No description available.

A dynamic model is developed and presented that predicts the voltage response for a Severinghaus electrode-based point-of-care pCO2 sensor. Eight partial differential equations are derived to describe the diffusion and reaction phenomena in the sensor. The model is able to predict the potential response versus time behaviour from different CO2 concentrations in the calibration fluid and control fluids. The two most influential and uncertain parameters in the model are determined to be the forward rate constant for benzoquinone consumption at the gold surface ( k_(f_Au ) ), and the partition coefficient for CO2 between the membrane and the electrolyte (κ_(〖CO〗_(2_m ) )). These parameters were adjusted heuristically to obtain a good fit (within 2 mV) between the dynamic voltage response data and the model predictions during a critical 4 second period. The model predictions are sufficient for design sensitivity studies, however an improved fit might be possible using a formal least-squares parameter estimation approach, or if additional parameters were estimated. Several design parameters are varied to study the influence of the electrolyte concentration and the sensor geometry on the voltage response. The most influential design parameter studied is the amount of water present in the electrolyte during sensor operation. This can be affected by the amount of water evaporated during manufacturing and storage, and by the amount of water present when the sensor “wets up” again during operation. The amount of water picked up by the sensor in turn is affected by design parameters such as component/membrane dimensions and thicknesses. The initial buffer concentration in the electrolyte is the second most influential parameter. The resulting model can be used to perform “what if” analyses in order to understand the impact of design decisions on the sensor performance, and to potentially improve the sensor from performance and manufacturing cost perspectives. / Thesis (Master, Chemical Engineering) -- Queen's University, 2014-02-06 15:00:47.555

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

UA Open Access Publishing Fund / Background: Emergency medicine milestones released by the Accreditation Council for Graduate Medical Education require residents to demonstrate competency in bedside ultrasound (US). The acquisition of these skills necessitates a combination of exposure to clinical pathology, hands-on US training, and feedback. Objectives: We describe a novel simulation-based educational and assessment tool designed to evaluate emergency medicine residents’ competency in point-of-care echocardiography for evaluation of a hypotensive patient with chest pain using bedside US. Methods: This was a cross-sectional study conducted at an academic medical center. A simulation-based module was developed to teach and assess the use of point-of-care echocardiography in the evaluation of the hypotensive patient. The focus of this module was sonographic imaging of cardiac pathology, and this focus was incorporated in all components of the session: asynchronous learning, didactic lecture, case-based learning, and hands-on stations. Results: A total of 52 residents with varying US experience participated in this study. Questions focused on knowledge assessment demonstrated improvement across the postgraduate year (PGY) of training. Objective standardized clinical examination evaluation demonstrated improvement between PGY I and PGY III; however, it was noted that there was a small dip in hands-on scanning skills during the PGY II. Clinical diagnosis and management skills also demonstrated incremental improvement across the PGY of training. Conclusion: The 1-day, simulation-based US workshop was an effective educational and assessment tool at our institution.

Background: Emergency medicine milestones released by the Accreditation Council for Graduate Medical Education require residents to demonstrate competency in bedside ultrasound (US). The acquisition of these skills necessitates a combination of exposure to clinical pathology, hands-on US training, and feedback. Objectives: We describe a novel simulation-based educational and assessment tool designed to evaluate emergency medicine residents' competency in point-of-care echocardiography for evaluation of a hypotensive patient with chest pain using bedside US. Methods: This was a cross-sectional study conducted at an academic medical center. A simulation-based module was developed to teach and assess the use of point-of-care echocardiography in the evaluation of the hypotensive patient. The focus of this module was sonographic imaging of cardiac pathology, and this focus was incorporated in all components of the session: asynchronous learning, didactic lecture, case-based learning, and hands-on stations. Results: A total of 52 residents with varying US experience participated in this study. Questions focused on knowledge assessment demonstrated improvement across the postgraduate year (PGY) of training. Objective standardized clinical examination evaluation demonstrated improvement between PGY I and PGY III; however, it was noted that there was a small dip in hands-on scanning skills during the PGY II. Clinical diagnosis and management skills also demonstrated incremental improvement across the PGY of training. Conclusion: The 1-day, simulation-based US workshop was an effective educational and assessment tool at our institution.

No description available.

In this dissertation, three types of paper-based analytical devices for point-of-care biosensing, a potentiometric method for analyzing percent hemoglobin A1c (%HbA1c) and a PDMS-glass microelectrochemical device for highly reproducible amperometric measurement in microdroplet, are described. The first paper-based sensing device is fabricated using the principles of origami (paper folding). The three-dimensional origami paper analytical device (oPAD) is fabricated on a single sheet of flat paper in a single photolithographic step and assembled by simply folding the paper by hand. Following analysis, the device can be unfolded to reveal each layer for optical and fluorescent read-out. The second type of paper-based device has an integral aluminum/air battery as the power source and reports its output using Prussian blue as an electrochromic indicator. The integrated aluminum/air battery powers both the electrochemical sensor and the electrochromic read-out. The applicability of the device to point-of-care sensing is demonstrated by qualitative detection of glucose and H2O2 in artificial urine. The third type of paper-based device (oPAD 2) uses an aptamer to recognize the analyte, adenosine, a glucose oxidase tag to modify the relative concentrations of an electroactive redox couple, and a digital multimeter to transduce the result of the assay. Adenosine is quantitatively determined using this device with a detection limit of 11.8 uM. The method for measuring HbA1c concentration, hemoglobin concentration, and thus %HbA1c in human blood is based on potentiometry. We use Alizarin red s (ARS) as a redox indicator. The potential shift of ARS owing to diol-boronic acid complexation is used to determine the HbA1c, which is a competitor of ARS for the complexation reaction. The concentration of Hb is determined by reacting it with Fe(CN)₆³⁻ and measuring the potential shift arising from the reduction of Fe(CN)₆³⁻ by Hb. The results obtained for %HBA1c in human blood are in good agreement with those determined using a reference method. The method for highly reproducible chronoamperometric analysis of the contents of microdroplets is developed. Aqueous microdroplets (~ 1 nL) and separated by a fluorocarbon solvent are generated within a microfluidic device using a T-shaped junction. Highly reproducible quasi-steady-state currents (relative standard deviations = ~ 2%) are observed when the microdroplets are stretched by a factor of 10 in a narrowed segment of a microchannel, which leads to desirable intradroplet mass transfer characteristics. Importantly, the design of the microelectrochemical device ensures direct contact between intradroplet redox molecules and the electrode surface to study inner-sphere electrocatalytic processes such as the oxygen reduction reaction. Finite-element simulations are presented that are in accord with the experimental findings. / text

