RU2366717C2 - Multiple use device for nucleic acids hybridisation and application thereof - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention can be used for regeneration of multiple use devices intended for hybridisation of NA, biochips and DNA-chips. The claimed device contains compartment for single-stranded NA consisting of repeating nucleotide sequence being able to join the single-stranded NA-test with formation of double-stranded structure - NA-carrier; compartment for NA-target; NA-carrier confined in NA-carrier compartment containing the liquid contacting with liquid situated in compartment for NA-targets; membrane permeable for single-stranded NA-tests and impermeable for NA-carriers and NA-targets with said membrane separating NA-carrier and NA-targets compartments; device suitable for moving of said NA-tests from said compartment for NA-carrier to said compartment for NA-targets and back.

EFFECT: simplifying and cheapening of work with DNA-test specific for determined genes.

21 cl, 13 dwg

Description

The invention relates to processes and devices for the separation, isolation or detection of nucleic acids, and in particular relates to processes and devices suitable for the regeneration of reusable devices for hybridization of nucleic acids, hereinafter biochips or DNA chips.

Hybridization DNA chips are a solid carrier, for example glass, polymeric material, silicon, on the surface of which zones are arranged in an orderly manner, in each of which many copies of certain DNA sequences are immobilized.

The most important feature of the technology of DNA chips or biochips from the point of view of practical use is the ability to analyze a large number of DNA or RNA molecules in a mixture for the presence of unique sequences.

The modern development of biochip technology allows us to determine which genes work in a given cell at any stage of development and which are in an inactive state. For example, using expression microchips, genes were established that are involved in the regulation of the yeast cell division cycle, as well as metabolic processes in Escherichia coli bacteria.

The developed expression microchips use two types of immobilized DNA: first, relatively short gene-specific DNA fragments with a length of 20-25 nucleotides, for example, Affymetrix oligonucleotide microchips; secondly, large fragments of coding DNA with a length of 300-500 nucleotides obtained by cloning, PCR (polymerase chain reaction) - amplification and DNA purification.

When using DNA chips, you can simultaneously monitor the change in tens of thousands of genes during the development of cells and tissues in various physiological and pathological situations, under the influence of therapeutic agents and toxins. The identification of clear pathology markers at the level of gene expression and the development of diagnostic DNA chips is one of the top-priority tasks of biomedical research. Work on it can contribute to solving a number of critical health problems.

Unfortunately, the high cost and complexity make it difficult to use this technique.

The invention solves the problem of developing simple, inexpensive and more affordable methods of working with DNA samples characterizing certain genes than working with modern DNA microarrays.

A process for the identification of nucleic acid (NK) complementary to another NK is proposed. The process involves hybridization of the NK sample with the NK sample carrier in order to form a single complex of the NK sample with the NK sample carrier.

The specified complex is placed in a compartment (compartment, chamber), bounded on one side by a partition made of a material permeable to the NK sample and impermeable to the specified carrier NK sample and the specified complex.

Then this complex is denatured and the NK sample is transported through the septum and brought into contact with the NK target. Under hybridization conditions, an NK sample hybridizes with a complementary NK target, resulting in a double-stranded complex NK sample - NK target. NK samples that are not complementary to the NK target and, for this reason, are not associated with it, are returned back to the original compartment, where they provide the conditions under which these NK samples hybridize back to the carrier of the NK sample.

Detection of complexes of an NK sample with both an NK target and a carrier of an NK sample is used to determine the complementarity of an NK sample to an NK target.

The proposed NK-hybridization chip (device) reusable contains a channel. The specified channel has a compartment in which the carrier of the NK-sample is located. The channel provides contact between liquids that are in the compartment for the NK target and in the compartment for the carrier of the NK sample. These compartments are separated from the channel by partitions permeable to the NK sample and impermeable to the NK target and the carrier of the NK sample. The carrier of the NK test cannot go beyond the compartment in which it is located.

The device selectively moves a single-stranded NK sample between the indicated compartments containing the NK target and the NK sample carrier.

A process has also been proposed for copying the reusable hybridization NK chips described in this invention. Inside the chamber, filled with a gel and containing at least one electrode for electrophoresis, many copies of the NA molecule are created. After that, the chamber is contacted with another similar chamber containing at least one electrode. Applying an electric field, provide the transition of some copies of NK from the specified first camera to the specified second camera. After separation of the chambers, two chambers are obtained containing copies of the NC. The invention thus allows to simultaneously copy multiple isolated from each other cameras.

The invention is further detailed using the following drawings, which illustrate specific embodiments of the present invention. They are not intended to limit the invention described above, but rather to provide an illustration of the merits of the claimed claims.

Short description.

Figure 1 (a) - (p) - schematically and in steps show the sequence of operation of the proposed NK chips with mobile NK samples;

Figure 2 - schematically depicts a multi-channel NK chip proposed in the present invention;

Figure 3 (a) - (d) - schematically show in cross section various embodiments of an NK chip containing a plurality of electrophoretic cameras, proposed in the present invention;

Figure 4 - shows schematically a series of cameras with wiring, providing electrical contact with each pair of electrodes;

Figure 5 is an exploded view of a combination of plates that together form an NK chip containing electrophoretic cameras such as those shown in Figure 4;

6 (a) - (d) - schematically show the successive steps of the procedure for copying NK chips, as a result of which the nucleic acid molecules are transferred from the original NK chip to its copy;

7 (a) - (r) - schematically show sequential diagnostic steps using such an electrophoretic variant of an NK chip proposed in the present invention, in which cameras containing both NK carriers of an NK sample and cameras containing NK- the target is partially or completely filled with gel.

Detailed Description of Preferred Embodiments

Existing NK chips can be divided into the following two types. DNA chips, on the surface of which DNA samples are organized in the form of spots. Within each such spot, single-stranded DNA molecules are immobilized at one end on the surface of an NK chip. The second type of NK chips are oligonucleotide chips, on the surface of which relatively short oligonucleotides are immobilized.

Both types of NK chips are used so that the NK target is hybridized with the NK probe directly on the surface of the NK chip. From the point of view of the functional role of NK molecules involved in the diagnostic procedure, modern methods use only two types of nucleic acid molecules: NK samples and NK targets.

The present invention introduces a third type of nucleic acid molecule, namely, a single-stranded NK sample carrier such that, under appropriate conditions, the NK carrier and NK sample are capable of forming a fully complementary double-stranded nucleic acid.

The invention uses an NK carrier of NK samples and thereby allows NK samples to exist under certain conditions in the form of free molecules in solution. At the same time, the use of an NK carrier of an NK sample allows the use of NK targets not only in the form of free molecules in solution, as is necessary in existing methods, but also in the form of molecules immobilized on the surface or inside a porous medium, for example, in a gel, into which free molecules of NK samples can easily penetrate.

As a result, the present invention allows to simplify the methods of use and manufacture of such NK chips, to develop a variety of simple options for managing them and to develop both disposable devices and NK chips for reusable use.

In accordance with the invention, it is possible to prepare a complex of an NK carrier with an NK sample as follows. First, make a long double-stranded NA molecule, which has a repeated primary structure. In this structure, the repeating unit in one of the strands is the structure of the NK sample, limited by sequences of signals that any single-stranded restrictase is recognized in such a way that after processing with this restrictase, single-stranded cuts will appear in these places. As a result, this double-stranded NK molecule will turn into one long single-stranded NK, to which many NK samples are sequentially attached.

The proposed NK carriers have the ability to specifically and reversibly bind NK samples. As part of NK chips (devices), such NK carriers of NK samples can be localized on the surface or in a limited volume.

