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

Abstract

The invention belongs to the field of information storage, and relates to an information encryption method and an information decoding method based on non-natural DNA, and the information encryption method based on the non-natural DNA comprises the following steps: 1) obtaining an information encryption storage medium; 2) performing binary coding on the target information; and (3) endowing the information encryption storage medium obtained in the step (1) into a corresponding bit of the binary code obtained in the step (2) to complete target information encryption. The non-natural DNA-based information decoding method comprises the following steps: 1) acquiring an information encryption storage medium corresponding to target information; and 2) detecting the information encryption storage medium in the step 1) in real time by using different secret keys based on a nanopore channel single molecule analysis technology, and decoding the target information.The invention provides the information encryption storage and decoding method which is higher in storage density, higher in reading efficiency and safer in information.

Description

Technical Field

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

[0002] Due to the explosive growth of electronic data, traditional materials used for information storage are no longer sufficient to store such high data capacity. In nature, a large amount of genetic information is stored in DNA molecules, which has prompted 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 respectively achieve information translation through four base sequences and DNA nanostructures. Among them, sequence-based DNA storage technology often uses PCR technology to synthesize DNA when encoding information. There is a possibility of error in the synthesis process, and for different information, new sequences often need to be synthesized. Nanostructure-based DNA storage technology generally uses chain exchange reactions to achieve information storage. In this storage method, at least 8 base pairs are required to correspond to one bit, and in addition to the main chain, short chains that promote structure formation need to be added to encode information. The storage density of these storage methods is difficult to be greatly improved, so improving the storage density and simplifying the storage scheme can make DNA storage easier to be applied to information storage.

[0003] In addition to using DNA for information storage, adding encryption functions when designing DNA storage media plays a vital role in ensuring the data security and privacy of users. There are research methods that store information in microdots or organic materials to create an information steganographic environment to achieve information encryption. However, 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 nanostructures can also be used to achieve encrypted information storage. For example, Zhang et al. used DNA origami technology to store encrypted information in a nanodot matrix structure similar to Braille. This structure can only be formed and decoded after adding matching short-chain DNA (Nat. Commun. 2019, 10, 5469); these methods require the addition of some substance to achieve information encryption, which means that these physical keys need to be transmitted together with the storage medium when transmitting information, which makes it easy to be intercepted or destroyed during transmission, so there is a risk of information leakage or loss.

[0004] Regarding 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. Nanostructure-based DNA storage methods can use AFM, fluorescence imaging, and nanopore single-molecule detection technologies to read and decode information. Among them, nanopore single-molecule technology is widely used in the field of DNA storage due to its high resolution, real-time and high 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 methods of using biological nanopores to detect DNA and achieve encrypted storage and decoding of information. Summary of the invention

[0005] Purpose of the invention: In order to solve the above-mentioned technical problems existing in the background technology, the present invention provides an information encryption storage and decoding method with higher storage density, higher reading efficiency and greater information security.

[0006] Technical solution: In order to achieve the above objectives, the present invention adopts the following technical solution:

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

[0008] 1) Obtaining information encryption storage medium;

[0009] 2) Binary encoding of target information;

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

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

[0012] 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;

[0013] 1.2) Determine the number of bits of the binary code based on the binary coding rules;

[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 does not exceed n;

[0015] 1.4) Covalently modifying the stimulus-responsive chemical group on the backbone of the single-stranded DNA or on different nucleotides of the single-stranded DNA to obtain n kinds of non-natural DNA polymer molecules, wherein the n kinds of non-natural DNA polymer molecules are: non-natural DNA polymer molecule M1, non-natural DNA polymer molecule M2, non-natural DNA polymer molecule M3, ..., non-natural DNA polymer molecule M n .

[0016] Preferably, the stimulus-responsive chemical group in step 1.1) is a photoresponsive chemical group that undergoes conformational transformation or bond-forming and bond-breaking reactions under light conditions; preferably, the photoresponsive chemical group includes but is not limited to azobenzene, spiropyran, o-nitrobenzyl and its derivatives; preferably, 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 identical or different.

