A DNA-nano-gold particle probe machine implementation method and device

Abstract

The present invention relates to a method and device for realizing a DNA-nano-gold particle probe machine. The method comprises mapping a problem to be solved into a graph problem; encoding DNA sequences for DNA-nano-gold particles and DNA single strands respectively according to the graph problem; constructing a database containing encoded DNA-nano-gold particles; constructing a probe library containing encoded DNA single strands, placing the required data set and the probe set into a computing platform for mixed reaction, and obtaining a reaction product; and detecting the reaction product to obtain a calculation result. The present invention utilizes the combination of DNA and nano-gold particles to realize a fully parallel computing mode of underlying data and improve the reliability of the calculation result. In addition, because the nano-gold particles have their own spectral characteristics, the calculation result of the probe machine is easier to detect.

Description

Technical Field

[0001] The present invention relates to the field of biological computing, and in particular to a method and device for realizing a DNA-nano-gold particle probe machine. Background Art

[0002] Electronic computers cannot effectively solve NP-hard problems. In essence, the computational model of electronic computers is a Turing machine, which is a serial operation structure. On the other hand, the chip manufacturing technology of electronic computers is about to reach its physical limit, and Moore's Law is about to fail. In particular, as the manufacturing technology of 3D chips and other processes is exhausted, data shows that in the next year, the progress of reducing the size of transistors inside chips will no longer slow down, but stop. In order to make up for the shortcomings of electronic computers, people have been trying to develop new computers that surpass electronic computers.

[0003] DNA computing is a computing model that uses DNA molecules and related biological enzymes as basic materials and biochemical reactions as the basic process of information processing. The DNA computing model was first proposed by Dr. Adleman in 1994. Its greatest advantage is that it fully utilizes the massive storage capacity of DNA molecules and the massive parallelism of biochemical reactions.

[0004] DNA computing can be divided into ordinary computing and logic gate computing. Logic gate computing is mainly based on DNA single-strand displacement, and its input and output are both DNA single strands. Ordinary computing is mainly based on the complementary pairing of DNA single-strand bases to form a macromolecular structure.

[0005] At present, detection is a difficult point in DNA computing. The mutual reactions are realized based on single DNA chains, and the calculation result is a large mass of DNA chains. The detection process is cumbersome and has low credibility. Summary of the invention

[0006] The purpose of the present invention is to provide a method and device for realizing a DNA-nanogold particle probe machine. The DNA-nanogold particle probe machine provided by the present invention can increase the specificity level of DNA calculations. While improving the accuracy of DNA calculation results, since the DNA calculation products carry nanogold particles, efficient and accurate detection can be achieved.

[0007] Specifically, the technical solution provided by the present invention is as follows.

[0008] In a first aspect, the present invention provides a method for implementing a probe machine based on DNA-nanogold particles, the method comprising:

[0009] Convert the problem to be solved into a graph problem;

[0010] Based on the graph problem and DNA origami, a DNA origami template structure is assembled, the short chain at a specific position of the DNA origami template structure is extended and the A base is modified, and the nanogold particles are incubated with the DNA origami structure to obtain DNA-nanogold particles.

[0011] In the probe machine implementation method provided by the present invention, the short chain modified with base A includes an A-rich sequence block and a functional sequence block; the A-rich sequence block is combined with nanogold particles to obtain DNA-nanogold particles.

[0012] In the probe machine implementation method provided by the present invention, nanogold particles and DNA origami structures are incubated at room temperature and purified by agarose gel electrophoresis; urea is then added for denaturation, and the DNA origami template and nanogold particles are centrifuged to obtain DNA-nanogold particles connected to a corresponding number.

