DNA data storage method and core-shell fiber

Abstract

The invention provides a DNA data storage method and a core-shell fiber, and relates to the technical field of DNA data storage, the method comprises the following steps: encoding to-be-stored information, and synthesizing DNA molecules carrying the to-be-stored information; preparing a core layer electrospinning solution by using the DNA molecules, a DNA stabilizing solution and a packaging material; preparing a shell layer electrospinning solution by utilizing a shell material packaging material; the core layer electrospinning solution and the shell layer electrospinning solution are utilized, electrospinning is carried out through a coaxial electrospinning technology, core-shell fibers are obtained, the core-shell fibers comprise a core layer and a shell layer, the DNA molecules are stored in the core layer, and the shell layer wraps the core layer to form a coaxial composite structure.

Description

Technical Field

[0001] The present application relates to the technical field of DNA data storage, and in particular to a DNA data storage method and a core-shell fiber. Background Art

[0002] As the volume of digital information grows exponentially, deoxyribonucleotides (DNA) are considered to be an excellent carrier for information storage and have become a research hotspot in the field of data storage. As a data storage medium, DNA has the characteristics of high storage density and easy long-term storage. At present, existing technologies can successfully encode digital information into nucleotide bases, artificially synthesize DNA, and sequence DNA to completely restore the original computer files.

[0003] In practical applications, DNA molecules carrying information are often stored in solutions. However, DNA is easily affected by various factors during long-term solution storage, which leads to a decrease in its stability, such as changes in environmental temperature and humidity, degradation, etc., and ultimately leads to data loss. Therefore, it is urgent to propose a DNA data storage method and core-shell fiber to improve the stability of DNA data storage. Summary of the invention

[0004] In view of the above problems, the embodiments of the present application provide a DNA data storage method and a core-shell fiber to overcome the above problems or at least partially solve the above problems.

[0005] In a first aspect of an embodiment of the present application, a DNA data storage method is provided, the method comprising: Encoding the information to be stored and synthesizing a DNA molecule carrying the information to be stored; Using the DNA molecules, DNA stabilizing solution and packaging materials, a core layer electrospinning solution is prepared; Using shell materials to encapsulate materials and prepare shell electrospinning solution; The core layer electrospinning solution and the shell layer electrospinning solution are used to perform electrospinning by coaxial electrospinning technology to obtain core-shell fibers. The core-shell fibers include a core layer and a shell layer. The core layer stores the DNA molecules, and the shell layer wraps the core layer to form a coaxial composite structure.

[0006] In a possible implementation, the packaging material is at least one of the following: polyvinyl alcohol, polyethylene oxide, and polycaprolactone.

[0007] In a possible implementation, the mass ratio of the DNA molecules, the DNA stabilizing solution and the packaging material in the core layer electrospinning solution is (0.01-40) g / L: (0.01-200) g / L: (50-200) g / L.

[0008] In a possible implementation manner, the mass ratio of the shell material packaging material in the shell layer electrospinning solution is 50-200 g / L.

[0009] In a possible implementation, the core layer electrospinning solution and the shell layer electrospinning solution are used to perform electrospinning by coaxial electrospinning technology to obtain the core-shell fiber, including: Injecting the core layer electrospinning solution into a core layer syringe, and injecting the shell layer electrospinning solution into a shell layer syringe; Connecting the core layer injector to the core layer electrospinning nozzle of the coaxial electrospinning nozzle device, connecting the shell layer injector to the shell layer electrospinning nozzle of the coaxial electrospinning nozzle device, and connecting the coaxial electrospinning nozzle device to an electrostatic high voltage generator via a wire; The coaxial electrospinning nozzle device is started by the electrostatic high voltage generator, and the fiber filaments ejected from the electrospinning nozzle of the coaxial electrospinning nozzle device are received by the receiving plate to obtain the core-shell fiber.

[0010] In one possible embodiment, the operating voltage of the electrostatic high-voltage generator is 12-20 kV, the injection rate of the shell layer syringe is 1.8-2.0 ml / h, the injection rate of the core layer syringe is 0.5-1.0 ml / h, and the receiving distance between the receiving plate and the electrospinning nozzle of the coaxial electrospinning nozzle device is 10-15 cm.

[0011] In a possible implementation manner, the inner diameter of the core layer electrospinning nozzle is 0.08 mm-1.0 mm, and the inner diameter of the shell layer electrospinning nozzle is 0.04 mm-0.4 mm.

[0012] In a possible implementation, the method further includes: The physical position of each core-shell fiber and the DNA molecules carried are encoded to generate a DNA information index table, which contains a mapping relationship between the DNA molecules and the physical positions of the core-shell fibers.

[0013] In a possible implementation, the method further includes: The core-sheath fibers are subjected to heat treatment or wet heat treatment.

