Endotoxin Quantification in Aqueous Media

水介质中的内毒素定量

• 批准号: 7127804
• 负责人: CRAIG A GRIMES
• 金额: $ 18.13万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127804
• 关键词: endotoxins

DESCRIPTION (provided by applicant): Annually in the United States there are approximately 750,000 cases of sepsis resulting in 200,000 deaths [1]. Since it is difficult to counter the effects of endotoxin, many medical experts suggest that the best way to prevent endotoxin-induced sepsis is a rigorous endotoxin screening process [2,3]. The proposed research seeks to enable development of a low-cost, hence widely available, highly sensitive and rapid endotoxin detection system based on the use of disposable remote-query magnetoelastic sensors. Utilizing the viscosity-monitoring capabilities of the magnetoelastic sensor platform, this system determines the endotoxin level by measuring the gel formation in Limulus Amoebocyte Lysate (LAL) assay, a popular assay derived from horseshoe crabs for endotoxin quantification. The miniature nature of the sensor, coupled with its excellent viscosity sensitivity, enables micro-Liter assays significantly reducing cost and facilitating ease of use. We believe that the proposed system will significantly reduce the rate of sepsis mortality by allowing healthcare providers to easily, rapidly, and inexpensively detect endotoxic infections in high-risk patients. Passive, ribbon-like magnetoelastic sensors, immersed within the LAL assay-test solution, are remotely interrogated via magnetic fields. Preliminary studies have shown that the resonance amplitude of the magnetoelastic sensor decreases during the coagulation of the LAL assay, and the magnitude of the time rate of change is proportional to the endotoxin concentration. The focus of this effort is to conduct the enabling science and engineering that will facilitate development of the magnetoelastic endotoxin detection device and optimize its performance. Specifically, over the two year project duration we will: {1} further miniaturize and optimize the sensors to reduce the amount of LAL assay needed with enhanced sensitivity. {2} refine the needed sensor reader electronics, extending the upper frequency operational limit and including an additional 40dB of gain. {3} develop a technique and/or algorithm to accurately calculate the endotoxin level based on the initial response of the sensor to enable endotoxin quantification in but a few minutes time. {4} Design and fabricate the pyrogen-free LAL-mixing disposable package for the sensor and the sample collection apparatus. We seek to significantly reduce the rate of sepsis mortality by providing healthcare providers an accurate, inexpensive, and rapid tool for detecting endotoxic infections in at-risk patients. Considering the annual mortality rate due to sepsis, over 200,000 deaths, we believe the success of this project will make a significant contribution in improving public health.

描述（由申请人提供）：美国每年约有750,000例败血症，导致200,000例死亡。由于难以对抗内毒素的影响，许多医学专家建议，预防内毒素引起的脓毒症的最佳方法是严格的内毒素筛查过程[2,3]。提出的研究旨在开发一种低成本，因此广泛可用，高灵敏度和快速的内毒素检测系统，该系统基于使用一次性远程查询磁弹性传感器。利用磁弹性传感器平台的粘度监测功能，该系统通过测量鲎变形虫细胞裂解液（LAL）测定中的凝胶形成来确定内毒素水平，LAL是一种流行的源自马蹄蟹的内毒素定量测定方法。传感器的微型特性，加上其优异的粘度灵敏度，使微升分析显着降低了成本，便于使用。我们相信，该系统将使医疗保健提供者能够轻松、快速、廉价地检测高风险患者的内毒素感染，从而显著降低败血症死亡率。被动式带状磁弹性传感器浸入LAL分析测试溶液中，通过磁场进行远程检测。初步研究表明，磁弹性传感器的共振幅度在LAL测定的凝固过程中减小，并且时间变化率的大小与内毒素浓度成正比。这项工作的重点是开展科学和工程，以促进磁弹性内毒素检测装置的发展并优化其性能。具体来说，在两年的项目期间，我们将：{1}进一步小型化和优化传感器，以减少所需的LAL测定量，同时提高灵敏度。{2}改进了所需的传感器读取电子设备，扩展了频率上限，并包括额外的40dB增益。{3}开发了一种技术和/或算法，可以根据传感器的初始响应准确计算内毒素水平，从而在几分钟内实现内毒素定量。为传感器和样品采集装置设计和制造无热原lal混合一次性封装。我们寻求通过为医疗保健提供者提供一种准确、廉价和快速的工具来检测高危患者的内毒素感染，从而显著降低败血症死亡率。考虑到每年因败血症死亡的人数超过20万人，我们相信这个项目的成功将对改善公共卫生作出重大贡献。