Assessing Preferences for Long-Acting Injectable Pre-Exposure Prophylaxis Among Young Adult Sexual Minority Men and Transgender Women.

OBJECTIVE: Oral pre-exposure prophylaxis (PrEP) is effective in preventing HIV transmission. However, oral PrEP uptake is low, particularly among sexual and gender minority youth who are vulnerable to HIV infection. Alternative methods of PrEP delivery, such as long-acting injectable (LAI) PrEP may overcome barriers and be preferred. However, attitudes and preferences of younger sexual and gender minorities towards LAI PrEP have not been well studied. The purpose of this study is to describe preferences for initiating LAI PrEP among sexual and gender minority youth. METHODS: We analyzed data collected as part of an HIV prevention randomized trial from January 2022 to February 2023, using multiple regression to identify factors associated with a preference for LAI PrEP. RESULTS: The study sample (N = 265) was 50% youth of color, mean age 25 years (SD=3.4, range=18-31), and primarily identified as gay (71%) and male (91%). Forty two percent had heard of LAI PrEP and 31% preferred LAI PrEP over other prevention methods. In multiple regression analysis, LAI PrEP preference was associated with identifying as White, previous PrEP experience, and perceived LAI PrEP efficacy. CONCLUSIONS: We conclude that gaps in awareness exist for LAI PrEP, however it may be preferred over other prevention methods especially in White youth, those with PrEP experience and higher perceptions of its efficacy. More education and outreach are needed to prevent extension of existing race and ethnicity disparities in use of oral daily PrEP to LAI PrEP.

Immunochromatographic POC-CCA Test for the diagnosis of intestinal schistosomiasis in a high endemic region in Brazil: Differences in the interpretation of results.

The POC-CCA test is subject to variations in reading interpretations depending on the intensity of its results, and trace test reading have implications for determining prevalence. The aim of this study was to assess whether the readings obtained from the POC-CCA tests, conducted using a semi-quantitative scale (the G-score classification for test determination), exhibited concurrence with the direct visual interpretation (positive, negative, or trace) performed by two distinct analysts, using photographs from previously performed POC-CCA test carried out in the municipality of Maruim, in the state of Sergipe-Brazil, a region of high endemicity. The devices used to read the photographs were smartphones, so as to simulate field usage, and a desktop, a tool with higher image quality that would help the researchers in the evaluation and establishment of the final result at a later. In direct visual interpretation of the POC-CCA photographs, the most discordant results occurred in the identification of the trace response (T). The Kappa index established for the direct visual interpretation between the two analysts, in which T is considered as positive, in the desktop was κ=0.826 and in the smartphone, κ=0.950. When we use the G-score as a reading standardization technique and classify the results according to the manufacturer, with trace being evaluated as positive, the highest level of agreement was obtained. Some disagreement remains between the direct visual interpretation and the G-score when performed on the desktop, with more individuals being classified as negative in the direct visual interpretation, by both analysts. However, this result was not statistically significant. The use of the G-score scale proved to be an excellent tool for standardizing the readings and classifying the results according to the semi-quantitative scale showed greater concordance of results both among analysts and among the different devices used to view the photographs.

A randomized controlled trial of an mHealth intervention for increasing access to HIV testing and care among young cisgender men and transgender women: the mLab App study protocol.

BACKGROUND: The number of youth living with HIV in the United States (US) continues to rise, and racial, ethnic, and sexual minority youth including young men who have sex with men (YMSM) and young transgender women (YTGW) bear a disproportionate burden of the HIV epidemic. Due to social and healthcare system factors, many YMSM and YTGW do not seek HIV testing services and are therefore less likely to be aware that they are infected. Mobile health technology (mHealth) has the ability to increase uptake of HIV testing among these populations. Thus, the mLab App-which combines HIV prevention information with a mobile phone imaging feature for interpreting at-home HIV test results-was developed to improve testing rates and linkage to care among Black, Latino, and other YMSM and YTGW living in New York City and Chicago and their surrounding areas. METHODS: This study is a three-arm randomized controlled trial among YMSM and YTGW aged 18-29 years. Participants are randomized to either the mLab App intervention including HIV home test kits and standard of preventive care, standard of preventive care only, or HIV home test kits and standard of preventive care only. DISCUSSION: mHealth technology used for HIV prevention is capable of delivering interventions in real-time, which creates an opportunity to remotely reach users across the country to strengthen their HIV care continuum engagement and treatment outcomes. Specifically during the COVID-19 pandemic, mHealth technology combined with at-home testing may prove to be essential in increasing HIV testing rates, especially among populations at high-risk or without regular access to HIV testing. TRIAL REGISTRATION: This trial was registered with Clinicaltrials.gov ( NCT03803683 ) on January 14, 2019.