[0014] The second aspect of the embodiment of the present application further provides a core-shell fiber for storing DNA information, the core-shell fiber comprising a core layer and a shell layer, the core layer storing the DNA molecules, the shell layer wrapping the core layer to form a coaxial composite structure; Wherein, the core-shell fiber is prepared by the DNA data storage method described in the first aspect of the embodiment of the present application.

[0015] An embodiment of the present application provides a DNA data storage method, the method comprising: encoding information to be stored, synthesizing DNA molecules carrying the information to be stored; preparing a core layer electrospinning solution using the DNA molecules, a DNA stabilizing solution and a packaging material; preparing a shell layer electrospinning solution using a shell material packaging material; and performing electrospinning using the core layer electrospinning solution and the shell layer electrospinning solution by coaxial electrospinning technology to obtain a core-shell fiber, the core-shell fiber comprising a core layer and a shell layer, the core layer storing the DNA molecules, and the shell layer wrapping the core layer to form a coaxial composite structure.

[0016] The embodiment of the present application uses the DNA molecules carrying the information to be stored to prepare the core layer electrospinning solution, and then uses the core layer electrospinning solution and the shell layer electrospinning solution to perform electrospinning through the coaxial electrospinning technology to obtain the core-shell fiber, thereby storing the DNA molecules in the inner layer (core layer) of the core-shell fiber, and using the shell layer that has no negative impact on the stability of the DNA and the structural properties of the nanowire as a protective layer to cover the core layer. Therefore, the present application adopts the coaxial electrospinning technology to achieve precise encapsulation at the nanoscale and maintain the stability of the encapsulated object, avoiding the risk of DNA being directly exposed to the environment and being destroyed, providing an efficient and practical DNA information storage method, and further improving the stability of DNA data storage. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the description of the embodiments of the present application will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0018] Figure 1 is a flow chart of the steps of a DNA data storage method provided in an embodiment of the present application; Figure 2 It is a schematic diagram of the structure of a core-shell fiber provided in an embodiment of the present application; Figure 3 is a schematic diagram of a coaxial electrospinning process provided in an embodiment of the present application; Description of the drawings: core layer 1, DNA molecule 2, shell layer 3, DNA stabilizer 4; Injection pump 101 , core layer injector 102 , shell layer injector 103 , electrostatic high voltage generator 104 , core-shell fiber 105 , receiving plate 106 . DETAILED DESCRIPTION

[0019] The exemplary embodiments of the present application will be described in more detail below in conjunction with the accompanying drawings in the embodiments of the present application. Although the exemplary embodiments of the present application are shown in the accompanying drawings, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments set forth herein. On the contrary, these embodiments are provided in order to enable a more thorough understanding of the present application and to enable the scope of the present application to be fully communicated to those skilled in the art.

[0020] Existing hardware storage technologies (such as disks, hard drives, flash memory, etc.) have limited storage density and their maintenance costs increase with the use of hardware. As the volume of digital information grows exponentially, deoxyribonucleotides (DNA) are considered to be an excellent carrier for information storage and have become a research hotspot in the field of data storage. As a storage medium, DNA has the characteristics of high storage density and easy long-term storage. In terms of storage density, existing DNA data storage technology can achieve a data density of more than 200PB per gram, which is much higher than conventional media; in terms of storage life, readable DNA has been recovered from fossils hundreds of thousands of years ago. Existing technologies can successfully encode digital information into nucleotide bases, artificially synthesize DNA, and sequence DNA to completely restore it to the original computer file.

[0021] In practical applications, DNA molecules carrying information are often preserved in a solution. However, DNA is easily affected by various factors during long-term solution storage, which leads to a decrease in its stability, such as changes in environmental temperature and humidity, degradation, etc., and ultimately leads to data loss. In solution, DNA molecules can be stably stored for about 10 years, which has no obvious advantages over other storage media. Therefore, the existing DNA data storage methods have the following two problems: one is that during the storage process, the degradation of DNA molecules will lead to data loss and make data recovery difficult. The other is that it is difficult to quickly access specific information, and the entire library needs to be sequenced when searching and reading.

[0022] In view of the above problems, the present application proposes a DNA data storage method and a core-shell fiber to improve the stability of DNA data storage. In conjunction with the accompanying drawings, a DNA data storage method provided by the present application is described in detail through some embodiments and their application scenarios.

[0023] The first aspect of the present application provides a DNA data storage method, referring to Figure 1 , Figure 1 A flow chart of the steps of a DNA data storage method provided in an embodiment of the present application is as follows: Figure 1 As shown, the method includes: Step S101, encoding the information to be stored, and synthesizing a DNA molecule carrying the information to be stored.

[0024] DNA is an excellent data storage medium, which shows an information density of one million bytes of data per gram and has high durability. In this embodiment, the corresponding DNA molecule can be synthesized based on the information to be stored (i.e., the information to be stored). The specific method of synthesizing DNA molecules is not limited in this embodiment of the application, and the steps mainly include: Step S1011, encoding the information to be stored, converting the selected information into a bit sequence in binary or other forms.

