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: 7663869
• 负责人: Mark S. DiIorio
• 金额: $ 41.25万
• 依托单位: MAGNESENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7663869
• 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的协作程序集中在一个基于纳米技术的新型平台上，该平台使用超敏感的磁性传感器和磁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扰装置（鱿鱼）来检测与磁性纳米颗粒标记的抗体的细胞表面受体的结合。我们将将平台应用于慢性淋巴细胞白血病（CLL）中最小残留疾病（MRD）的评估，以便更好地监测和指导疗法。一个主要的程序推力是开发改进的磁传感器和磁性纳米颗粒标签，并将其纳入下一代仪器中。该仪器将用于演示能够快速检测CLL细胞的磁性测定。 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试剂，与流式细胞仪相比（在107个细胞<45分钟的背景中检测50个细胞）4）表现出快速，灵敏的磁细胞测定法，用于对临床样品中慢性淋巴细胞性白血病的最小残留疾病评估（在<45分钟的107个单元格中检测到<45分钟的107个单元格）的慢性淋巴细胞性白血病（在<45分钟内检测到50个CLL细胞）的范围（1）。或表达较少受体的细胞。混合和测量格式大大减少了测定的准备时间并简化自动化（无需洗涤步骤）。这种几乎没有样品制备工作的能力有助于对临床样品进行快速，高吞吐量测试。跨学科的努力将Moores UCSD癌症中心和Nano肿瘤癌症纳米技术卓越中心，UCSD，白血病应用的UCSD，用于定制磁性纳米颗粒标签的免疫纳米粒子标签和稀有细胞检测专业知识的Incorties in Incorment and annoparties insnoparties and n nanoparties，inanoparties in nanoparties，innanoparties incompoties and inanoparties，innanoparties incomenties and.仪器和磁性测定专业知识。项目叙事性慢性淋巴细胞性白血病（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。 CLL与当前可用的治疗方法保持无法治愈，患者的预后差异很大。可用于评估最小残留疾病以优化治疗的现有技术，例如流式细胞仪和聚合酶链反应（PCR），不足以常规临床使用。一个能够快速，超敏感的检测稀有白血病细胞的磁性平台可以评估CLL中可检测到的最小疾病，并具有临床实用性，可通过使医生能够比目前可能更快地调整疗法来改善患者的结局。