Usability Evaluation of the mLab App for Improving Home HIV Testing Behaviors in Youth at Risk of HIV Infection.

Improving access to HIV testing among youth at high risk is essential for reaching those who are most at risk for HIV and least likely to access health care services. This study evaluates the usability of mLab, an app with image-processing feature that analyzes photos of OraQuick HIV self-tests and provides real-time, personalized feedback. mLab includes HIV prevention information, testing reminders, and instructions. It was developed through iterative feedback with a youth advisory board (N = 8). The final design underwent heuristic (N = 5) and end-user testing (N = 20). Experts rated mLab following Nielsen's heuristic checklist. End-users used the Health Information Technology Usability Evaluation Scale. While there were some usability problems, overall study participants found mLab useful and user-friendly. This study provides important insights into using a mobile app with imaging for interpreting HIV test results with the goal of improving HIV testing and prevention in populations at high risk.

mHAT app for automated malaria rapid test result analysis and aggregation: a pilot study.

BACKGROUND: There are a variety of approaches being used for malaria surveillance. While active and reactive case detection have been successful in localized areas of low transmission, concerns over scalability and sustainability keep the approaches from being widely accepted. Mobile health interventions are poised to address these shortcomings by automating and standardizing portions of the surveillance process. In this study, common challenges associated with current data aggregation methods have been quantified, and a web-based mobile phone application is presented to reduce the burden of reporting rapid diagnostic test (RDT) results in low-resource settings. METHODS: De-identified completed RDTs were collected at 14 rural health clinics as part of a malaria epidemiology study at Macha Research Trust, Macha, Zambia. Tests were imaged using the mHAT web application. Signal intensity was measured and a binary result was provided. App performance was validated by: (1) comparative limits of detection, investigated against currently used laboratory lateral flow assay readers; and, (2) receiver operating characteristic analysis comparing the application against visual inspection of RDTs by an expert. Secondary investigations included analysis of time-to-aggregation and data consistency within the existing surveillance structures established by Macha Research Trust. RESULTS: When compared to visual analysis, the mHAT app performed with 91.9% sensitivity (CI 78.7, 97.2) and specificity was 91.4% (CI 77.6, 97.0) regardless of device operating system. Additionally, an analysis of surveillance data from January 2017 through mid-February 2019 showed that while the majority of the data packets from satellite clinics contained correct data, 36% of data points required correction by verification teams. Between November 2018 and mid-February 2019, it was also found that 44.8% of data was received after the expected submission date, although most (65.1%) reports were received within 2 days. CONCLUSIONS: Overall, the mHAT mobile app was observed to be sensitive and specific when compared to both currently available benchtop lateral flow readers and visual inspection. The additional benefit of automating and standardizing LFA data collection and aggregation poses a vital improvement for low-resource health facilities and could increase the accuracy and speed of data reporting in surveillance campaigns.

Inductively coupled plasma optical emission spectroscopy as a tool for evaluating lateral flow assays.

Lateral flow assays (LFAs) are immunochromatographic point-of-care devices that have greatly impacted disease diagnosis through their rapid, inexpensive, and easy-to-use form factor. While LFAs have been successful as field-deployable tools, they have a relatively poor limit of detection when compared to more complex methods. Moreover, most design and manufacturing optimization is achieved through time- and resource-intensive brute-force optimization. Despite increased interests in LFA manufacturing, more quantitative tools are needed to study current manufacturing protocols and therefore, optimize and streamline development of these devices further. In this work, we focus on a critical LFA component, colloidal gold conjugated to a detection antibody, one of the most commonly used reporter elements. This study utilizes inductively coupled plasma optical emission spectroscopy (ICP-OES) in conjunction with a lateral flow reader to quantitatively analyze colloidal gold distributions at the read-out test and control lines, as well as residual gold on the conjugate pad and other flow through regions. Our goals are to develop a more rigorous understanding of current LFA designs as well as a quantitative understanding of shortcomings of operational characteristics for future improvement. To our knowledge, this is the first time that ICP-OES has been used to study the initial distribution of colloidal gold on an unused LFA and its redistribution after a test is performed. Using three different brands of commercially available malaria LFAs, gold content was measured within each section of an LFA at varying parasite test concentrations. As expected, the total mass of gold remained unchanged after LFA use; however, the total mass of initial gold and its redistribution varied among manufacturers. Importantly, there are also some inherent inefficiencies that exist in these commercial LFA designs; for example, only 30% of the total gold deposited onto Brand A LFAs binds to the test and control lines, sections of the test that contain interpretable signal. Using information gathered with this method, future devices could be more purposefully engineered to focus on improved binding efficiency, resulting in reduced costs, improved limit of detection, and diminished test-to-test and manufacturer-to-manufacturer variability.

