Dissertations / Theses on the topic 'Point-of-Care (PoC)'

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.
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.
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.

No
The aim of this review was to examine whether the measurement of lactate in capillary blood samples using point-of-care handheld analysers corresponds sufficiently closely with arterial and venous whole-blood samples analysed by hospital central laboratory or blood gas analyser to be used interchangeably. A systematic search, informed by focused inclusion/exclusion criteria, was performed using multiple databases up to October 2015. A total of 65 articles were considered to have potential relevance and were evaluated in full text, of which ultimately five articles met all inclusion/exclusion criteria, and a final four were selected after data extraction and quality appraisal. All four studies found a predominantly upward bias in the measurement of lactate in capillary samples tested using a handheld point-of-care device over arterial or venous samples tested by laboratory methods or blood gas analyser. In terms of correlation, there was consensus between the studies that the strength of association between the two methods of measurement was statistically significant. Three studies directly examined the extent of agreement between point-of-care capillary lactate measurements and those of laboratory or blood gas analyser reference determined to ±2 standard deviations; 95% confidence intervals, and report contextually broad limits of agreement, identifying a potential for both over triage and, to a lesser extent, under triage. The findings of the review do not support interchangeable use of handheld fingertip point-of-care lactate measurement with laboratory or blood gas analyser methods in the identification of sepsis.

Correct diagnosis of disease is essential in the effort to save and improve lives. Point of care (POC) diagnostics are in-vitro tests that assist in patient diagnosis and can be used at the location of patient care. POC diagnostics are easy to use and provide near-instant readouts allowing medical providers and patients to make rapid decisions about treatment. Increased access to POC testing is especially beneficial to low-income and low resource areas that cannot afford expensive lab testing. The World Health Organization (WHO) has outlined at least 113 diseases for which POC diagnostics are needed. Because of this, developing effective, efficient, and economical methods for creating new POC tests is essential. Work in section one of this thesis describes strategies by which new POC bio-diagnostics can be created. The use of oxidized cellulose as a vector for antibody immobilization was explored in several cellulose-based materials to provide quick, economical tests while still obtaining effective limits of detection when used to detect the pregnancy hormone Human Chorionic Gonadotropin (HCG) in a proof of concept study. The majority of these tests could detect as low as 100 ng/mL of HCG well below the clinical level necessary for detection at 2400 ng/mL. The use of a hand-powered syringe-based POC named the fast flow immunoassay (FFI) was tested for its ability to increase observable signal in a sandwich immunoassay by passing the sample through the test filter multiple times. 10 passes through the filter resulted in a signal approximately 17x more intense than a 1-hour dot-blot sandwich immunoassay. Both oxidized cotton and FFI systems can be used to develop new POC assays quickly and economically. Future use of these POC systems could help expand the availability of diagnostic testing to disadvantaged areas. Gold-based drugs have been used and investigated as medications multiple times throughout history to treat various diseases such as Rheumatoid arthritis, parasitic infections, and cancer. In the last few decades, gold nanoparticles have been used as drug delivery agents and catalysts for various reactions. Recently catalytic gold nanocrystals have been characterized for their ability to treat neurodegenerative diseases. Although these results were promising, much is still unknown about their mechanism of action. Section two of this thesis investigates potential molecular pathways that gold nanocrystals could be affecting, specifically the IL-6/Jak/STAT3 inflammation pathway and the Nrf2 antioxidant pathway. The gold nanocrystals we tested did not affect these pathways at physiologically obtainable concentrations. Additional work was done to characterize protein interactome or protein corona of gold nanocrystals. Preliminary proteomic characterization of this protein corona in fetal bovine serum (FBS) identified 118 potential interactors and classified those based on function and structure. Future work will need to be done to follow up on these identifications and to determine what mechanistic implications they may have.

Dissertação de Mestrado Integrado em Medicina Veterinária
Perante a suspeita de intoxicação aguda, a abordagem célere e sistemática ao doente, permite uma rápida prestação de cuidados específicos. A triagem, recolha da história clínica, avaliação e intervenção médica de urgência, o diagnóstico e a terapêutica são processos chave nessa abordagem. O diagnóstico, por norma, é suportado por um painel analítico inicial. O recurso a testes imediatos (“point of care”), permite avaliar não só a condição geral dos doentes em tempo real, mas também os efeitos que os xenobióticos possam ter a nível orgânico e que se traduzam, nomeadamente, em alterações do equilíbrio hidroeletrólitico e estado ácido base. O presente estudo pretendeu avaliar as alterações analíticas, detetadas através da ferramenta ePOC (“Enterprise Point of Care”), em animais suspeitos de intoxicação por inseticidas anticolinesterásicos e a sua eventual influência no diagnóstico e implementação da terapêutica. A amostra estudada consistiu em 14 canídeos, que na triagem médica apresentavam sintomas inespecíficos e outros compatíveis com intoxicação aguda por insecticidas anticolinesterásicos: tremores musculares (93%), hipersiália (64%), hipertermia (57%), cianose (50%), diarreia (57%) e vómito (36%). Foram colhidas amostras de sangue para a realização do teste ePOC e para ulterior análise toxicológica.Os resultados obtidos através do ePOC mostraram diminuição da pressão parcial de dióxido de carbono (pCO2) (64%), aumento da concentração de lactato (36%), aumento dos valores de hemoglobina e hematócrito (50%), hiperglicémia (36%) e aumento dos valores de creatinina (50%), não havendo, contudo, relação estatisticamente significativa entre as variáveis testadas e o diagnóstico toxicológico (p>0.05). Porém, em todos os animais considerados acidémicos houve detecção de compostos do grupo dos inseticidas anticolinesterásicos na análise toxicológica. O estudo clínico individualizado de cada caso permitiu verificar que, apesar da sintomatologia similar, os animais apresentavam distúrbios ácido-base diferentes, sendo por isso também necessária uma abordagem terapêutica diferenciada, fulcral especialmente em condições críticas. Estudos futuros, com uma amostra de maior dimensão e preferencialmente com exposição a diferentes xenobióticos, poderão permitir uma avaliação mais exata e abrangente da relação entre a etiologia das intoxicações e as alterações hidroeletrolíticas e de gases sanguíneas verificadas.
ABSTRACT - Clinical Approach to Poisoning in Canidae by Anticholinesterase Insecticides and use of immediate tests (Point of Care) - Faced with a suspected acute intoxication, a prompt and systematic approach to the patient, allows a fast provision of specific care. The triage, history taking, assessment and emergency medical intervention, diagnosis and treatment are key processes in this approach. The diagnosis is usually supported by an initial analytic panel. The use of immediate testing ("point of care"), allows the evaluation, not only of the patient’s general condition in real time, but also the effects that xenobiotics may have at an organic level, which may result in electrolyte and acid base disorders. The presente study intended to evaluate the analytical changes detected by ePOC ("Enterprise Point of Care") in animals suspected of poisoning by anticholinesterase insecticides and their possible influence on the diagnostic and therapeutic implementation. The sample consisted of 14 canines, which had nonspecific symptoms and other compatible with acute poisoning by anticholinesterase insecticides: muscle tremors (93%), hypersialia (64%), fever (57%), cyanosis (50%), diarrhea (57%) and vomiting (36%). Blood samples were collect to perform ePOC testing and for further toxicological analysis. Analytical changes (ePOC) showed a decreased partial pressure of carbon dioxide (pCO2) (64%), an increased lactate concentration (36%), na increase in hemoglobin and hematocrit levels (50%), hyperglycemia (36%) and an increased serum creatinine values (50%), without, however, statistically significant relationship between the variables tested and toxicological diagnosis (p> 0.05). Nevertheless, in all animals considered acidemic, toxicological analysis showed the detection of anticholinesterase insecticides. The individualized clinical study of each case has shown, that despite the similar symptoms, the animals had different acid-base disorders and is, therefore, also required a different therapeutic approach, especially in critical conditions. Further studies with a larger sample and preferably with exposure to different xenobiotics may allow a more accurate and comprehensive evaluation of the relationship between the etiology of poisoning and blood gas and electrolyte changes observed.

