Добірка наукової літератури з теми "Point-of-care devices"

The review presents the classification of point-of-care (POC) devices, and discusses the main characteristics of the devices and the requirements for them. The differences between the POC testing method and the laboratory method of analysis are considered. Examples of devices that fit the definition of POC for diagnosing infectious diseases are given.

This review highlights key development of point-of-care diagnostics for detecting DNA, proteins, bacteria/pathogens, and other species in samples that can be used for diagnosing disease and detecting harmful chemical and biochemical contaminants in samples. These technologies have great promise for improving the quality of life for those in the developing world.

AbstractDuring pregnancy and puerperium, there are pronounced hemostatic changes characterized by increased coagulability and decreased fibrinolysis. In addition, hemostasis can change dramatically during obstetric complications. Several reports have described substandard management of hemostatic defects in this setting and state the need for guidelines and better care. Point-of-care devices can assess hemostatic status and are especially suitable in perioperative settings. Using point-of-care devices, no time is required for transportation, allowing faster availability of results and providing potential for better care of the patient. This article will demonstrate the use of a viscoelastic method in six different patients; five with impaired hemostasis, and where the use of viscoelastic method contributes or should have contributed to better care. The cases represent patients with normal delivery; postpartum hemorrhage (PPH); PPH with low fibrinogen; placental abruption; preeclampsia with hemolysis, elevated liver enzymes, low platelet count syndrome; and finally, one patient with sepsis. This article also shows the need for good practices and good supervision to implement the devices in patient care.

Continued development of mobile technology now allows access to information at the point-of-care. This study was conducted to evaluate the use of one such tool on a mobile device, from the carer perspective. Caregivers across 12 aged-care facilities were supplied mobile devices to access a Picture Care Plan (PCP), a specific tool designed around the role of the personal carer. An anonymous questionnaire was subsequently completed by 85 carers with questions relating to participants’ experience. Perceived helpfulness of the PCP at the point-of-care was high (87%). A significant number of participants believed the use of the PCP increased resident safety and quality of care (76%). Practical components related to the carrying of the device, network speed and the requirement to maintain communication with senior members of staff to ascertain updates were also expressed by participants. Findings suggest that staff are receptive to adoption of mobile devices to access care directives at the point-of-care and that the technology is useful.

This article provides an overview of the current use of point-of-care testing (POCT) and its utility for patients’ self-management of chronic disease states. Pharmacists utilize POCT to provide rapid laboratory diagnostic results as a monitoring tool in the management of their patients and in order to improve medication outcomes. Considerations for the transition to use of POCT in the home to further improve disease management and improve health care cost-effectiveness are discussed. Devices available for home use include those suitable for management of diabetes mellitus, hypertension, congestive heart failure, and anticoagulation. Many of these devices include software capabilities enabling patients to share important health information with health care providers using a computer. Limitations and challenges surrounding implementation of home POCT for patients include reliability of instrumentation, ability to coordinate data collection, necessary training requirements, and cost-effectiveness. Looking forward, the successful integration of POCT into the homes of patients is contingent on a concerted effort made by all members of the health care team.

Developing non-invasive and accurate diagnostics that are easily manufactured, robust and reusable will provide monitoring of high-risk individuals in any clinical or point-of-care environment, particularly in the developing world. There is currently no rapid, low-cost and generic sensor fabrication technique capable of producing narrow-band, uniform, reversible colorimetric readouts with a high-tuneability range. This thesis aims to present a theoretical and experimental basis for the rapid fabrication, optimisation and testing of holographic sensors for the quantification of pH, organic solvents, metal cations, and glucose in solutions. The sensing mechanism was computationally modelled to optimise its optical characteristics and predict the readouts. A single pulse of a laser (6 ns, 532 nm, 350 mJ) in holographic “Denisyuk” reflection mode allowed rapid production of sensors through silver-halide chemistry, in situ particle size reduction and photopolymerisation. The fabricated sensors consisted of off-axis Bragg diffraction gratings of ordered silver nanoparticles and localised refractive index changes in poly(2-hydroxyethyl methacrylate) and polyacrylamide films. The sensors exhibited reversible Bragg peak shifts, and diffracted the spectrum of narrow-band light over the wavelength range λpeak ≈ 500-1100 nm. The application of the holographic sensors was demonstrated by sensing pH in artificial urine over the physiological range (4.5-9.0), with a sensitivity of 48 nm/pH unit between pH 5.0 and 6.0. For sensing metal cations, a porphyrin derivative was synthesised to act as the crosslinker, the light absorbing material, the component of a diffraction grating, as well as the cation chelating agent. The sensor allowed reversible quantification of Cu2+ and Fe2+ ions (50 mM - 1 M) with a response time within 50 s. Clinical trials of a glucose sensor in the urine samples of diabetic patients demonstrated that the glucose sensor has an improved performance compared to a commercial high-throughput urinalysis device. The experimental sensitivity of the glucose sensor exhibited a limit of detection of 90 µM, and permitted diagnosis of glucosuria up to 350 mM. The sensor response was achieved within 5 min and the sensor could be reused about 400 times without compromising its accuracy. Holographic sensors were also tested in flake form, and integrated with paper-iron oxide composites, dyed filter and chromatography papers, and nitrocellulose-based test strips. Finally, a generic smartphone application was developed and tested to quantify colorimetric tests for both Android and iOS operating systems. The developed sensing platform and the smartphone application have implications for the development of low-cost, reusable and equipment-free point-of-care diagnostic devices.

