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  • 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.

  • Journal article
    Yu Z, Jiang N, Kazarian SG, Tasoglu S, Yetisen AKet al., 2021,

    Optical sensors for continuous glucose monitoring

    , Progress in Biomedical Engineering, Vol: 3, Pages: 022004-022004

    For decades, diabetes mellitus has been of wide concern with its high global prevalence, resulting in increasing social and financial burdens for individuals, clinical systems and governments. Continuous glucose monitoring (CGM) has become a popular alternative to the portable finger-prick glucometers available in the market for the convenience of diabetic patients. Hence, it has attracted much interest in various glucose sensing technologies to develop novel glucose sensors with better performance and longer lifetime, especially non-invasive or minimally invasive glucose sensing. Effort has also been put into finding biocompatible materials for implantable applications to achieve effective in vivo CGM. Here, we review the state-of-the-art researches in the field of CGM. The currently commercially available CGM technologies have been analyzed and a summary is provided of the potential types of recently researched non-invasive glucose monitors. Furthermore, the challenges and advances towards implantable applications have also been introduced and discussed, especially the novel biocompatible hydrogel aimed at minimizing the adverse impact from foreign-body response. In addition, a large variety of promising glucose-sensing technologies under research have been reviewed, from traditional electrochemical-based glucose sensors to novel optical and other electrical glucose sensors. The recent development and achievement of the reviewed glucose sensing technologies are discussed, together with the market analysis in terms of the statistical data for the newly published patents in the related field. Thus, the promising direction for future work in this field could be concluded.

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

    Gold nanocomposite contact Lenses for color blindness management

    , ACS Nano, Vol: 15, Pages: 4870-4880, ISSN: 1936-0851

    Color vision deficiency (CVD) is an ocular congenital disorder that affects 8% of males and 0.5% of females. The most prevalent form of color vision deficiency (color blindness) affects protans and deutans and is more commonly known as “red–green color blindness”. Since there is no cure for this disorder, CVD patients opt for wearables that aid in enhancing their color perception. The most common wearable used by CVD patients is a form of tinted glass/lens. Those glasses filter out the problematic wavelengths (540–580 nm) for the red–green CVD patients using organic dyes. However, few studies have addressed the fabrication of contact lenses for color vision deficiency, and several problems related to their effectiveness and toxicity were reported. In this study, gold nanoparticles are integrated into contact lens material, thus forming nanocomposite contact lenses targeted for red–green CVD application. Three distinct sets of nanoparticles were characterized and incorporated with the hydrogel material of the lenses (pHEMA), and their resulting optical and material properties were assessed. The transmission spectra of the developed nanocomposite lenses were analogous to those of the commercial CVD wearables, and their water retention and wettability capabilities were superior to those in some of the commercially available contact lenses used for cosmetic/vision correction purposes. Hence, this work demonstrates the potential of gold nanocomposite lenses in CVD management and, more generally, color filtering applications.

  • Journal article
    Salih A, Elsherif M, Ali M, Moreddu R, Jones D, Alqattan B, Alam F, Yetisen AK, Butt Het al.,

    Light Diffractive Microstructures as a Platform for Polymers Wettability Control

    , ACS Omega, ISSN: 2470-1343
  • Journal article
    Liu Q, Ying G, Jiang N, Yetisen AK, Yao D, Xie X, Fan Y, Liu Het al., 2021,

    Three-dimensional silk fibroin microsphere-nanofiber scaffolds for vascular tissue engineering

    , Medicine in Novel Technology and Devices, Vol: 9, Pages: 100051-100051, ISSN: 2590-0935
  • Journal article
    AlQattan B, Doocey J, Ali M, Ahmed I, Salih AE, Alam F, Bajgrowicz-Cieslak M, Yetisen AK, Elsherif M, Butt Het al., 2021,

