Development of a Point-Of-Care Test for Determining Bilirubin in Whole Blood

DESCRIPTION (provided by applicant): Neonatal hyperbilirubinemia (excessive bilirubin) is one of the most common problems encountered in newborns. If caught in time, hyperbilirubinemia can be treated. In a newborn infant, severe hyperbilirubinemia can cause brain damage (kernicterus), hearing loss, physical abnormalities, and even death. Recently, there has been a re-emergence of kernicterus, a preventable brain injury resulting from severe neonatal hyprbilirubinemia. This is due to early discharge after delivery, inaccurate bilirubin measurements, and improper management of the patients [2]. The average hospital stay for a newborn delivered vaginally in 1970 was 3.9 days; today the average hospital stay is 1.7 days. Newborn bilirubin levels, however, do not peak until sometime between the third and fifth day after birth [6]. With early discharge, the opportunity and responsibility for observing the newborn during the period with the greatest risk of extreme hyperbilirubinemia has shifted from the hospital to the primary caregiver. The American Academy of Pediatrics (AAP) revised their clinical practice guidelines for managing hyperbilirubinemia in 2004. The new guidelines recommend that all bilirubin levels be interpreted according to the infant's age in hours [2]. Therefore, bilirubin test in newborns must be processed and reported urgently. Laboratories conducting testing may not be able to provide results in the relatively short time frame required for appropriate treatment decisions. This application proposes the development of a minimally invasive, inexpensive, point-of-care test that will provide the caregiver, both in the hospital and the office, direct and immediate access to whole blood total bilirubin levels. The test consists of a solid-phase test strip and reflectance based meter, similar to glucose models. The goal of the Phase I proposal is to determine the feasibility of building a functional prototype solid phase test strip. Phase I has five aims. Aim 1 is to identify a more suitable dye-substrate for the test. Aim 2 will focus on selecting membranes, stabilizers, and additives. Aim 3 will add a blood separation system to the test strip to allow for heel-stick samples. Aim 4 will build and test the initial prototype test strips. Aim 5 will start a stability study for the test strips. Phase II will continue the project by addressing how to handle small and special blood samples, couple the test strip with a hand-held meter, and continue to conduct performance and stability studies. PUBLIC HEALTH RELEVANCE: The proposed test strip will allow a physician to determine an infant's total bilirubin concentration from a whole blood sample without having to send out to a lab. With this information, the physician can identify and treat infants who are at high risk for bilirubin related conditions that are life threatening or that will adversely affect the quality of life.