[0013] The probe machine implementation method provided by the present invention includes:

[0014] Convert the problem to be solved into a graph problem;

[0015] According to the problem in the figure, DNA sequences are encoded for DNA-nanogold particles and DNA single strands respectively;

[0016] Construct a database including encoded DNA-gold nanoparticles;

[0017] constructing a probe library including the encoded single-stranded DNA;

[0018] The desired DNA-nanogold particles and DNA single strands are placed on the computing platform for mixed reaction to obtain reaction products;

[0019] The reaction products are detected and the calculation results are obtained.

[0020] In the probe machine implementation method provided by the present invention, the required DNA-nanogold particles and DNA single strands are placed in a solution containing sodium ions and polyethylene glycol for mixed dissolution reaction, and PCR is used for precise temperature control.

[0021] In the probe machine implementation method provided by the present invention, a transmission electron microscope is used to detect the reaction product.

[0022] In a second aspect, the present invention provides a probe machine implementation device based on DNA-nanogold particles, the device comprising:

[0023] A preprocessing module, connected to the programming module, is used to transform the problem to be solved into a graph problem;

[0024] The programming module is connected to the database and the probe library and is used to encode DNA sequences for DNA-nanogold particles and DNA single strands according to the graph problem;

[0025] A database, used to store the DNA-nanogold particles;

[0026] A probe library, used for storing the single-stranded DNA;

[0027] A computing platform, connected to the database, the probe library, the detector, and the controller, for providing a platform for the DNA-nanogold particles and the DNA single strand to undergo a mixed reaction;

[0028] A detector, used to detect the reaction product after the mixed reaction to obtain a calculation result;

[0029] The controller is connected to the database, the probe library and the detector, and is used to control the required DNA-nanogold particles and DNA single strands to be placed into the computing platform, and control the detector to detect the reaction products, and determine whether it is a true solution to the problem to be solved according to the detection results.

[0030] The probe machine implementation device provided by the present invention assembles a DNA origami template structure based on the graph problem and DNA origami, extends the short chain at a specific position of the DNA origami template structure and modifies the A base, incubates nanogold particles with the DNA origami structure, and obtains DNA-nanogold particles.

[0031] The probe machine implementation method provided by the present invention is that in the computing platform, the required DNA-nanogold particles and DNA single strands are placed in a solution containing sodium ions and polyethylene glycol for mixed dissolution reaction, and PCR is used for precise temperature control.

[0032] In the probe machine implementation method provided by the present invention, the detector is a transmission electron microscope.

[0033] The beneficial effects of the present invention are:

[0034] (1) The present invention uses the DNA-nano-gold particles formed by the combination of DNA and nano-gold particles to construct a data set, and uses DNA single strands to construct a probe set, which overcomes the problem of cumbersome and low reliability of reaction result detection based solely on DNA, and realizes a fully parallel computing mode for underlying data. In addition, due to the spectral characteristics of nano-gold particles, the calculation results of the probe machine are easier to detect.

[0035] (2) The A-rich sequence blocks provided by the present invention can not only fix the DNA single strand on the surface of the nanogold, but also shield the non-specific sites and non-specific adsorption between DNA and the nanogold, so that the functional sequence blocks are away from the surface of the nanogold and maintain an upright configuration. By controlling the assembly of DNA molecules in different regions on its surface, a multi-faceted, synergistic nano-interface that can synergistically exert multiple functions in a local space is constructed.

[0036] (3) In the present invention, due to the spectral characteristics of the gold nanoparticles, the topological structure of the reaction product can be clearly observed using a transmission electron microscope. All topological structures in the reaction product that are topologically isomorphic to the true solution are the desired true solutions. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 This is a schematic flow chart of a method for implementing a probe machine based on DNA-nanogold particles according to Example 1 of the present invention.

[0038] Figure 2 This is a schematic diagram of the DNA origami-based assembly template structure of Example 1 of the present invention.

[0039] Figure 3 This is a graph to be colored containing 6 vertices according to Example 2 of the present invention.

