A Low Blood Volume Platform for Global Newborn Screening of Common, Treatable Conditions

据估计，全世界出生的婴儿中有80%(每年约1亿)目前没有接受任何治疗 新生儿筛查护理。新生儿筛查(NBS)是一个非常成功的检测程序，它可以识别 那些常见的、可治疗的先天性疾病的风险增加的人；这些疾病的症状前识别 新生儿疾病能够迅速开始治疗，减少或防止严重的健康 造成精神残疾、神经功能障碍和过早死亡等后果。当每个孩子出生的时候 在美国进行了至少30种疾病的检测，绝大多数出生在发育中的儿童 各国甚至不会对任何一种疾病进行筛查。 帮助将新生儿筛查引入缺乏必要基础设施的地区 基于实验室的检测，我们将开发一种具有成本效益的、中低通量的数字微流控检测 站台。该平台将同时测量血清总胆红素(TSB)、葡萄糖-6-磷酸 脱氢酶(G6PD)、半乳糖-1-磷酸尿苷转移酶(GALT)和促甲状腺激素 全血促甲状腺激素(TSH)以筛查高胆红素血症、G6PD缺乏症、经典型的半乳糖血症和 分别为先天性甲状腺功能减退症。这些代表了四种最常见的、可治疗的新生儿 发展中国家的综合发病率约为十分之一。这些测试将是 使用基于FDA授权的数字微流控芯片的改进型墨盒和仪器 用于测量溶酶体储存障碍的酶活性的平台。的测试 使用一次性血盒，从小于50微米的L全血中进行TSB、G6PD、GALT和TSH检测 所有检测的总运行时间少于2小时。在第一阶段，我们将翻译三种生化分析和一种 新的蛋白质免疫分析(用于TSH)的数字微流控格式，并确定初步分析和 临床可行性。在第二阶段，我们将集中精力对仪器进行技术修改(增加 吸光度检测)和墨盒(改进的布局和增加了加热器)。曾经改装过的乐器和 开发了试剂盒，TSB、G6PD、GALT和TSH分析将被多路传输到一个试剂盒上运行，并 分析性能将得到验证。将进行方法比较研究以评估临床 针对“黄金标准”筛查方法的效用。 最终产品将是一个灵活的(中低吞吐量)新生儿筛查平台，适用于 发展中国家目前缺乏集中新生儿的中等复杂性(医院)环境 筛查计划。一旦为我们最初的4个化验小组建立了技术，我们计划扩大我们的测试 提供更多对时间敏感的新生儿情况。

An estimated 80% of babies born worldwide (approximately 100 million each year) currently do not receive any newborn screening care. Newborn screening (NBS) is an immensely successful testing program that identifies those at increased risk for common, treatable congenital disorders; the pre-symptomatic identification of these disorders in newborns enables the rapid initiation of treatments and reduces or prevents serious health consequences such as mental disability, neurological dysfunction and premature death. While every child born in the U.S. is tested for at least 30 disorders, the overwhelming majority of children born in developing countries are not screened for even a single disorder. To help introduce newborn screening to regions lacking the infrastructure necessary to implement central laboratory based testing, we will develop a cost effective, low-to-medium throughput digital microfluidic testing platform. The platform will simultaneously measure total serum bilirubin (TSB), glucose-6-phosphate dehydrogenase (G6PD), galactose-1-phosphate uridyltransferase (GALT) and thyroid stimulating hormone (TSH) in whole blood in order to screen for hyperbilirubinemia risk, G6PD deficiency, classic galactosemia and congenital hypothyroidism, respectively. These represent four of the most common, treatable neonatal conditions in the developing world with a combined incidence of approximately 1 in 10. These tests will be performed on a modified cartridge and instrument that is based on our FDA-authorized digital microfluidic platform for measurement of enzyme activities that are indicative of lysosomal storage disorders. The tests for TSB, G6PD, GALT and TSH will be performed from less than 50 µl of whole blood using disposable cartridges with a total run time of less than 2 hours for all assays. In Phase I, we will translate 3 biochemical assays and a novel protein immunoassay (for TSH) to the digital microfluidic format and determine preliminary analytical and clinical feasibility. In Phase II, we will concentrate on technology modifications to the instrument (addition of absorbance detection) and cartridge (modified layout and addition of heaters). Once a modified instrument and cartridge is developed, the TSB, G6PD, GALT and TSH assays will be multiplexed to run on one cartridge and the analytical performance will be validated. A method comparison study will be performed to assess clinical utility against “gold standard” screening methods. The final product will be a flexible (low to medium) throughput newborn screening platform suitable for use in moderate complexity (hospital) settings in developing countries that currently lack a centralized newborn screening program. Once the technology is established for our initial 4-assay panel, we plan to expand our test offerings to cover additional time-sensitive neonatal conditions.