Label‐Free Logic Modules and Two‐Layer Cascade Based on Stem‐Loop Probes Containing a G‐Quadruplex Domain

A simple, versatile, and label‐free DNA computing strategy was designed by using toehold‐mediated strand displacement and stem‐loop probes. A full set of logic gates (YES, NOT, OR, NAND, AND, INHIBIT, NOR, XOR, XNOR) and a two‐layer logic cascade were constructed. The probes contain a G‐quadruplex domain, which was blocked or unfolded through inputs initiating strand displacement and the obviously distinguishable light‐up fluorescent signal of G‐quadruplex/NMM complex was used as the output readout. The inputs are the disease‐specific nucleotide sequences with potential for clinic diagnosis. The developed versatile computing system based on our label‐free and modular strategy might be adapted in multi‐target diagnosis through DNA hybridization and aptamer‐target interaction.     

Multiple molecular logic functions and molecular calculations facilitated by surfactant's versatility

Two isomeric compounds and , combining intramolecular charge transfer (ICT) and photoinduced electron transfer (PET) mechanisms together, were designed and used as logic gates with configurable multiple outputs; ten different logic functions (AND, NAND, OR, NOR, XNOR, INHIBIT, YES, NO, PASS 1 and PASS 0) were achieved by varying the inputs threshold or by altering the inputs; furthermore, half addition and half subtraction were performed within (or ); the concept demonstrated here may provide a strategy for constructing more integrated molecular level devices with multiple functions.     

Logic gates and elementary computing by enzymes

Different selected enzymes, glucose oxidase (GOx), catalase (Cat), glucose dehydrogenase (GDH), horseradish peroxidase (HRP), and formaldehyde dehydrogenase (FDH), are used alone or coupled to construct eight different logic gates. The added substrates for the respective enzymes, glucose and H(2)O(2), act as the gate inputs, while the biocatalytically generated gluconic acid or NADH are the output signals that follow the operation of the gates. Different enzyme-based gates are XOR, INHIBIT A, INHIBIT B, AND, OR, NOR, Identity and Inverter gates. By combining the AND and XOR or the XOR and INHIBIT A gates, the half-adder and half-subtractor are constructed, respectively, opening the way to elementary computing by the use of enzymes.     

A differential ICT based molecular probe for multi-ions and multifunction logic circuits

This paper presents anthraquinone and benzimidazole based hybrid molecular architect as the state of the art for multifunctional molecular logic circuits. The moleculator exhibits differential output behavior towards F(-), Zn(2+) and Cu(2+) ions to provide opportunities for elaboration of XOR, INHIBIT, XNOR, AND, OR, NOR, logic functions and their integrated logic functions half-adder, half-subtractor and comparator within a single molecule. These integral logic functions can be reprogrammed by self-annihilation or by another additional input in the same cell. This single molecule behaves uniquely where different logic functions can be operated and reset by using different inputs and outputs.     

Fluorescent Molecular Logic Gates Driven by Temperature and by Protons in Solution and on Solid

Temperature-driven fluorescent NOT logic is demonstrated by exploiting predissociation in a 1,3,5-trisubstituted Δ²-pyrazoline on its own and when grafted onto silica microparticles. Related Δ²-pyrazolines become proton-driven YES and NOT logic gates on the basis of fluorescent photoinduced electron transfer (PET) switches. Additional PASS 1 and YES+PASS 1 logic gates on silica are also demonstrated within the same family. Beside these small-molecule systems, a polymeric molecular thermometer based on a benzofurazan-derivatized N-isopropylacrylamide copolymer is attached to silica to produce temperature-driven fluorescent YES logic.     

