Information encryption method based on non-natural DNA and information decoding method

Abstract

The application belongs to the field of information storage and relates to a non-natural DNA-based information encryption method and an information decoding method, wherein the non-natural DNA-based information encryption method comprises the following steps: 1) obtaining an information encryption storage medium; 2) performing binary coding on target information; and 3) assigning the information encryption storage medium obtained in step 1) to corresponding bits of the binary coded information obtained in step 2), so as to complete target information encryption. The non-natural DNA-based information decoding method comprises the following steps: 1) obtaining an information encryption storage medium corresponding to target information; and 2) using a nanopore single-molecule analysis technology to detect the information encryption storage medium in step 1) in real time based on different keys and decode the target information. The application provides an information encryption storage and decoding method with higher storage density, higher reading efficiency and more secure information.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of information storage, and relates to an information encryption storage method and an information decoding method, in particular to an information encryption method and an information decoding method based on non-natural DNA. BACKGROUND

[0002] Due to the explosive growth of electronic data, the traditional materials for information storage have been insufficient to store such a high data capacity. In nature, a large amount of genetic information is stored in DNA molecules, which prompts people to use DNA to achieve higher density information storage. Current DNA storage technologies are mainly divided into sequence-based and nanostructure-based information storage methods, which realize information translation through four base sequences and DNA nanostructures respectively. Among them, the sequence-based DNA storage technology often uses PCR technology for DNA synthesis when encoding information, which may have errors in the synthesis process, and often needs to synthesize new sequences for different information. The DNA storage technology based on nanostructure generally uses strand exchange reaction to realize information storage, which requires at least 8 base pairs corresponding to one bit, and in addition to the main chain, short chains are also needed to code information to form a structure. The storage density of these storage methods is difficult to greatly improve, so improving the storage density and simplifying the storage scheme can make DNA storage more easily applied to information storage.

[0003] In addition to using DNA for information storage, adding encryption function when designing DNA storage medium plays a crucial role in ensuring the safety and privacy of users' data. Some research methods store information in microdots or organic materials to create an information steganography environment to achieve information encryption, but this sequence-based storage method is prone to information leakage during DNA sequencing (Nature 1999, 399, 533-534; Nat. Biotechnol. 2020, 38, 39-43). DNA nanostructure can also be used to achieve encrypted storage of information, such as Zhang et al. using DNA origami technology to store encrypted information in a nano-dot array structure similar to Braille, which can only be formed and decoded after adding matching short-chain DNA (Nat. Commun. 2019, 10, 5469); these methods all need to add some substances to achieve information encryption, which means that these physical keys need to be transmitted together with the storage medium when transmitting information, which leads to the risk of interception or damage during transmission, so there is a risk of information leakage or loss.

[0004] For the information decoding process of DNA storage, sequence-based DNA storage technology often uses DNA sequencing to read and decode information. Common sequencing methods include Sanger sequencing, Illumina sequencing, and nanopore single molecule sequencing technology. DNA storage based on nanostructures can use AFM, fluorescence imaging, and nanopore single molecule detection technology to read and decode information. Among them, nanopore single molecule technology is widely used in DNA storage due to its high resolution and real-time efficiency. Chen et al. used solid-state nanopores to detect DNA polymer molecules containing nanostructures to achieve information encryption and storage (Nano letters 2020, 20, 3754-3760). However, there are few reports on using biological nanopores to detect DNA and achieve information encryption storage and decoding. SUMMARY

[0005] The present application provides an information encryption storage and decoding method with higher storage density, higher reading efficiency, and more secure information.

[0006] Technical scheme: In order to achieve the above purpose, the present application adopts the following technical scheme:

[0007] An information encryption method based on non-natural DNA, the information encryption method based on non-natural DNA comprising:

[0008] 1) Obtain an information encryption storage medium;

[0009] 2) Binary encode the target information;

[0010] 3) Assign the information encryption storage medium obtained in step 1) to the corresponding bit of the binary code obtained in step 2), complete the encryption of the target information.

[0011] Preferably, the specific implementation of step 1) is:

[0012] 1.1) Determine the composition of the information encryption storage medium; the information encryption storage medium is a mixture formed by a plurality of non-natural DNA polymer molecules; the non-natural DNA polymer molecules comprise a single-stranded DNA formed by a plurality of natural nucleotides and a stimulus-responsive chemical group covalently modified on the single-stranded DNA;

[0013] 1.2) Determine the number of binary coded bits based on the binary coding rule;

[0014] 1.3) determining the number of stimulus-responsive chemical groups and the number of natural nucleotides on the single-stranded DNA according to the number of bits of the binary code determined in step 1.2); the number of bits of the binary code is n, and the number of natural nucleotides on the single-stranded DNA is not more than n;

[0015] 1.4) covalently modifying the stimulus-responsive chemical groups on the backbone of the single-stranded DNA or on different nucleotides of the single-stranded DNA to obtain n kinds of unnatural DNA polymer molecules, which are specifically: unnatural DNA polymer molecule M1, unnatural DNA polymer molecule M2, unnatural DNA polymer molecule M3, …, and unnatural DNA polymer molecule Mn. n .

[0016] Preferably, the stimulus-responsive chemical groups in step 1.1) are photoresponsive chemical groups that undergo conformational transformation or bond-forming and bond-breaking reactions under light conditions; preferably, the photoresponsive chemical groups include but are not limited to azobenzene, spiropyran, o-nitrobenzyl and its derivatives; preferably, the number of stimulus-responsive chemical groups is one or more; the number of natural nucleotides is not less than the number of stimulus-responsive chemical groups; the natural nucleotides are the same or different.

[0017] Preferably, the binary coding rule in step 1.2) includes a 5-bit Baudot coding rule or an 8-bit ASCII coding rule.

[0018] Preferably, when the number of stimulus-responsive chemical groups is one, when the stimulus-responsive chemical groups are covalently modified on the backbone of the single-stranded DNA in step 1.4), the number of natural nucleotides on the single-stranded DNA is not more than n-1, and the specific implementation of the covalent modification in step 1.4) is:

[0019] sequentially covalently modifying the stimulus-responsive chemical groups at the front end of the 1st natural nucleotide, the front end of the 2nd natural nucleotide, the front end of the 3rd natural nucleotide, …, the front end of the n-1th natural nucleotide, and the end of the n-1th natural nucleotide of the single-stranded DNA from the 5' end;

[0020] Preferably, when the number of stimulus-responsive chemical groups is one, when the stimulus-responsive chemical groups are covalently modified on different nucleotides of the single-stranded DNA in step 1.4), the number of natural nucleotides on the single-stranded DNA is not more than n, and the specific implementation of the covalent modification in step 1.4) is:

[0021] covalently modifying a first stimulus-responsive chemical group on the 1st natural nucleotide, the 2nd natural nucleotide, the 3rd natural nucleotide, …, the n-1th natural nucleotide, and the nth natural nucleotide of the single-stranded DNA in sequence from the 5' end; and covalently modifying the remaining stimulus-responsive chemical groups, other than the first stimulus-responsive chemical group, on the remaining natural nucleotides, other than the remaining natural nucleotides on which the first stimulus-responsive chemical group is covalently modified, with at least one natural nucleotide as an interval.

[0022] Preferably, when the number of the stimulus-responsive chemical groups is plural, the number of the natural nucleotides on the single-stranded DNA is not more than n-1 in the covalent modification of the stimulus-responsive chemical groups on the backbone of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is:

[0023] Preferably, when the number of the stimulus-responsive chemical groups is plural, the number of the natural nucleotides on the single-stranded DNA is not more than n-1 in the covalent modification of the stimulus-responsive chemical groups on the backbone of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is:

[0024] Preferably, when the number of the stimulus-responsive chemical groups is plural, the number of the natural nucleotides on the single-stranded DNA is not more than n-1 in the covalent modification of the stimulus-responsive chemical groups on the backbone of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is:

[0025] Preferably, when the number of the stimulus-responsive chemical groups is plural, the number of the natural nucleotides on the single-stranded DNA is not more than n-1 in the covalent modification of the stimulus-responsive chemical groups on the backbone of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is:

[0026] Preferably, the binary coding in step 2) is achieved by using a binary coding rule, and the binary coding rule is completely identical to the binary coding rule in step 1.2).

[0027] Preferably, the specific implementation of step 3) is:

[0028] 3.1) determining the number of bits of the binary coding obtained in step 2); the bits from left to right are Bit-1, Bit-2, Bit-3, …, Bit-n;

[0029] 3.2) Check the corresponding numeric code on Bit-1. If the numeric code is 1, it means that there is a non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1; if the numeric code is 0, it means that there is no non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1.

[0030] 3.3) Repeat step 3.2) sequentially, checking the corresponding numerical codes on Bit-2, Bit-3, ..., Bit-n, and confirming and filling the non-natural DNA polymer molecules on the corresponding bits; preferably, the specific implementation of step 3.3) is as follows:

[0031] Check the corresponding numerical code on Bit-2. If the numerical code is 1, it means that there is a non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2; if the numerical code is 0, it means that there is no non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2.

[0032] Check the corresponding numeric code on Bit-3. If the numeric code is 1, it means that there is a non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3; if the numeric code is 0, it means that there is no non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3.

[0033] ...

[0034] Check the corresponding numerical code on Bit-n. If the numerical code is 1, it means that there is a non-natural DNA polymer molecule M corresponding to Bit-n on Bit-n. n If the numeric code is 0, it means that there is no non-natural DNA polymer molecule M corresponding to Bit-n on Bit-n. n ;

[0035] 3.4) Collect and mix the non-natural DNA polymer molecules corresponding to all bits having a numeric code of 1 to obtain a mixture of non-natural DNA polymer molecules; the mixture of non-natural DNA polymer molecules stores the encrypted target information.

[0036] A method for decoding information based on non-natural DNA, the method comprising the following steps:

[0037] 1) Obtain a mixture of non-natural DNA polymer molecules as described above; the mixture of non-natural DNA polymer molecules is the encrypted target information;

[0038] 2) Real-time detection of the mixture of non-natural DNA polymer molecules obtained in step 1) based on the nanopore single molecule analysis technology, and decoding the target information from the mixture of non-natural DNA polymer molecules.

[0039] Preferably, the specific implementation of step 2) is:

[0040] 2.1) Obtain a key matched with the mixture of non-natural DNA polymer molecules; the key is a external stimulus condition matched with the stimulus-responsive chemical group in the mixture of non-natural DNA polymer molecules; the external stimulus condition is not less than 2;

[0041] 2.2) Real-time detection of the mixture of non-natural DNA polymer molecules by using the nanopore single molecule analysis technology, and obtaining the current signal generated by the movement of different non-natural DNA polymer molecules in the mixture of non-natural DNA polymer molecules relative to the nanopore;

[0042] 2.3) Repeat step 2.2) to obtain a set of information of current signals under different key stimulus conditions by using the key obtained in step 2.1);

[0043] 2.4) Take the intersection of the set of information obtained in step 2.3) to obtain the target information, and complete the information decoding.

[0044] Advantages: Compared with the prior art, the advantages of the present application are: the present application provides a non-natural DNA information encryption storage and decoding method, which uses a stimulus-responsive information encryption storage medium, and uses 2 or more external stimulus conditions as keys. The advantage of this key design is that the key does not need to be transmitted simultaneously with the storage medium, preventing the risk of information leakage during transmission. The information encryption storage medium in the present application is a mixture of non-natural DNA positional isomers of multiple specific sequences, the number of isomers is the same as the number of bits of binary encoding and one-to-one correspondence, and the presence or absence of the corresponding non-natural DNA polymer molecule is determined according to the binary code corresponding to the target information. The advantage of this storage method is that information is encoded only by specific non-natural DNA polymer molecules, without the need for further synthesis, simplifying the information storage process, being more sustainable, and more resource-saving. Finally, the non-natural DNA polymer molecules corresponding to the target information are detected by the nanopore single molecule analysis technology, the current signal generated by the movement of the non-natural DNA polymer molecules relative to the nanopore is obtained, and the information set under different external stimulus conditions is decoded. The target information is obtained by taking the intersection of the information set. The advantage of this method is that there are multiple information confused with the target information in a single information set. Only by obtaining all the keys can all the information sets be obtained and the correct information be decoded, greatly enhancing the security of the information transmission and decoding process, and better protecting the user's information privacy.

[0045] The application discloses an information encryption storage and decoding method based on non-natural DNA. The method first uses non-natural DNA polymer molecules as information encryption storage media, then converts target information into binary codes, confirms the presence or absence of information polymer molecules corresponding to the corresponding bits according to the binary codes, obtains information storage polymer molecules corresponding to the target information, and finally uses a nanopore single molecule analysis technology to detect the information storage polymer in real time and decode the target information. The application provides an information encryption storage and decoding method with higher storage density, higher reading efficiency and more secure information. BRIEF DESCRIPTION OF DRAWINGS

[0046] Figure 1 FIG. 1 is a schematic diagram of the information encryption storage and decoding method based on non-natural DNA of the application;

[0047] Figure 2 FIG. 4 is a structural formula schematic diagram of a light stimulus responsive chemical group;

[0048] Figure 3 FIG. 5 is five kinds of stimulus responsive non-natural DNA information encryption storage media and information storage methods based on the Baudot code of the application;

[0049] Figure 4 FIG. 6 is eight kinds of stimulus responsive non-natural DNA information encryption storage media and information storage methods based on the ASCII code of the application;