[0025] Step S1012, designing a coding rule for the DNA sequence, mapping the bit sequence obtained by the coding in step S1011 to a DNA base pair, and translating the bit sequence into a corresponding DNA sequence according to the designed coding rule. Exemplarily, this can be achieved by designing a set of nucleotide base sequences to represent the numbers zero and one. The nucleotide bases "A" and "C" can be set to represent the number 0, while "G" and "T" can represent the number 1, and then the digital information to be stored is converted into the corresponding base sequence.

[0026] Step S1013, DNA synthesis. The DNA sequence designed in step S1012 is synthesized by chemical methods to obtain a DNA molecule carrying the information to be stored. The DNA molecule can be temporarily stored in the form of an oligonucleic acid pool.

[0027] The synthesized DNA molecules are stored, and when the information needs to be read later, the corresponding DNA molecules are extracted from the storage library, the DNA library is amplified using polymerase chain reaction, the DNA sequence is read using sequencing technology, and the read DNA sequence is decoded into a bit sequence. The decoded bit sequence is then converted back to the original digital information form to achieve information restoration and obtain the original information to be stored.

[0028] Step S102, preparing a core layer electrospinning solution using the DNA molecules, DNA stabilizing solution and packaging materials.

[0029] Specifically, in the embodiment of the present application, a mixed solution prepared by mixing DNA molecules, DNA stabilizing solution and encapsulating material is used as a core layer electrospinning solution, that is, as a core layer preparation material for electrospinning. Among them, the DNA stabilizing solution is used to protect the DNA molecules to improve the stability of the DNA molecules. The DNA stabilizing solution can be a commonly used solution for protecting the stability of the DNA molecular structure, such as oligochitosan, room temperature DNA preservation stabilizer, etc. In this embodiment, the specific type of DNA stabilizing solution is not limited. Encapsulating material refers to the material commonly used in coaxial electrospinning technology for electrospinning of the core layer, which plays a role in fiber plasticity. In one possible embodiment, the encapsulating material is at least one of the following: polyvinyl alcohol (PVA), polyethylene oxide (PEO), polycaprolactone (PCL).

[0030] In a possible embodiment, the mass ratio of the DNA molecules, the DNA stabilizing solution and the packaging material in the core layer electrospinning solution is (0.01-40) g / L: (0.01-200) g / L: (50-200) g / L. The above three components are mixed with distilled water, wherein the mass ratio of the materials means that in the prepared 1L core layer electrospinning solution, the mass content of the DNA molecules is 0.01-40g, the mass content of the DNA stabilizing solution is 0.01-200g, and the mass content of the packaging material is 50-200g. For example, the finally prepared 1L core layer electrospinning solution contains 40g of DNA molecules, 200g of DNA stabilizing solution and 200g of packaging material, and the rest is distilled water.

[0031] In this embodiment, the above three components (DNA molecules, DNA stabilizing solution and encapsulation material) are mixed according to the feeding mass ratio. The specific feeding order and method are not limited in this embodiment of the application. The following is an example: First, the oligonucleic acid pool composed of DNA molecules obtained in step S101, each oligonucleic acid comprises primer regions at both ends, an information load region and an error correction region.

[0032] Then, using polyvinyl alcohol as a packaging material, 10 grams of PVA powder was slowly poured into 100 milliliters of distilled water that was being stirred, and the temperature was raised to 95° C. while stirring until the PVA was completely dissolved, thereby obtaining a PVA spinning solution.

[0033] Add a DNA room temperature storage stabilizer to the oligonucleic acid pool to further improve the stability of the DNA.

[0034] Finally, the oligonucleic acid pool was dropped into the prepared 10 ml PVA spinning solution and stirred at room temperature for 30 minutes to obtain the core layer electrospinning solution.

[0035] Step S103, using the shell material to package the material to prepare a shell layer electrospinning solution.

[0036] The shell material packaging material is used as the component material of the outer layer (i.e., the shell layer) in the subsequent core-shell fiber. The shell material packaging material commonly used in the existing coaxial electrospinning technology can be selected, and the solution made of organic solvent-soluble polymers, water-soluble polymers, natural polymers and their derivatives can be selected. In the embodiment of the present application, the shell material packaging material can be any suitable material that has no negative impact on the stability of DNA and the structural properties of the nanowire (core-shell fiber). Among them, there is no sequential execution relationship between step S102 and step S103, and they can be performed simultaneously.

[0037] In a possible implementation manner, the mass ratio of the shell material packaging material in the shell layer electrospinning solution is 50-200 g / L.

[0038] Specifically, the shell material packaging material is mixed with the corresponding solution. If the shell material packaging material is a high molecular polymer soluble in an organic solvent, an organic solution is selected for mixing to obtain a shell electrospinning solution; if the shell material packaging material is a water-soluble high molecular polymer, distilled water is selected for mixing to obtain a shell electrospinning solution. The feed mass ratio refers to that in the prepared 1L shell electrospinning solution, the mass content of the shell material packaging material is 50-200g. For example, the final prepared 1L shell electrospinning solution contains 200g of the shell material packaging material, and the rest is the solution.