Understanding On-Campus Interactions With a Semiautomated, Barcode-Based Platform to Augment COVID-19 Contact Tracing: App Development and Usage.

BACKGROUND: The COVID-19 pandemic has forced drastic changes to daily life, from the implementation of stay-at-home orders to mandating facial coverings and limiting in-person gatherings. While the relaxation of these control measures has varied geographically, it is widely agreed that contact tracing efforts will play a major role in the successful reopening of businesses and schools. As the volume of positive cases has increased in the United States, it has become clear that there is room for digital health interventions to assist in contact tracing. OBJECTIVE: The goal of this study was to evaluate the use of a mobile-friendly app designed to supplement manual COVID-19 contact tracing efforts on a university campus. Here, we present the results of a development and validation study centered around the use of the MyCOVIDKey app on the Vanderbilt University campus during the summer of 2020. METHODS: We performed a 6-week pilot study in the Stevenson Center Science and Engineering Complex on Vanderbilt University's campus in Nashville, TN. Graduate students, postdoctoral fellows, faculty, and staff >18 years who worked in Stevenson Center and had access to a mobile phone were eligible to register for a MyCOVIDKey account. All users were encouraged to complete regular self-assessments of COVID-19 risk and to key in to sites by scanning a location-specific barcode. RESULTS: Between June 17, 2020, and July 29, 2020, 45 unique participants created MyCOVIDKey accounts. These users performed 227 self-assessments and 1410 key-ins. Self-assessments were performed by 89% (n=40) of users, 71% (n=32) of users keyed in, and 48 unique locations (of 71 possible locations) were visited. Overall, 89% (202/227) of assessments were determined to be low risk (ie, asymptomatic with no known exposures), and these assessments yielded a CLEAR status. The remaining self-assessments received a status of NOT CLEAR, indicating either risk of exposure or symptoms suggestive of COVID-19 (7.5% [n=17] and 3.5% [n=8] of self-assessments indicated moderate and high risk, respectively). These 25 instances came from 8 unique users, and in 19 of these instances, the at-risk user keyed in to a location on campus. CONCLUSIONS: Digital contact tracing tools may be useful in assisting organizations to identify persons at risk of COVID-19 through contact tracing, or in locating places that may need to be cleaned or disinfected after being visited by an index case. Incentives to continue the use of such tools can improve uptake, and their continued usage increases utility to both organizational and public health efforts. Parameters of digital tools, including MyCOVIDKey, should ideally be optimized to supplement existing contact tracing efforts. These tools represent a critical addition to manual contact tracing efforts during reopening and sustained regular activity.

App Use and Usability of a Barcode-Based Digital Platform to Augment COVID-19 Contact Tracing: Postpilot Survey and Paradata Analysis.

