Non-contact monitoring of glucose concentration and pH by integration of wearable and implantable hydrogel sensors with optical coherence tomography.

Optical coherence tomography (OCT) is a noninvasive imaging technique with large penetration depth into the tissue, but limited chemical specificity. By incorporating functional co-monomers, hydrogels can be designed to respond to specific molecules and undergo reversible volume changes. In this study, we present implantable and wearable biocompatible hydrogel sensors combined with OCT to monitor their thickness change as a tool for continuous and real-time monitoring of glucose concentration and pH. The results demonstrate the potential of combining hydrogel biosensors with OCT for non-contact continuous in-vivo monitoring of physiological parameters.

Wearable Bifocal Contact Lens for Continual Glucose Monitoring Integrated with Smartphone Readers.

Commercial implantable continuous glucose monitoring devices are invasive and discomfort. Here, a minimally-invasive glucose detection system is developed to provide quantitative glucose measurements continually based on bifocal contact lenses. A glucose-sensitive phenylboronic acid derivative is immobilized in a hydrogel matrix and the surface of the hydrogel is imprinted with a Fresnel lens. The glucose-responsive hydrogel is attached to a commercial soft contact lens to be transformed into a bifocal contact lens. The contact lens showed bifocal lengths; far-field focal length originated from the contact lens' curvature, and near-field focal length resulting from the Fresnel lens. When tear glucose increased, the refractive index and groove depth of the Fresnel lens changed, shifting the near-field focal length and the light focusing efficiency. The recorded optical signals are detected at an identical distance far from the contact lens change. The bifocal contact lens allowed for detecting the tear glucose concentration within the physiological range of healthy individuals and diabetics (0.0-3.3 mm). The contact lens rapidly responded to glucose concentration changes and reached 90% of equilibrium within 40 min. The bifocal contact lens is a wearable diagnostic platform for continual biomarker detection at point-of-care settings.

Lab-on-a-Contact Lens Platforms Fabricated by Multi-Axis Femtosecond Laser Ablation.

Contact lens sensing platforms have drawn interest in the last decade for the possibility of providing a sterile, fully integrated ocular screening technology. However, designing scalable and rapid contact lens processing methods while keeping a high resolution is still an unsolved challenge. In this article, femtosecond laser writing is employed as a rapid and precise procedure to engrave microfluidic networks into commercial contact lenses. Functional microfluidic components such as flow valves, resistors, multi-inlet geometries, and splitters are produced using a bespoke seven-axis femtosecond laser system, yielding a resolution of 80 µm. The ablation process and the tear flow within microfluidic structures is evaluated both experimentally and computationally using finite element modeling. Flow velocity drops of the 8.3%, 20.8%, and 29% were observed in valves with enlargements of the 100%, 200%, and 300%, respectively. Resistors yielded flow rate drops of 20.8%, 33%, and 50% in the small, medium, and large configurations, respectively. Two applications were introduced, namely a tear volume sensor and a tear uric acid sensor (sensitivity 16 mg L-1 ), which are both painless alternatives to current methods and provide reduced contamination risks of tear samples.

Challenges for biosimilars: focus on rheumatoid arthritis.

Healthcare systems worldwide are struggling to find ways to fund the cost of innovative treatments such as gene therapies, regenerative medicine, and monoclonal antibodies (mAbs). As the world's best known mAbs are close to facing patent expirations, the biosimilars market is poised to grow with the hope of bringing prices down for cancer treatment and autoimmune disorders, however, this has yet to be realized. The development costs of biosimilars are significantly higher than their generic equivalents due to therapeutic equivalence trials and higher manufacturing costs. It is imperative that academics and relevant companies understand the costs and stages associated with biologics processing. This article brings these costs to the forefront with a focus on biosimilars being developed for Rheumatoid Arthritis (RA). mAbs have remarkably changed the treatment landscape, establishing their superior efficacy over traditional small chemicals. Five blockbuster TNFα mAbs, considered as first line biologics against RA, are either at the end of their patent life or have already expired and manufacturers are seeking to capture a significant portion of that market. Although in principle, market-share should be available, withstanding that the challenges regarding the compliance and regulations are being resolved, particularly with regards to variation in the glycosylation patterns and challenges associated with manufacturing. Glycan variants can significantly affect the quality attributes requiring characterization throughout production. Successful penetration of biologics can drive down prices and this will be a welcome change for patients and the healthcare providers. Herein we review the biologic TNFα inhibitors, which are on the market, in development, and the challenges being faced by biosimilar manufacturers.

