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  • Journal article
    Shi Y, Zhang Y, Hu Y, Moreddu R, Fan Z, Jiang N, Yetisen AKet al., 2023,

    Smartphone-based fluorescent sensing platforms for point-of-care ocular lactoferrin detection

    , Sensors and Actuators B: Chemical, Vol: 378, ISSN: 0925-4005

    Lactoferrin is a critical glycoprotein that accounts for the major component in tear protein composition. Tear lactoferrin has been indicated as a potential biomarker in ocular health screening, such as dry eye disease diagnosis. Fluorescent biosensors are a desirable alternative to current diagnostic methods, due to their high selectivity and sensitivity, and rapid and cost-effective detection technologies at point-of-care (POC) platforms. Herein, fluorescent lactoferrin sensing is examined and applied on nitrocellulose membrane, capillary tube, and contact lens platforms in cooperation with a developed smartphone software for data collection and analysis. Fluorescent sensors based on trivalent terbium (TbCl3) are integrated into different platforms, including nitrocellulose membranes, capillary tubes, and contact lenses, and tested in artificial tear fluid. A bespoke 3D printed readout device integrated with a smartphone camera was employed for image acquisition and readout. The detection range of the lactoferrin sensors could be varied from 0 to 5 mg mL−1 with a strong linear relation and yielded a limit of detection (LOD) of 0.57 mg mL−1 for lateral flow sensing, 0.12 mg mL−1 for capillary tube sensing, and 0.44 mg mL−1 for contact lens sensing. The contact lens sensor obtained the highest linear regression, while the capillary tube sensor achieved a lowest LOD. This work could pave the way towards accessible lactoferrin monitoring at POC and could induce hospitalization at the UK national health service (NHS) for future clinical trials and examinations.

  • Journal article
    Zhang Y, Hu Y, Jiang N, Yetisen AKet al., 2023,

    Wearable artificial intelligence biosensor networks

    , BIOSENSORS & BIOELECTRONICS, Vol: 219, ISSN: 0956-5663
  • Journal article
    Atceken N, Munzer Alseed M, Dabbagh SR, Yetisen AK, Tasoglu Set al., 2023,

    Point‐of‐Care Diagnostic Platforms for Loop‐Mediated Isothermal Amplification

    , Advanced Engineering Materials, Pages: 2201174-2201174, ISSN: 1438-1656
  • Journal article
    Zhang Y, Hu Y, Liu Q, Lou K, Wang S, Zhang N, Jiang N, Yetisen AKet al., 2022,

    Multiplexed optical fiber sensors for dynamic brain monitoring

    , MATTER, Vol: 5, Pages: 3947-3976, ISSN: 2590-2393
  • Journal article
    Dong X, Zhang Y, Li H, Yan Y, Li J, Song J, Wang K, Jakobi M, Yetisen AK, Koch AWet al., 2022,

    Microscopic Image Deblurring by a Generative Adversarial Network for 2D Nanomaterials: Implications for Wafer-Scale Semiconductor Characterization

    , ACS APPLIED NANO MATERIALS, Vol: 5, Pages: 12855-12864
  • Journal article
    Wu Y, Hu Y, Jiang N, Anantharanjit R, Yetisen AK, Cordeiro MFet al., 2022,

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

    , Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 22, Pages: 3521-3532, ISSN: 1473-0189

    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.

