No description available.

Thesis (Ph.D.)--Case Western Reserve University, 2009 / Abstract Title from OhioLINK (viewed on 20 April 2009) Department of Biomedical Engineering Available online via the OhioLINK ETD Center

No description available.

No description available.

Yes / The COVID-19 pandemic placed the UK healthcare system under unprecedented pressure, and recovery will require whole-system investment in innovative, flexible and pragmatic solutions. Positioned at the heart of the healthcare system, ambulance services have been tasked with addressing avoidable hospital conveyance and reducing unnecessary emergency department and hospital attendances through the delivery of care closer to home. Having begun to implement models of care intended to increase ‘see and treat’ opportunities through greater numbers of senior clinical decision makers, emphasis has now been placed upon the use of remote clinical diagnostic tools and near-patient or point-of-care testing (POCT) to aid clinical decision making. In terms of POCT of blood samples obtained from patients in the pre-hospital setting, there is a paucity of evidence beyond its utility for measuring lactate and troponin in acute presentations such as sepsis, trauma and myocardial infarction, although potential exists for the analysis of a much wider panel of analytes beyond these isolated biomarkers. In addition, there is a relative dearth of evidence in respect of the practicalities of using POCT analysers in the pre-hospital setting. This single-site feasibility study aims to understand whether it is practical to use POCT for the analysis of patients’ blood samples in the urgent and emergency care pre-hospital setting, through descriptive data of POCT application and through qualitative focus group interviews of advanced practitioners (specialist paramedics) to inform the feasibility and design of a larger study. The primary outcome measure is focus group data measuring the experiences and perceived self-reported impact by specialist paramedics. Secondary outcome measures are number and type of cartridges used, number of successful and unsuccessful attempts in using the POCT analyser, length of time on scene, specialist paramedic recruitment and retention, number of patients who receive POCT, descriptive data of safe conveyance, patient demographics and presentations where POCT is applied and data quality. The study results will inform the design of a main trial if indicated. / The full-text of this article will be released for public view at the end of the publisher embargo on 1 Jun 2024.

Point-of-care (POC) tests can improve the management of infectious diseases and clinical outcomes, through prompt diagnosis and appropriate delivery of treatments for preventable and treatable diseases, especially in resource-limited settings where health care infrastructure is weak, and access to quality and timely medical care is challenging. Microfluidics or lab-on-chip technology is appropriate for POC tests when general design constraints such as integration, portability, low power consumption, automation, and ruggedness are met. Although many POC tests have been designed for use in developed countries, they might not be readily transferable to resource-limited settings. These new technologies need to be accessible, affordable and practical to be implemented at resource-limited settings to save lives in developing countries. The overall goal of this dissertation is to develop microfluidic diagnostic devices which are practical and reliable for global health. We first focused on immunoassays, an important class of diagnostic tests which utilize antibodies to quantify host immunity or pathogen protein markers. We developed and evaluated a rapid, accurate, multiplexed, and portable microfluidic immunoassay for diagnosis of HIV and syphilis on hundreds of archived specimens (whole blood, plasma, and sera). Our assay exhibited performance equal to lab-based immunoassays in less than 20 minutes. In addition, our technique quantified signals using a handheld instrument, allowing for objective measurements as opposed to current rapid HIV tests which require subjective interpretation of band intensities. We further integrated three important off-chip processes in a diagnostic test - liquid handling, optical signal detection, and data communication – in a low-cost, versatile, handheld instrument capable of performing immunoassays on reagent-loaded (i.e. “ready-to-run”) cassettes at high analytical performance characteristic of ELISA but with the speed, portability and ease-of-use of a rapid test. We also evaluated this immunoassay device in Rwanda on archived samples and achieved analytical performance comparable to that of benchtop standards. To simplify the user interface and reduce the cost of the diagnostic device, we integrated our microfluidic immunoassay with a smartphone to replace computers or high-cost processors for diagnostic devices in low-resource settings. Our low-cost ($34), smartphone-supported device for a multiplexed immunoassay detected three antibody markers from HIV, treponemal- and non-treponemal syphilis from fingerstick whole blood simultaneously in 15 minutes. This device was designed to eliminate the number of manual steps, through the use of lyophilized secondary antibodies and anti-coagulant, preloaded reagents on cassette, and an automatic result readout. A step-by-step user guide was included on the smartphone to make the device simple enough to be used by an untrained operator. The analytical performance of the device was evaluated in Rwanda by local health care workers. We also accessed user experiences for improvement of the device in future. While immunoassays offer rapid and accurate diagnosis for infectious diseases, various infections cannot be confirmed using protein markers. Due to increasing clinical demand for detection of DNA and RNA signatures for diagnosis and monitoring of patients in resource-limited settings, we also explored how microfluidic and nanoparticle technologies can improve nucleic acid amplification test at the point of care. Nucleic acid tests are arguably some of the most challenging assays to develop due to additional steps required for sample pre-treatment (e.g. cell sorting, isolation, and lysis, as well as nucleic acid extraction), signal amplification (due to low physiological concentrations, target contamination, and instability) and product detection. Here we developed a sputum processor to isolate and lyse mycobacteria (M.smegmatis) from a more complex sample matrix, using magnetic beads-based target isolation to replace the need of a centrifuge or other complicated sample preparation technique. We also investigated a technique to detect Mycobacterium tuberculosis using multiplex polymerase chain reaction (PCR) and silver-gold amplification detection.