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.

Shear-unlimited common-path speckle interferometer.

A single-aperture common-path speckle interferometer with an unlimited shear amount is developed. This unlimited shear amount is introduced when a Wollaston prism is placed near the Fourier plane of a common-path interferometer, which is built by using a quasi-${4f}$4f imaging system. The fundamentals of the shear amount and the spatial carrier frequency generation are analyzed mathematically, and the theoretical predictions are validated by a static experiment. Mode-I fracture experiments through the three-point bending are conducted to prove the feasibility and the capability of this method in full-field strain measurement with various shear amounts. A remarkable feature of this setup is that no tilt is required between the optical components to produce the unlimited shear amount in off-axis holography.

Real-time dual-sensitive shearography for simultaneous in-plane and out-of-plane strain measurements.

A real-time, dual-sensitive shearography system using a single-wavelength laser was developed for simultaneous and dynamic in-plane and out-of-plane strain measurements. The shearography system is capable of measuring crack-tip deformation fields quantitatively. A spatial multiplexing technique based on Fourier transform is employed for simultaneous and dynamic multi-component phase retrieval. Two slit spatial filters and a common-path shearing interferometer are used to obtain an improved phase quality for crack-tip deformation measurements. Mode-I fracture experiments under three-point bending were conducted to validate the feasibility and the capability of this method.

Dermal Tattoo Biosensors for Colorimetric Metabolite Detection.

Tattooing is a ubiquitous body modification involving the injection of ink and/or dye pigments into the dermis. Biosensors in the form of tattoos can be used to monitor metabolites in interstitial fluid. Here, minimally invasive, injectable dermal biosensors were developed for measuring pH, glucose, and albumin concentrations. The dermal pH sensor was based on methyl red, bromothymol blue, and phenolphthalein, which responded to a pH range from 5.0 to 9.0. The dermal glucose sensor consisted of glucose oxidase, 3,3',5,5'-tetramethylbenzidine, and peroxidase that detected concentrations up to 50.0 mmol L-1 . The dermal albumin sensor consisted of 3',3'',5',5''-tetrachlorophenol-3,4,5,6-tetrabromosulfophthalein to measure concentrations up to 5.0 g L-1 . The sensors were multiplexed in ex vivo skin tissue and quantitative readouts were obtained using a smartphone camera. These sensors can be used to manage of acid-base homeostasis, diabetes, and liver failure in point-of-care settings.

Microfluidic Contact Lenses.

Contact lens is a ubiquitous technology used for vision correction and cosmetics. Sensing in contact lenses has emerged as a potential platform for minimally invasive point-of-care diagnostics. Here, a microlithography method is developed to fabricate microconcavities and microchannels in a hydrogel-based contact lens via a combination of laser patterning and embedded templating. Optical microlithography parameters influencing the formation of microconcavities including ablation power (4.3 W) and beam speed (50 mm s-1 ) are optimized to control the microconcavity depth (100 µm) and diameter (1.5 mm). The fiber templating method allows the production of microchannels having a diameter range of 100-150 µm. Leak-proof microchannel and microconcavity connections in contact lenses are validated through flow testing of artificial tear containing fluorescent microbeads (Ø = 1-2 µm). The microconcavities of contact lenses are functionalized with multiplexed fluorophores (2 µL) to demonstrate optical excitation and emission capability within the visible spectrum. The fabricated microfluidic contact lenses may have applications in ophthalmic monitoring of metabolic disorders at point-of-care settings and controlled drug release for therapeutics.

