Interest in developing paper-based devices for point-of-care diagnostics in resource-limited settings has risen remarkably in recent decades. In this paper, we demonstrate what we refer to as “High Yield Passive Erythrocyte Removal” (HYPER) technology, which utilizes capillary forces in a unique cross-flow filtration for the separation of whole blood with performance comparable to centrifuges. As we will demonstrate, state-of-the-art passive blood separation methods implemented in paper-based systems exhibit rapid blood cell clogging on the filtration media or serum outlet and yield only about 10%−30% of the total serum present in the sample. Our innovation results from the inclusion of a differentiation pad, which exploits hydrodynamic effects to reduce the formation of a fouling layer on the blood filtration membrane resulting in more than 60% serum yield with undiluted whole blood as direct input. To demonstrate the effectiveness of the HYPER technology we implement it in a lateral flow system and demonstrate the accurate quantification of vitamin A and iron levels in whole blood samples in 15 minutes.

Micronutrient deficiencies such as those of vitamin A and iron affect a third of the world's population with consequences such as night blindness, higher child mortality, anemia, poor pregnancy outcomes, and reduced work capacity. Many efforts to prevent or treat these deficiencies are hampered by the lack of adequate, accessible, and affordable diagnostic methods that can enable better targeting of interventions. In this work, we demonstrate a rapid diagnostic test and mobile enabled platform for simultaneously quantifying iron (ferritin), vitamin A (retinol-binding protein), and inflammation (C-reactive protein) status. Our approach, enabled by combining multiple florescent markers and immunoassay approaches on a single test, allows us to provide accurate quantification in 15 min even though the physiological range of the markers of interest varies over five orders of magnitude. We report sensitivities of 88%, 100%, and 80% and specificities of 97%, 100%, and 97% for iron deficiency (ferritin <15 ng/mL or 32 pmol/L), vitamin A deficiency (retinol-binding protein <14.7 μg/mL or 0.70 μmol/L) and inflammation status (C-reactive protein >3.0 μg/mL or 120 nmol/L), respectively. This technology is suitable for point-of-care use in both resource-rich and resource-limited settings and can be read either by a standard laptop computer or through our previously developed NutriPhone technology. If implemented as either a population-level screening or clinical diagnostic tool, we believe this platform can transform nutritional status assessment and monitoring globally.

Micronutrient deficiency is widespread and negatively impacts morbidity, mortality, and quality of life globally. On-going advancements in nutritional biomarker discovery are enabling objective and accurate assessment of an individual's micronutrient and broader nutritional status. The vast majority of such assessment however still needs to be conducted in traditional centralized laboratory facilities which are not readily accessible in terms of cost and time in both the developed and developing countries. Lab-on-a-chip (LOC) technologies are enabling an increasing number of biochemical reactions at the point-of-need (PON) settings, and can significantly improve the current predicament in nutrition diagnostics by allowing rapid evaluation of one's nutritional status and providing an easy feedback mechanism for tracking changes in diet or supplementation. We believe that nutrition diagnostics represents a particularly appealing opportunity over other PON applications for two reasons: (1) healthy ranges for many micronutrients are well defined which allows for an unbiased diagnosis, and (2) many deficiencies can be reversed through changes in diet or supplementation before they become severe. In this paper, we provide background on nutritional biomarkers used in nutrition diagnostics and review the emerging technologies that exploit them at the point-of-need.

We demonstrate H.E.R.M.E.S, a novel magnetic-bead based method to perform rapid blood-plasma separation at the point of need that can augment the performance of present-day diagnostic testing platforms.

