Stakeholder-engaged development of a rapid test for detection of acute HIV infection.

Background/Objective: The utilization of rapid HIV tests has been effective at reducing transmission rates in high-risk populations by allowing individuals to receive diagnosis in as little as one minute and begin treatment. However, no current rapid tests can detect HIV immediately after infection in the acute HIV infection (AHI) phase, when the virus is at its most infectious, and instead require a waiting period of up to 90 days after exposure. Rapid HIV tests to detect AHI are currently under development. Investigation of stakeholder perspectives and context-specific needs are critical to ensure successful translation of novel AHI tests. The objectives of this study were to 1) understand context-specific factors such as barriers to HIV testing in Indiana, a state with one of 48 prioritized counties for HIV elimination; 2) assess the acceptability of a novel rapid AHI test, and 3) identify key implementation considerations for such a device, including ideal end-users. Methods: Semi-structured in-depth interviews were conducted with staff (n = 14) and clients (n = 5) of Indiana-based organizations that conduct HIV testing, including syringe service programs. Utilizing human-centered design frameworks, interview guides were developed and tailored to each participant group to understand their experiences with HIV testing, perspectives on a novel rapid AHI test in development, and preferences for self-testing versus testing by a community health worker (CHW) or a peer recovery coach. Thematic analysis was conducted to identify major themes, including barriers to HIV testing and perceived benefits and concerns of the proposed AHI test. Results: Overall acceptability for a novel AHI rapid test was high with a greater preference for CHW/Peerled testing. While self-testing was not a preferred modality, it was still seen as a potential tool to reach and address key barriers among high-risk individuals. Key considerations for implementation emphasized accuracy, cost-effectiveness, ease of use, ensuring access to counseling, education, and navigation to care while maintaining a human element to self-testing. Conclusion: Stakeholder engagement is meaningfully informing the design, development, and implementation of rapid AHI testing in order to facilitate adoption among populations at high-risk for HIV.

Preclinical validation of NeoWarm, a low-cost infant warmer and carrier device, to ameliorate induced hypothermia in newborn piglets as models for human neonates.

Introduction: Approximately 1.5 million neonatal deaths occur among premature and small (low birthweight or small-for gestational age) neonates annually, with a disproportionate amount of this mortality occurring in low- and middle-income countries (LMICs). Hypothermia, the inability of newborns to regulate their body temperature, is common among prematurely born and small babies, and often underlies high rates of mortality in this population. In high-resource settings, incubators and radiant warmers are the gold standard for hypothermia, but this equipment is often scarce in LMICs. Kangaroo Mother Care/Skin-to-skin care (KMC/STS) is an evidence-based intervention that has been targeted for scale-up among premature and small neonates. However, KMC/STS requires hours of daily contact between a neonate and an able adult caregiver, leaving little time for the caregiver to care for themselves. To address this, we created a novel self-warming biomedical device, NeoWarm, to augment KMC/STS. The present study aimed to validate the safety and efficacy of NeoWarm. Methods: Sixteen, 0-to-5-day-old piglets were used as an animal model due to similarities in their thermoregulatory capabilities, circulatory systems, and approximate skin composition to human neonates. The piglets were placed in an engineered cooling box to drop their core temperature below 36.5°C, the World Health Organizations definition of hypothermia for human neonates. The piglets were then warmed in NeoWarm (n = 6) or placed in the ambient 17.8°C ± 0.6°C lab environment (n = 5) as a control to assess the efficacy of NeoWarm in regulating their core body temperature. Results: All 6 piglets placed in NeoWarm recovered from hypothermia, while none of the 5 piglets in the ambient environment recovered. The piglets warmed in NeoWarm reached a significantly higher core body temperature (39.2°C ± 0.4°C, n = 6) than the piglets that were warmed in the ambient environment (37.9°C ± 0.4°C, n = 5) (p < 0.001). No piglet in the NeoWarm group suffered signs of burns or skin abrasions. Discussion: Our results in this pilot study indicate that NeoWarm can safely and effectively warm hypothermic piglets to a normal core body temperature and, with additional validation, shows promise for potential use among human premature and small neonates.

