Development of a Novel Aerosol Mass Spectrometric Technology for Rapid and Sensit

描述(由申请人提供)：开发一种用于快速和灵敏的环境毒物生物监测的新型气溶胶质谱学技术主要调查者的姓名、地址和电话号码：Manjula Canagaratna博士，Aerodyne Research，Inc.，45Manning Road，Billerica，MA 01821-3976，1-978-663-9500ext.285名其他关键人员的名字：张琦教授、松村文雄教授；参与机构：Aerodyne Research Inc.；加州大学戴维斯分校这个SBIR项目将开发一种新技术，用于对对人体造成不良健康影响的环境毒物进行生物监测。这项新技术将微雾化与高分辨率气雾质谱结合在一起，以实现对特定毒物以及微量血液或生物流体样本中毒物类别的灵敏检测和化学表征。按需液滴(DOD)界面将把微量液体转化为大小受到严格控制的气溶胶颗粒，并将它们定量送入气溶胶质谱仪(AMS)，用于检测和分析有毒物质的化学特征。DOD是一种经过验证的产生颗粒物的方法，十多年来，气溶胶质谱仪一直被用于对颗粒物相空气污染物进行灵敏和定量的分析，时间分辨率非常快(几秒钟到几分钟)。DOD与AMS的联用将允许直接在生物样品中或在液色谱(LC)分离后对液相物种进行实时表征。DOD-AMS组合仪器将能够同时检测和定量各种相关的有毒化学物质，包括无机、金属和有机物种。国防部将开发一个原型界面，并在实验室中用含有已知毒物的测试气雾剂和流行病学研究的存档血液样本进行表征。将开发数据挖掘技术，以识别质谱图分布中的组织模式，了解检测到的物种与健康结果之间的相关性，并检查多个分析物和分析物类别与系统影响的关联。为了证明这项技术的有效性，我们将对以前从哮喘和非哮喘儿童群体中收集的血清样本进行流行病学初步研究。首先，我们将同时检测血液样本中的许多毒物或其代谢产物，其次，使用数据挖掘技术来确定毒物的特征，第三，使用流行病学评估技术确定血清中与哮喘最显著相关的毒物类型和/或类别。 公共卫生相关性：该项目解决了对新的生物监测技术的迫切需求，以快速、灵敏和同时测量多种已知和可疑的毒物，这些毒物最终可以与流行病学和暴露研究中的系统效应联系在一起。拟议的技术将允许对少量血液或其他生物流体中的化学物种进行灵敏的检测和表征。

DESCRIPTION (provided by applicant): Development of a Novel Aerosol Mass Spectrometric Technology for Rapid and Sensitive Biomonitoring of Environmental Toxicants Name, address, and telephone number of the Principal Investigator: Dr. Manjula Canagaratna, Aerodyne Research, Inc., 45 Manning Rd., Billerica, MA 01821-3976, 1-978-663-9500 ext. 285 Names of other key personnel: Prof. Qi Zhang, Prof. Fumio Matsumura Participating institutions: Aerodyne Research Inc.; University of California, Davis This SBIR project will develop a novel technology for biomonitoring of environmental toxicants that cause adverse health effects in humans. The new technology will couple micro-nebulization with high resolution aerosol mass spectrometry to allow sensitive detection and chemical characterization of specific toxicants as well as toxicant classes in microvolumes of blood or biofluid samples. A droplet-on- demand (DOD) interface will convert microvolumes of liquids into aerosol particles of tightly controlled sizes and quantitatively deliver them into an aerosol mass spectrometer (AMS) for detection and chemical characterization of toxicants. DOD is a proven means of generating particles and aerosol mass spectrometry has been used for over a decade for sensitive and quantitative analysis of particle phase air pollutants with very fast time resolution (seconds to minutes). The coupling of DOD with AMS will allow characterization of liquid-phase species in real time, either directly in biological samples or after liquid chromatographic (LC) separation. The combined DOD-AMS instrument will be capable of simultaneously detecting and quantifying a wide variety of relevant toxic chemicals including inorganic, metal, and organic species. A prototype DOD interface will be developed and characterized in the laboratory with test aerosols containing known toxicants, and with archived blood samples from epidemiological studies. Data mining techniques will be developed to identify organizing patterns within the mass spectral distributions, understand correlations between detected species and health outcomes, and examine the association of multiple analytes and analyte classes with systemic effects. For the purpose of demonstrating the usefulness of this technology we will conduct an epidemiological pilot study on previously collected serum samples from asthmatic and non-asthmatic groups of children. We will first, simultaneously detect many toxicants or their metabolic products in the blood samples, second, use data mining techniques to characterize the toxicants, third identify the types and/or classes of toxicants in the serum that are most significantly associated with asthma using epidemiological assessment techniques. PUBLIC HEALTH RELEVANCE: This project addresses the critical need for new biomonitoring technology for rapid, sensitive, and simultaneous measurements of multiple known and suspected toxicants that can be ultimately linked with systematic effects in epidemiological and exposure studies. The proposed technology will allow sensitive detection and characterization of chemical species in small volumes of blood or other biofluids.