    Direct printing of nanostructured holograms on consumable substrates

    , ACS Nano, Vol: 15, Pages: 2340-2349, ISSN: 1936-0851

    Direct texturing of nanostructures on consumable substrates and products is a challenge because of incompatible ingredients and materials’ properties. Here, we developed a direct laser-based method to print nanostructured holograms on dried films of consumable corn syrup solutions. A holographic laser (λ = 1050 nm) interference system was used to construct the nanostructures of the holograms on food for rainbow effects. The relationship between wavelength and periodicity contributed to the changing diffraction angle through the change of the refractive index (1.642). Increasing the sugar concentration (25–175 mg) in the syrup increased the diffraction efficiency of these holograms. The added amount of sugar in the composition increased the refractive index (7%) and decreased the light absorption (12.9%), which influenced the change of diffraction angle by 4.4°. The surface holograms displayed wideband visual diffraction of light extending from violet to red wavelengths. These holograms on edible materials can be imprinted onto commercial food products for adding aesthetic value and controlling perception.

  • Journal article
    Sarabi MR, Jiang N, Ozturk E, Yetisen AK, Tasoglu Set al., 2021,

    Biomedical optical fibers

    , Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 21, Pages: 627-640, ISSN: 1473-0189

    Optical fibers with the ability to propagate and transfer data via optical signals have been used for decades in medicine. Biomaterials featuring the properties of softness, biocompatibility, and biodegradability enable the introduction of optical fibers' uses in biomedical engineering applications such as medical implants and health monitoring systems. Here, we review the emerging medical and health-field applications of optical fibers, illustrating the new wave for the fabrication of implantable devices, wearable sensors, and photodetection and therapy setups. A glimpse of fabrication methods is also provided, with the introduction of 3D printing as an emerging fabrication technology. The use of artificial intelligence for solving issues such as data analysis and outcome prediction is also discussed, paving the way for the new optical treatments for human health.

  • Journal article
    Bilirgen AC, Toker M, Odabas S, Yetisen AK, Garipcan B, Tasoglu Set al., 2021,

    Plant-based scaffolds in tissue engineering

    , ACS Biomaterials Science and Engineering, Vol: 7, Pages: 926-938, ISSN: 2373-9878

    A wide range of platforms has been developed for 3D culture of cells in vitro to aggregate and align cells to resemble in vivo conditions in order to enhance communication between cells and promote differentiation. The cellulose skeleton of plant tissue can serve as an attainable scaffold for mammalian cells after decellularization, which is advantageous when compared to synthetic polymers or animal-derived scaffolds. Adjustable variables to modify the physical and biochemical properties of the resulting scaffolds include the protocol for the sodium dodecyl sulfate (SDS)-based decellularization procedure, surface coatings for cell attachment, plant type for decellularization, differentiation media, and integrity and shape of the substrate. These tunable cellulose platforms can host a wide range of mammalian cell types from muscle to bone cells, as well as malignancies. Here, fundamentals and applications of decellularized plant-based scaffolds are discussed. These biocompatible, naturally perfused, tunable, and easily prepared decellularized scaffolds may allow eco-friendly manufacturing frameworks for application in tissue engineering and organs-on-a-chip.

  • Journal article
    Jiang N, Davies S, Jiao Y, Blyth J, Butt H, Montelongo Y, Yetisen AKet al., 2021,

    Doubly photopolymerized holographic sensors

    , ACS Sensors, Vol: 6, Pages: 915-924, ISSN: 2379-3694

    Holographic sensors are two-dimensional (2D) photonic crystals that diffract narrow-band light in the visible spectrum to quantify analytes in aqueous solutions. Here, a holographic fabrication setup was developed to produce holographic sensors through a doubly polymerization system of a poly-2-hydroxyethyl methacrylate hydrogel film using a pulsed Nd:YAG laser (λ = 355 nm, 5 ns, 100 mJ). Wavelength shifts of holographic Bragg peak in response to alcohol species (0–100 vol %) were characterized. Diffraction spectra showed that the holographic sensors could be used for short-chain alcohols at concentrations up to 60 vol %. The reversibility of the sensor was demonstrated, exhibiting a response time of 7.5 min for signal saturation. After 30 cycles, the Bragg peak and color remained the same in both 20 and 60 vol %. The fabrication parameters were simulated in MATLAB using a 2D finite-difference time-domain algorithm to model the interference pattern and energy flux profile of laser beam recording in the hydrogel medium. This work demonstrates a particle-free holographic sensor that offers continuous, reversible, and rapid colorimetric readouts for the real-time quantification of alcohols.