[0039] Step S104, using the core layer electrospinning solution and the shell layer electrospinning solution to perform electrospinning by coaxial electrospinning technology to obtain core-shell fibers, wherein the core-shell fibers include a core layer and a shell layer, the core layer stores the DNA molecules, and the shell layer wraps the core layer to form a coaxial composite structure.

[0040] Reference Figure 2 , Figure 2 A schematic diagram of the structure of a core-shell fiber is shown. Figure 2 As shown, the core-shell fiber is a double-layer structure nanowire, the core-shell fiber includes a core layer 1 and a shell layer 3, the core layer stores DNA molecules 2, and also contains a DNA stabilizer 4, and the shell layer 3 wraps the core layer 1 to form a coaxial composite structure. This embodiment proposes a method for encapsulating an oligonucleotide library (i.e., a DNA molecule) in a one-dimensional nanowire core (i.e., the core layer of the core-shell fiber) using coaxial electrospinning technology. Among them, the diameter of the prepared core-shell fiber is nanometer-scale, and the outer shell of the nanowire does not contain DNA, so as to achieve the purpose of embedding the DNA molecule.

[0041] Specifically, in the coaxial electrospinning process, the core electrospinning solution and the shell electrospinning solution are ejected through two coaxial nozzles (core electrospinning nozzle and shell electrospinning nozzle) respectively, and the solution is spun into nanofibers with shell structure under the guidance of strong high electric field. Due to the charge drive, after leaving the nozzle, the spinning solution will form a "Taylor cone" under the action of high electric field force, and then stretch in the air to form fibers, and finally form micro-nano fiber filaments on the receiving device (i.e., receiving plate); in this process, due to the evaporation of the solvent, the nanofiber filaments will naturally solidify to obtain core-shell fibers with stable structure. Moreover, in this process, the DNA molecules carrying the information to be stored will be stably wrapped inside the nanofibers (i.e., the shell layer wraps the core layer to form a coaxial composite structure). This wrapping structure can not only protect the DNA molecules from damage by environmental factors, but also enable the DNA molecules to be accurately positioned at specific positions of the core-shell fibers.

[0042] In a possible implementation, the step S104, using the core layer electrospinning solution and the shell layer electrospinning solution to perform electrospinning by coaxial electrospinning technology to obtain core-shell fibers, includes: Step S1041, injecting the core layer electrospinning solution into the core layer syringe, and injecting the shell layer electrospinning solution into the shell layer syringe.

[0043] Step S1042, connecting the core layer injector to the core layer electrospinning nozzle of the coaxial electrospinning nozzle device, connecting the shell layer injector to the shell layer electrospinning nozzle of the coaxial electrospinning nozzle device, and connecting the coaxial electrospinning nozzle device to an electrostatic high voltage generator via a wire.

[0044] Step S1043, using the electrostatic high voltage generator to start the coaxial electrospinning nozzle device, using the receiving plate to receive the fiber filaments sprayed from the electrospinning nozzle of the coaxial electrospinning nozzle device, to obtain the core-shell fiber.

[0045] Among them, the receiving plate can be a collection device with a specific surface morphology and material, which can be a rotating drum covered with aluminum foil, or a more sophisticated functional collection device such as a microarray chip, a nanoporous material or a flexible substrate. The surface of the device should have good chemical stability and biocompatibility so as to interact with the DNA nanowires. During the spraying process, the position of the coaxial electrospinning nozzle device is adjusted to spray directly, or precision spraying techniques such as aerosol spraying, microfluidics, etc. are used to spray the nanowires containing DNA to different positions of the receiving plate. By precisely controlling the parameters of the spraying equipment (such as nozzle distance, spraying speed, airflow pressure, etc.), it is ensured that the DNA nanowires can be distributed on the receiving plate according to the preset pattern and density.

[0046] In one possible embodiment, the operating voltage of the electrostatic high-voltage generator is 12-20 kV, the injection rate of the shell layer syringe is 1.8-2.0 ml / h, the injection rate of the core layer syringe is 0.5-1.0 ml / h, and the receiving distance between the receiving plate and the electrospinning nozzle of the coaxial electrospinning nozzle device is 10-15 cm.

[0047] In a possible implementation manner, the inner diameter of the core layer electrospinning nozzle is 0.08 mm-1.0 mm, and the inner diameter of the shell layer electrospinning nozzle is 0.04 mm-0.4 mm.

