Electrically-connected plasmonic metamaterials for capture and detection of CTC

用于捕获和检测 CTC 的电连接等离子体超材料

• 批准号: 8664819
• 负责人: Gennady Shvets
• 金额: $ 16.09万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8664819
• 关键词: Abnormal Cell; Address; Antibodies; Binding; Biochemical; Biochemistry; Biological Markers; Blood; Blood Cells; Blood specimen; Cancerous; Carbohydrates; Cell Count; Cell Separation; Cell membrane; Cell-Matrix Junction; Cells; Cellular Membrane; Clinical; Complex; Contrast Media; Data Set; Detection; Development; Devices; Diagnostic; ERBB2 gene; Electrodes; Ensure; Epidermal Growth Factor Receptor; Event; Fingerprint; Frequencies; Goals; Gold; Label; Leukocytes; Lipids; Location; Lymphocyte; Measurement; Membrane Proteins; Methods; Modeling; Modern Medicine; Molecular; Molecular Conformation; Molecular Profiling; Monitor; Nanotechnology; Neoplasm Circulating Cells; Neoplasm Metastasis; Normal Cell; Outcome; Penetration; Population; Principal Component Analysis; Proteins; Resolution; Sampling; Scientist; Services; Silicon Dioxide; Space Perception; Specificity; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Surface; TACSTD2 gene; Techniques; Therapeutic; Tumor Cell Line; Whole Blood; absorption; antigen antibody binding; base; cancer cell; cell type; design; improved; infrared spectroscopy; interest; nanometer; nanoparticle; nanorod; nanosensors; neoplastic cell; novel; plasmonics; point of care; prevent; programs; public health relevance; research study; sensor; tool

DESCRIPTION (provided by applicant): There is an urgent need to development reliable and accurate methods of detection and identification of low concentrations of circulating tumor cells (CTCs). Especially attractive would be detection of CTCs in whole blood samples that can be implemented at the point of service. Very small abundances of CTCs in blood pose a tremendous technological challenge, preventing direct detection and necessitating CTC isolation/enrichment prior to any sensing/diagnostic measurement. Recent advances in nanotechnology enable combining the isolation/enrichment and sensing/diagnostic functions in a single entity. The overall goal of our program is to develop a simple but accurate detection platform for CTCs from whole blood samples that will combine selective capturing of CTCs with their unique spectroscopic fingerprinting. Our approach is based on surface-enhanced infrared absorption spectroscopy (SEIRAS) of tumor cell membranes using a new metamaterial-based plasmonic platform: Fano-resonant Asymmetric Metamaterials (FRAMMs). Different FRAMM-based infrared "pixels" will be tuned to different infrared frequencies, thereby enabling spatial localization of the target cells attached to the sensor. To improve the specificity and robustness of target cell's attachment to the sensor, all FRAMM pixels will be functionalized by a range of antibodies. Cell's binding to the substrate will be interrogated using difference-reflectivity FTIR spectroscopy that will not only detect binding events, but will also yield highly specific cell fingerprints. Spectroscopic data sets will be analyzed using principal component analysis to differentiate between different target cells and to detect their spatial location. FRAMMs will provide field penetration of 50-100nm into the cell, ensuring that the entire cellular membrane is spectrally interrogated. By combining electrically connected FRAMMs into an AC electrode, we will use cell-specific dielectrophoresis (DEP) to greatly enrich the population of tumor cells on the sensor surface with respect to blood cells that are much more abundant in whole blood samples. Cell-specific DEP will be accomplished by labeling CTCs with molecular-specific silica-coated plasmonic nanorods, thereby greatly increasing the AC polarizability of CTCs with respect to blood cells. Captured tumor cells will be further distinguished from blood cells through their native distinct IR fingerprint, as well as through the vibrational fingerprints of the nanoro labels. The nanorods will serve as both infrared contrast agents and as delivery vehicles for cell-specific dielectrophoresis. The proposed approach combines the advantages of (a) highly-sensitive label-free identification of tumor cells using FRAMM-SEIRAS, and (b) robust enrichment/isolation mechanism for rare tumor cells in a single device.

描述（由申请人提供）：迫切需要开发可靠，准确的检测方法和鉴定低浓度的循环肿瘤细胞（CTC）。特别有吸引力的是在服务时可以检测全血样品中的CTC。血液中的CTC非常小的丰富性构成了巨大的技术挑战，可防止直接检测，并需要在进行任何感测/诊断测量之前进行CTC隔离/富集。纳米技术的最新进展使单个实体中的隔离/富集和传感/诊断功能可以结合使用。我们程序的总体目标是为CTC从全血样品中开发一个简单但准确的检测平台，将CTC的选择性捕获与其独特的光谱指纹结合在一起。 我们的方法基于使用新的基于超材料的等离子体平台的肿瘤细胞膜表面增强红外吸收光谱（SEIRA）：Fano谐振不对称的非对称材料（FRAMMS）。不同的基于FRAMM的红外“像素”将调整为不同的红外频率，从而实现了连接到传感器的目标细胞的空间定位。为了提高靶细胞在传感器上的附着的特异性和鲁棒性，所有FRAMM像素将通过一系列抗体功能化。细胞与底物的结合将使用差异反射性FTIR询问 光谱不仅会检测结合事件，还将产生高度特定的细胞指纹。光谱数据集将使用主成分分析进行分析，以区分不同的目标细胞并检测其空间位置。 Framms将提供50-100nm的场渗透到细胞中，以确保对整个细胞膜进行光谱的询问。 通过将电连接的FRAMMS结合到AC电极中，我们将使用细胞特异性的介电性（DEP）大大富集传感器表面上肿瘤细胞的种群，而在全血样品中更丰富的血细胞。细胞特异性DEP将通过将CTC用分子特异性二氧化硅涂层的等离子纳米棒标记来实现，从而大大提高了CTC相对于血细胞的AC极化性。捕获的肿瘤细胞将通过 它们的本地不同IR指纹以及通过纳米罗标签的振动指纹。纳米棒将既用作红外对比剂，又用作细胞特异性介电的递送车。所提出的方法结合了（a）使用Framm-Seiras对肿瘤细胞高度敏感的无标记鉴定的优势，以及（b）单个装置中稀有肿瘤细胞的强大富集/分离机制。