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1.
Anal Chem ; 94(48): 16887-16893, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36408858

RESUMO

Nanogap antennas with strong electromagnetic fields of the "hot spot" in the gap region of two adjacent particles that can significantly improve the optical properties of fluorophores hold great potential for ultrasensitive bioanalysis. Herein, a DNA computation-mediated self-assembly of Au NBP dimer-based plasmonic nanogap antennas was designed for imaging of intracellular correlated dual disease biomarkers. It is worth noting that with the benefit from the electromagnetic fields of the "hot spot" in the gap region and strand displacement amplification, the fluorescence intensity can be enhanced ∼14.7-fold by Au NBP dimer-based plasmonic nanogap antennas. In addition, the AND-gate sensing mechanism was confirmed through monitoring the response of three designed nAP-PH1, m-PH1, and PH1 probes, the fluorescence recovery in different cell lines (Hela and L02), and inhibitor-treated cells, respectively. Furthermore, thanks to the "dual keys" activation design, such an "AND-gate" sensing manner can be used for ultrasensitive correlated multiplexed molecular imaging, demonstrating its feasible prospect in correlated multiplexed molecular imaging.


Assuntos
Computadores Moleculares , Corantes Fluorescentes , Polímeros , Imagem Molecular
2.
Nature ; 610(7932): 496-501, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36261553

RESUMO

Artificial neural networks have revolutionized electronic computing. Similarly, molecular networks with neuromorphic architectures may enable molecular decision-making on a level comparable to gene regulatory networks1,2. Non-enzymatic networks could in principle support neuromorphic architectures, and seminal proofs-of-principle have been reported3,4. However, leakages (that is, the unwanted release of species), as well as issues with sensitivity, speed, preparation and the lack of strong nonlinear responses, make the composition of layers delicate, and molecular classifications equivalent to a multilayer neural network remain elusive (for example, the partitioning of a concentration space into regions that cannot be linearly separated). Here we introduce DNA-encoded enzymatic neurons with tuneable weights and biases, and which are assembled in multilayer architectures to classify nonlinearly separable regions. We first leverage the sharp decision margin of a neuron to compute various majority functions on 10 bits. We then compose neurons into a two-layer network and synthetize a parametric family of rectangular functions on a microRNA input. Finally, we connect neural and logical computations into a hybrid circuit that recursively partitions a concentration plane according to a decision tree in cell-sized droplets. This computational power and extreme miniaturization open avenues to query and manage molecular systems with complex contents, such as liquid biopsies or DNA databases.


Assuntos
Computadores Moleculares , Redes Neurais de Computação , Eletrônica , MicroRNAs , DNA , Miniaturização , Lógica
3.
Nanoscale ; 14(41): 15507-15515, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36227155

RESUMO

DNA nanotechnology provides a unique opportunity for molecular computation, with strand displacement reactions enabling controllable reorganization of nanostructures. Additional DNA strand exchange strategies with high selectivity for input will enable novel complex systems including biosensing applications. Herein, we propose an autocatalytic strand displacement (ACSD) circuit: initiated by DNA breathing and accelerated by a seesaw catalytic reaction, ACSD ensures that only the correct base sequence starts the catalytic cycle. Analogous to an electronic circuit with a variable resistor, two ACSD reactions with different rates are connected in parallel to mimic a parallel circuit containing branches with different resistances. Finally, we introduce a multiplexed nanopore sensing platform to report the output results of a parallel path selection system at the single-molecule level. By combining the ACSD strategy with fast and sensitive single-molecule nanopore readout, a new generation of DNA-based computing tools is established.


Assuntos
Nanoporos , DNA/química , Nanotecnologia/métodos , Computadores Moleculares , Sequência de Bases
4.
Anal Chem ; 94(41): 14467-14474, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36194489

RESUMO

Programming ultrasensitive and stimuli-responsive DNAzyme-based probes that contain logic gate biocomputation hold great potential for precise molecular imaging. In this work, a DNA computation-mediated DNAzyme platform that can be activated by 808 nm NIR light and target c-MYC was designed for spatiotemporally controlled ultrasensitive AND-gated molecular imaging. Particularly, the sensing and recognition function of the traditional DNAzyme platform was inhibited by introducing a blocking sequence containing a photo-cleavable linker (PC-linker) that can be indirectly cleaved by 808 nm NIR light and thus enables the AND-gated molecular imaging. According to the responses toward three designed SDz, nPC-SDz, and m-SDz DNAzyme probes, the fluorescence recovery in diverse cell lines (MCF-7, HeLa, and L02) and inhibitor-treated cells was investigated to confirm the AND-gated sensing mechanism. It is worth noting that thanks to the strand displacement amplification and the ability of gold nanopyramids (Au NBPs) to enhance fluorescence, the fluorescence intensity increased by ∼7.9 times and the detection limit decreased by nearly 40.5 times. Moreover, false positive signals can be also excluded due to such AND-gated design. Furthermore, such a designed "AND-gate" sensing manner can also be applied to spatiotemporally controlled ultrasensitive in vivo molecular imaging, indicating its promising potential in precise biological molecular imaging.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Técnicas Biossensoriais/métodos , Computadores Moleculares , DNA Catalítico/genética , Ouro , Imagem Molecular
5.
Comput Intell Neurosci ; 2022: 1450756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093485

