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.

Receptor-based biological detection techniques often suffer from the problem of non-specific interactions. This is largely due to the presence of weak electrostatic and Van der Waals forces between the receptor and the non-target substances in the analyte that are not easily dissociated in practice. Most existing detection techniques are unable to probe the interaction between the bound entity and the surface and differentiate between specific and non-specific interactions in terms of bond strength or activation energy. The resulting false positive responses lead to various issues, such as misdiagnosis and mistreatment in clinical diagnostics and false alarms in biosecurity. The problem is even more significant with direct direction techniques, such as the resonant frequency shift based detection using quartz crystal microbalance (QCM) or micro-cantilevers, which involve minimal sample processing and washing steps. The work presented in this thesis investigates, through modeling and experiments, the mechanical interactions of a resonator with microparticles attached via biomolecular linkers and analyses the resulting nonlinear acoustic modulation of the resonator from the transduced electrical signal. Physisorbed and specific interactions both in air and liquid medium are studied using thickness shear mode quartz crystal resonators and streptavidin-coated polystyrene microbeads (SCPM) of various sizes. It is found that the modification in the transduced electrical signal measured at the third harmonic (3f), or three times the driving frequency f, is significant in presence of the attached particles and approximately proportional to the number of particles. A detection limit of approximately 2 SCPM of 5.6 µm diameter in air and 6700 SCPM of 0.39 µm diameter in liquid is demonstrated, which corresponds to a mass detection limit of ~200 pg. Most interestingly, the deviation in the magnitude of the 3f signal as a function of the resonator oscillation amplitude is found to hold a distinct relationship with the type of particle-surface interaction. This provides a basis for selectivity in detection over and above the efficacy of the receptor. The function is also found to correlate well with the event of SCPM diffusion on the surface. This detection technique, based on the measurement of deviation in magnitude of the transduced electrical signal measured at a higher odd harmonic of the drive frequency due to the presence of surface-bound particles on a resonator, is termed as the anharmonic detection technique (ADT). A feasibility study with Bacillus subtilis spores in phosphate buffer saline (PBS) is carried out successfully where the modeling and experimental results with SCPM are successfully reproduced. A detection limit of 430 spores is demonstrated, which corresponds to a mass detection limit of ~650 pg. Capability for differentiation of the specifically-captured spores from unwashed physisorbed SCPM of similar dimensions is demonstrated using the shape of the ADT signal. These results indicate that the spore immobilization step may be directly followed by the detection step, which are 9 mins and 2 mins respectively in these experiments. ADT thus potentially enables a rapid, sensitive, reliable and direct detection without the need for any sample processing. Moreover, being an entirely electronic technique, ADT suitably lends itself to multiplexing, large scale fabrication and implementation on a miniaturized low-cost point-of-care detection platform that is of immense need in clinical diagnostics, food and environmental monitoring and biosecurity. Furthermore, fitting the experimental results with modeling estimates enables ADT to determine the force-extension characteristics of the binding biomolecular linker. The force-extension characteristics and the estimated unbinding force for a streptavidin-biotin complex estimated using ADT agrees well with those computed using molecular dynamics (MD) simulation at similar loading rates. Thus ADT contributes a unique force-spectroscopic method, which unlike conventional techniques such as the atomic force microscopy (AFM) provides statistically averaged data for multiple biomolecules in a relatively quicker and simpler experimental format. A method for determination of activation energy of the interaction is also proposed using ADT. This potentially enables a method for rapid and large scale biomolecular screening and studying of interaction networks, which have important applications in drug discovery and individualized therapy.

