Microfluidic Chips for Biomonitoring

描述（由申请人提供）：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，即快速和敏感地检测大量分析物（“暴露体”），反映个人环境中暴露的复杂性，使用人类标本，包括血液，尿液和唾液，这些可能从前瞻性和回顾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，特别是小体积样品。液相色谱-电喷雾质谱（LC-ESI/MS）是蛋白质和代谢物大规模定量和定性分析最强大的技术，即蛋白质组学和代谢组学。尽管在国家生物监测计划（NBP）中使用了各种质谱分析方法，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用于血液和血清分析。这使得它们在收集非常小体积血液的多种分析物的人口研究中不切实际。为响应RFA-ES-12-004， Newomics公司提出开发全集成微流控芯片，作为快速、灵敏的人体生物监测的新平台。该芯片基于微制造单片多喷嘴发射器和纳米ESI-MS多喷嘴发射器阵列芯片，共同为长期存在的硅微流控芯片与ESI-MS之间的高效耦合问题提供了简单而新颖的解决方案，为SBIR项目中提出的大规模集成铺平了道路。该微芯片将片上固相微萃取(SPME)/固相萃取（SPE）与片上/在线液相色谱(LC)-纳米电喷雾质谱（nano-ESI-MS）单片连接。SPME/SPE-LC-MS芯片将作为一种低成本的通用平台，用于使用小体积人体血液进行高灵敏度、高特异性、高通量、多路复用和多分析物生物监测。这反过来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的人体生物标本代谢组学、蛋白质组学和/或内收组学分析来表征个体暴露体。

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 blood 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. In response to RFA-ES-12-004, Newomics Inc. proposes to develop fully- integrated microfluidic chips, as a new platform for rapid and sensitive biomonitoring in humans. The chip is built on micro fabricated monolithic multinozzle emitters and multinozzle emitter array chips for nano-ESI-MS, which collectively offer a straightforward yet novel solution to the longstanding problem of the efficient coupling between the silicon microfluidic chip and ESI-MS, and pave the way for the large-scale integration proposed in this SBIR project. The proposed microchips will monolithically interface on-chip solid-phase microextraction (SPME)/solid-phase extraction (SPE) with on-chip/on-line liquid chromatography (LC)-nanoelectrospray mass spectrometry (nano-ESI-MS). The SPME/SPE-LC-MS 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 human blood. This in turn will offer new opportunities for epidemiologic studies which seek to characterize individual exposomes through MS-based metabolomics, proteomics and/or adductomics analyses of human biospecimens. PUBLIC HEALTH RELEVANCE: Cutting-edge technologies enable breakthroughs in biomedical research. Developments of mass spectrometry-based microchip platforms for rapid and sensitive biomonitoring in humans will improve risk assessment of personal exposure to environmental toxins, and thereby providing new strategies for public health.