Point-of-care (POC) diagnostic technologies aim to expand access to traditional laboratory-based testing to near-patient settings. These settings can range from emergency or intensive care-units (ICUs) in the United States, to remote health posts in sub Saharan Africa. Differences in budget and infrastructure play a role in characterizing the wide array of possible “near patient” settings and must be taken into consideration in the engineering design process. In this dissertation we use translational engineering to develop practical and accessible microfluidic POC immunoassays for diverse settings, that include both provider and consumer facing applications. First, we examined Lyme Disease in the U.S., where existing diagnostic technologies face the challenge of rapid and accurate serodiagnosis in the face of largely non-specific clinical symptoms. We developed a multiplexed rapid test that could replicate enzyme-linked immunosorbent assay (ELISA) performance for Lyme Disease diagnosis. After screening candidate biomarkers, we evaluated performance of the multiplexed microfluidic test against ELISA using clinical serum samples and illustrated the potential to streamline current clinical algorithms requiring two immunoassays (ELISA and Western Blot) into one standalone test suitable for physician’s offices or urgent care clinics in the U.S. We also showed exploratory work towards a similar multiplexed test design for another bacterial spirochete infection, Leptospirosis. Next, we built on previous work towards a POC HIV-syphilis antenatal screening tool, to develop a smartphone-integrated, microfluidic assay for healthcare workers to use in low resource settings. The low-cost ($34), re-usable device (“smartphone dongle”) costs $34 to produce and provides results in 15 minutes. In this work, we focus on assay development efforts undertaken towards development of a fully integrated POC product suitable for deployment in the field, with practical considerations for the use of fingerstick blood, stability, scale-up and transport. We also streamlined the number of manual steps for end-user operation, through the use of lyophilized secondary antibodies, preloaded reagents on cassette, and an automatic result readout. While laboratory demonstration with clinical samples is important for initial characterization of POC devices, field evaluation reveals diagnostic performance under real-world conditions. We tested the device in the hands of minimally trained healthcare workers in Rwanda and saw comparable performance to other immunoassays run under field conditions. We also performed a follow-up pilot field study in Rwanda to evaluate the feasibility of the smartphone dongle platform for self-testing by patients/consumers in a low-resource setting, one of the most challenging use-cases for POC devices. Finally, we sought to integrate intellectual frameworks from behavioral research and user-experience (UX) design in creating a new framework for evaluation of consumer-facing microfluidic devices, specifically towards HIV home-testing in the U.S. While overall rates of HIV are decreasing in the U.S., the population of gay, bisexual and other men who have sex with men (MSM) are disproportionately affected. Self-testing products for sexually transmitted infection (STI) testing could address unmet needs for these target populations in both increasing access and frequency of testing, as well as integrating use with sexual partners for early diagnosis or even prevention. We worked with a cohort of MSMs at high risk for HIV/STI transmission in New York City, and performed for the first time, a structured assessment of completely naïve users interacting with a smartphone interfaced microfluidic diagnostic device (“SMARTtest”). We integrated UX design value model of device usability, credibility, accessibility and acceptability into our evaluation framework, which influence user’s information, knowledge, motivation and behavioral skills towards engaging with a prevention method (“IMB” model). Thus far, such frameworks have rarely been applied to other consumer health monitoring devices, including microfluidic POC devices. As the microfluidic field moves towards more field demonstrations of devices, more untrained and minimally trained users will have access to such tools. It is important to understand how they use devices, what the device failure points are and what the most relevant design features are to spur user adoption and meaningful usage. Underlying our work in creating accessible and practical POC immunoassay tools for infectious disease detection, is the illustration of the translational development roadmap from proof-of-concept assay development to field studies and user-based evaluations for intended end-use settings that range from U.S. based primary care clinics, rural health centers in low-resource settings as well as self-testing environments in both. Incorporating an understanding of the target use-case setting is critical in translating technologies for clinical use, whether in the infrastructure and services that are available, or end-user needs and constraints such as clinical workflow patterns, level of technical expertise and perceptions of usefulness and value. We show how user/use-case focused application of downstream translational engineering and testing informs upstream design choices and accelerates development of POC devices for real-world use. The sum of this work aims to illustrate tenets of translational engineering design and testing to advance insight into building POC products that are poised for greater adoption by target end users, whether they are health providers or consumers.