[0050] Figure 5 FIG. 7 is a schematic diagram of the nanopore single molecule analysis system of the application;

[0051] Figure 6 FIG. 8 is a schematic diagram of the information encryption decoding method based on non-natural DNA of the application;

[0052] Figure 7 FIG. 9 is a nanopore current signal diagram of the five kinds of stimulus responsive non-natural DNA information encryption storage media described in the embodiment of the application;

[0053] Figure 8 FIG. 10 is a single molecule signal current distribution diagram of the five kinds of stimulus responsive non-natural DNA information encryption storage media described in the embodiment of the application before and after ultraviolet light irradiation;

[0054] Figure 9 FIG. 11 is a single molecule signal current distribution diagram of the encrypted information "HELLO" and the information set after decoding described in the embodiment of the application. DETAILED DESCRIPTION

[0055] The following describes the embodiments of the application through specific examples, which are only used to specifically describe the application and not to limit the use range of the application.

[0056] This invention provides a method for encrypting, storing, and decoding information based on non-natural DNA, the method comprising the following steps:

[0057] Step 1: Utilize non-natural DNA polymer molecules as an information encryption and storage medium;

[0058] The specific steps are as follows: The non-natural DNA polymer molecule, serving as the information encryption storage medium, is composed of stimulus-responsive chemical groups and natural nucleotides. The key to this information encryption storage medium is an external stimulus condition, which includes two or more types. The stimulus-responsive chemical groups in the non-natural DNA polymer molecule include photoresponsive chemical groups, which can be one or more covalently modified on the DNA polymer molecule. When the number of stimulus-responsive chemical groups is one, they are located at different positions in the polymer chain, forming various non-natural DNA positional isomers with specific sequences. When the number of binary encoding bits is n, there are N types of non-natural DNA polymer molecules. For example, photoresponsive chemical groups include, but are not limited to, azobenzene (…). Figure 2 (a)), Spiropyran ( Figure 2 (b) ), o-nitrobenzyl ( Figure 2 (c) and its derivatives can undergo conformational transformation or bonding and breaking reactions under light conditions; the photoresponsive chemical group used in this invention is an azophenyl group, and the trans conformation of the non-natural DNA polymer molecule modified by it can be converted to the cis conformation under ultraviolet light excitation.

[0059] According to a preferred embodiment of the present invention, the information storage medium is a non-natural DNA polymer molecule composed of an azophenyl group and adenine deoxyribonucleotide. The trans conformation of this molecule can be converted to the cis conformation under ultraviolet light excitation, which is a photo-induced isomerism information encryption storage medium. When ultraviolet light irradiation is used as the key, the medium contains two keys: one before irradiation and one after irradiation. When the binary encoding bit length is n, there are n types of non-natural DNA polymer molecules, and the number of stimulus-responsive groups is one or more. When there is one stimulus-responsive chemical group, the stimulus-responsive group is modified from the 5' end of the non-natural DNA strand to form M1 to Mn at positions 1 to n respectively. n There are n types of non-natural DNA polymer molecules with positional isomers; when there are two or more stimulus-responsive chemical groups, there must be at least one natural nucleotide between the two stimulus-responsive groups;

[0060] like Figure 3As shown in (b), when the binary encoding is Baudot code, the number of encoding bits is 5, the number of types of non-natural DNA polymer molecules is 5, and the number of stimulus-responsive chemical groups is 1, the stimulus-responsive groups modify the non-natural DNA strand from the 5' end to the 1st to 5th positions to form 5 types of positionally isomorphic non-natural DNA polymer molecules, M1 to M5.

[0061] like Figure 4 (b) When the binary encoding shown is ASCII encoding, the encoding bit length is 8, the number of types of non-natural DNA polymer molecules is 8, and the non-natural DNA polymer molecules contain 1 or 2 stimulus-responsive chemical groups, which may be the same or different; when there is 1 stimulus-responsive chemical group, the stimulus-responsive group modifies the 1st to 5th positions of the non-natural DNA strand starting from the 5' end to form 5 types of non-natural DNA polymer molecules, M1 to M5; when there are 2 stimulus-responsive chemical groups, one stimulus-responsive group modifies the 1st position starting from the 5' end of the non-natural DNA strand, and the other stimulus-responsive group modifies the 3rd, 4th, and 5th positions to form 3 types of non-natural DNA polymer molecules, M6, M7, and M8.

