Triplex-structure based DNA circuits with ultra-low leakage and high signal-to-noise ratio

DNA circuits are powerful tools in various applications such as logical computation,molecular diagnosis and synthetic biology.Leakage is a major problem in constructing complex DNA circuits.It directly affects the output signal and harms the circuit’s performance significantly.In the traditional DNA circuits,the gate complex is a duplex structure.There are insufficient energy barriers to prevent spontaneous detachment of strands,resulting in a leak prone.Herein,we have developed triplex-structure based DNA circuit with ultra-low leakage and high signal-to-noise ratio(SNR).The triplex structure improves the stability in the absence of input.At the same time,the driving force of the strand displacement cascades reduces the influence of the triplex structure on the desired reaction.The SNR of the DNA circuit was increased to 695,while the desired reaction rate remained 90%of the conventional translator circuit.The triplex-structure mediated leakage prevention strategy was further tested at different temperatures and in DNA translator and seesaw circuits.We also constructed modular basic logic gates with a high efficiency and low leakage.On this basis,we further constructed triplex-structure based tertiary DNA logic circuits,and the SNR reached 295,which,to the best of our knowledge,was among the highest of the field.We believe that our scheme provides a novel,valid,and general tool for reducing leakages,and we anticipate that it will be widely adopted in DNA nanotechnology.

Cascaded DNA circuits-programmed self-assembly of spherical nucleic acids for high signal amplification

Signal amplification is an important issue in DNA nanotechnology and molecular diagnostics.In this work,we report a strategy for the catalytic self-assembly of spherical nucleic acids(SNAs)programmed by two-layer cascaded DNA circuits through integrating an entropy-driven catalytic network,a catalytic hairpin assembly circuit,and a facile SNA assembly-based reporter system.This integrated system could implement^100,000-fold signal amplification in the presence of 1 pM of input target.Possessing powerful amplification ability of nucleic acid signal,our strategy should be of great potential in fabricating more robust dynamic networks to be applied for signal transduction,DNA computing,and nucleic acid-based diagnostics.

Locked nucleic acids based DNA circuits with ultra-low leakage

DNA circuits based on toehold-mediated DNA strand displacement reaction are powerful tools owing to their programmability and predictability.However,performance and practical application of the circuits are greatly restricted by leakage,which refers to the fact that there is no input(invading strand)in the circuit,and the output signal is still generated.Herein,we constructed locked nucleic acids-based DNA circuits with ultra-low leakage.High binding affinity of LNA(locked nucleic acid)-DNA/LNA suppressed the leakage by inhibiting the breathing effect.Based on the strategy,we have built various low-leakage DNA circuits,including translator circuit,catalytic hairpin assembly(CHA)circuit,entropy-driven circuit(EDC),and seesaw circuit.More importantly,our strategy would not affect the desired main reactions:The output signal remained above 85%for all tested circuits,and the signalto-noise ratios were elevated to 148.8-fold at the most.We believe our strategy will greatly promote the development and application of DNA circuits-based DNA nanotechnology.

Programming cell entry of molecules via reversible synthetic DNA circuits on cell membrane

Cellular uptake of biomolecules is crucial for regulating cell function.However,powerful and biocompatible tools for dynamically manipulating the cell entry of single-stranded DNAs(ssDNAs)remain elusive.Herein,we constructed synthetic DNA circuits on the cell membrane to program the cell entry of ssDNAs,using toehold-mediated DNA strand displacement reactions.We found that the dimerization and trimerization of cholesterol-ssDNAs enhanced membrane-anchoring and cellular uptake of ssDNAs.Moreover,we demonstrated that de-dimerization and de-trimerization of cholesterol-ssDNAs could be accomplished by inputting recovery ssDNAs into the synthetic DNA circuits,which could simultaneously decrease the cellular uptake of ssDNAs.We speculate that operating the synthetic DNA circuits on the cell membrane will be a powerful strategy for regulating the cellular uptake of exogenous materials,which has important implications for bioimaging,drug delivery,and gene therapy.