Medical practitioners are often unable to access medical and health information at the point-of-care, thus preventing them from providing quality healthcare. Family Health International 360 (FHI) provided medical practitioners with a locally relevant, reliable, and accurate comprehensive library of medical information on mobile computing devices (MCDs), at the point-of-care, as part of a project in collaboration with the Department of Health in the Eastern Cape Province. As part of the latter project, Ricks (2012:7) conducted an investigation into the impact that accessing health information at the point-of-care, via MCDs, had on the clinical decision-making practice of medical practitioners and professional nurses in public hospitals and primary healthcare settings in the Eastern Cape Province. The researcher identified a gap in the aforementioned study and was thus motivated to conduct this study to explore and describe the experiences of medical practitioners at public hospitals in further detail by conducting a qualitative study, as the previous study was quantitative. The purpose of this study was therefore to explore and describe the experiences of medical practitioners regarding the accessing of information at the point-of-care, via mobile technology, for clinical decision making at public hospitals. To achieve the purpose of the study, a qualitative, explorative, descriptive and contextual research design was used. The research population comprised medical practitioners who were using MCDs to access information at the point-of-care for clinical decision making. Purposive sampling was used to select the research sample. Semi-structured interviews were used to collect the necessary research data. Tesch’s steps were used to analyse the data. The principles for ensuring trustworthiness and ethical considerations were adhered to throughout the study. Two main themes and six sub-themes emerged in relation to the experiences of medical practitioners regarding the accessing of information at the point-of-care, for clinical decision making, via mobile technology. The main findings of the research highlighted the benefits and challenges that were experienced by the medical practitioners when using the MCDs for accessing information at the point-of-care for clinical decision making. The study concludes with recommendations pertaining to the areas of practise, education and research.

This thesis aims to address the challenges of the development of cost-effective and rapid assays for the accurate counting of CD4+ T cells and quantification of HIV-1 viral load for resource-constrained settings. The lack of such assays has severely affected people living in disease prevalent areas. CD4+ T cells count information plays a vital role in the effective management of HIV-1 disease. Here, we present a flow-free magnetic actuation platform that uses antibody-coated magnetic beads to efficiently capture CD4+ T cells from a 30 μL drop of whole blood. On-chip cell lysate electrical impedance spectroscopy has been utilized to quantify the isolated CD4 cells. The developed assay has a limit of detection of 25 cells per μL and provides accurate CD4 counts in the range of 25–800 cells per μL. The whole immunoassay along with the enumeration process is very rapid and provides CD4 quantification results within 5 min time frame. The assay does not require off-chip sample preparation steps and minimizes human involvement to a greater extent. The developed impedance-based immunoassay has the potential to significantly improve the CD4 enumeration process especially for POC settings. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

京都大学 / 新制・課程博士 / 博士(工学) / 甲第24234号 / 工博第5062号 / 新制||工||1790(附属図書館) / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 大塚 浩二, 教授 沼田 圭司, 教授 大内 誠 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM