RU2547597C1 - Multi-channel nozzle for extraction of nucleic acids, proteins and peptides - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: group of inventions relates to multi-channel devices, modified by nanocarriers of aniline-containing polymers. Claimed are: a multi-channel nozzle for the extraction of nucleic acids, proteins, peptides and a method of production of a multi-channel element, included in the composition of the multi-channel nozzle. The nozzle consists of a glass hexagonal multi-channel array, which includes multi-channel elements from a multitude of parallel capillaries. A sorption layer, which consists of one to three polymeric nanolayers, is applied on the internal surface of the capillaries. A multi-channel element is made with a protective framing from several rows of glass rods. The glass hexagonal multi-canal array consists of the laid repeatedly extended single multi-channel elements with the diameter of capillaries from 1 mcm and more, working surface to 500 cm², volume to 500 mcl. The method of the multi-channel element production includes the assembly of glass tubes into a multi-channel pack, fastening one of its ends in a supply unit grip, heating of the other end in a furnace with the formation of a bulb and extension to a required size. In order to obtain the structures with the diameter of the channel of the order and less than 1 mcm in the process of moulding the repeated extension of the multi-channel elements, preliminarily formed by laying the elements of the hexagonal shape, is realised.

EFFECT: inventions ensure carrying out the express-extraction and purification of both nucleic acids and proteins, peptides, as well as ensure the high reproducibility of results.

5 cl, 6 dwg, 3 tbl, 9 ex

Description

The invention relates to the field of molecular biology, to analytical chemistry, pharmacological biotechnology, in particular to multichannel devices modified by nanolayers of aniline-containing polymers, and to the technology of solid-phase extraction of nucleic acids, proteins, peptides based on multichannel structures modified by polymer layers, and can be used in single-stage separation procedures for mixtures containing nucleic acids, proteins, peptides when these components are isolated from biological samples A subsequent conduct molecular biological research in the laboratories of molecular genetic profile.

Various microcolumn bioseparation methods are known based on the use of spin columns or cartridges, through which the mobile phase (i.e., the eluent) is transmitted through the action of centrifugal force in a centrifuge. Such microcolumns contain unmodified silica, modified silica (using low molecular weight and high molecular weight modifiers), synthetic membranes, polymer monoliths, polymer or glass capillaries, etc.

Typically, methods for separating and isolating biopolymers are based on different solubilities of nucleic acids, proteins, and polysaccharides. Despite their effectiveness, most separation methods are multi-stage, time-consuming and often accompanied by losses of the excreted component. This is a consequence of the fact that such methods are based on the concept of “capture” and “retention” of the target biopolymer by the sorbent from the mixture at the first separation stage, followed by washing from impurities and elution of the target component from the sorption material at the subsequent stages.

A known method and device for molecular separation and extraction of nucleic acids US 7.943.393 B2 and US 6.451.260 B1, which use spin columns in the form of a polypropylene tube with one or more layers of adsorbent (glass fiber, glass beads, polymer granules, particles silica modified with silanes or polymers, etc.). This patent describes the implementation of the classical multi-stage principle of separation of biomolecules based on spin columns (cartridges) containing sorption material that reversibly holds the target sorbate. The passage of the sample and eluents (buffer solutions) through the spin column (following the incubation step) is carried out by spinning it in a centrifuge to a certain speed or under the influence of reduced or excess pressure. The process of isolation and purification of nucleic acid in these cases is based on the ability of nucleic acids to be reversibly adsorbed on the surface of the sorbent. Thus, spin columns have at least two significant drawbacks: the need to use a centrifuge (or a special pump) and the high cost of automating the separation (cleaning) process due to the multi-stage process. In addition, it should be noted that such a traditional approach to the isolation of nucleic acids excludes the possibility of simultaneous isolation of the total protein fraction (especially of individual fractions of proteins or peptides) from the sample (due to the low selectivity of the adsorbent surface in these cases).