[0048] Therefore, based on the core layer electrospinning and shell layer electrospinning solutions configured in steps S101-S103, the core layer electrospinning is a mixed solution with a moderate DNA concentration and a specific embedding material, which can ensure the good distribution of DNA molecules in the nanowires (core-shell fibers); the shell layer electrospinning solution can be any suitable material that has no negative impact on the stability of DNA and the structural properties of the nanowires. Figure 3 , Figure 3 A schematic diagram of a coaxial electrospinning process is shown, Figure 3 As shown, first, the core layer electrospinning solution and the shell layer electrospinning solution are respectively injected into the syringes (core layer syringe 102, shell layer syringe 103) of the injection pump 101. Figure 3 As shown, different syringes are connected to different electrospinning nozzles, and the coaxial electrospinning nozzle device is connected to the electrostatic high-voltage generator 104 through a wire, and the two nozzles of the coaxial electrospinning nozzle device are simultaneously started by the electrostatic high-voltage generator to perform coaxial electrospinning. In the coaxial electrospinning process, the core layer electrospinning solution and the shell layer electrospinning solution are respectively ejected through the inner and outer coaxial nozzles, and are guided by a strong high electric field to spin the solution into a core-shell fiber with a shell structure (such as Figure 3 105 shown). Due to the charge drive, after the spinning solution leaves the nozzle, it will form a "Taylor cone" under the action of the high electric field force, and then stretch in the air to form a fiber, and finally form a micro-nano fiber on the receiving plate 106; in this process, due to the evaporation of the solvent, the nanofiber will naturally solidify, and the DNA will be stably wrapped inside the nanofiber (core-shell fiber). This wrapping structure can not only protect the DNA from damage by environmental factors, but also allow the DNA to be precisely positioned at a specific position of the nanofiber.

[0049] In a possible implementation, the method further includes: The core-sheath fibers are subjected to heat treatment or wet heat treatment.

[0050] In order to further improve the structural stability of the prepared core-shell fiber, the post-treatment method can be further optimized, such as heat treatment, wet heat treatment, etc., to enhance the mechanical strength and stability of the nanowires. The specific parameters of the heat treatment and wet heat treatment are determined by the actual application process and are not limited in the embodiments of the present application.

[0051] For information stored in DNA, it is often difficult to quickly access specific information, and the entire library needs to be sequenced when searching and reading. Therefore, this application proposes a long-term packaging solution that is conducive to random access to information. Based on the characteristics of coaxial electrospinning solid-state film packaging, nanowires containing different nucleic acid pools are sprayed at different physical locations, and physical addresses are given to DNA information storage on the basis of long-term preservation to achieve random access function.

[0052] In a possible implementation, the method further includes: The physical position of each core-shell fiber and the DNA molecules carried are encoded to generate a DNA information index table, which contains a mapping relationship between the DNA molecules and the physical positions of the core-shell fibers.

[0053] In this embodiment, by steps S101-S104, the DNA molecules carrying information are encapsulated in one-dimensional nanowires (core-shell fibers) to provide the ability to locate and retrieve the DNA later. This one-dimensional nanowire can have a specific linear orientation, length and diameter, and the position of the DNA molecule in this core-shell fiber can be marked by a linear offset relative to a reference point (for example, along the length of the core-shell fiber, the distance from the starting point of the core-shell fiber is used as the position of the DNA). A collecting device (receiving plate) with a specific surface morphology and material can also be used to adjust the relative position of the electrospinning nozzle and the collecting device, and the core-shell fiber containing DNA can be sprayed to different positions of the collecting device. By accurately controlling the parameters of the spraying equipment, it is ensured that the DNA nanowires can be distributed on the collecting device according to a preset pattern and density. The core-shell fiber can store multiple DNA sequences inside it, and the content of each DNA sequence can be recorded together with its position in the core-shell fiber to provide corresponding addressability. This position record can display the identification of the DNA molecule and the identification of the digital information stored in the DNA sequence. During or after the spraying process, the position of each core-shell fiber and the DNA sequence carried are encoded and indexed to generate a DNA information index table. The mapping relationship between the physical position of the DNA molecule and the core-shell fiber is recorded in the DNA information index table, that is, the DNA molecules carrying different information have different DNA identifiers, each DNA identifier corresponds to a kind of information, and corresponds to different positions on the core-shell fiber. Exemplarily, DNA1 represents information 1 to be stored, which is located at a position 5 cm from the starting point of the core-shell fiber. In this way, based on the physical address technology of the method, the core-shell fiber carrying different DNA molecule information is sprayed on different collection points, and a physical address is assigned to the information. By querying the DNA information index table, a specific DNA nanowire is quickly located, thereby realizing random access to data. After spraying and encoding are completed, the receiving board becomes a DNA data storage device. When data needs to be read, specific biometric identification techniques (such as PCR amplification, sequencing, etc.) can be used to extract and decode data information from the core-shell fiber at a specified position.

