Nanotechnology based magnetic detection for rare cell assays

基于纳米技术的稀有细胞检测磁性检测

• 批准号: 7938192
• 负责人: Mark S. DiIorio
• 金额: $ 39.02万
• 依托单位: MAGNESENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938192
• 关键词: Academia; Accounting; Achievement; Amniocentesis; Antibodies; Area; Automation; B-Lymphocytes; Binding; Biological Assay; Biological Models; Biotechnology; Blood; Cancer Center; Cell Count; Cell Separation; Cell Surface Receptors; Cell surface; Cells; Chemistry; Chronic Lymphocytic Leukemia; Clinical; Complex; Contracts; Custom; Detection; Development; Devices; Diagnostics Research; Disease; Engineering; Europe; Figs - dietary; Flow Cytometry; Foundations; Generations; Head; High temperature of physical object; Hour; In Vitro; Incubated; Individual; Industry; Institutes; Label; Legal patent; Leukocytes; Life; Link; Magnetism; Malignant Neoplasms; Measurement; Measures; Methods; Modeling; Monitor; Monoclonal Antibodies; Nanotechnology; Nature; North America; Outcome; Patients; Pennsylvania; Phase; Physicians; Polymerase Chain Reaction; Population; Preparation; Principal Investigator; Process; Property; Publications; Reagent; Research; Residual Neoplasm; Sampling; Schools; Serum; Signal Transduction; Small Business Innovation Research Grant; Specimen; Surface; System; T-Lymphocyte; Techniques; Technology; Testing; Time; United States National Aeronautics and Space Administration; United States National Institutes of Health; Variant; Work; Writing; base; cancer cell; cost; design; experience; fetus cell; improved; in vivo; instrument; instrumentation; interest; leukemia; magnetic field; medical schools; meetings; nano; nanoparticle; next generation; novel; outcome forecast; professor; programs; prototype; rapid detection; receptor; research and development; sensor; superconducting quantum interference device; technology development; tool; tumor

DESCRIPTION (provided by applicant): MagneSensors' collaborative program is centered on a novel nanotechnology based platform that uses ultra-sensitive magnetic sensors and magnetic labels to perform powerful rare cell assays. This magnetic detection platform uses high temperature superconducting quantum interference devices (SQUIDs) to detect the binding to cell surface receptors of antibodies labeled with magnetic nanoparticles. We will apply the platform to the assessment of minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) in order to better monitor and guide therapies. A major program thrust is to develop improved magnetic sensors and magnetic nanoparticle labels and incorporate them into next generation instrumentation. This instrumentation will be used to demonstrate magnetic assays capable of rapidly detecting CLL cells. The specific aims are: 1) Improve magnetic nanoparticle labels and their conjugation to antibodies (d100 nm size with <15% size variability, 10X reduced aggregation after conjugation to detect Ab, low aggregation in serum) 2) Build new instrument for rare cell detection (10X improved sensitivity, 20X higher throughput) 3) Demonstrate ultra-sensitive detection of rare cells in simple CLL model system with new instrument and reagents, compare to flow cytometry (detect 50 cells in background of 107 cells <45 minutes) 4) Demonstrate rapid, sensitive magnetic cell assay for minimal residual disease assessment of chronic lymphocytic leukemia in clinical samples (detect as few as 50 CLL cells in 107 leukocytes in <45 min) The high sensitivity of magnetic platform enables the detection of rare cells (1 in 104-106), or cells expressing a low number of receptors. The mix and measure format significantly reduces assay preparation time and simplifies automation (no wash steps). This ability to work with little or no sample preparation facilitates rapid, high throughput testing on clinical samples. The interdisciplinary effort unites Moores UCSD Cancer Center and Nano Tumor Center of Excellence for Cancer Nanotechnology, UCSD for the leukemia application, Immunicon Corporation for the custom magnetic nanoparticle labels and rare cell detection expertise, SoluLink, Inc. for the bioconjugation chemistry for attaching antibodies to magnetic nanoparticles, and MagneSensors, Inc. for magnetic sensors, instrumentation, and magnetic assay expertise.Project Narrative Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in North America and Europe and accounts for over 30% of all leukemias. CLL remains incurable with the currently available treatments and the prognosis of patients varies substantially. Existing techniques available to assess minimal residual disease to optimize treatment, such as flow cytometry and polymerase chain reaction (PCR), are inadequate for routine clinical use. A magnetic platform capable of rapid, ultra-sensitive, assays to detect rare leukemia cells could assess minimal detectable disease in CLL and have clinical utility for improving patient outcomes by enabling physicians to adjust therapies sooner than is currently possible.

描述（由申请人提供）：MagneSensors 的合作项目以基于新型纳米技术的平台为中心，该平台使用超灵敏磁传感器和磁性标签来执行强大的稀有细胞测定。该磁性检测平台使用高温超导量子干涉装置（SQUID）来检测磁性纳米粒子标记的抗体与细胞表面受体的结合。我们将将该平台应用于慢性淋巴细胞白血病（CLL）的微小残留病（MRD）评估，以更好地监测和指导治疗。一个主要的项目主旨是开发改进的磁传感器和磁性纳米颗粒标签，并将它们整合到下一代仪器中。该仪器将用于演示能够快速检测 CLL 细胞的磁性测定。具体目标是： 1) 改进磁性纳米颗粒标记及其与抗体的结合（d100 nm 尺寸，尺寸变异性 <15%，结合检测抗体后聚集减少 10 倍，血清中的聚集减少） 2) 构建用于稀有细胞检测的新仪器（灵敏度提高 10 倍，通量提高 20 倍） 3) 展示使用新仪器和技术对简单 CLL 模型系统中稀有细胞的超灵敏检测 试剂，与流式细胞术相比（在 107 个细胞的背景中检测 50 个细胞 <45 分钟） 4) 展示快速、灵敏的磁性细胞测定，用于临床样本中慢性淋巴细胞白血病的微小残留病评估（在 <45 分钟内检测 107 个白细胞中少至 50 个 CLL 细胞） 磁性平台的高灵敏度能够检测稀有细胞（104-106 分之一）， 或表达少量受体的细胞。混合和测量格式显着减少了测定准备时间并简化了自动化（无清洗步骤）。这种无需或很少样品制备的能力有助于对临床样品进行快速、高通量的测试。这项跨学科的工作联合了摩尔斯加州大学圣地亚哥分校癌症中心和纳米肿瘤卓越中心的癌症纳米技术、加州大学圣地亚哥分校的白血病应用、Immunicon Corporation 的定制磁性纳米颗粒标签和稀有细胞检测专业知识、SoluLink, Inc. 的生物共轭化学将抗体附着到磁性纳米颗粒，以及 MagneSensors, Inc. 的磁性传感器。 项目叙述 慢性淋巴细胞白血病 (CLL) 是北美和欧洲最常见的白血病形式，占所有白血病的 30% 以上。目前可用的治疗方法仍然无法治愈 CLL，并且患者的预后差异很大。现有的可用于评估微小残留病以优化治疗的技术，例如流式细胞术和聚合酶链反应（PCR），不足以满足常规临床使用。能够快速、超灵敏地检测罕见白血病细胞的磁性平台可以评估 CLL 中最小的可检测疾病，并通过使医生能够比目前更快地调整治疗方法来改善患者的治疗结果，具有临床实用性。