RESUMO

The quota traveling salesman problem (QTSP) is a variant of the traveling salesman problem (TSP), which is a classical optimization problem. In the QTSP, the salesman visits some of the n cities to meet a given sales quota Q while having minimized travel costs. In this paper, we develop a DNA algorithm based on Adleman-Lipton model to solve the quota traveling salesman problem. Its time complexity is O(n 2+Q), which is a significant improvement over previous algorithms with exponential complexity. A coding scheme of element information is pointed out, and a reasonable biological algorithm is raised by using limited conditions, whose feasibility is verified by simulation experiments. The innovation of this study is to propose a polynomial time complexity algorithm to solve the QTSP. This advantage will become more obvious as the problem scale increases compared with the algorithm of exponential computational complexity. The proposed DNA algorithm also has the significant advantages of having a large storage capacity and consuming less energy during the operation. With the maturity of DNA manipulation technology, DNA computing, as one of the parallel biological computing methods, has the potential to solve more complex NP-hard problems.


Assuntos
Algoritmos , Computadores Moleculares , Simulação por Computador
6.
Nucleic Acids Res ; 50(15): 8974-8985, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-35947747

RESUMO

Information processing functions are essential for organisms to perceive and react to their complex environment, and for humans to analyze and rationalize them. While our brain is extraordinary at processing complex information, winner-take-all, as a type of biased competition is one of the simplest models of lateral inhibition and competition among biological neurons. It has been implemented as DNA-based neural networks, for example, to mimic pattern recognition. However, the utility of DNA-based computation in information processing for real biotechnological applications remains to be demonstrated. In this paper, a biased competition method for nonlinear manipulation and analysis of mixtures of DNA sequences was developed. Unlike conventional biological experiments, selected species were not directly subjected to analysis. Instead, parallel computation among a myriad of different DNA sequences was carried out to reduce the information entropy. The method could be used for various oligonucleotide-encoded libraries, as we have demonstrated its application in decoding and data analysis for selection experiments with DNA-encoded chemical libraries against protein targets.


Assuntos
Redes Neurais de Computação , Neurônios , Humanos , Neurônios/fisiologia , Computadores Moleculares , DNA/genética , DNA/química , Encéfalo
7.
Nucleic Acids Res ; 50(15): 8431-8440, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35904810

RESUMO

A series of multiple logic circuits based on a single biomolecular platform is constructed to perform nonarithmetic and arithmetic functions, including 4-to-2 encoder, 1-to-2 demultiplexer, 1-to-4 demultiplexer, and multi-input OR gate. The encoder to a DNA circuit is the equivalent of a sensory receptor to a reflex arc. They all function to encode information from outside the pathway (DNA circuit or reflex arc) into a form that subsequent pathways can recognize and utilize. Current molecular encoders are based on optical or electrical signals as outputs, while DNA circuits are based on DNA strands as transmission signals. The output of existing encoders cannot be recognized by subsequent DNA circuits. It is the first time the DNA-based encoder with DNA strands as outputs can be truly applied to the DNA circuit, enabling the application of DNA circuits in non-binary biological environments. Another novel feature of the designed system is that the developed nanodevices all have a simple structure, low leakage and low crosstalk, which allows them to implement higher-level encoders and demultiplexers easily. Our work is based on the idea of complex functionality in a simple form, which will also provide a new route for developing advanced molecular logic circuits.


Assuntos
DNA , Lógica , Computadores Moleculares , DNA/química , DNA/genética
8.
Chemphyschem ; 23(20): e202200352, 2022 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-35790068

RESUMO

Concatenated enzyme-based Boolean logic gates activated with 5 chemical input signals were analyzed with a smartphone photo camera. Simultaneous detection of 32 input combinations was conveniently performed using enzyme-modified fiberglass sensing spots generating fluorescence with different intensities for the 0 and 1 binary outputs. The developed technology offers an easy readout method for multi-channel logic systems.