Els test de tipus 'point-of-care' (POC) presenten un gran potencial per al maneig i el diagnòstic de malalties. Els dispositius POC permeten la realització de proves clíniques prop del pacient, permetent així un diagnòstic ràpid, una ràpida iniciació de tractaments, i en cas necessari, una derivació ràpida a altres centres mèdics. Aquests dispositius tenen a més el potencial de ser més econòmics, més robustos, i més fàcils d'usar que els dispositius mèdics tradicionals. Per aquests motius, els dispositius mèdics de tipus POC es consideren prometedors per als països en vies de desenvolupament, els quals són també els que necessiten de forma més urgent noves tecnologies mèdiques. En aquest context, aquesta tesi se centra en el desenvolupament de dispositius mèdics de diagnòstic in-vitro de tipus POC per salut global. Tenint en compte que els recursos per al desenvolupament i explotació de dispositius POC per a països amb baixos recursos són limitats, el Capítol 2 s'enfoca en el desenvolupament de prioritats d'investigació en salut. Mitjançant l'establiment d'aquestes prioritats es pretén facilitar la selecció d'objectius a fabricants d'instruments mèdics, així com incrementar l'impacte de les noves tecnologies desenvolupades. Els criteris de priorització considerats són molt amplis i inclouen l'impacte d'un nou test en la incidència d'una malaltia, la disponibilitat i preu dels tractaments de les malalties, la inversió tecnològica per al desenvolupament d'un nou dispositiu, i els principis bioètics. El tercer capítol descriu el desenvolupament d'un dispositiu mèdic senzill que pot ser fabricat fàcilment en laboratoris amb escassos recursos: tires reactives de diagnòstic de paper per a la detecció de biomarcadors presents en fluids biològics fabricats amb impressores de raig de tinta domèstiques i amb receptes senzilles per la preparació de les tintes. Aquesta tècnica de fabricació de tires reactives de diagnòstic va ser provada per a la detecció de deficiència de iode, un problema sever de salut global al món. En aquest capítol es presenten experiments de preparació de tintes químiques, impressió en paper, detecció de iode en les concentracions presents en l'orina, i consells per al desenvolupament de noves tintes per a la detecció d'altres biomarcadors de malalties. Aquest simple i versàtil procés de fabricació de tests de diagnòstic permetria a hospitals i laboratoris amb pocs recursos dissenyar els seus propis diagnòstics per a malalties rellevants, i en la forma i quantitat adaptada a les necessitats de cada comunitat. Desafortunadament, no totes les malalties es poden diagnosticar usant senzilles tires reactives de diagnòstic, i freqüentment es necessiten dispositius més complexos. El capítol 4 està enfocat en el desenvolupament de dispositius de PCR i RT-PCR de baix cost, a temps real, i de tipus POC que permeten detectar quantitativament patògens basats en DNA i RNA respectivament. El nostre sistema es basa en PCR de flux continu, el qual manté zones de temperatura fixes i empeny la solució de PCR entre les àrees calefactades, permetent així una transferència de calor més ràpida i conseqüentment, una PCR més veloç. Tots dos sistemes de PCR i RT-PCR van ser fabricats a partir d'un xip microfluídic sol ús dissenyat per a ser produït a baix cost industrialment mitjançant mètodes de 'roll-to-roll'. El sistema òptic permet la detecció de patògens en temps real mitjançant mesures de fluorescència. Per demostrar la funció del xip, dos bacteris infeccioses i un virus van ser seleccionats: Chlamydia trachomatis, Escherichia coli O157: H7, i Ebola virus. Per als tres patògens, es van provar diferents velocitats de flux, es va determinar el límit de detecció del sistema, i es van calcular les eficiències de les PCRs. L'èxit dels resultats obtinguts i la versatilitat del sistema, fa que aquests dispositius es considerin prometedors per al diagnòstic d'altres patògens com Zika o chikungunya, que constitueixen amenaces mundials a la salut pública. Tots dos dispositius de diagnòstic in vitro presentats en aquesta tesi són bons exemples de dispositius de diagnòstic apropiats per a salut global.<br>Los test de tipo ‘point-of-care’ (POC) presentan un gran potencial para el manejo y el diagnóstico de enfermedades. Los dispositivos POC permiten la realización de pruebas clínicas cerca del paciente, permitiendo así un diagnóstico rápido, una pronta iniciación de tratamientos, y en caso necesario, una derivación rápida a otros centros médicos. Estos dispositivos tienen además el potencial de ser más económicos, más robustos, y más fáciles de usar que los dispositivos médicos tradicionales. Por estos motivos, los dispositivos médicos de tipo POC se consideran prometedores para los países en vías de desarrollo, los cuales son también los que necesitan de forma más urgente nuevas tecnologías médicas. En este contexto, esta tesis se centra en el desarrollo de dispositivos médicos de diagnóstico in vitro de tipo POC para salud global. Teniendo en cuenta que los recursos para el desarrollo de dispositivos POC para países con bajos recursos son limitados, el Capítulo 2 se enfoca en el desarrollo de prioridades de investigación en salud. Mediante el establecimiento de estas prioridades se pretende facilitar la selección de objetivos a fabricantes de dispositivos médicos, así como incrementar el impacto de las nuevas tecnologías desarrolladas. Los criterios de priorización considerados son muy amplios e incluyen el impacto de un nuevo test en la incidencia de una enfermedad, la disponibilidad y precio de los tratamientos de las enfermedades, la inversión tecnológica para el desarrollo de un nuevo dispositivo, y los principios bioéticos. El segundo Capítulo 3 describe el desarrollo de un dispositivo médico sencillo que puede ser fabricado fácilmente en laboratorios con escasos recursos: tiras reactivas de diagnóstico de papel para la detección de biomarcadores presentes en fluidos biológicos fabricados con impresoras de chorro de tinta domésticas y con recetas sencillas para la preparación de las tintas. Esta técnica de fabricación de tiras reactivas de diagnóstico fue probada para la detección de deficiencia de yodo, un problema severo de salud global en el mundo. En este capítulo se presentan experimentos de preparación de tintas químicas, impresión en papel, detección de yodo en las concentraciones presentes en la orina, y directrices para el desarrollo de nuevas tintas para la detección de otros biomarcadores de enfermedades. Este simple y versátil proceso de fabricación de tests de diagnóstico permitiría a hospitales y laboratorios con pocos recursos diseñar sus propios diagnósticos para enfermedades relevantes, en una forma y cantidad adaptada a las necesidades de cada comunidad. Desafortunadamente, no todas las enfermedades pueden diagnosticarse usando sencillas tiras reactivas de diagnóstico, y frecuentemente se necesitan dispositivos más complejos. El Capítulo 4 está enfocado en el desarrollo de dispositivos de PCR y RT-PCR de bajo coste, de tiempo-real, y de tipo POC que permiten detectar cuantitativamente patógenos basados en DNA y RNA respectivamente. Nuestro sistema se basa en PCR de flujo continuo, el cual mantiene zonas de temperatura fijas y empuja la solución de PCR entre las áreas calefactadas, permitiendo así una transferencia de calor más rápida y consecuentemente, PCR más veloces. Ambos sistemas de PCR y RT-PCR fueron fabricados en base a un chip microfluídico desechable diseñado para ser producido a bajo coste industrialmente mediante métodos de ‘roll-to-roll’. El sistema óptico permite la detección de patógenos en tiempo real mediante medidas de fluorescencia. Para demostrar la función del chip, dos bacterias infecciosas y un virus fueron seleccionados: Chlamydia trachomatis, Escherichia coli O157:H7, y Ebola virus. Para los tres patógenos, se probaron diferentes velocidades de flujo, se determinó el límite de detección del sistema, y se calcularon las eficiencias de las PCRs. El éxito de los resultados obtenidos y la versatilidad del sistema, hace que estos dispositivos se consideren prometedores para el diagnóstico de otros patógenos como Zika o chikungunya, que constituyen amenazas mundiales a la salud pública. Ambos dispositivos de diagnóstico in vitro presentados en esta tesis son buenos ejemplos de dispositivos de diagnóstico apropiados para salud global.<br>Point-of-care (POC) testing has great potential for the management and diagnosis of disease. POC devices allow for testing close to the patient permitting rapid diagnosis, prompt treatment initiation, and when needed, quick referral to other health-care units. They have the potential to be lower-cost, more robust, and more user-friendly than traditional medical devices. For these reasons, POC diagnostic tests are a promising approach for the developing world, where there is also the most urgent need for new health technologies. In this context, this thesis is focused in the development of POC in vitro diagnostic tests for global health. Considering that the resources for developing POC devices for low-resource settings are limited, during Chapter 2 we focused on setting health research priorities to aid test developers setting their targets to increase the impact of the technology. The criteria for prioritization considered were very broad and took into account the impact of a new test on the burden of disease, the availability and expense of disease treatments, the technological investment to develop a new device, and the bioethical principles. Chapter 3 describes the development of a medical device that can be easily manufactured in limited resources laboratories: paper diagnostic chemical dipsticks to detect biomarkers present in biological fluids produced with domestic inkjet printers and simple ink preparation recipes. This fabrication technique for diagnostic strips was tested for the detection of iodine deficiency, a severe global health problem worldwide. In this chapter we present successful experiments for chemical inks preparation, printing on paper, detection of iodine in the concentrations present in the urine, and guidelines for new ink development to target other disease biomarkers. This simple and versatile manufacturing process for diagnostic tests would allow hospitals and laboratories with limited infrastructure to design diagnostics for relevant diseases in a format and quantity adapted to each community needs. Unfortunately, not all diseases can be diagnosed using simple chemical dipstick assays and more complex diagnostic devices are required. Chapter 4 is focused on the development of a low-cost, real-time, point-of-care PCR and RT-PCR systems for quantitative detection of DNA and RNA-based pathogens. Our systems are based on continuous-flow PCR which maintains fixed temperatures zones and pushes the PCR solution between heated areas allowing for faster heat transfer and as a result, faster PCRs. Both PCR and RT-PCR systems were built around disposable microfluidic chips designed to be economically produced industrially by roll-to-roll embossing methods. The optical system allows for pathogen detection via real-time fluorescence measurements. To demonstrate the function of the chips, two infectious bacteria and one viral target were selected: Chlamydia trachomatis, Escherichia coli O157:H7, and Ebola virus. For the three pathogens, different flow velocities were tested, the limit of detection of the system was determined, and PCR efficiencies were calculated. Our successful results, and the versatility of our system, make it promising for the detection of other DNA and RNA-based pathogens such as Zika or chikungunya, which constitute global health threats worldwide. The two in vitro diagnostic tests presented in this thesis are good examples of promising POC diagnostic devices appropriate for global health.