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

Thesis advisor: Thomas C. Chiles / Rapid diagnosis of infectious disease at the site of the patient is critical for preventing the escalation of an outbreak into an epidemic. This is particularly true for cholera, a disease known to spread swiftly within resource-limited populations. A device suited to point-of- care (POC) diagnosis of cholera must not only demonstrate laboratory levels of sensitivity and specificity, but it must do so in a highly portable, low-cost manner, with a simplistic readout. Here, we report novel proof-of-concept lab-on-a-chip (LOC) electrochemical immunosensors for the detection of cholera toxin subunit B (CTX), based on two nanostructured architectures: the gold dendritic array, and the extended core coax (ECC). The dendritic array has an ~18x greater surface area than a planar gold counterpart, per electrochemical measurements, allowing for a higher level of diagnostic sensitivity. An electrochemical enzyme-linked immunosorbant assay (ELISA) for CTX performed via differential pulse voltammetry (DPV) on the dendritic sensor demonstrated a limit-of detection of 1 ng/mL, per a signal-to-noise ratio of 2.6, which was more sensitive than a simple planar gold electrode (100 ng/mL). This sensitivity also matches a currently available diagnostic standard, the optical ELISA, but on a miniaturized platform with simple electrical readout. The ECC was optimized and explored, undergoing several changes in design to facilitate sensitive LOC electrochemical detection. The ECC matched the off-chip sensitivity towards CTX demonstrated by a previous non-extended core coaxial iteration, which was comparable to a standard optical ELISA. In contrast to the previous coaxial architecture, the ECC is amenable to functionalization of the gold core, allowing for LOC detection. ECCs were functionalized using a thiolated protein G, and CTX was detected via an electrochemical ELISA. While this work is ongoing, the ECC shows promise as a platform for LOC electrochemical ELISA. The ability to potentially meet POC demands makes biofunctionalized gold dendrites and ECCs promising architectures for further development as LOC sensors for the detection of infectious disease biomarkers. / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Objectives: The objective of this study was to better understand the needs of users of an academic health sciences library. Methods: A focus group was conducted using structured interviews. The groups interviewed consisted of three students each from Medicine, Pharmacy, and PhysicalTherapy. Interviewees were probed as to their experience with the library facility and the information training they received in their professional schools. Another focus group was conducted with six participants. Two faculty members each from Medicine, Pharmacy, and Physical Therapy were interviewed. Faculty were asked about the information training they provided students. The data was analyzed for trends using qualitative software. Results: Better relationships were developed between library users and staff. Staff enjoyed learning the focus group methodology and thought it was a valuable tool. New insights were gained for current and future library operations. Conclusions: A focus group is an excellent research tool for assessing the information needs of users, the degree to which the library is filling those needs, and learning of new needs

In this dissertation fluorescence-based sensors for dissolved gases were developed for remote health monitoring applications including urine analysis. Detection of dissolved gases demonstrate diagnostic potential in body fluids, and indicate the metabolism of microorganisms driven by contaminated water. The emphasis of this research was on optimizing the sensitivity of fluorescence-based fluid sensing systems by configuring key design parameters towards cost reduction. A review of urine analysis indicated several methods for imaging, particle analysis, and detection of dissolved analytes. The review encourages readers to consider integrating sensing systems to provide additional context to results. An optical Dissolved Oxygen (DO) sensor was reproduced using phosphorescent organometallic dyes. The sensitivity of the DO sensor was experimentally optimized by employing Total Internal Reflection (TIR) of excitation light within the multilayered device by controlling the incident angle and sensitive film thickness. Novel 3D ray tracing-based computer models were developed based on the experimental results to explain the sensitivity enhancement mechanism of TIR. The path of light within the device and fluorescence generation sites were visualized and relative sensitivity was predicted. The model was validated by comparison with experimental results and expanded to predict the relative sensitivity of devices using different coupling strategies. This new optical model enables researchers to select an optimal coupling and detection scheme given their unique sensor design and application. A fluorescence based optofluidic sensor for Ammonia was redesigned based on experiment and simulation results. An optofluidic chip reader was produced to measure fluorescence sensors using low cost consumer electronics. The sensitivity of the ammonia sensor module has not been demonstrated; however, identified design challenges will be overcome in future efforts. As a result of this research, the cost of optofluidic sensing systems may be reduced towards enabling widely deployed remote monitoring networks for health and water quality. / Thesis / Doctor of Philosophy (PhD) / Dissolved gases have been detected in fluid samples as indicators of health and microbial activity by measuring changes in the intensity of fluorescence emitted from gas sensitive fluorescent dyes. These sensors can often be miniaturized and integrated to measure several parameters from a single platform. Several sensing platforms may be integrated into a continuous monitoring network. However, the cost of complete remote sensing networks prohibits the widespread deployment of these devices. The aim of this research was to improve the sensitivity of fluorescence-based sensors, reducing dependence on expensive detectors and light sources. The sensitivity of a fluorescence based dissolved oxygen sensor was optimized using Total Internal Reflection. A computer model was developed to identify important design parameters and their contributions to sensor performance. The model was validated by comparison with experimental measurements. Finally, an optical ammonia sensor is under development based on the dissolved oxygen experiments and model results.

