Molecular logic devices (MLDs) constructed from DNA are promising for applications in bioanalysis, computing, and other applications requiring Boolean logic. These MLDs accept oligonucleotide inputs and generate fluorescence output through changes in structure. Although fluorescent dyes are most common in MLD designs, nontraditional luminescent materials with unique optical properties can potentially enhance MLD capabilities. In this context, luminescent lanthanide complexes (LLCs) have been largely overlooked. Here, we demonstrate a set of high-contrast DNA photonic logic gates based on toehold-mediated strand displacement and time-gated FRET. The gates include NAND, NOR, OR, and AND designs that accept two unlabeled target oligonucleotide sequences as inputs. Bright “true” output states utilize time-gated, FRET-sensitized emission from an Alexa Fluor 546 (A546) dye acceptor paired with a luminescent terbium cryptate (Tb) donor. Dark “false” output states are generated through either displacement of the A546, or through competitive and sequential quenching of the Tb or A546 by a dark quencher. Time-gated FRET and the long luminescence lifetime and spectrally narrow emission lines of the Tb donor enable 4–10-fold contrast between Boolean outputs, ≤10% signal variation for a common output, multicolor implementation of two logic gates in parallel, and effective performance in buffer and serum. These metrics exceed those reported for many other logic gate designs with only fluorescent dyes and with other non-LLC materials. Preliminary three-input AND and NAND gates are also demonstrated. The powerful combination of an LLC FRET donor with DNA-based logic gates is anticipated to have many future applications in bioanalysis.

中文翻译：

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时控FRET和基于DNA的光子分子逻辑门：AND，OR，NAND和NOR

由DNA构成的分子逻辑设备（MLD）在生物分析，计算和其他需要布尔逻辑的应用中很有前途。这些MLD接受寡核苷酸输入，并通过结构变化产生荧光输出。尽管荧光染料在MLD设计中最常见，但是具有独特光学特性的非传统发光材料可以潜在地增强MLD功能。在这种情况下，发光镧系元素络合物（LLC）已被大大忽略。在这里，我们展示了一组基于脚趾介导的链位移和时控FRET的高对比度DNA光子逻辑门。门包括NAND，NOR，OR和AND设计，它们接受两个未标记的目标寡核苷酸序列作为输入。明亮的“真实”输出状态利用时间门控，来自Alexa Fluor 546（A546）染料受体与发光化（Tb）供体配对的FRET敏化发射。暗的“假”输出状态是通过A546的位移或通过暗猝灭剂对Tb或A546的竞争性和顺序性猝灭而产生的。Tb供体的时间门控FRET和长发光寿命以及光谱窄的发射线使布尔输出之间的对比度达到4-10倍，对于公共输出，≤10％的信号变化，并行实现两个逻辑门的多色实现，并且有效在缓冲液和血清中的性能。这些指标超过了仅使用荧光染料和其他非LLC材料的许多其他逻辑门设计所报告的指标。还演示了初步的三输入与与非门。