[0040] Figure 4 This is a schematic diagram of the structure of the device for realizing a probe machine based on DNA-nanogold particles according to Example 3 of the present invention, wherein 11 is a preprocessing module; 12 is a programming module; 13 is a database; 14 is a probe library; 15 is a computing platform; 16 is a detector; and 17 is a controller. DETAILED DESCRIPTION

[0041] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0042] Example 1

[0043] This embodiment provides a general implementation method of a DNA-nanogold particle probe machine. Figure 1 The following is a flow chart of a method for implementing a probe machine based on DNA-nanogold particles according to an embodiment of the present invention.

[0044] Step S01: convert the problem to be solved into a graph problem;

[0045] In reality, many unsolved problems can be converted into graph problems. For example, scheduling problems, vulnerability mining, protein structure prediction, etc. can be converted into graph coloring problems, printed circuit board drilling problems, vehicle routing problems, design of navigation satellite system measurement networks, crew scheduling problems, warehouse picking problems, router layout problems, hot rolling scheduling problems, etc. can be converted into Hamilton circle problems.

[0046] Step S02: performing DNA sequence encoding on the DNA-nanogold particles and the DNA single strand respectively according to the graph problem;

[0047] The probe machine is a parallel computing model. When using the probe machine to solve graph problems, it is necessary to design DNA molecular codes for different problems. Specifically, the preset conditions are obtained according to the graph problem to be solved, and then the base sequence design on the DNA-nanogold particles and DNA single strands is completed according to the preset conditions.

[0048] Step S03: constructing a database, wherein the data is composed of encoded DNA-nanogold particles.

[0049] Step S04: construct a probe library, wherein the probes are composed of encoded single-stranded DNA.

[0050] There is no particular order for step S03 and step S04, and the actual situation can be determined according to the problem to be solved and the convenience of experimental operation.

[0051] The database and probe library can be containers filled with a certain buffer solution, and all the encoded DNA-nano-gold particles are placed in the database, and all the encoded DNA single strands are placed in the probe library. The number of structures contained in each library can reach 10 trillion / ml.

[0052] Step S05: Place the required DNA-nanogold particles and DNA single strands into the computing platform for mixed reaction to obtain a reaction product.

[0053] Determine the quantity of each kind of DNA-nanometer gold particles and DNA strands placed in the computing platform, and the determination method can be: according to the probability of the reactant topological structure obtained by the reaction of the DNA-nanometer gold particles corresponding to the true solution and the DNA strands, determine the quantity of each kind of DNA-nanometer gold particles and DNA strands required under the condition that each true solution exists after the reaction. In actual operation, each kind of DNA-nanometer gold particles and DNA strands more than the actual required quantity can also be placed in the computing platform, and the total number of DNA-nanometer gold particles and the number of DNA strands in the computing platform are controlled to a certain ratio according to actual needs. By adjusting the reaction environment of the computing platform, the DNA-nanometer gold particles and the DNA strands can be continuously moved in the computing platform at the molecular thermal motion speed in the liquid, and the two are specifically connected by molecular forces and hydrogen bond attraction. According to the difference of the DNA-nanometer gold particles, the number of DNA strands and the length of the DNA chain placed in the computing platform, the required time for reaction is different, which can be as short as a few hours or as long as a few weeks.

[0054] Step S06: Detect the reaction product and obtain the calculation result.

[0055] There are certain random factors in the specific base pairing process between DNA chains in the computing platform. Therefore, in addition to the desired calculation results, which are the so-called true solutions, there are also some undesirable calculation results, which are non-solutions, such as DNA-nanogold particles or DNA single strands that have not been successfully connected. Therefore, it is necessary to detect the obtained reaction products, and detect those reaction products that are topologically isomorphic to the true solution, which are the desired calculation results.

