Electrically-connected plasmonic metamaterials for capture and detection of CTC

描述（由申请人提供）：迫切需要开发可靠和准确的检测和鉴定低浓度循环肿瘤细胞（ctc）的方法。特别有吸引力的是全血样本中ctc的检测，可以在服务点实施。血液中非常小的CTC丰度构成了巨大的技术挑战，阻止了直接检测，并且需要在任何传感/诊断测量之前分离/富集CTC。纳米技术的最新进展能够将分离/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而准确的全血样本ctc检测平台，该平台将ctc的选择性捕获与其独特的光谱指纹相结合。我们的方法是基于肿瘤细胞膜的表面增强红外吸收光谱（SEIRAS），使用一种新的基于超材料的等离子体平台：法诺共振不对称超材料（FRAMMs）。基于fram的不同红外“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。为了提高目标细胞附着在传感器上的特异性和鲁棒性，所有FRAMM像素将被一系列抗体功能化。细胞与底物的结合将使用差反射率FTIR进行查询

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.