Plasmid-based high-resolution melting analysis for accurate detection of rpoB mutations in Mycobacterium tuberculosis isolates from Moroccan patients.

BACKGROUND: Rapid diagnosis of drug resistance in tuberculosis (TB) is pivotal for the timely initiation of effective antibiotic treatment to prevent the spread of drug-resistant strains. The development of low-cost, rapid and robust methods for drug-resistant TB detection is highly desirable for resource-limited settings. METHODS: We report the use of an in house plasmid-based quantitative polymerase chain reaction-high-resolution melting (qPCR-HRM) analysis for the detection of mutations related to rifampicin-resistant Mycobacterium tuberculosis (MTB) in clinical isolates from Moroccan patients. Five recombinant plasmids containing predominant mutations (S531L, S531W, H526Y and D516V) and the wild-type sequence of the Rifampicin Resistance-Determining Region (RRDR) have been used as controls to screen 45 rifampicin-resistant and 22 rifampicin-susceptible MTB isolates. RESULTS: The sensitivity and the specificity of the qPCR-HRM analysis were 88.8% and 100% respectively as compared to rifampicin Drug Susceptibility Testing (DST). The results of qPCR-HRM and DNA sequencing had a concordance of 100%. CONCLUSION: Our qPCR-HRM assay is a sensitive, accurate and cost-effective assay for the high-throughput screening of mutation-based drug resistance in TB reference laboratories.

Photonic nanosensor for colorimetric detection of metal ions.

The real-time sensing of metal ions at point of care requires integrated sensors with low energy and sample consumption, reversibility, and rapid recovery. Here, we report a photonic nanosensor that reversibly and quantitatively reports on variation in the concentrations of Pb(2+) and Cu(2+) ions in aqueous solutions (<500 µL) in the visible region of the spectrum (λ(max) ≈ 400-700 nm). A single 6 ns laser pulse (λ = 532 nm) was used to pattern an ∼10 µm thick photosensitive recording medium. This formed periodic AgBr nanocrystal (ø ∼ 5-20 nm) concentrated regions, which produced Bragg diffraction upon illumination with a white light source. The sensor functionalized with 8-hydroxyquinoline allowed sensing through inducing Donnan osmotic pressure and tuning its lattice spacing. The sensor quantitatively measured Pb(2+) and Cu(2+) ion concentrations within the dynamic range of 0.1-10.0 mM with limits of detection of 11.4 and 18.6 µM in under 10 min. The sensor could be reset in 3 min and was reused at least 100 times without compromising its accuracy. The plasmonic nanosensor represents a simple and label-free analytical platform with potential scalability for applications in medical diagnostics and environmental monitoring.

Reusable, robust, and accurate laser-generated photonic nanosensor.

Developing noninvasive and accurate diagnostics that are easily manufactured, robust, and reusable will provide monitoring of high-risk individuals in any clinical or point-of-care environment. We have developed a clinically relevant optical glucose nanosensor that can be reused at least 400 times without a compromise in accuracy. The use of a single 6 ns laser (λ = 532 nm, 200 mJ) pulse rapidly produced off-axis Bragg diffraction gratings consisting of ordered silver nanoparticles embedded within a phenylboronic acid-functionalized hydrogel. This sensor exhibited reversible large wavelength shifts and diffracted the spectrum of narrow-band light over the wavelength range λpeak ≈ 510-1100 nm. The experimental sensitivity of the sensor permits diagnosis of glucosuria in the urine samples of diabetic patients with an improved performance compared to commercial high-throughput urinalysis devices. The sensor response was achieved within 5 min, reset to baseline in ∼10 s. It is anticipated that this sensing platform will have implications for the development of reusable, equipment-free colorimetric point-of-care diagnostic devices for diabetes screening.

Biosensors for melanoma skin cancer diagnostics.

