Lineal DNA logic gate for microRNA diagnostics with strand displacement and fluorescence resonance energy transfer

Designing molecular logic gates to operate programmably for molecular diagnostics in molecular computing still remains challenging. Here, we designed a novel linear DNA logic gates for microRNA analysis based on strand displacement and fluorescence resonance energy transfer (FRET). Two labeled strands closed each other produce to FRET through hybridization with a complementary strand to form a basic work unit of logic gate. Two indicators of heart failure (microRNA-195 and microRNA-21) were selected as the logic inputs and the fluorescence mode was used as the logic output. We have demonstrated that the molecular logic gate mechanism worked well with the construction of YES and AND gates.     

Anion Sensors as Logic Gates: A Close Encounter?

Computers have become smarter, smaller, and more efficient due to the downscaling of silicon‐based components. Top‐down miniaturisation of silicon‐based computer components is fast reaching its limitations because of physical constraints and economical non‐feasibility. Therefore, the possibility of a bottom‐up approach that uses molecules to build nano‐sized devices has been initiated. As a result, molecular logic gates based on chemical inputs and measurable optical outputs have captured significant attention very recently. In addition, it would be interesting if such molecular logic gates could be developed by making use of ion sensors, which can give significantly sensitive output information. This review provides a brief introduction to anion receptors, molecular logic gates, a comprehensive review on describing recent advances and progress on development of ion receptors for molecular logic gates, and a brief idea about the application of molecular logic gates.     

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.     

Molecular photonic logic gates

The possibility of performing logical operations at the molecular level is being actively investigated at present with the aim of developing molecular logic gates, which can be used in information technologies. In this minireview, the design algorithm of molecular logic gates is considered and the requirements on molecular systems for use as logic gates are specified. Examples of molecular logic gates performing different logical operations are given. Attention is focused on all-photonic molecular logic gates, in which light is used as an input signal for transferring the system from one state to another and for reading the output signal by absorption or luminescence. In addition, optoelectronic devices with light as the input signal and electric current as the output signal are briefly discussed.     

Modular multi-level circuits from immobilized DNA-based logic gates

One of the fundamental goals of molecular computing is to reproduce the tenets of digital logic, such as component modularity and hierarchical circuit design. An important step toward this goal is the creation of molecular logic gates that can be rationally wired into multi-level circuits. Here we report the design and functional characterization of a complete set of modular DNA-based Boolean logic gates (AND, OR, and AND-NOT) and further demonstrate their wiring into a three-level circuit that exhibits Boolean XOR (exclusive OR) function. The approach is based on solid-supported DNA logic gates that are designed to operate with single-stranded DNA inputs and outputs. Since the solution-phase serves as the communication medium between gates, circuit wiring can be achieved by designating the DNA output of one gate as the input to another. Solid-supported logic gates provide enhanced gate modularity versus solution-phase systems by significantly simplifying the task of choosing appropriate DNA input and output sequences used in the construction of multi-level circuits. The molecular logic gates and circuits reported here were characterized by coupling DNA outputs to a single-input REPORT gate and monitoring the resulting fluorescent output signals.     

Logic Information Communication in a Fluorescent Molecular Switch

Based on the chemical‐sensitive fluorescence emission behaviors of the molecular switch 4‐bromo‐5‐methoxy‐2‐(2‐pyridyl)thiazole ( 2‐BMPT ), the communication of logic information between two functional units has been realized. With the rational control of the protonation and coordination reaction of 2‐BMPT , an upstream switching unit (a 1:2 demultiplexer) and two downstream data‐processing units are involved and interconnected in the communication. The two output states of the 1:2 demultiplexer serve as the initial input states of the two parallel downstream data‐processing units, which execute the information communication between the two circuit layers. Furthermore, in the parallel data‐processing layer, the logic gates of INHIBIT and YES accomplish their specific logic functions. Therefore, a molecular cascade circuit composed of an upstream switch and two downstream processing units has been constructed based on the chemical‐modulated fluorescence properties of 2‐BMPT .     

Design and operation of microelectrochemical gates and integrated circuits

Here we report a simple design philosophy, based on the principles of bipolar electrochemistry, for the operation of microelectrochemical integrated circuits. The inputs for these systems are simple voltage sources, but because they do not require much power they could be activated by chemical or biological reactions. Device output is an optical signal arising from electrogenerated chemiluminescence. Individual microelectrochemical logic gates are described first, and then multiple logic circuits are integrated into a single microfluidic channel to yield an integrated circuit that can perform parallel logic functions. AND, OR, NOR, and NAND gates are described. Eventually, systems such as those described here could provide on-chip data processing functions for lab-on-a-chip devices.     