Biomolecular Interaction Analysis Quantification with a Low-Volume Microfluidic Chip and Particle Diffusometry.

Microfluidic techniques are widely applied in biomolecular analysis and disease diagnostic assays. While the volume of the sample that is directly used in such assays is often only femto-to microliters, the "dead volume" of solutions supplied in syringes and tubing can be much larger, even up to milliliters, increasing overall reagent use and making analysis significantly more expensive. To reduce the difficulty and cost, we designed a new chip using a low volume solution for analysis and applied it to obtain real-time data for protein-protein interaction measurements. The chip takes advantage of air/aqueous two-phase droplet flow, on-chip rapid mixing within milliseconds, and a droplet capture method, that ultimately requires only 2 µL of reagent solution. The interaction is analyzed by particle diffusometry, a nonintrusive and precise optical detection method to analyze the properties of microparticle diffusion in solution. Herein, we demonstrate on-chip characterization of human immunodeficiency virus p24 antibody-antigen protein binding kinetics imaged via fluorescence microscopy and analyzed by PD. The measured kon and koff are 1 × 106 M-1 s-1 and 3.3 × 10-4 s-1, respectively, and agree with independent measurement via biolayer interferometry and previously calculated p24-antibody binding kinetics. This new microfluidic chip and the protein-protein interaction analysis method can also be applied in other fields that require low-volume solutions to perform accurate measurement, analysis, and detection.

Two-phase Porous Media Flow Model Based on the Incompressible Navier-Stokes Equation.

Two-phase porous media flow is important in many applications from drug delivery to groundwater diffusion and oil recovery and is of particular interest to biomedical diagnostic test developers using cellulose and nitrocellulose membranes with limited fluid sample volumes. This work presents a new two-phase porous media flow model based on the incompressible Navier-Stokes equation. The model aims to address the limitations of existing methods by incorporating a partial saturation distribution in porous media to account for limited fluid volumes. The basic parameters of the model are the pore size distribution and the contact angle. To validate the model, we solved five analytical solutions and compared them to corresponding experimental data. The experimentally measured penetration length data agreed with the model predictions, demonstrating model accuracy. Our findings suggest that this new two-phase porous media flow model can provide a valuable tool for researchers developing fluidic assays in paper and other porous media.

Development of an integrated sample amplification control for salivary point-of-care pathogen testing.

BACKGROUND: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive analytical sensitivity in the lab, the assessment of clinical accuracy with IACs is often overlooked. In some cases, the IACs were run spatially, complicating assay workflow. Therefore, the multiplex assay for pathogen and IAC is needed. RESULTS: We developed a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for saliva samples, a non-invasive and simple collected specimen for POC NAATs. The ORF1ab gene of SARS-CoV-2 was used as a target and a human 18S ribosomal RNA in human saliva was employed as an IAC to ensure clinical reliability of the RT-LAMP assay. The optimized assay could detect SARS-CoV-2 viral particles down to 100 copies/µL of saliva within 30 min without RNA extraction. The duplex RT-LAMP for SARS-CoV-2 and IAC is successfully amplified in the same reaction without cross-reactivity. The valid results were easily visualized in triple-line lateral flow immunoassay, in which two lines (flow control and IAC lines) represent valid negative results and three lines (flow control, IAC, and test line) represent valid positive results. This duplex assay demonstrated a clinical sensitivity of 95%, specificity of 100%, and accuracy of 96% in 30 clinical saliva samples. SIGNIFICANCE: IACs play a crucial role in ensuring user confidence with respect to the accuracy and reliability of at-home and POC molecular diagnostics. We demonstrated the multiplex capability of SARS-COV-2 and human18S ribosomal RNA RT-LAMP without complicating assay design. This generic platform can be extended in a similar manner to include human18S ribosomal RNA IACs into different clinical sample matrices.

