<p>In 2021, an estimated 1.5 million people were diagnosed with HIV globally, increasing the total to 38.4 million people. Approximately 16% of this population were unaware of their infected status and required HIV testing, which is a critical first step in HIV prevention, treatment, and care. Hence, there is a need to develop a rapid, user-friendly, and cost-effective point-of-care test for HIV detection. The time between HIV infection and a detectable host HIV antibody concentration can extend up to 90 days. By incorporating more sensitive testing for the HIV p24 antigen on the virus, the diagnosis lag can be reduced to 17 days. This window could be further shortened by using horseradish peroxidase (HRP) enzyme as a signal enhancement technique. The work herein focuses on developing an enzymatically signal-enhanced lateral flow assay test for the p24 antigen to detect HIV during the acute phase of infection. Conjugation chemistry for the sandwich assay was characterized using DLS and UV-Vis. Dot blots were then used to assess and enhance the functionality of the individual components via a visual color gradient formed by the protein coupled with antibody-conjugated gold nanoparticles. A quantitative analysis was performed using ImageJ software through signal pixel intensity analysis. A limit of detection (LoD) of 6 ng/mL was obtained for the detection of the p24 antigen. This LoD was improved to 0.2 ng/mL by incorporating HRP signal enhancement with the diaminobenzidine substrate. This 30x signal improvement could drive down the LoD even further to improve the sensitivity of the commercial p24 antigen tests. Different fabrication and scalability studies were performed to produce a cost- efficient, fully functional prototype of a paper-based lateral flow device incorporating the signal- enhanced p24 assay. This study serves as a solid foundation to research focused on creating more efficient point-of-care tests that can be used in resource-limited settings to provide early detection of HIV for the 6 million individuals who are currently unaware of their HIV status. </p>

<p>The 2020 pandemic emphasized the need for accessible and accurate point-of-care diagnostic tests. With the continued development of isothermal nucleic acid amplification tests, this can be achieved. A requirement of these tests includes heating and holding a specific temperature, in this case, 65C for 30 minutes, for amplification to occur. To achieve this, heaters often require external feedback to control the temperature; bringing up the device’s cost. Several self-regulating heaters have been made with materials having a positive thermal coefficient of resistance eliminating the need for complex circuitry. With this property, point-of-care diagnostic tests can be simplified and made more accessible. In this study, ink-based positive thermal coefficient of resistance heaters are developed and characterized using the scalable method of screen printing to achieve 65C and aid in the detection of SARS-CoV-2. Various curing methods and screen-printing parameters were evaluated to improve the stability and understanding of the reproducibility of the heaters. The longevity of the heaters was evaluated with oxidation studies and a COMSOL model was created to study the heat transfer within the device. Furthermore, the heaters were successfully implemented into a second-generation electronic point-of-care diagnostic device. Detection of SARS-CoV-2 using a self-regulating heater removes the need for complex circuitry, improving the accessibility of point-of-care tests with the potential to be expanded to a wide range of pathogen detection. </p>

Pulmonary edema occurs when fluid leaks from the pulmonary capillary network into the lung interstitium and alveoli. When the heart is not able to pump blood to the body efficiently, fluid can back up into the veins that take blood through the lungs to the left atrium. This then builds up the pressure in the blood vessels and fluid is pushed into the alveoli in the lungs. The fluid reduces normal oxygen movement through the lungs and can cause impaired gas exchange and respiratory failure. There are many causes of congestive heart failure that may lead to pulmonary edema such as heart attack, any diseases of the heart that weaken or stiffen the heart muscle, a leaking or narrowed heart valve, and sudden, severe high blood pressure. Pulmonary edema is a strong indicator of congestive heart failure in patients and therefore can be used as a gauge for congestive heart failure. One way to diagnose cardiogenic pulmonary edema constantly is through the continuous monitoring of the transthoracic impedance throughout the day. One method to achieve this constant monitoring is through the use of a cardiac pacemaker or an implantable cardioverter defibrillator (ICD). Many patients who are at risk of heart failure have these medical devices implanted already. In these implantable cardiac devices, the connected cardiac leads can be utilized to continually screen several impedance vectors for decreases in impedance in the thoracic cavity. A pacemaker or ICD that implements Pulmonary Edema Monitoring is designed to continuously monitor these impedance vectors and alert the patient to seek medical attention. This thesis will discuss the implementation of Pulmonary Edema Monitoring via screening of multiple impedance vectors in a pacemaker or implantable cardioverter defibrillator and the effectiveness of this monitoring method. Furthermore, the design, implementation, and testing of this feature will be explored in greater detail.