[0062] For example, when there is only one stimulus-responsive chemical group, the number of natural nucleotides on the single-stranded DNA backbone is no more than n-1 when the stimulus-responsive chemical group is covalently modified onto the backbone. Specifically, the covalent modification is implemented by sequentially covalently modifying the stimulus-responsive chemical group at the 1st, 2nd, 3rd, ..., n-1th natural nucleotide front and n-1th natural nucleotide end of the single-stranded DNA, starting from the 5' end. It should be noted that the front end is located on the DNA backbone between the previous nucleotide and the adjacent nucleotide. Taking the 3rd natural nucleotide front as an example, this front end has the following structure:

[0063] The second natural nucleotide—the stimulus-responsive chemical group—the third natural nucleotide, that is: the stimulus-responsive chemical group is covalently modified on the DNA backbone.

[0064] When the number of stimulus-responsive chemical groups is one, in step 1.4), when the stimulus-responsive chemical groups are covalently modified onto different nucleotides of the single-stranded DNA, the number of natural nucleotides on the single-stranded DNA does not exceed n. The specific implementation of the covalent modification in step 1.4) is as follows: starting from the 5' end, the stimulus-responsive chemical groups are sequentially covalently modified onto the first, second, third, ..., (n-1)th, and nth natural nucleotides of the single-stranded DNA. Taking the third natural nucleotide as an example:

[0065] 2nd natural nucleotide - 3rd natural nucleotide (covalently modified with a stimuli-responsive chemical group) - 4th natural nucleotide.

[0066] Step two: converting the target information into binary code, the "1" or "0" of the corresponding bit of the binary code corresponds to the presence or absence of the information polymer molecule, the bits Bit-1 to Bit-n of the binary code correspond to the specific sequence of unnatural DNA polymer molecules M1 to M n one-to-one correspondence, obtaining the information storage polymer molecule corresponding to the binary code; when the number of binary code bits is n, there are n kinds of unnatural DNA polymer molecules; when the binary code is Baudot code, the number of code bits is 5, and there are 5 kinds of unnatural DNA polymer molecules; one character represented by the binary code corresponds to the combination of the corresponding unnatural DNA polymer molecule; the bit of the binary code corresponds to the presence or absence of a corresponding sequence of unnatural DNA polymer molecules, which is specifically manifested as: when the corresponding bit of the binary code corresponding to the target information is "0", there is no polymer molecule corresponding to the bit; when the corresponding bit of the binary code corresponding to the target information is "1", there is a polymer molecule corresponding to the bit. Of course, the 8-bit ASCII encoding mode can also be used in the present application, and the encoding mode is exactly the same as that of Baudot code.

[0067] This step is specifically: converting the target information into binary code, the bits of the binary code correspond one-to-one to the specific sequence of unnatural DNA polymer molecules, and in the order from low bit to high bit, if the number of the bit is "0", there is no unnatural DNA polymer molecule corresponding to the bit, if the number of the bit is "1", there is an unnatural DNA polymer molecule corresponding to the bit, and one character represented by the binary code is written by the combination of the mixture of unnatural DNA polymer molecules corresponding to the "1" of the corresponding bit in the code;

[0068] According to a preferred embodiment of the present application, as shown in (a), taking the letter "L" as the target information, it is converted into Baudot code "10010", according to the binary code, it can be confirmed that the information encryption storage medium exists M1 and M4 information polymer molecules corresponding to Bit-1 and Bit-4, and does not exist M2, M4 and M5 information polymer molecules corresponding to Bit-2, Bit-3 and Bit-5, and the information encryption storage medium corresponding to the letter "L" is the mixture of M1 and M4 molecules; as shown in (b), taking the letter "L" as the target information, it is converted into ASCII code "01101100", according to the binary code, it can be confirmed that the information encryption storage medium exists M1 and M4 information polymer molecules corresponding to Bit-1 and Bit-4, and does not exist M2, M4 and M5 information polymer molecules corresponding to Bit-2, Bit-3 and Bit-5, and the information encryption storage medium corresponding to the letter "L" is the mixture of M1 and M4 molecules. Figure 3 (a) shown, taking the letter "L" as the target information, it is converted into Baudot code "10010", according to the binary code, it can be confirmed that the information encryption storage medium exists M1 and M4 information polymer molecules corresponding to Bit-1 and Bit-4, and does not exist M2, M4 and M5 information polymer molecules corresponding to Bit-2, Bit-3 and Bit-5, and the information encryption storage medium corresponding to the letter "L" is the mixture of M1 and M4 molecules; as Figure 4(a) as shown, the target information is letter "L", which is converted into ASCII code "01001100", according to the binary code, it can be confirmed that there are M2, M5 and M6 information polymer molecules corresponding to Bit-2, Bit-5 and Bit-6 in the information encryption storage medium, and there are no M1, M3, M4, M7 and M8 information polymer molecules corresponding to Bit-1, Bit-3, Bit-4, Bit-7 and Bit-8, and the information encryption storage medium corresponding to the letter "L" is a mixture of M1 and M4 molecules;