分子基逻辑材料*

在适当的条件下分子开关将输入的信息转换为输出信号,利用这一特点,可在分子体系根据二进位布尔逻辑规则实现信号转换。目前,用化学体系进行基本的布尔逻辑功能执行 (PASS、YES、NOT、AND、NAND、OR、NOR、XNOR和INH)都已成为可能。在此基础上,逻辑门的整合与编程,以及更进一步的复杂分子运算开始受到人们的关注。迄今为止,以高灵敏性的荧光输出信号为主,人们在分子水平上设计实现了多种复杂的逻辑电路,包括组合逻辑电路和时序逻辑电路等,并开始涉及信息处理的安全平台设计。本文主要介绍了近年来利用分子荧光开关体系模拟数字逻辑电路过程中所取得的最新进展,对分子逻辑电路研究的热点和问题进行了展望。     

Resettable fluorescence logic gate based on calcein/layered double hydroxide ultrathin films

A fluorescent logic gate was fabricated based on calcein/layered double hydroxide ultrathin films (UTFs) via alternate assembly technique, which exhibits high stability, reversibility, and resettability. The logic gate was manipulated by utilizing pH value, Hg(2+) and Cl(-) ion as inputs, and the fluorescence emission of the (calcein/LDH)(16) UTF as output, serving as a three-input logic gate that combines the YES and INHIBIT operation.     

以DNA为模板的银纳米簇荧光检测及逻辑门的构建

以DNA为模板, 合成了具有荧光性质的银纳米簇(DNA-Ag NCs), 利用荧光光谱、 紫外光谱和红外光谱等手段对其进行了表征. 基于DNA-Ag NCs与离子相互作用时产生的荧光变化可实现对离子浓度的检测. 实验结果表明, 在最佳实验条件下, Ni ²⁺及Hg ²⁺的浓度与DNA-Ag NCs荧光强度呈线性关系; 并验证了该荧光探针用于检测自来水样品中汞离子和镍离子的实用性. 由于以DNA为模板的DNA-Ag NCs能够响应多种刺激, 如Ni ²⁺, S ^2-, Hg ²⁺和pH等, 利用相应的荧光强度可构建多输入的DNA-Ag NCs逻辑门及其组合逻辑门. 当荧光输出强度(I_output)>初始荧光强度(I_origin)时, 设定输出为1, 采用各种刺激及其组合作为输入, 构建了YES, INH和组合的NOR与INH逻辑门. 而只有当I_output≥I_origin时定义为输出为1, 可建立NOT, NOR, 组合的IMP加上NOR与AND逻辑门. 基于DNA-Ag NCs可以构建响应多元输入的复杂逻辑门, 实现化学信息的转变和传输, 在构建新的分子器件方面有较大应用前景.     

Versatile logic devices based on programmable DNA-regulated silver-nanocluster signal transducers

A DNA-encoding strategy is reported for the programmable regulation of the fluorescence properties of silver nanoclusters (AgNCs). By taking advantage of the DNA-encoding strategy, aqueous AgNCs were used as signal transducers to convert DNA inputs into fluorescence outputs for the construction of various DNA-based logic gates (AND, OR, INHIBIT, XOR, NOR, XNOR, NAND, and a sequential logic gate). Moreover, a biomolecular keypad that was capable of constructing crossword puzzles was also fabricated. These AgNC-based logic systems showed several advantages, including a simple transducer-introduction strategy, universal design, and biocompatible operation. In addition, this proof of concept opens the door to a new generation of signal transducer materials and provides a general route to versatile biomolecular logic devices for practical applications.     

Effective PET and ICT switching of boradiazaindacene emission: a unimolecular, emission-mode, molecular half-subtractor with reconfigurable logic gates

[reaction, structure: see text] We report a unimolecular system functioning as a combinatorial logic circuit for half-subtractor. The emission characteristics can be modulated by chemical inputs, and when followed at two different wavelengths, two functionally integrated logic gates XOR and INHIBIT are obtained. Both logic gates function in the emission mode, and with very large differences in the signal intensity allowing unequivocal assignment of logic-0 and logic-1.     

Versatile Logic Devices Based on Programmable DNA‐Regulated Silver‐Nanocluster Signal Transducers

A DNA‐encoding strategy is reported for the programmable regulation of the fluorescence properties of silver nanoclusters (AgNCs). By taking advantage of the DNA‐encoding strategy, aqueous AgNCs were used as signal transducers to convert DNA inputs into fluorescence outputs for the construction of various DNA‐based logic gates (AND, OR, INHIBIT, XOR, NOR, XNOR, NAND, and a sequential logic gate). Moreover, a biomolecular keypad that was capable of constructing crossword puzzles was also fabricated. These AgNC‐based logic systems showed several advantages, including a simple transducer‐introduction strategy, universal design, and biocompatible operation. In addition, this proof of concept opens the door to a new generation of signal transducer materials and provides a general route to versatile biomolecular logic devices for practical applications.     

