CTC Purification System Based on Thermoresponsive NanoSubstrates

基于热响应纳米基质的CTC纯化系统

• 批准号: 9133318
• 负责人: Sean Xiao Liu
• 金额: $ 99.24万
• 依托单位: CYTOLUMINA TECHNOLOGIES CORPORATION, INC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9133318
• 关键词: Accounting; Advanced Development; Affinity; Antibodies; Bioinformatics; Biological Assay; Biometry; Biopsy; Blood Substitutes; Blood specimen; Businesses; Cancer Center; Cancer Etiology; Cancer Patient; Cancer cell line; Cell Culture System; Cell Culture Techniques; Cell Line; Cells; Cessation of life; Chemistry; Clinical; Collaborations; Custom; DNA Sequence Alteration; Data; Development; Devices; Diagnosis; Diagnostic; Dissection; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Exhibits; Genes; Genetic; Genomics; Goals; Harvest; Health; Image Guided Biopsy; In Vitro; Individual; Institutes; Joints; Link; Malignant - descriptor; Malignant neoplasm of lung; Medical center; Methods; Microfluidics; Molecular; Molecular Conformation; Molecular Profiling; Motivation; Mutation; Nanotechnology; Neoplasm Circulating Cells; Non-Small-Cell Lung Carcinoma; Oncogenic; Operative Surgical Procedures; Patients; Pattern; Performance; Pharmaceutical Preparations; Phase; Polymers; Population; Predisposition; Primary Neoplasm; Procedures; Property; Radiation; Research; Risk; Sampling; Site; Small Business Innovation Research Grant; Solid Neoplasm; Specificity; Specimen; Staging; Surface; System; Technology; Temperature; The Sun; Tissues; Universities; Validation; Whole Blood; actionable mutation; base; c-erbB-1 Proto-Oncogenes; cancer cell; cancer type; chemotherapy; design; digital; experience; genetic analysis; innovation; liquid biopsy; minimally invasive; mortality; peripheral blood; programs; prototype; targeted treatment; technology development; three dimensional cell culture; tumor; user-friendly

 DESCRIPTION (provided by applicant): The goal of this SBIR Phase II proposal is to conduct the advanced development of the 3rd-gen Thermoresponsive NanoVelcro assay in order to achieve rapid purification of circulating tumor cells (CTCs) from non-small cell lung cancer (NSCLC) patient blood samples, paving the way for CTC-derived molecular signatures and functional readouts. This project is led by Dr. Garcia (PI), who has extensive experience in early-stage development of the technology and has a background in surface chemistry, microfluidics, and in vitro diagnostic technologies. He is supported by an interdisciplinary team comprising business development, FDA expertise, QC/QA management, nanotechnology support, lung cancer, clinical utility, genetic analysis, biostatistics, industrial collaborators, nd downstream potential customers. NSCLC accounts for >70% of lung cancer cases. Since NSCLCs are usually not very sensitive to chemotherapy and/or radiation, the advent of targeted therapy by epidermal growth factor receptor (EGFR) inhibitors offer a great treatment options to a sub-population of NSCLC patients who carry oncogenic driver mutations in their EGFR genes. To guide the implementation of targeted therapy, invasive biopsy or surgery is employed to sample NSCLC tissues for determining the presence of these EGFR mutations. However, these invasive sampling procedures impose significant risk to the patients. As an alternative, CTCs can be captured repetitively and analyzed in a minimally invasive manner thus providing a systemic picture of the malignant clones that possess high metastatic capacity. The proposed Thermoresponsive NanoVelcro assay is composed of two individual components: i) a digital fluidic handler with an embedded temperature control module, and ii) a custom-designed chip holder, in which a clamp-down design allows instant assembly of a NanoVelcro substrate with an overlaid PDMS component, will be designed and fabricated at CytoLumina. To highlight the significance of our downstream studies, we will gather serial blood samples from lung cancer patients. We will collect the purified CTCs and subject them to mutational analysis for eight genes, including EGFR., Further, the purified CTCs will be introduced to a variety of in vitro cell culture systems (i.e., microfluidic and 3D cell-culture platforms) established by our joint team (UCLA and CytoLumina) to create viable CTC cell lines. The personalized cell lines will be used to study patterns in drug susceptibility, which is linked to the underlying genetic driver mutation.

 描述（由申请人提供）：本SBIR II期提案的目标是进行第3代热敏NanoVelcro检测试剂盒的高级开发，以实现从非小细胞肺癌（NSCLC）患者血液样本中快速纯化循环肿瘤细胞（CTC），为CTC衍生分子特征和功能读数铺平道路。该项目由Garcia博士（PI）领导，他在该技术的早期开发方面拥有丰富的经验，并具有表面化学，微流体和体外诊断技术的背景。他得到了一个跨学科团队的支持，包括业务开发，FDA专业知识，QC/QA管理，纳米技术支持，肺癌，临床实用性，遗传分析，生物统计学，工业合作者和下游潜在客户。 NSCLC占肺癌病例的>70%。由于NSCLC通常对化疗和/或放疗不太敏感，因此表皮生长因子受体（EGFR）抑制剂靶向治疗的出现为EGFR基因中携带致癌驱动突变的NSCLC患者亚群提供了很好的治疗选择。为了指导靶向治疗的实施，采用侵入性活检或手术对NSCLC组织进行采样以确定这些EGFR突变的存在。然而，这些侵入性采样程序对患者造成了重大风险。作为替代方案，可以重复捕获CTC并以微创方式进行分析，从而提供具有高转移能力的恶性克隆的系统图像。 拟定的热敏NanoVelcro检测试剂盒由两个单独组件组成：i）带有嵌入式温度控制模块的数字流体处理器，和ii）定制设计的芯片保持器，其中夹持设计允许NanoVelcro基底与覆盖的PDMS组件即时组装，将在CytoLumina设计和制造。为了突出我们下游研究的重要性，我们将从肺癌患者中收集系列血液样本。我们将收集纯化的CTC，并对其进行包括EGFR在内的8个基因的突变分析。此外，将纯化的CTC引入多种体外细胞中， 培养系统（即，微流控和3D细胞培养平台）建立了我们的联合团队（加州大学洛杉矶分校和CytoLumina的创建可行的CTC细胞系。个性化的细胞系将用于研究药物敏感性的模式，这与潜在的遗传驱动突变有关。