Microfluidic Chips for Biomonitoring

 描述(申请人提供)：环境科学和技术中最令人兴奋的发展之一是“暴露组学”的新兴领域，即快速和灵敏地检测大量分析物(“暴露组”)，反映在个人环境中暴露的复杂性，使用包括血液、尿液和唾液在内的人类样本，这些样本可能从前瞻性和回溯性流行病学队列中获得。然而，目前缺乏能够对这些样品进行高灵敏度、高特异性和多分析物检测的技术平台，特别是在小容量的情况下。高效液相色谱-电喷雾电离质谱仪(LC-ESI/MS)是对蛋白质和代谢物进行大规模定性和定量分析的最有力的技术，也就是蛋白质组学和代谢组学。尽管国家生物监测计划(NBP)使用了各种质谱学方法，但由于目标分析物的浓度极低，它们通常需要相对较大的样本量来进行血浆和血清分析。这使得它们对于采集和存储非常少量的血液的多个分析物的总体研究是不现实的。为响应RFA-ES-14-005，Neomeics Inc.提出了SBIR第二阶段项目，以完成其产品全集成硅微流控芯片的开发，作为快速和灵敏地对多个和 多类别分析物。该项目建立在我们的SBIR第一阶段项目产生的非常有希望的结果的基础上。我们的新型微芯片在单个设备上实现了固相萃取(SPE)与液相(LC)-纳米电喷雾质谱(NanESI-MS)的整体接口。SPE-LC-MS芯片，我们称之为“生物监测芯片”，将作为一个低成本的通用平台，使用少量的生物标本(包括血液样本)实现高灵敏度、高特异性、高通量、多重和多分析物的生物监测。我们的生物监测芯片将为流行病学研究提供新的机会，这些研究试图通过基于MS的代谢组学、蛋白质组学和对人类生物样本中不同类别分析物的加合分析来表征个体暴露。

 DESCRIPTION (provided by applicant): One of the most exciting developments in environmental science and technology is the emerging field of "exposomics", i.e., rapid and sensitive detection of large sets of analytes ("exposome") reflecting the complexity of exposure in the personal environment using human specimens including blood, urine, and saliva, which are likely to be available from both prospective and retrospective epidemiological cohorts. However, technology platforms that could perform high-sensitivity, high-specificity, and multi-analyte detection of these samples, particularly in small volumes, are currently lacking. Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) is the most powerful technique for large-scale quantitative and qualitative analyses of proteins and metabolites, i.e., proteomics and metabolomics. Although a variety of mass spectrometry approaches have been used in the National Biomonitoring Program (NBP), they typically require relatively large sample volumes for plasma and serum analyses because of the extremely low concentrations of target analytes. This renders them impractical for population studies of multiple analytes where very small volumes of blood are collected and stored. In response to RFA-ES-14-005, Newomics Inc. proposes this SBIR Phase II project to complete development of its product, the fully-integrated silicon microfluidic chips, as a new platform for rapid and sensitive biomonitoring of multiple and multiclass analytes. The project is built upon the extremely promising results generated from our SBIR Phase I project. Our novel microchips monolithically interface solid-phase extraction (SPE) with liquid chromatography (LC)-nanoelectrospray mass spectrometry (nanoESI-MS) on a single device. The SPE-LC-MS chips, which we term "Biomonitoring Chips", will serve as a low-cost universal platform for enabling high-sensitivity, high-specificity, high-throughput, multiplexed, and multi-analyte biomonitoring using small volumes of biospecimens including blood samples. Our biomonitoring chips will offer new opportunities for epidemiologic studies which seek to characterize individual exposomes through MS-based metabolomics, proteomics, and adductomics analyses of diverse classes of analytes in human biospecimens.