The manufacture of multichannel structures is implemented using fiber technology, the classical moments of which are described in a number of books [V. B. Weinberg, D.K. Sattarov "Fiber Optics", Moscow, 1965; N.S. Kapani "Fiber optics, principles and applications", London, 1967]. Known methods of fiber technology include the manufacture of multichannel structures by extracting glass tubes, laying and again constricting to reduce the diameter of the channels, followed by sintering, for example GB-PS 1.064.072. The device according to US-PS 4.127.398 describes a method for manufacturing multichannel tubular structures, which describes the assembly of tubes into a bag of a certain cross section, repeated hauling into the hexagonal structure to the required geometric dimensions, filling with gas while sealing the ends and sintering in the tube. US-PS 4.010.019, US-PS 4.127.398 describes tube assembly, heating, hauling and molding of a hexagonal structure. A known method of manufacturing a patent of the Russian Federation RU№2096353 and DE 4.411.330 A1, which sets forth a method of manufacturing a multi-channel rigid structure or element. The method includes assembling the glass tubes into a preform bag, securing one end in the gripper of the feed unit, heating the other end in the furnace with the formation of the bulb, and molding, characterized in that in the molding process the cylindrical part of the structure or element is formed by sealing the glass tube package with subsequent shrinkage during rarefaction, and then stretching the glass up or down, depending on the given shape of the side surface.

The disadvantages of the known technical solutions are: technological problems in obtaining homogeneous structures with a high degree of regularity of laying. The problems of the boundary deformation of capillaries in a packet are not solved. With constrictions, breaks in the structure occur, which is unacceptable for many applications. The manufacturing technology described above does not allow to obtain structures with channel diameters less than 1 μm due to problems with laying hexagonal elements, the side of which

becomes corrugated, and it is impossible to lay such structures in compliance with regularity conditions, since a shift of stacked structures appears.

US Pat. No. 7,118,671 B2 describes a multicapillary chromatographic column and a method for its manufacture. According to this patent, a multicapillary chromatographic column contains a plurality of parallel channels isolated from each other, the walls of which are coated with a sorbent on the inside and fused with the walls of adjacent channels on the outside. The peculiarity of the column is that it is made in the form of a set of modules of various levels, while the module of the lowest level is hexagonally packed and having a cross section of the shape of a regular hexagon, a set of channels resulting from joint stretching of the capillary beam in a softened state. The module of each higher level is a hexagonally packed and having in cross section the form of a regular hexagon, the set of modules of the previous level, which is the result of their joint stretching in a softened state. A method of manufacturing columns consists in the implementation of several stages of drawing packages of blanks, each of which is the result of drawing in the previous stage and cutting obtained when pulling the product into parts of a certain length - the workpiece. The disadvantage of this design and technology is the low porosity and strength of the structure.

The above methods do not allow to obtain homogeneous structures with good sintering boundaries, channel deformations, stacking shear, low porosity due to the presence of many frames of single blocks and the absence of a guaranteed protective shell of the structure as a whole are observed in the structures.

In the patent of the Russian Federation RU№2300024 a device is described that can be used in means for pumping small amounts of liquid without moving mechanical parts using the electrokinetic effect. The micropump contains

polycapillary structure of non-conductive material with through microchannels, the inputs and outputs of which form the input and output ends of the structure. Such a structure can be made, for example, according to the technology described in patents RU No. 2096353, DE 4.411.330, US 3.923.426, RU No. 31859.

Closest to the proposed solution is the United States Patent Application Publication US 2007/0017870 A1 and US 2011/0092686 A1, which presents the most effective methods for separation / isolation / purification of biopolymers based on the use of multicapillary systems modified with nanocoatings of specific polymers or low molecular weight modifiers.

In them, for the separation and purification of nucleic acids, insoluble sorption material is deposited on the inner surfaces of the walls of each capillary, and then a monolithic capillary element is installed in the corresponding housing of the polymer tip. For operation, a multicapillary device is used with standard pipettes, syringes, or similar analytical instruments.

However, in these patents, the designs of multicapillary devices and isolation methods based on the classical concept of binding, i.e. at the first stage, nucleic acids are sorbed on the surface of the sorbent (in this case, on the inner surface of the capillaries) modified by various stationary phases (mainly non-polymer), then the nucleic acids are washed (eluted). According to the above examples, peptides, proteins and other biological components of the mixture are removed in the first stage, and nucleic acids that are deposited on the walls of the capillaries are washed off with an appropriate buffer in the second stage.

The objective of the invention is to obtain a multi-channel bio-separating element based on a glass multi-channel system soldered to the tip for

mechanical dispenser, syringe or other device, the inner surfaces of the capillaries in the specified system modified by nanocoating based on polyaniline or a copolymer of aniline with substituted aniline, which ensures the separation and purification of mixtures of nucleic acids and proteins in one stage. The sorption layer consists of one to three polymer nanolayers formed as a result of the precipitation oxidative polymerization of aniline or its copolymerization with 3-aminobenzoic acid and having a thickness of 3 to 10 nm, and the multichannel element is made with a protective frame of several rows of glass rods, while a single glass hexagonal rod has a shell of low-melting glass, and a glass hexagonal multichannel array consists of stacked repeatedly elongated single multichannels elements with a capillary diameter of 1 μm or more, a working surface of up to 500 cm ² , a volume of up to 500 μl and additional surfaces in the form of interchannel holes of smaller diameter, while the protective frame can also be made in the form of a tube, the internal geometry of which is dimensioned and the shape of the multi-channel element.