[0069] Step three: real-time detection of the information storage polymer in step (2) by using the nanochannel single molecule analysis technology and decoding the target information;

[0070] The step is specifically: adding the information encryption storage medium in step two into the nanochannel single molecule analysis system, and obtaining the current signal generated by the movement of the non-natural DNA polymer molecule relative to the nanochannel; the current signal includes current signals with differences obtained under at least two different external stimulation conditions, the kind of the corresponding non-natural DNA polymer molecule is identified according to the current signals with differences obtained under different external stimulation conditions, the identification results under different external stimulation conditions are different, at least two information sets containing multiple information are decoded and obtained according to different identification results, the external stimulation condition is used as a key for information encryption, when the receiver does not have the key or does not have all the keys, the correct information cannot be decoded; only when the receiver has all the keys, all the information sets can be obtained, and the correct target information is obtained by taking the intersection of the information sets.

[0071] The kind of the corresponding non-natural DNA polymer molecule is identified according to the current signals with differences obtained under different external stimulation conditions, and the identification results under different external stimulation conditions are different; information decoding is performed according to the identification results under different external stimulation conditions, one or more information sets containing the target information are obtained under each stimulation condition; when there is only one information in the information set 1, there are multiple confused information in the information set 2; when there is only one information in the information set 2, there are multiple confused information in the information set 1; the external stimulation condition is used as a key for information encryption, when the receiver does not have the key, the correct information cannot be decoded; only when the receiver has all the keys, all the information sets can be obtained, and the correct target information is obtained by taking the intersection of the information sets.

[0072] According to a preferred embodiment of the present application, as shown in Figure 5 The information encryption storage medium, that is, the mixture of M1 and M4 molecules, is added into the nanochannel detection system, and the presence or absence of ultraviolet light is used as a key, if the receiver has the two keys, two detection results can be obtained, and the current distribution is as shown in Figure 6As shown, the current distribution map before light irradiation can identify that there are M1 molecules in the information encryption storage medium, there are no M3 and M5 molecules, and the existence of M2 and M4 molecules is doubtful. The decoding of the information set 1 containing the letters "G", "L" and "O" can be obtained through the identification result. The current distribution map after light irradiation can identify that there are M4 molecules in the information encryption storage medium, there are no M2 and M3 molecules, and the existence of M1 and M5 molecules is doubtful. The decoding of the information set 2 containing the letters "A", "L" and "W" can be obtained through the identification result. Through the information set 1 and the information set 2, the receiver finally obtains the correct target information letter "L".

[0073] Figure 5 is a schematic diagram of a nanopore single molecule analysis system, which comprises a molecular detection system, a signal sensing system and a data recording and processing system; wherein the molecular detection system comprises a detection cell 1 and a nanopore 2, when the nanopore is a biological nanopore, it is located in the center of the detection cell; the detection microcell on both sides of the nanopore contains an electrolyte solution 3, and an information encryption storage medium 4 is added to the electrolyte solution; the membrane pore system comprises a polytetrafluoroethylene support membrane 5 containing dozens of micrometer pores and a phospholipid bilayer 6, the phospholipid bilayer is attached to the support membrane containing 30-50 micrometer pores, and the biological nanopore 7 is self-assembled on the phospholipid bilayer membrane to form a single transmembrane channel, which is the only way to connect the electrolyte solutions on both sides of the detection cell; preferably, the biological nanopore is an Aerolysin biological nanopore. The signal sensing system comprises an Ag / AgCl electrode 8, a preamplifier probe 9, a weak current amplifier 10 and a digital-to-analog converter 11; one end of the electrode is immersed in the electrolyte solution on both sides of the detection cell, the other end of the electrode is connected with the preamplifier probe and a potential is applied, the ions in the electrolyte solution are driven by the voltage to pass through the nanopore to generate an ionic current signal, when a single molecule passes through the nanopore, the current decreases to generate an ionic current blocking signal, the analog signal is converted into a digital signal through the digital-to-analog converter, and the digital-to-analog converter is connected with the data recording and processing system; the data recording and processing system 12 comprises a computer and data acquisition and processing analysis software, the current signal is recorded and stored by the data acquisition software (such as the commercial Clampex software (Molecular Devices, LLC. Company)) on the computer, and then the signal processing and analysis are carried out through the data processing analysis software (such as the commercial Clamfit software (Molecular Devices, LLC. Company) and the OriginLab software (OringinLab Company)), so that the final experimental results are obtained, including a single molecule current signal distribution map.

