Yes / Polymerase chain reaction (PCR) has become a powerful tool for detecting various diseases due to its high sensitivity and specificity. However, the long thermocycling time and the bulky system have limited the application of PCR devices in Point-of-care testing. Herein, we have proposed an efficient, low-cost, and hand-hold PCR microdevice, mainly including a control module based on water-cooling technology and an amplification module fabricated by 3D printing. The whole device is tiny and can be easily hand-held with a size of about 110 mm × 100 mm × 40 mm and a weight of about 300 g at a low cost of about $170.83. Based on the water-cooling technology, the device can efficiently perform 30 thermal cycles within 46 min at a heating/cooling rate of 4.0/8.1 ℃/s. To test our instrument, plasmid DNA dilutions were amplified with this device; the results demonstrate successful nucleic acid amplification of the …

abstract: This work describes efforts made toward the development of a compact, quantitative fluorescence-based multiplexed detection platform for point-of-care diagnostics. This includes the development of a microfluidic delivery and actuation system for multistep detection assays. Early detection of infectious diseases requires high sensitivity dependent on the precise actuation of fluids. Methods of fluid actuation were explored to allow delayed delivery of fluidic reagents in multistep detection lateral flow assays (LFAs). Certain hydrophobic materials such as wax were successfully implemented in the LFA with the use of precision dispensed valves. Sublimating materials such as naphthalene were also characterized along with the implementation of a heating system for precision printing of the valves. Various techniques of blood fractionation were also investigated and this work demonstrates successful blood fractionation in an LFA. The fluid flow of reagents was also characterized and validated with the use of mathematical models and multiphysics modeling software. Lastly intuitive, user-friendly mobile and desktop applications were developed to interface the underlying Arduino software. The work advances the development of a system which successfully integrates all components of fluid separation and delivery along with highly sensitive detection and a user-friendly interface; the system will ultimately provide clinically significant diagnostics in a of point-of-care device. / Dissertation/Thesis / Masters Thesis Biomedical Engineering 2018

Point-of-care testing (POCT) devices have received increasing attention because of their potential to address the urgent need for quick and accurate diagnostic tools, especially in areas of personal care and clinical medicine. They offer several benefits over current diagnostic systems, including rapid diagnostic results in comparison to microbial cultures, simple interpretation of results, portability, and requiring no specialised laboratory equipment or technical training to operate. These are essential for diagnosing critical illnesses, such as sepsis, in areas of poor healthcare infrastructure. Sepsis, an innate physiological response to infection, is a growing problem worldwide with high associated costs and mortality rates, and affects a wide range of patients including neonates, infants, the elderly, and immunocompromised individuals. A literature review of the biomarkers of sepsis and the currently available diagnostic systems indicates the need for a biosensor capable of meeting the requirements of designing POCT systems and achieving detection of low concentrations of biomarkers. To meet these demands, two significant contributions to developing POCT platforms have been achieved and described in this thesis, including: 1) development of a colorimetric, magnetically separable biosensor that can be easily fabricated and demonstrates an easily identifiable colour response upon analyte detection, as well as the ability to capture and detection target biomarkers at low concentrations from complex solutions; and 2) tuning of the biosensor’s colorimetric response to achieve low detection limits, as well as demonstration of the versatility of the biosensor for sensing different target analytes. The developed biosensor in this work combines colour responsive polydiacetylenes and superparamagnetic iron oxide for the first time to achieve a biosensor capable of meeting these demands. The sensors exhibit identifiable colour responses to biomolecule detection, capture of a target analyte from complex solutions, sensing of different target analytes, a lower detection limit of 0.01 mg/mL, and rapid separation from solution with a common magnet. This work has been a significant demonstration of the capabilities of this biosensor as a new platform for POCT systems to diagnosis sepsis, and potentially other sensing applications.

