD chips that are being developed with smaller pixels.
Project description:Despite the rapid progress in optical imaging, most of the advanced microscopy modalities still require complex and costly set-ups that unfortunately limit their use beyond well equipped laboratories. In the meantime, microscopy in resource-limited settings has requirements significantly different from those encountered in advanced laboratories, and such imaging devices should be cost-effective, compact, light-weight and appropriately accurate and simple to be usable by minimally trained personnel. Furthermore, these portable microscopes should ideally be digitally integrated as part of a telemedicine network that connects various mobile health-care providers to a central laboratory or hospital. Toward this end, here we demonstrate a lensless on-chip microscope weighing approximately 46 grams with dimensions smaller than 4.2 cm x 4.2 cm x 5.8 cm that achieves sub-cellular resolution over a large field of view of approximately 24 mm(2). This compact and light-weight microscope is based on digital in-line holography and does not need any lenses, bulky optical/mechanical components or coherent sources such as lasers. Instead, it utilizes a simple light-emitting-diode (LED) and a compact opto-electronic sensor-array to record lensless holograms of the objects, which then permits rapid digital reconstruction of regular transmission or differential interference contrast (DIC) images of the objects. Because this lensless incoherent holographic microscope has orders-of-magnitude improved light collection efficiency and is very robust to mechanical misalignments it may offer a cost-effective tool especially for telemedicine applications involving various global health problems in resource limited settings.
Project description:Background. Microscopes are omnipresent throughout the field of biological research. With microscopes one can see in detail what is going on at the cellular level in tissues. Though it is a ubiquitous tool, the limitation is that with high magnification there is a small field of view. It is often advantageous to see an entire sample at high magnification. Over the years technological advancements in optics have helped to provide solutions to this limitation of microscopes by creating the so-called dedicated "slide scanners" which can provide a "whole slide digital image." These scanners can provide seamless, large-field-of-view, high resolution image of entire tissue section. The only disadvantage of such complete slide imaging system is its outrageous cost, thereby hindering their practical use by most laboratories, especially in developing and low resource countries. Methods. In a quest for their substitute, we tried commonly used image editing software Adobe Photoshop along with a basic image capturing device attached to a trinocular microscope to create a digital pathology slide. Results. The seamless image created using Adobe Photoshop maintained its diagnostic quality. Conclusion. With time and effort photomicrographs obtained from a basic camera-microscope set up can be combined and merged in Adobe Photoshop to create a whole slide digital image of practically usable quality at a negligible cost.
Project description:<h4>Background</h4>Many surgical specialties are increasingly looking towards robot-assisted surgeries to improve patient outcome. Surgeons conducting robot-assisted operations require real-time surgical view. Ophthalmic robots can lead to novel vitreoretinal treatments, such as cannulating retinal vessels or even gene delivery to targeted retinal cells. This study investigates the feasibility of smartphone-delivered stereoscopic vision for microsurgical use.<h4>Methods</h4>A stereo-camera, connected to a laptop, was used to capture the 3D view from a binocular surgical microscope. Wi-Fi connection was used to live-stream the laptop display onto the smartphone screen wirelessly. Finally, a Virtual Reality (VR) headset, which acts as a stereoscope, was used to house the smartphone. The headset wearer then fused these images to achieve stereoscopic perception.<h4>Results</h4>Using smartphone-delivered 3D vision, the author performed a simulated cataract extraction operation successfully, despite a time lag of 0.354?s?±?0.038. To the author's knowledge, this is the first simulated ophthalmic operation performed via smartphone-delivered stereoscopic vision.<h4>Conclusions</h4>Microscopic output in 3D with minimal time lag can be readily achievable with smartphones and VR headsets. Uncoupling the surgeon from the operating microscope is required to achieve tele-presence, an essential step in tele-robotics. Where operating theatre space is a concern, head-mounted displays may be more convenient than 3D televisions. This 3D live-casting technique can be used in teaching and mentoring settings, where microsurgeries can be live-streamed stereoscopically onto smartphones via local Wi-Fi network. When connected to the internet, microsurgeries can be broadcasted live and viewers worldwide can see the surgeon's view wearing their VR headsets.
Project description:In order to increase the monitoring capabilities of inland and coastal waters, there is a need for new, affordable, sensitive and mobile instruments that could be operated semi-automatically in the field. This paper presents a prototype device to measure chlorophyll a fluorescence: the SmartFluo. The device is a combination of a smartphone offering an intuitive operation interface and an adapter implying a cuvette holder, as well as a suitable illumination source. SmartFluo is based on stimulated fluorescence of water constituents such as chlorophyll a. The red band of the digital smartphone camera is sensitive enough to detect quantitatively the characteristic red fluorescence emission. The adapter contains a light source, a strong light emitting diode and additional filters to enhance the signal-to-noise ratio and to suppress the impact of scattering. A novel algorithm utilizing the red band of the camera is provided. Laboratory experiments of the SmartFluo show a linear correlation (R 2 = 0.98) to the chlorophyll a concentrations measured by reference instruments, such as a high-performance benchtop laboratory fluorometer (LS 55, PerkinElmer).
Project description:Blood testing has been used as an essential tool to diagnose diseases for decades. Recently, there has been a rapid developing trend in using Quantitative Phase Imaging (QPI) methods for blood cell screening. Compared to traditional blood testing techniques, QPI has the advantage of avoiding dyeing or staining the specimen, which may cause damage to the cells. However, most existing systems are bulky and costly, requiring experienced personnel to operate. This work demonstrates the integration of one QPI method onto a smartphone platform and the application of imaging red blood cells. The adopted QPI method is based on solving the Intensity Transport Equation (ITE) from two de-focused pupil images taken in one shot by the smartphone camera. The device demonstrates a system resolution of about 1 ?m, and is ready to be used for 3D morphological study of red blood cells.