  • Journal article
    Alam F, Elsherif M, AiQattan B, Salih A, Lee SM, Yetisen AK, Park S, Butt Het al., 2021,

    3D printed contact lenses

    , ACS Biomaterials Science and Engineering, Vol: 7, Pages: 794-803, ISSN: 2373-9878

    Although the manufacturing processes of contact lenses are well established, the use of additive manufacturing for their fabrication opens many new possibilities to explore. The current study demonstrates the fabrication of personalized smart contract lenses utilizing additive manufacturing. The study includes 3-dimensional (3D) modeling of contact lenses with the assistance of a computer aided designing tool based on standard commercial contact lens dimension, followed by the selection of the suitable materials and 3D printing of contact lenses. The 3D printing parameters were optimized to achieve the desired lens geometries, and a post processing treatment was performed to achieve a smooth surface finish. The study also presents functionalized contact lenses with built-in sensing abilities by utilizing microchannels at the contact lens edges. Tinted contact lenses were printed and nanopatterns were textured onto the contact lens surfaces through holographic laser ablation. 3D printed contact lenses have advantages over conventional contact lenses, offering customized ophthalmic devices and the capability to integrate with optical sensors for diagnostics.

  • Journal article
    Dabbagh SR, Becher E, Ghaderinezhad F, Havlucu H, Ozcan O, Ozkan M, Yetisen AK, Tasoglu Set al., 2021,

    Increasing the packing density of assays in paper-based microfluidic devices

    , Biomicrofluidics, Vol: 15, ISSN: 1932-1058

    Paper-based devices have a wide range of applications in point-of-care diagnostics, environmental analysis, and food monitoring. Paper-based devices can be deployed to resource-limited countries and remote settings in developed countries. Paper-based point-of-care devices can provide access to diagnostic assays without significant user training to perform the tests accurately and timely. The market penetration of paper-based assays requires decreased device fabrication costs, including larger packing density of assays (i.e., closely packed features) and minimization of assay reagents. In this review, we discuss fabrication methods that allow for increasing packing density and generating closely packed features in paper-based devices. To ensure that the paper-based device is low-cost, advanced fabrication methods have been developed for the mass production of closely packed assays. These emerging methods will enable minimizing the volume of required samples (e.g., liquid biopsies) and reagents in paper-based microfluidic devices

  • Journal article
    Dabbagh SR, Sarabi MR, Rahbarghazi R, Sokullu E, Yetisen AK, Tasoglu Set al., 2021,

    3D-printed microneedles in biomedical applications

    , iScience, Vol: 24, ISSN: 2589-0042

    Conventional needle technologies can be advanced with emerging nano- and micro-fabrication methods to fabricate microneedles. Nano-/micro-fabricated microneedles seek to mitigate penetration pain and tissue damage, as well as providing accurately controlled robust channels for administrating bioagents and collecting body fluids. Here, design and 3D printing strategies of microneedles are discussed with emerging applications in biomedical devices and healthcare technologies. 3D printing offers customization, cost-efficiency, a rapid turnaround time between design iterations, and enhanced accessibility. Increasing the printing resolution, the accuracy of the features, and the accessibility of low-cost raw printing materials have empowered 3D printing to be utilized for the fabrication of microneedle platforms. The development of 3D-printed microneedles has enabled the evolution of pain-free controlled release drug delivery systems, devices for extracting fluids from the cutaneous tissue, biosignal acquisition, and point-of-care diagnostic devices in personalized medicine.

