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（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（核黄疸）、听力丧失、身体异常，甚至死亡。最近，又出现了核黄疸，这是一种可预防的由新生儿高胆红素血症引起的脑损伤。这是由于分娩后过早出院，胆红素测量不准确，以及患者管理不当。1970年，顺产新生儿的平均住院时间为3.9天；如今，平均住院时间为1.7天。然而，新生儿的胆红素水平直到出生后第三天到第五天之间才达到峰值。随着早期出院，在极端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护理人员。2004年，美国儿科学会（AAP）修订了治疗高胆红素血症的临床实践指南。新指南建议所有的胆红素水平都要根据婴儿的年龄（以小时为单位）来解释。因此，新生儿胆红素检测必须尽快处理和报告。进行检测的实验室可能无法在相对较短的时间内提供适当治疗决策所需的结果。该应用程序提出了一种微创、廉价、即时检测的方法，为医院和办公室的护理人员提供全血总胆红素水平的直接和即时检测。该测试由固相测试条和基于反射率的计组成，类似于葡萄糖模型。第一阶段研究的具体目标已经全部实现。第二阶段提案的目标是开发一个最终原型固相测试条和手持式数字阅读器。第二阶段有三个主要目标：(1)完成盒式磁带的开发并评估其性能；(2)开发具有连接功能的阅读器；(3)扩大生产工艺，并使用新的读卡器评估盒式磁带的性能。在III期商业化阶段，主要重点将是签约营销合作伙伴，获得额外资金以准备产品上市，并通过进行临床研究收集数据以获得监管市场批准。拟议的PortaTBili产品的可用性将防止发现那些注定要发展为严重高胆红素血症的婴儿的延误，对国家的婴儿健康管理产生重大影响。这种低成本仪器还将改善全球婴儿保健实践。

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. 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. With early discharge, the opportunity and responsibility for observing the newborn during the period of greatest extreme hyperbilirubinemia risk 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. 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. Specific aims of the Phase I research have all been met. The goal of the Phase II proposal is to develop a final prototype solid phase test strip and hand-held digital reader. Phase II has three major aims: (1) finish development of the cassette and evaluate its performance; (2) develop reader with connectivity features; and (3) scale-up the manufacturing process and evaluate the casettes for performance using new reader. In Phase III commercialization phase, the main focus will be to sign up marketing partners, secure additional funding to prepare the product for launch, and by performing clinical studies to collect data for regulatory market approvals. The availability of the proposed PortaTBili product will prevent delays in finding those infants destined to develop severe hyperbilirubinemia, making significant impact in the nation's health management for infants. The low cost instrument will also allow improvement in infant healthcare practice globally. 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.