  • Journal article
    Sarabi MR, Yetisen AK, Tasoglu S, 2022,

    Magnetic levitation for space exploration

    , TRENDS IN BIOTECHNOLOGY, Vol: 40, Pages: 915-917, ISSN: 0167-7799
  • Journal article
    Davies S, Hu Y, Guo D, Jiang N, Montelongo Y, Naydenova I, Yetisen Aet al., 2022,

    Computational modelling of doubly-photopolymerised holographic biosensors

    , Advanced Theory and Simulations, Vol: 5, Pages: 1-11, ISSN: 2513-0390

    Holographic sensors are optical devices capable of tuning reflection wavelength, dependent upon nanostructured variations in refractive index. Computational modelling is utilised to simulate the recording and swelling characteristics of developed doubly photopolymerized (DP) holographic sensors. The holographic devices simplify fabrication processes, reduce financial costs, and improve biocompatibility. A holographic grating is achieved through in-situ photopolymerization of a highly crosslinked polymer to produce nanostructured refractive index modulation. The unique swelling characteristics DP holographic sensors possess necessitates the development of system-specific computational modelling. Hydrogel parameters, including film thickness, refractive index change, layer number, and external medium refractive index are examined for their effect on reflection spectra. Optimised computational models are utilised to study the effect of differential swelling rates of individual layer spacings on sensor response, indicating an idealised reduction in swelling of 50% for the highly crosslinked region. A 2D photonic crystal geometry with additional periodicity is developed, to inform further sensor design opportunities. Optimised parameters for both 1D and 2D photonic structures will assist the further development of DP holographic sensors.

  • Journal article
    Dong X, Li H, Yan Y, Cheng H, Zhang HX, Zhang Y, Le TD, Wang K, Dong J, Jakobi M, Yetisen AK, Koch AWet al., 2022,

    Deep-Learning-Based Microscopic Imagery Classification, Segmentation, and Detection for the Identification of 2D Semiconductors

    , ADVANCED THEORY AND SIMULATIONS
  • Journal article
    Davis S, Hu Y, Jiang N, Montelongo Y, Richardson A, Blyth J, Yetisen Aet al., 2022,

    Reversible photonic hydrogel sensors via holographic interference lithography

    , Biosensors and Bioelectronics, Vol: 207, ISSN: 0956-5663

    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.

  • Journal article
    Khelifa L, Hu Y, Jiang N, Yetisen AKet al., 2022,

    Lateral flow assays for hormone detection

    , LAB ON A CHIP, ISSN: 1473-0197
  • Journal article
    Shi Y, Hu Y, Jiang N, Yetisen AKet al., 2022,

    Fluorescence sensing technologies for ophthalmic diagnosis

    , ACS Sensors, Vol: 7, ISSN: 2379-3694

    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.

  • Journal article
    Ahmed I, Elsherif M, Park S, Yetisen AK, Butt Het al., 2022,

    Nanostructured Photonic Hydrogels for Real-Time Alcohol Detection

    , ACS Applied Nano Materials, ISSN: 2574-0970
  • Journal article
    Salih AE, Elsherif M, Alam F, Alqattan B, Yetisen AK, Butt Het al., 2022,

    Syntheses of gold and silver nanocomposite contact lenses via chemical volumetric modulation of hydrogels

    , ACS Biomaterials Science and Engineering, Vol: 8, Pages: 2111-2120, ISSN: 2373-9878

    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.

  • Journal article
    Wang W, Chang L, Shao Y, Yu D, Parajuli J, Xu C, Ying G, Yetisen AK, Yin Y, Jiang Net al., 2022,

    Conductive ionic liquid/chitosan hydrogels for neuronal cell differentiation

    , Engineered Regeneration, Vol: 3, Pages: 1-12, ISSN: 2666-1381
  • Journal article
    Rabbi F, Dabbagh SR, Angin P, Yetisen AK, Tasoglu Set al., 2022,

    Deep learning-enabled technologies for bioimage analysis.

    , Micromachines (Basel), Vol: 13, Pages: 1-28, ISSN: 2072-666X

    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.