The value proposition of Personalized Medicine is to deliver the “right drug, to the right patient, at the right time”. Companion diagnostics is the required tool for Personalized Medicine used to aid clinical decision making with the aim to identify patients who are most suitable for a given treatment approach and to avoid adverse effects. However, even 16 years after the first co-approval of a therapeutic drug and an associated diagnostic test (trastuzumab (Herceptin1) from Genentech and the HercepTest1 from Dako), the co-development and co-approval of drug-diagnostic pairs is a challenging task.This study has the aim to identify major challenges for diagnostics companies when developing and commercializing companion diagnostics. This is achieved by (1) a literature research and (2) an empirical case study in form of interviews with diagnostics companies. The collected data is analyzed and discussed with focus on current regulatory and reimbursement frameworks in the USA and European Union. The co-development strategies and business models of companion diagnostics developers are identified.The conclusion of this study is that the major hurdles for companion diagnostics development and commercialization are gaps in scientific evidence and lacking regulatory guidelines for co-development and clinical biomarker studies. Companion diagnostics commercialization is further challenged by poor reimbursement levels. The main strategy of diagnostics companies to address these challenges is the demonstration of a beneficial outcome for patients in form of clinical studies. Small companies with limited resources for clinical research receive funding from academic research grants, patient support groups, pharmaceutical industry, and governmental Innovation agencies.Finally the formation of a new “pharma-diagnostics” sectoral innovation system as a result of the emerging paradigm of stratified medicine has been proposed.

Vid handkirurgiska kliniken på Södersjukhuset i Stockholm (SÖS) har ett projekt med målet att utföra en handtransplantation pågått under flera år. I projektet har man tagit fram två egentillverkade produkter, ett sågblock för att förenkla sågningen genom ben samt en uppsättning med brickor för märkning av olika strukturer i handen. Målet med denna rapport var att ta fram underlag som kan användas för att bestämma om produkterna är lämpliga att använda vid transplantationen. Lämpligheten utvärderades utifrån de medicintekniska regelverken samt analys av risker. För att bedöma hur produkterna förhöll sig till kraven i regelverken studerades EU:s förordning 2017/745 Medical Device Regulation (MDR) samt de svenska författningar som kompletterar denna. Varje krav analyserades för båda produkterna och en motivering upprättades kring dess relevans samt huruvida produkten klarade kravet. En riskhanteringsprocess genomfördes för att identifiera och utvärdera riskerna kopplat till den kliniska användningen.  Riskhanteringen visade att användning av produkterna kan medföra fem risker för respektive produkt, där två av riskerna för brickorna inte gick att utvärdera på grund av bristande information kring materialet. Övriga risker för båda produkterna bedömdes som relativt lindriga. Gällande regelverken nådde produkterna inte upp till flera av kraven, mycket på grund av otillräcklig dokumentation och testning samt avsaknad av rutiner för att bevisa uppfyllnad av kraven.  Slutsatsen som drogs var att denna rapport delvis kan användas som underlag för att bestämma lämpligheten av produkterna. Dock krävs ytterligare arbete för att kunna bevisa att produkterna helt når upp till kraven i regelverken och således garanteras vara säkra att använda. / The clinic for hand surgery at Södersjukhuset in Stockholm (SÖS) has for several years been working on a project with the aim to perform a hand transplantation. As a part of this project two self-manufactured medical devices have been produced, one surgical guide to facilitate sawing through the bones and one set of tags to mark different structures in the hand. The aim with this report was to produce a basis that could be used to decide whether the products are suitable to use during the transplantation. The suitability was evaluated based on medical device regulations and analyzing the risks. To assess how well the products met the requirements from the regulations, relevant constitutions were studied (EU 2017/745 Medical Device Regulation (MDR) and the Swedish constitutions that complement MDR). Every requirement’s relevance and fulfillment were motivated for both products. A risk management process was implemented to identify and evaluate the risks. The result from the risk management process showed that usage of the products could entail five risks for each product, where two of the risks for the tags could not be evaluated due to lack of information about the material. The other risks for both products were assessed as relatively mild. Regarding the regulations, the products did not meet several of the requirements, mainly due to insufficient documentation and testing together with lack of routines to prove compliance with the requirements. The conclusion was that this report could partly be used as a basis for determining the suitability of the products. Though, further work is required to be able to prove that the products meet the requirements from the regulations and thus are safe to use.