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

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

[0019] Starting from the 5' end, the stimulus-responsive chemical groups are covalently modified at the front end of the first natural nucleotide, the front end of the second natural nucleotide, the front end of the third natural nucleotide, ..., the front end of the n-1 natural nucleotide and the end of the n-1 natural nucleotide of the single-stranded DNA;

[0020] When the number of the 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 does not exceed n, and the specific implementation method of the covalent modification in step 1.4) is:

[0021] Starting from the 5' end, the stimulus-responsive chemical groups are 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.

[0022] Preferably, when the number of the stimulus-responsive chemical groups is multiple, 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 does not exceed n-1, and the specific implementation method of the covalent modification in step 1.4) is:

[0023] Starting from the 5' end, the first stimulus-responsive chemical group is covalently modified at the front end of the first natural nucleotide, the front end of the second natural nucleotide, the front end of the third natural nucleotide, ..., the front end of the n-1 natural nucleotide and the end of the n-1 natural nucleotide of the single-stranded DNA; the remaining stimulus-responsive chemical groups except the first stimulus-responsive chemical group are covalently modified at the front ends of the remaining natural nucleotides except the first stimulus-responsive chemical group with at least one natural nucleotide as an interval;

[0024] When the number of the stimulus-responsive chemical groups is n, 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 does not exceed n, and the specific implementation method of the covalent modification of step 1.4) is:

[0025] Starting from the 5' end, the first stimulus-responsive chemical group is covalently modified 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; the remaining stimulus-responsive chemical groups except the first stimulus-responsive chemical group are covalently modified on the remaining natural nucleotides except the first stimulus-responsive chemical group with at least one natural nucleotide as an interval;

[0026] Preferably, the binary encoding in step 2) is implemented using binary encoding rules, and the binary encoding rules are exactly the same as the binary encoding rules in step 1.2).

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

[0028] 3.1) Determine the number of bits of the binary code obtained in step 2); the number of bits from left to right is Bit-1, Bit-2, Bit-3, ..., Bit-n;

[0029] 3.2) Check the digital code corresponding to Bit-1. If the digital code is 1, it means that there is a non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1; if the digital 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), check the corresponding digital codes on Bit-2, Bit-3, ..., Bit-n in turn, and complete the confirmation and filling of the non-natural DNA polymer molecule on the corresponding Bit; preferably, the specific implementation method of step 3.3) is:

[0031] Check the digital code corresponding to Bit-2. If the digital code is 1, it means that there is a non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2; if the digital 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 digital code corresponding to Bit-3. If the digital code is 1, it means that there is a non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3; if the digital 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 digital code on Bit-n. If the digital 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 digital 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 the digital codes on 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.

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

[0037] 1) obtaining 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) Detecting the mixture of non-natural DNA polymer molecules obtained in step 1) in real time based on nanopore single molecule analysis technology, and decoding target information from the mixture of non-natural DNA polymer molecules.

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

[0040] 2.1) obtaining a key that matches the mixture of non-natural DNA polymer molecules; the key is an external stimulus condition that matches the stimulus-responsive chemical group in the mixture of non-natural DNA polymer molecules; the external stimulus conditions are no less than 2;

[0041] 2.2) using nanopore single molecule analysis technology to detect the mixture of non-natural DNA polymer molecules in real time, 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) using the key obtained in step 2.1), repeating step 2.2) to obtain information sets of current signals under different key stimulation conditions;

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

[0044] Beneficial effect: Compared with the prior art, the advantages of the present invention are: the present invention provides a method for encrypting, storing and decoding information based on non-natural DNA, which adopts a stimulus-responsive information encryption storage medium, and uses two 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, thereby preventing the risk of information leakage during the transmission process; the information encryption storage medium in the present invention is a mixture of non-natural DNA positional isomers of multiple specific sequences, and the types of isomers are the same as the number of bits in the binary code and correspond one to one. The presence or absence of non-natural DNA polymer molecules corresponding to the corresponding bits is determined according to the binary code corresponding to the target information. The advantage of this storage method is that information is only transmitted through The information is encoded through specific non-natural DNA polymer molecules without the need for re-synthesis, which simplifies the information storage process, makes it more sustainable and saves resources. Finally, the non-natural DNA polymer molecules corresponding to the target information are detected through nanopore single-molecule analysis technology, and the current signal generated by the movement of the non-natural DNA polymer molecules relative to the nanopore is obtained. The information set under different external stimulation conditions is decoded, and the target information is obtained by taking the intersection of the information set. The advantage of this method is that there are multiple pieces of 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 decoded, which greatly enhances the security of the information transmission and decoding process, and can better protect the privacy of user information.