Metal‐Ion‐Triggered Exonuclease III Activity for the Construction of DNA Colorimetric Logic Gates

The logic system is obtained by using a series of double‐stranded (ds) DNA templates with mismatched base pairs (T–T or C–C) and ion‐modulated exonuclease III (Exo III) activity, in which the Exo III cofactors, Hg²⁺ and Ag⁺ ions, are used as inputs for the activation of the respective scission of Exo III based on the formation of T–Hg²⁺–T or C–Ag⁺–C base pairs. Additionally, two kinds of signal probes are utilized to transduce the logic operations. One is the two split G‐rich DNA strands that are used to design the OR, AND, INHIBIT, and XOR gates, whereas the other is the self‐assembled split G‐quadruplex structure to construct NOR, NAND, IMPLICATION, and XNOR operations based on DNA hybridization and strand displacement. In the presence of hemin, the split G‐quadruplex biocatalyzes the formation of a colored product, which is an output signal for the different logic gates. Thus, we have constructed a complete set of colorimetric DNA logic gates based on the Exo III and split G‐quadruplex for the first time. In addition, we are able to effortlessly recognize the logic output signals by the naked eye and their simplicity and cost‐effective design is the most apparent feature for the logic gates developed in this work.     

Biocomputing for Portable,Resettable, and Quantitative Point‐of‐Care Diagnostics: Making the Glucose Meter a Logic‐Gate Responsive Device for Measuring Many Clinically Relevant Targets

It is recognized that biocomputing can provide intelligent solutions to complex biosensing projects. However, it remains challenging to transform biomolecular logic gates into convenient, portable, resettable and quantitative sensing systems for point‐of‐care (POC) diagnostics in a low‐resource setting. To overcome these limitations, the first design of biocomputing on personal glucose meters (PGMs) is reported, which utilizes glucose and the reduced form of nicotinamide adenine dinucleotide as signal outputs, DNAzymes and protein enzymes as building blocks, and demonstrates a general platform for installing logic‐gate responses (YES, NOT, INHIBIT, NOR, NAND, and OR) to a variety of biological species, such as cations (Na⁺), anions (citrate), organic metabolites (adenosine diphosphate and adenosine triphosphate) and enzymes (pyruvate kinase, alkaline phosphatase, and alcohol dehydrogenases). A concatenated logical gate platform that is resettable is also demonstrated. The system is highly modular and can be generally applied to POC diagnostics of many diseases, such as hyponatremia, hypernatremia, and hemolytic anemia. In addition to broadening the clinical applications of the PGM, the method reported opens a new avenue in biomolecular logic gates for the development of intelligent POC devices for on‐site applications.     

Molecular logic: a half-subtractor based on tetraphenylporphyrin

Spectroscopic changes from a solution of the amphophile 5,10,15,20-tetraphenylporphyrin in N,N-dimethylformamide using inputs of acid (HClaq) and base (KOBut) are interpreted as XOR and INHIBIT logic operations. The combination of these two operations gives rise to a device that acts as a molecular half-subtractor.     

Biocomputing for Portable,Resettable, and Quantitative Point‐of‐Care Diagnostics: Making the Glucose Meter a Logic‐Gate Responsive Device for Measuring Many Clinically Relevant Targets

It is recognized that biocomputing can provide intelligent solutions to complex biosensing projects. However, it remains challenging to transform biomolecular logic gates into convenient, portable, resettable and quantitative sensing systems for point‐of‐care (POC) diagnostics in a low‐resource setting. To overcome these limitations, the first design of biocomputing on personal glucose meters (PGMs) is reported, which utilizes glucose and the reduced form of nicotinamide adenine dinucleotide as signal outputs, DNAzymes and protein enzymes as building blocks, and demonstrates a general platform for installing logic‐gate responses (YES, NOT, INHIBIT, NOR, NAND, and OR) to a variety of biological species, such as cations (Na⁺), anions (citrate), organic metabolites (adenosine diphosphate and adenosine triphosphate) and enzymes (pyruvate kinase, alkaline phosphatase, and alcohol dehydrogenases). A concatenated logical gate platform that is resettable is also demonstrated. The system is highly modular and can be generally applied to POC diagnostics of many diseases, such as hyponatremia, hypernatremia, and hemolytic anemia. In addition to broadening the clinical applications of the PGM, the method reported opens a new avenue in biomolecular logic gates for the development of intelligent POC devices for on‐site applications.     