Closed circle DNA algorithm of change positive-weighted Hamilton circuit problem

Chain length of closed circle DNA is equal. The same closed circle DNA＇s position corresponds to different recognition sequence, and the same recognition sequence corresponds to different foreign DNA segment, so closed circle DNA computing model is generalized. For change positive-weighted Hamilton circuit problem, closed circle DNA algorithm is put forward. First, three groups of DNA encoding are encoded for all arcs, and deck groups are designed for all vertices. All possible solutions are composed. Then, the feasible solutions are filtered out by using group detect experiment, and the optimization solutions are obtained by using group insert experiment and electrophoresis experiment. Finally, all optimization solutions are found by using detect experiment. Complexity of algorithm is concluded and validity of DNA algorithm is explained by an example. Three dominances of the closed circle DNA algorithm are analyzed, and characteristics and dominances of group delete experiment are discussed.

DNA计算的研究进展

DNA计算是近年来出现的一种新的自然计算方法,因为其具有高度的并行性和海量的存储能力,引起了科学家的关注.本文将主要从DNA计算模型、布尔电路的模拟、基于DNA的大规模数据库及其在生物信息学中的应用等几个方面,介绍DNA计算近年来的研究和发展状况.最后,我们对DNA计算研究的前景和今后的发展方向进行了展望.

DNA计算研究概述与分析

基于生化反应机理的DNA计算模型受到科学领域内许多不同学科学者们的关注。DNA计算已经形成国际科学前沿领域内研究的一个新的热点。主要介绍了Sticker模型的应用及布尔电路的仿真应用,并分析了DNA计算模型中存在的问题。最后,简要介绍了DNA计算研究存在的问题及未来的研究方向。

DNA链置换技术的研究现状与展望

综述了利用DNA分子元件构造人工逻辑生化电路的新技术——DNA链置换技术在构造逻辑门运算模型、生化逻辑电路与神经网络、DNA纳米机器人、DNA反应网络等领域的研究进展,并通过对半加器/全加器逻辑运算模型和编码器逻辑运算模型的设计及仿真,对DNA链置换技术的相关应用进行了实验验证.在此基础上提出:构建运动及功能型DNA纳米机器,整合DNA逻辑门、自底向上地构建DNA计算机体系结构,将是DNA链置换技术应用的发展方向.

基于DNA链置换反应的自然数素性判定问题研究

借助自组装DNA计算的显著优势,采用DNA链置换反应原理开展了自然数的素性判定问题研究.首先,构造了有关DNA分子逻辑门,并构建了相应的DNA分子计算模型,然后设计了用于自然数素性判定的分子逻辑电路.最后基于Visual DSD仿真平台,对分子逻辑电路进行仿真.结果表明:采用的分子逻辑电路能够实现自然数的素性判断.

基于DNA链置换反应的编码器逻辑运算模型研究

作为自组装DNA计算领域中一门新技术,DNA链置换反应在分子计算领域得到了广泛的应用.基于自组装DNA计算原理,设计了对应不同逻辑门的DNA分子电路.基于DNA链置换反应机理构建了编码器逻辑电路的分子计算模型.当输入DNA分子信号链时,将不同分子浓度比的DNA分子逻辑门电路混合,借助分子间的特异性杂交反应及分子间链置换反应,最终可输出信号链分子.Visual DSD仿真结果表明了本文设计的编码器逻辑计算模型的可行性与准确性.为拓展分子逻辑电路的应用做出有益的探索.

哈密顿回路问题的DNA表面计算模型

基于生化反应原理的DNA计算具有强大的并行运算能力,DNA计算机在求解NP问题上存在着硅计算机无法比拟的先天的优越性。论文采用荧光标记的策略,给出了一种新的哈密顿回路问题的DNA表面计算模型。该模型首先将问题解空间的DNA分子固定在固体载体上,然后通过进行相应的生化反应来求得哈密顿回路问题的所有解。在新模型中,解空间的生成过程与边的排列顺序无关。

哈密尔顿回路问题的DNA表面计算模型

首次提出用DNA表面计算模型来解决无向图哈密尔顿回路问题。该模型基于哈密尔顿回路问题的解空间,将问题解空间的DNA分子固定在固体载体上,对其进行荧光标记,然后通过相应的生化反应筛选出哈密尔顿回路问题的所有解。与已有的哈密尔顿路径问题的其它模型相比,新模型具有错误率低,编码简易,读取方便等更好的性能。

DNA计算研究现状

随着科学技术的飞速发展,人们对计算机性能提升的需求愈发迫切.然而,传统的基于硅的计算机性能几乎已经达到了极限,很难再实现大的提升.DNA计算凭借其出色的并行处理能力,巨大的数据存储量以及运行的低能耗在目前计算技术领域受到极高的关注,成为了研究的重点.文章介绍了DNA计算近几年的最新研究成果,重点阐述了DNA逻辑电路的最新发展,对DNA计算在密码学、生物医疗及仿真软件等不同领域的综合应用进行了总结与展望.