[0054] In addition, due to their excellent flexibility, core-shell fibers can be arranged and stored in a manner similar to magnetic tape storage media. That is, the core-shell fibers can be wound around an axis to form a compact configuration. This wound core-shell fiber storage form is structurally similar to a cassette or reel, which enables a larger amount of DNA to be encapsulated in a certain volume, thereby achieving higher density information storage. In this wound configuration, the DNA sequence on each section of the core-shell fiber still maintains a fixed linear position. Just like in magnetic tape storage media, specific information can be found by the relative position of the head on the tape. Here, we can also address and retrieve information by determining the linear position of the DNA relative to the starting point of the core-shell fiber. In addition, the winding position of each core-shell fiber around the axis can also be recorded and used, similar to the radial position of the tape in a magnetic tape storage medium, thereby achieving the positioning and addressability of DNA in a more complex space. In other words, in addition to the coordinates on the length of the core-shell fiber, a new winding coordinate can be introduced, thus forming a two-dimensional address space, which greatly improves the address capability. By arranging and storing the core-shell fibers in a coiled form, high-density, high-efficiency, physically addressable DNA information storage can be achieved with a compact structure and ease of use.

[0055] The embodiment of the present application provides a method for making and preserving a geometrically addressable, long-lasting, anti-degradable oligonucleotide information carrier, using a DNA molecule carrying information to be stored to prepare a core electrospinning solution, and then using the core electrospinning solution and the shell electrospinning solution, electrospinning is performed by coaxial electrospinning technology to obtain a core-shell fiber, thereby storing the DNA molecule in the inner layer (core layer) of the core-shell fiber, and using the shell layer that has no negative impact on the stability of DNA and the structural properties of the nanowire as a protective layer to coat the core layer. Thus, the present application adopts coaxial electrospinning technology to achieve precise encapsulation at the nanoscale and maintain the stability of the encapsulated material, avoiding the risk of DNA being directly exposed to the environment and being destroyed, providing an efficient and practical DNA information storage method, and further improving the stability of DNA data storage. Moreover, since the core-shell fiber belongs to nanowires and is flexible, it can meet the needs of future flexible information storage media. In addition, the shell electrospinning solution can be freely regulated to manufacture storage carriers with different properties to meet a variety of usage scenarios.

[0056] Example 1: Step S201, writing information into an oligonucleic acid pool, each oligonucleic acid comprises primer regions at both ends, an information load region and an error correction region.

[0057] Step S202, preparing PVA spinning solution: slowly pouring 10 grams of PVA powder into 100 milliliters of distilled water that is being stirred, heating it to 95° C. while stirring, and stirring until the PVA is completely dissolved.

[0058] Step S203, oligonucleic acid pool pretreatment: Before embedding, a DNA room temperature storage stabilizer can be optionally added to further improve the stability of the DNA.

[0059] Step S204, prepare the core layer electrospinning solution, i.e. the core material PVA-DNA mixture spinning solution: Take 10 ml of PVA spinning solution and drop the oligonucleic acid pool into the spinning solution prepared in step S202, and stir at room temperature for 30 minutes. The core layer electrospinning solution and the shell layer electrospinning solution are respectively loaded into two different needle tubes. If multiple oligonucleic acid pools are embedded at the same time, different oligonucleic acid pools can be placed in different needle tubes.

[0060] Step S205, using coaxial electrospinning technology to encapsulate DNA in nanowires, parameters include: voltage +10kV, core layer nozzle liquid supply rate 0.8mL / h, shell layer nozzle liquid supply rate 1.0mL / h; roller: voltage -20kV, ambient humidity 50%RH, ambient temperature 34°C.

[0061] Step S206, using a receiving plate to collect the spun nanowires. Different nanowire collection schemes can be used according to different storage requirements. If multiple nucleic acid pools need to be encapsulated, the core needle tube can be replaced after embedding a nucleic acid pool, and the nanowires can be collected to different locations according to requirements.

[0062] Example 2: The sequence of DNA can be read by an oligonucleotide sequencer. If the sequence of DNA encodes digital information, the digital information can be recovered by decoding the sequence.

[0063] The core-shell fiber containing the DNA molecule is dissolved in TE buffer to prepare a 10wt% solution for PCR amplification. Appropriate PCR amplification conditions, including temperature, primers, and reaction time, are selected to ensure efficient amplification of the DNA molecule. The composition of the solution is shown in Table 1.

[0064] Table 1

[0065] Perform DNA amplification according to the amplification temperature cycle provided in Table 2.

[0066] Table 2

[0067] In the present embodiment, the quantitative cycle number (Cq) of the unembedded DNA and the embedded DNA of the same mass in the quantitative PCR experiment is compared. In the qPCR experiment, the Cq value represents the cycle number that reaches the fixed threshold value in the amplification process. The embedded DNA and the pure DNA all show the same amplification curve and Cq value in the PCR amplification, which shows that the DNA molecule embedded by the nanowires is not subjected to any negative effects in the PCR process. This result further shows that the advantages and effectiveness of the nanowire-embedded DNA as an empty carrier are because it protects the integrity and stability of the DNA molecule, so that its performance in the PCR experiment is the same as the pure DNA. This consistency provides a reliable data basis for subsequent experiments, and ensures that the embedded DNA can be normally analyzed and applied in subsequent experiments. In general, the identical Ct value shows that the nanowire-embedded DNA processing method does not produce any adverse effects for subsequent experiments. This shows the reliability and stability of the processing method, so that the embedded DNA molecule can be effectively used as a data storage carrier.