The structure of the proposed NK-carriers of NK-samples allows you to use the following method of obtaining NK-samples. A single-stranded NK sample is able to attach only complementary NK sequences to itself with the formation of a double-stranded structure. Therefore, in the case of processing such an NK carrier with a solution of a mixture of statistically prepared oligonucleotides (for example, having a length of 5 to 50 bases), only complementary sequences hybridize with the NK carrier and form a complex of the NK carrier with an NK probe.

As used herein, the term “NK probe carrier” is defined as a substance that can specifically and reversibly bind to an NK probe and, in particular, includes single-stranded nucleic acids, other organic molecules and porous structures complementary to the NK probe. In the present invention, such a carrier is considered as a complex carrier, which can be used as free molecules in solution, immobilized molecules and porous structures.

The variety of molecules of a different nature than nucleic acid, capable of attaching to the NK carrier of NK samples in accordance with the present invention, is practically unlimited. These molecules can carry groups that provide functions such as specific recognition and binding to various substrates and NK samples, spectroscopically active labels, and combinations thereof.

The location of the NK-sample carriers not only on the plane, but also in space provides new opportunities for both manufacturing and functioning of the proposed PC chips (devices).

For example, NK carriers can be connected end-to-end in series, forming a long filamentary structure in which identical NK carriers or a predetermined combination of different NK carriers are repeatedly repeated. This structure may include special demarcation sites, which, for example, eliminate possible steric hindrances in the operation of neighboring NK carriers and, if necessary, replace one NK carrier with another without damaging these NK carriers.

The invention takes into account that for NK carriers of NK samples, restriction sites can be such delimiters.

The use of NK carriers of NK samples, which are long single-stranded NK molecules, eliminates the problems that arise when trying to hybridize single-stranded NK molecules in close proximity to the surface to which one of these molecules is immobilized. As a result, the proposed NK carriers of NK samples should be useful when using particularly long NK samples, for example, when the length of NK samples is more than 60 bases.

The proposed NK carriers of NK samples can be immobilized on the surface of an NK chip in the same way as on ordinary DNA chips (in the form of spots). The use of the proposed NK carriers allows the transition from a two-dimensional arrangement of molecules of NK samples to an arrangement in space. Currently, such a transition occurs in the manufacture of gel chips, a significant limitation of which is that the target DNA molecules must diffuse inside the gel in order to hybridize with DNA samples immobilized inside this gel. The present invention takes into account the possibility of immobilization of carriers not only on any surface, but also in the volume of the gel or porous material.

To identify the proposed NK carriers of NK samples, one can use not only their spatial positioning. For example, these NK carriers of NK samples can orderly move through a detector that recognizes them. Identification can be carried out by various signs, for example, the size and conformation of molecules, various labels and different combinations of these signs. The detector may also determine the time or sequence of media passing through the detector.

Due to the fact that single-stranded NK targets according to the invention interact not with immobilized NK targets complementary to them, but with free NK samples, it becomes possible to simplify the procedure for preparing a NK target for the hybridization procedure. For example, can be used to hybridize NK targets that are located inside the gel or immobilized on the surface of the particles. For example, it can be paramagnetic, metal, semiconductor and polymer particles. In particular, these can be paramagnetic particles, which are commonly used in purification and amplification of nanocrystals.

In one of the modes of using the proposed NK chips, it was proposed to hybridize single-stranded NK samples with a single-stranded NK target in solution and after that to separate the double-stranded target-sample complexes from single-stranded NK samples. It was proposed to hybridize these free single-stranded NK samples at a different location with NK carriers to obtain double-stranded carrier-sample complexes.

The invention takes into account that in this mode of operation, NK targets can be immobilized on the surface of another NK chip, for example, made to work with other NK samples; on the surface of paramagnetic particles, which are widely used in the separation and amplification of nanocrystals; and also inside the gel, as is the case with nucleic acid electrophoresis.

Hybridization results can be determined by analyzing the appearance or absence of complexes of both the NK target with the NK probe and the complexes of the NK carrier with the NK probe. It is also possible to detect free NK samples that are located or move between the NK target and the NK carrier.

