Fluorescence Color by Data-Driven Design of Genomic Silver Clusters

Abstract

DNA nucleobase sequence controls the size of DNA-stabilized silver clusters, leading to their well-known yet little understood sequence-tuned colors. The enormous space of possible DNA sequences for templating clusters has challenged the understanding of how sequence selects cluster properties and has limited the design of applications that employ these clusters. We investigate the genomic role of DNA sequence for fluorescent silver clusters using a data-driven approach. Employing rapid parallel silver cluster synthesis and fluorimetry, we determine the fluorescence spectra of silver cluster products stabilized by 1432 distinct DNA oligomers. By applying pattern recognition algorithms to this large experimental data set, we discover certain DNA base patterns, or "motifs," that correlate to silver clusters with similar fluorescence spectra. These motifs are employed in machine learning classifiers to predictively design DNA template sequences for specific fluorescence color bands. Our method improves selectivity of templates by 330% for silver clusters with peak emission wavelengths beyond 660 nm. The discovered base motifs also provide physical insights into how DNA sequence controls silver cluster size and color. This predictive design approach for color of DNA-stabilized silver clusters exhibits the potential of machine learning and data mining to increase the precision and efficiency of nanomaterials design, even for a soft-matter-inorganic hybrid system characterized by an extremely large parameter space.

Mutation of position 5 as a crystal engineering tool for a NIR-emitting DNA-stabilized Ag16 nanocluster

“…Screening of DNA sequences and machine-learning algorithms have assisted in recent years to discover a series of interesting DNA-AgNCs and started to unravel the intricate relationship of sequences versus the final photophysical properties of the encapsulated AgNC. [14][15][16][17] We recently reported the crystal structure of a Ag 16 NC that can be stabilized by either two 5'-CACCTAGCGA-3' strands (here referred to as T5) 9 or two shortened versions without the terminal adenosine: 5'-CACCTAGCG-3' (here referred to as T5-A 10 ). 18 An intriguing finding of these studies was that the thymine in position 5 is pointed outwards and does not interact with the Ag 16 NC.…”

Unusually large fluorescence quantum yield for a near-infrared emitting DNA-stabilized silver nanocluster

“…2,3 The easiest way to tune the optical properties is by varying the DNA sequence, which has an effect on the type of silver cluster that can be stabilized. [3][4][5] Not all DNA sequences yield DNA-AgNCs with useful properties, e.g. high brightness or photostability.…”

“…This 10-base DNA oligomer was initially reported by Copp et al in a study on the relationship between emission color and DNA sequence. 4 The NIR part of the electromagnetic spectrum is of particular interest for imaging biological material due to regions of high transparency. 12 However, a drawback of designing fluorophores in the NIR range is that, due to the small energy gap between excited state and ground state, non-radiative decay pathways tend to outcompete the radiative pathways, resulting in low fluorescence quantum yields.…”

Crystal structure of a NIR‐Emitting DNA‐Stabilized Ag16 Nanocluster

“…The sequence employed here was selected from a large data set developed by Copp et al. who used machine learning tools for prediction of sequences that stabilize fluorescent AgNCs with designed colors . In order to verify that the crystal structure of the DNA–Ag 16 NC did not dramatically differ from the solution structure, fluorescence measurements were performed.…”