To obtain polymer-modified multichannel systems for one-stage separation of biopolymers, glass multichannel structures with channel diameters from 1 to 100 μm are made as carriers by constricting a hexagonal packet of multichannel capillaries, along the perimeter of which one or three rows of glass framing rods are laid, the diameter of the rods being comparable with the size of the rods according to the double apothem of multichannel capillaries, a single glass rod has a shell of low-melting glass.

The inventive technology allows for the laying and hauling of elements with micro-sizes in the structure and external macro-sizes, which distinguishes it from all known technologies that allow only two hauling, and styling

the latter is carried out from elements with a double apofem size of 0.4-0.6 mm. For the manufacture of multichannel structures with channel diameters of the order of less than 1 micron, the main difficulties arise precisely because of problems with laying hexagonal elements, the side of which becomes corrugated due to numerous constrictions, it is very difficult to lay such structures in compliance with regularity conditions, a shift of structures in general multichannel array, and the size of stacked multichannel blanks smaller than 1 mm leads to problems of straightness and twisting of elements in the package.

Therefore, taking into account the above difficulties, a fundamentally new technology for the manufacture of multichannel blanks with micro- and nanoscale channels, developed in the application, was developed. The main difference is that it allows the manufacture of intermediate multichannel elements with external dimensions, which make it possible to collect packages without any shear and twist problems in compliance with all the laying requirements for the following constrictions. Multichannel elements are obtained by laying hexagonal elements bordering each other with a diagonal, in the corners of which are located trihedral blanks

The technical result of the invention is a bio-separating element containing a glass multichannel array modified with an aniline-containing polymer, soldered to a tip for a mechanical dispenser, a syringe or other device.

The problem is solved, and the technical result is achieved by the fact that the glass multi-channel element, consisting of a regular hexagonal multi-capillary array, along the perimeter of which are laid one to several rows of glass framing rods, and framing rods are placed in the corners of the hexagonal array instead of multi-channel capillaries, are pulled to the required channel parameters and outer tip size.

This solution to the frame allows you to guaranteedly obtain a protective coating of the structure without tearing and to ensure the tight soldering of the glass multi-channel element without overheating and deformation in a standard polypropylene tip or syringe. Thus, a multichannel array sealed in a polypropylene tip is obtained with reproducible geometric parameters (length from 10 mm or more, channel diameter from 1 μm or more, volume up to 500 μl and surface area up to 500 cm ² ).

Also, the technical result is achieved by the method of obtaining structures with a channel diameter of up to 1 μm, which includes multiple constrictions of structures previously formed by laying hexagonal elements bordering each other with a diagonal, in the corners of which are trihedral blanks, and the number of elements on the side of the trihedron is m = (n -1) / 2, where n is the number of elements on the diagonal of the hexagon, moreover, all packets of the first or multiple constriction with the insulation of the end face with silicone sealant or glue. The predetermined cross-sectional profile of the multichannel element is determined by the profile of the drawn package. In this case, the capillaries of the required profile and the necessary porosity are first pulled out. Then they form packages of trihedral and hexagonal shapes. The geometric similarity of the profile is maintained during the process of drawing the package, which is facilitated by the hexagonal laying of the capillaries. A multichannel element is a plurality of holes, both the shape of the holes and the external geometry can be cylindrical, hexagonal, rectangular, triangular, etc. From the multichannel elements obtained by pulling the packet, a new triangular and hexagonal packet can be formed, and this process is repeated. As a result, channels, necessary in size and shape, are formed, for example, a structure with the following characteristics: a length of 10 mm or more,

a channel diameter of 1 μm or more, a volume of up to 500 μl and a surface area of up to 500 cm ² ).

The technical result is also achieved by the method of applying a polymer nanocoating on the inner surface of capillaries in a multichannel element, which consists in applying from one to three polymer nanolayers formed as a result of precipitating oxidative polymerization of aniline or its copolymerization with 3-aminobenzoic acid, and having a thickness of 3 to 10 nm, respectively. As a result of this procedure, the sorption properties of the surface of the capillaries are changed due to the formation of a stable, uniform, defect-free biocompatible polymer coating on the inner surface of the walls of the capillaries, which provides high selectivity in the processes of separation of components of mixtures of biopolymers (nucleic acids, proteins and peptides) in one stage with their simultaneous purification from impurities.

