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Asail Hendi,1 Muhammad Umair Hassan,2 Mohamed Elsherif,3 Bader Alqattan,4 Seongjun Park,5,6 Ali Kemal Yetisen,7 Haider Butt4 1School of Engineering, University of Birmingham, Birmingham B15 2TT, UK; 2Optoelectronics Research Lab, COMSATS University, Islamabad 45550, Pakistan; 3Department of Experimental Nuclear Physics, Nuclear Research Center, Egyptian Atomic Energy Authority, Cairo, Egypt; 4Department of Mechanical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates; 5Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; 6KAIST Institute for Health Science and Technology (KIHST), Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea; 7Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UKCorrespondence: Mohamed ElsherifDepartment of Experimental Nuclear Physics, Nuclear Research Center, Egyptian Atomic Energy Authority, Cairo, EgyptEmail elsherifmohamed109@gmail.comHaider ButtDepartment of Mechanical Engineering, Khalifa University, Abu Dhabi, United Arab EmiratesEmail haider.butt@ku.ac.aeAbstract: pH-sensitive hydrogels have been developed greatly over the past few years. This has been possible due to the synthesis of new hydrogel systems with increased sensitivity – a sensitivity of up to 10− 5 pH units has already been established. Recently, pH-sensitive hydrogels have shown to be very useful in biomedical applications, such as targeted cancer treatment and treatment of skin lesions. Prolonged drug release has been made available through the use of such hydrogels. The synthesis of pH-sensitive hydrogels is also quick and cost-effective. This review presents a background on the properties of pH-sensitive hydrogels and discusses some of the hydrogels with different sensitivity ranges and their possible applications. A range of synthesis processes have also been briefly introduced along with the fabrication of different structures such as microcantilevers and contact lenses.Keywords: pH-sensitive, sensors, hydrogels, biomedical applications, biocompatible

Continuous glucose monitors are crucial for diabetes management, but invasive sampling, signal drift and frequent calibrations restrict their widespread usage. Microneedle sensors are emerging as a minimally-invasive platform for real-time monitoring of clinical parameters in interstitial fluid. Herein, a painless and flexible microneedle sensing patch is constructed by a mechanically-strong microneedle base and a thin layer of fluorescent hydrogel sensor for on-site, accurate, and continuous glucose monitoring. The Förster resonance energy transfer (FRET)-based hydrogel sensors are fabricated by facile photopolymerizations of acryloylated FRET pairs and glucose-specific phenylboronic acid. The optimized hydrogel sensor enables quantification of glucose with reversibility, high selectivity, and signal stability against photobleaching. Poly (ethylene glycol diacrylate)-co-polyacrylamide hydrogel is utilized as the microneedle base, facilitating effective skin piercing and biofluid extraction. The integrated microneedle sensor patch displays a sensitivity of 0.029 mM -1 in the (patho)physiological range, a low detection limit of 0.193 mM, and a response time of 7.7 min in human serum. Hypoglycemia, euglycemia and hyperglycemia are continuously monitored over 6 h simulated meal and rest activities in a porcine skin model. This microneedle sensor with high transdermal analytical performance offers a powerful tool for continuous diabetes monitoring at point-of-care settings., Competing Interests: Declaration of competing interest The authors have declared no financial/personal interest or belief that could affect the objectivity of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

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., Competing Interests: Declaration of competing interest The authors declare no competing financial interests regarding the work described in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Safe, accurate, and reliable analysis of urinary biomarkers is clinically important for early detection and monitoring of the progression of chronic kidney disease (CKD), as it has become one of the world's most prevalent non-communicable diseases. However, current technologies for measuring urinary biomarkers are either time-consuming and limited to well-equipped hospitals or lack the necessary sensitivity for quantitative analysis and post a health risk to frontline practitioners. Here we report a robust paper-based dual functional biosensor, which is integrated with the clinical urine sampling vial, for the simultaneous and quantitative analysis of pH and glucose in urine. The pH sensor was fabricated by electrochemically depositing IrOx onto a paper substrate using optimised parameters, which enabled an ultrahigh sensitivity of 71.58 mV pH -1 . Glucose oxidase (GOx) was used in combination with an electrochemically deposited Prussian blue layer for the detection of glucose, and its performance was enhanced by gold nanoparticles (AuNPs), chitosan, and graphite composites, achieving a sensitivity of 1.5 μA mM -1 . This dual function biosensor was validated using clinical urine samples, where a correlation coefficient of 0.96 for pH and 0.98 for glucose detection was achieved with commercial methods as references. More importantly, the urine sampling vial was kept sealed throughout the sample-to-result process, which minimised the health risk to frontline practitioners and simplified the diagnostic procedures. This diagnostic platform, therefore, holds high promise as a rapid, accurate, safe, and user-friendly point-of-care (POC) technology for the analysis of urinary biomarkers in frontline clinical settings.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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 (KMnO 4 /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., Competing Interests: Declaration of competing interest A.K.Y. and Y. H. acknowledge the Engineering and Physical Sciences Research Council (EPSRC) for a research grant (EP/T013567/1). N.J. acknowledges the Fundamental Research Funds for the Central Universities (no. YJ202152), and JinFeng Laboratory, Chongqing, China (jfkyjf202203001)., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

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., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

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.