Wearable Sensor Patch with Hydrogel Microneedles for In Situ Analysis of Interstitial Fluid.

Continuous real-time monitoring of biomarkers in interstitial fluid is essential for tracking metabolic changes and facilitating the early detection and management of chronic diseases such as diabetes. However, developing minimally invasive sensors for the in situ analysis of interstitial fluid and addressing signal delays remain a challenge. Here, we introduce a wearable sensor patch incorporating hydrogel microneedles for rapid, minimally invasive collection of interstitial fluid from the skin while simultaneously measuring biomarker levels in situ. The sensor patch is stretchable to accommodate the swelling of the hydrogel microneedles upon extracting interstitial fluid and adapts to skin deformation during measurements, ensuring consistent sensing performance in detecting model biomarker concentrations, such as glucose and lactate, in a mouse model. The sensor patch exhibits in vitro sensitivities of 0.024 ± 0.002 µA mM-1 for glucose and 0.0030 ± 0.0004 µA mM-1 for lactate, with corresponding linear ranges of 0.1-3 and 0.1-12 mM, respectively. For in vivo glucose sensing, the sensor patch demonstrates a sensitivity of 0.020 ± 0.001 µA mM-1 and a detection range of 1-8 mM. By integrating a predictive model, the sensor patch can analyze and compensate for signal delays, improving calibration reliability and providing guidance for potential optimization in sensing performance. The sensor patch is expected to serve as a minimally invasive platform for the in situ analysis of multiple biomarkers in interstitial fluid, offering a promising solution for continuous health monitoring and disease management.

Development of an Integrated Sample Amplification Control for Salivary Point-of-Care Pathogen Testing.

Background: The COVID-19 pandemic has led to a rise in point-of-care (POC) and home-based tests, but concerns over usability, accuracy, and effectiveness have arisen. The incorporation of internal amplification controls (IACs), essential control for translational POC diagnostics, could mitigate false-negative and false-positive results due to sample matrix interference or inhibition. Although emerging POC nucleic acid amplification tests (NAATs) for detecting SARS-CoV-2 show impressive analytical sensitivity in the lab, the assessment of clinical accuracy with IACs is often overlooked. In some cases, the IACs were run spatially, complicating assay workflow. Therefore, the multiplex assay for pathogen and IAC is needed. Results: We developed a one-pot duplex reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay for saliva samples, a non-invasive and simple collected specimen for POC NAATs. The ORF1ab gene of SARS-CoV-2 was used as a target and a human 18S ribosomal RNA in human saliva was employed as an IAC to ensure clinical reliability of the RT-LAMP assay. The optimized assay could detect SARS-CoV-2 viral particles down to 100 copies/µL of saliva within 30 minutes without RNA extraction. The duplex RT-LAMP for SARS-CoV-2 and IAC is successfully amplified in the same reaction without cross-reactivity. The valid results were easily visualized in triple-line lateral flow immunoassay, in which two lines (flow control and IAC lines) represent valid negative results and three lines (flow control, IAC, and test line) represent valid positive results. This duplex assay demonstrated a clinical sensitivity of 95%, specificity of 100%, and accuracy of 96% in 30 clinical saliva samples. Significance: IACs play a crucial role in ensuring user confidence with respect to the accuracy and reliability of at-home and POC molecular diagnostics. We demonstrated the multiplex capability of SARS-COV-2 and human18S ribosomal RNA RT-LAMP without complicating assay design. This generic platform can be extended in a similar manner to include human18S ribosomal RNA IACs into different clinical sample matrices.

Selective Collection of Exhaled Breath Condensate for Noninvasive Screening of Breath Glucose.