BACKGROUND: The COVID-19 pandemic has drastically changed life in the United States, as the country has recorded over 23 million cases and 383,000 deaths to date. In the leadup to widespread vaccine deployment, testing and surveillance are critical for detecting and stopping possible routes of transmission. Contact tracing has become an important surveillance measure to control COVID-19 in the United States, and mobile health interventions have found increased prominence in this space. OBJECTIVE: The aim of this study was to investigate the use and usability of MyCOVIDKey, a mobile-based web app to assist COVID-19 contact tracing efforts, during the 6-week pilot period. METHODS: A 6-week study was conducted on the Vanderbilt University campus in Nashville, Tennessee. The study participants, consisting primarily of graduate students, postdoctoral researchers, and faculty in the Chemistry Department at Vanderbilt University, were asked to use the MyCOVIDKey web app during the course of the study period. Paradata were collected as users engaged with the MyCOVIDKey web app. At the end of the study, all participants were asked to report on their user experience in a survey, and the results were analyzed in the context of the user paradata. RESULTS: During the pilot period, 45 users enrolled in MyCOVIDKey. An analysis of their enrollment suggests that initial recruiting efforts were effective; however, participant recruitment and engagement efforts at the midpoint of the study were less effective. App use paralleled the number of users, indicating that incentives were useful for recruiting new users to sign up but did not result in users attempting to artificially inflate their use as a result of prize offers. Times to completion of key tasks were low, indicating that the main features of the app could be used quickly. Of the 45 users, 30 provided feedback through a postpilot survey, with 26 (58%) completing it in its entirety. The MyCOVIDKey app as a whole was rated 70.0 on the System Usability Scale, indicating that it performed above the accepted threshold for usability. When the key-in and self-assessment features were examined on their own, it was found that they individually crossed the same thresholds for acceptable usability but that the key-in feature had a higher margin for improvement. CONCLUSIONS: The MyCOVIDKey app was found overall to be a useful tool for COVID-19 contact tracing in a university setting. Most users suggested simple-to-implement improvements, such as replacing the web app framework with a native app format or changing the placement of the scanner within the app workflow. After these updates, this tool could be readily deployed and easily adapted to other settings across the country. The need for digital contact tracing tools is becoming increasingly apparent, particularly as COVID-19 case numbers continue to increase while more businesses begin to reopen.

Evaluating Network Readiness for mHealth Interventions Using the Beacon Mobile Phone App: Application Development and Validation Study.

BACKGROUND: Mobile health (mHealth) interventions have the potential to transform the global health care landscape. The processing power of mobile devices continues to increase, and growth of mobile phone use has been observed worldwide. Uncertainty remains among key stakeholders and decision makers as to whether global health interventions can successfully tap into this trend. However, when correctly implemented, mHealth can reduce geographic, financial, and social barriers to quality health care. OBJECTIVE: The aim of this study was to design and test Beacon, a mobile phone-based tool for evaluating mHealth readiness in global health interventions. Here, we present the results of an application validation study designed to understand the mobile network landscape in and around Macha, Zambia, in 2019. METHODS: Beacon was developed as an automated mobile phone app that continually collects spatiotemporal data and measures indicators of network performance. Beacon was used in and around Macha, Zambia, in 2019. Results were collected, even in the absence of network connectivity, and asynchronously uploaded to a database for further analysis. RESULTS: Beacon was used to evaluate three mobile phone networks around Macha. Carriers A and B completed 6820/7034 (97.0%) and 6701/7034 (95.3%) downloads and 1349/1608 (83.9%) and 1431/1608 (89.0%) uploads, respectively, while Carrier C completed only 62/1373 (4.5%) file downloads and 0/1373 (0.0%) file uploads. File downloads generally occurred within 4 to 12 seconds, and their maximum download speeds occurred between 2 AM and 5 AM. A decrease in network performance, demonstrated by increases in upload and download durations, was observed beginning at 5 PM and continued throughout the evening. CONCLUSIONS: Beacon was able to compare the performance of different cellular networks, show times of day when cellular networks experience heavy loads and slow down, and identify geographic "dead zones" with limited or no cellular service. Beacon is a ready-to-use tool that could be used by organizations that are considering implementing mHealth interventions in low- and middle-income countries but are questioning the feasibility of the interventions, including infrastructure and cost. It could also be used by organizations that are looking to optimize the delivery of an existing mHealth intervention with improved logistics management.

Hybrid Synthetic-Biological Hydrogel System for Adipose Tissue Regeneration.

Hydrogels are promising scaffolds for adipose tissue regeneration. Currently, the incorporation of bioactive molecules in hydrogel system is used, which can increase the cell proliferation rate or improve adipogenic differentiation performance of stromal stem cells but often suffers from high expense or cytotoxicity because of light/thermal curing used for polymerization. In this study, decellularized adipose tissue is incorporated, at varying concentrations, with a thiol-acrylate fraction that is then polymerized to produce hydrogels via a Michael addition reaction. The results reveal that the major component of isolated adipose-derived extracellular matrix (ECM) is Collagen I. Mechanical properties of ECM polyethylene glycol (PEG) are not negatively affected by the incorporation of ECM. Additionally, human adipose-derived stem cells (hASCs) are encapsulated in ECM PEG hydrogel with ECM concentrations varying from 0% to 1%. The results indicate that hASCs maintained the highest viability and proliferation rate in 1% ECM PEG hydrogel with most lipids formation when cultured in adipogenic conditions. Furthermore, more adipose regeneration is observed in 1% ECM group with in vivo study by Day 14 compared to other ECM PEG hydrogels with lower ECM content. Taken together, these findings suggest the ECM PEG hydrogel is a promising substitute for adipose tissue regeneration applications.