DNA-based photonic logic gates: AND,NAND, and INHIBIT

Conventional microprocessors use elementary logic gates to perform complex computational tasks. Mimicking such computational processes using purely molecular systems has been limited in most cases by the lack of design generality or potential addressability of existing molecular logic gates. Herein we report that by employing the universal recognition properties of DNA simple photonic logic gates can be created that are capable of AND, NAND, and INHIBIT logic operations.     

DNA‐Based Adaptive Plasmonic Logic Gates

Self‐assembled plasmonic logic gates that read DNA molecules as input and return plasmonic chiroptical signals as outputs are reported. Such logic gates are achieved on a DNA‐based platform that logically regulate the conformation of a chiral plasmonic nanostructure, upon specific input DNA strands and internal computing units. With systematical designs, a complete set of Boolean logical gates are realized. Intriguingly, the logic gates could be endowed with adaptiveness, so they can autonomously alter their logics when the environment changes. As a demonstration, a logic gate that performs AND function at body temperature while OR function at cold storage temperature is constructed. In addition, the plasmonic chiroptical output has three distinctive states, which makes a three‐state molecular logic gate readily achievable on this platform. Such DNA‐based plasmonic logic gates are envisioned to execute more complex tasks giving these unique characteristics.     

DNA computation: a photochemically controlled AND gate

DNA computation is an emerging field that enables the assembly of complex circuits based on defined DNA logic gates. DNA-based logic gates have previously been operated through purely chemical means, controlling logic operations through DNA strands or other biomolecules. Although gates can operate through this manner, it limits temporal and spatial control of DNA-based logic operations. A photochemically controlled AND gate was developed through the incorporation of caged thymidine nucleotides into a DNA-based logic gate. By using light as the logic inputs, both spatial control and temporal control were achieved. In addition, design rules for light-regulated DNA logic gates were derived. A step-response, which can be found in a controller, was demonstrated. Photochemical inputs close the gap between DNA computation and silicon-based electrical circuitry, since light waves can be directly converted into electrical output signals and vice versa. This connection is important for the further development of an interface between DNA logic gates and electronic devices, enabling the connection of biological systems with electrical circuits.     

DNA‐Programmed Dynamic Assembly of Quantum Dots for Molecular Computation

Despite the widespread use of quantum dots (QDs) for biosensing and bioimaging, QD‐based bio‐interfaceable and reconfigurable molecular computing systems have not yet been realized. DNA‐programmed dynamic assembly of multi‐color QDs is presented for the construction of a new class of fluorescence resonance energy transfer (FRET)‐based QD computing systems. A complete set of seven elementary logic gates (OR, AND, NOR, NAND, INH, XOR, XNOR) are realized using a series of binary and ternary QD complexes operated by strand displacement reactions. The integration of different logic gates into a half‐adder circuit for molecular computation is also demonstrated. This strategy is quite versatile and straightforward for logical operations and would pave the way for QD‐biocomputing‐based intelligent molecular diagnostics.     

A natural-product-inspired photonic logic gate based on photoinduced electron-transfer-generated dual-channel fluorescence

[structure: see text] Modified 1-benzylisoquinoline N-oxides can operate as molecular logic gates. The combination of dual-channel fluorescence emissions and the preferred interaction for selected chemical inputs allows one to design multifunction and self-reprogrammable molecular logic gates.     

All‐Optical Integrated Logic Operations Based on Chemical Communication between Molecular Switches

Molecular logic gates process physical or chemical “inputs” to generate “outputs” based on a set of logical operators. We report the design and operation of a chemical ensemble in solution that behaves as integrated AND, OR, and XNOR gates with optical input and output signals. The ensemble is composed of a reversible merocyanine‐type photoacid and a ruthenium polypyridine complex that functions as a pH‐controlled three‐state luminescent switch. The light‐triggered release of protons from the photoacid is used to control the state of the transition‐metal complex. Therefore, the two molecular switching devices communicate with one another through the exchange of ionic signals. By means of such a double (optical–chemical–optical) signal‐transduction mechanism, inputs of violet light modulate a luminescence output in the red/far‐red region of the visible spectrum. Nondestructive reading is guaranteed because the green light used for excitation in the photoluminescence experiments does not affect the state of the gate. The reset is thermally driven and, thus, does not involve the addition of chemicals and accumulation of byproducts. Owing to its reversibility and stability, this molecular device can afford many cycles of digital operation.     