BACKGROUND: Although exhaled breath condensate (EBC) is a promising noninvasive sample for detecting respiratory analytes such as glucose, current EBC collection methods yield inconsistent results. METHODS: We developed a custom EBC collection device with a temperature-based algorithm to selectively condense alveolar air for reproducible EBC glucose detection. We characterized the condensate volumes and the corresponding glucose concentrations. We performed a pilot study demonstrating its use during oral glucose tolerance tests. RESULTS: The novel device selectively captured alveolar air resulting in slightly higher and less variable glucose concentrations than the overall EBC. Participants with type 2 diabetes demonstrated significantly higher blood plasma-EBC glucose ratios than normoglycemic participants. CONCLUSIONS: Temperature-based selective EBC collection allows EBC glucose measurement and is a promising sampling method to distinguish patients with and without diabetes.

Thinking Beyond the Device: An Overview of Human- and Equity-Centered Approaches for Health Technology Design.

A shift in the traditional technocentric view of medical device design to a human-centered one is needed to bridge existing translational gaps and improve health equity. To ensure the successful and equitable adoption of health technology innovations, engineers must think beyond the device and the direct end user and must seek a more holistic understanding of broader stakeholder needs and the intended context of use early in a design process. The objectives of this review article are (a) to provide rationale for the need to incorporate meaningful stakeholder analysis and contextual investigation in health technology development and biomedical engineering pedagogy, (b) to review existing frameworks and human- and equity-centered approaches to stakeholder engagement and contextual investigation for improved adoption of innovative technologies, and (c) to present case studyexamples of medical device design that apply these approaches to bridge the gaps between biomedical engineers and the contexts for which they are designing.

Promise and perils of paper-based point-of-care nucleic acid detection for endemic and pandemic pathogens.

From HIV and influenza to emerging pathogens like COVID-19, each new infectious disease outbreak has highlighted the need for massively-scalable testing that can be performed outside centralized laboratory settings at the point-of-care (POC) in order to prevent, track, and monitor endemic and pandemic threats. Nucleic acid amplification tests (NAATs) are highly sensitive and can be developed and scaled within weeks while protein-based rapid tests require months for production. Combining NAATs with paper-based detection platforms are promising due to the manufacturability, scalability, and simplicity of each of these components. Typically, paper-based NAATs consist of three sequential steps: sample collection and preparation, amplification of DNA or RNA from pathogens of interest, and detection. However, these exist within a larger ecosystem of sample collection and interpretation workflow, usability, and manufacturability which can be vastly perturbed during a pandemic emergence. This review aims to explore the challenges of paper-based NAATs covering sample-to-answer procedures along with three main types of clinical samples; blood, urine, and saliva, as well as broader operational, scale up, and regulatory aspects of device development and implementation. To fill the technological gaps in paper-based NAATs, a sample-in-result-out system that incorporates the integrated sample collection, sample preparation, and integrated internal amplification control while also balancing needs of users and manufacturability upfront in the early design process is required.

Quantifying Brownian motion in the presence of simple shear flow with particle diffusometry.

Particle diffusometry, a technology derived from particle image velocimetry, quantifies the Brownian motion of particles suspended in a quiescent solution by computing the diffusion coefficient. Particle diffusometry has been used for pathogen detection by measuring the change in solution viscosity due to amplified DNA from a specific gene target. However, particle diffusometry fails to calculate accurate measurements at elevated temperatures and fluid flow. Therefore, these two current limitations hinder the potential application where particle diffusometry can further be used. In this work, we expanded the usability of particle diffusometry to be applied to fluid samples with simple shear flow and at various temperatures. A range of diffusion coefficient videos is created to simulate the Brownian motion of particles under flow and temperature conditions. Our updated particle diffusometry analysis forms a correction equation under three different polynomial degrees of shear flow with varying flow rates and temperatures between 25 and 65 °C. An experiment in a channel with a rectangular cross section using a syringe pump to generate a constant flow is done to analyze the modified algorithm. In simulation analysis, the modified algorithm successfully computes the diffusion coefficients with ±  10% error for an average flow rate of up to 8 pixel / Δ t on all three flow types. Complementary experiments confirm the simulation results.

Microporous affinity membranes and their incorporation into microfluidic devices for monitoring of therapeutic antibodies.