[0045] The present invention 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 the 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 nanopore single molecule analysis technology to detect the information storage polymer in real time and decode the target information. The present invention provides an information encryption storage and decoding method with higher storage density, higher reading efficiency and more secure information. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

[0048] Figure 3 The present invention provides five stimulus-responsive non-natural DNA information encryption storage media and information storage methods based on Bodo coding;

[0049] Figure 4 The present invention provides 8 types of stimulus-responsive non-natural DNA information encryption storage media and information storage methods based on ASCII encoding;

[0050] Figure 5 Schematic diagram of the nanopore single molecule analysis system of the present invention;

[0051] Figure 6 Schematic diagram of the encrypted information decoding method based on non-natural DNA of the present invention;

[0052] Figure 7 Nanopore current signal diagrams of five stimulus-responsive non-natural DNA information encryption storage media described in the embodiments of the present invention;

[0053] Figure 8 The single-molecule signal current distribution diagram of the five stimulus-responsive non-natural DNA information encryption storage media before and after ultraviolet light irradiation described in the implementation examples of the present invention;

[0054] Fig. 9 It is a single molecule signal current distribution diagram of the encrypted information "HELLO" described in the implementation example of the present invention and a decoded information set. DETAILED DESCRIPTION

[0055] The following is an explanation of the embodiments of the present invention by means of specific examples. The examples are only used to explain the present invention in detail but not to limit the scope of application of the present invention.

[0056] The present invention provides a method for information encryption, storage and decoding based on non-natural DNA, the method comprising the following steps:

[0057] Step 1: Using non-natural DNA polymer molecules as information encryption storage media;

[0058] The specific steps are as follows: the non-natural DNA polymer molecule as the information encryption storage medium is composed of stimulus-responsive chemical groups and natural nucleotides, the key of the information encryption storage medium is the external stimulus condition, and the external stimulus condition includes 2 or more; the stimulus-responsive chemical groups in the non-natural DNA polymer molecule include light-responsive chemical groups, and the stimulus-responsive chemical groups can be one or more covalently modified on the DNA polymer molecule; when the number of stimulus-responsive chemical groups is 1, they are located at different positions of the polymer chain, and can form non-natural DNA positional isomers of multiple specific sequences; when the number of binary coding bits is n, the non-natural DNA polymer molecules have a total of N types. Exemplarily, the light-responsive chemical groups include but are not limited to azobenzene ( Figure 2 (a)), spiropyran ( Figure 2 (b)), o-nitrobenzyl ( Figure 2 (c)) and its derivatives, which can undergo conformational transformation or bond-forming and bond-breaking reactions under light conditions; the light-responsive chemical group used in the present invention is an azobenzene group, and the trans conformation of the non-natural DNA polymer molecule modified by it can be converted into a 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 azobenzene group and adenine deoxyribonucleotide, the trans conformation of the molecule can be converted into a cis conformation under ultraviolet light excitation, and is a photoisomerizable information encryption storage medium. When the medium uses ultraviolet light as a key, it contains two keys before and after illumination; when the number of binary coding bits is n, there are n types of non-natural DNA polymer molecules, and the number of stimulus-responsive groups is 1 or more; when the number of stimulus-responsive chemical groups is 1, the stimulus-responsive group is modified from the 5' end of the non-natural DNA chain to form M1 to M2 at the 1st to the nth positions, respectively. n There are n kinds of non-natural DNA polymer molecules with positional isomerism; when there are two or more stimulus-responsive chemical groups, at least one natural nucleotide is separated between two stimulus-responsive groups;

