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

描述(申请人提供)：新生儿高胆红素血症(过量胆红素)是新生儿最常见的问题之一。如果及时发现，高胆红素血症是可以治疗的。在新生儿中，严重的高胆红素血症可导致脑损伤(核黄体)、听力损失、身体异常，甚至死亡。最近，核黄体再次出现，这是一种由严重的新生儿高胆红素血症引起的可预防的脑损伤。这是由于分娩后过早出院，胆红素测量不准确，以及对患者的管理不当[2]。 1970年，经阴道分娩的新生儿平均住院时间为3.9天；如今，平均住院时间为1.7天。然而，新生儿胆红素水平直到出生后第三天到第五天之间才达到峰值[6]。由于提前出院，在极高胆红素血症风险最大的时期观察新生儿的机会和责任已从医院转移到主要照顾者身上。 美国儿科学会(AAP)修订了他们的临床实践指南 2004年出现高胆红素血症。新的指南建议，所有胆红素水平应根据婴儿的年龄以小时为单位进行解释[2]。因此，新生儿胆红素检测亟待处理和报告。进行检测的实验室可能无法在作出适当治疗决定所需的相对较短的时间内提供结果。 这项应用建议开发一种微创、廉价的护理点检测方法，为医院和办公室的护理人员提供直接和即时的全血总胆红素水平。该测试由固相测试条和反射率计组成，类似于葡萄糖模型。 第一阶段提案的目标是确定建立功能原型固相测试条的可行性。第一阶段有五个目标。目标1是确定一种更适合试验的染料底物。目标2将侧重于膜、稳定剂和添加剂的选择。AIM 3将在试纸上增加一个血液分离系统，以允许脚后跟粘在一起的样本。目标4号将建造和测试最初的原型测试条。AIM 5将开始测试条的稳定性研究。 第二阶段将继续该项目，解决如何处理小和特殊的血液样本，将试纸与手持仪表耦合，并继续进行性能和稳定性研究。与公共健康相关：拟议中的试纸将允许医生从全血样本中确定婴儿的总胆红素浓度，而不必将其送往实验室。有了这些信息，医生可以识别和治疗胆红素相关疾病的高危婴儿，这些疾病危及生命或将对生活质量产生不利影响。

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.