Ultra-sensitive magnetic assays for sepsis diagnostics

用于脓毒症诊断的超灵敏磁性测定

• 批准号: 6999557
• 负责人: Mark S. DiIorio
• 金额: $ 31.7万
• 依托单位: MAGNESENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999557
• 关键词: Escherichia coli; Staphylococcus aureus; biomedical equipment development; clinical biomedical equipment; clinical research; diagnosis design /evaluation; early diagnosis; human tissue; magnetic field; rapid diagnosis; septicemia

DESCRIPTION (provided by applicant): The program is aimed at applying an ultra-sensitive magnetic detection platform to the rapid and early diagnosis of pathogens causing sepsis. The technology platform is based on labeling biomolecules with magnetic nanoparticles and detecting the magnetic field generated upon binding using patented ultra-sensitive magnetic sensors. While the initial focus will be on a "proof-of-principle" demonstration for the direct detection of two major pathogens, Staphylococcus aureus and Escherichia coli, responsible for sepsis, the diagnostic platform should be generally applicable to a wide range of pathogens. Direct detection of live bacteria will be demonstrated by measuring the binding of magnetic labeled antibodies to a surface antigen on the target pathogen. Purchased bacteria will first be used to demonstrate a proof-of-concept for high sensitivity in a rapid, "mix and measure" magnetic assay. A next generation prototype instrument will then be produced and placed at our collaborator, Children's Hospital Boston. An existing IRB-approved library of clinical specimens with documented infections (600 blood and urine samples, 150 trachea) aspirates) will be examined in order to demonstrate clinical utility, including sensitivity, specificity and short assay times. The ultimate goal of this program is to show a limit of detection < 100 bacteria/ml in clinical samples with a total (preparation and measurement) assay time of less than 15 minutes. Additionally, detection limits as low as 5-10 bacteria in small samples (e.g., 20 ul) may be possible by using the unique ability to externally manipulate magnetic nanoparticle labels using magnetic fields. Note that magnetic detection is not hampered by measurement in biological fluids and the mix and measure format in microplate wells requires little sample preparation, thereby minimizing errors.

描述（由申请人提供）：该程序旨在将超敏感的磁检测平台应用于引起败血症的病原体的快速和早期诊断。该技术平台基于使用磁性纳米颗粒的生物分子标记，并使用专利的超敏感磁传感器在结合后检测磁场。 虽然最初的重点将用于直接检测两个主要的“原理证明”演示 病原体，金黄色葡萄球菌和大肠杆菌，负责败血症，诊断平台 通常应适用于多种病原体。 通过测量标记的磁性结合，将展示活细菌的直接检测 对靶病原体上表面抗原的抗体。购买的细菌将首先用于 在快速的“混合和测量”磁性测定中证明具有高灵敏度的概念验证。然后，将制作下一代原型仪器，并放置在我们的合作者波士顿儿童医院。将检查现有的IRB批准的临床标本库，并检查具有记录的感染（600个血液和尿液样本，150个气管）的抽吸物），以证明临床实用性，包括敏感性，特异性和短期测定时间。 该程序的最终目的是在临床样品中显示出<100细菌/mL的限制，总（制备和测量）测定时间少于15分钟。此外，通过使用磁场对外部操纵磁性纳米颗粒标签的独特能力，可以在小样品中低至5-10个细菌（例如20 ul）的检测极限。请注意，磁性检测不会通过测量生物流体的测量和微板井中的混合和测量格式受到阻碍，因此几乎不需要样品制备，从而最大程度地减少了误差。