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

用于全球新生儿常见可治疗疾病筛查的低血量平台

基本信息

批准号：
10018059
负责人：
Rainer Ng
金额：
$ 71.74万
依托单位：
BAEBIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018059
关键词：
Address Bilirubin Biochemical Biochemistry Biological Assay Blood Volume Blood specimen Capital Caring Cessation of life Child China Classical galactosemia Clinical Clinical Chemistry Complex Congenital Disorders Congenital adrenal hyperplasia Country Cretinism Detection Developed Countries Developing Countries Development Disease Drops Early Diagnosis European Union Galactosemias Glucosephosphate Dehydrogenase Glucosephosphate Dehydrogenase Deficiency Goals Gold Health Heel Hospitals Hour Hyperbilirubinemia Immunoassay Incidence India Individual Infrastructure Kernicterus Laboratories Lead Letters Life Maintenance Measurement Measures Methods Microfluidics Modification Morbidity - disease rate Neonatal Neonatal Mortality Neonatal Screening Neonatology Neurologic Dysfunctions Newborn Infant Outcome Performance Phase Physician Executives Prevention Proteins Psyche structure Reaction Reference Standards Resources Risk Running Serum Sickle Cell Anemia Small Business Innovation Research Grant Technology Temperature Testing Thyrotropin Time Translating Universities Validation Whole Blood Work base cost cost effective design digital disability enzyme activity flexibility galactose-1-phosphate improved innovation instrument microfluidic technology mortality neonatal period novel phase 2 study premature prevent programs screening screening program

项目摘要

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.

据估计，全球 80% 的婴儿（每年约 1 亿）目前没有接受任何治疗新生儿筛查护理 (NBS) 是一项非常成功的检测计划，可识别新生儿的情况。那些患有常见、可治疗的先天性疾病的风险较高的人；在出现症状前识别这些疾病；新生儿疾病可以快速开始治疗并减少或预防严重的健康问题每个孩子出生时都会产生精神残疾、神经功能障碍和过早死亡等后果。在美国，至少对 30 种疾病进行了检测，绝大多数儿童出生在发展中国家一些国家甚至没有对任何一种疾病进行筛查。帮助缺乏实施中央筛查所需基础设施的地区引入新生儿筛查基于实验室的测试，我们将开发一种具有成本效益的、中低通量的数字微流体测试该平台将同时测量血清总胆红素（TSB）、葡萄糖-6-磷酸盐。脱氢酶 (G6PD)、1-磷酸半乳糖尿苷转移酶 (GALT) 和促甲状腺激素 (TSH) 检测全血，以筛查高胆红素血症风险、G6PD 缺乏症、典型半乳糖血症和先天性甲状腺功能减退症分别代表四种最常见、可治疗的新生儿疾病。发展中国家的情况，综合发病率约为十分之一。这些测试将在基于 FDA 授权的数字微流体的改良墨盒和仪器上进行用于测量指示溶酶体贮积症的酶活性的平台。 TSB、G6PD、GALT 和 TSH 将使用一次性试剂盒从少于 50 µl 的全血中进行所有检测的总运行时间不到 2 小时在第一阶段，我们将翻译 3 项生化检测和 1 项检测。新型蛋白质免疫测定（TSH）到数字微流体格式并确定初步分析和在第二阶段，我们将集中精力对仪器进行技术改造（增加吸光度检测）和墨盒（修改布局并添加加热器）。试剂盒开发完成后，TSB、G6PD、GALT 和 TSH 检测将多重运行在一个试剂盒上，将进行方法比较研究以评估临床。与“黄金标准”筛选方法相比的实用性。最终产品将是一个灵活的（低到中）通量新生儿筛查平台，适用于目前缺乏集中新生儿的发展中国家的中等复杂性（医院）环境一旦我们的初始 4 检测小组的技术确立，我们计划扩大我们的测试。提供覆盖其他时间敏感的新生儿疾病的服务。