De nos jours, efficacité et précision des diagnostics médicaux sont des éléments essentiels pour la prévention en termes de santé et permettre une prise en charge rapide des maladies des patients. Les récentes innovations technologiques, particulièrement dans les domaines de la microélectronique et des sciences des matériaux ont permis le développement de nouvelles plateformes personnalisées de diagnostics portatifs. Les matériaux électroniques organiques qui ont déjà par le passé démontré leur potentiel en étant intégrés dans des produits de grande consommation tels que les écrans de smartphones ou encore les cellules solaires montrent un fort potentiel pour une intégration dans des dispositifs biomédicaux. En effet, de par leurs natures et leurs propriétés physiques et chimiques, ils peuvent être à la fois en contact avec les milieux biologiques et constituer l’interface entre les éléments biologiques à l’étude, et les dispositifs électroniques. L’objectif de mes travaux de thèse et d’étudier et évaluer les performances des matériaux organiques électroniques intégrés dans des dispositifs biomédicaux en étudiant leurs interactions avec des milieux biologiques et par l’utilisation et l’optimisation de ces dispositifs permettre la détection de métabolites tel que le glucose ou lactate par exemple. Pendant ma thèse, j’ai notamment créé une plateforme de diagnostics combinant à la fois microfluidique et électronique organique permettant la multi détection de métabolites présents dans des fluides corporels humains, j’ai également conçu des capteurs intégrant des transistors organiques au sein des circuits électroniques classiques afin de détecter la présence des cellules tumorales. D’autres applications biologiques ont également été envisagées telles que la détection d’acides nucléiques par l’utilisation d’une approche simple de biofonctionnalisation. Bien que l’objectif ma thèse était de de créer des capteurs biomédicaux en utilisant une approche in vitro, il pourrait être également possible d’intégrer ces dispositifs « in vivo » ou encore dans des e-textiles<br>Rapid and early diagnosis of disease plays a major role in preventative healthcare. Undoubtedly, technological evolutions, particularly in microelectronics and materials science, have made the hitherto utopian scenario of portable, point-of-care personalized diagnostics a reality. Organic electronic materials, having already demonstrated a significant technological maturity with the development of high tech products such as displays for smartphones or portable solar cells, have emerged as especially promising candidates for biomedical applications. Their soft and fuzzy nature allows for an almost seamless interface with the biological milieu rendering these materials ideally capable of bridging the gap between electronics and biology. The aim of this thesis is to explore and validate the capabilities of organic electronic materials and devices in real-world biological sensing applications focusing on metabolite sensing, by combining both the right materials and device engineering. We show proof-of-concept studies including microfluidic integrated organic electronic platforms for multiple metabolite detection in bodily fluids, as well as more complex organic transistor circuits for detection in tumor cell cultures. We finally show the versatility of organic electronic materials and devices by demonstrating other sensing strategies such as nucleic acid detection using a simple biofunctionalization approach. Although the focus is on in vitro metabolite monitoring, the findings generated throughout this work can be extended to a variety of other sensing strategies as well as to applications including on body (wearable) or even in vivo sensing

