Advanced Probes Apexed by Carbon Nanotubes for Biomaterials Science and Cellular

描述（由申请人提供）：长期目标是开发一系列专为生物材料表征、细胞成像和位点特异性单细胞手术定制的先进探针。每个探针的最顶部或顶点被设计为具有一个或多个碳纳米管，其几何形状和机械结构基于应用的需求而设计。该SBIR第I阶段的具体目标是制造基于CNT的SPM探针，其对几何形状和力学具有上级控制，因此这些探针适用于难以实现的应用：例如生物成像、单细胞手术、触发和探测细胞信号传导过程以及最终的细胞行为。计划开展三个项目：（1）用于高分辨率成像的单根CNT基AFM探针的生产;（2）用于位点特异性细胞穿透的CNT基AFM探针的生产;（3）由顶点处的两个CNT组成的AFM探针的生产及其在研究细胞信号传导过程中的应用。这些项目将由COVS（基于CNT的探针的先进制造）和UCD（生物材料和细胞的高分辨率成像，以及单细胞水平的细胞力学和信号传导的研究）的共同努力完成。这种合作已经证明了原理的证明，拟议的努力应该揭示这些探针的优越性和应用潜力。与现有技术相比，利用这些探针的优点包括：（a）由于管的直径为1 nm和高纵横比，因此具有高分辨率和大的成像范围;（B）能够穿透单个细胞而不干扰其功能;（c）能够在单个细胞水平上获得位点特异性穿透，从而能够在单个细胞内递送药物和在特定位点进行手术;（d）支持设计的化学官能团以增强对比度或触发特定细胞信号传导过程的能力。在第一阶段成功的基础上，我们计划在第二阶段大规模生产和商业化基于CNT的探针，用于生物成像和软材料成像的通用应用，以及生产客户特定的单，双和多个基于CNT的探针，用于细胞生物学研究的触发和调查。我们希望这些基于碳纳米管的探针将取代现有的微加工AFM杠杆在软材料成像的竞技场，以及在细胞生物学研究中提供新的应用，其中AFM应用的市场潜力继续迅速增长。公共卫生相关性：COVS计划制造基于碳纳米管（CNT）的AFM探针，具有客户所需的几何形状，长度和力学。这些探针在诸如蛋白质和细胞的软材料的结构表征以及在位点特异性渗透到细胞（包括细胞质和细胞核）中方面具有巨大的潜力。该SBIR阶段I代表了制造基于CNT的AFM探针的初始步骤，其上级性能使其适用于难以实现的应用，例如生物成像，单细胞手术，触发和探测细胞信号传导过程以及最终的细胞行为，其中对人类健康非常重要。

DESCRIPTION (provided by applicant): The long-term goal is to develop a series of advanced probes tailored for biomaterials characterization, cell imaging, and site-specific single cell surgery. The very top or the apex of each probe is engineered to have one or multiple carbon nanotubes whose geometry and mechanics are engineered based on the applications' needs. The specific goal for this SBIR Phase I is to manufacture CNT based SPM probes with superior control over their geometry and mechanics, and as such those probes are suitable for applications that are otherwise difficult to realize: e.g. bioimaging, single cell surgery, triggering and probing cellular signaling process and ultimately cellular behaviors. Three projects are planned: (1) Production of single CNT based AFM probes for high-resolution imaging; (2) Production of CNT based AFM probes for their applications in site specific cell penetration; (3) Production of AFM probes consisting of two CNTs at the apex and their applications in studying cellular signaling processes. These projects will be accomplished by the joint effort of COVS (advanced fabrication of CNT based probes) and UCD (high resolution imaging of biomaterials and cells, as well as investigation of cell mechanics and signaling at the single cell level). This collaboration has demonstrated the proof-of-principle and the proposed effort should reveal the superiority and application potential of those probes. The advantages of utilizing these probes over current state-of-the-art include: (a) high resolution and large imaging range, due to the 1 nm diameter of the tube and high aspect ratio; (b) ability to penetrate an individual cell without perturbing its function; (c) ability to attain site specific penetration at single cell level, thus to enable drug delivery within individual cells and surgery at specific sites; (d) ability to support designed chemical functional groups to enhance contrast or to trigger specific cellular signaling process. Building on the success of Phase I, we plan to massively produce and commercialize CNT based probes in Phase II for generic application of bioimaging and soft materials imaging, as well as to produce customer specific single, double and multiple CNT based probes for the triggering and investigation of cellular biology research. We hope these CNT based probes will replace existing microfabricated AFM cantilevers in the arena of soft materials imaging, as well as provide new applications in cellular biology research, where the market potential of AFM application continue to grow rapidly. PUBLIC HEALTH RELEVANCE: COVS plans to manufacture carbon nanotube (CNT) based AFM probes with customer desired geometry, length and mechanics. These probes have great potential in the structural characterization of soft materials such as proteins and cells as well as in site-specific penetration into cells, including cytoplasm and nuclei. This SBIR Phase I represents the initial steps of manufacturing CNT based AFM probes for their superior performance making them suitable for applications that are otherwise difficult to realize, e.g. bioimaging, single cell surgery, triggering and probing cellular signaling processes and ultimately cellular behaviors, of which are of great importance to human health.