  • Journal article
    Alam F, Salih AE, Elsherif M, Yetisen AK, Butt Het al., 2022,

    3D printed contact lenses for the management of color blindness

    , Additive Manufacturing, Vol: 49, Pages: 102464-102464, ISSN: 2214-8604
  • Journal article
    Dong J, Yetisen AK, Zhao C, Dong X, Braendle F, Wang Q, Jakobi M, Saur D, Koch AWet al., 2021,

    Single-Shot High-Throughput Phase Imaging with Multibeam Array Interferometric Microscopy

    , ACS PHOTONICS, Vol: 8, Pages: 3536-3547, ISSN: 2330-4022
  • Journal article
    Ruiz-Esparza GU, Wang X, Zhang X, Jimenez-Vazquez S, Diaz-Gomez L, Lavoie A-M, Afewerki S, Fuentes-Baldemar AA, Parra-Saldivar R, Jiang N, Annabi N, Saleh B, Yetisen AK, Sheikhi A, Jozefiak TH, Shin SR, Dong N, Khademhosseini Aet al., 2021,

    Nanoengineered shear-thinning hydrogel barrier for preventing postoperative abdominal adhesions

    , Nano-Micro Letters, Vol: 13, Pages: 1-16, ISSN: 2150-5551

    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.

  • Journal article
    Davies S, Hu Y, Jiang N, Blyth J, Kaminska M, Liu Y, Yetisen Aet al., 2021,

    Holographic sensors in biotechnology

    , Advanced Functional Materials, Vol: 31, Pages: 1-24, ISSN: 1616-301X

    As populations expand worldwide, medical care will need to diversify its data collection techniques to be able to provide adequate healthcare to global populations, this could be achieved through point-of-care analysis by wearable analytical devices. Holographic sensors are reusable optical biosensors with the capability to continuously monitor variations, generating the prospect of in vivo monitoring of patient homeostasis. Holographic optical sensors have emerged as an opportunity for low cost and real-time point-of-care analysis of biomarkers to be realised. This review aims to summarise the fundamentals and fabrications of holographic sensors; a key focus will be directed to examining the biotechnology applications in a variety of analytical settings. Techniques covered include surface relief gratings, inverse opals, metal nanoparticle and nanoparticle free holographic sensors. This article provides an overview of holographic biosensing in applications such as pH, alcohol, ion, glucose, and drug detection, alongside antibiotic monitoring. Details of developments in fabrication and sensitising techniques will be examined and how they have improved the applicability of holographic sensors to point-of-care analytics. Although holographic sensors have made significant progress in recent years, the current challenges, and requirements for advanced holographic technology to fulfil their future potential applications in biomedical devices will be discussed.

  • Journal article
    Salih AE, Shanti A, Elsherif M, Alam F, Lee S, Polychronopoulou K, Almaskari F, AlSafar H, Yetisen AK, Butt Het al., 2021,

    Silver nanoparticle-loaded contact lenses for blue-yellow color vision deficiency

    , Physica Status Solidi A: Applications and Materials Science, Vol: 219, ISSN: 1862-6300

    Contact lenses can be functionalized to offer advanced capabilities transcending their primary applications in vision correction and cosmetics. Herein, 40 and 60 nm spherical silver nanoparticles (SNPs) are integrated within poly(2-hydroxyethyl methacrylate) (pHEMA) contact lenses toward fabrication of SNP-loaded contact lenses with excellent optical and material properties as wearables for blue-yellow color vision deficiency (CVD) patients. The morphology and optical properties of the SNPs are characterized prepolymerization using the transmission electron microscopy (TEM) and an optical spectrophotometer. Then, the transmission spectra of the SNP-loaded contact lenses at different concentrations along with the wettability and water content are measured, to demonstrate the effect of NPs’ addition on the lenses’ optical and material characteristics. Results indicate that the transmission spectra of SNP-loaded contact lenses, with optimum concentrations, filter out problematic wavelengths of visible light (485–495 nm), which will facilitate better color distinction for blue-yellow CVD patients. The contact lenses’ optical properties are analogous to the commercial colorblind glasses, indicating their effectiveness as color filtering wearables. Finally, the cytobiocompatability analysis of the contact lenses to RAW 264.7 culture of cells shows that they are biocompatible, and the cell viability remains higher than 75% after 24 h in contact with the lenses.

