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

描述（由申请人提供）：新生儿高胆红素血症（胆红素过多）是新生儿最常见的问题之一。如果及时发现，高胆红素血症可以治疗。在新生儿中，严重的高胆红素血症可导致脑损伤（核黄疸）、听力损失、身体异常，甚至死亡。最近，核黄疸重新出现，这是一种由严重新生儿高胆红素血症引起的可预防的脑损伤。这是由于分娩后提前出院、胆红素测量不准确和患者管理不当所致[2]。 1970年，经阴道分娩的新生儿平均住院时间为3.9天;今天，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和第五天之间的某个时候才达到峰值[6]。随着早期出院，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经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，高胆红素血症。新指南建议根据婴儿的年龄（小时）解释所有胆红素水平[2]。因此，新生儿胆红素检测必须紧急处理和报告。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。 该申请提议开发一种微创、廉价的护理点测试，该测试将为医院和办公室的护理人员提供直接、立即的全血总胆红素水平。该测试由固相测试条和基于反射率的测量仪组成，类似于葡萄糖模型。 第一阶段提案的目标是确定构建功能原型固相试纸条的可行性。第一阶段有五个目标。目的1是确定一种更合适的染料底物进行测试。目标2将集中在选择膜，稳定剂和添加剂。目标3将在试纸上增加一个血液分离系统，以允许足跟贴样本。目标4将建立和测试最初的原型测试条。Aim 5将开始试纸的稳定性研究。 第二阶段将继续该项目，解决如何处理小的和特殊的血液样本，耦合测试条与手持仪，并继续进行性能和稳定性研究。 公共卫生相关性：拟议的测试条将允许医生从全血样本中确定婴儿的总胆红素浓度，而无需发送到实验室。有了这些信息，医生可以识别和治疗胆红素相关疾病的高风险婴儿，这些疾病危及生命或会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.