Control of monoclonal antibody (mAb) concentrations in serum is important for maintaining the safety and efficacy of these lifesaving therapeutics. Point-of-care (POC) quantification of therapeutic mAbs could ensure that patients have effective mAb levels without compromising safety. This work uses mimotope-functionalized microporous alumina affinity membranes in vertical flow assays for detection and quantitation of therapeutic mAbs. Selective capture of bevacizumab from 1000:1 diluted serum or plasma and binding of a fluorescently labelled anti-human IgG secondary antibody enable fluorescence-based analysis of bevacizumab at its therapeutically relevant concentration range of ∼50-300 µg/mL. The assay results in a linear relationship between the fluorescence intensity of the antibody capture spot and the bevacizumab concentration. A simple prototype microfluidic device containing these membranes allows washing, reagent additions and visualization of signal within 15 min using a total of 5 mL of fluid. The prototype devices can monitor physiologically relevant bevacizumab levels in diluted serum, and future refinements might lead to a POC device for therapeutic drug monitoring.

Human-centered design of a smartphone-based self-test for HIV viral load monitoring.

Background/Objective: HIV viral load self-testing could enable people living with HIV (PLHIV) to monitor their viral suppression status more easily, potentially facilitating medication adherence and safe behavior decision-making. Smartphone-based viral load testing innovations have the potential to reach resource-limited and vulnerable communities to address inequities in access to HIV care. However, successful development and translation of these tests requires meaningful investigation of end-user contexts and incorporation of those context-specific needs early in the design process. The objective of this study is to engage PLHIV and HIV healthcare providers in human-centered design research to inform key design and implementation considerations for a smartphone-based HIV viral load self-testing device prototype in development. Methods: Semi-structured in-depth interviews were conducted with PLHIV (n = 10) and HIV providers (n = 4) in Indiana, a state with suboptimal viral suppression rates and marked disparities in access to HIV care. Interview guides were developed based on contextual investigation and human-centered design frameworks and included a demonstration of the device prototype with feedback-gathering questions. Results: Thematic analysis of interview transcripts revealed important benefits, concerns, and user requirements for smartphone-based HIV VL self-testing within the context of PLHIV lived experience, knowledge, and barriers to care in Indiana. Conclusion: End-user needs and preferences were identified as key design specifications and implementation considerations to facilitate the acceptability and inform ongoing development and ultimately real-world translation of the HIV VL monitoring device prototype.

Measurement of Protein-Protein Interaction Dynamics Using Microfluidics and Particle Diffusometry.

The measurement and optimization of protein-protein interactions are critical in the design of biotherapeutics, biomolecular sensing elements, and functional protein-based biomaterials among other biomolecular sciences and engineering. Current gold standard assays require specifically designed core facilities, equipment, and expertise to implement the measurement, making it inconvenient for most labs unless implemented routinely. We developed a new method aiming at measuring protein binding kinetics based on microfluidics and particle diffusometry (PD), which only needs very general lab equipment, including a fluorescence microscope, a syringe pump, and a simple microchannel fabricated on a glass slide. Protein binding pairs are immobilized on two kinds of nanoparticles with different diameters using widely available conjugation chemistries. The two diluted particle suspensions are injected using a syringe pump into a Y-junction microchannel, where they bind and form particle complexes with increasing size, thereby decreasing particles' Brownian motion amplitude and diffusivity, which can be detected by PD. By taking images at a series of specific points along the microchannel, the particle diffusivity is measured at different time points after the introduction of protein-protein binding. These data are then used to quantify the protein binding kinetic constant. This label-free particle-based method is simple to operate and as accurate as the current gold standard. We demonstrate the feasibility of this accessible method by quantifying the streptavidin-biotin association constant (1.74 ± 0.51 × 107 M-1 s-1), which compares well with previously published results.

Characterization of wax valving and µPIV analysis of microscale flow in paper-fluidic devices for improved modeling and design.