[0060] like Figure 3As shown in (b), when the binary code is Baudot code, the number of coding bits is 5, the number of types of non-natural DNA polymer molecules is 5, and the number of stimuli-responsive chemical groups is 1, the stimuli-responsive group starts from the 5' end of the non-natural DNA chain and modifies the 1st to 5th positions thereof to form 5 types of positionally isomeric non-natural DNA polymer molecules from M1 to M5;

[0061] like Figure 4 When the binary code shown in (b) is ASCII code, the number of coding bits 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, and the stimulus-responsive chemical groups are the same or different; when the number of stimulus-responsive chemical groups is 1, the stimulus-responsive group is modified at the 1st to 5th positions starting from the 5' end of the non-natural DNA chain to form 5 types of non-natural DNA polymer molecules M1 to M5, and when the number of stimulus-responsive chemical groups is 2, one of the stimulus-responsive groups is modified at the 1st position starting from the 5' end of the non-natural DNA chain, and the other stimulus-responsive group is modified at the 3rd, 4th and 5th positions to form 3 types of non-natural DNA polymer molecules M6, M7 and M8.

[0062] Exemplarily, when the number of stimulus-responsive chemical groups is one, when the stimulus-responsive chemical group is covalently modified on the backbone of the single-stranded DNA, the number of natural nucleotides on the single-stranded DNA does not exceed n-1, wherein the specific implementation method of the covalent modification is: starting from the 5' end, the stimulus-responsive chemical group is covalently modified on 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. It should be noted that the front end is on the DNA backbone and is located between the previous nucleotide and the adjacent nucleotide. Taking the front end of the 3rd natural nucleotide as an example, the front end has such a 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, when the stimulus-responsive chemical group is covalently modified on different nucleotides of the single-stranded DNA in step 1.4), the number of natural nucleotides on the single-stranded DNA does not exceed n. The specific implementation method of the covalent modification of step 1.4) is: starting from the 5' end, the 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. Still taking the third natural nucleotide as an example:

[0065] Natural nucleotide at position 2—natural nucleotide at position 3 (covalently modified with a stimulus responsive chemical group)—natural nucleotide at position 4.

[0066] Step 2: Convert the target information into binary code. The corresponding bit of the binary code is "1" or "0" corresponding to the presence or absence of the information polymer molecule. The bits Bit-1 to Bit-n of the binary code are respectively associated with the non-natural DNA polymer molecules M1 to M2 of the specific sequence. n One-to-one correspondence is used to obtain information storage polymer molecules corresponding to binary codes; when the number of binary code bits is n, there are n types of non-natural DNA polymer molecules; when the binary code is Baudot code, the number of code bits is 5, and there are 5 types of non-natural DNA polymer molecules; a character represented by the binary code corresponds to a combination of corresponding non-natural DNA polymer molecules; the bit of the binary code corresponds to the presence or absence of a corresponding sequence of non-natural DNA polymer molecules, which is specifically manifested as: when the corresponding bit in the binary code corresponding to the target information is "0", there is no polymer molecule corresponding to the bit, and when the corresponding bit in 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 method can also be used in the present invention, and its encoding method is exactly the same as that of the Baudot code.

[0067] The step is specifically as follows: converting the target information into a binary code, wherein the bits of the binary code correspond one to one with the non-natural DNA polymer molecules of the specific sequence, and in order from low to high bits, if the number of the bit is "0", then there is no non-natural DNA polymer molecule corresponding to the bit, and if the number of the bit is "1", then there is a non-natural DNA polymer molecule corresponding to the bit, and a character represented by the binary code is written by a mixture combination of non-natural DNA polymer molecules corresponding to the corresponding bits of the code being "1";

[0068] According to a preferred embodiment of the present invention, Figure 3 As shown in (a), the letter "L" is used as the target information and converted into the Baudot code "10010". According to the binary code, it can be confirmed that the information encryption storage medium has M1 and M4 information polymer molecules corresponding to Bit-1 and Bit-4, and does not have M2, M4 and M5 information polymer molecules corresponding to Bit-2, Bit-3 and Bit-5. The information encryption storage medium corresponding to the letter "L" is a mixture of M1 and M4 molecules; Figure 4As shown in (a), the letter "L" is taken as the target information and converted into the ASCII code "01001100". According to the binary code, it can be confirmed that the information encryption storage medium contains M2, M5 and M6 information polymer molecules corresponding to Bit-2, Bit-5 and Bit-6, but does not contain M1, M3, M4, M7 and M8 information polymer molecules corresponding to Bit-1, Bit-3, Bit-4, Bit-7 and Bit-8. The information encryption storage medium corresponding to the letter "L" is a mixture of M1 and M4 molecules.

