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.
DNA-templated silver clusters (AgN-DNA) are
known to
exhibit a wide range of fluorescence colors for different choices
of the DNA template sequence. While these clusters are promising biosensors
and biomarkers, rational design of AgN-DNA is challenged
by the huge space of possible DNA template sequences. Recent work
employed machine learning methods trained on experimental data to
design new DNA templates that select for AgN-DNA color,
for the specific case of 10-base DNA oligomers. An important open
question is whether such a design process developed for a specific
biopolymer template length is applicable at other lengths, with different
numbers and diverse configurations of cluster nucleation sites. Here,
we develop a flexible design approach that builds on color-correlated
DNA base motifs learned from data on more than 2000 10-base DNA oligomers.
We test this motif-based design for templates ranging from 8 bases
to 16 bases long, for which the sizes of the sequence spaces differ
by nearly 5 orders of magnitude. The experimental data show that designed
strands of all lengths are selective for AgN-DNA color
in the target wavelength band of 600–660 nm, strongly suggesting
that color-selective motifs learned for one template length generalize
to other lengths. Thus, a motif-based design approach may be broadly
suitable for future AgN-DNA applications.
We present an inexpensive, generalizable approach for modifying visible wavelength fluorescence microplate readers to detect emission in the near-infrared (NIR) I (650–950 nm) and NIR II (1000-1350 nm) tissue imaging windows. These wavelength ranges are promising for high sensitivity fluorescence-based cell assays and biological imaging, but the inaccessibility of NIR microplate readers is limiting development of the requisite, biocompatible fluorescent probes. Our modifications enable rapid screening of NIR candidate probes, using short pulses of UV light to provide excitation of diverse systems including dye molecules, semiconductor quantum dots, and metal clusters. To confirm the utility of our approach for rapid discovery of new NIR probes, we examine the silver cluster synthesis products formed on 375 candidate DNA strands that were originally designed to produce green-emitting, DNA-stabilized silver clusters. The fast, sensitive system developed here discovered DNA strands that unexpectedly stabilize NIR-emitting silver clusters.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.