Endotoxin Quantification in Aqueous Media

水介质中的内毒素定量

• 批准号: 7268127
• 负责人: CRAIG A GRIMES
• 金额: $ 21.12万
• 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 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7268127
• 关键词: Algorithms; Amplifiers; Biological Assay; Boxing; Cellular Phone; Cessation of life; Characteristics; Coagulation Process; Coupled; Detection; Development; Devices; Elasticity; Electronics; End Point; Endotoxins; Engineering; Frequencies; Gel; Health Personnel; Hour; Infection; Kaolin; Length; Life; Limulus; Measurement; Measures; Medical; Microprocessor; Miniaturization; Monitor; Nature; Noise; Outcome; Outcomes Research; Patient Care; Patients; Performance; Procedures; Process; Public Health; Pyrogens; Range; Rate; Reaction Time; Reader; Reading; Research; Research Personnel; Resolution; Rest; Risk; Rotation; Sampling; Science; Screening procedure; Secure; Sepsis; Signal Transduction; Solutions; Staging; Standards of Weights and Measures; Syringes; System; Techniques; Testing; Time; United States; Vial device; Viscosity; Width; Xiphosura; aqueous; base; concept; cost; density; design; endotoxin binding protein; improved; magnetic field; miniaturize; mortality; prevent; prototype; rapid diagnosis; research study; response; sample collection; sensor; size; success; tool; vibration

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）：每年在美国，大约有750,000例败血症案件导致200,000例死亡[1]。由于很难应对内毒素的影响，因此许多医学专家认为，预防内毒素引起的败血症的最佳方法是严格的内毒素筛查过程[2,3]。拟议的研究旨在基于使用一次性遥控磁弹性传感器的使用，以开发低成本，高度可获得的，高度敏感和快速的内毒素检测系统。利用磁弹性传感器平台的粘度监测功能，该系统通过测量Limulus Amoebocyte裂解物（LAL）测定的凝胶形成来确定内毒素水平，这是一种源自马蹄蟹的流行测定，用于内毒素定量。传感器的微型性质，再加上其出色的粘度敏感性，可实现微量级测定，可显着降低成本并促进易用性。我们认为，提出的系统将通过允许医疗保健提供者轻松，迅速和廉价地检测到高危患者的内毒素感染来大大降低败血症死亡率的率。通过磁场对被浸入LAL测定测试溶液中的被动的带状磁弹性传感器进行了远程审查。初步研究表明，在LAL测定的凝结过程中，磁弹性传感器的共振幅度降低，并且变化时间率的幅度与内毒素浓度成正比。这项工作的重点是进行启示的科学和工程，以促进磁弹性内毒素检测装置的开发并优化其性能。具体而言，在两年的项目持续时间内，我们将：{1}进一步微型化并优化传感器，以减少灵敏度增强所需的LAL测定量。 {2}完善所需的传感器读取器电子设备，扩大了上限操作限制，并包括增加40dB的增益。 {3}开发一种技术和/或算法，以基于传感器的初始响应来准确计算内毒素水平，以在几分钟时间内启用内毒素定量。 {4}为传感器和样品收集设备设计并制造并制造了无焦糖的LAL混合装置包装。我们寻求通过为医疗保健提供者提供一种准确，廉价且快速的工具来显着降低败血症死亡率的率，以检测处于高危患者的内毒性感染。考虑到由于败血症而导致的年死亡率，超过200,000人死亡，我们认为该项目的成功将在改善公共卫生方面做出重大贡献。

项目成果

Wireless, remote-query, and high sensitivity Escherichia coli O157:H7 biosensor based on the recognition action of concanavalin A.

• DOI: 10.1021/ac9008572
• 发表时间: 2009-07-15
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Lu, Qingzhu;Lin, Hailan;Ge, Shutian;Luo, Shenglian;Cai, Qingyun;Grimes, Craig A.
• 通讯作者: Grimes, Craig A.