Infectious diseases continue to pose an imminent threat to global public health, leading to high numbers of deaths every year and disproportionately impacting developing countries where access to healthcare is limited. Biological, environmental, and social phenomena, including climate change, globalization, increased population density, and social inequity, contribute to the emergence of novel communicable diseases. Rapid and accurate diagnoses of infectious diseases are essential to preventing the transmission of infectious diseases. Although some commonly used diagnostic technologies provide highly sensitive and specific measurements, limitations including the requirement for complex equipment/infrastructure and refrigeration, the need for trained personnel, long sample processing times, and high cost remain unresolved. To ensure global access to affordable diagnostic methods, loop-mediated isothermal amplification (LAMP) integrated clustered regularly interspaced short palindromic repeat (CRISPR) based pathogen detection has emerged as a promising technology. Here, LAMP-integrated CRISPR-based nucleic acid detection methods are discussed in point-of-care (PoC) pathogen detection platforms, and current limitations and future directions are also identified., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Prostate cancer (PC) is one of the most common tumors and a leading cause of mortality among men, resulting in ~375 000 deaths annually worldwide. Various analytical methods have been designed for quantitative and rapid detection of PC biomarkers. Electrochemical (EC), optical, and magnetic biosensors have been developed to detect tumor biomarkers in clinical and point-of-care (POC) settings. Although POC biosensors have shown potential for detection of PC biomarkers, some limitations, such as the sample preparation, should be considered. To tackle such shortcomings, new technologies have been utilized for development of more practical biosensors. Here, biosensing platforms for the detection of PC biomarkers such as immunosensors, aptasensors, genosensors, paper-based devices, microfluidic systems, and multiplex high-throughput platforms, are discussed., Competing Interests: Declaration of interests No interests are declared by the authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Micromixers play an imperative role in chemical and biomedical systems. Designing compact micromixers for laminar flows owning a low Reynolds number is more challenging than flows with higher turbulence. Machine learning models can enable the optimization of the designs and capabilities of microfluidic systems by receiving input from a training library and producing algorithms that can predict the outcomes prior to the fabrication process to minimize development cost and time. Here, an educational interactive microfluidic module is developed to enable the design of compact and efficient micromixers at low Reynolds regimes for Newtonian and non-Newtonian fluids. The optimization of Newtonian fluids designs was based on a machine learning model, which was trained by simulating and calculating the mixing index of 1890 different micromixer designs. This approach utilized a combination of six design parameters and the results as an input data set to a two-layer deep neural network with 100 nodes in each hidden layer. A trained model was achieved with R 2  = 0.9543 that can be used to predict the mixing index and find the optimal parameters needed to design micromixers. Non-Newtonian fluid cases were also optimized using 56700 simulated designs with eight varying input parameters, reduced to 1890 designs, and then trained using the same deep neural network used for Newtonian fluids to obtain R 2  = 0.9063. The framework was subsequently used as an interactive educational module, demonstrating a well-structured integration of technology-based modules such as using artificial intelligence in the engineering curriculum, which can highly contribute to engineering education., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Bioprinting as an extension of 3D printing offers capabilities for printing tissues and organs for application in biomedical engineering. Conducting bioprinting in space, where the gravity is zero, can enable new frontiers in tissue engineering. Fabrication of soft tissues, which usually collapse under their own weight, can be accelerated in microgravity conditions as the external forces are eliminated. Furthermore, human colonization in space can be supported by providing critical needs of life and ecosystems by 3D bioprinting without relying on cargos from Earth, e.g., by development and long-term employment of living engineered filters (such as sea sponges-known as critical for initiating and maintaining an ecosystem). This review covers bioprinting methods in microgravity along with providing an analysis on the process of shipping bioprinters to space and presenting a perspective on the prospects of zero-gravity bioprinting.