  • Journal article
    Pazos MD, Hu Y, Elani Y, Browning KL, Jiang N, Yetisen AKet al., 2021,

    Tattoo inks for optical biosensing in interstitial fluid

    , Advanced Healthcare Materials, Vol: 10, Pages: 1-22, ISSN: 2192-2640

    The persistence of traditional tattoo inks presents an advantage for continuous andlong-term health monitoring in point of care devices. The replacement of tattoo pigments withoptical biosensors aims a promising alternative for monitoring blood biomarkers. Tattoo inksfunctionalization enables the control of interstitial biomarkers with correlated concentrations inplasma, to diagnose diseases, evaluate progression, and prevent complications associated withphysio pathological disorders or medication mismatches. The specific biomarkers in interstitialfluid provide a new source of information, especially for skin diseases. The study of tattoo inksdisplays insufficient regulation in their composition, a lack of reports of the relatedcomplications and a need for further studies on their degradation kinetics. This review focuseson tattoo optical biosensors for monitoring dermal interstitial biomarkers and discusses theyclinical advantages and main challenges for in vivo implantation. Tattoo functionalizationprovides a minimally invasive, reversible, biocompatible, real-time sensing with long-termpermanence 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 therecords to the doctor.

  • Journal article
    Ali M, Alam F, Ahmed I, AlQattan B, Yetisen AK, Butt Het al., 2021,

    3D printing of Fresnel lenses with wavelength selective tinted materials

    , Additive Manufacturing, Vol: 47, Pages: 1-11, ISSN: 2214-8604

    Well-established manufacturing processes for Fresnel lenses fabrication are available. However, adapting additive manufacturing is often desirable, as it opens a plethora of design and manufacturing possibilities. The current study aims to demonstrate the feasibility of 3D printing of optical devices such as Fresnel lenses with customized designs and optical properties. The study investigates the 3D modeling of Fresnel lenses with a computer-aided design tool and selecting suitable materials for the 3D printing process. The process parameters of digital light processing 3D printing were tailored to get the desired features with accurate geometric dimensions in the final printed lenses. The suitable ink colors were introduced into the liquid monomer resin to 3D print tinted Fresnel lenses having the potential in selective color filtering, focusing and sensing applications. The focusing ability of the printed lenses was characterized by using customized optical setups with the help of relative power intensity and transmission spectra measurements. Surface wettability was analyzed using contact angle measurement that revealed the hydrophilic nature of lens material. 3D printed Fresnel lenses are promising optical elements, offering custom-built optical designs, tailored tinted materials and they have the potential to be integrated with both active and passive optical sensors for sensing applications.

  • Journal article
    Deshmukh KP, Dabbagh SR, Jiang N, Tasoglu S, Yetisen AKet al., 2021,

    Recent technological developments in the diagnosis and treatment of cerebral edema

    , Advanced NanoBiomed Research, Vol: 1, ISSN: 2699-9307

    Latest technological advancements in neurocritical care have translated to improved clinical outcomes and have paved the way for the effective diagnosis and treatment of cerebral edema. Effective management of cerebral edema has the potential to provide a personalized treatment by obtaining the complete pathophysiological information of the patient. The aims of this review are to inform the reader about the research and development in this field in the past decade as well as the materialization of scientific literature through patents. There is a growing interest in multimodal monitoring of the diseased brain as it provides a necessary means to implement effective intervention strategies. Although there is a gradual shift toward the adoption of noninvasive devices for research purposes, their clinical applications are hindered by their inaccuracies. However, the inherent risk of complication and high costs of implementation challenge the status quo. The role of neuroprotectants is explored and the combination of neurodiagnostic and neuroprotective approaches is proposed. Finally, the impacts of the current state of global affairs are discussed and it is predicted that the rising number of traumatic brain injury patents will inevitably translate to improvements in technologies to effectively address cerebral edema.

