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.     

Manufacturing Reusable NAND Logic Gates and Their Initial Circuits for DNA Nanoprocessors

DNA-based computers can potentially analyze complex sets of biological markers, thereby advancing diagnostics and the treatment of diseases. Despite extensive efforts, DNA processors have not yet been developed due, in part, to limitations in the ability to integrate available logic gates into circuits. We have designed a NAND gate, which is one of the functionally complete set of logic connectives. The gate's design avoids stem-loop-folded DNA fragments, and is capable of reusable operations in RNase H-containing buffer. The output of the gate can be translated into RNA-cleaving activity or a fluorescent signal produced either by a deoxyribozyme or a molecular beacon probe. Furthermore, three NAND-gate-forming DNA strands were crosslinked by click chemistry and purified in a simple procedure that allowed ≈10¹³ gates to be manufactured in 16 h, with a hands-on time of about 30 min. Two NAND gates can be joined into one association that performs a new logic function simply by adding a DNA linker strand. Approaches developed in this work could contribute to the development of biocompatible DNA logic circuits for biotechnological and medical applications.     

Reconfigurable three-dimensional DNA nanostructures for the construction of intracellular logic sensors

Right out of the (logic) gate: Logic gates made from 3D DNA nanotetrahedra were constructed that are responsive to various ions, small molecules, and short strands of DNA. By including dynamic sequences in one or more edges of the tetrahedra, a FRET signal can be generated in the manner of AND, OR, XOR, and INH logic gates, as well as a half-adder circuit. These DNA logic gates were also applied to intracellular detection of ATP.     

AND molecular logic gates based on host-guest complexation operational in live cells

We report supramolecular AND logic gates based on host-guest complexation between acid-labile acyclic cucurbit[n]uril(CB[n]) molecular container and Na Cl O-responsive dye. Supramolecular AND logic gate is turned on due to acid-triggered degradation of molecular container and the release of the dye, followed by Na Cl O-induced fluorescence “switch on” effect of the dye. The reason for AND molecular logic gate is discovered to be the combination of oxidation inhibition and fluorescence “switch of...     

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.     

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.     

A multianalyte chemosensor on a single molecule: promising structure for an integrated logic gate

A novel fluorescent probe that possess both BODIPY and Rhodamine moieties has been designed for the selective detection of Hg(2+) and Ba(2+) ions on the controlling by a logic gate. The characteristic fluorescence of the Ba(2+)-selective OFF-ON and the Hg(2+)-selective fluorescence bathochromic shift can be observed, and the concept has been used to construct a combinational logic circuit at the molecular level. These results will be useful for further molecular design to mimic the function of the complex logic gates on controlling.     

Deoxyribozyme-based half-adder

We have constructed a solution-phase array of three deoxyribozyme-based logic gates that behaves as a half-adder. Two deoxyribozymes mimic i(1)ANDNOTi(2) and i(2)ANDNOTi(1) gates that cleave a fluorogenic substrate, reporting through an increase in fluorescence emission at 570 nm. The third deoxyribozyme mimics an i(1)ANDi(2) gate and cleaves the other fluorogenic substrate, reporting through an increase in fluorescence emission at 520 nm. Together, this system represents the first example of a decision-making enzymatic network with two inputs and two outputs. Similar systems could be applied to control autonomous therapeutic and diagnostic devices.     

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-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.     

Photonic logic gates based on control of FRET by a solvatochromic perylene bisimide

New perylenebisimide derivatives hydroxyperylenebisimide and naphthoperylenebisimide were obtained and applied to construct a new solvatochromic dyad 9. The solvatochromic behavior of hydroxyperylenebisimide was studied, and the structure of naphthoperylenebisimide was determined by X-ray crystallography. The spectral studies indicated that the hydroxyperylenebisimide and naphthoperylenebisimide units of dyad 9 were strongly coupled in the ground state, and as a result the fluorescence of the naphthoperylenebisimide unit was almost quenched and that of the hydroxyperylenebisimide unit was greatly enhanced due to the fluorescence resonance energy transfer (FRET). As we expected, this FRET process could be tuned with the addition of protons, base, and ferric ions. This behavior of dyad 9 could be interpreted by a two-input INH logic gate, while in the presence of Fe(III), the ion complex of 9 could execute a two-input XOR logic gate. By changing the output signal, a combinational logic circuit with three inputs could also be interpreted.     

Molecular AND and INHIBIT gates based on control of porphyrin fluorescence by photochromes

A molecular triad consisting of a porphyrin (P) covalently linked to two photochromes-one from the dihydroindolizine family (DHI) and one from the dihydropyrene family (DHP)-has been synthesized and found to act as either a molecular AND logic gate or an INHIBIT gate, depending on the inputs and initial state of the photochromes. The basis of these functions is quenching of porphyrin fluorescence (output of the gates) by the photochromes. The spiro form of DHI does not quench porphyrin fluorescence, whereas its betaine isomer strongly quenches by photoinduced electron transfer. DHP also quenches porphyrin fluorescence, but its cyclophanediene isomer does not. The triad has been designed using suitable energetics and electronic interactions, so that although these quenching phenomena may be observed, independent isomerization of the attached photochromes still occurs. This makes it possible to switch porphyrin fluorescence on or off by isomerization of the photochromes using various combinations of inputs such as UV light, red light, and heat.     