A molecular half-subtractor based on a fluorescence and absorption dual-modal sensor for copper ions

A l-phenyl alanine derivative (L) could be used as a fluorescence and absorption dual-modal sensor, which was highly sensitive and selective to copper ion at physiological pH. We have drawn attention to the use of its copper complex to acquire a half-subtractor with parallel operating INHIBIT and XOR logic gates, by monitoring, fluorescence and absorbance as output signals, respectively.     

A Taco Complex Derived from a Bis-Crown Ether Capable of Executing Molecular Logic Operation through Reversible Complexation

As learned from natural systems, self-assembly and self-sorting help in interconnecting different molecular logic gates and thus achieve high-level logic functions. In this context, demonstration of important logic operations using changes in optical responses due to the formation of molecular assemblies is even more desirable for the construction of a molecular computer. Synthesis of an appropriate divalent as well as a luminescent crown ether based host 1 and paraquat derivatives, 2(PF(6))(2) and 3(PF(6))(2), as guests helped in demonstrating a reversible [3](taco complex) (1·{2(PF(6))(2)}(2) or 1·{3(PF(6))(2)}(2)) formation in nonpolar solvent. Detailed (1)H NMR studies revealed that two paraquat units were bound cooperatively by the two crown units in 1. Because of preorganization, the flexible host molecule 1 adopts a folded conformation, where each of two paraquat units remain sandwiched between the two aromatic units of each folded crown ether moiety in 1. Disassembly of the "taco" complex in the presence of KPF(6) and reassembly on subsequent addition of DB18C6 was initially demonstrated by (1)H NMR spectral studies, which were subsequently corroborated through luminescence spectral studies. Further, luminescence spectral responses as output signals with appropriate and two independent molecular inputs could be correlated to demonstrate basic logic operation like OR and YES gates, while the results of the three molecular inputs could be utilized to demonstrate important logic operation like an INHIBIT gate.     

All-photonic multifunctional molecular logic device

Photochromes are photoswitchable, bistable chromophores which, like transistors, can implement binary logic operations. When several photochromes are combined in one molecule, interactions between them such as energy and electron transfer allow design of simple Boolean logic gates and more complex logic devices with all-photonic inputs and outputs. Selective isomerization of individual photochromes can be achieved using light of different wavelengths, and logic outputs can employ absorption and emission properties at different wavelengths, thus allowing a single molecular species to perform several different functions, even simultaneously. Here, we report a molecule consisting of three linked photochromes that can be configured as AND, XOR, INH, half-adder, half-subtractor, multiplexer, demultiplexer, encoder, decoder, keypad lock, and logically reversible transfer gate logic devices, all with a common initial state. The system demonstrates the advantages of light-responsive molecules as multifunctional, reconfigurable nanoscale logic devices that represent an approach to true molecular information processing units.     

Deoxyribozyme-based logic gates

We report herein a set of deoxyribozyme-based logic gates capable of generating any Boolean function. We construct basic NOT and AND gates, followed by the more complex XOR gate. These gates were constructed through a modular design that combines molecular beacon stem-loops with hammerhead-type deoxyribozymes. Importantly, as the gates have oligonucleotides as both inputs and output, they open the possibility of communication between various computation elements in solution. The operation of these gates is conveniently connected to a fluorescent readout.     

Salicylaldehyde fluorescein hydrazone: a colorimetric logic chemosensor for pH and Cu(II)

In this work, salicylaldehyde fluorescein hydrazone (1) was synthesized and characterized. Exhibiting reversible color changes responding to different pH in the presence of Cu(II) in buffered media, 1 could be applied as a colorimetric chemosensor for the detection of pH and Cu(II) bi-functionally. It presented a tunable system integrated with a Cu(II)-driven YES logic gate as well as an INHIBIT logic gate, with pH and Cu(II) as its chemical inputs based on encoding binary digits of logical conventions.