[0056] Further, the reaction product is detected, specifically by using a transmission electron microscope. The resolution of a transmission electron microscope can reach 0.1 to 0.2 nm, and the magnification is tens of thousands to millions of times. The fine structure of the object to be tested can be observed using a transmission electron microscope. The transmission electron microscope works by projecting an accelerated and focused electron beam onto a very thin object to be tested, thereby generating a stereoscopic angle scattering. The scattering angle is related to the density and thickness of the object to be tested, thereby forming images of different brightness. The reaction product in the embodiment of the present invention is a polymer formed by connecting a number of DNA-nano gold particles to a single strand of DNA. According to its size and thickness, the result obtained by using a transmission electron microscope to detect is more reliable and accurate.

[0057] The present invention uses DNA-nano-gold particles formed by the combination of DNA and nano-gold particles to construct a data set, and uses DNA single strands to construct a probe set, which overcomes the problem of cumbersome and low credibility of reaction result detection based solely on DNA, and realizes a fully parallel calculation mode for underlying data. In addition, due to the spectral characteristics of nano-gold particles, the calculation results of the probe machine are easier to detect.

[0058] Different from the traditional DNA-nano-gold particle assembly method, the DNA-nano-gold particles designed in the embodiment of the present invention are designed with multiple continuous adenine (A) bases in the DNA sequence, and the DNA molecules are assembled on the nano-gold surface based on the strong interaction between the A base and gold. Since A has a stronger adsorption capacity with gold than the other three bases constituting DNA, it can preferentially bind to the nano-gold surface. The sequence blocks rich in A can not only fix the DNA single strand on the nano-gold surface, but also shield the non-specific sites and non-specific adsorption between DNA and nano-gold, so that the functional sequence blocks are away from the nano-gold surface and maintain an upright configuration. By controlling the assembly of DNA molecules in different regions on its surface, a multi-faceted, collaborative nano-interface that can synergistically exert multifunctionality in a local space is constructed.

[0059] Furthermore, the hydrophilicity and charge density of the DNA-nanogold particles are regulated to reduce impurity adsorption and environmental interference, thereby achieving high-specific recognition between the DNA-nanogold particles and the DNA single strand.

[0060] DNA origami can assemble structures of various shapes such as one-dimensional, two-dimensional, and three-dimensional, and has nanoscale addressability, and can arrange various elements such as proteins, virus capsids, nanoparticles, etc. The DNA-nano-gold particles designed in the embodiment of the present invention are assembled by programmably connecting DNA single strands on the nano-gold particles. In this embodiment, the assembly diagram of the DNA-nano-gold particles is shown in FIG. Figure 2 shown.

[0061] First, the corresponding template structure is assembled based on DNA origami, and the DNA pattern information is transmitted to the gold nanoparticles as needed to extend the short chain at a specific position and modify the A base; the gold nanoparticles and the DNA origami structure are then incubated at room temperature and purified by agarose gel electrophoresis; the DNA origami template and the gold nanoparticles are then denatured by adding urea, and the gold nanoparticles are centrifuged to obtain gold nanoparticles connected to the corresponding number of DNA chains.

[0062] Based on the above embodiment, further, the required DNA-nano-gold particles and DNA single strands are placed in a computing platform for mixed reaction, specifically, the required DNA-nano-gold particles and DNA single strands are placed in a solution containing sodium ions and polyethylene glycol for mixed dissolution reaction, and PCR is used for precise temperature control. The solution containing sodium ions and polyethylene glycol is used to fully mix and dissolve the DNA-nano-gold particles and DNA single strands, and the gradient annealing temperature and time are set using a PCR instrument, which effectively improves the reaction efficiency and realizes efficient solution of the probe machine model.

[0063] Due to the spectral characteristics of the nano-gold particles, the topological structure of the reaction product can be clearly observed using a transmission electron microscope, and all the topological structures in the reaction product that are topologically isomorphic to the true solution are the desired true solution. Furthermore, the embodiment of the present invention can also mark the surface of the nano-gold particles, such as symbols or color markings, to distinguish the types of data represented, so that the detection results of the reaction product are more intuitive.

[0064] Example 2

[0065] This embodiment provides a specific implementation method of a DNA-nanogold particle probe machine.