Patient monitoring equipment is evolving from smaller, less complex, installation systems to- wards large, complex, systems that require much resources. This led to the development of a new installation procedure involving a so called Delivery Center (DC). Introducing the DC instal- lation procedure affects all stakeholders, and this thesis aimed to assess how the DC installation procedure was perceived by those involved in it. It also investigated if there existed groupings among the participants who share points of views, and whether or not the DC should be kept. The study used Q-Methodology in order to retrieve opinions among employees at Philips who were involved in the installation of Philips patient monitoring equipment at New Karolinska Solna Phase 4. This study has shown that all involved persons to the DC installation procedure are positive to it. Although significant differences has been shown within the studied group, a positive atti- tude towards the concept of the DC has been found. The specific areas of quality management, environmental aspects, the work environment and the efficiency and utilizations of resources have been addressed. This study has also shown that within the participants of this study there exists three distinct groupings based on their opinions. The groups focuses respectively on processes, project planning and on the work environment. These groupings are shown to all have their own characteristics. Understanding them and taking them into consideration can likely make all participants more positive towards a future DC, and could also potentially make it even more efficient. The results shows that from the perspective of the involved stakeholders, a future DC should be kept, and it has also shown a number of areas where there is room for improvement. / Patientmonitoreringsutrustning håller på att utvecklas från mindre, låg-komplexa installation- ssystem mot större, komplexare, system som kräver mycket resurser. Detta har lett till utvecklin- gen av ett nytt installationsförfarande som involverar ett så kallat leveranscenter. Introduktionen av en leveranscenter-baserat installationsförfarande påverkar alla inblandade, och detta exam- ensarbete ämnade att utvärdera hur det leveranscenter-baserade installationsförfarandet upp- fattades av de involverade. Det undersökte också om det existerade grupper bland deltagarna som delar åsikter, och undersökte huruvida leveranscentret borde behållas. Arbetet använde Q-Methodology för att samla in åsikter bland alla de anstälda på Philips som var involverade i installationen av Philips patientmonitoreringsutrustning vid Nya Karolinska Solnas fas 4. Denna studie har visat att alla involverade personer i det leveranscenter-baserade installa- tionsförfarande är positivt inställda till det. Även om signifikanta skillnader bland de studerade grupperna har uppfattats, har en positiv attityd gentemot konceptet med leveranscentret hittats. De specifika områdena kvalitetshantering, miljöpåverkan, arbetsmiljö och effektivitet och uttnyt- jande av resurser har adresserats. Denna studie har också visat att det bland studiedeltagarna finns tre distinkta grupper baserat på åsikter. Grupperna fokuserar på processer, projektplaner- ing och arbetsmiljö. Grupparna har uppvisat egna karaktärsdrag. Förståelse för grupperna och att beakta dem kan troligen göra alla deltagarna än mer positiva gentemot ett framtida lever- anscenter, och även göra det effektivare. Resultaten visar att utifrån deltagarnas perspektiv att ett framtida leveranscenter bör behållas, och det visar även att det finns ett antal områden där det finns utvecklingspotential.

<p dir="ltr">Since the beginning of the HIV/AIDS epidemic, 85.6 million people worldwide have become infected with HIV; more than half of whom have died from AIDS-related complications.[1] Sustained viral suppression below the clinically relevant threshold (1000 copies per mL) with highly active antiretroviral therapy (HAART) has proven effective at managing and prolonging the life expectancy of people living with HIV (PLHIV). However, in 2022, 11.3 million PLHIV had still not achieved viral suppression and may become susceptible to both HIV transmission and a variety of opportunistic infections. Of particular importance is the complex issue of patient non-compliance in global HIV management due to social, economic, behavioral, and healthcare access barriers, potentially disconnecting many PLHIV from the HIV care continuum. Therefore, to boost patient engagement in clinical care and to improve overall patient outcomes, new approaches to viral load monitoring practices need to be developed to increase access, particularly in regions of high HIV prevalence.</p><p dir="ltr">Nucleic acid amplification tests (NAATs) have emerged as potent tools for monitoring viral load, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) being recognized as the benchmark due to its sensitivity and ability for real-time quantification enabled by fluorescence signal emission. Nevertheless, RT-qPCR is burdened by drawbacks including extended processing times, high operational costs, and the requirement for specialized laboratory facilities. In this study, we propose a novel method for HIV-1 viral load monitoring by integrating reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) with real-time particle diffusometry (PD). This approach allows for the continuous monitoring of changes in the diffusion of 400 nm fluorescent particles during RT-LAMP amplification, targeting the <i>p24</i> gene region of HIV-1 RNA. This enables the real-time detection of amplification curves, achieving a detection sensitivity in water samples as low as 25 virus particles per μL within a short duration of 30 minutes. Additionally, to address challenges related to amplification inhibition in complex human specimens, we developed a power-free sample processing system specifically designed for extracting HIV-1 RNA from both whole blood and plasma.Top of FormBottom of FormThis system modifies a commercially available spin-column protocol by integrating a syringe device and handheld bulb dryer, thus eliminating the requirement for a centrifuge. The adaptation allows for the completion of the entire extraction procedure, encompassing viral lysis, RNA capture, washing, and elution of purified HIV-1 RNA, within a timeframe of less than 16 minutes. Subsequent analyses, including RT-LAMP and RT-qPCR, demonstrate a limit of detection of 100 copies per μL and an average RNA recovery of 32% (for blood) and 70% (for plasma) in the elution fraction. Further investigations emphasize the significant presence of purified RNA in the spin column volume (termed as dead volume), and the cumulative recovered RNA copies align with those obtained using the gold standard centrifugation extraction method. Ultimately, we incorporated the real-time quantitative PD-RT-LAMP assay onto a field-compatible handheld portable platform suitable for field use, featuring built-in quality control measures. This platform enables sample-to-answer viral load testing near the point of care (POC). Subsequently, we undertook essential preparatory steps, such as reagent drying to obviate the need for cold storage, initial device calibration, and hands-on training of laboratory personnel regarding device operation, to validate device performance within a cohort of individuals living with HIV (PLHIV). These innovations facilitate quick and comprehensive viral load determination, offering promise for enhanced HIV management and patient care</p>