Assuntos
Computadores Moleculares , Lógica
9.
J Am Chem Soc ; 144(27): 12443-12449, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35785961

RESUMO

Molecular circuits capable of processing temporal information are essential for complex decision making in response to both the presence and history of a molecular environment. A particular type of temporal information that has been recognized to be important is the relative timing of signals. Here we demonstrate the strategy of temporal memory combined with logic computation in DNA strand-displacement circuits capable of making decisions based on specific combinations of inputs as well as their relative timing. The circuit encodes the timing information on inputs in a set of memory strands, which allows for the construction of logic gates that act on current and historical signals. We show that mismatches can be employed to reduce the complexity of circuit design and that shortening specific toeholds can be useful for improving the robustness of circuit behavior. We also show that a detailed model can provide critical insights for guiding certain aspects of experimental investigations that an abstract model cannot. We envision that the design principles explored in this study can be generalized to more complex temporal logic circuits and incorporated into other types of circuit architectures, including DNA-based neural networks, enabling the implementation of timing-dependent learning rules and opening up new opportunities for embedding intelligent behaviors into artificial molecular machines.


Assuntos
Computadores Moleculares , Lógica , DNA
10.
Mater Horiz ; 9(8): 2109-2114, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35792070

RESUMO

Boolean operations utilizing DNA as a platform for biocomputing have become a promising tool for next-generation bio-molecular computers. In the whole process of any binary data transmission, bit errors are unavoidable and commonly occur. Cascades of exclusive-OR (XOR) operations show the great potential to evaluate these errors by introducing a parity generator (pG) and a parity checker (pC). Herein, we constructed a DNA hybrid architecture platform employing a chemosensing ensemble of mercury-mediated DNA-Au/Ag nanoclusters (M-Au/Ag NCs) to operate unconventional pG/pC for "error detection". Taking advantage of pG/pC, the transmitted and received data is converted to secure information using a binary to gray code encoder. To the best of our knowledge, this is the first molecular gray code encoder for biocomputing, which discovers an exciting avenue to protect information security through sophisticated logic circuits.


Assuntos
Mercúrio , Computadores Moleculares , DNA , Lógica
11.
IEEE Trans Biomed Circuits Syst ; 16(3): 479-488, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35727777

RESUMO

Due to its high programmability and storage, DNA circuits have been widely used in biological computing. In this paper, the addition, subtraction, multiplication, division, n-order and 1/n-order gates are built through DNA strand displacement reactions. The chemical reaction networks of the exponential function are established by using the six DNA analog computation gates. The integrated DNA strand displacement circuits are built through the chemical reaction networks. The exponential function polynomials can be computed through the integrated DNA strand displacement circuits. Finally, through visual DSD software verification, this design can realise the computation of exponential function polynomials, which provides a reference for solving exponential function equations and neural network computations in the future.


Assuntos
Computadores Moleculares , DNA , Algoritmos , DNA/genética , Redes Neurais de Computação , Recombinação Genética
12.
Biosystems ; 219: 104715, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35690290

RESUMO

The process of computing may be defined simply as the goal-directed selection process (GDSP) that selects m out of n possible choices to achieve some desired goals, thereby generating or utilizing the amount of Shannon information, I, that can be approximated as I = - log2 (m/n) bits. There are at least 3 distinct kinds of the physicochemical systems that can execute GDSP; (i) enzymes (i.e., microscopic or molecular computers), (ii) living cells (as mesoscopic computers), and (iii) brains (as macroscopic computers). In order to help define the principles and mechanisms underlying cell computing, it was thought necessary to compare cell computers with molecular computers (e.g., enzymes) on the one hand and with the macroscopic computers (e.g., Turing machine) on the other. It was concluded that all these different kinds of computers are ultimately driven by the information-energy particle called gnergons, consistent with the Gnergy Principle of Organization formulated by the present auditor in 2018. Also, it was concluded that to delineate how cells compute supported by enzymes necessitated treating enzymes not only as particles but also as standing waves, thus leading to the postulate of the wave-particle duality of enzymes formulated in this paper for the first time, in analogy to the wave-particle duality of light formulated in physics about 100 years ago.


Assuntos
Computadores Moleculares , Física , Fenômenos Físicos
13.
ACS Synth Biol ; 11(7): 2504-2512, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35771957

RESUMO

DNA computing has gained considerable attention due to the characteristics of high-density information storage and high parallel computing for solving computational problems. Building addressable logic gates with biomolecules is the basis for establishing biological computers. In the current calculation model, the multiinput AND operation often needs to be realized through a multilevel cascade between logic gates. Through experiments, it was found that the multilevel cascade causes signal leakage and affects the stability of the system. Using DNA strand displacement technology, we constructed a domino-like multiinput AND gate computing system instead of a cascade of operations, realizing multiinput AND computing on one logic gate and abandoning the traditional multilevel cascade of operations. Fluorescence experiments demonstrated that our methods significantly reduce system construction costs and improve the stability and robustness of the system. Finally, we proved stability and robustness of the domino AND gate by simulating the tic-tac-toe process with a massively parallel computing strategy.