Skin cancer is a critical global public health concern, with melanoma being the deadliest variant, correlated to 80% of skin cancer-related deaths and a remarkable propensity to metastasize. Despite notable progress in skin cancer prevention and diagnosis, the limitations of existing methods accentuate the demand for precise diagnostic tools. Biosensors have emerged as valuable clinical tools, enabling rapid and reliable point-of-care (POC) testing of skin cancer. This review offers insights into skin cancer development, highlights essential cutaneous melanoma biomarkers, and assesses the current landscape of biosensing technologies for diagnosis. The comprehensive analysis in this review underscores the transformative potential of biosensors in revolutionizing melanoma skin cancer diagnosis, emphasizing their critical role in advancing patient outcomes and healthcare efficiency. The increasing availability of these approaches supports direct diagnosis and aims to reduce the reliance on biopsies, enhancing POC diagnosis. Recent advancements in biosensors for skin cancer diagnosis hold great promise, with their integration into healthcare expected to enhance early detection accuracy and reliability, thereby mitigating socioeconomic disparities.

Biosensors for psychiatric biomarkers in mental health monitoring.

Psychiatric disorders are associated with serve disturbances in cognition, emotional control, and/or behavior regulation, yet few routine clinical tools are available for the real-time evaluation and early-stage diagnosis of mental health. Abnormal levels of relevant biomarkers may imply biological, neurological, and developmental dysfunctions of psychiatric patients. Exploring biosensors that can provide rapid, in-situ, and real-time monitoring of psychiatric biomarkers is therefore vital for prevention, diagnosis, treatment, and prognosis of mental disorders. Recently, psychiatric biosensors with high sensitivity, selectivity, and reproducibility have been widely developed, which are mainly based on electrochemical and optical sensing technologies. This review presented psychiatric disorders with high morbidity, disability, and mortality, followed by describing pathophysiology in a biomarker-implying manner. The latest biosensors developed for the detection of representative psychiatric biomarkers (e.g., cortisol, dopamine, and serotonin) were comprehensively summarized and compared in their sensitivities, sensing technologies, applicable biological platforms, and integrative readouts. These well-developed biosensors are promising for facilitating the clinical utility and commercialization of point-of-care diagnostics. It is anticipated that mental healthcare could be gradually improved in multiple perspectives, ranging from innovations in psychiatric biosensors in terms of biometric elements, transducing principles, and flexible readouts, to the construction of 'Big-Data' networks utilized for sharing intractable psychiatric indicators and cases.

Photonic Solutions for Challenges in Sensing.

Sensing technologies support timely and critical decisions to save precious resources in healthcare, veterinary care, food safety, and environmental protection. However, the design of sensors demands strict technical characteristics for real-world applications. In this Viewpoint, we discuss the main challenges to tackle in the sensing field and how photonics represents a valuable tool in this sphere.

Microneedle Sensors for Point-of-Care Diagnostics.

Point-of-care (POC) has the capacity to support low-cost, accurate and real-time actionable diagnostic data. Microneedle sensors have received considerable attention as an emerging technique to evolve blood-based diagnostics owing to their direct and painless access to a rich source of biomarkers from interstitial fluid. This review systematically summarizes the recent innovations in microneedle sensors with a particular focus on their utility in POC diagnostics and personalized medicine. The integration of various sensing techniques, mostly electrochemical and optical sensing, has been established in diverse architectures of "lab-on-a-microneedle" platforms. Microneedle sensors with tailored geometries, mechanical flexibility, and biocompatibility are constructed with a variety of materials and fabrication methods. Microneedles categorized into four types: metals, inorganics, polymers, and hydrogels, have been elaborated with state-of-the-art bioengineering strategies for minimally invasive, continuous, and multiplexed sensing. Microneedle sensors have been employed to detect a wide range of biomarkers from electrolytes, metabolites, polysaccharides, nucleic acids, proteins to drugs. Insightful perspectives are outlined from biofluid, microneedles, biosensors, POC devices, and theragnostic instruments, which depict a bright future of the upcoming personalized and intelligent health management.

Engineered Bacteria as Living Biosensors in Dermal Tattoos.