[0066] This embodiment takes a 3-coloring solution of a 6-vertex graph as an example for illustration. Figure 3 This is a 6-vertex graph to be colored in an embodiment of the present invention. Vertices 1, 2, and 3 form a triangle, so their colors are different. Let's assume that vertices 1, 2, and 3 are colored red, green, and blue respectively. Now we need to assign colors to vertices 4, 5, and 6 so that adjacent vertices are colored in different colors.

[0067] According to the above problems and known conditions, DNA sequences are designed and DNA encoding is performed to complete the assembly of programmable DNA single strands on gold nanoparticles, and the encoded database containing DNA-gold nanoparticles and the probe library containing DNA single strands are obtained. It is possible to consider marking the surface of gold nanoparticles, such as using two markers at the same time to distinguish the vertices corresponding to the DNA-gold nanoparticles and the colors they are marked with.

[0068] According to the known conditions, in the corresponding mathematical model, there are 10 types of DNA-nanogold particles, and there are 18 possible combinations of DNA-nanogold particles and DNA single strands. Therefore, there are 10 types of data in the database, and the probe library contains 18 types of probes. The above data and probes are placed in a solution computing platform containing sodium ions and polyethylene glycol for reaction, and PCR is used for precise temperature control to obtain the reaction product. The topological structure of the reaction product is observed using a transmission electron microscope. All polymers in the reaction product that are topologically isomorphic to the true solution are the true solution, and all true solutions are obtained in one reaction operation.

[0069] Example 3

[0070] This embodiment provides a corresponding device based on the above-mentioned probe machine implementation method, such as Figure 4 As shown, the device includes: a preprocessing module 11, an encoding module 12, a database 13, a probe library 14, a computing platform 15, a detector 16 and a controller 17.

[0071] Among them, the preprocessing module 11 is connected to the programming module 12, and is used to convert the problem to be solved into a graph problem; the programming module 12 is connected to the database 13 and the probe library 14, and is used to encode the DNA sequence of the DNA-nanogold particles and the DNA single strands according to the graph problem; the database 13 is used to store the DNA-nanogold particles; the probe library 14 is used to store the DNA single strands; the computing platform 15 is connected to the database 13, the probe library 14, the detector 16, and the controller 17, and is used to provide a platform for the DNA-nanogold particles and the DNA single strands to undergo a mixed reaction; the detector 16 is used to detect the reaction products after the mixed reaction to obtain the calculation results; the controller 17 is connected to the database 13, the probe library 14, and the detector 16, and is used to control the required DNA-nanogold particles and DNA single strands to be placed in the computing platform, and control the detector to detect the reaction products, and determine whether it is a true solution to the problem to be solved based on the detection results. In reality, many unsolved problems can be converted into graph problems. For example, scheduling problems, vulnerability mining, protein structure prediction, etc. can be converted into graph coloring problems. For example, printed circuit board drilling problems, vehicle routing problems, navigation satellite system measurement network design, crew scheduling problems, warehouse picking problems, router layout problems, hot rolling scheduling problems, etc. can be converted into Hamilton circle problems.

[0072] The probe machine provided in this embodiment is a parallel computing model. When using the probe machine to solve graph problems, it is necessary to design DNA molecular coding for different problems. The DNA sequence coding of DNA-nano-gold particles and DNA single strands is specifically to obtain preset conditions according to the graph problem to be solved, and then complete the base sequence design on the DNA-nano-gold particles and DNA single strands according to the preset conditions.

[0073] The database 13 and the probe library 14 can be containers filled with buffer solution, and all the encoded DNA-nano-gold particles are placed in the database, and all the encoded DNA single strands are placed in the probe library. The number of structures contained in each library can reach 10 trillion / ml.

[0074] The controller 17 places the DNA-nanogold particles stored in the database 13 and the DNA single strands stored in the probe library 14 into the computing platform 15 for mixed reaction to obtain a reaction product.