A microfluidic device for motility and osmolality analysis of zebrafish sperm.

A microfluidic chip is described that facilitates research and quality control analysis of zebrafish sperm which, due to its miniscule (i.e., 2-5 µl) sample volume and short duration of motility (i.e., <1 min), present a challenge for traditional manual assessment methods. A micromixer molded in polydimethylsiloxane (PDMS) bonded to a glass substrate was used to activate sperm samples by mixing with water, initiated by the user depressing a transfer pipette connected to the chip. Sample flow in the microfluidic viewing chamber was able to be halted within 1 s, allowing for rapid analysis of the sample using established computer-assisted sperm analysis (CASA) methods. Zebrafish sperm cell activation was consistent with manual hand mixing and yielded higher values of motility at earlier time points, as well as more subtle time-dependent trends in motility, than those processed by hand. Sperm activation curves, which indicate sample quality by evaluating percentage and duration of motility at various solution osmolalities, were generated with on-chip microfabricated gold floor electrodes interrogated by impedance spectroscopy. The magnitude of admittance was linearly proportional to osmolality and was not affected by the presence of sperm cells in the vicinity of the electrodes. This device represents a pivotal step in streamlining methods for consistent, rapid assessment of sperm quality for aquatic species. The capability to rapidly activate sperm and consistently measure motility with CASA using the microfluidic device described herein will help improve the reproducibility of studies on sperm and assist development of germplasm repositories.

Application of mass transfer theory to biomarker capture by surface functionalized magnetic beads in microcentrifuge tubes.

In many diagnostic assays, specific biomarker extraction and purification from a patient sample is performed in microcentrifuge tubes using surface-functionalized magnetic beads. Although assay binding times are known to be highly dependent on sample viscosity, sample volume, capture reagent, and fluid mixing, the theoretical mass transport framework that has been developed and validated in engineering has yet to be applied in this context. In this work, we adapt this existing framework for simultaneous mass transfer and surface reaction and apply it to the binding of biomarkers in clinical samples to surface-functionalized magnetic beads. We discuss the fundamental fluid dynamics of vortex mixing within microcentrifuge tubes as well as describe how particles and biomolecules interact with the fluid. The model is solved over a wide range of parameters, and we present scenarios when a simplified analytical expression would be most accurate. Next, we review of some relevant techniques for model parameter estimation. Finally, we apply the mass transfer theory to practical use-case scenarios of immediate use to clinicians and assay developers. Throughout, we highlight where further characterization is necessary to bridge the gap between theory and practical application.

Magnetically-enabled biomarker extraction and delivery system: towards integrated ASSURED diagnostic tools.

Diagnosis of asymptomatic malaria poses a great challenge to global disease elimination efforts. Healthcare infrastructure in rural settings cannot support existing state-of-the-art tools necessary to diagnose asymptomatic malaria infections. Instead, lateral flow immunoassays (LFAs) are widely used as a diagnostic tool in malaria endemic areas. While LFAs are simple and easy to use, they are unable to detect low levels of parasite infection. We have developed a field deployable Magnetically-enabled Biomarker Extraction And Delivery System (mBEADS) that significantly improves limits of detection for several commercially available LFAs. Integration of mBEADS with leading commercial Plasmodium falciparum malaria LFAs improves detection limits to encompass an estimated 95% of the disease reservoir. This user-centered mBEADS platform makes significant improvements to a previously cumbersome malaria biomarker enrichment strategy by improving reagent stability, decreasing the processing time 10-fold, and reducing the assay cost 10-fold. The resulting mBEADS process adds just three minutes and less than $0.25 to the total cost of a single LFA, thus balancing sensitivity and practicality to align with the World Health Organization's ASSURED criteria for point-of-care (POC) testing.

An embedded barcode for "connected" malaria rapid diagnostic tests.