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

Early detection is crucial in delivering timely treatment and improving patient outcomes. Point-of-care (POC) biosensors play an essential role in early detection, allowing for rapid and accurate diagnosis of diseases at the patient’s bedside without the need for expensive equipment or specialized personnel. By performing the analysis on-site, POC diagnostics can offer continuous monitoring and real-time data acquisition of a patient's health status. Thus, there is strong incentive in creating POC biosensors to provide healthcare professionals with greater access to diagnostic information, ultimately improving outcomes and reducing healthcare costs. Herein, the development of a POC lab-in-a-tube biosensor that utilizes simple and scalable fabrication techniques is presented. Electrodes are patterned on low-cost plastic substrates, which can be subsequently rolled and heat-shrunk into miniaturized tubing for flow-through analysis of liquid samples. Heat-shrinking of the device results in 3-dimensional, hierarchically wrinkled electrodes with morphological feature that span several orders of magnitude in size. These wrinkled electrodes demonstrate dramatically increased surface area in a given footprint compared to traditional planar electrodes. Incorporation of modified gold and silver wires allows for sensitive and stable electrochemical detection, enabling fast and quantitative results. These devices are capable of millilitre-per-minute flow rates to allow for rapid sample processing and for increased mass-transport to the electrode surface. The ability to capture analytes was characterized with nucleic acid sequences using pump-driven and blood-collection tube induced flow for rapid and accurate detection. Overall, this work demonstrates the successful development of an electrochemical platform integrated into a plastic tubing capable of rapid detection of flowing analytes. With its ease-of-use and compatibility with a wide range of flow rates, the device has the potential to be incorporated with existing medical tubing and procedures to achieve POC diagnostics. / Thesis / Master of Applied Science (MASc) / Early detection is critical for timely treatment and better patient outcomes. Point-of-care (POC) biosensors allow for disease diagnosis and real-time monitoring of a patient's health status directly at the patient's bedside without the need for expensive equipment or specialized personnel. A lab-in-a-tube biosensor was developed using sensing surfaces on low-cost plastic that is rolled and heat-shrunk into miniaturized tubing for analysis of liquid samples. The wrinkled sensing surface that results from heat-shrinking dramatically increase surface area and interaction with the sample, enabling sensitive detection that is fast and quantitative. These devices are capable of capturing samples at high flow rates, allowing for rapid analysis of large samples. Overall, this work demonstrates the successful creation of a biosensor platform that could be incorporated with existing medical tubing for POC diagnostics.

According to the third international consensus definition (sepsis-3), sepsis is characterized as life-threatening organ dysfunction resulting from an uncontrolled host response to infection. Sepsis stands as a prominent contributor to worldwide mortality. A study revealed approximately 50 million reported cases of sepsis and 11 million associated deaths worldwide, constituting nearly 20% of all global fatalities. Various biomarkers have been investigated for sepsis prognosis including Procalcitonin (PCT), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and protein C. In addition to proteomic markers genomic biomarkers have also been investigated for sepsis. For instance, research indicates a substantial rise in plasma cell-free DNA (cfDNA) and total circulating histones levels during sepsis, correlating with its severity and mortality. The complexity arises in creating a measurement tool for sepsis, given the diverse nature of these biomarkers, each requiring distinct detection methods. The objective of this doctoral thesis is to develop a low-cost fully integrated microfluidic device for detecting a genomic biomarker (cfDNA) and a proteomic biomarker (total circulating histones) using a new method for integration of hydrogels inside microfluidic devices during the fabrication process. This method involves using porous and fibrous membranes as scaffolds to support gels. The scaffold facilitates the drying and reconstitution of these gels without any loss of shape or leakage, making it advantageous in various applications, especially in point-of-care (POC) devices where long-term storage of gels inside the device is required. This hydrogel integration method was applied to demonstrate gel electrophoretic concentration and isoelectric trapping of cfDNA and histones respectively in rehydrated agarose gates with proper pH embedded in a porous membrane in a microfluidic device. Then, these two detections were performed in a single fully integrated microfluidic device. Additionally, nonspecific fluorescent dyes were incorporated within the device, eliminating the necessity for off-chip sample preparation. This enables direct testing of plasma samples without the need to label DNA and histones with fluorescent dyes beforehand. In all the fabrication steps of the microfluidic device, xurography, a cost-effective and rapid fabrication method, was utilized. This device demonstrated the effective separation of cfDNA and histones in the agarose gates in a total time of 20 minutes, employing 10 and 30 Volts for cfDNA and histone accumulation, respectively. This device could be further developed to create a POC device for the quantification of cfDNA and histones simultaneously in severe sepsis patients plasma sample. / Thesis / Doctor of Philosophy (PhD)