Thesis (MEng)--Stellenbosch University, 2015.
ENGLISH ABSTRACT: South Africa has a severe HIV (human immunodeficiency virus) burden and the management of the disease is a priority, especially in the public healthcare sector. One element of managing the disease, is determining when to initiate an HIV positive individual onto anti-retroviral therapy (ART), a treatment that the patient will remain on for the remainder of their lifetime. For the majority of HIV positive individuals in the country, this decision is governed by the results of a CD4 (cluster of differentiation 4) test that is performed at set time intervals from the time that the patient is diagnosed with HIV until the patient is initiated onto ART. A device for CD4 measurement at the point of care (POC), the Alere PIMA™, has recently become commercially available. This has prompted a need to evaluate whether CD4 testing at the POC (i.e. at the patient serving healthcare facility) should be incorporated into the South African public healthcare sector's HIV diagnostic service provision model. One challenge associated with the management of HIV in the country is the relatively large percentage of patients that are lost to follow-up at various points in the HIV treatment process. There is extensive evidence that testing CD4 levels at the POC (rather than in a laboratory, as is the current practice) reduces the percentage of patients that are lost to follow-up before being initiated onto ART. Therefore, though POC CD4 testing is more expensive than laboratory-based CD4 testing, the use of this technology in South Africa should be investigated for its potential to positively influence health outcomes. In this research, a multi-objective location science model is used to generate scenarios for the provision of CD4 testing capability. For each scenario, CD4 testing provision at 3 279 ART initiation facilities is considered. For each facility, either (i) a POC device is placed at the site; or (ii) the site's testing workload is referred to one of the 61 CD4 laboratories in the country. To develop this model, the characteristics of eight basic facility location models are compared to the attributes of the real-world problem in order to select the most suitable one for application. The selected model's objective, assumptions and inputs are adjusted in order to adequately model the realworld problem. The model is solved using the cross-entropy method for multi-objective optimisation and the results are verified using a commercial algorithm. Nine scenarios are selected from the acquired Pareto set for detailed presentation. In addition, details on the status quo as well as a scenario where POC testing is used as widely as possible are also presented. These scenarios are selected to provide decision-makers with information on the range of options that should be considered, from no or very limited use to widespread use of POC testing. Arguably the most valuable contribution of this research is to provide an indication of the optimal trade-off points between an improved healthcare outcome due to POC CD4 testing and increased healthcare spending on POC CD4 testing in the South African public healthcare context. This research also contributes to the location science literature and the metaheuristic literature.
AFRIKAANSE OPSOMMING: Suid-Afrika gaan gebuk onder `n swaar MIV- (menslike-immuniteitsgebreksvirus-) las en die bestuur van die siekte is `n prioriteit, veral in die openbare gesondheidsorgsektor. Een element in die bestuur van die siekte is om te bepaal wanneer `n MIV-positiewe individu met antiretrovirale- (ARV-)behandeling behoort te begin, waarop pasiënte dan vir die res van hul lewens bly. Vir die meeste MIV-positiewe individue in die land word hierdie besluit bepaal deur die uitslae van `n CD4- (cluster of differentiation 4-)toets wat met vasgestelde tussenposes uitgevoer word vandat die pasiënt met MIV gediagnoseer word totdat hy of sy met ARV-behandeling begin. `n Toestel vir CD4-meting by die punt van sorg (\POC"), die Alere PIMA™, is onlangs kommersieel beskikbaar gestel. Dit het `n behoefte laat ontstaan om te bepaal of CD4-toetsing by die POC (met ander woorde, by die gesondheidsorgfasiliteit waar die pasiënt bedien word) by die MIV-diagnostiese diensleweringsmodel van die Suid-Afrikaanse openbare gesondheidsorgsektor ingesluit behoort te word. Een uitdaging met betrekking tot MIV-bestuur in die land is die betreklik groot persentasie pasiënte wat verlore gaan vir nasorg in die verskillende stadiums van die MIV-behandelingsproses. Heelwat bewyse dui daarop dat die toetsing van CD4-vlakke by die POC (eerder as in `n laboratorium, soos wat tans die praktyk is) die persentasie pasiënte wat verlore gaan vir nasorg voordat hulle met ARV-behandeling kan begin, verminder. Daarom, hoewel CD4-toetsing by die POC duurder is as toetsing in `n laboratorium, behoort die gebruik van hierdie tegnologie in Suid-Afrika ondersoek te word. In hierdie studie is `n meerdoelige liggingswetenskapmodel gebruik om scenario's vir die voorsiening van CD4-toetsvermoë te skep. Vir elke scenario word CD4-toetsvermoë by 3 279 ARV-inisiasie fasiliteite oorweeg. Vir elke fasiliteit word toetsvermoë verskaf deur (i) die plasing van POC-toestelle by die fasiliteit, of (ii) verwysing vir laboratoriumgebaseerde toetsing by een van die 61 CD4-laboratoriums in die land. Die kenmerke van agt basiese fasiliteitsliggingsmodelle is met die kenmerke van die werklike probleem vergelyk om die mees geskikte model vir toepassing op die werklike probleem te bepaal. Die doelwitte, aannames en insette van die gekose model is daarna aangepas om die werklike probleem voldoende te modelleer. Die model is opgelos met behulp van die kruis-entropie-metode vir meerdoelige optimering, waarna die resultate deur middel van `n kommersiële algoritme bevestig is. Nege scenario's uit die verworwe Pareto-stel word uitvoerig aangebied. Daarbenewens beskryf die studieresultate die besonderhede van die status quo sowel as `n scenario waar POC-toetsing so wyd moontlik gebruik word. Hierdie scenario's word aangebied om besluitnemers van inligting te voorsien oor die verskeidenheid moontlikhede wat oorweeg kan word, wat wissel van geen of baie beperkte tot wydverspreide gebruik van POC-toetsing. Die mees beduidende bydrae van hierdie navorsing is stellig dat dit `n aanduiding bied van die optimale kompromie tussen `n verbeterde gesondheidsorguitkoms weens CD4-toetsing by die POC, en verhoogde gesondheidsorgbesteding aan CD4-toetsing by die POC, in die konteks van Suid-Afrikaanse openbare gesondheidsorg. Die navorsing dra ook by tot die ligingswetenskapliteratuur sowel as tot die metaheuristiekliteratuur.

