Developing a Low-Cost Spectrophotometric System to Detect and Monitor Newborn Conditions at the Point-of-Care in Low-Resource Settings
| dc.contributor.advisor | Richards-Kortum, Rebecca | en_US |
| dc.creator | Shapiro, Alyssa M | en_US |
| dc.date.accessioned | 2022-09-23T16:00:00Z | en_US |
| dc.date.available | 2022-11-01T05:01:10Z | en_US |
| dc.date.created | 2022-05 | en_US |
| dc.date.issued | 2022-05-24 | en_US |
| dc.date.submitted | May 2022 | en_US |
| dc.date.updated | 2022-09-23T16:00:00Z | en_US |
| dc.description.abstract | This thesis describes my work to develop low-cost spectrophotometric tools to measure total serum bilirubin concentration and pH from neonatal blood samples at the point-of-care. I designed these technologies to help clinicians in low-resource settings better monitor babies receiving treatment for neonatal jaundice and respiratory distress. Severe neonatal jaundice disproportionately affects babies born in low-resource settings; 75% of all mortalities due to jaundice occur in sub-Saharan Africa and South Asia. Though effective phototherapy treatment is increasingly available in low- and middle-income countries (LMICs), affordable, reliable, and accurate methods to diagnose and monitor neonatal jaundice are not readily available. To meet this need, the Richards-Kortum lab previously developed BiliSpec, an early prototype of a low-cost spectrophotometric bilirubinometer and a paper-based lateral flow card designed for point-of-care bilirubin measurement. While the first generation BiliSpec system showed excellent agreement with a reference standard in a pilot study, further work was needed to determine the system’s performance over a wide range of bilirubin and hematocrit levels, as well as with multiple users in multiple environments and to evaluate device-to-device variability. This thesis describes my work to develop a 2nd generation BiliSpec reader and lateral flow card for rapid, robust, accurate serum bilirubin measurement. The performance of multiple BiliSpec devices operated by multiple users was evaluated using 475 patient samples collected from 375 neonates ranging from 0.0 – 33.7 mg/dL obtained at the point of care over a five-month period at two hospital locations – Queen Elizabeth Central Hospital in Blantyre, Malawi and Kamuzu Central Hospital in Lilongwe, Malawi. Bland-Altman analysis of BiliSpec measurements compared to a reference standard showed a small mean bias of -0.48 and 95% limits of agreement of -5.09 to +4.12 mg/dL; BiliSpec was found to be accurate for bilirubin levels as high as 33.7 mg/dL and in samples with hematocrit up to 78%. While my results showed that BiliSpec met clinically relevant performance needs, the handmade two-dimensional lateral flow card design cannot be produced using traditional lateral flow manufacturing approaches at scale. As described here, I worked to design and evaluate a cassette consisting of a lateral flow card and plastic housing which are made using traditional manufacturing techniques. This cassette, along with the 2nd generation reader, are together referred to as BiliDx. The BiliDx system was optimized and validated in multiple hospital settings in multiple countries (Malawi and Nigeria) among multiple users. I carried out testing to evaluate system performance over a wide range of bilirubin levels, a wide range of hematocrit levels, over longer periods of time, and with samples with various bilirubin fractions. The accuracy of BiliDx was evaluated using 1101 blood samples collected from 723 neonates ranging from 0.2 – 45.9 mg/dL. Of these samples, 811 were also measured using a bilirubinometer that could distinguish bilirubin fractions. Bland-Altman analysis of BiliDx measurements of sixty-nine samples with HCT > 60% were found to have a small mean bias of +1.12 and 95% limits of agreement of -2.70 to +4.93, a result comparable to that of 374 samples with HCT < 60%; additionally, error grid analysis of all twenty-three samples with high levels of direct bilirubin found that BiliDx measurements of these samples would result in the same clinical decision as the reference standard. BiliDx was found to be accurate for samples with high hematocrit levels and samples with various bilirubin fractions. Preterm birth is the leading cause of global child mortality worldwide1, and severe neonatal respiratory distress is a common and serious complication of preterm birth2. Respiratory distress refers to one or more signs of increased work of breathing3,4. In high-resource settings, clinicians use blood gas analysis, including blood pH, to monitor neonates receiving treatment for respiratory distress including CPAP and mechanical ventilation. Standard-of-care techniques for blood pH measurement are costly, stationary, and require expensive reagents. This thesis work describes the development of a low-cost spectrophotometric method to measure blood pH on a paper-based lateral flow card. In this method, a lateral flow card separates plasma from whole blood and mixes plasma with dried phenol red, a colorimetric pH indicator. I evaluated system accuracy using blood samples obtained from normal adult volunteers. While this pH measurement method was accurate for samples pre-mixed thoroughly with phenol red prior to addition to a paper-based strip, further work is required to improve the accuracy of this system using a paper-based strip that incorporates dried phenol red. This evaluation lays the foundation for the use of pH Strip alongside a low-cost spectrophotometric reader to provide accurate, low-cost, point-of-care blood pH measurement at the bedside in low-resource hospitals. | en_US |
| dc.embargo.terms | 2022-11-01 | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.citation | Shapiro, Alyssa M. "Developing a Low-Cost Spectrophotometric System to Detect and Monitor Newborn Conditions at the Point-of-Care in Low-Resource Settings." (2022) Diss., Rice University. <a href="https://hdl.handle.net/1911/113219">https://hdl.handle.net/1911/113219</a>. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1911/113219 | en_US |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder. | en_US |
| dc.subject | Low-cost | en_US |
| dc.subject | spectrophotometry | en_US |
| dc.subject | jaundice | en_US |
| dc.subject | hyperbilirubinemia | en_US |
| dc.subject | neonatology | en_US |
| dc.subject | respiratory distress | en_US |
| dc.subject | pH | en_US |
| dc.subject | blood pH | en_US |
| dc.subject | blood gas | en_US |
| dc.title | Developing a Low-Cost Spectrophotometric System to Detect and Monitor Newborn Conditions at the Point-of-Care in Low-Resource Settings | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | Text | en_US |
| thesis.degree.department | Bioengineering | en_US |
| thesis.degree.discipline | Engineering | en_US |
| thesis.degree.grantor | Rice University | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Doctor of Philosophy | en_US |
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