Connectable DNA Logic Gates: OR and XOR Logics

Modern computer processors are based on semiconductor logic gates connected to each other in complex circuits. This study contributes to the development of a new class of connectable logic gates made of DNA in which the transfer of oligonucleotide fragments as input/output signals occurs upon hybridization of DNA sequences. The DNA strands responsible for a logic function form associates containing immobile DNA four‐way junction structures when the signal is high and dissociate into separate strands when the signal is low. A basic set of logic gates (NOT, AND, and OR) was designed. Two NOT gates, two AND gates, and an OR gate were connected in a network that corresponds to an XOR logic function. The design of the logic gates presented here may contribute to the development of the first biocompatible molecular computer.     

A switch in a cage with a memory

[structure: see text] Chemical and optical stimulations control the interconversion of a three-state molecular switch trapped inside a silica monolith. The resulting absorbance changes in the visible region can be exploited to reproduce a sequential logic operator with one optical input and one optical output. This strategy to transfer operating principles for digital processing from bulk solutions to rigid materials can lead to the development of chemical logic gates based on functional solid components.     

Dicyanomethylene-4H-pyran chromophores for OLED emitters, logic gates and optical chemosensors

Dicyanomethylene-4H-pyran (DCM) chromophores are typical donor-π-acceptor (D-π-A) type chromophores with a broad absorption band resulting from an ultra-fast internal charge-transfer (ICT) process. In 1989, Tang et al. firstly introduced a DCM derivative as a highly fluorescent dopant in organic electroluminescent diodes (OLEDs). Integration of ICT chromophore-receptor systems based on DCM chromophores with ion-induced shifts in absorption or emission is a convenient method to perform the logic expression for molecular logic gates. In recent years, various DCM-type derivatives have been explored due to their excellent optical-electronic properties and diverse structural modification. This feature article provides an insight into how the structural modification of DCM chromophores can be utilized for OLED emitters, logic gates and optical chemosensors. In addition, the aggregation-induced-emission (AIE) of DCM derivatives for further optical applications was also introduced.     

Digital processing with a three-state molecular switch

Certain molecular switches respond to input stimulations producing detectable outputs. The interplay of these signals can be exploited to reproduce basic logic operations at the molecular level. The transition from simple logic gates to complex digital circuits requires the design of chemical systems able to process multiple inputs and outputs. We have identified a three-state molecular switch that responds to one chemical and two optical inputs producing two optical outputs. We have encoded binary digits in its inputs and outputs applying positive logic conventions and demonstrated that this chemical system converts three-digit input strings into two-digit output strings. The logic function executed by the three-state molecular switch is equivalent to that of a combinational logic circuit integrating two AND, two NOT, and one OR gate. The three states of the molecular switch are a colorless spiropyran, a purple trans-merocyanine, and its yellow-green protonated form. We have elucidated their structures by X-ray crystallography, (1)H NMR spectroscopy, COSY and NOE experiments, as well as density functional calculations. The three input stimulations controlling the interconversion of the three states of the molecular switch are ultraviolet light, visible light, and H(+). The two outputs are the absorption bands in the visible region of the two colored states of the molecular switch. We have monitored the switching processes and quantified the associated thermodynamic and kinetic parameters with the aid of (1)H NMR and visible absorption spectroscopies.     

Reversible Logic Gates Based on Enzyme‐Biocatalyzed Reactions and Realized in Flow Cells: A Modular Approach

Reversible logic gates, such as the double Feynman gate, Toffoli gate and Peres gate, with 3‐input/3‐output channels are realized using reactions biocatalyzed with enzymes and performed in flow systems. The flow devices are constructed using a modular approach, where each flow cell is modified with one enzyme that biocatalyzes one chemical reaction. The multi‐step processes mimicking the reversible logic gates are organized by combining the biocatalytic cells in different networks. This work emphasizes logical but not physical reversibility of the constructed systems. Their advantages and disadvantages are discussed and potential use in biosensing systems, rather than in computing devices, is suggested.     

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.     

Deoxyribozyme-based ligase logic gates and their initial circuits

A complete set (YES, NOT, AND, and ANDNOT) of molecular scale logic gates based on ligase deoxyribozymes was constructed. The activity of these gates was visualized through the formation of cascades with downstream phosphodieseterase YES gates, which performed fluorogenic cleavage.