Recently, photoelectrochemical (PEC) signal transduction, with optical excitation and electronic readout, has been identified as a powerful transduction strategy for bioanalysis due to its high sensitivity and low limit-of-detection. Semiconductive materials have been used as the building blocks of PEC transducers, while plasmonic nanoparticles (NPs) are frequently used as signal amplifiers in these biosensors. Though these approaches have been previously used in PEC biosensing, the interaction between plasmonic and semiconductors NPs linked together through biomolecules are not currently well-understood. Herein, we developed new strategies for preparing photoelectrodes using solution-based methods to enhance the photocurrent of PEC transducers. These transducers were then used to investigate the interaction mechanisms between plasmonic NPs and the photoelectrodes with the goal of enhancing the limit-of-detection of PEC biosensors. In order to create photoelectrodes that were fabricated using facile benchtop methods designed to enhance the photocurrent of PEC transducers, wrinkled scaffolds were used to fabricate photoelectrodes that show an order of magnitude enhancement in photocurrent compared to the planar electrodes. These electrodes were further used in label-free signal-off DNA biosensing without any amplification steps. Limit-of-detection of 200 times lower were reported using these wrinkled photoelectrodes, than planar electrodes. Gold (Au) and TiO2¬ NPs were used as model materials to investigate the interaction between plasmonic and semiconductor NPs on a photoelectrode. The modulation of photocurrent was examined by varying the concentration of Au NPs and under different optical excitation wavelengths. UV light excitation provided larger photocurrent enhancement – at low concentration of Au NP – than visible light excitation. Furthermore, anodic photocurrent generation efficiencies by the photoelectrodes, which were prepared by using only Au NPs, were compared between interband and intraband excitation. The Au NP photoelectrodes demonstrated higher anodic photocurrent at interband excitation than intraband excitation and were further optimized by varying the size and deposition time of the Au NPs. Following this, Au NP- labeled DNA was used to study the effect of the distance between Au NPs and TiO2 NPs on the magnitude of the measured photocurrent. When Au NPs were in proximity with TiO2, they increased the generated photocurrent; however, they reduced the measured photocurrent when they were positioned further away from TiO2 NPs. Utilizing this switching behavior of PEC signals, a differential signal generation strategy was adopted to achieve a biosensor with enhanced sensitivity and signal-to-noise ratio. Ultimately, we designed a PEC signal transduction strategy to detect nucleic acids without target labeling. In this assay, Au NP-labeled DNA was used as a signal-amplification-barcode that was introduced to the assay following target binding. This label-free PEC biosensor showed a low limit-of-detection (3 fM), broad (1 fM – 100 pM) linear range, and capability to detect single and double base-mismatched sequences of DNA. Thus, this work presents materials and signal transduction innovations that enhance the performance metrics of biosensors. / Dissertation / Doctor of Philosophy (PhD) / Detection and quantification of biomolecules is of utmost importance in early diagnosis, disease monitoring, prognosis, and disease management. In the past few decades, enormous efforts have been put towards utilizing photoelectrochemical (PEC) processes for biomolecular detection due to their high sensitivity. Gold nanoparticles are frequently being used to amplify the signal in the PEC bio-detection assay due to their plasmonic properties. However, the exact nature of the interaction between gold nanoparticles and the electrode material has not been determined. In this thesis, we investigated the interaction of gold nanoparticles with photoelectrode materials when they are separated by nucleic-acid sequences. Excitation energy and nucleic-acid length were varied to modulate the PEC current. The improved understanding of this interaction was further utilized to achieve a programmable response of nucleotide sensor from the photoelectrodes upon detecting the analyte of interest. We further developed different types of biosensing assay designs and examined their performance in terms of limit-of-detection, sensitivity, and specificity. Finally, we developed a new class of biosensor for detecting nucleic acids in bodily fluid and assessed the assay by using both electrochemical and PEC signal readout.