Although advanced medical technology has been progressively developed, access to quality healthcare services is still a major problem, especially in developing countries. Advanced medical technology requires enormous and expensive resources; therefore, affordable, easy to use and accessible technology could bridge the gap, improving people’s lives, and attracting venture capital investment. Moreover, it is expected that the diagnostic device market would grow exponentially, particularly for paper-based technology. As a result, technology development could promote the local economy by creating jobs. Paper-based analytical devices have been introduced and developed over the last decades. This technology has been widely used as a tool for diagnosis in fields such as environment, food quality and healthcare. Point-of-care (POC) diagnosis has attracted a great deal of attention from the research community, eventually aiming for the development of a platform that can evaluate biological markers in body fluids such as saliva and urine. Paper-based diagnostic devices make an impact because of their low cost, environmentally friendliness and biodegradability. The significant advantage of paperbased devices is the capillarity driven fluid transport through the paper network without the need for additional equipment. This thesis starts with a detailed literature review on paper-based devices. The literature review includes material selection, fundamentals, applications and design criteria, and mainly discusses the technical challenges in engineering and biochemical aspects. Additionally, this section will discuss the current research trends and perspectives of advanced technologies for enhancing assay performance. The study of wicking in paper strips predicts the flow behaviour to control fluid flow and perform programmable fluid handling tasks. An accurate model to predict flow in paper is required for designing paper-based devices. In this thesis, a novel model explains wicking in paper strips altogether with liquid absorption capacity. Based on observation, paper can store liquid in a matrix because after removing the reservoir, the fluid continues flowing. We employ the electrical circuit analogy to formulate the model. The capacitance should be included in the model because the capability to store and release charges is analogous to liquid absorption capacity in the matrix which contain and discharge the fluid. The theoretical data from the model agrees well with the experimental data obtained for wicking in paper strips in a vertical configuration. Additionally, fitting the model with experimental data confirms the critical parameters of liquid absorption capacity and capillary pressure. Considering liquid absorption capacity as a capacitance in electrical circuit analogy could elucidate the relationship between materials and wicking mechanism. Next, the thesis focuses on developing of paper-based analytical device fabrication technology that allows the defined hydrophobic pattern on paper to guide fluid along a hydrophilic path in a controlled manner. There have been many fabrication processes reported in recent decades. However, some methods using harsh chemicals result in contamination of the subsequent reagents for analytical assays. Some other techniques have complicated processes requiring expensive equipment, impractical for mass production. The subsequent study focused on a parametric fabrication of parafilm hot pressing, which is inexpensive, rapid, and straightforward. The basic concept is providing heat and pressure to melt and squeeze parafilm into the paper matrix resulting in a hydrophobic pattern defined by a laminate mask. The smallest hydrophobic barrier made by this technique is 821 um, resulting from the resolution of the laminate mask. Likewise, this study also demonstrated the suitability of paper for both physical and biochemical functions. In terms of physical function, the wicking speed on fabricated paper is slower than on non-fabricated paper because the pore could be reduced due to pressure. Diffusive mixing in 2D and 3D paperfluidics are also reported. We employed a sandwich immunological assay for biochemical functions to evaluate protein binding capacity on the paper. Demonstrating the paper device from this fabrication process is potentially applicable to analytical instrument for wicking studies and biomolecule detection. Besides investigating wicking in paper strips and the fabrication process to handle engineering challenges, biomarker detection has been studied to demonstrate diagnostic applications for the developed devices. Biomarkers used in this study include SARSCoV-2 humanised antibody and cell-derived exosomes. The readout methods implemented in this study are colourimetric, fluorescent, and electrochemical. First, we employed a paper-based colorimetric assay using the horseradish peroxidase and 3,3’,5,5’-tetramethylbenzidine (TMB)/hydrogen peroxide system. The colourimetric readout was obtained from a self-made image acquisition system and is quantified using the MATLAB program. The detection limit of SARS-CoV-2 humanised antibody assay was 9.00 ng/uL, which is lower than commercially available kits (0.112 IU/mL vs 5 IU/mL). However, the result for exosome detection encountered many challenges. Firstly, the exosome concentration may be inadequate to reach a detectable range. Secondly, high background signal resulting from non-specific binding on the platform leads to a lack of sensitivity and specificity for exosome detection. A paper-based colourimetric assay has the potential to be further developed into a point-of-care diagnostic device. Further modification of the paper may be required to promote protein binding for specific targets and prevent non-specific binding to reduce the background signal. Next, the thesis reports a paper-based immunofluorescent assay for biomarker detection using fluorophore conjugation with detecting antibodies. The fluorescent-based assay requires a specific excitation wavelength and retrieves a wavelength of emission. Fluorescent microscopy was used to observe the readout. Before, the images were processed and quantified using a MATLAB program. The assay selectively detects SARS-CoV-2 humanised antibodies spiked in PBS and healthy human serum samples. The limit of detection of the assay was 2 ng/uL (0.025 IU/mL) and 10 ng/uL (0.125 IU/mL) in PBS and human serums, respectively. This assay can detect 1010 exosome/mL obtained from cell culture media, but also faced many obstacles. First, exosome concentration prepared from cell culture media may be insufficient to reach the detectable range. Second, minimising chemical contamination could enhance assay specificity and sensitivity to prevent non-specific absorption. Therefore, a paper-based fluorescent assay could be further developed into a portable device. The light source to excite the fluorophore and to emit the signal, including an optical system, could be scaled down from fluorescent microscopy into a handheld-size device. Lastly, this thesis presents a proof-of-concept electrochemical paper-based device for biomarker detection. The paper-based device is fabricated using parafilm hot pressing, as reported previously. The electrochemical chacracterisation on paper-based carbon electrodes was thoroughly investigated using cyclic voltammetry. The detection employed a sandwich immunological assay using carbon electrodes on paper. Differential pulse voltammetry was used to observe the current response in the subsequent steps. The stepwise addition of biomolecules on paper-based carbon electrodes results in the attenuation of the current response caused by stepwise biomolecules binding on the electrode surface. The current reaction after target binding corresponds to the target concentrations. In addition, electrochemical impedance spectroscopy is utilised to affirm the validity of the assay by observing the electron transfer resistance coming from the interfacial electron transfer at the electrode surface. The assay for SARS-CoV-2 antibody detection in PBS samples detected the target concentration in the range of 10 to 100 ng/uL. The detection limit is estimated to be 9.37 ng/uL. For exosome detection prepared from cell culture media, this assay quantified the total exosome and ovarian cell-derived exosome concentration with a limit of detection of 9.3 X 10 exosomes/mL and 7.1 x 10 exosomes/mL with < 10% relative standard deviation for samples of n =3. However, the limit of detection can be enhanced by strengthening antibody immobilisation on the paper-based device and stabilising the carbon electrodes on paper to be conductive enough to sense the change of the subsequent loading of biomolecules. Our electrochemical paper-based assay could be an alternative tool for detecting diseasespecific exosomes in biological samples for point-of-care diagnosis. In conclusion, this study aims to overcome engineering and biochemical challenges posed by paper-based analytical devices. To tackle the engineering issues, a novel wicking model with consideration of liquid absorption capacity offers an alternative way to predict flow behaviour in capillary rise experiments and explain the material characteristics. Additionally, the thesis studies the fabrication parameters to control the paper-based device fabrication better using parafilm hot pressing, demonstrating the functionality of paper for both physical and biochemical applications. Regarding biochemical challenges, the thesis reports colourimetric, fluorescent, and electrochemical techniques implemented on paper-based platforms, employing a sandwich immunological assay to detect biomarkers, which include SARS-CoV-2 humanised antibody and cell-derived exosome samples. These established protocols have the potential to be further improved for automation and portability, which could be compatible with other advanced technologies such as wearable sensing devices, artificial intelligence and machine learning.<br>Thesis (PhD Doctorate)<br>Doctor of Philosophy (PhD)<br>School of Eng & Built Env<br>Science, Environment, Engineering and Technology<br>Full Text

