Lab-on-a-Chip for Multiplexed Newborn Screening of Lysosomal Storage Disorders

用于溶酶体贮积症多重新生儿筛查的芯片实验室

• 批准号: 8252254
• 负责人: VAMSEE K. PAMULA
• 金额: $ 99.73万
• 依托单位: ADVANCED LIQUID LOGIC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8252254
• 关键词: Address; Automation; Biochemical Genetics; Biological Assay; Biotinidase Deficiency; Birth; Blood; Brazil; Budgets; Capital; Cessation of life; Clinical Treatment; Computer software; Congenital adrenal hyperplasia; Cretinism; Cystic Fibrosis; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Electronics; Enzymes; FDA approved; Fabry Disease; Feedback; Fluorometry; Funding; Galactosemias; Gaucher Disease; Globoid cell leukodystrophy; Glycogen storage disease type II; Gold; Hemoglobinopathies; Human Resources; Illinois; India; Infant; Inherited; Laboratories; Laws; Lead; Letters; Liquid substance; Logic; Lysosomal Storage Diseases; Mass Spectrum Analysis; Measures; Metabolic Diseases; Metachromatic Leukodystrophy; Methods; Microfluidics; Missouri; Neonatal Screening; Neonatology; New Mexico; Newborn Infant; Niemann-Pick Diseases; Operating System; Organ; Phase; Phenylketonurias; Pilot Projects; Psyche structure; Public Health; Reagent; Research Personnel; Sampling; Savings; Screening procedure; Severe Combined Immunodeficiency; Site; Specimen; Spottings; Stretching; System; Technology; Testing; Time; United States; Universities; Validation; base; cost; cost effective; design; digital; disability; enzyme replacement therapy; innovation; instrument; interest; meetings; micro-total analysis system; multiplex detection; pilot trial; programs; tandem mass spectrometry; technology development; technology validation; therapy development; verification and validation

DESCRIPTION (provided by applicant): Newborn screening is currently performed by collecting dried bloodspots from infants and then sending them to a lab for analysis. It is primarily performed to detect disorders which lead to severe physical and mental disabilities. There is an increasing necessity to screen for a number of lysosomal storage disorders for which therapies are becoming available. Tandem mass spectrometry is a multiplex detection technology widely utilized in newborn screening, but when applied to enzyme assays it is expensive, time consuming, and labor intensive. There is a need for an inexpensive, rapid, and automated technology for performing newborn screening assays. A digital microfluidic cartridge, which is essentially a liquid handling system operating on sub- microliter droplets, has been developed for performing fluorometric enzymatic assays for screening lysosomal storage disorders using dried blood spots. This system is configured to enable walkaway automation and multiplex several assays inexpensively. In phase II, we have successfully demonstrated assays for Pompe, Fabry, Gaucher, Hunter and Hurler disorders using a single punch from a dried blood spot. The digital microfluidic method compared favorably with a "gold standard" fluorometric enzymatic method performed in microtiter plates at Duke University for all the 5 disorders. The digital microfluidic system is currently under a pilot trial in the Illinois Newborn Screening Laboratory. Over 6,000 dried blood spots have been screened for Pompe, Fabry, and Gaucher during the ongoing pilot study. Following a positive results on this platform, 4 infants were further confirmed with Fabry disease and 1 infant with Gaucher disease. Phase IIB continuation will focus on addressing several user issues that were identified during the pilot trial, submission of a 510(k) application to the FDA, and expansion of the newborn screening assay panel to include other LSDs which are mandated or which have therapies available/under development. PUBLIC HEALTH RELEVANCE: Newborn screening is performed on almost every infant born in the US. Due to the availability of therapies, there is a growing interest in adding lysosomal storage disorders (LSDs) to the panel of tests. In this project, a cost-effective microfluidic platform will be developed and validated for newborn screening of LSDs. Illinois, Missouri and New Mexico have mandated laws requiring screening all the babies for LSDs and availability of this inexpensive platform will make it affordable for cash-strapped states. During a limited pilot trial of this platform in Illinois, some babies with LSDs were already identified.

描述（由申请人提供）：新生儿筛查目前通过收集婴儿的干血斑，然后将其送到实验室进行分析来进行。它主要用于检测导致严重身体和精神残疾的疾病。有越来越多的必要性，以筛选一些溶酶体贮积症的治疗方法变得可用。串联质谱是一种广泛用于新生儿筛查的多重检测技术，但当应用于酶测定时，它是昂贵的，耗时的，劳动密集型的。需要一种廉价、快速和自动化的技术来进行新生儿筛查测定。 一种数字微流体盒，其本质上是一种在亚微升液滴上操作的液体处理系统， 已开发用于使用干血斑进行荧光酶测定以筛选溶酶体贮积症。该系统被配置为能够实现自动化，并以低廉的价格多路复用多个测定。在第二阶段，我们已经成功地证明了庞贝氏症，法布里，戈谢，亨特和赫尔勒疾病使用一个单一的打孔从干血斑的测定。数字微流控方法与杜克大学在微量滴定板中进行的“金标准”荧光酶法相比，对所有5种疾病都有利。数字微流体系统目前正在伊利诺伊州的新生儿进行试点试验 筛选实验室。在正在进行的试点研究中，已经对6,000多个干血斑进行了庞贝氏症、法布里病和戈谢病的筛查。在该平台上获得阳性结果后，4名婴儿被进一步确认患有法布里病，1名婴儿患有戈谢病。IIB期继续将重点解决在试点试验期间发现的几个用户问题，向FDA提交510（k）申请，并扩展新生儿筛查检测试剂盒，以包括其他强制性或具有可用/正在开发的疗法的LSD。 公共卫生相关性：新生儿筛查几乎对美国出生的每一个婴儿进行。由于治疗的可用性，人们越来越关注将溶酶体贮积症（LSD）添加到测试组中。在该项目中，将开发一种具有成本效益的微流体平台，并验证其用于新生儿LSD筛查。伊利诺斯州、密苏里州和新墨西哥州已经强制要求对所有婴儿进行LSD筛查，而这个廉价平台的可用性将使资金短缺的州负担得起。在伊利诺伊州对该平台进行的有限试点试验中，已经发现了一些患有LSD的婴儿。