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先进的探针，用于生物材料表征、细胞成像和特定部位的单细胞手术。每个探头的顶端或顶端都被设计成具有一个或多个碳纳米管，其几何结构和机械结构是根据应用的需要进行设计的。SBIR第一阶段的具体目标是制造对其几何和力学具有卓越控制的基于碳纳米管的SPM探针，因此这些探针适用于其他难以实现的应用：例如生物成像、单细胞手术、触发和探测细胞信号过程以及最终的细胞行为。计划开展三个项目：(1)生产用于高分辨率成像的单个碳纳米管AFM探针；(2)生产用于特定部位细胞穿透的碳纳米管AFM探针；(3)生产由两个碳纳米管组成的AFM探针及其在研究细胞信号过程中的应用。这些项目将通过COVS(基于碳纳米管的探针的先进制造)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研究)的共同努力来完成。这一合作证明了原则的证明，拟议的努力应该揭示这些探头的优势和应用潜力。与目前最先进的探头相比，使用这些探头的优势包括：(A)高分辨率和大成像范围，因为管子的直径为1 nm，长宽比高；(B)能够在不干扰其功能的情况下穿透单个细胞；(C)能够在单个细胞水平上实现特定部位的穿透，从而能够在单个细胞内给药和在特定部位进行手术；(D)能够支持设计的化学官能团，以增强对比度或触发特定的细胞信号过程。在第一阶段取得成功的基础上，我们计划在第二阶段大规模生产和商业化基于碳纳米管的探针，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、双和多碳纳米管探针，用于触发和研究细胞生物学研究。我们希望这些基于碳纳米管的探针将在软材料成像领域取代现有的微制AFM悬臂，并在AFM应用的市场潜力继续快速增长的细胞生物学研究中提供新的应用。与公众健康相关：COVS计划制造基于碳纳米管(CNT)的AFM探头，具有客户所需的几何形状、长度和机械性能。这些探针在蛋白质和细胞等软材料的结构表征以及定位穿透细胞(包括细胞质和细胞核)方面具有巨大的潜力。该SBIR第一阶段代表了制造基于CNT的AFM探针的第一步，因为其卓越的性能使其适合于其他难以实现的应用，例如生物成像、单细胞手术、触发和探测细胞信号过程以及最终对人类健康非常重要的细胞行为。

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.