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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

基本信息

批准号：
8657946
负责人：
VAMSEE K. PAMULA
金额：
$ 84.04万
依托单位：
BAEBIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8657946
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 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 screening tandem mass spectrometry technology development technology validation therapy development verification and validation

项目摘要

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.

描述(申请人提供)：目前进行新生儿筛查的方法是从婴儿身上采集干燥的血迹，然后将其送往实验室进行分析。它主要是为了检测导致严重身体和精神残疾的障碍。越来越有必要对一些溶酶体储存障碍进行筛查，治疗方法正在变得可用。串联质谱仪是一种广泛应用于新生儿筛查的多重检测技术，但将其应用于酶分析存在成本高、耗时长、劳动强度大等缺点。需要一种廉价、快速和自动化的新生儿筛查分析技术。一种数字微流体盒，本质上是在亚微升液滴上操作的液体处理系统，具有已开发用于使用干血斑进行用于筛选溶酶体储存障碍的荧光酶分析。该系统被配置为能够实现自动操作并廉价地多路传输多个化验。在第二阶段，我们已经成功地演示了Pompe、Fabry、Gaucher、Hunter和Hurler疾病的分析方法，只需从干血点上一击即可。在所有5种疾病中，数字微流控方法与杜克大学在微量平板上进行的“金标准”荧光酶分析方法相比都是有利的。数字微流控系统目前正在伊利诺伊州的新生儿中进行试点试验筛查实验室。在正在进行的试点研究中，已经对6000多个干血点进行了筛查，以确定庞佩、法布里和高歇尔的情况。在该平台上获得阳性结果后，4名婴儿进一步确诊为法布里病，1名婴儿确诊为高谢病。第二阶段B的继续工作将侧重于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，并扩大新生儿筛查化验小组，以包括其他已获授权或已有治疗方法/正在开发的LSD。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Rapid assays for Gaucher and Hurler diseases in dried blood spots using digital microfluidics.

DOI：
10.1016/j.ymgme.2013.03.010
发表时间：
2013-06
期刊：
MOLECULAR GENETICS AND METABOLISM
影响因子：
3.8
作者：
Sista, Ramakrishna S.;Wang, Tong;Wu, Ning;Graham, Carrie;Eckhardt, Allen;Bali, Deeksha;Millington, David S.;Pamula, Vamsee K.
通讯作者：
Pamula, Vamsee K.

Fluorimetric assay with a novel substrate for quantification of galactocerebrosidase activity in dried blood spot specimens.

使用新型底物进行荧光测定，用于定量干血斑标本中的半乳糖脑苷脂酶活性。

DOI：
10.1016/j.plabm.2019.e00141
发表时间：
2020
期刊：
Practical laboratory medicine
影响因子：
1.9
作者：
Ullal,AnirudhJ;Pham,Hong;Singh,Rajendra;Ross,Peter;Graham,CarrieA;Norton,ScottM;Nuffer,MiriamH;Burns,DebbieS;Eckhardt,AllenE;Escolar,Maria;Bali,Deeksha;Pamula,VamseeK
通讯作者：
Pamula,VamseeK

Multiplex newborn screening for Pompe, Fabry, Hunter, Gaucher, and Hurler diseases using a digital microfluidic platform.

DOI：
10.1016/j.cca.2013.05.001
发表时间：
2013-09-23
期刊：
Clinica chimica acta; international journal of clinical chemistry
影响因子：
0
作者：
Sista RS;Wang T;Wu N;Graham C;Eckhardt A;Winger T;Srinivasan V;Bali D;Millington DS;Pamula VK
通讯作者：
Pamula VK

Digital microfluidics: a future technology in the newborn screening laboratory?

DOI：
10.1053/j.semperi.2009.12.008
发表时间：
2010-04
期刊：
Seminars in perinatology
影响因子：
3.4
作者：
Millington DS;Sista R;Eckhardt A;Rouse J;Bali D;Goldberg R;Cotten M;Buckley R;Pamula V
通讯作者：
Pamula V

Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns.

数字微流体会年龄：对新生儿遗传疾病的高通量筛查对床旁诊断测试。