A magnetic bead-based DNA extraction and purification device has been designed to be used for extraction of the target DNA molecules from whole blood sample. Mixing and separation steps are performed using functionalised superparamagnetic beads suspended in the cell lysis buffer in a circular chamber that is sandwiched between two electromagnets. Non-uniform nature of the magnetic field causes temporal and spatial distribution of the beads within the chamber. This process efficiently mixes the lysis buffer and whole blood in order to extract DNA from target cells. Functionalized surface of the magnetic beads then attract the exposed DNA molecules. Finally, DNA-attached magnetic beads are attracted to the bottom of the chamber by activating the bottom electrode. DNA molecules are extracted from the magnetic beads by washing and re-suspension processes. The numerical simulation approach has been adopted in order to design the magnetic field source. The performance of the magnetic field source has been investigated against different physical and geometrical parameters and optimised dimensions are obtained with two different magnetic field sources; integrated internal source and external source. A new magnetic field pattern has been introduced in order to efficiently control the bulk of magnetic beads inside the mixing chamber by dynamic shifting of magnetic field regions from the centre of the coils to the outer edge of the coils and vice versa. A Matlab code has been developed to simulate beads trajectories inside the designed extraction chip in order to investigate the efficiency of the magnetic mixing. A preliminary target molecule capturing simulation has also been performed using the simulated bead trajectories to evaluate the DNA-capturing efficiency of the designed extraction chip. The performance of the designed extraction chip has been tested by conducting a series of biological experiments. Different magnetic bead-based extraction kits have been used in a series of preliminary experiments in order to extract a more automation friendly extraction protocol. The efficiency of the designed device has been evaluated using the spiked bacterial DNA and non-pathogenic bacterial cell cultures (B. subtilis, Gram positive bacteria and E. coli, Gram negative bacteria) into the blood sample. Excellent DNA yields and recovery rates are obtained with the designed extraction chip through a simple and fast extraction protocol.

Objectives: To evaluate the long term total imprecision of HbA1c testing within the county of Uppsala in relation to the Swedish analytical goal of coefficient of variation (CV) <3% for HbA1c and to study the cost of an external quality assurance program for point-of-care HbA1c The county uses Bayer DCA 2000™ for point-of care HbA1c testing currently having 23 of these instruments.

Methods: Method imprecision was assessed by analysis of patient samples performed as split samples during a 3 year period (2002-2004) as part of the quality assurance program for point-of-care HbA1c testing. The samples were first analysed on a Bayer DCA 2000™ and the samples were then sent to the centralised laboratory for reanalysis with an HPLC system (Variant II™, Biorad). The testing was performed approximately 8 times per year with each instrument.

Results: The median CV between the HPLC method and the point-of-care instruments for each unit was slightly higher than 3%.

Conclusion: The DCA 2000™ systems have an acceptable imprecision and agreement with the central laboratory. The test results show acceptable agreements within the county regardless where the patient is tested. The cost of the external quality assurance program is calculated to be approximately SEK 1340 (Euro 150) per instrument.

HIV, syphilis, malaria, and anaemia are major causes of adverse pregnancy outcomes in sub-Saharan Africa (SSA). Despite global and national policies advocating for screening of these conditions, only HIV testing has achieved good coverage, precluding early detection and appropriate management in pregnancy. Rapid pointof-care tests (POCTs) provide an opportunity to integrate diagnosis and provide timely treatment of these conditions in rural antenatal care (ANC) settings. After an introductory chapter, a review of the literature on these four conditions in pregnancy is presented with a focus on SSA. The thesis then shifts attention to Kenya, a country that embodies many of the disease challenges and health system characteristics of the region. Kenyan ANC policy recommends testing for HIV, syphilis and anaemia and preventive strategies for malaria. The following chapters are comprised of three linked studies conducted in western Kenya, that use different methods to progressively investigate the implementation success of integrated point-of-care testing (POCT) for HIV, syphilis, malaria and anaemia at seven peripheral dispensaries. Baseline data confirmed that testing requirements for syphilis, malaria and anaemia are not currently met at dispensary level. We implemented an intervention where test kits were supplied and training plus supervision were provided to enable healthcare workers to conduct integrated POCT for pregnant women. Adoption and fidelity were measured quantitatively using exit interviews, antenatal registers and proficiency scores (Study 1: Integrating point-of-care testing (POCT) for HIV, syphilis, malaria and anaemia in antenatal care at dispensary level in western Kenya: an implementation study) while acceptability, appropriateness and feasibility were assessed qualitatively (Study 2: Exploring healthcare workers and pregnant women’s perspectives on appropriateness, acceptability and feasibility of integrating point-of care testing: A qualitative study). Our findings show that the innovation was highly adopted, meaning almost all pregnant women received the essential tests. This was supported by the qualitative findings where healthcare workers and pregnant women found the innovation acceptable and appropriate. However, fidelity to clinical management guidelines can still be improved. Our qualitative findings provide some explanation for these gaps. One common sentiment among interviews with healthcare workers was that workload was perceived to be a barrier to providing quality care. We explored this further with discrete-event simulation modelling (Study 3: Investigating the operational impact of integrating HIV, syphilis, malaria and anaemia point-of-care testing in antenatal care clinics in western Kenya: a discrete event simulation model) and found the healthcare workers were actually under-utilized. This suggests that nurses should, in theory, have sufficient time to deliver essential ANC services. While integrating POCT addresses one gap, additional interventions to support and supervise healthcare workers are needed to ensure appropriate and high quality of care. An integrated approach to health systems strengthening and more investment in implementation and translation research using multi-methods are needed.

Thesis (Ph.D.)--University of Cincinnati, 2006.
Advisor: Dr. Chong H. Ahn. Title from electronic thesis title page (viewed Dec. 22, 2009). Keywords: Lab-on-a-chip; Cardiac biomarker; multi-analyte; Protein chip; Chemiluminescence; immunoassay; BioMEMS; Polymer microfabrication. Includes abstract. Includes bibliographical references.

Objective: The aim of this study was to evaluate a new underfill-function in a POCT-instrument from HemoCue AB (Ängelholm, Sweden). The instrument is in use today among diabetes patients for self-monitoring blood glucose (SMBG). The new function is supposed to guarantee that measuring only will be performed on a sufficient sample volume to assure that the correct glucose value is received.