Paper-fluidic devices are a popular platform for point-of-care diagnostics due to their low cost, ease of use, and equipment-free detection of target molecules. They are limited, however, by their lack of sensitivity and inability to incorporate more complex processes, such as nucleic acid amplification or enzymatic signal enhancement. To address these limitations, various valves have previously been implemented in paper-fluidic devices to control fluid obstruction and release. However, incorporation of valves into new devices is a highly iterative, time-intensive process due to limited experimental data describing the microscale flow that drives the biophysical reactions in the assay. In this paper, we tested and modeled different geometries of thermally actuated valves to investigate how they can be more easily implemented in an LFIA with precise control of actuation time, flow rate, and flow pattern. We demonstrate that bulk flow measurements alone cannot estimate the highly variable microscale properties and effects on LFIA signal development. To further quantify the microfluidic properties of paper-fluidic devices, micro-particle image velocimetry was used to quantify fluorescent nanoparticle flow through the membranes and demonstrated divergent properties from bulk flow that may explain additional variability in LFIA signal generation. Altogether, we demonstrate that a more robust characterization of paper-fluidic devices can permit fine-tuning of parameters for precise automation of multi-step assays and inform analytical models for more efficient design.

From crisis to crisis: impacts of the COVID-19 pandemic on people living with HIV and HIV/AIDS service organizations in Indiana.

BACKGROUND: The COVID-19 pandemic thrust people living with HIV (PLWH) and HIV/AIDS service organizations into an environment ripe with uncertainty. This study examined Indiana HIV/AIDS service provider perceptions of how COVID-19 affected the overall health and access to care of their clients, and how the organizations prepared for, adapted, and responded to the needs of PLWH during the pandemic. METHODS: Guided by the socioecological model, fifteen semi-structured interviews were conducted with ten different HIV/AIDS service organizations across the state of Indiana. RESULTS: Despite the profound disruptions experienced by HIV programs, HIV/AIDS service organizations responded quickly to the challenges posed by the COVID-19 pandemic through myriad innovative strategies, largely informed by prior experiences with the HIV epidemic. CONCLUSIONS: The lessons provided by HIV/AIDS service organizations are invaluable to informing future pandemic response for PLWH. Service delivery innovations in response to the COVID-19 crisis may provide insights to improve HIV care continuity strategies for vulnerable populations far beyond the pandemic.

PD-LAMP smartphone detection of SARS-CoV-2 on chip.

In 2019 the COVID-19 pandemic, caused by SARS-CoV-2, demonstrated the urgent need for rapid, reliable, and portable diagnostics. The COVID-19 pandemic was declared in January 2020 and surges of the outbreak continue to reoccur. It is clear that early identification of infected individuals, especially asymptomatic carriers, plays a huge role in preventing the spread of the disease. The current gold standard diagnostic for SARS-CoV-2 is quantitative reverse transcription polymerase chain reaction (qRT-PCR) test based on the detection of the viral RNA. While RT-PCR is reliable and sensitive, it requires expensive centralized equipment and is time consuming (∼2 h or more); limiting its applicability in low resource areas. The FDA issued Emergency Use Authorizations (EUAs) for several COVID-19 diagnostics with an emphasis on point-of care (PoC) testing. Numerous RT-PCR and serological tests were approved for use at the point of care. Abbott's ID NOW, and Cue Health's COVID-19 test are of particular interest, which use isothermal amplification methods for rapid detection in under 20 min. We look to expand on the range of current PoC testing platforms with a new rapid and portable isothermal nucleic acid detection device. We pair reverse transcription loop mediated isothermal amplification (RT-LAMP) with a particle imaging technique, particle diffusometry (PD), to successfully detect SARS-CoV-2 in only 35 min on a portable chip with integrated heating. A smartphone device is used to image the samples containing fluorescent beads post-RT-LAMP and correlates decreased diffusivity to positive samples. We detect as little as 30 virus particles per µL from a RT-LAMP reaction in a microfluidic chip using a portable heating unit. Further, we can perform RT-LAMP from a diluted unprocessed saliva sample without RNA extraction. Additionally, we lyophilize SARS-CoV-2-specific RT-LAMP reactions that target both the N gene and the ORF1ab gene in the microfluidic chip, eliminating the need for cold storage. Our assay meets specific target product profiles outlined by the World Health Organization: it is specific to SARS-CoV-2, does not require cold storage, is compatible with digital connectivity, and has a detection limit of less than 35 × 104 viral particles per mL in saliva. PD-LAMP is rapid, simple, and attractive for screening and use at the point of care.

