Lab-on-a-chip for Neonatal Hyperbilirubinemia Screening

描述（由申请人提供）：严重的高胆红素血症（定义为血清胆红素水平大于99百分位）可引起一系列神经功能障碍，其中核黄疸具有最具破坏性的神经功能后果。核黄疸表现为伴随视力和听觉功能障碍的终身运动障碍。在印度等发展中国家，据报告所有新生儿中有5%-12%在新生儿期出现严重高胆红素血症。据报道，在早产儿中，需要治疗的高胆红素血症发生率高达78%。在中国，35%的足月新生儿有明显的高胆红素血症。即使考虑到高胆红素血症的发病率比美国高得多，以及相关的有害后果，在这些发展中国家，目前还没有对新生儿进行普遍的高胆红素血症筛查。在长期黄疸的情况下，单独测量总胆红素是不够的。应强烈考虑潜在的原因，如葡萄糖-6-磷酸脱氢酶（G6PD）缺乏和先天性甲状腺功能减退（CH）。继发于这些疾病的黄疸婴儿可能对传统的治疗模式（如光疗）没有反应，直到潜在的疾病得到解决。在印度和中国等发展中国家成功实施以人口为基础的新生儿筛查计划所面临的挑战与已建立计划的国家大不相同。在发达国家效果良好的集中新生儿筛查模式，在印度或中国等人口稠密的发展中国家实施起来颇具挑战性。这是由于出生人数较多，住院分娩比例较低，以及缺乏运输样本的后勤基础设施。因此，迫切需要一种廉价、可扩展和可分发的新生儿筛查平台，供这些国家使用。基于第一阶段的成功结果，我们建议建立一个适合在印度和中国使用的高度可分配的低成本新生儿筛查平台的实验室原型（目标1）。我们将设计一种低成本的数字微流控试剂盒，用于检测总胆红素、G6PD和TSH，并验证分析性能（目标2）和临床性能（目标3）。

DESCRIPTION (provided by applicant): Severe hyperbilirubinemia (defined as serum bilirubin levels greater than 99th percentile) can cause a spectrum of neurologic dysfunction, of which kernicterus has the most devastating neurologic consequences. Kernicterus manifests as a life-long movement disorder with occulomotor and auditory dysfunction. In developing countries such as India, 5%-12% of all newborns are reported to develop severe hyperbilirubinemia in the newborn period. Among premature infants, incidence of hyperbilirubinemia warranting treatment has been reported to be as high as 78%. In China, 35% of full term newborns were noted to have significant hyperbilirubinemia. Even in light of incidence that is much higher than noted in the United States and the detrimental consequences associated, universal screening for hyperbilirubinemia is not currently available to the newborns in these developing nations. In cases of prolonged jaundice, measurement of total bilirubin alone does not suffice. Underlying causes such as glucose-6-phosphate dehydrogenase (G6PD) deficiency and congenital hypothyroidism (CH) should be strongly considered. Infants with jaundice secondary to these conditions may not respond to traditional modes of therapy (such as phototherapy) until the underlying illness is addressed. The challenges of implementing a successful population-based newborn screening program in developing countries such as India and China are very different from countries with established programs. The paradigm of centralized newborn screening that works well in developed countries is quite challenging to implement in highly populated developing countries such as India or China. This is due to larger number of births, lower percentage of hospital births, and lack of logistical infrastructure to transport samples. There is therefore a compelling need for an inexpensive, scalable, and distributable newborn screening platform for use in these countries. Building upon successful results from phase I, we propose to build a laboratory prototype of a highly distributable low cost newborn screening platform suitable for use in India and China (Aim 1). We will design a low cost digital microfluidic cartridge to perform assays for total bilirubin, G6PD and TSH and verify analytical performance (Aim 2) and clinical performance (Aim 3). PUBLIC HEALTH RELEVANCE: Advanced Liquid Logic, Inc. is developing a lab-on-a-chip on its proprietary digital microfluidic platform for newborn screening. The proposed project aims to demonstrate a near-patient platform for screening neonates for hyperbilirubinemia which, if not detected in time, could lead to kernicterus leaving the child developmentally challenged for entire life. This inexpensive device would be greatly useful in rapid identification and to enable early treatment.