Methods and results: Blood samples (whole blood) from 12 patients were analysed with the instrument. Measuring were performed using different volumes in the cuvette. Full cuvette, 3µL, 2µL, 1µL and a measuring on an empty cuvette. The instrument performed measurements on all volumes added to the cuvette except for the empty cuvette. The less sample volume that was used the lower glucose values were reported by the instrument.

Conclusions: The new under fill-function did not work satisfactory. If such function would be more reliable it would be beneficial for the patient controlling hers/his bloodglucose provided that the testing procedure is being correctly done. This is very important because the results are often used to treat the patient.

Today, the growing and aging population, and the rise of new global threats on human health puts an increasing demand on the healthcare system and calls for preventive actions. To make existing medical treatments more efficient and widely accessible and to prevent the emergence of new threats such as drug-resistant bacteria, improved diagnostic technologies are needed. Potential solutions to address these medical challenges could come from the development of novel lab-on-chip (LoC) for point-of-care (PoC) diagnostics. At the same time, the increasing demand for sustainable energy calls for the development of novel approaches for energy conversion and storage systems (ECS), to which micro- and nanotechnologies could also contribute. This thesis has for objective to contribute to these developments and presents the results of interdisciplinary research at the crossing of three disciplines of physics and engineering: electrokinetic transport in fluids, manufacturing of micro- and nanofluidic systems, and surface control and modification. By combining knowledge from each of these disciplines, novel solutions and functionalities were developed at the macro-, micro- and nanoscale, towards applications in PoC diagnostics and ECS systems. At the macroscale, electrokinetic transport was applied to the development of a novel PoC sampler for the efficient capture of exhaled breath aerosol onto a microfluidic platform. At the microscale, several methods for polymer micromanufacturing and surface modification were developed. Using direct photolithography in off-stoichiometry thiol-ene (OSTE) polymers, a novel manufacturing method for mold-free rapid prototyping of microfluidic devices was developed. An investigation of the photolithography of OSTE polymers revealed that a novel photopatterning mechanism arises from the off-stoichiometric polymer formulation. Using photografting on OSTE surfaces, a novel surface modification method was developed for the photopatterning of the surface energy. Finally, a novel method was developed for single-step microstructuring and micropatterning of surface energy, using a molecular self-alignment process resulting in spontaneous mimicking, in the replica, of the surface energy of the mold. At the nanoscale, several solutions for the study of electrokinetic transport toward selective biofiltration and energy conversion were developed. A novel, comprehensive model was developed for electrostatic gating of the electrokinetic transport in nanofluidics. A novel method for the manufacturing of electrostatically-gated nanofluidic membranes was developed, using atomic layer deposition (ALD) in deep anodic alumina oxide (AAO) nanopores. Finally, a preliminary investigation of the nanopatterning of OSTE polymers was performed for the manufacturing of polymer nanofluidic devices.

QC 20140509

Rappid
NanoGate
Norosensor

Diagnostics of disease at POC (point of care) has been declared one of the Grand Challenge by the Bill and Melina Gates Foundation (BMGF). Infectious diseases constitute a major cause of disease burden and cause more than half a billion Disability-Adjusted Life Years (DALYs) and millions of deaths each year. They have an especially large effect on children under 5 years of age. We have analyzed data from the GBD 2010 (Global Burden of Disease) project to emphasize the damage caused by infectious diseases, and highlight the opportunity of using diagnostic tools to rapidly identify and treat diseases. To motivate the work of this thesis, we quantify the expected impact of appropriate diagnostic technologies.

We have also analyzed the requirements that a diagnostic tool should meet to generate the maximal global impact. We present various existing TPPs (Target Product Profiles) from different organizations and suggest some additions to these existing TPPs. We explain the particular molecular pathology technologies which have the potential to allow deployment of functional products in the developing world for point-of-care pathogen detection, especially in low-resource settings.

We perform a detailed analysis on existing polymerase chain reaction (PCR) systems and describe the problems caused with thermal performance and optical interrogation. We list the requirements that disposable cartridges for such instruments should meet and suggest a metal base design with polymer top. After detailed FEA simulations, we demonstrate that the thermal response can be modeled using a one-dimensional (1D) lumped element system. We show improvements in thermal response due to using a metal base and the effect of fluid height. We also performed thermal-structural simulations to quantify the stresses on the adhesive bonds of metal/polymer cartridges. Next, we explain fabrication of these cartridges. We show methods to dispense adhesive using a robot and a custom made jig to spread the adhesive during curing. The cartridge was tested with different PCR reagents and we obtained reaction efficiencies approaching those of the commercial real time PCR machines. Our fabrication technique is useful to join dissimilar materials and is production friendly. By developing custom software, we observed the cartridge performance in a continuous manner. We could see the thermal response of cartridges by continuous fluorescence monitoring, and used reflective aluminum which increase light collection efficiency.

We then present a simple and robust new way for thermal cycling. Robust thermal cycling has been a major challenge conducting PCR, especially in point of care situations. Here, we suggest a contact cooling approach, in which the cartridge rests on a thin metal plate with an integrated thin heater constructed from flexible printed circuit board (PCB) material. We use a solenoid to move a metal plate to cool down the sample cartridge during cycling. The metal plate then rests on a larger heat sink to disperse the shuttled heat. Our design is dust and water proof and was verified on a bench-top prototype.

A novel optical design for fluorescence detection during qPCR is also described. We suggest a lateral illumination waveguide geometry with prism coupling that eliminates lenses and is integrated into an injection molded cartridge. The light is homogenized using a light guide, and we quantify the sources of scattered stray light from the chamber edge by performing ray tracing simulations to optimize the precise geometry. The design is tolerant to misalignments and enables easy coupling of LED light into the chamber. As the light collection efficiency is high, the size of the chamber can be very small. We tested real PCR reactions using this concept and observed a rapid integration time, enabling very fast reading.

Sample preparation has been another challenge for all point-of-care (POC) lab-on-chip devices for many years. Here, we propose a new design which is robust, fast, flexible and simple, and uses a sliding seal to move the collected sample between various reservoir chambers. The sample moves on a slider sandwiched between seals that shuttles a DNA binding membrane between different reactions. Thus, size and volumes of reagents can be increased without increasing dead volumes. This design is easily automated, and positive displacement of fluids can work with many reagents without worrying about their characteristics such as foaming. The speed of the sample preparation protocols is high and complex protocols can be ported on this design concept, which we tested on real clinical samples and obtained impressive results. We designed and injection molded devices to test and verify this concept.

Finally, we focus on instrumentation and software required to allow our technology to be used at the POC. We describe our embedded electronics and describe the powerful micro-controller and various high performance ICs that are used to construct a fully functional for sample to answer instrument. We developed various versions of software. The developer software allows us to control our system and bench top setup. Our end user product includes a tablet and cell phone software interface. Software was developed for a windows 8 tablet, windows 8 phone and an Android based devices.

To conclude, we very briefly describe the POC systems that are under development: A portable qPCR system with a separate cartridge design, and a universal sample to answer system that performs qPCR, sample preparation and sample to answer protocols in one box depending on the cartridge.