[0069] Step 3: Using nanopore single molecule analysis technology to detect the information storage polymer in step (2) in real time and decode the target information;

[0070] This step is specifically as follows: adding the information encryption storage medium in step 2 to the nanopore single molecule analysis system to obtain the current signal generated by the movement of the non-natural DNA polymer molecule relative to the nanopore; the current signal includes different current signals obtained under at least two different external stimulation conditions, and the type of the corresponding non-natural DNA polymer molecule is identified according to the different current signals obtained under different external stimulation conditions, the identification results under different external stimulation conditions are different, and at least two information sets containing multiple information are decoded and obtained according to the different identification results, and the external stimulation conditions are used as the 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 can all the information sets be obtained, and the correct target information is obtained by taking the intersection of the information sets.

[0071] According to the different current signals obtained under different external stimulation conditions, the types of non-natural DNA polymer molecules corresponding to the non-natural DNA polymer molecules are identified, 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, and one or more information sets containing target information are obtained under each stimulation condition; when there is and only one information in information set 1, information set 2 contains multiple obfuscated information; when there is and only one information in information set 2, information set 1 contains multiple obfuscated information; external stimulation conditions are used as keys for information encryption, and when the receiver does not have the keys, the correct information cannot be decoded; only when the receiver has all the keys can all information sets 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 invention, Figure 5 As shown in Figure 2, the information encryption storage medium, i.e., a mixture of M1 and M4 molecules, is added to the nanopore detection system, and the presence or absence of ultraviolet light is used as the key. If the receiver has these two keys, two detection results can be obtained, and the current distribution is as follows: Figure 6As shown, through the current distribution diagram before illumination, it can be identified that there must be M1 molecules in the information encryption storage medium, there are no M3 and M5 molecules, and the existence of M2 and M4 molecules is questionable. Through this identification result, information set 1 containing the letters "G", "L" and "O" can be decoded. Through the current distribution diagram after illumination, it can be identified that there must be M4 molecules in the information encryption storage medium, there are no M2 and M3 molecules, and the existence of M1 and M5 molecules is questionable. Through this identification result, information set 2 containing the letters "A", "L" and "W" can be decoded; by taking information set 1 and information set 2, the receiver finally obtains the correct target information letter "L".

[0073] Figure 5 It is a schematic diagram of a nanopore single molecule analysis system, which includes a molecular detection system, a signal sensing system and a data recording and processing system; wherein, the molecular detection system includes a detection pool 1 and a nanopore 2, and when the nanopore is a biological nanopore, it is located in the center of the detection pool; the detection microcells on both sides of the nanopore contain an electrolyte solution 3, and an information encryption storage medium 4 is added to the electrolyte solution; the membrane pore system includes a polytetrafluoroethylene support membrane 5 containing pores of tens of microns and a phospholipid bilayer 6, the phospholipid bilayer is attached to the support membrane containing pores of 30 to 50 microns, and the biological nanopore 7 self-assembles on the phospholipid bilayer membrane to form a single transmembrane channel, which is the only one that conducts the electrolyte solutions on both sides of the detection pool; preferably, the biological nanopore is an Aerolysin biological nanopore. The signal sensing system includes Ag / AgCl electrodes 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, and the other end of the electrode is connected to the preamplifier probe and a potential is applied. The ions in the electrolyte solution are directed through the nanopores under voltage drive to generate ion current signals. When a single molecule passes through the pore, the current decreases to generate an ion current blocking signal. The analog signal is converted into a digital signal by the digital-to-analog converter, and the digital-to-analog converter is connected to the data recording and processing system; the data recording and processing system 12 includes a computer and data acquisition and processing analysis software. The current signal is recorded and stored by the data acquisition software on the computer (such as the commercial Clampex software (Molecular Devices, LLC.)), and then the signal is processed and analyzed by the data processing and analysis software (such as the commercial Clamfit software (Molecular Devices, LLC.) and OriginLab software (OringinLab)) to obtain the final experimental results, including the single molecule current signal distribution diagram.