  • Journal article
    Wu Y, Szymanska M, Hu Y, Fazal MI, Jiang N, Yetisen AK, Cordeiro MFet al., 2021,

    Measures of disease activity in glaucoma

    , Biosensors and Bioelectronics, Vol: 196, ISSN: 0956-5663

    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.

  • Journal article
    Moreddu R, Mahmoodi N, Kassanos P, Vigolo D, Mendes PM, Yetisen AKet al., 2021,

    Stretchable nanostructures as optomechanical strain sensors for ophthalmic applications

    , ACS APPLIED POLYMER MATERIALS, Vol: 3, Pages: 5416-5424, ISSN: 2637-6105

    The intraocular pressure (IOP) is a physiological parameter that plays a crucial role in preventing, diagnosing, and treating ocular diseases. For example, lowering the IOP is the primary focus of glaucoma management. However, IOP is a widely varying parameter, and one-off measurements are prompt to errors. Developing portable solutions for continuous monitoring the IOP is a critical goal in ophthalmology. Here, stretchable nanostructures were developed as strain-tunable diffraction gratings and integrated into a contact lens. They exhibited a limit of detection (LOD) <2 mmHg and a linear response in the range of interest (15–35 mmHg). Nanopatterns were characterized under monochromatic laser sources and further integrated into a soft contact lens. A smartphone readout method based on preferentially reflected colors was proposed to pave the way toward smartphone-based ocular health monitoring.

  • Journal article
    Elsherif M, Alam F, Salih AE, AlQattan B, Yetisen AK, Butt Het al., 2021,

    Wearable bifocal contact lens for continual glucose monitoring integrated with smartphone readers

    , Small, Vol: 17, ISSN: 1613-6810

    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.

  • Journal article
    Shi Y, Jiang N, Bikkannavar P, Cordeiro MF, Yetisen AKet al., 2021,

    Ophthalmic sensing technologies for ocular disease diagnostics

    , Analyst, Vol: 146, Pages: 6416-6444, ISSN: 0003-2654

    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.

  • Journal article
    Balbach S, Jiang N, Moreddu R, Dong X, Kurz W, Wang C, Dong J, Yin Y, Butt H, Brischwein M, Hayden O, Jakobi M, Tasoglu S, Koch A, Yetisen AKet al., 2021,

    Smartphone-based colorimetric detection system for portable health tracking

    , Analytical Methods: advancing methods and applications, Vol: 13, Pages: 4361-4369, ISSN: 1759-9660

    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.

  • Journal article
    Jiang N, Flyax S, Kurz W, Jakobi M, Tasoglu S, Koch AW, Yetisen AKet al., 2021,

    Intracranial sensors for continuous monitoring of neurophysiology

    , Advanced Materials Technologies, Vol: 6, ISSN: 2365-709X

    Monitoring physiological parameters in the brain is important to identify early signs of secondary brain injuries. A variety of different intracranial sensors enable continuous monitoring of important brain parameters in clinical applications. However, many of the clinically approved and established technologies show drawbacks in zero-drift properties, accuracy and magnet resonance imaging (MRI) compatibility. This review gives a comparative overview of the established technologies and provides an outlook on fiber-optic sensors (FOS) with potential use in future intracranial monitoring applications. Neurophysiological parameters recorded by bioelectrical signals include intracranial pressure (ICP), brain temperature, brain tissue oxygenation, cerebral blood flow, and cerebral metabolism. The comparison of ICP sensors revealed that piezoresistive strain gauge sensors provide the highest accuracy and the smallest zero-drift in clinical catheters. Fiber-optic pressure sensors show a potential to be used in future intracranial applications. Thermistors and thermocouples prove to be reliable for temperature measurement in intracranial catheters, but have limited MRI compatibility. FOS show potential to be used in future intracranial catheters for temperature and oxygen measurement, as they provide higher accuracy and a better response time. Microdialysis catheters, in combination with new automated electrochemical and optical analyzers, provide the possibility of routine metabolism monitoring in clinics.

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