As per best of our knowledge the cost of this technology is much lower than any other option in its class. The sample to answer instrument is expected to cost less than $500. The test cost is expected to be less than $5. The performance is not compromised. We hope that this work can help bring a transformative change in the practice of pathology especially in the developing world.

Medical devices are used widely at every stage of disease diagnosis and treatment. To eradicate certain infectious diseases, the development of highly sensitive diagnostic tools and techniques is essential. The work reported in this thesis presents a novel approach, which can be used for the diagnosis of various diseases in the field of clinical cytology. The central theme of this approach was to develop a simple, holistic and completely automated system for point-of-care (POC) diagnostics. This is realized through the Development of an Absorption Flow-Cytometer with Synergistic Integration of Microfluidic, Optics and simple Electronics. Quantitative diagnosis of malaria has been taken as test case for the characterization and validation of the developed technology. Malaria is a life-threatening disease widely prevalent in developing countries. Approximately half the world population undergoes a test of malaria and it kills close to half a million people every year. Early detection and treatment will reduce the number of fatalities and also decrease its transmission rate. In the recent past, several diagnostic tools have been developed to detect malaria but there are varied demands on diagnostic instruments in healthcare settings and endemic contexts. The objective of this thesis is to develop an instrument capable of identifying malaria-infected red blood cells (i-RBCs) from a given few micro-liters of whole blood. The optical absorption properties of blood cells were measured at a single-cell level to diagnose malaria. The proof-of-concept for the instrument was established in four stages, after which a prototype was also developed and validated. In the first stage, a system capable of simultaneously imaging cells and also measuring their optical absorbance properties was developed. The developed system was employed to characterize absorption properties of red blood cells (malaria-infected and healthy ones) on blood-smear. A custom-made bright-field transmission microscope in combination with a pair of laser diode and photo-detector was used to simultaneously image and measure transmittance of infected and uninfected RBCs. In the second stage, the technique was extended to enable high-throughput measurements with the use of microfluidic sample handling and synchronous data acquisition. Using this technique, the optical absorbance and morphology of infected and healthy RBCs have been characterized in statistically significant numbers. The correlation between cell morphology (from images) and single-cell optical absorbance level helped to establish the thresholds for differentiating healthy and infected cells. In the third stage, a portable prototype capable of assessing optical absorbance levels of single cells was fabricated. The developed prototype is capable of assessing cells at throughputs of about 1800 cells/ second. It was initially validated with sample suspensions containing infected and healthy RBCs obtained from malaria cultures. For the device to be usable at the field-level, it has to function in the presence of all other cellular components of whole blood. The optical absorbance of other cellular components of blood like white blood cells and platelets, were characterized. The device was finally tested with blood samples spiked with malaria-infected RBCs validating the overall proof-of-concept and the developed prototype. The deployment of such cost-effective, automated POC system would enable malaria diagnosis at remote locations and play a crucial role in the ongoing efforts to eradicate malaria. In future, the presented technology can be extended to develop POC diagnostic tool for other diseases as well. As it enables quantitative estimation of malaria, the present optical absorption flow analyzer would also find application in disease prognosis monitoring, anti-malarial drug development and other studies requiring measurements on a single-cell basis. The hyper-imaging system can be used to characterize and validate the threshold information, and can be incorporated in the prototype. Thus, it is a continuous process to characterization and implementation in the prototype. The optofluidic absorption flow analyzer will help enable affordable clinical diagnostic testing in resource limited settings. This approach will be extended to diagnose other diseases, using differences in optical absorption as criteria for differentiating healthy and infected cells.

Medical devices are used widely at every stage of disease diagnosis and treatment. To eradicate certain infectious diseases, the development of highly sensitive diagnostic tools and techniques is essential. The work reported in this thesis presents a novel approach, which can be used for the diagnosis of various diseases in the field of clinical cytology. The central theme of this approach was to develop a simple, holistic and completely automated system for point-of-care (POC) diagnostics. This is realized through the Development of an Absorption Flow-Cytometer with Synergistic Integration of Microfluidic, Optics and simple Electronics. Quantitative diagnosis of malaria has been taken as test case for the characterization and validation of the developed technology. Malaria is a life-threatening disease widely prevalent in developing countries. Approximately half the world population undergoes a test of malaria and it kills close to half a million people every year. Early detection and treatment will reduce the number of fatalities and also decrease its transmission rate. In the recent past, several diagnostic tools have been developed to detect malaria but there are varied demands on diagnostic instruments in healthcare settings and endemic contexts. The objective of this thesis is to develop an instrument capable of identifying malaria-infected red blood cells (i-RBCs) from a given few micro-liters of whole blood. The optical absorption properties of blood cells were measured at a single-cell level to diagnose malaria. The proof-of-concept for the instrument was established in four stages, after which a prototype was also developed and validated. In the first stage, a system capable of simultaneously imaging cells and also measuring their optical absorbance properties was developed. The developed system was employed to characterize absorption properties of red blood cells (malaria-infected and healthy ones) on blood-smear. A custom-made bright-field transmission microscope in combination with a pair of laser diode and photo-detector was used to simultaneously image and measure transmittance of infected and uninfected RBCs. In the second stage, the technique was extended to enable high-throughput measurements with the use of microfluidic sample handling and synchronous data acquisition. Using this technique, the optical absorbance and morphology of infected and healthy RBCs have been characterized in statistically significant numbers. The correlation between cell morphology (from images) and single-cell optical absorbance level helped to establish the thresholds for differentiating healthy and infected cells. In the third stage, a portable prototype capable of assessing optical absorbance levels of single cells was fabricated. The developed prototype is capable of assessing cells at throughputs of about 1800 cells/ second. It was initially validated with sample suspensions containing infected and healthy RBCs obtained from malaria cultures. For the device to be usable at the field-level, it has to function in the presence of all other cellular components of whole blood. The optical absorbance of other cellular components of blood like white blood cells and platelets, were characterized. The device was finally tested with blood samples spiked with malaria-infected RBCs validating the overall proof-of-concept and the developed prototype. The deployment of such cost-effective, automated POC system would enable malaria diagnosis at remote locations and play a crucial role in the ongoing efforts to eradicate malaria. In future, the presented technology can be extended to develop POC diagnostic tool for other diseases as well. As it enables quantitative estimation of malaria, the present optical absorption flow analyzer would also find application in disease prognosis monitoring, anti-malarial drug development and other studies requiring measurements on a single-cell basis. The hyper-imaging system can be used to characterize and validate the threshold information, and can be incorporated in the prototype. Thus, it is a continuous process to characterization and implementation in the prototype. The optofluidic absorption flow analyzer will help enable affordable clinical diagnostic testing in resource limited settings. This approach will be extended to diagnose other diseases, using differences in optical absorption as criteria for differentiating healthy and infected cells.

