Point-of-Care Nucleic Acid Test for Cytomegalovirus for Newborn Hearing Screening

描述（由申请人提供）：在美国，普遍的新生儿听力筛查是强制性的，并在产后医院进行。目前基于生理学的听力筛查试验无法检测巨细胞病毒（CMV）感染引起的迟发性听力损失。因此，建议采用一种补充筛查方法，通过早期发现和干预来预防cmv相关性听力损失相关的残疾。已经描述了一种利用唾液标本筛查新生儿先天性巨细胞病毒感染的核酸试验，它比新生儿筛查实验室传统上使用的干血点更敏感。新生儿筛查项目没有必要的基础设施来使用新生儿唾液样本和分子分析。Advanced Liquid Logic的数字微流控技术是一种公认的创新、低成本和自动化的液体处理系统，可以解决这一挑战。该快速通道申请的目的是开发一种集成的芯片实验室，利用唾液样本对新生儿先天性巨细胞病毒感染进行筛查。第一阶段的具体目标是制定从唾液样本中纯化巨细胞病毒的方案，以及在试剂盒上进行病毒DNA扩增，并在数字微流控平台上整合“从样本到答案”的巨细胞病毒筛选试验。第一阶段的成功将导致第二阶段的继续，其中具体目标将是(I)开发一个即时新生儿筛查平台，（II）优化该平台中的“样本到答案”CMV方案并评估其分析性能，以及（iii）与阿拉巴马大学伯明翰分校合作使用新生儿唾液样本与“金标准”快速唾液培养进行方法比较。

DESCRIPTION (provided by applicant): Universal newborn hearing screening is mandated in the US and is performed in the postpartum hospital setting. Current physiology-based hearing screening tests are unable to detect late-onset hearing loss caused by cytomegalovirus (CMV) infection. Therefore, a complementary screening approach has been suggested to prevent disabilities associated with CMV-related hearing loss by early detection and intervention. A nucleic acid test has been described to screen newborns for congenital CMV infection using saliva specimens where it is more sensitive than the dried blood spots traditionally used by the newborn screening laboratories. Newborn screening programs do not have the infrastructure necessary to use newborn saliva samples and molecular assays. Advanced Liquid Logic's digital microfluidic technology is a recognized innovative, low-cost, and automated liquid handling system that can address this challenge. The objective of this Fast-Track application is to develop an integrated lab-on-a-chip to perform screening of congenital CMV infection in newborns using saliva samples. Specific aims in Phase I are to develop protocols for CMV purification from saliva samples and for viral DNA amplification on-cartridge, and to integrate a "sample-to-answer" CMV screening assay on the digital microfluidic platform. Success in Phase I will result in a Phase II continuation where the specific aims will be (i) to develop a point-of-care newborn screening platform, (ii) to optimize the "sample-to-answer" CMV protocol in this platform and assess its analytical performance, and (iii) to perform a method comparison with the "gold standard" rapid saliva culture using neonatal saliva samples in collaboration with the University of Alabama at Birmingham.