Lab-on-a-chip for Neonatal Hyperbilirubinemia Screening

用于新生儿高胆红素血症筛查的芯片实验室

• 批准号: 8124534
• 负责人: Vijay Srinivasan
• 金额: $ 73.35万
• 依托单位: ADVANCED LIQUID LOGIC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8124534
• 关键词: Address; Auditory; Bilirubin; Biological Assay; Biotinidase Deficiency; Birth; Birthing Centers; Capital; Child; China; Clinical; Computer software; Consumption; Country; Cretinism; Cystic Fibrosis; Detection; Developed Countries; Developing Countries; Development; Devices; Disease; Early treatment; Electronics; Environment; Functional disorder; Galactosemias; Generic Drugs; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hospitals; Hyperbilirubinemia; Icterus; Incidence; India; Infant; Kernicterus; Laboratories; Lead; Left; Letters; Life; Light; Liquid substance; Logic; Maintenance; Marketing; Maternity Hospitals; Mechanics; Methods; Microfluidics; Movement Disorders; Neonatal Screening; Neonatology; Neurologic; Neurologic Dysfunctions; Newborn Infant; Patients; Performance; Phase; Phototherapy; Premature Infant; Reader; Reagent; Reporting; Research Infrastructure; Research Personnel; Resources; Risk; Sampling; Savings; Screening procedure; Secondary to; Serum; Site; Specificity; System; Technology; Testing; Texas; Thyrotropin; Time; Translating; United States; Universities; Validation; Work; adrenal hyperplasia; base; cost; design; digital; innovation; instrument; mass spectrometer; micro-total analysis system; neonatal hyperbilirubinemia; neonate; new technology; population based; portability; programs; prototype; total measurement Bilirubin

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.

描述（由申请方提供）：重度高胆红素血症（定义为血清胆红素水平大于第99百分位数）可导致一系列神经功能障碍，其中核黄疸具有最具破坏性的神经系统后果。核黄疸表现为一种终生的运动障碍，伴有视力和听觉功能障碍。在印度等发展中国家，据报道，所有新生儿中有5%-12%在新生儿期发生严重的高胆红素血症。据报道，在早产儿中，高胆红素血症的发生率高达78%。在中国，35%的足月新生儿被发现患有显著的高胆红素血症。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，这些发展中国家的新生儿目前还没有进行高胆红素血症的普遍筛查。在长期黄疸的情况下，仅测量总胆红素是不够的。潜在的原因，如葡萄糖-6-磷酸脱氢酶（G6 PD）缺乏症和先天性甲状腺功能减退症（CH）应予以强烈考虑。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实施成功的基于人群的新生儿筛查项目所面临的挑战与已建立项目的国家截然不同。在发达国家运作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具有相当大的挑战性。这是由于出生人数较多，住院分娩的比例较低，以及缺乏运输样本的后勤基础设施。因此，迫切需要一个廉价的，可扩展的，可分发的新生儿筛查平台，在这些国家使用。基于第一阶段的成功结果，我们建议建立一个适用于印度和中国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盒，用于检测总胆红素、G6 PD和TSH，并验证分析性能（目标2）和临床性能（目标3）。 公共卫生相关性：Advanced Liquid Logic，Inc.正在其专有的数字微流体平台上开发一种用于新生儿筛查的芯片实验室。拟议项目旨在展示一个近患者平台，用于筛查新生儿高胆红素血症，如果不及时发现，可能导致核黄疸，使儿童终身发育障碍。这种廉价的装置将在快速识别和早期治疗方面非常有用。