The Polymerase Chain Reaction (PCR) is one of the most sensitive and specific diagnostic tools available today. Yet, it stands out of reach for many vulnerable populations because commercial solutions are expensive, bulky, and require a steady electrical connection. The vast majority of designs that attempt to fill in this gap use Peltier elements for heating and cooling. In this work, I develop a mechanism that promises the same benefits, but without the drawbacks: optical heating. Peltier elements are easy to use, have no moving parts, and are widely available, but suffer from a critical flaw: energy inefficiency. This is because they cannot directly deliver heat to a 10μL drop of reagent: they need extra scaffolding, such as a thermal block, to conduct the heat. Optical heating can sidestep this by directly heating a tiny chamber that holds the drop, minimising wasted heat. Commercially available LEDs with 65% radiant efficiency, coupled with highly absorbing inks (>99% absorption) promise extremely high efficiencies with correspondingly long battery life, but in this dissertation I demonstrate that even generic high-power LEDs combined with black permanent marker from the local stationery store are efficient enough to do the job. The bulk of my work has focused on developing a framework for a device that can be realised with no moving parts, no optics, and cheap, widely available components, materials, and processes. With this apparatus, I demonstrate heating and cooling rates of 11 and 8°C/s respectively, permitting ultrafast PCR operation, bringing the time required for a full 35-cycle PCR (with a 3 min hot-start and 2 min final elongation) down from an hour to only 15 minutes. Fast thermal cycling is only a part of the task at hand. Ensuring that an ultrafast PCR diagnostic assay works with the device requires further tuning of the device and work with the chemistries. The final sections of this work outline a variety of paths forward, towards realising a working ultrafast PCR device, ultrafast qPCR, and increasing the throughput of the device to more than 1 sample at a time.
NNetra Project jointly funded by MEITY and DST, BIRAC through IKP Knowledge Park as part of "Grand Challenges Exploration (GCE) India" grant

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Nos últimos anos, vários têm sido os esforços no combate da pandemia da infeção pelo vírus da imunodeficiência humana (HIV). Sem a existência de uma cura, as medidas atuais baseiam-se no controlo da doença através do tratamento antirretroviral. Para que este tratamento seja instituído de forma eficaz, é essencial o diagnóstico precoce de todos os infetados, bem como uma contínua monitorização do tratamento. Mais de metade de todos os infetados por HIV vivem em países Africanos. Nestes países subdesenvolvidos, principalmente em zonas mais remotas, existem grandes falhas nos sistemas de saúde, devido a vários problemas infraestruturais e de escassez de recursos, tornando difícil a realização de procedimentos laboratoriais. Como tal, tem sido dada uma grande importância à criação de testes de diagnóstico e monitorização baratos, rápidos, de fácil utilização e que necessitem de poucos meios, que possam ser utilizados de forma confiável no point-of-care (POC), junto da população destas zonas. Nos últimos anos, tem havido um grande desenvolvimento nesta área e vários testes POC para o diagnóstico, determinação carga viral e contagem de linfócitos T CD4+ já estão a ser utilizados, o que permitiu um aumento do número de pessoas diagnosticadas, monitorizadas e a receber tratamento. Este trabalho tem como objetivo fazer uma revisão dos vários testes POC disponíveis, em desenvolvimento ou em estudo para as diferentes vertentes do diagnóstico e monitorização da infeção por HIV. São referidas as características destas plataformas e as suas falhas, bem como o modo de implementação e utilização.
In recent years, there were made several efforts to combat the human immunodeficiency virus (HIV) pandemic. Without a cure, the current actions aim to control the disease by using the existing antiretroviral therapy. To achieve an effective treatment, it’s essential to early diagnose all infected people, as well as maintain a continuous treatment monitoring. More than half of all HIV-infected people in the world live in African countries. In these underdeveloped countries, especially in more remote areas, there are major gaps in health systems, due to various infrastructure problems and shortage of resources, making it difficult to perform laboratory procedures. Therefore, a great importance has been given to the creation of inexpensive, fast, easy-to-use diagnostic and monitoring tests that require few resources and can be reliably used at the point-of-care (POC), near the population of these areas. In recent years, there has been a great development in this topic and several point-of-care tests for diagnosis, determination of viral load and CD4+ T cell count are already being used. These have allowed an increase in the number of people diagnosed, monitored and receiving HIV treatment. This dissertation aims to review the various point-of-care tests available, under development or being studied for the different fields of diagnosis and monitoring of HIV infection. The characteristics of these platforms and their flaws are mentioned, as well as the way of use and implementation.

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Os testes point-of-care (POCT) ou testes rápidos de diagnóstico surgiram como resultado de uma necessidade de evolução na prestação de cuidados de saúde, aliada ao desenvolvimento tecnológico. Caracterizam-se pela sua simplicidade e rapidez, podendo ser executados por qualquer profissional de saúde, ou mesmo pelo próprio doente no seu local de atendimento. Nos últimos anos, em Portugal, o envelhecimento da população, o aumento da incidência de doenças crónicas (diabetes, doenças cardiovasculares), bem como a adoção de estilos de vidas pouco saudáveis, têm obrigado a um maior controlo face ao diagnóstico, assim como à prevenção e controlo da doença.Numa altura em que a concorrência no setor farmacêutico, sobretudo na farmácia comunitária, tem vindo a aumentar, é também de salientar as reduções sucessivas do preço dos medicamentos e das suas margens de comercialização. Tais medidas, fizeram com que o setor das farmácias tenha atravessado, nos últimos anos, uma crise económica, levando ao encerramento de inúmeros estabelecimentos.O farmacêutico comunitário funciona como elo de ligação privilegiado entre o doente e a promoção da saúde, estando apto a acompanhar o utente e auxiliando no rastreio, diagnóstico e monitorização de fármacos com segurança, eficácia e qualidade, uma vez que possui, seguramente, as competências necessárias para tal. A implementação do Point-of-care testing no âmbito da farmácia comunitária é, assim, considerada uma mais-valia para os cuidados de saúde do doente, bem como para o farmacêutico, enquanto profissional, podendo este tirar partido das suas competências e colocá-las ao serviço do bem-estar do utente.
Point-of-care testing (POCT) or rapid diagnostic tests are the result of a combined evolution in health care delivery coupled up with a technological rise. Characterised by their simplicity and quick results, they can be done by any health professional or even by the patient in any consultation location.In recent years, in Portugal, the aging of the population, the increasing incidence of chronic diseases (diabetes, cardiovascular diseases), as well as the adoption of unhealthy lifestyles, have forced greater control over diagnosis, as well as disease prevention and control.At the time that the competition in the pharmaceutical sector, especially in the Community pharmacy, is increasing, successive reductions in the price of medicinal products and their marketing margins should also be highlighted. Such measures have caused the pharmacy sector to have experienced an economic crisis in recent years, leading to the closure of numerous establishments.The community pharmacist acts as a privileged link between the patient and health promotion, being able to guide the patient through medical screening, diagnose and safe drug administration, effectiveness and quality, since they certainly have the skills necessary for this. The implementation of Point-of-care testing in your local pharmacy is not only beneficial to the patient health care but also to the pharmacist as a health professional, who can take advantage of their skills, as these provide additional data when looking after the patients of the pharmacy.