Another mode of operation may be one in which the NK carrier is immobilized on the open surface or inside the pores of the porous body and hybridized with the NK sample, forming a double-stranded NK. It was proposed to denature such a NK carrier complex with an NK probe and to release the NK probe so that it could detect the NK target and hybridize with it in a free state. Denaturation methods, for example, can be heating, changing the pH of the medium, and applying an electric field.

Figure 1 shows the sequence of steps of a single channel NK chip (device), proposed in the present invention.

The invention takes into account that although Fig. 1 shows that the entire solution moves from one compartment to another, it is possible, by applying an electric field to the compartments filled with an electrolyte, to move only charged molecules between the compartments. Similarly, it is possible to use an electric field for the case shown in FIG. 2.

In cases where an electric field is used to move the molecules, it is possible to do without the use of optical and other methods of visualizing molecules that require specific modification of nucleic acids. Instead, parameters such as ion current and other non-specific characteristics of moving electrically charged polymer nucleic acid molecules can be measured.

The channel shown in FIG. 1 is a single-channel device, which is generally designated as 10. The device 10 has a channel 2 filled with liquid and having a porous partition 14 that is permeable to NK samples 28 and impermeable to NK carriers 30 and NK targets 32. One side of the porous septum 14 is designated 16 and the other 18. The porous septum 14 separates the compartment containing the NK carriers compartment 20 from the compartment containing the NK targets 22. If necessary, the compartment containing the NK carriers compartment 20 is enclosed by a liquid-permeable porous partition 24, which is impermeable to NK carriers 30, NK samples 28 and NK targets 32. Similarly, if necessary, the compartment 22 containing the NK targets is enclosed by a liquid permeable porous septum 24 ', which is impermeable to NK carriers, NK probe and NK targets. The apparatus 26, inducing the movement of nucleic acids, is necessary in order to ensure the movement of NK samples 28 from compartment 20 to 22 and vice versa. The nature of the apparatus 26 may be different depending on the nature of the forces chosen to move the nucleic acids between the compartments. For example, in cases where NK samples 28 move between compartments 20 and 22 together with the fluid flow, apparatus 26 is a pump.

Alternatively, in cases where NK samples 28 move between compartments 20 and 22 under the influence of electrostatic potential, apparatus 26 is a power source with electrodes that induce an electric field between partitions 24 and 24 '. For illustrative purposes, apparatus 26 is shown as a pump moving NK samples 28 along with a fluid stream.

Figure 1 (a) shows many copies of the NK-sample 28, which are hybridized with the NK-carrier 30 and are in the compartment 20. The invention takes into account that the NK-carrier 30 can be in the compartment 20 in the form of molecules free in solution, molecules immobilized on the partition 24 or / and the partition 14 from the side 16, or located inside the porous partitions 24 or / and 14.

As shown in FIG. 1 (b), the complex of the NK-sample 28 with the NK-carrier 30 is denatured to release the NK-sample 28 into the volume of the solution of the compartment 20. The complexes of the NK-samples 28 with the NK-carrier 30 can be denatured using different methods, for example by heating, changing pH, electric field.

In Fig. (1c) it is shown that NK samples 28 are moved to compartment 22. As shown in this drawing, such movement can be achieved by pumping liquid into compartment 22 using a pump through channel 2 or by sucking liquid from compartment 22 .

As shown in FIG. 1 (d), the NK target molecules 32 are introduced into the compartment 22 using a dispenser 34, which, for example, can be a micropipette, microdispenser, or other similar device. The invention takes into account that single-stranded NK target molecules 32 can be placed in compartment 22 before NK samples 28 are placed there. In the embodiment shown in FIG. 1, single-stranded NK samples 32 molecules are immobilized on paramagnetic particles 36.