[0068] After completing the PCR amplification, the amplified DNA sequence can be read by using an oligonucleotide synthesizer. The oligonucleotide synthesizer will provide sequence information for each DNA molecule. If the sequence of the DNA is encoded, it needs to be decoded to recover the digital information. The specific method of decoding depends on the encoding scheme used. For different encoding methods, different decoding algorithms may need to be used or specific decoding tools may be introduced. By decoding the DNA sequence according to the appropriate decoding method, the stored digital information can be recovered.

[0069] Through this embodiment, information is stored in DNA molecules, and digital information can be reliably restored through PCR amplification and decoding technology. This method has efficient, reliable and stable information storage and recovery characteristics, and has the mechanical properties of nanofibers, and can be widely used in various application fields.

[0070] Example 3: In order to verify the protective properties of the embedding method in the embodiment of the present application against DNA chain breakage, this embodiment uses accelerated aging experiments and qPCR quantitative experiments to verify the protective ability of nanowire embedding for DNA, and compares the amount of DNA quantified using qPCR technology before storage with the amount of DNA remaining after incubation for 7 days at 70°C and 50%RH. qPCR uses the linearity of DNA amplification to determine the absolute or relative amount of DNA in a sample. By using fluorescent reporter molecules, the DNA produced in the PCR reaction can be measured in real time. When the fluorescent signal in the PCR cycle exceeds the detection threshold and can be measured, it is called a quantitative cycle (Cq). Since each PCR cycle doubles the amount of DNA, an increase of 1 in the Cq value indicates that the amount of DNA is halved. Samples containing more DNA in the starting sample require fewer PCR cycles to reach the detection threshold than samples containing less DNA. Therefore, the Cq value is inversely proportional to the amount of target DNA in the sample. This embodiment simulates the high temperature stress that DNA is subjected to when stored at room temperature for about 400 years. The quantitative PCR (qPCR) cycling differences between unprotected DNA samples stored under high temperature and high humidity conditions and DNA samples protected by nanowire encapsulation were compared, and the results showed significant differences on a daily basis.

[0071] The samples that were not embedded, protected by oligochitosan, and protected by oligochitosan plus nanowires were all subjected to high heat and high humidity (70°C and 50%RH) to simulate extended aging. During the 7-day test period, the unprotected sample lost about 9.6 PCR cycles per day, indicating that about 99% of the DNA was degraded within one day. The nanowires embedded + room temperature protection stabilizer protected sample lost about 0.3 PCR cycles per day, indicating that about 34% of the DNA was degraded within one day. Nanowire embedding provided significant protection.

[0072] Example 4: First, perform physical address encapsulation. Using the experimental parameters in Example 1, collect two nucleic acid encapsulated nucleic acid pools at different positions of the collection device (receiving plate). The nucleic acid pools are separated by 5 cm and marked with a marker to facilitate identification and distinction, while avoiding cross contamination between the two DNA pools.

[0073] Then, a specific nucleic acid pool is selected as the target database to extract a DNA sample from the position on the aluminum foil, and PCR amplification, sequencing and other analysis steps are performed. The analysis results are compared with the expected data to verify the accuracy and reliability of random access. The random access reading results in this embodiment are shown in Table 3 below.

[0074] Table 3

[0075] Through the implementation of this embodiment, samples of two different DNA pools (nucleic acid pool A and nucleic acid pool B) were successfully encapsulated in different positions of aluminum foil, and random access to DNA data was achieved through a preset coding system and index table. The test results show that this method has good feasibility and reliability, and provides strong support for the application of DNA data storage technology on non-traditional media.

[0076] The second aspect of the embodiment of the present application further provides a core-shell fiber for storing DNA information, the core-shell fiber comprising a core layer and a shell layer, the core layer storing the DNA molecules, the shell layer wrapping the core layer to form a coaxial composite structure; Wherein, the core-shell fiber is prepared by the DNA data storage method described in the first aspect of the embodiment of the present application.

[0077] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0078] The embodiments of the present application are described with reference to the flowcharts and / or block diagrams of the methods, devices, electronic devices, and computer program products according to the embodiments of the present application. It should be understood that each process and / or box in the flowchart and / or block diagram, as well as the combination of the processes and / or boxes in the flowchart and / or block diagram, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, an embedded processor, or other programmable data processing terminal device to generate a machine, so that the instructions executed by the processor of the computer or other programmable data processing terminal device generate instructions for implementing the processes in the flowchart and / or block diagram. Figure 1 A process or multiple processes and / or boxes Figure 1 A device that provides the functions specified in a block or multiple blocks.

