Fluorescence sensing technologies for ophthalmic diagnosis

Personalized and point-of-care (POC) diagnoses are critical for ocular physiology and disease diagnosis. Real-time monitoring and continuous sampling abilities of tear fluid and user-friendliness have become the key characteristics for the applied ophthalmic techniques. Fluorescence technologies, as one of the most popular methods that can fulfill the requirements of clinical ophthalmic applications for optical sensing, have been raised and applied for tear sensing and diagnostic platforms in recent decades. Wearable sensors in this case have been increasingly developed for ocular diagnosis. Contact lenses, as one of the commercialized and popular tools for ocular dysfunction, have been developed as a platform for fluorescence sensing in tears diagnostics and real-time monitoring. Numbers of biochemical analytes have been examined through developed fluorescent contact lens sensors, including pH values, electrolytes, glucose, and enzymes. These sensors have been proven for monitoring ocular conditions, enhancing and detecting medical treatments, and tracking efficiency of related ophthalmic surgeries at POC settings. This review summarizes the applied ophthalmic fluorescence sensing technologies in tears for ocular diagnosis and monitoring. In addition, the cooperation of fabricated fluorescent sensor with mobile phone readout devices for diagnosing ocular diseases with specific biomarkers continuously is also discussed. Further perspectives for the developments and applications of fluorescent ocular sensing and diagnosing technologies are also provided

Deep learning-enabled technologies for bioimage analysis.

Deep learning (DL) is a subfield of machine learning (ML), which has recently demonstrated its potency to significantly improve the quantification and classification workflows in biomedical and clinical applications. Among the end applications profoundly benefitting from DL, cellular morphology quantification is one of the pioneers. Here, we first briefly explain fundamental concepts in DL and then we review some of the emerging DL-enabled applications in cell morphology quantification in the fields of embryology, point-of-care ovulation testing, as a predictive tool for fetal heart pregnancy, cancer diagnostics via classification of cancer histology images, autosomal polycystic kidney disease, and chronic kidney diseases

Ophthalmic sensing technologies for ocular disease diagnostics

Point-of-care diagnosis and personalized treatments are critical in ocular physiology and disease. Continuous sampling of tear fluid for ocular diagnosis is a need for further exploration. Several techniques have been developed for possible ophthalmological applications, from traditional spectroscopies to wearable sensors. Contact lenses are commonly used devices for vision correction, as well as for other therapeutic and cosmetic purposes. They are increasingly being developed into ocular sensors, being used to sense and monitor biochemical analytes in tear fluid, ocular surface temperature, intraocular pressure, and pH value. These sensors have had success in detecting ocular conditions, optimizing pharmaceutical treatments, and tracking treatment efficacy in point-of-care settings. However, there is a paucity of new and effective instrumentation reported in ophthalmology. Hence, this review will summarize the applied ophthalmic technologies for ocular diagnostics and tear monitoring, including both conventional and biosensing technologies. Besides applications of smart readout devices for continuous monitoring, targeted biomarkers are also discussed for the convenience of diagnosis of various ocular diseases. A further discussion is also provided for future aspects and market requirements related to the commercialization of novel types of contact lens sensors

Direct laser writing of nanophotonic structures on contact lenses

Contact lenses are ubiquitous biomedical devices used for vision correction and cosmetic purposes. Their application as quantitative analytical devices is highly promising for point-of-care diagnostics. However, it is a challenge to integrate nanoscale features into commercial contact lenses for application in low-cost biosensors. A neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (1064 nm, 3 ns pulse, 240 mJ) in holographic interference patterning mode was utilized to produce optical nanostructures over the surface of a hydrogel contact lens. One-dimensional (925 nm) and two-dimensional (925 nm × 925 nm) nanostructures were produced on contact lenses and analyzed by spectroscopy and angle-resolve measurements. The holographic properties of these nanostructures were tested in ambient moisture, fully hydrated, and artificial tear conditions. The measurements showed a rapid tuning of optical diffraction from these nanostructures from 41 to 48°. The nanostructures were patterned near the edges of the contact lens to avoid any interference and obstruction to the human vision. The formation of 2D nanostructures on lenses increased the diffraction efficiency by more than 10%. The versatility of the holographic laser ablation method was demonstrated by producing four different 2D nanopattern geometries on contact lenses. Hydrophobicity of the contact lens was characterized by contact angle measurements, which increased from 59.0° at pristine condition to 62.5° at post-nanofabrication. The holographic nanostructures on the contact lens were used to sense the concentration of Na+ ions. Artificial tear solution was used to simulate the conditions in dry eye syndrome, and nanostructures on the contact lenses were used to detect the electrolyte concentration changes (±47 mmol L–1). Nanopatterns on a contact lens may be used to sense other ocular diseases in early stages at point-of-care settings

Rewritable three-dimensional holographic data storage via optical forces

The development of nanostructures that can be reversibly arranged and assembled into 3D patterns may enable optical tunability. However, current dynamic recording materials such as photorefractive polymers cannot be used to store information permanently while also retaining configurability. Here, we describe the synthesis and optimization of a silver nanoparticle doped poly(2-hydroxyethyl methacrylate-co-methacrylic acid) recording medium for reversibly recording 3D holograms. We theoretically and experimentally demonstrate organizing nanoparticles into 3D assemblies in the recording medium using optical forces produced by the gradients of standing waves. The nanoparticles in the recording medium are organized by multiple nanosecond laser pulses to produce reconfigurable slanted multilayer structures. We demonstrate the capability of producing rewritable optical elements such as multilayer Bragg diffraction gratings, 1D photonic crystals, and 3D multiplexed optical gratings. We also show that 3D virtual holograms can be reversibly recorded. This recording strategy may have applications in reconfigurable optical elements, data storage devices, and dynamic holographic displays