  • Journal article
    Dong X, Li H, Jiang Z, Gruenleitner T, Gueler I, Dong J, Wang K, Koehler MH, Jakobi M, Menze BH, Yetisen AK, Sharp ID, Stier A, Finley JJ, Koch AWet al., 2021,

    3D deep learning enables accurate layer mapping of 2D materials

    , ACS Nano, Vol: 15, Pages: 3139-3151, ISSN: 1936-0851

    Layered, two-dimensional (2D) materials are promising for next-generation photonics devices. Typically, the thickness of mechanically cleaved flakes and chemical vapor deposited thin films is distributed randomly over a large area, where accurate identification of atomic layer numbers is time-consuming. Hyperspectral imaging microscopy yields spectral information that can be used to distinguish the spectral differences of varying thickness specimens. However, its spatial resolution is relatively low due to the spectral imaging nature. In this work, we present a 3D deep learning solution called DALM (deep-learning-enabled atomic layer mapping) to merge hyperspectral reflection images (high spectral resolution) and RGB images (high spatial resolution) for the identification and segmentation of MoS2 flakes with mono-, bi-, tri-, and multilayer thicknesses. DALM is trained on a small set of labeled images, automatically predicts layer distributions and segments individual layers with high accuracy, and shows robustness to illumination and contrast variations. Further, we show its advantageous performance over the state-of-the-art model that is solely based on RGB microscope images. This AI-supported technique with high speed, spatial resolution, and accuracy allows for reliable computer-aided identification of atomically thin materials.

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

    Near-infrared-II nanoparticles for cancer imaging of immune checkpoint programmed death-ligand 1 and photodynamic/immune therapy

    , ACS Nano, Vol: 15, Pages: 515-525, ISSN: 1936-0851

    Development of second near-infrared (NIR-II) nanoparticles (NPs) with high biocompatibility, low toxicity, and high singlet oxygen quantum yield (ΦΔ) to prevent tumor recurrence is highly desirable in molecular imaging and photodynamic/immune combination therapy. Here, theranostic photosensitizer BODIPY (BDP)-I-N-anti-PD-L1 NPs were developed by encapsulating the photosensitizer BDP-I-N with amphipathic poly(styrene-co-chloromethylstyrene)-graft-poly(ethylene glycol) nanocarriers through self-assembly functionalization with programmed cell death-ligand 1 (PD-L1) monoclonal antibody. These NPs exhibit highly intensive luminescence in the NIR-II window (1000–1700 nm) to real-time imaging of immune checkpoint PD-L1, high singlet oxygen quantum yield (ΦΔ = 73%), and an eliminating effect of primary cancers. The NPs also allow for profiling PD-L1 expression as well as accumulating in MC38 tumor and enabling molecular imaging in vivo. Upon an 808 nm laser excitation, the targeted NPs produce an emission wavelength above 1200 nm to image a tumor to a normal tissue signal ratio (T/NT) at an approximate value of 14.1. Moreover, the MC38 tumors in mice are eliminated by combining photodynamic therapy and immunotherapy within 30 days, with no tumor recurrence within a period of 40 days. In addition, the tumors do not grow in the rechallenged mice within 7 days of inoculation. Such a strategy shows a durable immune memory effect against tumor rechallenging without toxic side effects to major organs.

  • Journal article
    Ates HC, Yetisen AK, Guder F, Dincer Cet al., 2021,

    Wearable devices for the detection of COVID-19

    , NATURE ELECTRONICS, Vol: 4, Pages: 13-14, ISSN: 2520-1131
  • Journal article
    Dabbagh SR, Rabbi F, Dogan Z, Yetisen AK, Tasoglu Set al., 2020,

    Machine learning-enabled multiplexed microfluidic sensors

    , Biomicrofluidics, Vol: 14, ISSN: 1932-1058

    High-throughput, cost-effective, and portable devices can enhance the performance of point-of-care tests. Such devices are able to acquire images from samples at a high rate in combination with microfluidic chips in point-of-care applications. However, interpreting and analyzing the large amount of acquired data is not only a labor-intensive and time-consuming process, but also prone to the bias of the user and low accuracy. Integrating machine learning (ML) with the image acquisition capability of smartphones as well as increasing computing power could address the need for high-throughput, accurate, and automatized detection, data processing, and quantification of results. Here, ML-supported diagnostic technologies are presented. These technologies include quantification of colorimetric tests, classification of biological samples (cells and sperms), soft sensors, assay type detection, and recognition of the fluid properties. Challenges regarding the implementation of ML methods, including the required number of data points, image acquisition prerequisites, and execution of data-limited experiments are also discussed.