These distinguishing features are significant.

The use of aniline-containing polymer modifier allows for quick one-step isolation and purification of nucleic acids (DNA, RNA), as well as the separation of protein components depending on the value of their piezoelectric point (pi) without adding additional organic components to the mobile phase and without the use of additional equipment (pumps centrifuges, etc.). Nanolayers of the bioseparating polymer reversibly retain proteins, peptides, or other organic molecules, and only nucleic acids (DNA and RNA) are secreted, while the nucleic acids are not retained by the surface of the material (the elution stage is eliminated when nucleic acids are isolated) due to a change in the structure of the polymer macromolecule with changing pH Wednesday. Moreover, proteins and peptides can then be sequentially stripped in

the result of elution with a buffer with a high pH value without adding additional organic components to the mobile phase.

Thus, the proposed bio-separating element is a simple, cost-effective device that allows for the rapid isolation and purification of both nucleic acids and proteins and peptides, does not require the use of expensive materials or special equipment, and also provides high reproducibility of results, uniformity, consistency and almost identical sample paths.

Thus, these distinguishing features are in a single inextricable relationship, providing a causal relationship with the technical result, which is achieved by a combination of these features.

The invention is illustrated by the following examples.

Example 1

1. We make round glass capillaries with an outer diameter of 1.2 mm and an inner diameter of 1 mm in the amount of 2107 pieces and seal one end.

2. We place glass capillaries with an outer diameter of 1.2 mm and an inner diameter of 1 mm in a hexagonal shape package. We have 27 capillaries on the hexagon side, 53 capillaries on the diagonal, 32.4 mm side size, 63.5 mm diagonal size, 55.2 mm double apofee size (choose such sizes based on the dimensions of the heated space of the furnace <75 mm), number capillaries in a package of 2107 pieces.

3. Heat to glass softening temperature and drag the bag 10 times into hexagonal blanks with a diagonal size of 6.4 mm, a side size of 3.2 mm, a double apofem size of 5.5 mm, the number of channels 2107 with a diameter of 100 microns.

4. Solder one end face 91 of the hexagonal workpiece.

5. We put the obtained hexagonal blanks in a hexagonal packet, the number of hexagons on the diagonal 11, on the side 6. The size of the received packet on the diagonal is 60.5 mm, on the double apofee 52.6 mm, the number of hexagons in the packet is 91.

6. Heat to glass softening temperature and drag the bag 10 times into hexagonal blanks with a diagonal size of 6.0 mm, a side size of 3 mm, a double apofee size of 5.3 mm, the number of channels (2107 × 91 = 191737), and a diameter of 10 μm .

7. We put the hexagonal blanks received (in paragraph 3) into a trihedral packet, the total number of hexagons in a packet of 15, on the side of the trihedron is 5 hexagons, calculated on the basis of laying the previous (paragraph 5) hexagonal packet, which has 11 hexagons on the diagonal, then on the side the trihedral packet will be (11-1) / 2 = 5 hexagons, the side size is 27.5 mm, the height size of the trihedral packet is 23.8 mm.

8. Heat to the glass softening temperature and drag the bag 10 times into trihedral blanks with a side size of 2.7 mm and a height of 2.4 mm, the number of channels 31605, and a diameter of 10 μm.

9. 3 solder one end face 91 of the hexagon obtained in paragraph 6, and 180 trihedrons obtained in paragraph 8.

10. Putting the final package: 11 hexagons on the diagonal are lined up diagonally to each other, 6 hexagons on the side, there are 91 hexagons and 180 trihedra in the package, which are laid in the corners of the hexagons, forming a “star of David”, six-pointed star, or hexagram . Thus, we obtained a six-sided packet with a diagonal size of 6 × 11 = 66 mm, a double apofee size of 57.2 mm, the number of channels (191737 × 91 = 17448067) in the hexagons (31605 × 180 = 5688900), the total number of 23136967, diameter 10 microns. The assembled bag is placed in a glass tube with an outer diameter of 70 mm and an inner 67 mm.

11. Tighten the assembled bag, for example 10 times, obtaining a structure for the MK tip, with an outer diameter of 7 mm, a channel diameter of 1 μm, an amount of 25602157. If you need to obtain, for example, a channel diameter of 500 nm, the structure is pulled 20 times - the outer diameter becomes 3 5 mm. To obtain 100 nm diameter of the channel, the package is pulled 100 times, the outer diameter will be 700 microns.