Vitamin D is necessary for the healthy growth and development of bone and muscle. Vitamin D deficiency, which is present in 42% of the US population, is often undiagnosed as symptoms may not manifest for several years and long-term deficiency has been linked to osteoporosis, diabetes and cancer. Currently the majority of vitamin D testing is performed in large-scale commercial laboratories which have high operational costs and long times-to-result. Development of a low-cost point-of-need assay could be transformative to deficiency analysis in limited-resource settings. The best biomarker of vitamin D status, 25hydroxyvitamin D3 (25(OH)D3), however, is particularly challenging to measure in such a format due to complexities involved in sample preparation, including the need to separate the marker from its binding protein. Here we present a rapid diagnostic test for the accurate, quantitative assessment of 25(OH)D3 in finger-stick blood. The assay is accompanied by a smartphone-assisted portable imaging device that can autonomously perform the necessary image processing. To achieve accurate quantification of 25(OH)D3, we also demonstrate a novel elution buffer that separates 25(OH)D3 from its binding protein in situ, eliminating the need for sample preparation. In human trials, the accuracy of our platform is 90.5%.

The centrifuge is the gold standard for lab-based sample processing. While extremely efficient and robust, centrifuges are seldom used in the field due to the high-power requirements, size, and operational complexity. The lack of viable alternatives for remote sample collection has crippled the ability for mobile practitioners in human and animal medicine to reliably collect blood samples from their patients. There is no truly resource-independent solution that is able to perform highly efficient blood–plasma separation. Here, we describe our initial efforts in developing the High Efficiency Rapid Magnetic Erythrocyte Separator (H.E.R.M.E.S) sleeve, an apparatus that uses a magnetic bead-based separation assay in a scaled-up form factor to achieve highly efficient separation of erythrocytes from plasma within a short amount of time. The sleeve is easy-to-use, is completely resource independent, and achieves highly efficient separation in sample volumes as large as 1 mL by means of a unique mixing scheme. We demonstrate the performance of the sleeve with human blood samples and compare it against conventional end-over-end mixing.

Antimicrobial resistance is recognized as one of the greatest emerging threats to public health. Antimicrobial resistant (AMR) microorganisms affect nearly 2 million people a year in the United States alone and place an estimated $20 billion burden on the healthcare system. The rise of AMR microorganisms can be attributed to a combination of overprescription of antimicrobials and a lack of accessible diagnostic methods. Delayed diagnosis is one of the primary reasons for empiric therapy, and diagnostic methods that enable rapid and accurate results are highly desirable to facilitate evidence-based treatment. This is particularly true for clinical situations at the point-of-care where access to state-of-the-art diagnostic equipment is scarce. Here, we present a capillary-based antimicrobial susceptibility testing platform (cAST), a unique approach that offers accelerated assessment of antimicrobial susceptibility in a low-cost and simple testing format. cAST delivers an expedited time-to-readout by means of optical assessment of bacteria incubated in a small capillary form factor along with a resazurin dye. cAST was designed using a combination of off-the-shelf and custom 3D-printed parts, making it extremely suitable for use in resource-limited settings. We demonstrate that growth of bacteria in cAST is approximately 25% faster than in a conventional microplate, further validate the diagnostic performance with clinical isolates, and show that cAST can deliver accurate antimicrobial susceptibility test results within 4–8 h.

Rapid SARS-COV-2 related serology testing can help identify and manage the spread of infection in decentralized testing environments but the limitation in performance of existing tests in blood has restricted implementation of testing at the point-of-care. Optimization of existing rapid tests in whole blood will require significant effort in the short-term and there is a need for solutions to help bridge the gap in performance between plasma and whole blood. We demonstrate here the implementation of the H.E.R.M.E.S platform, a portable plasma separation system that can enhance the performance of blood-based diagnostic testing, with a commercially available SARS-COV-2 IgG/IgM serology rapid diagnostic test (RDT) in a blinded study with 61 human samples. We compare the performance of the RDT in whole blood and separated plasma and highlight that plasma yields a 39% increase in positivity agreement with PCR in samples collected from patients with early infections. We further legitimize the increase in positivity agreement rate with the help of an independent evaluation by 10 previously untrained users. The H.E.R.M.E.S plasma separation system circumvents the need for assay optimization in whole blood and furthers the legitimacy of incorporating SARS-COV-2 serology RDTs at the point-of-care. The data highlighted in this work makes a compelling case for the incorporation of the H.E.R.M.E.S system in large scale efforts to perform SARS-COV-2 serology testing in decentralized testing environments.