La tecnologia "a inkjet-Printing" està cridada a liderar la propera generació d'electrònica flexible capaç de realitzar funcions a què només es podia accedir amb tecnologies de microfabricació d'última generació. El inkjet-Printing és un mètode de fabricació additiva que es basa en imprimir sense contacte microgotes d'un material funcional amb precisió micromètrica en l'àrea de l'substrat desitjat, a través d'un disseny digital. A més, és capaç de modificar el disseny d'impressió en temps real. En conseqüència, es permet crear dissenys personalitzats amb característiques úniques. Avui en dia, el inkjet-Printing a nivell industrial ha assolit alts estàndards de rendiment, flexibilitat, robustesa i confiança. Es preveu és que el inkjet-Printing facilitarà la producció de productes electrònics flexibles de forma rendible, basant-se conceptes d'economia circular i reduint el malbaratament, el que permetrà el desenvolupament de dispositius portàtils i d'un sol ús no disponibles actualment. Aquest és el punt en el qual els dispositius de Point-of-Care (PoC) entren en l'equació causa de la seva importància en les proves mèdiques. Aquests dispositius es defineixen com a proves de diagnòstic mèdic en el pacient o prop d'ell mateix. Els dispositius PoC es basen en una mesura ràpida i precisa basada en sensors que ofereixen a el metge dades importants per realitzar un diagnòstic. No obstant això, les principals limitacions d'aquests dispositius, fins i tot avui dia, són el cost, la disponibilitat, la biodegradabilitat i la fiabilitat. El inkjet-Printing ofereix solucions per abordar aquests problemes on els seus grans promeses són la fabricació ràpida de prototips, de baix cost, utilitzant una gran varietat de materials i una àmplia gamma de substrats. No obstant això, la nostra comprensió de la tecnologia i les seves capacitats roman en una etapa prometedora, i cal adquirir més experiència per facilitar el desenvolupament de dispositius PoC complets i totalment impresos. Identificant aquests problemes i possibles solucions, aquesta tesi se centra en mostrar el potencial de l'inkjet Printing per desenvolupar sensors sobre substrats de plàstic flexible i paper porós, desafiant la tecnologia fins al seu límit actual. En una primera part s'aborda la formulació, impressió i caracterització de noves tintes funcionals que permetin obtenir noves tintes conductores per a ser usades en l'àrea de l'sensat d'analits d'interès. Sobre plàstic flexible, s'han desenvolupat dos sensors de pH potenciomètrics. El primer mostra la importància de la propietat de rugositat intrínseca d'una nova tinta de platí en base a nanopartícules per dotar d'estabilitat mecànica a l'òxid d'iridi, material sensible a l'pH, crescut electroquímicament sobre ell. Per a aquest propòsit, es va desenvolupar un sensor de pH en PEN utilitzant la nova tinta de Pt i es va estudiar l'estabilitat al llarg d'un any d'aquesta capa d'òxid d'iridi, que va mostrar una clara millora del seu rendiment. El segon sensor de pH va un pas més i és totalment imprès per a inkjet-Printing. Per complir aquest objectiu, es va formular una nova tinta polimèrica sensible a el pH. En una segona part es va abordar el repte de la impressió d'un sensor sobre un substrat més ecosostenible com és el paper, factor important per als PoC sol ús. En un primer treball es va abordar el desafiament d'imprimir tintes funcionals conductores com l'or o la plata, i dielèctriques com el SU8 sobre el substrat de manera eficient i fàcil de reproduir per a l'obtenció d'un sensor electroquímic. Finalment, en un segon treball es va implementar un immunosensor de cortisol sobre aquests sensors impresos sobre substrat de paper i es va caracteritzar i comparar la seva resposta respecte d'altres sensors reportats, demostrant el bon rendiment d'aquesta tecnologia en la detecció de molècules biològiques.<br>La tecnología "Inkjet-Printing" está llamada a liderar la próxima generación de electrónica flexible capaz de realizar funciones a las que sólo se podía acceder con tecnologías de microfabricación de última generación. El Inkjet-Printing es un método de fabricación aditiva que se basa en imprimir sin contacto microgotas de un material funcional con precisión micrométrica en el área del sustrato deseado, a través de un diseño digital. Además, es capaz de modificar el diseño de impresión en tiempo real. En consecuencia, se permite crear diseños personalizados con características únicas. Hoy en día, el Inkjet-Printing a nivel industrial ha alcanzado altos estándares de rendimiento, flexibilidad, robustez y confianza. Se prevé es que el Inkjet-Printing facilitará la producción de productos electrónicos flexibles de forma rentable, en base a conceptos de economía circular y reduciendo el desperdicio, lo que permitirá el desarrollo de dispositivos portátiles y desechables no disponibles actualmente. Este es el punto en el que los dispositivos de Point-of-Care (PoC) entran en la ecuación debido a su importancia en las pruebas médicas. Estos dispositivos se definen como pruebas de diagnóstico médico en el paciente o cerca del mismo. Los dispositivos PoC se basan en una medición rápida y precisa basada en sensores que ofrecen al médico datos importantes para realizar un diagnóstico. Sin embargo, las principales limitaciones de estos dispositivos, incluso hoy en día, son el coste, la disponibilidad, la biodegradabilidad y la fiabilidad. El Inkjet-Printing ofrece soluciones para abordar estos problemas donde sus grandes promesas son la fabricación rápida de prototipos, de bajo coste, usando una gran variedad de materiales y una amplia gama de sustratos. Sin embargo, nuestra comprensión de la tecnología y sus capacidades permanece en una etapa prometedora, y es necesario adquirir más experiencia para facilitar el desarrollo de dispositivos PoC completos y totalmente impresos. Identificando estos problemas y posibles soluciones, esta tesis se centra en mostrar el potencial del Inkjet Printing para desarrollar sensores sobre sustratos de plástico flexible y papel poroso, desafiando la tecnología hasta su límite actual. En una primera parte se aborda la formulación, impresión y caracterización de nuevas tintas funcionales que permitan obtener nuevas tintas conductoras para ser usadas en el área del sensado de analitos de interés. Sobre plástico flexible, se han desarrollado dos sensores de pH potenciométricos. El primero muestra la importancia de la propiedad de rugosidad intrínseca de una nueva tinta de platino en base a nanopartículas para dotar de estabilidad mecánica al óxido de iridio, material sensible al pH, crecido electroquímicamente sobre él. Para este propósito, se desarrolló un sensor de pH en PEN utilizando la nueva tinta de Pt y se estudió la estabilidad a lo largo de un año de esta capa de óxido de iridio, que mostró una clara mejora de su rendimiento. El segundo sensor de pH va un paso más y es totalmente impreso por Inkjet-Printing. Para cumplir este objetivo, se formuló una nueva tinta polimérica sensible al pH. En una segunda parte se abordó el reto de la impresión de un sensor sobre un sustrato más ecosostenible como es el papel, factor importante para los PoC desechables. En un primer trabajo se abordó el desafío de imprimir tintas funcionales conductoras como el oro o la plata, y dieléctricas como el SU8 sobre el sustrato de manera eficiente y fácil de reproducir para la obtención de un sensor electroquímico. Finalmente, en un segundo trabajo se implementó un immunosensor de cortisol sobre estos sensores impresos sobre sustrato de papel y se caracterizó y comparó su respuesta respecto a otros sensores reportados, demostrando el buen rendimiento de esta tecnología en la detección de moléculas biológicas en matrices fisiológicas.<br>Universitat Autònoma de Barcelona. Programa de Doctorat en Enginyeria Electrònica i de Telecomunicació

La thrombine est l'enzyme principale dans le processus d'hémostase. Les dérèglements de la concentration de thrombine clinique prédisposent les patients à des complications hémorragiques ou thromboemboliques. Le suivi en temps réel de la thrombine dans le sang est donc nécessaire pour améliorer le traitement de patients en état critique. Les aptamères, qui sont de courts nucléotides monobrins semblent constituer des candidats prometteurs pour la reconnaissance moléculaire dans les biocapteurs. L'objectif de ces travaux est l'étude de différentes solutions d'intégration des aptamères dans des dispositifs de diagnostic de type "point of care" pour le suivi en continu de la thrombine dans le plasma. La cinétique d'interaction des aptamères avec la thrombine et leur spécificité vis-à-vis de la prothrombine et des inhibiteurs de la thrombine ont été étudiés par résonance par plasmons de surface. Ces travaux ont démontré la faible spécificité de l'aptamère HD1 vis-à-vis de la thrombine, et la présence d'interactions non-spécifiques avec la prothrombine, les inhibiteurs naturels de la thrombine et l'albumine. Inversement, nous avons observé une bonne affinité de l'aptamère HD22 avec la même liste de cible. Parallèlement, nous avons évalué des stratégies d'intégration d'aptamères dans des dispositifs d'analyse. Le principe de reconnaissance a ensuite été validé et la possibilité de détecter la thrombine dans des gammes de concentration de 5 à 500nM a été démontrée. Enfin, afin d'augmenter la spécificité de la détection de la thrombine, nous avons proposé une nouvelle approche basée sur l'ingénierie de structures dimères interconnectant HD1 et HD22<br>Thrombin is the central enzyme in the process of hemostasis. Normally, in vivo concentration of thrombin is rigorously regulated; however, clinically impaired or unregulated thrombin generation predisposes patients either to hemorrhagic or thromboembolic complications. Monitoring thrombin in real-time is therefore needed to enable rapid and accurate determination of drug administration strategy for patients under vital threat. Aptamers, short single-stranded oligonucleotide ligands represent promising candidates as biorecognition elements for new-generation biosensors. The aim of this PhD work therefore is to investigate different solutions for the integration of thrombin-binding aptamers in point-of-care devices for continuous monitoring of thrombin in plasma. The kinetics of aptamer interaction with thrombin and specificity towards prothrombin and thrombin - inhibitor complexes was rigorously investigated using Surface Plasmon Resonance. These experiments unveiled the complex character of interaction of the HD1 with thrombin, confirming nonspecific interactions with prothrombin, natural inhibitors of thrombin, serum albumin whereas another 29-bp aptamer HD22 proved to be highly affine and specific towards thrombin. On the other hand we explored aptamer integration options. We validated the principle and at the same managed to detect different concentrations of thrombin (5-500 nM). We finally proposed a novel approach to increase sensitivity and specificity for thrombin detection based on the engineering of aptadimer structures bearing aptamers HD1and HD22 interconnected with a nucleic acid spacer