  • Journal article
    Elsherif M, Salih AE, Yetisen AK, Butt Het al., 2020,

    Contact lenses for color vision deficiency

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

    Color blindness or color vision deficiency (CVD) affects around 4.5% of the population in Europe. There have been several attempts to assist color-blind individuals using color filter glasses. Here, contact lenses are developed to assist individuals suffering from color blindness. Two dyes (Atto 488 and 565) that provide the desired absorption wavelength ranges are selected to be immobilized in soft contact lenses. The chosen dyes have absorption bands in wavelength ranges of 480–500 and 550–580 nm. Both dyes are individually immobilized in contact lenses, and over 95% of the light in the undesired ranges are blocked. The dyes do not diffuse out from lenses in artificial tears and contact lens storage solution. Performances of the developed contact lenses are compared to commercial color-blind glasses. The contact lenses are tested in color vision deficient patients using Ishihara test. Participants indicate enhancement in the visibility of the colors and their contrast in a color rich environment. The proposed contact lenses show enhanced results as compared to commercial color-blind glasses in indoors and achieved similar outcomes outdoors.

  • Journal article
    Chen Y, Zhang S, Cui Q, Ni J, Wang X, Cheng X, Alem H, Tebon P, Xu C, Guo C, Nasiri R, Moreddu R, Yetisen AK, Ahadian S, Ashammakhi N, Emaminejad S, Jucaud V, Dokmeci MR, Khademhosseini Aet al., 2020,

    Microengineered poly(HEMA) hydrogels for wearable contact lens biosensing

    , Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 20, Pages: 4205-4214, ISSN: 1473-0189

    Microchannels in hydrogels play an essential role in enabling a smart contact lens. However, microchannels have rarely been created in commercial hydrogel contact lenses due to their sensitivity to conventional microfabrication techniques. Here, we report the fabrication of microchannels in poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels that are used in commercial contact lenses with a three-dimensional (3D) printed mold. We investigated the corresponding capillary flow behaviors in these microchannels. We observed different capillary flow regimes in these microchannels, depending on their hydration level. In particular, we found that a peristaltic pressure could reinstate flow in a dehydrated channel, indicating that the motion of eye-blinking may help tears flow in a microchannel-containing contact lens. Colorimetric pH and electrochemical Na+ sensing capabilities were demonstrated in these microchannels. This work paves the way for the development of microengineered poly(HEMA) hydrogels for various biomedical applications such as eye-care and wearable biosensing.

  • Journal article
    Moreddu R, Elsherif M, Adams H, Moschou D, Cordeiro MF, Wolffsohn JS, Vigolo D, Butt H, Cooper JM, Yetisen AKet al., 2020,

    Integration of paper microfluidic sensors into contact lenses for tear fluid analysis

    , Lab on a Chip: miniaturisation for chemistry, physics, biology, materials science and bioengineering, Vol: 20, Pages: 3970-3979, ISSN: 1473-0189

    In this article, using the integration of paper microfluidics within laser-inscribed commercial contact lenses, we demonstrate the multiplexed detection of clinically relevant analytes including hydrogen ions, proteins, glucose, nitrites and L-ascorbic acid, all sampled directly from model tears. In vitro measurements involved the optimization of colorimetric assays, with readouts collected, stored and analyzed using a bespoke Tears Diagnostics smartphone application prototype. We demonstrate the potential of the device to perform discrete measurements either for medical diagnosis or disease screening in the clinic or at the point-of-care (PoC), with future applications including monitoring of ocular infections, uveitis, diabetes, keratopathies and assessing oxidative stress.

  • Journal article
    Akram MS, Pery N, Butler L, Shafiq MI, Batool N, Rehman MFU, Grahame-Dunn LG, Yetisen AKet al., 2020,

    Challenges for biosimilars: focus on rheumatoid arthritis

    , Critical Reviews in Biotechnology, Vol: 41, Pages: 121-153, ISSN: 0738-8551

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

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