[0075] Determine the quantity of each kind of DNA-nanometer gold particles and DNA strands placed in the computing platform 15, and the determination method can be: according to the probability of the reactant topological structure produced by the DNA-nanometer gold particles corresponding to the true solution and the DNA strands reaction, under the condition that each true solution exists after the reaction, determine the quantity of each kind of DNA-nanometer gold particles and DNA strands required. In actual operation, each kind of DNA-nanometer gold particles and DNA strands more than the actual required quantity can also be placed in the computing platform, and according to actual needs, the total DNA-nanometer gold particles quantity and DNA strand quantity in the computing platform are controlled at a certain ratio. By adjusting the reaction environment of the computing platform, the DNA-nanometer gold particles and the DNA strands can be continuously moved in the computing platform with the molecular thermal motion speed in the liquid, and the two are specifically connected by molecular forces and hydrogen bond attraction. According to the difference of the DNA-nanometer gold particles, DNA strand quantity and DNA chain length placed in the computing platform, the required reaction time is also different, which can be as short as a few hours or as long as a few weeks.

[0076] There are certain random factors in the specific base pairing process between DNA chains in the computing platform. Therefore, in the obtained reaction products, in addition to the desired calculation results, which are the so-called true solutions, there are also some undesirable calculation results, which are non-solutions, such as DNA-nanogold particles or DNA single strands that have not been successfully connected. Therefore, it is necessary to detect the obtained reaction products, and detect those reaction products that are topologically isomorphic to the true solution, which are the desired calculation results.

[0077] Furthermore, the detector 16 is a transmission electron microscope. The reaction product in the embodiment of the present invention is a polymer formed by connecting a number of DNA-nano-gold particles and a single-stranded DNA. According to its size and thickness, the result obtained by using a transmission electron microscope for detection is more reliable and accurate.

[0078] The present invention uses DNA-nano-gold particles formed by the combination of DNA and nano-gold particles to construct a data set, and uses DNA single strands to construct a probe set, which overcomes the problem of cumbersome and low credibility of reaction result detection based solely on DNA, and realizes a fully parallel calculation mode for underlying data. In addition, due to the spectral characteristics of nano-gold particles, the calculation results of the probe machine are easier to detect.

[0079] Different from the traditional DNA-nano-gold particle assembly method, the DNA-nano-gold particles designed in the embodiment of the present invention are designed with multiple continuous adenine (A) bases in the DNA sequence, and the DNA molecules are assembled on the nano-gold surface based on the strong interaction between the A base and gold. Since A has a stronger adsorption capacity with gold than the other three bases constituting DNA, it can preferentially bind to the nano-gold surface. The sequence blocks rich in A can not only fix the DNA single strand on the nano-gold surface, but also shield the non-specific sites and non-specific adsorption between DNA and nano-gold, so that the functional sequence blocks are away from the nano-gold surface and maintain an upright configuration. By controlling the assembly of DNA molecules in different regions of the nano-gold surface, a multi-faceted, collaborative nano-interface that can synergistically exert multifunctionality in a local space is constructed.

[0080] Furthermore, the hydrophilicity and charge density of the DNA-nanogold particles are regulated to reduce impurity adsorption and environmental interference, thereby achieving high-specific recognition between the DNA-nanogold particles and the DNA single strand.

[0081] The DNA-nano-gold particles designed in the embodiment of the present invention are assembled by programmably connecting single-stranded DNA to the nano-gold particles. First, the corresponding template structure is assembled based on DNA origami. Figure 2 As shown, according to the DNA pattern information transmitted to the gold nanoparticles as needed, the short chain at a specific position is extended and the A base is modified; the gold nanoparticles and the DNA origami structure are then incubated at room temperature and purified by agarose gel electrophoresis; the DNA origami template and the gold nanoparticles are then denatured by adding urea, and the gold nanoparticles connected to the corresponding number of DNA chains are obtained.