Many countries are shifting their efforts from malaria control to disease elimination. New technologies will be necessary to meet the more stringent demands of elimination campaigns, including improved quality control of malaria diagnostic tests, as well as an improved means for communicating test results among field healthcare workers, test manufacturers, and national ministries of health. In this report, we describe and evaluate an embedded barcode within standard rapid diagnostic tests as one potential solution. This information-augmented diagnostic test operates on the familiar principles of traditional lateral flow assays and simply replaces the control line with a control grid patterned in the shape of a QR (quick response) code. After the test is processed, the QR code appears on both positive or negative tests. In this report we demonstrate how this multipurpose code can be used not only to fulfill the control line role of test validation, but also to embed test manufacturing details, serve as a trigger for image capture, enable registration for image analysis, and correct for lighting effects. An accompanying mobile phone application automatically captures an image of the test when the QR code is recognized, decodes the QR code, performs image processing to determine the concentration of the malarial biomarker histidine-rich protein 2 at the test line, and transmits the test results and QR code payload to a secure web portal. This approach blends automated, sub-nanomolar biomarker detection, with near real-time reporting to provide quality assurance data that will help to achieve malaria elimination.

Direct transfer of HRPII-magnetic bead complexes to malaria rapid diagnostic tests significantly improves test sensitivity.

BACKGROUND: The characteristic ease of use, rapid time to result, and low cost of malaria rapid diagnostic tests (RDTs) promote their widespread use at the point-of-care for malaria detection and surveillance. However, in many settings, the success of malaria elimination campaigns depends on point-of-care diagnostics with greater sensitivity than currently available RDTs. To address this need, a sample preparation method was developed to deliver more biomarkers onto a malaria RDT by concentrating the biomarker from blood sample volumes that are too large to be directly applied to a lateral flow strip. METHODS: In this design, Ni-NTA-functionalized magnetic beads captured the Plasmodium falciparum biomarker HRPII from a P. falciparum D6 culture spiked blood sample. This transfer of magnetic beads to the RDT was facilitated by an inexpensive 3D-printed apparatus that aligned the sample tube with the sample deposition pad and a magnet beneath the RDT. Biomarkers were released from the bead surface onto the lateral flow strip using imidazole-spiked running buffer. Kinetics of HRPII binding to the Ni-NTA beads as a function of blood sample volume were explored prior to determining the effect of the proposed method on the limit of detection of Paracheck RDTs. RESULTS: More than 80 % of HRPII biomarkers were extracted from blood sample volumes ranging from 25 to 250 µL. The time required to reach 80 % binding ranged from 5 to 60 min, depending on sample volume. Using 250 µL of blood and a 30-min biomarker binding time, the limit of detection of the Paracheck Pf RDT brand was improved by 21-fold, resulting in a limit of detection below 1 parasite/µL. CONCLUSIONS: This approach has the sensitivity and simplicity required to assist in malaria elimination campaigns in settings with limited access to clinical and laboratory resources.

Mobile phone imaging and cloud-based analysis for standardized malaria detection and reporting.

Rapid diagnostic tests (RDTs) have been widely deployed in low-resource settings. These tests are typically read by visual inspection, and accurate record keeping and data aggregation remains a substantial challenge. A successful malaria elimination campaign will require new strategies that maximize the sensitivity of RDTs, reduce user error, and integrate results reporting tools. In this report, an unmodified mobile phone was used to photograph RDTs, which were subsequently uploaded into a globally accessible database, REDCap, and then analyzed three ways: with an automated image processing program, visual inspection, and a commercial lateral flow reader. The mobile phone image processing detected 20.6 malaria parasites/microliter of blood, compared to the commercial lateral flow reader which detected 64.4 parasites/microliter. Experienced observers visually identified positive malaria cases at 12.5 parasites/microliter, but encountered reporting errors and false negatives. Visual interpretation by inexperienced users resulted in only an 80.2% true negative rate, with substantial disagreement in the lower parasitemia range. We have demonstrated that combining a globally accessible database, such as REDCap, with mobile phone based imaging of RDTs provides objective, secure, automated, data collection and result reporting. This simple combination of existing technologies would appear to be an attractive tool for malaria elimination campaigns.

A two-magnet strategy for improved mixing and capture from biofluids.