[0074] Figure 7It is a single-molecule current signal diagram generated when the nanopore detects M1 to M5 in the preferred embodiment of the present invention, and the characteristics of the single-molecule current signal are extracted, including the residual current value I and the open pore current value I0, to obtain a statistical distribution diagram of the residual current degree I / I0, wherein the residual current value I is the ionic current value when a single molecule is in the pore, and the open pore current value I0 is the ionic current value when there is no molecule in the pore.

[0075] Figure 8 is a single molecule signal current distribution diagram obtained by nanopore detection M1 to M5 in the preferred embodiment of the present invention, Figure 8 (a) is the current distribution diagram when M1 to M5 molecules are detected separately before illumination; Figure 8 (b) is the current distribution diagram when the M1 to M5 molecules are detected separately after illumination. This diagram is the basis for determining the type of non-natural DNA polymer molecules in the information encryption storage medium based on the current distribution diagram of the mixture.

[0076] Fig. 9 It is the current distribution diagram of the five letters "H", "E", "L", "L", and "O" and the corresponding information set. If the target information is the word "HELLO", the information set 1 before illumination contains 27 kinds of confusing information ( Fig. 9 (a)), the information set 2 after illumination contains 243 kinds of confusing information ( Fig. 9 (b)), the target information “HELLO” can be obtained by taking the intersection of information set 1 and information set 2.

Claims

1. A method for information encryption based on non-natural DNA, characterized in that: The information encryption method based on non-natural DNA comprises: 1) Obtaining information encryption storage medium; 2) Binary encoding of target information; 3) The information encryption storage medium obtained in step 1) is assigned to the corresponding bit of the binary code obtained in step 2) to complete the encryption of the target information.

2. The information encryption method based on non-natural DNA according to claim 1, characterized in that: The specific implementation method 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) Determine the number of bits of the binary code based on the binary coding rules; 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 does not exceed n; 1.4) Covalently modifying the stimulus-responsive chemical group on the backbone of the single-stranded DNA or on different nucleotides of the single-stranded DNA to obtain n kinds of non-natural DNA polymer molecules, wherein the n kinds of non-natural DNA polymer molecules are: non-natural DNA polymer molecule M1, non-natural DNA polymer molecule M2, non-natural DNA polymer molecule M3, ..., non-natural DNA polymer molecule M n .

3. The information encryption method based on non-natural DNA according to claim 2, characterized in that: The stimulus-responsive chemical group in step 1.1) is a light-responsive chemical group that undergoes conformational transformation or bond-forming and bond-breaking reactions under light conditions; preferably, the light-responsive chemical group includes but is not limited to azobenzene, spiropyran, o-nitrobenzyl and its derivatives; preferably, 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 identical or different.

4. The information encryption method based on non-natural DNA according to claim 3, characterized in that: The binary encoding rule in step 1.2) includes a 5-bit Baudot encoding rule or an 8-bit ASCII encoding rule.

5. The information encryption method based on non-natural DNA according to claim 4, characterized in that: When the number of the stimulus-responsive chemical group is one, when the stimulus-responsive chemical group is covalently modified on the backbone of the single-stranded DNA in step 1.4), the number of natural nucleotides on the single-stranded DNA does not exceed n-1, and the specific implementation method of the covalent modification in step 1.4) is: Starting from the 5' end, the stimulus-responsive chemical groups are covalently modified at the front end of the first natural nucleotide, the front end of the second natural nucleotide, the front end of the third natural nucleotide, ..., the front end of the n-1 natural nucleotide and the end of the n-1 natural nucleotide of the single-stranded DNA; When the number of the 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 does not exceed n, and the specific implementation method of the covalent modification in step 1.4) is: Starting from the 5' end, the stimulus-responsive chemical groups are 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.