Un dels majors reptes per a monitoritzar i millorar la salut de la població a nivell mundial és la manca de proves de diagnòstic apropiades per a la detecció primerenca de malalties, la selecció de tractaments apropiats i el seguiment de pacients al llarg del temps. La disponibilitat d’eines de diagnòstic prou ràpides, sensibles i robustes és crucial per aconseguir el benestar dels pacients a tot el món. En aquest context, la nanotecnologia i el desenvolupament de biosensors són camps en ràpida evolució que han generat grans expectatives, produint proves més ràpides i més fàcils de realitzar que la majoria dels mètodes clàssics. Els biosensors s’han descrit en base a l’ús d’una àmplia varietat d’elements de biotecnologia i tipus de transducció de senyals. Entre ells, els biosensors electroquímics són el tipus més comú en ús avui en dia gràcies a la portabilitat i el baix cost de l’equip de mesura, les mesures ràpides, robustes i quantitatives proporcionades, i la facilitat de miniaturització de tot el sistema de detecció. La recent incorporació de paper per a la producció d’elèctrodes impresos en paper i assajos electroquímics de flux lateral està fomentant el desenvolupament de dispositius extremadament econòmics que, gràcies a les propietats fluídicas del paper, permeten reduir la complexitat de l’assaig i el nivell de manipulació per al usuari final. Això afavoreix el desenvolupament de dispositius de diagnòstic de \”Point-of-care\” (POC), que poden ser utilitzats directament pel pacient o als centres d’atenció primària de salut. D’altra banda, les partícules magnètiques (PM) s’han utilitzat amb gran èxit en l’optimització dels magneto-biosensors. Les PM són atractives per a aquest propòsit perquè, un cop modificades amb un bioreceptor apropiat, atorguen una preconcentració simple, ràpida i específica de l’analit objectiu. Les PM també ofereixen superfícies actives en 3D relativament grans, que es barregen amb agitació constant amb les mostres i permeten una ràpida unió amb els analits. No obstant això, les PM també presenta limitacions, com el seu maneig tediós i lent que només està a l’abast d’usuaris altament capacitats. L’objectiu principal d’aquest projecte de tesi doctoral va ser la producció de magneto-biosensors electroquímics ràpids, fàcils de realitzar, robustos i sensibles per a la detecció de biomarcadors de diagnòstic en mostres de sèrum, plasma i sang. Com es mostrarà, això s’ha aconseguit en dos nivells. Primer, desenvolupant un format de magneto-immunoassaig extremadament ràpid i simple. En segon lloc, fabricant elèctrodes de paper microfluids simples i econòmics, que van ser explotats per dur a terme en el xip la majoria dels passos del magneto-immunoassaig simplificat amb la mínima intervenció de l’usuari.<br>Uno de los mayores desafíos para monitorear y mejorar la salud de la población a nivel mundial es la falta de pruebas de diagnóstico apropiadas para la detección temprana de enfermedades, la selección de tratamientos apropiados y el seguimiento de pacientes a lo largo del tiempo. La disponibilidad de herramientas de diagnóstico suficientemente rápidas, sensibles y robustas es crucial para lograr el bienestar de los pacientes en todo el mundo. En este contexto, la nanotecnología y el desarrollo de biosensores son campos en rápida evolución que han generado grandes expectativas, produciendo pruebas más rápidas y más fáciles de realizar que la mayoría de los métodos clásicos. Los biosensores se han descrito en base al uso de una amplia variedad de elementos de biotecnología y tipos de transducción de señales. Entre ellos, los biosensores electroquímicos son el tipo más común en uso hoy en día gracias a la portabilidad y el bajo costo del equipo de medición, las medidas rápidas, robustas y cuantitativas proporcionadas, y la facilidad de miniaturización de todo el sistema de detección. La reciente incorporación de papel para la producción de electrodos impresos en papel y ensayos electroquímicos de flujo lateral está fomentando el desarrollo de dispositivos extremadamente económicos que, gracias a las propiedades fluídicas del papel, permiten reducir la complejidad del ensayo y el nivel de manipulación para el usuario final. Esto favorece el desarrollo de dispositivos de diagnóstico de \”Point-of-care\” (POC), que pueden ser utilizados directamente por el paciente o en los centros de atención primaria de salud. Por otro lado, las partículas magnéticas (PM) se han utilizado con gran éxito en la optimización de los magneto-biosensores. Las PM son atractivos para este propósito porque, una vez modificados con un bioreceptor apropiado, otorgan una preconcentración simple, rápida y específica del analito objetivo. Las PM también ofrecen superficies activas en 3D relativamente grandes, que se mezclan bajo agitación constante con las muestras y permiten una rápida unión con los analitos. Sin embargo, las PM también presenta limitaciones, como su manejo tedioso y lento que solo está al alcance de usuarios altamente capacitados. El objetivo principal de este proyecto de tesis doctoral fue la producción de magneto-biosensores electroquímicos rápidos, fáciles de realizar, robustos y sensibles para la detección de biomarcadores de diagnóstico en muestras de suero, plasma y sangre. Como se mostrará, esto se ha logrado en dos niveles. Primero, desarrollando un formato de magneto-inmunoensayo extremadamente rápido y simple. En segundo lugar, fabricando electrodos de papel microfluidos simples y económicos, que fueron explotados para llevar a cabo en el chip la mayoría de los pasos del magneto-inmunoensayo simplificado con la mínima intervención del usuario.<br>One of the greatest challenges for monitoring and improving the health of the population at a global level is the lack of appropriate diagnostic tests for early detection of diseases, selection of appropriate treatments and patient follow-up over time. The availability of sufficiently fast, sensitive and robust diagnostic tools will be crucial to achieve patients’ well-being worldwide. In this context, nanotechnology and biosensor development are rapidly evolving fields that have generated great expectations, producing tests faster and easier to carry out than most classical methods. Biosensors have been described based on the use of a wide variety of biotechnology elements and types of signal transduction. Among them, electrochemical biosensors are the most common type in use today thanks to the portability and low cost of the measuring equipment, fast, robust and quantitative measures provided, and easiness of miniaturization of the whole detection system. The recent incorporation of paper and paper-like materials for the production of paper printed electrodes and lateral flow electrochemical assays is fostering the development of extremely inexpensive devices that, thanks to the fluidic properties of paper, allow reducing assay complexity and level of manipulation for the end user. This favours the development of "Point-of-Care" diagnostic devices (POC), which can be used directly by the patient or at primary health care centres. On the other hand, magnetic beads (MB) have been used with great success in the optimization of magneto-biosensors. MB are attractive for this purpose because, once modified with an appropriate bioreceptor, they grant simple, rapid and specific preconcentration of the targeted analyte. MB offer also relatively large 3D active surfaces, which mixed under constant agitation with the sample supply efficient and fast analyte binding as well. Nevertheless, MB display limitations too, requiring tedious and time-consuming handling that is only at reach of highly trained users. The main objective of this PhD Thesis project was the production of rapid, easy to perform, robust and sensitive electrochemical magneto-biosensors for the detection of diagnostic biomarkers in serum, plasma and blood samples. As it will be shown, this has been achieved at two levels. First, by developing an extremely fast and simple magnetoimmunoassay format. Second, by fabricating simple and inexpensive microfluidic paper electrodes, which were exploited to carry out on-chip most of the steps of the simplified magneto-immunoassay with minimal user intervention.

