Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution
Tip-Enhanced Raman Imaging of Single-Stranded DNA with Single Base Resolution
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DOI：
10.1021/jacs.8b11506
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发表时间：
2019-01-16
影响因子：
15
通讯作者：
Scully, Marlan O.
中科院分区：
文献类型：
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作者：
He, Zhe;Han, Zehua;Scully, Marlan O.
尖端增强拉曼散射是一种很有前途的光学和分析技术，用于单分子分辨率的化学成像和传感。特别是，由银尖端与金底物耦合的间隙模式配置产生的TERS信号可以以低于1nm的空间分辨率分辨单链DNA （ssDNA）分子。为了证明亚纳米分辨率的证据，我们展示了使用噬菌体ssDNA （M13mp18）的直接核酸测序。M13mp18提供了一个已知的序列，通过我们的沉积策略，它可以被拉伸（展开）并通过其磷酸基团附着在底物上，同时将其核碱基暴露在尖端。沉积后，我们沿着ssDNA扫描银尖，并以0.5 nm的步长收集TERS信号，这相当于两个相邻DNA碱基之间的键长。通过演示ssDNA结构的实时分析，以及其他生物聚合物单体单元的独特TERS信号，我们预计该技术可以扩展到各种纳米结构的高分辨率成像以及其他重要生物聚合物的直接测序，包括RNA，多糖和多肽。
Tip-enhanced Raman scattering (TERS) is a promising optical and analytical technique for chemical imaging and sensing at single molecule resolution. In particular, TERS signals generated by a gap-mode configuration where a silver tip is coupled with a gold substrate can resolve a single-stranded DNA (ssDNA) molecule with a spatial resolution below 1 nm. To demonstrate the proof of subnanometer resolution, we show direct nucleic acid sequencing using TERS of a phage ssDNA (M13mp18). M13mp18 provides a known sequence and, through our deposition strategy, can be stretched (uncoiled) and attached to the substrate by its phosphate groups, while exposing its nucleobases to the tip. After deposition, we scan the silver tip along the ssDNA and collect TERS signals with a step of 0.5 nm, comparable to the bond length between two adjacent DNA bases. By demonstrating the real-time profiling of a ssDNA configuration and furthermore, with unique TERS signals of monomeric units of other biopolymers, we anticipate that this technique can be extended to the high-resolution imaging of various nanostructures as well as the direct sequencing of other important biopolymers including RNA, polysaccharides, and polypeptides.