Microneedles (MNs) allow for biological fluid sampling and drug delivery toward the development of minimally invasive diagnostics and treatment in medicine. MNs have been fabricated based on empirical data such as mechanical testing, and their physical parameters have been optimized through the trial-and-error method. While these methods showed adequate results, the performance of MNs can be enhanced by analyzing a large data set of parameters and their respective performance using artificial intelligence. In this study, finite element methods (FEMs) and machine learning (ML) models were integrated to determine the optimal physical parameters for a MN design in order to maximize the amount of collected fluid. The fluid behavior in a MN patch is simulated with several different physical and geometrical parameters using FEM, and the resulting data set is used as the input for ML algorithms including multiple linear regression, random forest regression, support vector regression, and neural networks. Decision tree regression (DTR) yielded the best prediction of optimal parameters. ML modeling methods can be utilized to optimize the geometrical design parameters of MNs in wearable devices for application in point-of-care diagnostics and targeted drug delivery., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The science of microrobots is accelerating towards the creation of new functionalities for biomedical applications such as targeted delivery of agents, surgical procedures, tracking and imaging, and sensing. Using magnetic properties to control the motion of microrobots for these applications is emerging. Here, 3D printing methods are introduced for the fabrication of microrobots and their future perspectives are discussed to elucidate the path for enabling their clinical translation.

The demand for high-quality healthcare and well-being services is remarkably increasing due to the ageing global population and modern lifestyles. Recently, the integration of wearables and artificial intelligence (AI) has attracted extensive academic and technological attention for its powerful high-dimensional data processing of wearable biosensing networks. This work reviews the recent developments in AI-assisted wearable biosensing devices in disease diagnostics and fatigue monitoring demonstrating the trend towards personalised medicine with highly efficient, cost-effective, and accurate point-of-care diagnosis by finding hidden patterns in biosensing data and detecting abnormalities. The reliability of adaptive learning and synthetic data and data privacy still need further investigation to realise personalised medicine in the next decade. Due to the worldwide popularity of smartphones, they have been utilised for sensor readout, wireless data transfer, data processing and storage, result display, and cloud server communication leading to the development of smartphone-based biosensing systems. The recent advances have demonstrated a promising future for the healthcare system because of the increasing data processing power, transfer efficiency and storage capacity and diversifying functionalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

Magnetic levitation allows for simulating the microgravity conditions to advance bottom-up tissue engineering, forging regenerative medicine ahead to enable space exploration. Here, magnetic levitation methods for microgravity studies and the biofabrication of 3D cellular structures are discussed., Competing Interests: Declaration of interests The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Continuous monitoring of physiological conditions and biomarkers via optical holographic sensors is an area of growing interest to facilitate the expansion of personalised medicine. Here, a facile laser-induced dual polymerization method is developed to fabricate holographic hydrogel sensors for the continuous and reversible colorimetric determination of pH variations over a physiological range in serum (pH 7-9). Readout parameters simulated through a Finite-difference time-domain Yee's algorithm retrieve the spectral response through expansion. Laser lithography of holographic hydrogel sensor fabrication is achieved via a single 355 nm laser pulse to initiate polymerization of ultrafine hydrogel fringes. Eliminating the requirement for complex processing of toxic components and streamlining the synthetic procedure provides a simpler route to mass production. Optimised pH-responsive hydrogels contain amine bearing functional co-monomers demonstrating reversible Bragg wavelength shifts of 172 nm across the entire visible wavelength range with pH variation from 7.0 to 9.0 upon illumination with broadband light. Photolithographic recording of information shows the ability to convey detailed information to users for qualitative identification of pH. Holographic sensor reversibility over 20 cycles showed minimal variation in replay wavelength supporting reliable and consistent readout, with optimised sensors showing rapid response times of <5 min. The developed sensors demonstrate the application to continuous monitoring in biological fluids, withstanding interference from electrolytes, saccharides, and proteins colorimetrically identifying bovine serum pH over a physiological range. The holographic sensors benefit point-of-care pH analysis of biological analytes which could be applied to the identification of blood gas disorders and wound regeneration monitoring through colorimetric readouts., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Endocrine diseases are the fifth most common cause of death and have a considerable impact on society given that they induce long-term morbidity in patients. For many decades, the measurement of hormones has been of great interest since this can be used to diagnose a plethora of pathological conditions. As a result, the endocrine testing market has experienced exponential growth. Several techniques have been utilised for the detection of hormones; however, they are expensive, laborious and require specialist training. Conversely, lateral flow assays (LFAs) are cheap (<£1) and rapid (<5 min) devices. LFAs typically rely on biochemical interactions between antibodies and antigens to produce coloured signals proportional to analyte concentrations, which can be visually inspected. Given their simplicity, LFAs are now considered the most attractive point-of-care device in medicine. However, the measurement of hormones in biofluids using LFAs faces many challenges including (i) the necessity for sensitive detection methods, (ii) the need for multiplexed devices for the confirmation of a diagnosis, and (iii) difficulties in sample preparation and pre-concentration. As such, most hormone LFAs remain in the research phase, and the few that have been commercialised require further optimisation before they can be employed for routine use. This review summarises the basic principles underlying lateral flow technology and provides an overview of recent advances, challenges, and potential solutions for the detection of hormone biomarkers via LFAs. Finally, hormone LFA kits available on the market are presented, with a look towards future developments and trends in the field.