Figure 1 (e) shows that the molecules of the NK-sample 32, immobilized on paramagnetic particles 36, interact with many copies of the NK-sample 28. As can be seen in Figure 1 (f), the interaction occurs under hybridization conditions that allow the formation of double-stranded complexes between complementary NK targets and NK samples. Hybridization methods and conditions are well known and, for example, can be provided due to special regimes of changes in temperature, pH, and ionic strength.

The invention takes into account that at this stage the contents of compartment 22 can be extracted and examined outside the described device by various well-known methods in order to determine the results of hybridization of the NK target and NK sample.

However, in a preferred embodiment, as shown in FIG. 1 (g), the solution is transferred from compartment 22 back to compartment 20, awaiting the following result. If the NK-sample 28 is complementary to at least part of the NK-target 30, then the NK-samples 28 will remain in compartment 22 as part of the complex of the NK-target with the NK-sample, for which the partition 14 is impermeable.

Direct detection of an NK carrier 30 under hybridization conditions by conventional methods, for example, using fluorescent dyes, can make it possible to determine whether NK samples 28 returned to compartment 20. If it turns out that the NK sample 28 returns to compartment 20 and forms double-stranded complexes with NK-carrier 30, this will mean that NK-samples 28 are not complementary to NK-targets 32. If NK-samples 28 are not complementary to NK-targets 32, removal of this target and, if necessary, additional washing of compartment 22 will return channel 10to the initial state shown in FIG. 1 (a). If the NK sample turned out to be complementary to the tested NK target, then before removing the NK target from compartment 20, it will be necessary to denature the complex of the NK target with the NK sample and move the released NK sample to compartment 22.

Thus, in the event that the NK samples 28 are complementary to the NK targets 30, the compartment 22 needs to be re-filled with liquid, as shown in Figure 1 (h). The denaturation of double-stranded complexes of the NK sample with the NK target, shown in Figure 1 (i), can be carried out under the same conditions as described for Figure 1 (b).

The following steps ensure the separation of the NK target 32, which was placed in compartment 22 as shown in Fig. 1 (d), and NK samples 28, which, as a result of denaturation, were released from the complex with the NK target. The invention takes into account that such separation can be achieved outside of channel 10 by well-known methods, for example, such as electrophoresis and chromatography, as well as through the use of paramagnetic particles on which the NK target is immobilized. However, in the preferred embodiment shown in FIG. 1 (j), the released NK samples 28 are transferred from compartment 22 to compartment 20. Thereafter, in compartment 20, the NK sample 28 is hybridized with the NK carrier 30, as shown in FIG. 1 (k). After this, the compartment 22 is filled with liquid so that the molecules of the NK targets 32 immobilized on paramagnetic particles 36 are floating in solution, as shown in Figure 1 (l).

Figure 1 (m) shows that a magnet 40 is inserted into compartment 22, to which all paramagnetic particles 36 are adhered. On the next Figure 1 (n) it is shown that magnet 40 removed from compartment 22 has carried away all paramagnetic particles 36 and NK targets 32 immobilized thereon. As shown in FIG. 1 (o), removal of the solution from compartment 22 returns channel 10 to the initial state shown in FIG. 1 (a).

Subsequent denaturation of the NK-carrier complex 30 with the NK-probe 28 and filling the compartment 22 with a solution containing the NK-probe 22 prepares channel 10 for operation with the next NK-target 32 '. As shown in FIG. 1 (p), the next NK target 32 ′ may, for example, be immobilized on paramagnetic particles.

Figure 2 shows schematically a multi-channel NK chip (device), in which individual channels operate as described for Figure 1. The numbers in FIG. 2. have the same explanations as in figure 1.

Many pairs of compartments of NK carriers 20 and NK targets 22 form a two-dimensional or three-dimensional NK chip (device). An advantage of a multi-channel NK chip (device) 50, schematically shown in FIG. 2, is that the presence of a plurality of pairs of compartments 20 and 22 allows you to automate the device and increase its performance.