DNA优化的BP神经网络在故障诊断中的应用

针对BP神经网络收敛速度慢和容易陷入局部极小值问题,将DNA算法和神经网络有机结合,利用DNA算法的全局搜索能力,优化网络的初始权值和阈值,解决其本身固有的两个缺陷,进而提高了BP神经网络诊断故障时的准确性和快速性。以道岔控制电路的故障诊断为研究对象,建立了基于DNA优化的BP神经网络的故障诊断优化模型,使用MATLAB仿真软件对故障诊断模型进行了仿真分析。结果表明,DNA算法优化的BP神经网络的泛化能力、诊断精确性都要优于BP神经网络。

运用DNA计算解决最短路径问题

用通俗易懂的语言解释了最短路概念以及解决多顶点最短路问题面临的困境,介绍了DNA计算的研究背景,阐明了DNA计算解决最短路的优势以及算法步骤,并对DNA计算的未来发展作出展望。

异或门的DNA计算模型

利用DNA链置换反应分别求解二输入和三输入异或门逻辑电路.对于二输入异或门电路,将不同输入值编译成不同数量输入链,将特定数量的输入链加入反应器中,与反应器中的反应链发生链置换反应,充分反应后,通过判断检验器中绿色荧光分子明灭从而得到异或门电路的解;二输入异或门逻辑电路可以推广到三输入异或门逻辑电路.该方法具有操作简单,实验成本低,可行性高等优点.

基于单链DNA开关调控的多功能生物电路（英文）

合成生物电路在生物传感及生物计算方面成为了广泛应用的工具。工程化生物电路系统具有良好的灵活性,同时也具备模块化的特征。在本文中,研究了基于单链DNA开关调控的多功能生物电路的构建方法。通过将计算机辅助设计的单链DNA开关作为核心控制元件,并利用长度为20 bp的toehold区域来激活单链DNA开关,驱动了简单的单向式、循环式以及级联的多层次的生物电路系统。在级联式电路系统中,通过调整单链DNA开关的结构,使信噪比从2.996变成5.274。同时,单链DNA开关作为长单链DNA(784 bp)的一部分,在无细胞蛋白质系统中实现了基因表达调控。因此,本文研究的工程化方法为今后复杂的人工生物电路的构建提供了坚实的技术基础。

DNA计算中的可级联分子全加器

DNA链置换技术是近年来DNA计算领域的一个重要研究方向,它是在DNA粘贴模型基础上发展起来的一种动态DNA分子计算方法.这种方法以DNA编码序列中的toehold域为起点,通过覆盖置换域上的链来完成链置换.文章讨论了以这种方法为出发点设计的一种由分子逻辑门器件构成的分子全加器,并使用Visual DSD软件进行了仿真实验.实验结果表明,文章中提出的分子全加器是可行的,并且它还可以通过级联实现任意多位加法运算.

分子计算机的研究进展

研制分子计算机也许是突破传统半导体电子计算机发展极限的唯一出路。本文简述了最近十年分子计算机的研究进展 ,重点讨论了 DNA计算机和生物分子计算机的研究成果 ,并对可能为人类提供思考和尝试范本的生物活细胞中蛋白质的各种计算机制的研究给予了充分的关注。引用了 43篇文献。

有源磁控忆阻超混沌电路实现及图像加密

在一个广义三阶Rucklidge系统的基础上提出基于二次非线性有源磁控忆阻器的四阶超混沌电路系统。对该系统的动力学行为进行理论分析和数值仿真,系统相图、Lyapunov指数谱、分岔图和共存吸引子均表明该系统具有丰富的动力学行为和新的拓扑结构。并利用Multisim电路仿真软件和FPGA数字硬件电路设计实现了该系统的电路,实验结果与数值仿真结果一致。最后将置乱-扩散算法与DNA加密相结合设计了一种图像加密算法,利用新系统混沌序列对图像进行加密,并对加密后的图像进行了加密直方图、相邻像素相关性、敏感性、鲁棒性和信息熵等分析。结果表明,新系统对混沌密钥及明文都非常敏感,密钥空间较大,提出的混沌系统应用于图像加密具有较高的安全性能。