The recent growing interest and development of microfluidic paper-based analytical devices (μPADs) for point-of-care (POC) testing in human health in low-resource settings has great potential for the exploitation of these technologies in animal disease diagnosis. Sheep scab is a highly infectious, widespread and notifiable disease of sheep, which poses major economic and welfare concerns for the UK farming industry. The possibility of diagnosing sheep scab at the POC is, consequently, very important to controlling this disease. The overall aim of this project was, therefore, to develop μPADs based on a novel method of fabrication, in order to translate the existing lab-based sheep scab ELISA (Pso o 2) and a biomarker test for haptoglobin (Hp) into paper-based ELISA (P-ELISA), to enable POC diagnosis of this animal disease. In Chapter 3, the novel fabrication method is described, in Chapters 4 and 5, the translation of the lab-based ELISAs (Hp and Pso o 2 respectively) are explained and in Chapter 6 the development of a μPAD for incorporation of the POC tests into a multiplexed, rapid assay is covered. Experiments showed that both ELISAs were successfully transferred onto paper and that the devices developed were suitable for POC testing. This study has resulted in a novel fabrication method for μPADs, in successfully translated existing ELISAs to P-ELISA and in novel solutions for the POC diagnosis of an important veterinary disease.

Photonic biosensors hold a unique potential to become the next-generation diagnostic tools, offering a versatile technology for rapid and sensitive clinical analysis in a label-free format and integrated in point-of-care devices. Full-text article not available; see video presentation

The goal of a QIBA Profile is to help achieve a useful level of performance for a given biomarker. The Claim (Section 2) describes the biomarker performance. The Activities (Section 3) contribute to generating the biomarker. Requirements are placed on the Actors that participate in those activities as necessary to achieve the Claim. Assessment Procedures (Section 4) for evaluating specific requirements are defined as needed. This QIBA Profile (MR-based cartilage compositional biomarkers (T1ρ, T2) ) addresses the application of T1ρ and T2 for the quantification of cartilage composition, which can be used as an imaging biomarker to diagnose, predict and monitor early osteoarthritis. It places requirements on Acquisition Devices, Technologists, MRI Physicists, Radiologists, Reconstruction Software and Image Analysis Tools involved in Subject Handling, Image Data Acquisition, Image Data Reconstruction, Image Quality Assurance (QA) and Image Analysis. The requirements are focused on achieving sufficient reproducibility and accuracy for measuring cartilage composition. The clinical performance target is to achieve a reproducibility of 4-5% for measurements of global cartilage composition with T2 and T1ρ relaxation time measurements and a 95% confidence level for a true/critical change in cartilage composition (least significant change) with a precision of 11-14% and 9-12% if only an increase is expected (claim is one-sided). The target applies to 3T MR scanners of one manufacturer with identical scan parameters across different sites. It does not apply to scanners from different manufacturers. This document is intended to help clinicians basing decisions on this biomarker, imaging staff generating this biomarker, vendor staff developing related products, purchasers of such products and investigators designing trials with imaging endpoints. Note that this document only states requirements to achieve the claim, not “requirements on standard of care.” Conformance to this Profile is secondary to properly caring for the patient. Summary for Clinical Trial Use The MR-based cartilage compositional biomarkers profile defines the behavioral performance levels and quality control specifications for T1ρ, T2 scans used in single- and multi-center clinical trials of osteoarthritis and other trials assessing cartilage composition longitudinally with a focus on therapies to treat degenerative joint disease. While the emphasis is on clinical trials, this process is also intended to be applied for clinical practice. The specific claims for accuracy are detailed below in the Claims. The specifications that must be met to achieve conformance with this Profile correspond to acceptable levels specified in the T1ρ, T2 Protocols. The aim of the QIBA Profile specifications is to minimize intra- and inter-subject, intra- and inter-platform, and interinstitutional variability of quantitative scan data due to factors other than the intervention under investigation. T1ρ and T2 studies performed according to the technical specifications of this QIBA Profile in clinical trials can provide quantitative data for single timepoint assessments (e.g. disease burden, investigation of predictive and/or prognostic biomarker(s)) and/or for multi-time-point comparative assessments (e.g., response assessment, investigation of predictive and/or prognostic biomarkers of treatment efficacy). A motivation for the development of this Profile is that while a typical MR T1ρ and T2 measurement may be stable over days or weeks, this stability cannot be expected over the time that it takes to complete a clinical trial. In addition, there are well known differences between scanners and the operation of the same type of scanner at different imaging sites. The intended audiences of this document include: Biopharmaceutical companies, rheumatologists and orthopedic surgeons, and clinical trial scientists designing trials with imaging endpoints. Clinical research professionals. Radiologists, technologists, physicists and administrators at healthcare institutions considering specifications for procuring new MRI equipment for cartilage measurements. Radiologists, technologists, and physicists designing T1ρ and T2 acquisition protocols. Radiologists, and other physicians making quantitative measurements from T1ρ and T2 sequence protocols. Regulators, rheumatologists, orthopedic surgeons, and others making decisions based on quantitative image measurements. Technical staff of software and device manufacturers who create products for this purpose. Note that specifications stated as 'requirements' in this document are only requirements to achieve the claim, not 'requirements on standard of care.' Specifically, meeting the goals of this Profile is secondary to properly caring for the patient.