An essential feature of the invention is that NK samples run between compartments 20 and 22 and are not consumed. The proposed NK chip is a simple reusable device suitable for developing multiple options for low-cost and reliable mass diagnostics.

Many variants of a multichannel electrophoresis-based NK chip (device) are shown in FIG. 3 (a) -3 (d). The specified multi-channel NK chip (device) has a compartment for the NK carrier 60, limited by the end electrode 62. The compartment 60 is designed for NK carriers or NK targets. Porous material 64 is practically impermeable to NK carriers and NK targets, but permeable to NK samples. The compartment 60 can be completely or partially filled with a gel 66, in which long and for this reason molecules of NK carriers or NK targets can be enclosed in an electric field that are practically not shifted in the electric field. If the compartment 60 is incompletely filled with gel 66 and when porous material 64 is used, compartment 60 also contains solution 63. compartment 60 also contains two (or more) electrodes 68 and 70 located on the sides of the compartment.

As shown in FIG. 4, the first plate, similar to 72, which is shown in FIG. 3d, contains a set of compartments to which conductive wires 74 are connected, providing fluid contact in the compartments with electrodes 68 and 70, which were also shown in FIG. 3 .

Figure 5 presents an exploded view of a combination of plates 72 and 78, which together form the electrophoretic chamber described in Figure 3.

6 (a) -6 (d) schematically shows the procedure for copying an NK chip (device), each compartment of which contains many copies of any NK carrier of an NK sample or NK target. Digital designations are the same as described for Fig.3-5.

NK 80 is amplified using polymerase chain reaction (PCR) inside compartment 60 so that it contains many copies of this nucleic acid. After that, the NK chip (device) 72, which contains in the compartments 60 many copies of the NK immersed in gel 66, is brought into contact with the same NK chip 72 'and 78', which has end electrodes 62 '. As shown in FIG. 6 (b), in an electric field formed between the electrodes 62 and 62 ', a portion of the NK 80 will move from compartment 60 to compartment 60'. After moving part of the NK 80 to the compartment 60 ', the plates 70 and 72 are disconnected, as shown in Fig.6 (c). After that, using PCR, a small amount of PC 80, which was transferred to compartments 60 ', is expanded to the amounts corresponding to the number of these NK 80 in the NK chip (device) formed by plates 72 and 78. Thus, a complete copy of the original NK chip is obtained (devices).

Figures 7 (a) - (r) show successive diagnostic steps for the case when the NK carrier of NK samples and NK targets are each immersed in their compartment inside the gel so that, under the influence of the electric field, NK samples can enter and exit the corresponding compartment, while NK carriers and NK targets will practically not budge.

The diagnostic NK chip, which consists of plates 72 and 78 containing the end electrode 62 and side electrodes 68 and 70, in accordance with the descriptions given for the previous drawings, has a compartment 60 containing many copies of short NK samples 28 hybridized with long single-stranded NK-carriers 30. The compartment 60, filled with gel 66, is indicated in the drawing as 86.

The compartment containing the NK target 30 placed in gel 66 is designated 88. As shown in FIG. 7 (b), the complex of the NK sample 28 and the NK carrier 30 is placed under conditions under which it denatures to form single-stranded NK- Samples 28 and NK carrier 30.

Fig. 7 (d) shows that plate 90, together with plate 78 'attached to it, is brought into contact with plate 72 and electric potentials are applied to electrodes 62 and 62', as a result of which NK samples 28 begin to move from compartment 86 to compartment 88, which contains NK targets. Fig. 7 (e) shows that, as a result of electrophoresis, all NK samples 28 leave compartment 86 and accumulate in compartment 88. After that, as shown in Fig. 7 (f), plate 90 is separated from plate 72.

Next, the plate with compartments 88 is placed under hybridization conditions, in which complexes of NK samples 28 with NK targets 34 can form. Complementary NK samples 28 and NK targets 34 form double-stranded complexes as a result of hybridization, as shown in Fig. 7 ( g) After that, the plate 90 is again contacted with the plate 72, as shown in Fig. 7 (h), and electrophoresis is carried out in the direction opposite to that shown in Fig. 7 (d) in order to return all free NK samples 28 from the compartment 88 back to compartment 86 with NK carriers.

