Multiplexed biosensor for personal wildfire exposure assessment

用于个人野火暴露评估的多重生物传感器

• 批准号: 10601152
• 负责人: Dan Du
• 金额: $ 25.9万
• 依托单位: DL ADV-TECH, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-02 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10601152
• 关键词: Acetylcysteine; Address; Air; Aliquot; Aromatic Polycyclic Hydrocarbons; Assessment tool; Benzene; Biological; Biological Markers; Biological Monitoring; Biomass; Biosensing Techniques; Biosensor; Businesses; Chemicals; Data; Detection; Development; Dose; Europium; Evaluation; Exposure to; Glucuronides; Goals; Health; Human; Immunoassay; Individual; Label; Laboratories; Lateral; Marketing; Measurement; Measures; Meteorology; Methods; Modeling; Monitor; Naphthols; National Institute of Environmental Health Sciences; Occupational; Paper; Perception; Personal Satisfaction; Persons; Phase; Population; Preparation; Property; Public Health; Reader; Reporting; Reproducibility; Research; Risk; Sampling; Scientist; Signal Transduction; Site; Small Business Innovation Research Grant; Smoke; Specificity; System; Techniques; Technology; Testing; Time; Toxic effect; Universities; Urine; Validation; Variant; Washington; Wildfire; absorption; antibody conjugate; climate change; cost; detection limit; detection sensitivity; fabrication; improved; innovation; nanomaterials; nanoparticle; operation; portability; predictive modeling; response; scale up; sensor; success; targeted biomarker; test strip; tool; urinary

Summary/Abstract: Wildfire are becoming more frequently and severe due to climate change, resulting in growing exposures of major population to high level of benzene and polycyclic aromatic hydrocarbons from biomass-burning emissions. Wildfire exposure pose a serious threat to the health and the well-being of humans. Currently, assessment of personal exposure to wildfire is dependent on taking environmental samples and analyzing the samples using expensive analytical techniques, which cannot adequately represent personal exposure due to the temporal and spatial variation of the metabolite concentrations. Biological detection of biomarkers has great potential to overcome the limitation of conventional techniques and provides accurate measurements of personal exposure levels. In this SBIR project, DL ADV-Tech proposes to develop an advanced europium-nanoparticles enhanced time-resolved fluorescent (TRF) immunoassay biosensor which provides extremely sensitivity (pg/ml level), short turnaround time (<10 minutes), simple operation and low cost (<$5 for each test) for non-invasively analyzing wildfire exposure in urine samples. A major significance of this proposed approach is the ability to on-site and very accurately analyze low amount of biomarkers by leveraging our advanced nanomaterials signal amplification technique and multiplex sensing technique. The proposed biosensor includes a paper-based strip to simultaneously measure multiple metabolites, 2-naphthol (2-NAP), 1- hydroxypyrene glucuronide (1-OHPG) and S-phenyl mercapturic acid (S-PMA), where newly developed nanomaterial, europium (Eu)-based nanoparticles (YVO4:Eu) is introduced to achieve high sensitivity. A portable TRF reader will be equipped to quantify the concentrations of targets. We have demonstrated that using the advanced Eu-based nanoparticles as signal label, the proposed fluorescent immunoassay is expected to improve the stability, reliability and accuracy in detection of wildfire-associated biomarkers in urine. Incorporated with this innovative signal amplification strategy, the sensitivity of the proposed biosensor is expected to be significantly increased. Using the proposed biosensor, the measurement of personal wildfire smoke exposure biomarkers can be completed within 10 minutes and the detection limit can as low as 0.1 ng/ml. In this Phase I project of proof-of-concept, we will focus on the biosensor with two test zones that simultaneously quantify three urinary metabolites (2-NAP, 1-OHPG and SPMA). The proposed biosensor will be fabricated and validated, and the analytical 'figures of merits' of the biosensor will be established. In Phase II, the biosensor will be further optimized for on-site applications in real world conditions and scaled-up for detecting more biomarkers associated with wildfire exposure. This highly precise and truly portable TRF biosensor will provide a non- invasive, sensitive, simple, rapid, robust, and inexpensive assessment tool, which will revolutionize current biomonitoring technique for assessing personal exposure levels with shorter time and lower cost. 1

摘要/摘要： 由于气候变化，野火变得更加频繁和严重，导致野火的暴露量不断增加 主要人口因生物质燃烧排放而产生高浓度的苯和多环芳烃。 野火暴露对人类的健康和福祉构成严重威胁。目前，评估 个人是否接触野火取决于采集环境样本并使用以下方法分析样本 昂贵的分析技术，由于时间和时间的原因，无法充分代表个人暴露情况 代谢物浓度的空间变化。生物标志物的生物检测具有巨大的潜力 克服传统技术的局限性，提供个人暴露的准确测量 水平。在这个 SBIR 项目中，DL ADV-Tech 提议开发一种先进的铕纳米粒子 增强型时间分辨荧光 (TRF) 免疫分析生物传感器，具有极高的灵敏度 （pg/ml 水平）、周转时间短（<10 分钟）、操作简单且成本低（每次测试 <5 美元） 非侵入性地分析尿液样本中的野火暴露情况。这一提议的重大意义 方法是利用我们的技术，能够现场并非常准确地分析少量生物标志物 先进的纳米材料信号放大技术和多重传感技术。拟议的 生物传感器包括纸基条带，可同时测量多种代谢物、2-萘酚 (2-NAP)、1- 新开发的羟基芘葡萄糖醛酸（1-OHPG）和S-苯基硫醇酸（S-PMA） 纳米材料，引入铕 (Eu) 基纳米粒子 (YVO4:Eu) 以实现高灵敏度。便携式 TRF 阅读器将配备量化目标浓度。我们已经证明，使用 先进的基于铕的纳米颗粒作为信号标记，所提出的荧光免疫测定法有望 提高尿液中野火相关生物标志物检测的稳定性、可靠性和准确性。法人 通过这种创新的信号放大策略，所提出的生物传感器的灵敏度预计将达到 显着增加。使用所提出的生物传感器，测量个人野火烟雾暴露 生物标志物可在10分钟内完成，检测限可低至0.1 ng/ml。在这个第一阶段 在概念验证项目中，我们将重点关注具有两个测试区的生物传感器，可同时量化三个 尿代谢物（2-NAP、1-OHPG 和 SPMA）。所提出的生物传感器将被制造和验证，并且 将建立生物传感器的分析“​​品质因数”。在第二阶段，生物传感器将进一步 针对现实条件下的现场应用进行了优化，并进行了放大以检测更多生物标志物 与野火暴露有关。这种高精度且真正便携式的 TRF 生物传感器将提供非 侵入性、灵敏、简单、快速、强大且廉价的评估工具，这将彻底改变当前的评估工具 用于以更短的时间和更低的成本评估个人暴露水平的生物监测技术。 1