Cracking the Color Code of DNA-stabilized Metal Nanoclusters with Rapid Optical Array Characterization and Machine Learning

加州大学圣巴巴拉分校的Elisabeth Gwinn获得了计算和数据驱动材料研究项目的奖励，该研究将计算机器学习工具与从快速阵列格式光学表征中获得的战略数据相结合，目标是发现和开发一种多功能的新型光子纳米材料。具体来说，这项工作将研究荧光、dna稳定、少原子金属纳米团簇或DNA-mNCs。基于银簇的dna跨国公司已经开始用于创新成像、分子逻辑和选择性传感器应用。最近发现的铜基DNA- mncs表明，在DNA宿主中形成荧光簇可能会推广到其他铸造金属。PI先前的工作揭示了银簇荧光对宿主DNA序列和二级结构的特殊敏感性。对各种DNA链的小组研究发现DNA- agnc具有500 - 900 nm的荧光颜色。再加上DNA- mncs的紧凑尺寸，这与DNA纳米技术获得的最佳分辨率相兼容，这种广阔的色彩空间可能会在纳米级光子阵列的信息处理和生化和物理事件的信号传导方面开辟新的领域，超越当前的解决方案应用。然而，目前对DNA- mncs的特性与宿主DNA序列的关系还没有基本的了解。即使对于研究相对充分的dna - agnc，也没有确定的控制荧光颜色、亮度或稳定性的序列基序。尽管这些性质对所有应用和基础材料科学具有根本的重要性。但是，只有约100股被检测为化学稳定的dna - agnc的潜在宿主。这是可能序列空间的一个极小的抽样。本研究旨在通过将机器学习工具应用于更大的、战略性选择的数据集，破解控制dna跨国公司属性的序列特征的代码。数据将通过机器人合成和银基dna mncs的快速阵列光学表征获得。链选择将利用PI先前工作中开发的dna - agnc知识。为了阐明形成团簇的特定金属的作用，还将对包括铜在内的其他铸币金属进行实验。参与这项工作的本科生和研究生将接受包括材料科学、计算机科学和纳米技术在内的先进技术培训。高中学生将通过UCSB的科学思想学院（SST）接触到工作的各个方面。这项工作的重点是由几个金属原子组成的微小簇，通过将簇包裹在短链DNA中，使其在水中保持稳定。多年来，人们已经知道，由几个金属原子组成的“裸”团簇具有非常有趣的光学性质。特别是，它们可以是荧光的，这意味着这些簇在处于激发态后会发射光子。这些DNA封装的、少原子的金属纳米簇可能有许多潜在的用途，如有毒离子的荧光传感和靶向DNA和RNA链。这些材料最令人着迷和潜在有用的特点是，不同的DNA序列可以产生不同颜色的簇。破解控制这种颜色的DNA序列特征的密码是这项工作的重点。在先前工作的基础上，主要重点将放在银簇上，但为了阐明形成银簇的特定金属的作用，还将对包括铜在内的其他金属进行实验。参与这项工作的本科生和研究生将接受包括材料科学、计算机科学和纳米技术在内的先进技术培训。高中学生将通过UCSB的科学思想学院（SST）接触到工作的各个方面。

Technical Abstract Elisabeth Gwinn of the University of California, Santa Barbara is supported by an award from the Computational and Data Driven Materials Research program for research to combine computational machine learning tools with strategic data obtained from fast, array format optical characterization, with the goal of discovering and developing a versatile new class of photonic nanomaterial. Specifically, the work will investigate fluorescent, DNA-stabilized, few-atom metal nanoclusters, or DNA-mNCs. DNA-mNCs based on silver clusters are already beginning to be used in innovative imaging, molecular logic, and selective sensor applications. The recent discovery of copper-based DNA-mNCs suggests that the formation of fluorescent clusters in DNA hosts may generalize to other coinage metals.The PI's prior work revealed the special sensitivity of silver cluster fluorescence to the sequence and secondary structure of the host DNA. Studies of small sets of various DNA strands have found DNA-AgNCs with fluorescence colors spanning 500 - 900 nm. Together with the compact sizes of DNA-mNCs, which are compatible with the finest resolutions accessed by DNA nanotechnology, this wide color space may open new arenas beyond current solution applications, in nanoscale photonic arrays for information processing and signaling of biochemical and physical events. However, there is essentially no current understanding of how the properties of DNA-mNCs relate to the sequence of the host DNA. Even for the relatively well-studied DNA-AgNCs, there are no identified sequence motifs that govern fluorescence color, brightness or stability. This is despite the fundamental importance of these properties to all applications, and to the underlying materials science. But, only ~100 strands have been examined as potential hosts for chemically stable DNA-AgNCs. This is a miniscule sampling of the space of possible sequences. This research aims to crack the code for the sequence characteristics that govern the properties of DNA-mNCs, by applying machine learning tools to much larger, strategically selected data sets. The data will be acquired by robotic synthesis and rapid array optical characterization of Ag-based DNA-mNCs. Strand selection will leverage the knowledge of DNA-AgNCs developed in the PI's prior work. To elucidate the role of the specific metal from which the cluster is formed, experiments on other coinage metals, including copper, will also be made.The undergraduate and graduate students who participate in the work will be trained in advanced techniques encompassing materials science, computer science and nanotechnology. High school students will be exposed to aspects of the work through UCSB's School for Scientific Thought (SST).Non-Technical AbstractThis work focuses on tiny clusters composed of just a few atoms of metal, that are made stable in water by wrapping the clusters up in short strands of DNA. It has been known for many years that "bare" clusters made of a few metal atoms have very interesting optical properties. In particular, they can be fluorescent, meaning that the clusters emit photons after they are placed in an excited state. These DNA-encapsulated, few-atom metal nanoclusters may have many potential uses, such as fluorescent sensing of toxic ions and of targeted DNA and RNA strands. The most fascinating and potentially useful feature of these materials is the fact that different DNA sequences can produce clusters of different color. Cracking the code for the DNA sequence characteristics that govern this color is the focus of this work. The primary focus will be on silver clusters, building on previous work, but to elucidate the role of the specific metal from which the cluster is formed, experiments on other metals, including copper, will also be carried out. The undergraduate and graduate students who participate in the work will be trained in advanced techniques encompassing materials science, computer science and nanotechnology. High school students will be exposed to aspects of the work through UCSB's School for Scientific Thought (SST).