Overview Skin cancer prevention is a component of the new Cancer Plan 2022–27, which guides the work of the Cancer Institute NSW. To lessen the impact of skin cancer on the community, the Cancer Institute NSW works closely with the NSW Skin Cancer Prevention Advisory Committee, comprising governmental and non-governmental organisation representatives, to develop and implement the NSW Skin Cancer Prevention Strategy. Primary Health Networks and primary care providers are seen as important stakeholders in this work. To guide improvements in skin cancer prevention and inform the development of the next NSW Skin Cancer Prevention Strategy, an up-to-date review of the evidence on the effectiveness and feasibility of skin cancer prevention activities in primary care is required. A research team led by the Daffodil Centre, a joint venture between the University of Sydney and Cancer Council NSW, was contracted to undertake an Evidence Check review to address the questions below. Evidence Check questions This Evidence Check aimed to address the following questions: Question 1: What skin cancer primary prevention activities can be effectively administered in primary care settings? As part of this, identify the key components of such messages, strategies, programs or initiatives that have been effectively implemented and their feasibility in the NSW/Australian context. Question 2: What are the main barriers and enablers for primary care providers in delivering skin cancer primary prevention activities within their setting? Summary of methods The research team conducted a detailed analysis of the published and grey literature, based on a comprehensive search. We developed the search strategy in consultation with a medical librarian at the University of Sydney and the Cancer Institute NSW team, and implemented it across the databases Embase, MEDLINE, PsycInfo, Scopus, Cochrane Central and CINAHL. Results were exported and uploaded to Covidence for screening and further selection. The search strategy was designed according to the SPIDER tool for Qualitative and Mixed-Methods Evidence Synthesis, which is a systematic strategy for searching qualitative and mixed-methods research studies. The SPIDER tool facilitates rigour in research by defining key elements of non-quantitative research questions. We included peer-reviewed and grey literature that included skin cancer primary prevention strategies/ interventions/ techniques/ programs within primary care settings, e.g. involving general practitioners and primary care nurses. The literature was limited to publications since 2014, and for studies or programs conducted in Australia, the UK, New Zealand, Canada, Ireland, Western Europe and Scandinavia. We also included relevant systematic reviews and evidence syntheses based on a range of international evidence where also relevant to the Australian context. To address Question 1, about the effectiveness of skin cancer prevention activities in primary care settings, we summarised findings from the Evidence Check according to different skin cancer prevention activities. To address Question 2, about the barriers and enablers of skin cancer prevention activities in primary care settings, we summarised findings according to the Consolidated Framework for Implementation Research (CFIR). The CFIR is a framework for identifying important implementation considerations for novel interventions in healthcare settings and provides a practical guide for systematically assessing potential barriers and facilitators in preparation for implementing a new activity or program. We assessed study quality using the National Health and Medical Research Council (NHMRC) levels of evidence. Key findings We identified 25 peer-reviewed journal articles that met the eligibility criteria and we included these in the Evidence Check. Eight of the studies were conducted in Australia, six in the UK, and the others elsewhere (mainly other European countries). In addition, the grey literature search identified four relevant guidelines, 12 education/training resources, two Cancer Care pathways, two position statements, three reports and five other resources that we included in the Evidence Check. Question 1 (related to effectiveness) We categorised the studies into different types of skin cancer prevention activities: behavioural counselling (n=3); risk assessment and delivering risk-tailored information (n=10); new technologies for early detection and accompanying prevention advice (n=4); and education and training programs for general practitioners (GPs) and primary care nurses regarding skin cancer prevention (n=3). There was good evidence that behavioural counselling interventions can result in a small improvement in sun protection behaviours among adults with fair skin types (defined as ivory or pale skin, light hair and eye colour, freckles, or those who sunburn easily), which would include the majority of Australians. It was found that clinicians play an important role in counselling patients about sun-protective behaviours, and recommended tailoring messages to the age and demographics of target groups (e.g. high-risk groups) to have maximal influence on behaviours. Several web-based melanoma risk prediction tools are now available in Australia, mainly designed for health professionals to identify patients’ risk of a new or subsequent primary melanoma and guide discussions with patients about primary prevention and early detection. Intervention studies have demonstrated that use of these melanoma risk prediction tools is feasible and acceptable to participants in primary care settings, and there is some evidence, including from Australian studies, that using these risk prediction tools to tailor primary prevention and early detection messages can improve sun-related behaviours. Some studies examined novel technologies, such as apps, to support early detection through skin examinations, including a very limited focus on the provision of preventive advice. These novel technologies are still largely in the research domain rather than recommended for routine use but provide a potential future opportunity to incorporate more primary prevention tailored advice. There are a number of online short courses available for primary healthcare professionals specifically focusing on skin cancer prevention. Most education and training programs for GPs and primary care nurses in the field of skin cancer focus on treatment and early detection, though some programs have specifically incorporated primary prevention education and training. A notable example is the Dermoscopy for Victorian General Practice Program, in which 93% of participating GPs reported that they had increased preventive information provided to high-risk patients and during skin examinations. Question 2 (related to barriers and enablers) Key enablers of performing skin cancer prevention activities in primary care settings included: • Easy access and availability of guidelines and point-of-care tools and resources • A fit with existing workflows and systems, so there is minimal disruption to flow of care • Easy-to-understand patient information • Using the waiting room for collection of risk assessment information on an electronic device such as an iPad/tablet where possible • Pairing with early detection activities • Sharing of successful programs across jurisdictions. Key barriers to performing skin cancer prevention activities in primary care settings included: • Unclear requirements and lack of confidence (self-efficacy) about prevention counselling • Limited availability of GP services especially in regional and remote areas • Competing demands, low priority, lack of time • Lack of incentives.

Analytical chemistry is the one of the most importance not only to all branches of chemistry but also to all the biological sciences, to engineering, and, more recently, medicine, public health, food, environment and the supply of energy in all forms. Therefore, the developments of novel detection methods play an important role to obtain both qualitative analysis and quantification of the chemical or biomolecule components of natural and artificial materials. This work has been separated into 3 groups for finishing the novelty in detection methods. First, novel nanomaterials-based or nanocomposite chemical sensors based on nanomaterial/conducting polymer will be prepared and used to modify the electrode surface for sensitive electrochemical and/or optical detection of chemicals and biomolecules. The bioreceptor functionalization will be applied if it is necessary. Under the optimal conditions, the proposed system will be used for sensitive detection of target analytes (e.g. heavy metals, pesticides, food contaminants and biomolecules). This approach is an alternative tool for environmental monitoring, food inspection as well as clinical diagnosis. Second, the paper-based device is proposed. They have the potential to be good alternatives for point-of-care testing because they are portable, easy to use, require only a small volume of sample and provide rapid analysis. To create the detection method for lab-on-paper, colorimetric and electrochemical detection are proposed. These provide the benefits of simplicity, speed, low cost, and portability for applying to various applications. Last, a simple microfluidic or sequential injection system for chemical or biomedical analysis will be developed. Exploiting a microfluidic or sequential injection system, short analysis times can be achieved with high analytical performances, in addition, only small amount of samples and reagents are required, which is beneficial for samples which are expensive or limited, especially biological samples. Moreover, microfluidic or sequential injection analysis holds great promise for high-throughput analysis and screening, which offers an alternative platform for analysis and would be an ideal tool for a portable analysis system for clinical diagnosis.

At any point in the drug development process, systematic reviews and meta-analysis can provide important information to guide the future path of the development programme and any actions that might be needed in the post-marketing setting. This report gives the rationale for why and when a meta-analysis should be considered, all in the context of regulatory decision-making, and the tasks, data collection, and analyses that need to be carried out to inform those decisions. -- There is increasing demand by decision-makers in health care, the biopharmaceutical industry, and society at large to have access to the best available evidence on benefits and risks of medicinal products. The best strategy will take an overview of all the evidence and where it is possible and sensible, combine the evidence and summarize the results. For efficacy, the outcomes generally use the same or very similar predefined events for each of the trials to be included. Most regulatory guidance and many Cochrane Collaboration reviews have usually given more attention to assessment of benefits, while issues around combining evidence on harms have not been as well-covered. However, the (inevitably) unplanned nature of the data on safety makes the process more difficult. -- Combining evidence on adverse events (AEs), where these were not the focus of the original studies, is more challenging than combining evidence on pre-specified benefits. This focus on AEs represents the main contribution of the current CIOMS X report. The goal of the CIOMS X report is to provide principles on appropriate application of meta-analysis in assessing safety of pharmaceutical products to inform regulatory decision-making. This report is about meta-analysis in this narrow area, but the present report should also provide conceptually helpful points to consider for a wider range of applications, such as vaccines, medical devices, veterinary medicines or even products that are combinations of medicinal products and medical devices. -- Although some of the content of this report describes highly technical statistical concepts and methods (in particular Chapter 4), the ambition of the working group has been to make it comprehensible to non-statisticians for its use in clinical epidemiology and regulatory science. To that end, Chapters 3 and 4, which contain the main technical statistical aspects of the appropriate design, analysis and reporting of a meta-analysis of safety data are followed by Chapter 5 with a thought process for evaluating the findings of a meta-analysis and how to communicate these.