[0074] Figure 7is a single molecule current signal graph produced when nanochannel detects M1 to M5 in the preferred embodiment of the present application, and the features of the single molecule current signal are extracted, including residual current value I and open channel current value I0, to obtain a statistical distribution graph of residual current degree I / I0, wherein the residual current value I is the ion current value of a single molecule in the channel, and the open channel current value I0 is the ion current value of no molecule in the channel.

[0075] Figure 8 is a single molecule signal current distribution graph obtained when nanochannel detects M1 to M5 in the preferred embodiment of the present application, Figure 8 (a) is a current distribution graph of M1 to M5 molecules respectively detected individually before light irradiation; Figure 8 (b) is a current distribution graph of M1 to M5 molecules respectively detected individually after light irradiation, which is a judgment basis for identifying the types of non-natural DNA polymer molecules in the information encryption storage medium according to the current distribution graph of the mixture.

[0076] Figure 9 is the current distribution graph of the letters "H", "E", "L", "L", "O" and the corresponding information set, if the target information is the word "HELLO", then the information set 1 before light irradiation contains 27 kinds of confused information Figure 9 (a)), and the information set 2 after light irradiation contains 243 kinds of confused information Figure 9 (b)), and the target information "HELLO" can be obtained by taking the intersection of the information set 1 and the information set 2.

Claims

1. A non-natural DNA-based information encryption method, characterized by: The non-natural DNA-based information encryption method comprises: 1) obtaining an information encryption storage medium; 2) binary coding the target information; 3) assigning the information encryption storage medium obtained in step 1) to the corresponding bits of the binary coded information obtained in step 2), and completing the target information encryption; The specific implementation of step 1) is: 1.1) determining the composition of the information encryption storage medium; the information encryption storage medium is a mixture formed by a plurality of non-natural DNA polymer molecules; the non-natural DNA polymer molecules comprise a single-stranded DNA formed by a plurality of natural nucleotides and a stimulus-responsive chemical group covalently modified on the single-stranded DNA; 1.2) determining the number of binary coded bits based on the binary coding rule; 1.3) determining the number of stimulus-responsive chemical groups and the number of natural nucleotides on the single-stranded DNA according to the number of binary coded bits determined in step 1.2); the number of binary coded bits is n, and the number of natural nucleotides on the single-stranded DNA is not more than n; 1.4) covalently modifying the stimuli-responsive chemical groups on the backbone of the single-stranded DNA or on different nucleotides of the single-stranded DNA, to obtain n kinds of unnatural DNA polymer molecules, which are specifically: unnatural DNA polymer molecule M1, unnatural DNA polymer molecule M2, unnatural DNA polymer molecule M3, …, unnatural DNA polymer molecule M n ; When the number of stimulus-responsive chemical groups is one, the number of natural nucleotides on the single-stranded DNA is not more than n-1 when the stimulus-responsive chemical group is covalently modified on the backbone of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is: sequentially covalently modifying the stimulus-responsive chemical group at the front end of the 1st natural nucleotide, the front end of the 2nd natural nucleotide, the front end of the 3rd natural nucleotide, …, the front end of the n-1th natural nucleotide, and the end of the n-1th natural nucleotide of the single-stranded DNA from the 5' end; When the number of stimulus-responsive chemical groups is one, the number of natural nucleotides on the single-stranded DNA is not more than n when the stimulus-responsive chemical group is covalently modified on different nucleotides of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is: sequentially covalently modifying the stimulus-responsive chemical group at the 1st natural nucleotide, the 2nd natural nucleotide, the 3rd natural nucleotide, …, the n-1th natural nucleotide, and the nth natural nucleotide of the single-stranded DNA from the 5' end; When the number of stimulus-responsive chemical groups is multiple, the number of natural nucleotides on the single-stranded DNA is not more than n-1 when the stimulus-responsive chemical group is covalently modified on the backbone of the single-stranded DNA in step 1.4), and the specific implementation of the covalent modification in step 1.4) is: sequentially covalently modifying the first stimulus-responsive chemical group at the front end of the 1st natural nucleotide, the front end of the 2nd natural nucleotide, the front end of the 3rd natural nucleotide, …, the front end of the n-1th natural nucleotide, and the end of the n-1th natural nucleotide of the single-stranded DNA from the 5' end; the remaining stimulus-responsive chemical groups except the first stimulus-responsive chemical group are covalently modified at least with one natural nucleotide as an interval in front of the remaining natural nucleotides except the natural nucleotide covalently modified by the first stimulus-responsive chemical group. The number of the stimulus-responsive chemical groups is multiple, the covalent modification of the stimulus-responsive chemical groups on different nucleotides of the single-stranded DNA in step 1.4) is as follows: The first stimulus-responsive chemical group is covalently modified on the first natural nucleotide, the second natural nucleotide, the third natural nucleotide, …, the n-1th natural nucleotide, and the nth natural nucleotide of the single-stranded DNA in sequence from the 5' end; the remaining stimulus-responsive chemical groups are covalently modified on the remaining natural nucleotides except the natural nucleotides covalently modified by the first stimulus-responsive chemical group, with at least one natural nucleotide as an interval; The specific implementation of step 3) is as follows: 3.1) determining the number of bits of the binary code obtained in step 2); the bits are Bit-1, Bit-2, Bit-3, …, Bit-n in sequence from left to right; 3.2) checking the corresponding digital code on Bit-1, if the digital code is 1, it indicates that there is a non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1; if the digital code is 0, it indicates that there is no non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1; 3.3) repeating step 3.2), checking the corresponding digital code on Bit-2, Bit-3, …, Bit-n in sequence, and completing the confirmation and filling of the non-natural DNA polymer molecules on the corresponding bits; the specific implementation of step 3.3) is as follows: checking the corresponding digital code on Bit-2, if the digital code is 1, it indicates that there is a non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2; if the digital code is 0, it indicates that there is no non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2; checking the corresponding digital code on Bit-3, if the digital code is 1, it indicates that there is a non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3; if the digital code is 0, it indicates that there is no non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3; …… Looking at the corresponding digital code on Bit-n, if the digital code is 1, it indicates that there is a non-natural DNA polymer molecule M corresponding to Bit-n on Bit-n n ; if the digital code is 0, it indicates that there is no non-natural DNA polymer molecule M corresponding to Bit-n on Bit-n n ; 3.4) collecting and mixing the non-natural DNA polymer molecules corresponding to the digital codes of all bits being 1 to obtain a mixture of non-natural DNA polymer molecules; the mixture of non-natural DNA polymer molecules stores the encrypted target information.