6. The information encryption method based on non-natural DNA according to claim 4, characterized in that: When the number of the stimulus-responsive chemical groups is multiple, 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 does not exceed n-1, and the specific implementation method of the covalent modification in step 1.4) is: Starting from the 5' end, the first stimulus-responsive chemical group is covalently modified at the front end of the first natural nucleotide, the front end of the second natural nucleotide, the front end of the third natural nucleotide, ..., the front end of the n-1 natural nucleotide and the end of the n-1 natural nucleotide of the single-stranded DNA; the remaining stimulus-responsive chemical groups except the first stimulus-responsive chemical group are covalently modified at the front ends of the remaining natural nucleotides except the first stimulus-responsive chemical group with at least one natural nucleotide as an interval; When the number of the 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 does not exceed n, and the specific implementation method of the covalent modification in step 1.4) is: Starting from the 5' end, the first stimulus responsive chemical group is covalently modified 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; the remaining stimulus responsive chemical groups except the first stimulus responsive chemical group are covalently modified on the remaining natural nucleotides except the first stimulus responsive chemical group with at least one natural nucleotide as an interval.

7. The information encryption method based on non-natural DNA according to claim 2 or 3 or 4 or 5 or 6, characterized in that: The binary coding in step 2) is implemented by using binary coding rules, and the binary coding rules are exactly the same as the binary coding rules in step 1.2).

8. The information encryption method based on non-natural DNA according to claim 7, characterized in that: The specific implementation method of step 3) is: 3.1) Determine the number of bits of the binary code obtained in step 2); the number of bits from left to right is Bit-1, Bit-2, Bit-3, ..., Bit-n; 3.2) Check the digital code corresponding to Bit-1. If the digital code is 1, it means that there is a non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1; if the digital code is 0, it means that there is no non-natural DNA polymer molecule M1 corresponding to Bit-1 on Bit-1; 3.3) Repeat step 3.2), check the corresponding digital codes on Bit-2, Bit-3, ..., Bit-n in turn, and complete the confirmation and filling of the non-natural DNA polymer molecule on the corresponding Bit; preferably, the specific implementation method of step 3.3) is: Check the digital code corresponding to Bit-2. If the digital code is 1, it means that there is a non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2; if the digital code is 0, it means that there is no non-natural DNA polymer molecule M2 corresponding to Bit-2 on Bit-2; Check the digital code corresponding to Bit-3. If the digital code is 1, it means that there is a non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3; if the digital code is 0, it means that there is no non-natural DNA polymer molecule M3 corresponding to Bit-3 on Bit-3; …… Check the corresponding digital code on Bit-n. If the digital 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 digital code is 0, it means that there is no non-natural DNA polymer molecule M corresponding to Bit-n on Bit-n n ; 3.4) Collect and mix the non-natural DNA polymer molecules corresponding to the digital codes on 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.

9. A method for decoding information based on non-natural DNA, characterized in that: The information decoding method based on non-natural DNA comprises the following steps: 1) obtaining a mixture of non-natural DNA polymer molecules as described in claim 8; the mixture of non-natural DNA polymer molecules is encrypted target information; 2) Detecting the mixture of non-natural DNA polymer molecules obtained in step 1) in real time based on nanopore single molecule analysis technology, and decoding target information from the mixture of non-natural DNA polymer molecules.

10. The information decoding method based on non-natural DNA according to claim 9, characterized in that: The specific implementation method of step 2) is: 2.1) obtaining a key that matches the mixture of non-natural DNA polymer molecules; the key is an external stimulus condition that matches the stimulus-responsive chemical group in the mixture of non-natural DNA polymer molecules; the external stimulus conditions are no less than 2; 2.2) using nanopore single molecule analysis technology to detect the mixture of non-natural DNA polymer molecules in real time, 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; 2.3) using the key obtained in step 2.1), repeating step 2.2) to obtain information sets of current signals under different key stimulation conditions; 2.4) Take the intersection of the information sets obtained in step 2.3) to obtain the target information and complete the information decoding.

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