Molecular Logic Operations Based on Surfactant Nanoaggregates

Two molecular logic gates, FS1 and FS2, which display a UV and fluorescence behavior that is dependent on the pH value and the sodium dodecyl sulfate (SDS) surfactant concentration, are demonstrated based on the intramolecular charge‐transfer mechanism. They are constructed according to the inorganic salts that induce transformation from premicelle to micelle. The absorption band of FS1 at 480 nm is significantly enhanced only when both SDS and Na₂SO₄ are the input at high concentrations, in accordance with an AND logic gate. The OR logic function can be realized in a 3.5 mM SDS/FS2 aqueous solution with SDS and Na₂SO₄ as inputs along with the emission intensity as output. Furthermore, half addition and half subtraction can be incorporated in FS1. This is facilitated by the surfactant, due to its versatility.     

DNA-based visual majority logic gate with one-vote veto function

A molecular logic gate is a basic element and plays a key role in molecular computing. Herein, we have developed a label-free and enzyme-free three-input visual majority logic gate which is realized for the first time according to DNA hybridization only, without DNA replacement and enzyme catalysis. Furthermore, a one-vote veto function was integrated into the DNA-based majority logic gate, in which one input has priority over other inputs. The developed system can also implement multiple basic and cascade logic gates.     

Target-driven DNA association to initiate cyclic assembly of hairpins for biosensing and logic gate operation

A target-driven DNA association was designed to initiate cyclic assembly of hairpins, which led to an enzyme-free amplification strategy for detection of a nucleic acid or aptamer substrate and flexible construction of logic gates. The cyclic system contained two ssDNA (S1 and S2) and two hairpins (H1 and H2). These ssDNA could co-recognize the target to produce an S1–target–S2 structure, which brought their toehold and branch-migration domains into close proximity to initiate the cyclic assembly of hairpins. The assembly product further induced the dissociation of a double-stranded probe DNA (Q:F) via toehold-mediated strand displacement to switch the fluorescence signal. This method could detect DNA and ATP as model analytes down to 21.6 pM and 38 nM, respectively. By designing different DNA input strands, the “AND”, “INHIBIT” and “NAND” logic gates could be activated to achieve the output signal. The proposed biosensing and logic gate operation platform showed potential applications in disease diagnosis.     

DNA logic gates

A conceptually new logic gate based on DNA has been devised. Methoxybenzodeazaadenine ((MD)A), an artificial nucleobase which we recently developed for efficient hole transport through DNA, formed stable base pairs with T and C. However, a reasonable hole-transport efficiency was observed in the reaction for the duplex containing an (MD)A/T base pair, whereas the hole transport was strongly suppressed in the reaction using a duplex where the base opposite (MD)A was replaced by C. The influence of complementary pyrimidines on the efficiency of hole transport through (MD)A was quite contrary to the selectivity observed for hole transport through G. The orthogonality of the modulation of these hole-transport properties by complementary pyrimidine bases is promising for the design of a new molecular logic gate. The logic gate system was executed by hole transport through short DNA duplexes, which consisted of the "logic gate strand", containing hole-transporting nucleobases, and the "input strand", containing pyrimidines which modulate the hole-transport efficiency of logic bases. A logic gate strand containing multiple (MD)A bases in series provided the basis for a sharp AND logic action. On the other hand, for OR logic and combinational logic, conversion of Boolean expressions to standard sum-of-product (SOP) expressions was indispensable. Three logic gate strands were designed for OR logic according to each product term in the standard SOP expression of OR logic. The hole-transport efficiency observed for the mixed sample of logic gate strands exhibited an OR logic behavior. This approach is generally applicable to the design of other complicated combinational logic circuits such as the full-adder.     

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.     

Boolean and fuzzy logic gates based on the interaction of flindersine with bovine serum albumin and tryptophan

The naturally occurring photochromic compound, flindersine (FL), interplays with bovine serum albumin (BSA) and tryptophan (Trp). The intermolecular forces that establish between the couples FL/BSA and FL/Trp exert mutual effects on their photobehavior. These reciprocal effects can be exploited, in the field of molecular computing, to implement specific binary logic gates based on chemical inputs, physical outputs, and UV photons as power supply. Moreover, the smooth dependence of BSA and Trp fluorescence quantum yields on addition of FL moles (n(FL)) and temperature (T), allows us to process fuzzy logic. The synergistic action of the two inputs (n(FL) and T) allows the fuzzy AND logic gate to be implemented.     

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.     

Implication and Inhibition Boolean Logic Gates Mimicked with Enzyme Reactions

The enzyme system mimicking Implication (IMPLY) and Inhibition (INHIB) Boolean logic gates has been designed. The same enzyme system was used to operate as the IMPLY or INHIB gate simply by reformulating the input signals. The optical analysis of the logic operation confirmed the output generation as expected for the studied logic gates. The conceptual approach to the IMPLY and INHIB logic gates allows their construction with many other enzymes operating in a similar way.