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。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，新生儿的胆红素水平直到出生后第三天到第五天之间才会达到峰值。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)于2004年修订了治疗高胆红素血症的临床实践指南。新的指导方针建议，所有胆红素水平都应根据婴儿的年龄以小时为单位进行解释。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。第一阶段研究的具体目标已全部实现。第二阶段提案的目标是开发最终的原型固相测试条和手持数字阅读器。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)扩大制造工艺，并使用新的阅读器评估盒式磁带的性能。在第三阶段商业化阶段，主要重点将是与营销合作伙伴签约，获得额外资金以准备推出该产品，并进行临床研究以收集数据以获得监管市场批准。建议中的PortaTBili产品的上市将防止延迟发现那些注定要患上严重高胆红素血症的婴儿，对国家的婴儿健康管理产生重大影响。这种低成本的工具还将使全球婴儿保健实践得到改善。 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. 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.