Chlamydia trachomatis accounts for 3.6% of blindness worldwide, and is the leading cause of bacterial-induced blindness in the world. With the subtle initial presentation of the disease and the difficulty in clearing the infection without the aid of antibiotics, C. trachomatis can spread rapidly following introduction into a population. This problem is further compounded in resource limited areas due to the lack of trained personnel (i.e. Medical Doctors, Nurses), equipment, and finances to test and treat large portions of the population. A testing method that is both cheap and easy to interpret is necessary. Lateral flow assays (LFA) have been used for years to evaluate pregnancy status in the developed world, and their low cost, ease of use and disposable nature make them a worthwhile candidate, but the current use of visual reporters (i.e. gold or latex nanoparticles) does not allow for adequate sensitivity for true clinical use. Fluorescent reporters, particularly fluorescent nanoparticles, would lower the limit of detection (LOD) and allow for the detection of acute and subclinical infections, which would allow for an effective and objective screening method for trachoma and many other diseases. An effective, rapid, and disposable test would allow for mass screening to be implemented which, in turn, would allow for rapid and targeted treatment. The results in this study show that the use of fluorescent-based reporters greatly improve the LOD of the LFA, with both FITC and RuSNP reporters showing a reduction in the LOD by 1 and 2.5 logs respectively when compared to traditional colorimetric reporters. This substantial improvement in the LOD of the LFA allows for the tests to be used to detect relevant levels of viral pathogens. A similar improvement in the LOD was seen when using FITC-labeled antibodies which improved the sensitivity of LFAs with regards to the detection of C. trachomatis. The use of fluorescent-based reporters in LFAs greatly improves the LOD for both viruses and bacteria, allowing for their detection at clinically relevant levels.

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The authors are pleased to introduce themselves as the new co-editors. They are Nadiya Sunderji and Jodi Polaha, midcareer academic clinicians whose careers have balanced research, teaching, and clinical practice in integrated care. They continue the Families, Systems, & Health (FSH) tradition of interprofessional co-editor teams (Dr. Sunderji is a psychiatrist and Dr. Polaha is a psychologist) and add a new twist: international collaboration. Dr. Sunderji is Canadian, and they welcome the new contributors and readers this collaboration will bring. The authors thank those who worked so diligently to develop a strong journal with a tradition of contributing important work in health care. They thank outgoing Associate Editors, Drs. Douglas Brock and Todd Edwards, as well as outgoing Department Editors, Drs. Ben Miller and Randall Reitz, who served the journal faithfully for many years. They also note that in 2003, Zerhouni (2003) laid out a roadmap for research in the journal Science, using a bridge as a metaphor to explain how scientific infrastructure (journals, grants, training, and the development and dissemination of advanced scientific methods) supports the translation of knowledge from bench to bedside. The authors borrow the bridge metaphor here to discuss the direction for FSH under their leadership.