Dermal tattoo biosensors are promising platforms for real-time monitoring of biomarkers, with skin used as a diagnostic interface. Traditional tattoo sensors have utilized small molecules as biosensing elements. However, the rise of synthetic biology has enabled the potential employment of engineered bacteria as living analytical tools. Exploiting engineered bacterial sensors will allow for potentially more sensitive detection across a broad biomarker range, with advanced processing and sense/response functionalities using genetic circuits. Here, the interfacing of bacterial biosensors as living analytics in tattoos is shown. Engineered bacteria are encapsulated into micron-scale hydrogel beads prepared through scalable microfluidics. These biosensors can sense both biochemical cues (model biomarkers) and biophysical cues (temperature changes, using RNA thermometers), with fluorescent readouts. By tattooing beads into skin models and confirming sensor activity post-tattooing, our study establishes a foundation for integrating bacteria as living biosensing entities in tattoos.

Plasmonic Contact Lenses Based on Silver Nanoparticles for Blue Light Protection.

Constant exposure to blue light emanating from screens, lamps, digital devices, or other artificial sources at night can suppress melatonin secretion, potentially compromising both sleep quality and overall health. Daytime exposure to elevated levels of blue light can also lead to permanent damage to the eyes. Here, we have developed blue light protective plasmonic contact lenses (PCLs) to mitigate blue light exposure. Crafted from poly(hydroxyethyl methacrylate) (pHEMA) and infused with silver nanoparticles, these contact lenses serve as a protective barrier to filter blue light. Leveraging the plasmonic properties of silver nanoparticles, the lenses effectively filtered out the undesirable blue light (400-510 nm), demonstrating substantial protection (22-71%) while maintaining high transparency (80-96%) for the desirable light (511-780 nm). The maximum protection level reaches a peak of 79% at 455 nm, aligned with the emission peak for the blue light sourced from LEDs in consumer displays. The presence of silver nanoparticles was found to have an insignificant impact on the water content of the developed contact lenses. The lenses maintained high water retention levels within the range of 50-70 wt %, comparable to commercial contact lenses. The optical performance of the developed lenses remains unaffected in both artificial tears and contact lens storage solution over a month with no detected leakage of the nanoparticles. Additionally, the MTT assay confirmed that the lenses were biocompatible and noncytotoxic, maintaining cell viability at over 85% after 24 h of incubation. These lenses could be a potential solution to protect against the most intense wavelengths emitted by consumer displays and offer a remedy to counteract the deleterious effects of prolonged blue light exposure.

Contact lens sensor for ocular inflammation monitoring.

Contact lens sensors have been emerging as point-of-care devices in recent healthcare developments for ocular physiological condition monitoring and diagnosis. Fluorescence sensing technologies have been widely applied in contact lens sensors due to their accuracy, high sensitivity, and specificity. As ascorbic acid (AA) level in tears is closely related to ocular inflammation, a fluorescent contact lens sensor incorporating a BSA-Au nanocluster (NC) probe is developed for in situ tear AA detection. The NCs are firstly synthesized to obtain a fluorescent probe, which exhibits high reusability through the quench/recover (KMnO4/AA) process. The probe is then encapsulated with 15 wt% of poly(vinyl alcohol) (PVA) and 1.5 wt% of citric acid (CA) film, and implemented on a closed microfluidic contact lens sensing region. The laser-ablated microfluidic channel in contact lens sensors allows for tear fluid to flow through the sensing region, enabling an in-situ detection of AA. Meanwhile, a smartphone application accompanied by a customized 3D printed readout box is developed for image caption and algorism to quantitative analysis of AA levels. The contact lens sensor is tested within the readout box and the emission signal is collected through the smartphone camera at room temperature with an achieved LOD of 0.178 mmol L-1 (0.0-1.2 mmol L-1). The operational and storage lifetime is also evaluated to characterize the sensor properties and resulted in 20 h and 10 days, respectively. The reusable AA contact lens sensor is promising to lead to an alternative accessible diagnostic method for ocular inflammation in point-of-care settings.