Innovative Biomonitoring Device for Rapid Diagnosis of Exposure to Nerve Agents

用于快速诊断神经毒剂暴露情况的创新生物监测装置

• 批准号: 7918864
• 负责人: Yuehe Lin
• 金额: $ 67.88万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7918864
• 关键词: Acetylcholinesterase; Adult; Antibodies; Binding; Biological Assay; Biological Markers; Biological Models; Biological Monitoring; Biosensor; Blood; Butyrylcholinesterase; Chemical Weapons; Chemicals; Cholinesterase Inhibitors; Cholinesterases; Clinical; Complex; Coupled; Detection; Development; Devices; Diagnostic; Diagnostic Procedure; Dose; Electrodes; Emergency Situation; Enzyme-Linked Immunosorbent Assay; Enzymes; Erythrocytes; Evaluation; Exposure to; Goals; Hand; Harvest; Human; Immunoassay; In Vitro; Incubated; Ions; Laboratories; Lead; Link; Mass Spectrum Analysis; Medical; Metals; Methods; Microfluidics; Non-Invasive Cancer Detection; Peptides; Performance; Pesticides; Plasma; Preparation; Production; Proteins; Rattus; Reaction Time; Research Personnel; Research Project Grants; Risk; Saliva; Sampling; Sarin; Site; Sprague-Dawley Rats; System; Techniques; Testing; Time; Translational Research; Validation; adduct; antibody conjugate; base; chelation; detector; emergency service responder; experience; improved; in vivo; innovation; male; minimally invasive; nanoparticle; nerve agent; novel diagnostics; novel strategies; programs; rapid detection; rapid diagnosis; research study; response; sensor; tool; zirconium oxide

DESCRIPTION (provided by applicant): With an increased risk of terrorist attacks involving chemical weapons, including nerve agents, there is a need to develop new and improved countermeasures for the rapid detection of exposure. Hence, this project will develop a portable micro-analytical system for the rapid evaluation of exposure to organophosphorus (OP) nerve agents utilizing phosphorylated cholinesterase (ChE) as a biomarker (OP-ChE adducts) in blood and saliva. Our hypothesis is that a highly selective, ultra sensitive, and disposable biosensor can be developed to detect sub-clinical exposure to nerve agents by using nanoparticle linked antibodies and metal chelation to selectively capture OP-ChE biomarkers followed by electrochemical detection. This project is directly responsive to RFA-NS-06-004 concerning CounterACT research projects (U01) for the development of new diagnostic techniques and tools to enhance our medical response capabilities during an emergency. The approach will involve initial development of an immuno-capture electrochemical detector for OP-ChE biomarkers and the subsequent development of a disposable immunochromatographic electrochemical biosensor (IEB). Diisopropylphosphorofluoridate (DFP) and Sarin will be used as the chemical nerve agents in in vitro and in vivo exposures to generate OP-ChE protein biomarkers in the plasma, RBC, and saliva of rats and humans. OP-ChE biomarkers will be detected with the microfluidic IEB using an approach similar to the ELISA assay, except that primary recognition is performed by nanoparticle-tagged antibodies and secondary recognition is performed by zirconium oxide (ZrO2) chelation with the phosphorylated moiety, followed by detection that is based on generating metal ions by dissolving the nanoparticle and detecting the metal ions upon accumulation to an electrode. The development of a real-time biomonitoring IEB device for analysis of blood and/or saliva represents a significant advancement over current biomonitoring strategies for nerve agent exposure. The utilization of minimally invasive biomatrices, coupled with on-site and rapid detection represents a novel approach with broad application for evaluating deliberate or accidental exposures to chemical nerve agents.

描述（由申请人提供）：随着涉及化学武器（包括神经因素）的恐怖袭击的风险增加，需要开发新的和改进的对策，以快速检测暴露。因此，该项目将开发出一种便携式微型分析系统，以快速评估使用磷酸化的胆碱酯酶（CHE）作为血液和唾液中的生物标志物（Op-Che加合物）的有机磷（OP）神经剂。我们的假设是，可以开发高度选择性，超灵敏和一次性生物传感器，以通过使用纳米颗粒链接的抗体和金属螯合来检测到临床上的暴露于神经剂，以选择性地捕获Op-CHE生物标记物，然后进行电化学检测。该项目直接响应RFA-NS-06-004，涉及反对研究项目（U01），以开发新的诊断技术和工具，以增强紧急情况下的医疗响应能力。该方法将涉及用于卫生生物标志物的免疫捕获电化学检测器的初步发展，以及随后的一次性免疫色谱电解电化学生物传感器（IEB）。在体外和体内暴露中，将使用二异丙基磷氟氟氟氟甲化酸（DFP）和SARIN用作化学神经剂，以在血浆，RBC和大鼠和人类的血浆中产生Op-Che蛋白生物标志物。将使用类似于ELISA测定的方法检测到Op-CHE生物标志物，除了通过纳米颗粒标记的抗体进行的主要识别，除了通过磷酸化的金属与磷酸化的金属相比，通过纳米颗粒标记的抗体进行二次识别，并通过氧化二氧化碳（ZRO2）进行。离子积聚到电极。用于分析血液和/或唾液的实时生物监测IEB设备的开发代表了与当前的生物监测策略的显着进步。在现场和快速检测中，最小侵入性的生物剂的利用是一种新颖的方法，该方法具有广泛的应用，用于评估对化学神经剂的故意或意外暴露。

项目成果

The vital function of Fe3O4@Au nanocomposites for hydrolase biosensor design and its application in detection of methyl parathion.

• DOI: 10.1039/c2nr33107a
• 发表时间: 2013-01
• 期刊: Nanoscale
• 影响因子: 6.7
• 作者: Yuting Zhao;Weiying Zhang;Yuehe Lin;Dan Du

Bioelectrochemical immunoassay of polychlorinated biphenyl.

多氯联苯的生物电化学免疫分析。

• DOI: 10.1016/j.aca.2008.01.080
• 发表时间: 2008
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: Lin,Ying-Ying;Liu,Guodong;Wai,CM;Lin,Yuehe
• 通讯作者: Lin,Yuehe

An integrated electrochemical device based on immunochromatographic test strip and enzyme labels for sensitive detection of disease-related biomarkers.

• DOI: 10.1016/j.talanta.2012.02.046
• 发表时间: 2012-05
• 期刊: Talanta
• 影响因子: 6.1
• 作者: Zhexiang Zou;Jun Wang;Hua Wang;Yaoyao Li;Yuehe Lin

Enzyme-linked immunosorbent assay for detection of organophosphorylated butyrylcholinesterase: a biomarker of exposure to organophosphate agents.

• DOI: 10.1016/j.aca.2011.03.013
• 发表时间: 2011-05
• 期刊: Analytica chimica acta
• 影响因子: 6.2
• 作者: Limin Wang;Dan Du;Donglai Lu;Chiann-Tso Lin;J. Smith;C. Timchalk;Fengquan Liu;Jun Wang;Yuehe Lin

CdSe/ZnS quantum dots based electrochemical immunoassay for the detection of phosphorylated bovine serum albumin.

• DOI: 10.1016/j.bios.2010.08.021
• 发表时间: 2010-11
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Kulwadee Pinwattana;Jun Wang;Chiann-Tso Lin;Hong Wu;Dan Du;Yuehe Lin;O. Chailapakul