Point-of-care Diagnostics (POCD) is one of the rapidly growing areas of health-care sector that avails to the needs of the patient at the point-of-care. An ideal POCD device is required to be compact, portable, offer quick results, require no or minimal sample preparation, and inexpensive with a low cost per test. Micro fluidics has a potential to cater to these needs, thereby leading to a growing research interest to develop micro uidic POCD (POCD) devices. POCD devices can be broadly categorized into cellular diagnostics and non-cellular diagnostics. Micro fluidic flow cytometers (imaging and laser based) are the emerging diagnostics tools for biological cell identi cation, categorization, and counting. Despite the advances in this area these flow cytometers have not yet been turned into POCD devices. This thesis focuses on finding solutions for the major problems associated with these micro fluidic flow cytometers towards becoming POCD devices. However, the developed techniques are quite general and can be equally well applied for non-cellular diagnostics as well. More specfi cally this thesis presents techniques for focusing of cells in flow, in- flow decantation, and pumping along with the experimental demonstration of these techniques in the context of deformability estimation of cells in ow, blood cell counting, and quantitative microscopic urinalysis. Focusing of the cells while in flow is at the heart of the operation of flow cytometers. The developed technique reduces the complexity of fabrication and offers its applicability for a wide range of flow rates, thereby decreasing the cost per device and simultaneously offering the flexibility of its use in both imaging and laser-based flow cytometers. The in- flow decantation technique adds an extra dimension to the possibility of realizing sheath-free ow focusing, by separating the particle-free fluid from the sample itself. The simplicity of the design and the applicability of the technique for wide varieties of ow rates, particle concentrations, and sizes while having the ability to offer 100 % purity at high yields, offers its potential applications into the realization of POCD that can operate on plasma separated from whole blood for several biochemical assays, rare cell enrichment in cancer diagnostics, immunodiagnostics etc. Pumping is an unavoidable task to cause ow of either sample or sheath fluids into the micro fluidic device. The developed pump uses the mechanical energy from the fingers and stores inside an elastic block to cause pumping action when released subsequently. The pumping mechanism is very general and is independent of the type of elastomeric block involved. However, the low rate quantity and stability depend upon the nature of stress-strain curve and the stiffness of the elastomeric block used inside the pump. This pump is inexpensive (< 4 USD), compact, portable, and reusable (> 500 times) making it as an ideal choice for the POCDs. Using the developed ow focusing device, deformability and the associated elastic moduli of RBCs (that are obtained from healthy and diabetic subjects) and cancer cells (with and without Emodine Anticancer drug treatment) were obtained and the results were found to be in agreement with literature. To further demonstrate the applicability of the ow focusing device for blood cell imaging and counting, blood cells (Red Blood Cells - RBCs and White Blood Cells - WBCs) in ow were imaged and the counts were compared with standard hematological analyzer counts. Similar experiments were performed on urine samples to demonstrate the technique's applicability for quantitative microscopic urinalysis. Wide variety of cells that can be found in Urine such as RBCs, WBCs, Epithelial cells, and Casts were imaged, and a quantitative analysis was performed to infer the diagnosis and the observations were compared with clinical results. All these results indicate the robustness of the developed techniques and their excellent applicability for a wide range of POCDs.

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library.
The key research question examined in this thesis was: Could POCT ( point-of-care pathology testing) models that were analytically sound and clinically and culturally effective be established in Australian Indigenous medical services for the prevention and management of diabetes and renal disease? The systematic approach to answer this overarching research question included the scientific validation of the analytical performance of suitable point-of-care (POC) devices, the development of a culturally appropriate education and training program for Aboriginal Health Workers (and nurses) as POCT operators, the implementation of a quality management framework for maintaining surveillance of the analytical quality of POCT results, and an assessment of qualitative and quantitative research outcomes to determine the clinical and cultural effectiveness of POCT.
http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1277656
Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2007

Title page, table of contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library.
The key research question examined in this thesis was: Could POCT ( point-of-care pathology testing) models that were analytically sound and clinically and culturally effective be established in Australian Indigenous medical services for the prevention and management of diabetes and renal disease? The systematic approach to answer this overarching research question included the scientific validation of the analytical performance of suitable point-of-care (POC) devices, the development of a culturally appropriate education and training program for Aboriginal Health Workers (and nurses) as POCT operators, the implementation of a quality management framework for maintaining surveillance of the analytical quality of POCT results, and an assessment of qualitative and quantitative research outcomes to determine the clinical and cultural effectiveness of POCT.
Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2007

Relatório de Estágio do Mestrado Integrado em Ciências Farmacêuticas apresentado à Faculdade de Farmácia
Cardiac biomarkers are often measured to provide guidance in regards to the welfare of patient in regards to cardiac health. Troponin I, a biomarker specific to myocardial injury, will be the subject of study in this monography. In recent years, troponin I has been the subject of several studies with the intent of better understanding its structure and pathophysiology finding some evidence that certain alterations of its isoform influence cardiac regulation. This lead to this protein being considered determinant for the diagnosis of cardiac injury, making it a valuable means of diagnosis to rule in/out myocardial infarction.In this context, the need arises for testing methods that allow for troponin I detection with necessary rigor and speed. Point-of-care tests (POCT) involve testing in the presence of the patient. They have faster response times when compared to tests performed in clinical analysis laboratories and require less sample volume. It becomes an ideal approach when implanted in a medical triage setting, with potential to significantly reduce waiting times in hospital emergency services. POCT should provide quantitative values of cardiac troponin I. However, there are several that need to, conjunctly, be optimised so that the POC platform can be successfully implemented. In recent years, highly specific techniques for the detection of troponin I have arisen with purpose of integrating the POC platform. In this monography, some bench POCT assays for detection of troponin I, that are currently being commercialised, will be characterized, and the more recent developments about the implementation of biosensors in point-of-care tests to make them more sensitive. The analytical and clinical challenges found in the measurements of troponine I will also be approached.
Os biomarcadores cardíacos são frequentemente medidos para fornecer orientação sobre o bem-estar dos pacientes em relação à saúde cardíaca. A troponina I, biomarcador específico de lesão do miocárdio, irá ser alvo de estudo na presente monografia. Ao longo dos últimos anos, a troponina I tem sido alvo de vários estudos com o intuito de compreender melhor a sua estrutura e fisiopatologia, existindo já alguma evidência de que determinadas alterações estruturais da sua isoforma influenciam a regulação cardíaca. Desta forma, esta proteína passou a ser considerada determinante para o diagnóstico de lesão cardíaca, passando a ser um meio de diagnóstico valioso para descartar/confirmar a possibilidade de enfarte do miocárdio.Neste contexto, surge a necessidade de encontrar métodos que permitam a deteção da troponina I com o rigor e rapidez necessários. Os testes point-of-care (POCT) envolvem a realização do teste de diagnóstico na presença do paciente. Têm tempos de resposta mais curtos quando comparados com os testes realizados nos laboratórios de análises clínicas, e requerem o uso de reduzidos volumes de amostra. Torna-se uma abordagem ideal para implementar na triagem médica, com potencial para aliviar consideravelmente os tempos de espera nos serviços de urgência hospitalar. Os POCT devem fornecer medidas quantitativas da troponina I cardíaca. No entanto, existem vários fatores que, em conjunto, precisam de ser otimizados para que a plataforma POC seja implementada com sucesso. Nos últimos anos, têm surgido técnicas de deteção de troponina I altamente sensíveis com vista a integração nas plataformas POC. Na presente monografia serão caracterizados alguns ensaios POCT de bancada atualmente comercializados para deteção da troponina I, e analisados os desenvolvimentos mais recentes sobre a implementação de biossensores nos testes point-of-care, por forma torná-los mais sensíveis. Os desafios analíticos e clínicos encontrados durante as medições de troponina I serão também abordados.

