Isolation of rare circulating tumor cells from blood using microbubbles

使用微泡从血液中分离罕见的循环肿瘤细胞

• 批准号: 7586521
• 负责人: Dmitri Simberg
• 金额: $ 16.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7586521
• 关键词: Address; Adherence; Antibodies; Award; Binding; Blood; Blood Cells; Blood gas; Blood specimen; Bone Marrow; Cancer Patient; Cell Adhesion Molecules; Cell Culture Techniques; Cell Separation; Cells; Centrifugation; Coupling; Cultured Tumor Cells; Data; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Distant Metastasis; Drug Formulations; Early Diagnosis; Epithelial Cells; Erythrocytes; Fluorescein; Fluoresceins; Force of Gravity; Gases; Goals; Label; Leukocytes; Literature; Magnetism; Malignant Neoplasms; Medicine; Methods; Microbubbles; Microscopy; Microspheres; Mus; Neoplasm Metastasis; One-Step dentin bonding system; Organic solvent product; Phase; Process; Productivity; Property; Recovery; Sampling; Scheme; Seeds; Specificity; Speed; TACSTD2 gene; Techniques; Technology; Testing; Time; base; cancer cell; cancer diagnosis; cancer genomics; improved; magnetic beads; neoplastic cell; outcome forecast; public health relevance

DESCRIPTION (provided by applicant): It is well established that metastatic tumor cells are present in blood and bone marrow throughout the course of cancer disease (1-4). These circulating tumor cells (CTCs) are thought to seed the disease and distant metastases in the body (5,6). Isolating and characterizing the CTCs could provide invaluable information for diagnosis, treatment and prognosis of different stages of cancer (2,3,7). The concentration of CTCs in blood is typically low and can be as low as 1 cell/ml of blood (8). An ideal isolation technique has to be able to specifically capture and isolate single CTCs from billions of blood cells with close to 100% efficiency, without significant contamination by non-specific cells. We propose to use targeted microbubbles (hereafter ¿bubbles) to develop a method for isolation and analysis of rare tumor cells. ¿Bubbles could offer potential advantages over magnetic beads as a cell isolation technique. We show in our preliminary data that targeted ¿bubbles efficiently attach to their target cells in blood, so that the cells become buoyant and easily separate from all other cells using gravity/centrifugation. The goal of this proposal is to test whether the ¿bubble separation can achieve the sensitivity of magnetic bead separation, but with higher specificity, speed and productivity (ability to process >10 ml blood). These goals are achievable within the time frame of this award to allow us to assess whether further development is warranted. PUBLIC HEALTH RELEVANCE: To develop and to test tumor cell isolation technique for diagnosis of cancer. The technique will be based on the use of gas microbubbles that will attach to metastatic tumor cells in blood sample and will separate by buoyancy.

描述（由申请人提供）：已经确定，在癌症疾病的整个过程中，转移性肿瘤细胞存在于血液和骨髓中（1-4）。这些循环肿瘤细胞（CTC）被认为是体内疾病和远处转移的种子（5，6）。分离和表征CTC可以为不同阶段癌症的诊断、治疗和预后提供宝贵的信息（2，3，7）。血液中CTC的浓度通常较低，可以低至1个细胞/ml血液（8）。理想的分离技术必须能够以接近100%的效率从数十亿个血细胞中特异性地捕获和分离单个CTC，而不受非特异性细胞的显著污染。我们建议使用靶向微泡（以下简称“气泡”）来开发一种分离和分析罕见肿瘤细胞的方法。作为一种细胞分离技术，气泡可以提供优于磁珠的潜在优势。我们在初步数据中表明，靶向气泡有效地附着在血液中的靶细胞上，使细胞变得有浮力，并利用重力/离心作用容易地与所有其他细胞分离。该提案的目的是测试气泡分离是否可以达到磁珠分离的灵敏度，但具有更高的特异性，速度和生产率（处理>10 ml血液的能力）。这些目标可以在此奖项的时间框架内实现，以便我们评估是否需要进一步开发。 公共卫生相关性：开发和测试用于癌症诊断的肿瘤细胞分离技术。该技术将基于使用气体微泡，其将附着于血液样品中的转移性肿瘤细胞并通过浮力分离。