DNA-carbon Assemblies for Multispectral Imaging

描述(申请人提供)：这项研究的目的是利用DNA主干构建分子定义的石墨烯和石墨的碳氢化合物片段，以形成高荧光组件。这些DNA-碳组件具有许多半导体量子点的有用的光物理特性。然而，它们为这些量子点的许多局限性提供了解决方案：它们结构均匀，易于合成，很容易与生物分子结合，具有细胞渗透性，几乎没有毒性。这项工作在几个方面都是新颖的：它提供了一种组装具有完全结构控制的层状碳氢化合物(石墨烯)薄片的新方法；它提供了这些不寻常的量子发光组件的新型生物偶联物；它提供了能够同时对多个细胞抗原进行成像的新标记。我们的初步工作表明，这种DNA-碳组件(CA)是多光谱标记，是细胞穿透的，可以很容易地与抗体和其他感兴趣的蛋白质结合。然而，要开发这些用于生物医学应用的DNA-CA，还需要做更多的工作。我们的具体研究计划是系统地改变CA的大小和几何形状，以更好地了解结构如何影响其基本光物理性质。利用这些知识，我们将构建在广泛波长范围内发射的CA，用于多光谱成像的实际应用；我们将为它们的生物结合开发新的策略；然后我们将通过两种方法将它们应用于生物和临床相关抗原的成像。这项研究对基础生物医学和应用生物医学都具有重要意义。我们的方法提供了对纳米级分层碳组件的完全结构控制，通过产生可重复和易于制造的结构解决了该领域的一个主要问题。我们的结构设计保留了量子点有用的光物理性质，同时解决了它们在生物应用中的许多主要限制：难以结合、多价、溶解性差、毒性、细胞渗透性差。我们期待这项工作的近期有用结果，包括可广泛应用于生物成像的标记，以及多抗原成像在B细胞淋巴瘤诊断中的改进方法的展示。

DESCRIPTION (provided by applicant): This research is aimed at the use of the DNA backbone to construct molecularly defined hydrocarbon fragments of graphene and graphite to form highly fluorescent assemblies. These DNA-carbon assemblies possess many of the useful photophysical characteristics of semiconductor quantum dots. However, they offer solutions to many of the limitations of those quantum dots: they are structurally homogeneous, are easily synthesized and readily conjugated to biomolecules, are cell permeable, and have little or no toxicity. This work is novel in several ways: it offers a new way to assemble layered hydrocabon (graphene) sheets with complete structural control; it offers novel bioconjugates of these unusual quantum luminescent assemblies; and it provides new labels that enable the imaging of multiple cellular antigens simultaneously. Our preliminary work has shown that such DNA-carbon assemblies (CAs) are multispectral labels that are cell-permeable and can be easily conjugated to antibodies and other proteins of interest. To develop these DNA-CAs for biomedical applications, however, more work is needed. Our specific research plans are to vary CA size and geometry systematically to gain an improved understanding of how structure influences their basic photophysical properties. Using this knowledge, we will construct CAs emitting in a wide range of wavelengths for practical applications in multispectral imaging; we will develop new strategies for their bioconjugation; and we will then apply them in imaging biologically and clinically relevant antigens by two approaches. This research will be important both to basic biomedical science and to applied biomedicine. Our approach offers complete structural control over nanometer-scale layered carbon assemblies, solving a major problem in the field by yielding repeatable and easily produced structures. Our structural design retains the useful photophysical properties of quantum dots, while addressing many of their major limitations in biological applications: difficult conjugation, polyvalency, poor solubility, toxiciy, poor cell permeability. We expect near-term useful results from this work, including labels that can be broadly applied in biological imaging, and demonstration of improved methods for multiantigen imaging in diagnosis of B-cell lymphomas.