[0082] Furthermore, the required DNA-nano-gold particles and DNA single strands are placed in a computing platform, specifically, the required DNA-nano-gold particles and DNA single strands are placed in a solution containing sodium ions and polyethylene glycol for mixed dissolution reaction, and PCR is used for precise temperature control. The solution containing sodium ions and polyethylene glycol is used to fully mix and dissolve the DNA-nano-gold particles and DNA single strands, and the gradient annealing temperature and time are set using a PCR instrument, which effectively improves the reaction efficiency and realizes efficient solution of the probe machine model.

[0083] Due to the spectral characteristics of gold nanoparticles, the topological structure of the reaction product can be clearly observed using a transmission electron microscope. The desired true solution is the polymer topological structure in the reaction product that is isomorphic to the true solution topology.

[0084] Furthermore, the nano-gold in the embodiment of the present invention may have a mark on its surface, such as a symbol or a color mark, to distinguish the data it represents, so that the detection result of the reaction product is more intuitive.

[0085] Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A method for realizing a probe machine based on DNA-nanogold particles, characterized in that: The probe machine implementation method includes: Convert the problem to be solved into a graph problem; According to the problem in the figure, DNA sequences are encoded for DNA-nanogold particles and DNA single strands respectively; Construct a database including encoded DNA-gold nanoparticles; constructing a probe library including the encoded single-stranded DNA; The desired DNA-nanogold particles and DNA single strands are placed on the computing platform for mixed reaction to obtain reaction products; Detect the reaction products and obtain the calculation results; The DNA-nano-gold particles are assembled by the following method: Based on the graph problem and DNA origami, a DNA origami template structure is assembled, and a short chain at a specific position of the DNA origami template structure is extended and modified with A base, and the short chain modified with base A includes an A-rich sequence block and a functional sequence block; the A-rich sequence block is combined with nanogold particles, and the nanogold particles are incubated with the DNA origami template structure and purified by agarose gel electrophoresis; urea is then added for denaturation, and the DNA origami template structure and the nanogold particles are centrifuged to obtain DNA-nanogold particles.

2. The method according to claim 1, characterized in that The required DNA-nanogold particles and DNA single strands are placed in a solution containing sodium ions and polyethylene glycol for mixed dissolution reaction, and PCR is used for precise temperature control.

3. The method according to claim 1, characterized in that The reaction products were detected by transmission electron microscopy.

4. A probe machine implementation device based on DNA-nanogold particles, characterized in that: The device comprises: A preprocessing module, connected to the programming module, is used to transform the problem to be solved into a graph problem; The programming module is connected to the database and the probe library and is used to encode DNA sequences for DNA-nanogold particles and DNA single strands according to the graph problem; A database, used to store the DNA-nanogold particles; A probe library, used for storing the single-stranded DNA; A computing platform, connected to the database, the probe library, the detector, and the controller, for providing a platform for the DNA-nanogold particles and the DNA single strand to undergo a mixed reaction; A detector, used to detect the reaction product after the mixed reaction to obtain a calculation result; A controller is connected to the database, the probe library, and the detector, and is used to control the placement of the required DNA-nanogold particles and DNA single strands into the computing platform, and to control the detector to detect the reaction product, and to determine whether it is a true solution to the problem to be solved according to the detection result; Based on the graph problem and DNA origami, a DNA origami template structure is assembled, the short chain at a specific position of the DNA origami template structure is extended and the A base is modified, and the nanogold particles are incubated with the DNA origami structure to obtain DNA-nanogold particles.

5. The probe machine implementation device according to claim 4, characterized in that: In the computing platform, the required DNA-nanogold particles and DNA single strands are placed in a solution containing sodium ions and polyethylene glycol for mixed dissolution reaction, and PCR is used for precise temperature control.

6. The probe machine implementation device according to claim 4, characterized in that: The detector is a transmission electron microscope.

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