Nowadays the hospitals and the medical centres face a huge challenge finding solutions to improve the efficiency of medical diagnosis. The scope of this project was to develop a “Point-of-Care Diagnostic” (POCD) device, that can give a better alternative for genetic analysis, instead of the usual methods of PCR (polymerase chain reaction). This device is composed by three layers. The first layer which works as a transporter and filter was built on paper. The second layer is the substitute of the regular thermocycling phase in the PCR technique and the third layer incorporates an interdigital capacitor that works as a DNA (deoxyribonucleic acid) sensor with high sensitivity to detect DNA hybridisation. These last two layers were made in kapton film. The devices were produced with microfabrication methods using inkjet printing, lithographic and deposition processes. The device’s characterisation was based on impedance spectroscopy methods. With the purpose of testing the device, the capacitor was functionalised with the YWHAZ gene. However, this process can be performed with any other gene. Due to its characteristics, the device under study was designed to run RT-qPCR (Real time quantitative polymerase chain reaction) and presents itself as an effective way to substitute the traditional PCR techniques. Even more, as the transport of samples to a laboratory and the recruitment of specialised personnel are not necessary, costs and response time are reduced.

Submitted in fulfillment of the requirements for the Doctoral Degree in Nursing, Durban University of Technology, Durban, South Africa, 2016.
This mixed methods study aimed to assess the functioning and processes of the Fast Queue Service Point in order to analyse the quality of care rendered in primary health care (PHC) facilities in the eThekwini district of the KwaZulu­ Natal Province in South Africa. The Fast Queue Service Point provides service in PHC facilities for health care users requiring short consultations. Congestion of PHC facilities is a result of increased access to PHC services with the introduction of free PHC services. This congestion was aggravated by the decentralization of services from hospitals to PHC level such as the introduction on Nurse Initiated Management of Anti-Retroviral Therapy (NIMART). In 2010, the National Core Standards (NCS) for health establishments were formulated further to the PHC Service package, to address issues of quality. An explanatory sequential mixed methods study design was used and data collection was conducted in two phases; the quantitative data collection phase consisting of two subsets of observations namely; the retrospective record review and structured observations of the Fast Queue Service Point process. The Statistical Package for the Social Sciences (SPSS) version 22 was used to analyse data. During the second phase semi-structured interviews were conducted with PHC staff members to describe their experiences of the Fast Queue Service Point and to clarify issues from the quantitative phase. Although Fast Queue Service users received sufficient care, there were important care assessments that had been inadequately performed or omitted. These included discussing side effects of medications and or immunizations and management thereof. Childrens' weights were not interpreted, an important aspect for children under five years of age. There was also lack of supportive supervision coupled with shortage of resources and too many time-consuming written records that were required to compile accurate statistics. Retraining and in-servicing of health personnel and making resources available, would assist in strengthening patient assessment, management and recording thereof. While clinic managers require to offer supportive supervision to health care providers, provision of lower categories of staff would be beneficial in supporting PNs and ENs so that they have time to compile records for statistics purposes, which were found to be taking up the bulk of their time. The framework for continuous quality improvement in implementing a Fast Queue Service in PHC settings was developed based on the findings of the study
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Despite the concerted efforts in promoting prevention and testing campaigns and the availability of highly effective treatments, HIV and other sexually transmitted infections (STIs) continue to represent a pressing public health issue worldwide. These infections disproportionally affect the so-called vulnerable populations. In Europe, the majority of HIV/STIs new diagnosis are amongst Men who have Sex with Men. Notwithstanding the rapid development of diagnostic technologies for HIV and other STIs, laboratory-based tests are not always suitable for being used both in resource-limited settings, where diagnostic access and delivery are difficult, and in high-income countries to reach the vulnerable groups. To overcome this issue, WHO endorsed the development of STIs Point-Of-Care Tests (POCTs) to tackle HIV/STIs worldwide. So far, little is known either about the STIs POCTs performance in real life setting or about the potential impact of the replacement of standard laboratory methods with the POCTs approach among different high-risk target populations. To collect robust and reliable data on those issues, in 2017 the Reproductive Health and Research (RHR) Department of WHO launched an independent evaluation on the performance of STIs POCTs among target populations called Project on Sexually Transmitted Infections Point-of-care testing established by the Reproductive Health and Research Department of WHO (ProSPeRo initiative). This thesis is to report the methodological structure and the main finding of the two studies carried out at the HIV/STIs clinic of Verona, Italy between 2017 and 2018. Considered that in the European context, and in Italy as well, the most at risk population for HIV, syphilis and gonorrhoeae is that of Men who have Sex with Men, we decided to implement the two clinical-based studies amongst them: the evaluation of the dual HIV/syphilis POCTs and that of the NG/CT POCT in genital and extragenital sites. Between May 2018 and February 2019, 492 individuals were enrolled in the HIV/Syphilis study and 300 in the NG/CT one. In the HIV/Syphilis POCT evaluation, the rapid tests yielded an almost perfect performance as far as the HIV component is concerned. As for the treponemal component, despite specificity was very high, sensitivity was found to range between 75,8 and 81,7%. In the NG/CT POCT study, the performance varied according to the anatomical site and the considered pathogen. Indeed, although specificity was found to be always above 98%, when the NG component of the POCT is taken into account, the sensitivity ranged from 75% at pharyngeal site to 87,5% at rectal and urethral site. As for the CT component of the POCT, sensitivity was 100% with pharyngeal samples and 90%, 83,3% with rectal and urethral samples, respectively. STIs POCTs are valuable tools to tackle HIV/STIs worldwide although their routinary use have to be considered in close relation with the epidemiological characteristics of the population itself, beyond the analytical characteristics of the test. The findings of this thesis support the need for independent evaluation of new diagnostic technology before being integrated in the clinical practice as well as importance of alignment of such an evaluation with the best international standards.