Utilizing self-assembled monolayer nanotechnology, micro-electro-mechanical systems (MEMS) and IC technologies, a novel flexural plate-wave (FPW) biosensor is developed in this dissertation for detecting the immunoglobulin-E (IgE) concentration of human serum. The acoustic waves of the proposed FPW devices are launched by the 25-pair inter-digital transducer (IDT) input electrodes and propagated through the 4.82 £gm-thick Si/SiO2/Si3N4/Cr/Au/ZnO floating thin-plate. Since the thickness of such floating thin-plate is much smaller than the designed wavelength of FPW device (80 £gm), most of the propagating wave energy will not be dissipated into outside of thin-plate and the mass sensitivity is very high. To further reduce the insertion loss of the proposed FPW devices, two 3 £gm-thick Al reflection grating electrodes (RGE) are designed beside the input and output IDTs. To implement a FPW-based IgE biosensor, a Cr/Au electrode layer has to be deposited on the backside of the floating thin-plate to serve as a substrate for further coating the cystamine SAM/glutaraldehyde/IgE antibody layers. Once the IgE antigens of human serum are bound to the IgE antibody layer, the small change in the mass of floating thin-plate will result in a shift of center frequency of the testing FPW-based biosensor. Compared to the reference FPW biosensors, the shift of center frequency generated by the testing FPW biosensor under different IgE antigen concentration can be detected by commercial network analyzer or the frequency-shift readout system developed by our collaboration laboratory (VLSI Design Lab. of NSYSU). Compared to commercial enzyme linked immunosorbent assay (ELISA) analyzer (sample volume >25 £gl/well, testing time >60 min, dimension>40 cm ¡Ñ30 cm¡Ñ10 cm), the implemented FPW-based IgE biosensor presents a smaller sample volume (<5 £gl), faster response (<10 min) and smaller size (<9 mm¡Ñ6 mm¡Ñ0.5 mm). In addition, a very low insertion loss (-9.2 dB), a very high mass sensitivity (-6.08¡Ñ109 cm2 g-1) and a very high sensing linearity (99.46 %) of the proposed IgE biosensor can be demonstrated at 6.6 MHz center frequency. This study successfully developed a novel FPW-based allergy biosensor by MEMS technology, which has great potential to be further applied into point-of-care testing (POCT) microsystem.

In Sweden, lowest acceptable haemoglobin levels in blood donators are 125g/L for women and 135g/L for men for a test sample taken in the beginning of the blood donation. Levels, which are 10g/L lower, are accepted if the sample is taken after the blood donation. Earlier studies show that the haemoglobin level decreases for a person that is lying down. The two aims of this study were to examine how much the haemoglobin levels change during blood donation and to examine if the photometrical instrument Pronto-7TM shows equivalent results to that of the established method Cell-Dyn Sapphire. In the study, 120 blood donors participated. Blood samples were taken in the beginning and in the end of the donation. Analyses by Pronto-7TM were done before and after the donation. The haemoglobin level decreased significantly during the blood donation. The difference was in mean value 5,9g/L according to Cell-Dyn Sapphire. The decrease was significantly less than 10g/L. The Pronto-7TM gave levels that were 1,6g/L higher than Cell-Dyn Sapphire in mean and the standard deviation was higher for Pronto-7TM than for Cell-Dyn Sapphire. In conclusion, the decrease of the haemoglobin levels was significantly less than the expected difference 10g/L. Pronto-7TM gives results that differs a little from the results of the established method.

Point-of-care testing (POCT) devices have received increasing attention because of their potential to address the urgent need for quick and accurate diagnostic tools, especially in areas of personal care and clinical medicine. They offer several benefits over current diagnostic systems, including rapid diagnostic results in comparison to microbial cultures, simple interpretation of results, portability, and requiring no specialised laboratory equipment or technical training to operate. These are essential for diagnosing critical illnesses, such as sepsis, in areas of poor healthcare infrastructure. Sepsis, an innate physiological response to infection, is a growing problem worldwide with high associated costs and mortality rates, and affects a wide range of patients including neonates, infants, the elderly, and immunocompromised individuals. A literature review of the biomarkers of sepsis and the currently available diagnostic systems indicates the need for a biosensor capable of meeting the requirements of designing POCT systems and achieving detection of low concentrations of biomarkers. To meet these demands, two significant contributions to developing POCT platforms have been achieved and described in this thesis, including: 1) development of a colorimetric, magnetically separable biosensor that can be easily fabricated and demonstrates an easily identifiable colour response upon analyte detection, as well as the ability to capture and detection target biomarkers at low concentrations from complex solutions; and 2) tuning of the biosensor’s colorimetric response to achieve low detection limits, as well as demonstration of the versatility of the biosensor for sensing different target analytes. The developed biosensor in this work combines colour responsive polydiacetylenes and superparamagnetic iron oxide for the first time to achieve a biosensor capable of meeting these demands. The sensors exhibit identifiable colour responses to biomolecule detection, capture of a target analyte from complex solutions, sensing of different target analytes, a lower detection limit of 0.01 mg/mL, and rapid separation from solution with a common magnet. This work has been a significant demonstration of the capabilities of this biosensor as a new platform for POCT systems to diagnosis sepsis, and potentially other sensing applications.

