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

    Magnetic levitation for space exploration.

    , Trends Biotechnol, Vol: 40, Pages: 915-917

    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.

  • Journal article
    Davies S, Hu Y, Jiang N, Montelongo Y, Richardson A, Blyth J, Yetisena AKet al., 2022,

    Reversible photonic hydrogel sensors via holographic interference lithography

    , BIOSENSORS & BIOELECTRONICS, Vol: 207, ISSN: 0956-5663
  • 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, 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
    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
    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
    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
    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.

  • Journal article
    Moreddu R, Nasrollahi V, Kassanos P, Dimov S, Vigolo D, Yetisen AKet al., 2021,

    Lab-on-a-contact lens platforms fabricated by multi-axis femtosecond laser ablation

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

    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.

  • Journal article
    Alseed MM, Syed H, Onbasli MC, Yetisen AK, Tasoglu Set al., 2021,

    Design and adoption of low-cost point-of-care diagnostic devices: Syrian case

    , Micromachines, Vol: 12, Pages: 1-11, ISSN: 2072-666X

    Civil wars produce immense humanitarian crises, causing millions of individuals to seek refuge in other countries. The rate of disease prevalence has inclined among the refugees, increasing the cost of healthcare. Complex medical conditions and high numbers of patients at healthcare centers overwhelm the healthcare system and delay diagnosis and treatment. Point-of-care (PoC) testing can provide efficient solutions to high equipment cost, late diagnosis, and low accessibility of healthcare services. However, the development of PoC devices in developing countries is challenged by several barriers. Such PoC devices may not be adopted due to prejudices about new technologies and the need for special training to use some of these devices. Here, we investigated the concerns of end users regarding PoC devices by surveying healthcare workers and doctors. The tendency to adopt PoC device changes is based on demographic factors such as work sector, education, and technology experience. The most apparent concern about PoC devices was issues regarding low accuracy, according to the surveyed clinicians.

  • Journal article
    Dong X, Yetisen AK, Dong J, Wang K, Kienle P, Jakobi M, Koch AWet al., 2021,

    Hyperspectral fingerprints for atomic layer mapping of two-dimensional materials with single-layer accuracy

    , The Journal of Physical Chemistry C: Energy Conversion and Storage, Optical and Electronic Devices, Interfaces, Nanomaterials, and Hard Matter, Vol: 125, Pages: 16583-16590, ISSN: 1932-7447

    Hyperspectral imaging microscopy with multivariate analysis is an efficient technique for rapid and accurate atomic layer mapping of two-dimensional materials, of which the thickness distributes randomly over a large area. In this work, the identification accuracy of a dual-illumination hyperspectral imaging microscope was systematically studied for mapping mono-, bi-, tri-, and few-layer MoS2 flakes fabricated by the chemical vapor deposition method. Hyperspectral fingerprints of MoS2 flakes were extracted and implemented to identify distinct flakes of new samples for cross-validation and generalizability analysis with single-layer accuracy. Mechanically exfoliated WSe2 flakes on the SiO2/Si substrate with small sizes were identified by multiline laser illumination. To reduce the computational consumption when processing hyperspectral data sets with high dimensions, the influence of the number of hyperspectral channels on the identification performance was investigated using hyperspectral fingerprints of mono- and bilayer flakes with high spectral similarity.

  • Journal article
    Montelongo A, Becker JL, Roman R, de Oliveira EB, Umpierre RN, Goncalves MR, Silva R, Doniec K, Yetisen AKet al., 2021,

    The management of COVID-19 cases through telemedicine in Brazil

    , PLoS One, Vol: 16, Pages: 1-14, ISSN: 1932-6203

    In Dec 2020 Brazil became one of the worldwide epicenters of the COVID-19 pandemic with more than 7.2M reported cases. Brazil has a large territory with unequal distribution of healthcare resources including physicians. Resource limitation has been one of the main factors hampering Brazil’s response to the COVID-19 crisis. Telemedicine has been an effective approach for COVID-19 management as it allows to reduce the risk of cross-contamination and provides support to remote rural locations. Here we present the analyses of teleconsultations from a countrywide telemedicine service (TelessáudeRS-UFRGS, TRS), that provides physician-to-physician remote support during the COVID-19 pandemic in Brazil. We performed a descriptive analysis of the teleconsultation incoming calls and a text analysis from the call transcripts. Our findings indicate that TRS teleconsultations in Brazil experienced an exponential increment of 802.% during a period of 6 days, after the first death due to COVID-19 was reported. However, the number of teleconsultations cases decreased over time, despite the number of reported COVID-19 cases continuously increasing. The results also showed that physicians in low-income municipalities, based on GDP per capita, are less likely to consult the telemedicine service despite facing higher rates of COVID-19 cases. The text analysis of call transcripts from medical teleconsultations showed that the main concern of physicians were “asymptomatic” patients. We suggest an immediate reinforcement of telehealth services in the regions of lower income as a strategy to support COVID-19 management.

  • Journal article
    Savariraj AD, Salih A, Alam F, Elsherif M, AlQattan B, Khan AA, Yetisen AK, Butt Het al., 2021,

    Ophthalmic sensors and drug delivery

    , ACS Sensors, Vol: 6, Pages: 2046-2076, ISSN: 2379-3694

    Advances in multifunctional materials and technologies have allowed contact lenses to serve as wearable devices for continuous monitoring of physiological parameters and delivering drugs for ocular diseases. Since the tear fluids comprise a library of biomarkers, direct measurement of different parameters such as concentration of glucose, urea, proteins, nitrite, and chloride ions, intraocular pressure (IOP), corneal temperature, and pH can be carried out non-invasively using contact lens sensors. Microfluidic contact lens sensor based colorimetric sensing and liquid control mechanisms enable the wearers to perform self-examinations at home using smartphones. Furthermore, drug-laden contact lenses have emerged as delivery platforms using a low dosage of drugs with extended residence time and increased ocular bioavailability. This review provides an overview of contact lenses for ocular diagnostics and drug delivery applications. The designs, working principles, and sensing mechanisms of sensors and drug delivery systems are reviewed. The potential applications of contact lenses in point-of-care diagnostics and personalized medicine, along with the significance of integrating multiplexed sensing units together with drug delivery systems, have also been discussed.