Assuntos
DNA , Lógica , Computadores Moleculares , DNA/genética
14.
J Am Chem Soc ; 144(21): 9479-9488, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35603742

RESUMO

DNA logic circuits are based on DNA molecular programming that implements specific algorithms using dynamic reaction networks. Particularly, DNA adder circuits are key building blocks for performing digital computation. Nevertheless, existing circuit architectures are limited by scalability for implementing multi-bit adder due to the number of required gates and strands. Here, we develop a compact-yet-efficient architecture using cooperative strand displacement reactions (cSDRs) to construct DNA full adder. By exploiting a parity-check algorithm, double-logic XOR-AND gates are constructed with a single set of double-stranded molecule. One-bit full adder is implemented with three gates containing 13 strands, with up to 90% reduction in strand complexity compared to conventional circuit designs. Using this architecture and a transmitter on magnetic beads, we demonstrate DNA implementation of 6-bit adder on a scale comparable to that of a classic electronic full adder chip, providing the potential for application-specific circuit customization for scalable digital computing with minimal reactions.


Assuntos
Computadores Moleculares , DNA , Algoritmos , DNA/genética , Eletrônica , Lógica
15.
Biosens Bioelectron ; 209: 114260, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35430409

RESUMO

Inspired by information processing and communication in nature based on molecular recognition and structural diversity, ongoing efforts aim to development of artificial molecular or nano-systems for sensing, logic computing, and even data storage and safety. However, due to their preparation/functionalization shortcomings (laborious and time-consuming), poor flexibility and compatibility, and limited paradigm, it is still a big challenge whether simple molecules can be used to achieve comprehensive and universal applications from sensing to information storage and protection. Herein, we for the first time demonstrated a molecular paradigm-computer-like "basic input output system (BIOS)" which can realize "plug-and-play" sensing, information encoding, molecular cryptography, and steganography based on a simple artificial molecule (p-nitrophenol, PNP). Based on its molecular recognition and inherent chemical identities, PNP was utilized for colorimetric detection of multiple metal ions (Hg2+, Fe3+, Al3+, Cr3+) and distinguishing their valence (like Cr3+/Cr6+, Fe3+/Fe2+). Interestingly, PNP can achieve the "plug-and-play" fluorescent expansion of detection channels by directly mixing with fluorescent molecules, indicating that PNP molecule can be served as a molecular BIOS with flexibility and compatibility. Impressively, the selectivity embedded in PNP-based BIOS sensing system can be developed as molecular-level double cryptographic steganography to encode, encrypt and hide specific information (like the content of classical literature). This research not only provides a basic idea for building a molecular paradigm with "plug-and-play" flexibility and compatibility, but also provides ideas for the use of molecular sensing and informatization to open up the digitalization of the molecular world.


Assuntos
Técnicas Biossensoriais , Colorimetria , Computadores Moleculares , Íons
16.
Biomolecules ; 12(4)2022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35454084

RESUMO

In DNA computing, the implementation of complex and stable logic operations in a universal system is a critical challenge. It is necessary to develop a system with complex logic functions based on a simple mechanism. Here, the strategy to control the secondary structure of assembled DNAzymes' conserved domain is adopted to regulate the activity of DNAzymes and avoid the generation of four-way junctions, and makes it possible to implement basic logic gates and their cascade circuits in the same system. In addition, the purpose of threshold control achieved by the allosteric secondary structure implements a three-input DNA voter with one-vote veto function. The scalability of the system can be remarkably improved by adjusting the threshold to implement a DNA voter with 2n + 1 inputs. The proposed strategy provides a feasible idea for constructing more complex DNA circuits and a highly integrated computing system.