Navigating the Regulatory Pathway for Medical Devices-a Conversation with the FDA, Clinicians, Researchers, and Industry Experts.

Successful translation of new and innovative medical products from concept to clinical use is a complex endeavor that requires understanding and overcoming a variety of challenges. In particular, regulatory pathways and processes are often unfamiliar to academic researchers and start-ups, and even larger companies. Growing evidence suggests that the successful translation of ideas to products requires collaboration and cooperation between clinicians, researchers, industry, and regulators. A multi-stakeholder group developed this review to enhance regulatory knowledge and thereby improve translational success for medical devices. Communication between and among stakeholders is identified as a critical factor. Current regulatory programs and processes to facilitate communication and translation of innovative devices are described and discussed. Case studies are used to highlight the importance of flexibility when considering evidence requirements. We provide a review of emerging strategies, opportunities, and best practices to increase the regulatory knowledge base and facilitate medical device translation by all stakeholders. Clinicians, regulators, industry, and researchers require regulatory knowledge and collaboration for successful translation of innovative medical devices.

Review of non-invasive detection of SARS-CoV-2 and other respiratory pathogens in exhaled breath condensate.

In 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged to cause high viral infectivity and severe respiratory illness in humans (COVID-19). Worldwide, limited pandemic mitigation strategies, including lack of diagnostic test availability, resulted in COVID-19 overrunning health systems and spreading throughout the global population. Currently, proximal respiratory tract (PRT) specimens such as nasopharyngeal swabs are used to diagnose COVID-19 because of their relative ease of collection and applicability in large scale screening. However, localization of SARS-CoV-2 in the distal respiratory tract (DRT) is associated with more severe infection and symptoms. Exhaled breath condensate (EBC) is a sample matrix comprising aerosolized droplets originating from alveolar lining fluid that are further diluted in the DRT and then PRT and collected via condensation during tidal breathing. The COVID-19 pandemic has resulted in recent resurgence of interest in EBC collection as an alternative, non-invasive sampling method for the staging and accurate detection of SARS-CoV-2 infections. Herein, we review the potential utility of EBC collection for detection of SARS-CoV-2 and other respiratory infections. While much remains to be discovered in fundamental EBC physiology, pathogen-airway interactions, and optimal sampling protocols, EBC, combined with emerging detection methods, presents a promising non-invasive sample matrix for detection of SARS-CoV-2.

From Crisis To Crisis: Impacts Of The COVID-19 Pandemic On People Living With HIV And AIDS Service Organizations In Indiana.

Background: The COVID-19 pandemic thrust people living with HIV (PLWH) and HIV/AIDS service organizations into an environment ripe with uncertainty. This study examined Indiana AIDS services provider perceptions of how COVID-19 affected the overall health and access to care of their clients, and how the organizations prepared for, adapted, and responded to the needs of PLWH during the pandemic. Methods: Guided by the socioecological model, fifteen semi-structured interviews were conducted with ten different HIV/AIDS service organizations across the state of Indiana. Results: Despite the profound disruptions experienced by HIV programs, HIV/AIDS service organizations responded quickly to the challenges posed by the COVID-19 pandemic through myriad innovative strategies, largely informed by prior experiences with the HIV epidemic. Conclusions: The lessons provided by HIV/AIDS service organizations are invaluable to informing future pandemic response for PLWH. Service delivery innovations in response to the COVID-19 crisis may provide insights to improve HIV care continuity strategies for vulnerable populations far beyond the pandemic.