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

技术摘要加州大学圣巴巴拉分校的伊丽莎白·格温得到了计算和数据驱动材料研究计划颁发的奖项的支持，该奖项旨在将计算机器学习工具与从快速、阵列格式光学表征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。具体地说，这项工作将研究荧光的、DNA稳定的、少原子的金属纳米团簇，或DNA-MNC。基于银团簇的DNA-MNC已经开始用于创新的成像、分子逻辑和选择性传感器应用。最近发现的铜基DNA-MNC表明，DNA主体中荧光团簇的形成可能适用于其他硬币金属。PI先前的工作揭示了银团簇荧光对宿主DNA的序列和二级结构的特殊敏感性。对不同DNA链的小集合研究发现，DNA-AgNC的荧光颜色跨度为500-900 nm。再加上与DNA纳米技术获得的最精细分辨率兼容的紧凑尺寸的DNA-MNC，这种宽广的颜色空间可能会在当前的解决方案应用之外开辟新的领域，在纳米级光子阵列中用于信息处理和生化和物理事件的信号发送。然而，目前基本上还没有关于DNA-MNC的性质与宿主DNA序列之间的关系的了解。即使对于相对研究较好的DNA-AgNC，也没有确定的序列基序来控制荧光的颜色、亮度或稳定性。尽管这些性质对所有应用和基础材料科学都很重要，但这一点仍然存在。但是，只有大约100条链被检测为化学稳定的DNA-AgNCs的潜在宿主。这是可能序列空间的极小样本。这项研究旨在通过将机器学习工具应用于更大的、战略性地选择的数据集，来破解支配DNA-MNC属性的序列特征的代码。这些数据将通过机器人合成和快速阵列光学表征银基DNA-MNC来获得。链选择将利用在PI以前的工作中开发的DNA-AgNC的知识。为了阐明形成星团的特定金属的作用，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的培训。高中生将通过UCSB的科学思想学院(SST)接触到这项工作的各个方面。非技术摘要这项工作重点放在只由几个金属原子组成的微小簇上，这些原子通过将簇包裹在短链DNA中使其在水中稳定。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，这意味着这些星团在处于激发状态后会发出光子。这些DNA包裹的、少原子的金属纳米簇可能有许多潜在的用途，例如对有毒离子以及靶向DNA和RNA链的荧光传感。这些材料最吸引人和潜在有用的特征是，不同的DNA序列可以产生不同颜色的簇。破解支配这种颜色的DNA序列特征的密码是这项工作的重点。在以前工作的基础上，主要重点将放在银团簇上，但为了阐明形成银团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的培训。高中生将通过UCSB的科学思想学院(SST)接触到这项工作的各个方面。

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).