As shown in FIG. 7 (i), the plate 90 is again separated from the plate 72 and a horizontal electric field is organized in compartments 86 in order to move the free NK samples 28. After that, the direction of the horizontal electrophoresis is reversed, as shown in FIG. .7 (k). In both cases, electrophoresis is organized so that it is possible to measure the electrical characteristics of moving NK samples 28, for example, the magnitude of the ion current. After that, as shown in Fig. 7 (l), compartments 86 provide hybridization conditions for the formation of complexes between NK samples 28 and NK carriers 30.

After that, compartments 88 containing double-stranded complexes of NK targets 34 with NK samples 28 are placed under denaturation conditions. The plates 90 and 72 again contact and organize an electric field between the electrodes 62 and 62 'in the same direction as in Fig. 7 (h), in order to allow the transfer of NK samples 28, complementary to the NK target 34, back to compartment 86 In Fig. 7 (o), it is shown that after all NK samples 28 have returned to compartment 86, the electric field is turned off.

Plates 90 and 72 are then disconnected. The contents of the compartments 88 in the plate 90 becomes the same as it was at the beginning of the procedure in Fig. 7 (a).

Figure 7 (q) shows that compartments 86 provide hybridization conditions, as a result of which all NK samples 28 that are complementary to the NK targets 34 form double-stranded NK complexes with NK carriers 30. Thus, in Fig. 7 ( r) it is shown that the NK chip (device) containing compartments 86 is fully prepared for the diagnosis of another NK target; similarly, compartments 88 are ready for testing other NK samples.

Claims (21)