[0079] These computer program instructions may also be stored in a computer-readable memory capable of directing a computer or other programmable data processing terminal device to operate in a specific manner, so that the instructions stored in the computer-readable memory produce a manufactured product including an instruction device, which implements the process Figure 1 A process or multiple processes and / or boxes Figure 1 A function specified in one or more boxes.

[0080] These computer program instructions can also be loaded onto a computer or other programmable data processing terminal device so that a series of operating steps are executed on the computer or other programmable terminal device to produce a computer-implemented process, thereby providing instructions for executing on the computer or other programmable terminal device to implement the process. Figure 1 A process or multiple processes and / or boxes Figure 1 The steps for the functions specified in one or more boxes.

[0081] Although the preferred embodiments of the present application have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the embodiments of the present application.

[0082] Finally, it should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or terminal device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or terminal device. In the absence of further restrictions, the elements defined by the sentence "including one..." do not exclude the existence of other identical elements in the process, method, article or terminal device including the elements.

[0083] The above is a detailed introduction to a DNA data storage method and core-shell fiber provided by the present application. Specific examples are used in this article to illustrate the principles and implementation methods of the present application. The description of the above embodiments is only used to help understand the method of the present application and its core idea; at the same time, for general technicians in this field, according to the idea of ​​the present application, there will be changes in the specific implementation method and application scope. In summary, the content of this specification should not be understood as a limitation on the present application.

Claims

1. A DNA data storage method, characterized in that: The method comprises: Encoding the information to be stored and synthesizing a DNA molecule carrying the information to be stored; Using the DNA molecules, DNA stabilizing solution and packaging materials, a core layer electrospinning solution is prepared; Using shell materials to encapsulate materials and prepare shell electrospinning solution; The core layer electrospinning solution and the shell layer electrospinning solution are used to perform electrospinning by coaxial electrospinning technology to obtain core-shell fibers. The core-shell fibers include a core layer and a shell layer. The core layer stores the DNA molecules, and the shell layer wraps the core layer to form a coaxial composite structure.

2. The DNA data storage method according to claim 1, characterized in that: The packaging material is at least one of the following: polyvinyl alcohol, polyethylene oxide, and polycaprolactone.

3. The DNA data storage method according to claim 1, characterized in that: The mass ratio of the DNA molecules, the DNA stabilizing solution and the packaging material in the core layer electrospinning solution is (0.01-40) g / L: (0.01-200) g / L: (50-200) g / L.

4. The DNA data storage method according to claim 1, characterized in that: The mass ratio of the shell material packaging material in the shell layer electrospinning solution is 50-200 g / L.

5. The DNA data storage method according to claim 1, characterized in that: The core layer electrospinning solution and the shell layer electrospinning solution are used to electrospin by coaxial electrospinning technology to obtain core-shell fibers, including: Injecting the core layer electrospinning solution into a core layer syringe, and injecting the shell layer electrospinning solution into a shell layer syringe; Connecting the core layer injector to the core layer electrospinning nozzle of the coaxial electrospinning nozzle device, connecting the shell layer injector to the shell layer electrospinning nozzle of the coaxial electrospinning nozzle device, and connecting the coaxial electrospinning nozzle device to an electrostatic high voltage generator via a wire; The coaxial electrospinning nozzle device is started by the electrostatic high voltage generator, and the fiber filaments ejected from the electrospinning nozzle of the coaxial electrospinning nozzle device are received by the receiving plate to obtain the core-shell fiber.

6. The DNA data storage method according to claim 5, characterized in that: The working voltage of the electrostatic high-voltage generator is 12-20 kV, the injection rate of the shell layer syringe is 1.8-2.0 ml / h, the injection rate of the core layer syringe is 0.5-1.0 ml / h, and the receiving distance between the receiving plate and the electrospinning nozzle of the coaxial electrospinning nozzle device is 10-15 cm.

7. The DNA data storage method according to claim 5, characterized in that: The inner diameter of the core layer electrospinning nozzle is 0.08 mm-1.0 mm, and the inner diameter of the shell layer electrospinning nozzle is 0.04 mm-0.4 mm.

8. The DNA data storage method according to claim 1, characterized in that: The method further comprises: The physical position of each core-shell fiber and the DNA molecules carried are encoded to generate a DNA information index table, which contains a mapping relationship between the DNA molecules and the physical positions of the core-shell fibers.

9. The DNA data storage method according to claim 1, characterized in that: The method further comprises: The core-sheath fibers are subjected to heat treatment or wet heat treatment.

10. A core-shell fiber for storing DNA information, characterized in that: The core-shell fiber comprises a core layer and a shell layer, the core layer stores the DNA molecule, and the shell layer wraps the core layer to form a coaxial composite structure; Wherein, the core-shell fiber is prepared by the DNA data storage method according to any one of claims 1-9.

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