Project (M.S.)--Brigham Young University. Dept. of Statistics, 2007. / Includes bibliographical references (p. 60-61).

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.

abstract: In this thesis, I present a lab-on-a-chip (LOC) that can separate and detect Escherichia Coli (E. coli) in simulated urine samples for Urinary Tract Infection (UTI) diagnosis. The LOC consists of two (concentration and sensing) chambers connected in series and an integrated impedance detector. The two-chamber approach is designed to reduce the non-specific absorption of proteins, e.g. albumin, that potentially co-exist with E. coli in urine. I directly separate E. coli K-12 from a urine cocktail in a concentration chamber containing micro-sized magnetic beads (5 µm in diameter) conjugated with anti-E. coli antibodies. The immobilized E. coli are transferred to a sensing chamber for the impedance measurement. The measurement at the concentration chamber suffers from non-specific absorption of albumin on the gold electrode, which may lead to a false positive response. By contrast, the measured impedance at the sensing chamber shows ~60 kÙ impedance change between 6.4x104 and 6.4x105 CFU/mL, covering the threshold of UTI (105 CFU/mL). The sensitivity of the LOC for detecting E. coli is characterized to be at least 3.4x104 CFU/mL. I also characterized the LOC for different age groups and white blood cell spiked samples. These preliminary data show promising potential for application in portable LOC devices for UTI detection. / Dissertation/Thesis / M.S. Electrical Engineering 2011

Magister Public Health - MPH / Background: Point of Care Testing (POCT) refers to qualitative or quantitative tests done in health facilities where the patient is being attended to (on-site), and not in the conventional hospital laboratory setting. As a consequence of many developing countries not having access to conventional laboratory services (with trained laboratory personnel), diagnostic testing often relies on the availability of valid POC tests. All pregnant women attending antenatal care clinics in the Sedibeng District Primary Health Care (PHC) centres should be screened for syphilis, anaemia and HIV. This can be done by means of POC testing, which is easy to perform. These POC tests provide results promptly allowing treatment to be commenced immediately, if required. Despite this highly desirable benefit of POCT, there is circumstantial evidence which suggests that staff is choosing to send specimens to the laboratory for testing, instead of doing POCT themselves. The extent to which this happens and the factors contributing to this practice are not clear. Aim: The aim of this study was to assess the prevalence of screening for syphilis, anaemia, and HIV amongst pregnant women during their first antenatal care visit to PHC facilities in the Sedibeng District, and to establish the factors affecting the prevalence of appropriately using POCT for screening tests. Methodology: Study design: A quantitative, analytical, cross-sectional study was conducted. Study Population and Sample: Patient registers, staff expected to perform POCT and facility managers. 33 District’s health care workers expected to perform POCT on pregnant women during the first ANC visit and 30 facility managers from these facilities; 360 patient records (these were collected from a total of 7 200 patients’ records). The data was collected over a six month period (from 1st July 2012 to 31st December 2012). Data collection: Data was collected from 360 patient records to determine the rate, appropriateness and mechanism of screening for syphilis, anaemia and, HIV in pregnant women on their first antenatal visit. Interviewer-administered closed-ended questions was asked from 30 antenatal care clinic staff tasked with performing POC tests and from 30 PHC facility managers to determine the factors affecting the rate of conducting POCT. Data analysis: Data was analysed using univariate, bivariate and multivariate analyses. Ethical considerations: No harm was anticipated to anyone participating in the study or from the findings of the study. A major benefit of the study was that clarity on the factors affecting the rate of screening and the use of POCT was gained. This will hopefully facilitate the implementation of evidence–based interventions to improve POCT uptake if required.