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.

Integration of nanomaterials into hydrogels has emerged as a prominent research tool utilized in applications such as sensing, cancer therapy, and bone tissue engineering. Wearable contact lenses functionalized with nanoparticles have been exploited in therapeutics and targeted therapy. Here, we report the fabrication of gold and silver nanocomposite commercial contact lenses using a breathing-in/breathing-out (BI-BO) method, whereby a hydrated contact lens is shrunk in an aprotic solvent and then allowed to swell in an aqueous solution containing nanoparticles. The morphology and optical properties of the gold and silver nanoparticles were characterized through transmission electron microscopy and ultraviolet-visible spectroscopy. The transmission spectra of nanocomposite contact lenses indicated that the nanoparticles' loading amount within the lens depended primarily on the number of BI-BO cycles. Nanocomposites were stable for a minimum period of 1 month, and no nanoparticle leaching was observed. Wettability and water content analysis of the nanocomposites revealed that the contact lenses retained their intrinsic material properties after the fabrication process. The dispersion of the nanoparticles within the contact lens media was determined through scanning electron microscopy imaging. The nanocomposite lenses can be deployed in color filtering and antibacterial applications. In fact, the silver nanocomposite contact lens showed blue-light blocking capabilities by filtering a harmful high-energy blue-light range (400-450 nm) while transmitting the visible light beyond 470 nm, which facilitates enhanced night vision and color distinction. The ease of fabricating these nanocomposite contact lenses via the BI-BO method could enable the incorporation of nanoparticles with diverse morphologies into contact lenses for various biomedical applications.

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.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 The Authors. Small published by Wiley-VCH GmbH.)

The persistence of traditional tattoo inks presents an advantage for continuous and long-term health monitoring in point of care devices. The replacement of tattoo pigments with optical biosensors aims a promising alternative for monitoring blood biomarkers. Tattoo inks functionalization enables the control of interstitial biomarkers with correlated concentrations in plasma, to diagnose diseases, evaluate progression, and prevent complications associated with physio pathological disorders or medication mismatches. The specific biomarkers in interstitial fluid provide a new source of information, especially for skin diseases. The study of tattoo inks displays insufficient regulation in their composition, a lack of reports of the related complications, and a need for further studies on their degradation kinetics. This review focuses on tattoo optical biosensors for monitoring dermal interstitial biomarkers and discusses the clinical advantages and main challenges for in vivo implantation. Tattoo functionalization provides a minimally invasive, reversible, biocompatible, real-time sensing with long-term permanence and multiplexing capabilities for the control, diagnosis, and prevention of illness; it enables self-controlling management by the patient, but also the possibility of sending the records to the doctor., (© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

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.

More than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions., (© 2021. The Author(s).)

Colorimetric tests for at-home health monitoring became popular 50 years ago with the advent of the urinalysis test strips, due to their reduced costs, practicality, and ease of operation. However, developing digital systems that can interface these sensors in an efficient manner remains a challenge. Efforts have been put towards the development of portable optical readout systems, such as smartphones. However, their use in daily settings is still limited by their error-prone nature associated to optical noise from the ambient lighting, and their low sensitivity. Here, a smartphone application (Colourine) to readout colorimetric signals was developed on Android OS and tested on commercial urinalysis test strips for pH, proteins, and glucose detection. The novelty of this approach includes two features: a pre-calibration step where the user is asked to take a photo of the commercial reference chart, and a CIE-RGB-to-HSV color space transformation of the acquired data. These two elements allow the background noise given by environmental lighting to be minimized. The sensors were characterized in the ambient light range 100-400 lx, yielding a reliable output. Readouts were taken from urine strips in buffer solutions of pH (5.0-9.0 units), proteins (0-500 mg dL -1 ) and glucose (0-1000 mg dL -1 ), yielding a limit of detection (LOD) of 0.13 units (pH), 7.5 mg dL -1 (proteins) and 22 mg dL -1 (glucose), resulting in an average LOD decrease by about 2.8 fold compared to the visual method.

Brain neurochemical monitoring aims to provide continuous and accurate measurements of brain biomarkers. It has enabled significant advances in neuroscience for application in clinical diagnostics, treatment, and prevention of brain diseases. Microfabricated electrochemical and optical spectroscopy sensing technologies have been developed for precise monitoring of brain neurochemicals. Here, a comprehensive review on the progress of sensing technologies developed for brain neurochemical monitoring is presented. The review provides a summary of the widely measured clinically relevant neurochemicals and commonly adopted recognition technologies. Recent advances in sampling, electrochemistry, and optical spectroscopy for brain neurochemical monitoring are highlighted and their application are discussed. Existing gaps in current technologies and future directions to design industry standard brain neurochemical sensing devices for clinical applications are addressed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 Wiley-VCH GmbH.)