2. The non-natural DNA-based information encryption method according to claim 1, characterized by: The stimulus-responsive chemical group in step 1.1) is a photo-responsive chemical group that undergoes conformational transformation or bond formation and cleavage reaction under light conditions.

3. The non-natural DNA-based information encryption method according to claim 2, characterized by: The photo-responsive chemical group includes azobenzene, spiropyran, o-nitrobenzyl and its derivatives.

4. The non-natural DNA-based information encryption method according to claim 2, characterized by: The number of the stimulus-responsive chemical groups is one or more; the number of the natural nucleotides is not less than the number of the stimulus-responsive chemical groups; the natural nucleotides are the same or different.

5. The non-natural DNA-based information encryption method according to claim 1, characterized by: The binary coding rule in step 1.2) includes a 5-bit Baudot coding rule or an 8-bit ASCII coding rule.

6. The non-natural DNA based information encryption method according to claim 1 or 2 or 3 or 4 or 5, characterized in that: The binary coding in step 2) is achieved by using a binary coding rule, which is completely identical to the binary coding rule in step 1.2).

7. A non-natural DNA-based information decoding method for decoding the non-natural DNA-based information encoding method according to claim 1, characterized by: The information decoding method based on the non-natural DNA includes the following steps: 1) obtaining the mixture of non-natural DNA polymer molecules as claimed in claim 1; the mixture of non-natural DNA polymer molecules is the encrypted target information; 2) detecting the mixture of non-natural DNA polymer molecules obtained in step 1) in real time based on the nanochannel single molecule analysis technology, and decoding the target information from the mixture of non-natural DNA polymer molecules.

8. The non-natural DNA-based information decoding method according to claim 7, characterized by: The specific implementation of step 2) is: 2.1) obtaining the key matched with the mixture of non-natural DNA polymer molecules; the key is the external stimulation condition matched with the stimulus-responsive chemical group in the mixture of non-natural DNA polymer molecules; the external stimulation condition is not less than 2; 2.2) detecting the mixture of non-natural DNA polymer molecules in real time by using the nanochannel single molecule analysis technology, and obtaining the current signal generated by the movement of different non-natural DNA polymer molecules in the mixture of non-natural DNA polymer molecules relative to the nanochannel; 2.3) using the key obtained in step 2.1), repeating step 2.2), and respectively obtaining the information set of the current signal under different key stimulation conditions; 2.4) taking the intersection of the information set obtained in step 2.3), obtaining the target information, and completing the information decoding.

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