Quantitative brain-derived neurotrophic factor lateral flow assay for point-of-care detection of glaucoma

Glaucoma, a ruinous group of eye diseases with progressive degeneration of the optic nerve and vision loss, is the leading cause of irreversible blindness. Accurate and timely diagnosis of glaucoma is critical to promote secondary prevention and early disease-modifying therapies. Reliable, cheap, and rapid tests for measuring disease activities are highly required. Brain-derived neurotrophic factor (BDNF) plays an important role in maintaining the function and survival of the central nervous system. Decreased BDNF levels in tear fluid can be seen in glaucoma patients, which indicates that BDNF can be regarded as a novel biomarker for glaucoma. Conventional ELISA is the standard method to measure the BDNF level, but the multi-step operation and strict storage conditions limit its usage in point-of-care settings. Herein, a one-step and a portable glaucoma detection method was developed based on the lateral flow assay (LFA) to quantify the BDNF concentration in artificial tear fluids. The results of the LFA were analyzed by using a portable and low-cost system consisting of a smartphone camera and a dark readout box fabricated by 3D printing. The concentration of BDNF was quantified by analyzing the colorimetric intensity of the test line and the control line. This assay yields reliable quantitative results from 25 to 300 pg mL-1 with an experimental detection limit of 14.12 pg mL-1. The LFA shows a high selectivity for BDNF and high stability in different pH environments. It can be readily adapted for sensitive and quantitative testing of BDNF in a point-of-care setting. The BDNF LFA strip shows it has great potential to be used in early glaucoma detection

Wearable contact lens biosensors for continuous glucose monitoring using smartphones

Low-cost, robust, and reusable continuous glucose monitoring systems that can provide quantitative measurements at point-of-care settings is an unmet medical need. Optical glucose sensors require complex and time-consuming fabrication processes, and their readouts are not practical for quantitative analyses. Here, a wearable contact lens optical sensor was created for the continuous quantification of glucose at physiological conditions, simplifying the fabrication process and facilitating smartphone readouts. A photonic microstructure having a periodicity of 1.6 μm was printed on a glucose-selective hydrogel film functionalized with phenylboronic acid. Upon binding with glucose, the microstructure volume swelled, which modulated the periodicity constant. The resulting change in the Bragg diffraction modulated the space between zero- and first-order spots. A correlation was established between the periodicity constant and glucose concentration within 0–50 mM. The sensitivity of the sensor was 12 nm mM–1, and the saturation response time was less than 30 min. The sensor was integrated with commercial contact lenses and utilized for continuous glucose monitoring using smartphone camera readouts. The reflected power of the first-order diffraction was measured via a smartphone application and correlated to the glucose concentrations. A short response time of 3 s and a saturation time of 4 min was achieved in the continuous monitoring mode. Glucose-sensitive photonic microstructures may have applications in point-of-care continuous monitoring devices and diagnostics at home settings

Measures of disease activity in glaucoma

Glaucoma is the leading cause of irreversible blindness globally which significantly affects the quality of life and has a substantial economic impact. Effective detective methods are necessary to identify glaucoma as early as possible. Regular eye examinations are important for detecting the disease early and preventing deterioration of vision and quality of life. Current methods of measuring disease activity are powerful in describing the functional and structural changes in glaucomatous eyes. However, there is still a need for a novel tool to detect glaucoma earlier and more accurately. Tear fluid biomarker analysis and new imaging technology provide novel surrogate endpoints of glaucoma. Artificial intelligence is a post-diagnostic tool that can analyse ophthalmic test results. A detail review of currently used clinical tests in glaucoma include intraocular pressure test, visual field test and optical coherence tomography are presented. The advanced technologies for glaucoma measurement which can identify specific disease characteristics, as well as the mechanism, performance and future perspectives of these devices are highlighted. Applications of AI in diagnosis and prediction in glaucoma are mentioned. With the development in imaging tools, sensor technologies and artificial intelligence, diagnostic evaluation of glaucoma must assess more variables to facilitate earlier diagnosis and management in the future

Nanosecond pulsed laser texturing of optical diffusers

High-quality optical glass diffusers have applications in aerospace, displays, imaging systems, medical devices, and optical sensors. The development of rapid and accurate fabrication techniques is highly desirable for their production. Here, a micropatterning method for the fast fabrication of optical diffusers by means of nanosecond pulsed laser ablation is demonstrated (λ=1064 nm, power=7.02, 9.36 and 11.7 W and scanning speed=200 and 800 mm s-1). The experiments were carried out by point-to-point texturing of a glass surface in spiral shape. The laser machining parameters, the number of pulses and their power had significant effect on surface features. The optical characteristics of the diffusers were characterized at different scattering angles. The features of the microscale structures influenced average roughness from 0.8 μm to 1.97 μm. The glass diffusers scattered light at angles up to 20° and their transmission efficiency were measured up to ∼97% across the visible spectrum. The produced optical devices diffuse light less but do so with less scattering and energy losses as compared to opal diffusing glass. The presented fabrication method can be applied to any other transparent material to create optical diffusers. It is anticipated that the optical diffusers presented in this work will have applications in the production of LED spotlights and imaging devices

Identity, reputation and social interaction with an application to sequential voting

We analyze binary choices in a random utility model assuming that the agent's preferences are affected by conformism (with respect to the behavior of the society) and coherence (with respect to his identity). We apply the analysis to sequential voting when voters like to win