Magnetic beads are a popular method for concentrating biomolecules from solution and have been more recently used in multistep pre-arrayed microfluidic cartridges. Typical processing strategies rely on a single magnet, resulting in a tight cluster of beads and requiring long incubation times to achieve high capture efficiencies, especially in highly viscous patient samples. This report describes a two-magnet strategy to improve the interaction of the bead surface with the surrounding fluid inside of a pre-arrayed, self-contained assay-in-a-tube. In the two-magnet system, target biomarker capture occurs at a rate three times faster than the single-magnet system. In clinically relevant biomatrices, we find a 2.5-fold improvement in biomarker capture at lower sample viscosities with the two-magnet system. In addition, we observe a 20% increase in the amount of protein captured at high viscosity for the two-magnet configuration relative to the single magnet approach. The two-magnet approach offers a means to achieve higher biomolecule extraction yields and shorter assay times in magnetic capture assays and in self-contained processor designs.

In vitro evaluation of thermal frontally polymerized thiol-ene composites as bone augments.

Because of the large number of total knee replacement (TKR) surgeries conducted per year, and with projections of increased demand to almost a million primary TKR surgeries per year by 2030 in the United States alone, there is a need to discover more efficient working materials as alternatives to current bone cements. There is a need for surgeons and hospitals to become more efficient and better control over the operative environment. One area of inefficiency is the cement steps during TKR. Currently the surgeon has very little control over cement polymerization. This leads to an increase in time, waste, and procedural inefficiencies. There is a clear need to create an extended working time, moldable, osteoconductive, and osteoinductive bone augment as a substitution for the current clinically used bone cement where the surgeon has better control over the polymerization process. This study explored several compositions of pentaerythritol-co-trimethylolpropane tris-(3-mercaptopropionate) hydroxyapatite composite materials prepared via benzoyl peroxide-initiated thermal frontal polymerization. The 4:1 acrylate to thiol ratio containing augment material shows promise with a maximal propagation temperature of 160°C ± 10°C, with mechanical strength of 3.65 MPa, and 111% cytocompatibility, relative to the positive control. This frontally polymerized material may have application as an augment with controlled polymerization supporting cemented implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1152-1160, 2016.

Microfluidics and numerical simulation as methods for standardization of zebrafish sperm cell activation.

Sperm cell activation plays a critical role in a range of biological and engineering processes, from fertilization to cryopreservation protocol evaluation. Across a range of species, ionic and osmotic effects have been discovered that lead to activation. Sperm cells of zebrafish (Danio rerio) initiate motility in a hypoosmotic environment. In this study, we employ a microfluidic mixer for the purpose of rapidly diluting the extracellular medium to initiate the onset of cell motility. The use of a microchannel offers a rapid and reproducible mixing profile throughout the device. This greatly reduces variability from trial to trial relative to the current methods of analysis. Coupling these experiments with numerical simulations, we were able to investigate the dynamics of intracellular osmolality as each cell moves along its path through the micromixer. Our results suggest that intracellular osmolality, and hence intracellular ion concentration, only slightly decreases, contrary to the common thought that larger changes in these parameters are required for activation. Utilizing this framework, microfluidics for controlled extracellular environments and associated numerical modeling, has practical applicability in standardizing high-throughput aquatic sperm activation, and more fundamentally, investigations of the intracellular environment leading to motility.

In vitro characterization of polyesters of aconitic acid, glycerol, and cinnamic acid for bone tissue engineering.

In this study, a novel class of polyesters of glycerol, aconitic acid, and cinnamic acid were synthesized along with their hydroxyapatite (HA) composites, and studied for their potential application in bone defect repair. An osteogenic study was conducted with human adipose derived mesenchymal stem cells (hASCs) to determine the osteoinductive ability of aconitic acid-glycerol (AG) polyesters, AG:HA (80:20), aconitic acid-glycerol-cinnamic acid (AGC) polyesters, and AGC:HA (80:20) to serve as bone scaffolds. The results indicate that AGC scaffolds have the highest mechanical strength in comparison to AG, AG:HA (80:20), and AGC:HA (80:20) scaffolds due to its low porosity. It was determined by cytotoxicity and osteogenesis experiments that hASCs cultured for 21 days on AG:HA (80:20) scaffolds in stromal medium exhibited a greater number of live cells than control PCL:HA composites. Moreover, hASCs cultured on foamed AG:HA (80:20) scaffolds resulted in the highest levels of mineralization, increased alkaline phosphatase (ALP) expression, and the greatest osteocalcin (OCN) expression after 21 days. Overall, AG:HA (100:0 and 80:20) scaffolds had higher mechanical strength and cytocompatibility than the PCL:HA control. In vitro osteogenic study demonstrated that AG:HA (100:0 and 80:20) synthesized using sugarcane industry by-products hold potential as scaffolds for bone tissue engineering applications.