  • Report
    Brophy K, Davies S, Olenik S, Cotur Y, Ming D, Van Zalk N, O'Hare D, Guder F, Yetisen AKet al., 2021,

    The future of wearable technologies

    , Briefing Paper
  • Journal article
    Jiang N, Tansukawat ND, Gonzalez-Macia L, Ates HC, Dincer C, Guder F, Tasoglu S, Yetisen AKet al., 2021,

    Low-cost optical assays for point-of-care diagnosis in resource-limited settings

    , ACS Sensors, Vol: 6, Pages: 2108-2124, ISSN: 2379-3694

    Readily deployable, low-cost point-of-care medical devices such as lateral flow assays (LFAs), microfluidic paper-based analytical devices (μPADs), and microfluidic thread-based analytical devices (μTADs) are urgently needed in resource-poor settings. Governed by the ASSURED criteria (affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and deliverability) set by the World Health Organization, these reliable platforms can screen a myriad of chemical and biological analytes including viruses, bacteria, proteins, electrolytes, and narcotics. The Ebola epidemic in 2014 and the ongoing pandemic of SARS-CoV-2 have exemplified the ever-increasing importance of timely diagnostics to limit the spread of diseases. This review provides a comprehensive survey of LFAs, μPADs, and μTADs that can be deployed in resource-limited settings. The subsequent commercialization of these technologies will benefit the public health, especially in areas where access to healthcare is limited.

  • Journal article
    Sarabi MR, Ahmadpour A, Yetisen AK, Tasoglu Set al., 2021,

    Finger-actuated microneedle array for sampling body fluids

    , Applied Sciences-Basel, Vol: 11, ISSN: 2076-3417

    The application of microneedles (MNs) for minimally invasive biological fluid sampling is rapidly emerging, offering a user-friendly approach with decreased insertion pain and less harm to the tissues compared to conventional needles. Here, a finger-powered microneedle array (MNA) integrated with a microfluidic chip was conceptualized to extract body fluid samples. Actuated by finger pressure, the microfluidic device enables an efficient approach for the user to collect their own body fluids in a simple and fast manner without the requirement for a healthcare worker. The processes for extracting human blood and interstitial fluid (ISF) from the body and the flow across the device, estimating the amount of the extracted fluid, were simulated. The design in this work can be utilized for the minimally invasive personalized medical equipment offering a simple usage procedure

  • Journal article
    Zhang Y, Jiang N, Yetisen AK, 2021,

    Brain neurochemical monitoring

    , Biosensors and Bioelectronics, Vol: 189, ISSN: 0956-5663

    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.

  • Journal article
    Liu Q, Tian J, Tian Y, Sun Q, Sun D, Liu D, Wang F, Xu H, Ying G, Wang J, Yetisen AK, Jiang Net al., 2021,

    Thiophene donor for NIR-II fluorescence imaging-guided photothermal/photodynamic/chemo combination therapy

    , Acta Biomaterialia, Vol: 127, Pages: 287-297, ISSN: 1742-7061

    Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared (NIR-I) window. However, their applications in the second near-infrared (NIR-II) window are still limited primarily due to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) is created as a molecularly engineered thiophene donor unit with high QYs to the redshift. Thiophene insertion initiates substantial redshifts of the absorbance as compared to its counterparts in which iodine is introduced. The fluorescent molecule can be triggered by an NIR laser with a single wavelength, thereby producing emission in the NIR-II windows. Single NIR laser-triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and the chemotherapeutic drug docetaxel (DTX) by using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen QY (ΦΔ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics. After intravenous administration of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor showed a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the combination of photodynamic therapy (PDT) and photothermic therapy (PTT).

  • Journal article
    Yin Y, Wang W, Shao Q, Li B, Yu D, Zhou X, Parajuli J, Xu H, Qiu T, Yetisen AK, Jiang Net al., 2021,

    Pentapeptide IKVAV-engineered hydrogels for neural stem cell attachment

    , Biomaterials Science, Vol: 9, Pages: 2887-2892, ISSN: 2047-4830

    Spinal cord injury remains irreversible with current treatment paradigms, due to the inability to rebuild the regenerative environment for neurons after injury. Neural tissue engineering that encapsulates the neural stem/progenitor cells within an artificial scaffold provides a possibility to regenerate neurons for spinal cord injury repair. The attachment and survival of these neural cells usually require similar microenvironments to the extracellular matrix for support. Here, a three-dimensional pentapeptide IKVAV-functionalized poly(lactide ethylene oxide fumarate) (PLEOF) hydrogel is developed. In vitro tests demonstrate that the IKVAV-PLEOF hydrogels are biodegradable and hemo-biocompatible. This IKVAV-PLEOF hydrogel is shown to support neural stem cell attachment, growth, proliferation, and differentiation. Additionally, the neural stem cells could be readily formed as spheroids that subsequently encapsulated, attached, and proliferated within the three-dimensional hydrogel constructs. Additionally, an in vivo test confirms the biodegradability and biocompatibility of the IKVAV-PLEOF hydrogels revealing that the hydrogels biodegrade, new blood vessels form, and few inflammatory responses are observed after 4-week implantation. The neural stem cell spheroid-laden hydrogels may have further implications in spinal cord injury regenerative and brain repair in neural tissue engineering.

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