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: 8431127
• 负责人: Gennady Shvets
• 金额: $ 17.79万
• 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/8431127
• 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）：迫切需要开发可靠且准确的方法来检测和鉴定低浓度的循环肿瘤细胞（CTC）。特别有吸引力的是可以在服务点实施的全血样本中的 CTC 检测。血液中极少量的 CTC 构成了巨大的技术挑战，阻碍了直接检测，并且需要在任何传感/诊断测量之前进行 CTC 分离/富集。纳米技术的最新进展使得能够将分离/富集和传感/诊断功能结合在一个实体中。我们项目的总体目标是开发一个简单但准确的全血样本 CTC 检测平台，该平台将选择性捕获 CTC 与其独特的光谱指纹识别相结合。 我们的方法基于肿瘤细胞膜的表面增强红外吸收光谱 (SEIRAS)，使用基于超材料的新型等离子体平台：Fano 共振非对称超材料 (FRAMM)。不同的基于 FRAMM 的红外“像素”将被调谐到不同的红外频率，从而实现附着在传感器上的目标细胞的空间定位。为了提高目标细胞与传感器附着的特异性和稳健性，所有 FRAMM 像素都将通过一系列抗体进行功能化。使用差值反射率 FTIR 检测细胞与基质的结合 光谱不仅可以检测结合事件，还可以产生高度特异性的细胞指纹。将使用主成分分析来分析光谱数据集，以区分不同的目标细胞并检测它们的空间位置。 FRAMM 将提供 50-100 nm 的场穿透进入细胞，确保对整个细胞膜进行光谱分析。 通过将电连接的 FRAMM 组合到交流电极中，我们将使用细胞特异性介电电泳 (DEP) 来大大丰富传感器表面上的肿瘤细胞群，而血细胞在全血样本中含量要丰富得多。细胞特异性 DEP 将通过用分子特异性二氧化硅涂层等离子体纳米棒标记 CTC 来实现，从而大大增加 CTC 相对于血细胞的 AC 极化率。捕获的肿瘤细胞将通过以下方式进一步与血细胞区分开： 它们固有的独特红外指纹，以及通过纳米标签的振动指纹。纳米棒将用作红外造影剂和细胞特异性介电泳的递送载体。所提出的方法结合了以下优点：(a) 使用 FRAMM-SEIRAS 对肿瘤细胞进行高度灵敏的无标记识别，以及 (b) 在单个设备中对稀有肿瘤细胞进行稳健的富集/分离机制。