Yes / Infection by pathogenic bacteria on implanted and indwelling medical devices during surgery causes large morbidity and mortality worldwide. Attempts to ameliorate this important medical issue have included development of antimicrobial surfaces on materials, “no touch” surgical procedures, and development of materials with inherent low pathogen attachment. The search for new materials is increasingly being carried out by high throughput methods. Efficient methods for extracting knowledge from these large data sets are essential. Data from a large polymer microarray exposed to three clinical pathogens is used to derive robust and predictive machine-learning models of pathogen attachment. The models can predict pathogen attachment for the polymer library quantitatively. The models also successfully predict pathogen attachment for a second-generation library, and identify polymer surface chemistries that enhance or diminish pathogen attachment. / CSIRO Advanced Materials Transformational Capability Platform. Newton Turner Award for Exceptional Senior Scientists. Wellcome Trust. Grant Number: 085245. NIH. Grant Number: R01 DE016516

<p dir="ltr">Parkinson’s Disease (PD) is the second most common neurodegenerative disorder with tremor being its primary motor symptom. Although the MS-UPDRS is the current clinical method for evaluating the severity of tremors in PD, it has several drawbacks resulting from the subjective, visual-based examination, and the ordinal scale used to rate the tremors. Since, the MS-UPDRS is agnostic to the etiology of the tremor, age related increase in naturally occurring physiological tremors may confound the precise rating of PD tremors. However, replacing the judgment of the neurologist in determining the holistic progression of PD and treatment protocol is neither feasible nor advisable. This research used lightweight, wearable, non-invasive sensors to detect, analyze, and differentiate changes in wrist kinematics due to physiological and PD tremors. Findings reveal key differences and similarities in composition between these different types of tremors. Dominant frequency analysis using a data-based approach shows interesting parallels with the frequency range found in literature for these tremors. Finally, using features of tremor signal obtained from the sensors, a novel Tremor Severity Score rating scale was created that shows greater sensitivity in differentiating rest and postural tremors as well as medication effects on these tremors in PD patients compared to the MS-UPDRS. This study offers a simple method for objectively evaluating Parkinsonian tremors, identifying kinematic distinctions between rest and postural tremors, analyzing the effect of anti-parkinsonian medication on these tremors, and sensitively scoring tremors. These objective methods could be valuable for early diagnosis and distinguishing between different tremor causes in both clinical and telehealth settings, as well as for investigating the effects of various treatment methods on tremors.</p>

<p>Since the late 1970s, biomedical researchers have heavily invested in the development of portable insulin pumps that allow people with Type 1 Diabetes (T1D) to carry several days-worth of insulin to be injected on an as-needed basis. That means fewer needles and syringes, making regular insulin injections less time consuming and troublesome. As insulin pump use has become more widespread over the past twenty years among people with T1D, the social and cultural effects of using these medical devices on their everyday experiences have become both increasingly apparent for individuals yet consistently absent from social and cultural studies of the disease.</p><p><br></p><p>In this dissertation, I explore the technological, medical, and cultural networks of insulin pump treatment to identify the role(s) these biomedicalized treatment acts play in the structuring of people, their bodies, and the cultural values constructed around various medical technologies. As I will show, insulin pump treatment alters people’s bodies and identities as devices become integrated as co-productive actors within patient-users’ biological and social systems. By analyzing personal interviews and digital media produced by people with T1D alongside archival materials, this study identifies compulsory patterns in the practices, structures, and narratives related to insulin pump use to center chapters around the productive (and sometimes stifling) relationship between people, bodies, technologies, and American culture.</p><p><br></p><p>By analyzing the layered and intersecting sites of insulin pump treatment together, this project reveals how medical technologies, health identities, bodies, and cultures are co-constructed and co-defined in ways that bind them together—mutually constitutive, medically compelled, cultural and social. New bodies and new systems, I argue, come with new (in)visibilities, and while this new technologically-produced legibility of the body provides unprecedented management of the symptoms and side-effects of the disease, it also brings with it unforeseen social consequences that require changes to people’s everyday lives and practices. </p>