Assuntos
DNA Catalítico , Computadores Moleculares , DNA/química , DNA/genética , Lógica
17.
Int J Mol Sci ; 23(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35457085

RESUMO

The development of computational logic that carries programmable and predictable features is one of the key requirements for next-generation synthetic biological devices. Despite considerable progress, the construction of synthetic biological arithmetic logic units presents numerous challenges. In this paper, utilizing the unique advantages of RNA molecules in building complex logic circuits in the cellular environment, we demonstrate the RNA-only bitwise logical operation of XOR gates and basic arithmetic operations, including a half adder, a half subtractor, and a Feynman gate, in Escherichia coli. Specifically, de-novo-designed riboregulators, known as toehold switches, were concatenated to enhance the functionality of an OR gate, and a previously utilized antisense RNA strategy was further optimized to construct orthogonal NIMPLY gates. These optimized synthetic logic gates were able to be seamlessly integrated to achieve final arithmetic operations on small molecule inputs in cells. Toehold-switch-based ribocomputing devices may provide a fundamental basis for synthetic RNA-based arithmetic logic units or higher-order systems in cells.


Assuntos
Computadores Moleculares , Lógica , Escherichia coli/genética , RNA Antissenso
18.
Methods Mol Biol ; 2430: 219-230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35476335

RESUMO

Swarm robotics has been attracting much attention in recent years in the field of robotics. This chapter describes a methodology for the construction of molecular swarm robots through precise control of active self-assembly of microtubules (MTs). Detailed protocols are presented for the construction of molecular robots through conjugation of DNA to MTs and demonstration of swarming of the MTs. The swarming is mediated by DNA-based interaction and photoirradiation which act as processors and sensors respectively for the robots. Furthermore, the required protocols to utilize the swarming of MTs for molecular computation is also described.


Assuntos
Robótica , Computadores Moleculares , DNA/genética , Microtúbulos , Robótica/métodos
19.
Sensors (Basel) ; 22(7)2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35408108

RESUMO

Molecular communication (MC) is a promising bioinspired paradigm for exchanging molecule information among nanomachines. In this paper, we propose a synchronization-assist photolysis MC system that aims to transmit the biosensing signal of the tumor microenvironment, facilitated by mitigating redundant molecules for improved bit error rate (BER) performance. Benefits from biocompatible MC, biosensors could transmit biosensing signals of the tumor in vivo instead of converting them to electrical signals. Due to diffusion motion's slow and stochastic nature, intersymbol interference (ISI), resulting from previous symbols' residual information molecules, inevitably occurs in diffusion-based MC. ISI is one of the challenges in diffusion-based MC, which significantly impacts signal detection. Inspired by on-off keying (OOK) modulation, the proposed modulation implements a switch of molecules and light alternatively. The light emitted is triggered by a synchronization signal, and the photolysis reactions could reduce the redundant molecules. An expression for the relevant channel impulse response (CIR) is derived from a hybrid channel model of diffusion and photolysis reaction. In this paper, we implement the maximum posterior estimation scheme to find the optimal decision threshold and analysis the BER performance in terms of different time intervals of the system. Numerical simulations demonstrate that the proposed method can improve the channel capacity and BER performance. We believe that our work may pave the way for MC application in biosensing.


Assuntos
Computadores Moleculares , Neoplasias , Comunicação , Humanos , Nanotecnologia/métodos , Neoplasias/diagnóstico , Fotólise , Microambiente Tumoral
20.
Biosystems ; 217: 104684, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35443201

RESUMO

In 1972, Efim Liberman, a Soviet biophysicist, pioneered a brand-new approach to studying the operation of the brain, the live cell and the human mind by publishing a paper titled "Cell as a molecular computer" (1972). In this paper, Liberman posited that a consecutive/parallel stochastic molecular computer (MCC) controls a living cell. An MCC operates with molecule-words (DNA, RNA, proteins) according to the program recorded in DNA and RNA. Computational operations are implemented by molecular operators acting as enzymes. An MCC is present in each live cell. A neuron cell MCC can be involved in solving tasks for the entire organism. Neuron MCC investigation was started with studying an impact of an intracellular injection of cyclic AMP on electric activity of a neuron. Cyclic nucleotides were considered as input words for an MCC, which are generated inside a neuron as a result of synaptic activity. This led Efim Liberman to the idea that, in order to solve complex physical problems, which are encountered by a neuron and require rapid solutions, the molecular computer adjusts the operation of the quantum molecular regulator, which uses the "computational environment" of the cytoskeleton and quantum properties of the elementary hypersound quasiparticles for completing mathematical operations for the minimum price of action. Efim Liberman suggested that the human self-consciousness is a quantum computer of even a higher level and designated it as an extreme quantum regulator. In order to describe such systems, he suggested to join biology, physics and mathematics into a unified science, and formulated its four fundamental principles. Results of Efim Liberman's theoretical and experimental studies on the topic of biological computation are summarized in this review.


Assuntos
Computadores Moleculares , Neurônios , Computadores , DNA/genética , Humanos , Neurônios/fisiologia , Teoria Quântica , RNA
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