Design and field evaluation of a lateral flow cassette device for point-of-care bilirubin measurement.

Neonatal jaundice is an important cause of morbidity and mortality worldwide, and neonates born in low and middle-income countries bear a disproportionate burden. We previously developed a low-cost, point-of-care system to measure total serum bilirubin (TSB) in neonates. This device was effective at detecting and monitoring jaundice; however, the disposable strips were difficult to produce at scale. Here, we report a new lateral flow cassette design, called BiliDx, that was produced at scale using traditional manufacturing techniques. We evaluated the performance of BiliDx at sites in Nigeria and Malawi. The lateral flow strip consists of plasma separation membranes, nitrocellulose, and a plastic cassette. We evaluated the performance of the strips and reader at two hospitals located in Nigeria and Malawi compared to reference standard TSB. We also assessed performance for samples with high direct bilirubin (DB) and high hematocrit (HCT). We collected 1,144 samples from 758 neonates (TSB ranged from 0.2 to 45.9 mg/dL). The mean bias of BiliDx measurements in the validation set was +0.75 mg/dL, and 95% limits of agreement were -2.57 to 4.07 mg/dL. The mean bias and limits of agreement were comparable for samples with HCT < 60% and HCT ≥ 60%, and for samples with low and intermediate DB levels; the samples with high DB levels had wider 95% limits of agreement (-4.50 to +3.03 mg/dL). Error grid analysis shows that 96.9% of samples measured with BiliDx would have resulted in the same clinical decision as the reference standard. This performance is comparable to previous results that used a handmade two-dimensional strip. Additionally, error grid analysis shows that all 20 samples with high DB levels would have resulted in the same clinical decision as the reference standard. This evaluation supports the use of BiliDx lateral flow cassettes to provide accurate point-of-care measurements in low-resource settings.

Point-of-care device to diagnose and monitor neonatal jaundice in low-resource settings.

Newborns are at increased risk of jaundice, a condition in which excess bilirubin accumulates in blood. Left untreated, jaundice can lead to neurological impairment and death. Jaundice resulting from unconjugated hyperbilirubinemia is easily treated with exposure to blue light, and phototherapy systems have been developed for low-resource settings; however, there are no appropriate solutions to diagnose and monitor jaundice in these settings. To address this need we present BiliSpec, a low-cost reader and disposable lateral flow card designed to measure the concentration of total bilirubin from several drops of blood at the point of care. We evaluated the performance of BiliSpec, using blood from normal volunteers spiked with varying amounts of bilirubin; results measured using BiliSpec correlated well with a reference laboratory bilirubinometer (r = 0.996). We then performed a pilot clinical study using BiliSpec to measure total bilirubin in neonates at risk for jaundice at Queen Elizabeth Central Hospital in Blantyre, Malawi. Concentrations measured using BiliSpec correlated well with those measured using a laboratory reference standard in 94 patient samples ranging from 1.1 mg/dL to 23.0 mg/dL in concentration (r = 0.973). The mean difference between bilirubin levels measured with BiliSpec and the reference standard was 0.3 mg/dL (95[Formula: see text] CI: -1.7-2.2 mg/dL).

Design and preliminary analysis of a vaginal inserter for speculum-free cervical cancer screening.

OBJECTIVE: Cervical cancer screening usually requires use of a speculum to provide a clear view of the cervix. The speculum is one potential barrier to screening due to fear of pain, discomfort and embarrassment. The aim of this paper is to present and demonstrate the feasibility of a tampon-sized inserter and the POCkeT Colposcope, a miniature pen sized-colposcope, for comfortable, speculum-free and potentially self-colposcopy. STUDY DESIGN: We explored different designs using 3D computer-aided design (CAD) software and performed mechanical testing simulations on each. Designs were rapid prototyped and tested using a custom vaginal phantom across a range of vaginal pressures and uterine tilts to select an optimal design. Two final designs were tested with fifteen volunteers to assess cervix visualization, comfort and usability compared to the speculum and the optimal design, the curved-tip inserter, was selected for testing in volunteers. RESULTS: We present a vaginal inserter as an alternative to the standard speculum for use with the POCkeT Colposcope. The device has a slim tubular body with a funnel-like curved tip measuring approximately 2.5 cm in diameter. The inserter has a channel through which a 2 megapixel (MP) mini camera with LED illumination fits to enable image capture. Mechanical finite element testing simulations with an applied pressure of 15 cm H2O indicated a high factor of safety (90.9) for the inserter. Testing of the device with a custom vaginal phantom, across a range of supine vaginal pressures and uterine tilts (retroverted, anteverted and sideverted), demonstrated image capture with a visual area comparable to the speculum for a normal/axial positioned uteri and significantly better than the speculum for anteverted and sideverted uteri (p<0.00001). Volunteer studies with self-insertion and physician-assisted cervix image capture showed adequate cervix visualization for 83% of patients. In addition, questionnaire responses from volunteers indicated a 92.3% overall preference for the inserter over the speculum and all indicated that the inserter was more comfortable than the speculum. The inserter provides a platform for self-cervical cancer screening and also enables acetic acid/Lugol's iodine application and insertion of swabs for Pap smear sample collection. CONCLUSION: This study demonstrates the feasibility of an inserter and miniature-imaging device for comfortable cervical image capture of women with potential for synergistic HPV and Pap smear sample collection.

Maji: a new tool to prevent overhydration of children receiving intravenous fluid therapy in low-resource settings.

We designed and evaluated the accuracy and usability of a device to regulate the volume of fluid dispensed during intravenous drip therapy. The mechanical system was developed in response to a pressing need articulated by clinicians in pediatric wards throughout sub-Saharan Africa, who require a tool to prevent overhydration in children receiving intravenous fluid in settings that lack burettes or electronic infusion pumps. The device is compatible with most intravenous bags and limits the volume dispensed to a preset amount that can be adjusted in 50 mL increments. Laboratory accuracy over a range of clinically-relevant flow rates, initial bag volumes, and target volumes was within 12.0 mL of the target volume. The ease of use is "excellent," with a mean system usability score of 84.4 out of 100. Use of the device limits the volume of fluid dispensed during intravenous therapy and could potentially reduce the morbidity and mortality associated with overhydration in children receiving intravenous therapy.

A high-value, low-cost bubble continuous positive airway pressure system for low-resource settings: technical assessment and initial case reports.

Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple design--consumer-grade pumps, medical tubing, and regulators--it requires only the simple replacement of a <$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device.