1. The device is reusable, designed for the reaction of hybridization of nucleic acids (NK), characterized in that it contains:
a compartment for a single-stranded NK, consisting of a repeating sequence of nucleotides, which is able to attach to itself a single-stranded NK-sample with the formation of a double-stranded structure - NK-carrier;
compartment for the NK target;
NK-carrier enclosed in a compartment for NK-carriers, wherein said compartment contains a liquid that is in contact with a liquid located in the compartment for NK-targets;
a partition that is permeable to single-stranded NK samples and impermeable to NK carriers and NK targets, while this partition separates the compartment for NK carriers from the compartment for NK targets;
a device suitable for moving said NK samples from said compartment for NK carriers to said compartment for NK targets and vice versa. 2. The device according to claim 1, characterized in that at least one of these compartments for NK carriers and for NK targets contains a gel. 3. The device according to claim 1, characterized in that the NK-carrier is located in the compartment for NK-carriers in one of the following types: immobilized on the surface of the gel, immersed inside the gel, a combination of the two previous conditions. 4. The device according to claim 1, characterized in that said compartment for NK carriers and said compartment for NK targets contain electrodes that create an electric field between these compartments. 5. The device according to claim 4, characterized in that the compartment for the NK carriers and the specified compartment for the NK targets contain additional electrodes that create an electric field inside the specified compartment. 6. The device according to claim 1, characterized in that said device for moving NK samples is a pump that moves liquid between these compartments for NK carriers and NK targets. 7. The device according to claim 1, characterized in that it contains many pairs connected to each other of these compartments for NK carriers and NK targets located in the form of a flat body. 8. The device according to claim 1, characterized in that it contains many pairs connected to each other of these compartments for NK carriers and NK targets located in the form of a three-dimensional body. 9. A method for comparing two sequences of nucleic acids (NK), defined as an NK probe, a NK target and a single-stranded NK, which consists of a repeating nucleotide sequence and which is capable of attaching a single-stranded NK sample to form a double-stranded structure - an NK carrier, hybridization method, characterized in that it is carried out in the presence of two compartments No. 1 and No. 2, which are separated by a partition and contain a liquid that allows you to move the NK sample through the partition, and includes the following steps:
hybridization of the NK sample of a complementary NK target with such an NK carrier to which the NK sample is complementary, and thus obtaining a double-stranded complex of the NK sample with an NK carrier;
placing the double-stranded complex of an NK-sample with an NK-carrier in compartment No. 1, limited by side 1 of the partition, which has side 1 and side 2, bounding compartment No. 2, and is permeable to the specified NK-sample and impermeable to the specified NK carrier and the specified NK-sample complex with NK-carrier;
placing a single-stranded NK target in compartment No. 2, limited by side 2 of the partition having side 1 and side 2, and permeable to the indicated NK sample and impermeable to the specified NK target;
denaturation of the indicated complex of the NK sample with the NK carrier and the return of all copies of the indicated NK sample to compartment No. 1;
providing the possibility of passing the specified NK-test through the specified partition from side 1 to side 2 of the specified partitions;
providing contact of a complementary NK target with the indicated NK sample in compartment No. 2;
providing such hybridization conditions under which the specified NK-sample will be able to hybridize with a complementary NK-target with the formation of a complex of NK-samples with an NK-target;
providing the ability to move NK samples that are not hybridized with the NK target to side 1 of the partition to compartment No. 1 after providing conditions for hybridization of these samples with a complementary NK target;
enabling hybridization of the indicated NK sample with the indicated NK carrier in compartment No. 1 after the return of the indicated sample from compartment No. 2 through the specified partition;
determining the complementarity of the indicated NK sample and the indicated NK target by determining whether the indicated NK sample is part of the complex of the NK sample with the NK target in compartment No. 2 or the NK sample with the NK carrier in compartment No. 1. 10. The method according to claim 9, characterized in that the denatured complex of the NK sample with the NK target is denatured and all copies of the indicated NK sample are returned to side 1 of the specified partition and the NK sample complex is formed with the NK carrier. 11. The method according to claim 9, characterized in that the NK-sample migrates through the specified partition from side 1 to side 2 and back together with the fluid flow. 12. The method according to claim 9, characterized in that said NK sample migrates through said partition from side 1 to side 2 and vice versa, using an electric field that passes through said partition due to the difference in electric potentials on both sides of said partition. 13. The method according to claim 9, characterized in that the complex of the NK carrier with the NK sample is detected by fluorescence methods after the conditions for hybridization and the formation of the complex of the NK sample with the NK target are provided. 14. The method according to claim 9, characterized in that the complementary NK target is immobilized on a paramagnetic particle. 15. The method according to claim 9, characterized in that the complementary NK target is immersed inside a gel-like medium. 16. The method according to claim 9, characterized in that the complementary NK target carries any mark that can be detected by an external detector. 17. The method according to claim 9, characterized in that all the steps described in clause 9 occur simultaneously in a plurality of isolated compartments, each of which contains one type of NK sample, different from the NK samples in the other compartments. 18. A method of copying multiple isolated from each other chambers containing an electrophoresis electrode, a gel and a copy of a single-stranded nucleic acid consisting of a repeating nucleotide sequence that is capable of attaching a single-stranded NK sample to itself with the formation of a double-stranded structure, including:
copying a nucleic acid to form multiple copies in a compartment containing a gel and an electrode;
contacting said compartment with another compartment containing a gel and an electrode;
providing electrophoretic movement of part of the copies of the specified NK from one specified compartment to another specified compartment;
separation of these compartments. 19. The method according to p. 18, characterized in that the nucleic acid is a single-stranded nucleic acid, consisting of a repeating nucleotide sequence, which is able to attach a single-stranded NK-sample with the formation of a double-stranded structure. 20. The method according to p. 18, characterized in that in the second specified compartment after separation of the devices, amplification of those copies of NK that were moved from the first specified compartment is carried out. 21. The method according to claim 20, characterized in that the amplification of the NK is performed using a polymerase chain reaction.

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