Example 2

A glass multichannel structure with a double apofem size of 50 mm and a channel diameter of 650 μm, lined with one row of frames; moreover, in the corners of the capillary structure, instead of multi-channel capillaries, three glass framing rods are inserted, pulled to a channel diameter of 40 μm and an external size of 3.35 mm. In a regular hexagonal capillary structure, three angular capillaries are replaced by glass rods, which allows the structure to be extremely protected from deformation during hauling. A multi-channel tip is obtained containing 4417 capillaries with a diameter of 40 μm, the thickness of the multi-channel system being 3.35 mm, and a length of 50 mm.

Example 3

The glass block is wrapped with a heat-resistant fabric, mounted on a spinneret assembly, which is located in the furnace. Next, the block is heated to a softening temperature. Then, through the spinneret assembly, the softened glass is pressed under its own weight and goes down, where the product is clamped into the hood. Thus, the tube is pulled (and the internal dimensions of the tube correspond to the geometry and dimensions of the multichannel element). The cross-sectional shape of the product and its dimensions are determined by the geometry of the spinneret assembly, the drawing speed and the softening temperature of the glass. The stability and accuracy of maintaining the temperature in the furnace and the rotation speed of the exhaust drive largely determine the stability and accuracy of the geometric dimensions and the cross section of the resulting product.

Example 4

To modify capillaries with a length of 30 mm and a capillary diameter of 30 μm with a polyaniline coating, 1.3 moles of aniline were dissolved in 8 ml of 1M HCl. 200 μl of the resulting solution was taken and cooled to 10-11 ° C. 60 μl of an aqueous solution of an oxidizing agent (ammonium persulfate, 5% wt) was added. The reaction mixture was collected in a multi-channel tip and incubated for 20 min at room temperature. At the end of the polymerization, the tip was washed with water and ethanol and immediately dried in an oven at 80 ° C for 4 hours.

Example 5

The modification was carried out as in Example 2. After washing with water, the polymer coating procedure was repeated twice more. At the end of the polymerization, the multichannel tips were washed with water, ethanol and immediately dried in an oven at 80 ° C for 4 hours.

Example 6

To modify capillaries, a coating of aniline-3-aminobenzoic acid copolymer with monomers (0.975 mol and 0.325 mol, respectively) was dissolved in 8 ml of 1 M HCl. The solution was cooled to 10-11 ° C and 60 μl of an aqueous solution of an oxidizing agent (ammonium persulfate, 5% wt) was added. The reaction mixture was drawn into each multichannel tip and incubated for 20 min at room temperature. At the end of the polymerization, the multichannel tips were washed with water, ethanol and immediately dried in an oven at 80 ° C for 4 hours.

Example 7

Polymer-modified multichannel tips were used for one-step purification and DNA extraction from a clinical blood sample. 100 μl of blood with EDTA (100 μl) was added to an Eppendorf type microtube. 100 μl of lysis buffer was added, mixed and incubated for 15 min at 95 ° C. The lysate was centrifuged for 10 min at 10,000 rpm (3.584 kg), then the supernatant was taken into the multichannel tip and incubated for 2 min at room temperature. The eluate from the multichannel tip was transferred to a clean tube and then analyzed by real-time PCR. Sample lysis, DNA purification procedures using commercial columns and PCR kits were performed as in [D.V. Kapustin, A.I. Prostyakova, D.Yu. Ryazantcev, V.P. Zubov. Novel composite matrices modified with nanolayers of fluoropolymers as perspective materials for separation of biomolecules and bioanalysis. Nanomedicine Vol. 6 (2), (2011). P. 241-255.].

PCR results are presented in table 1.

Example 8

100 μl of a model mixture containing calf thymus DNA (10 μg) and bovine serum albumin (550 μg) were added to a 1.5 ml plastic microtube. The multichannel tip was washed several times with an aliquot of the model mixture (100 μl in an Eppendorf tube), then an aliquot was collected in the nozzle and incubated at room temperature for 3 min. The eluate from the multichannel tip was transferred to a clean tube and analyzed electrophoretically. The results of electrophoresis are presented in FIG. 1 (Fig. 1 - electrophoresis in 0.8% agarose gel. 1 - marker, 2 - the initial mixture of DNA-protein, 3 - eluate from the multichannel tip without incubation (only twice washing), 4 - eluate from the multichannel tip after washing and incubation ( 3 min.) The obtained eluates were also analyzed spectrophotometrically, determining the absorbance at 260 and 280 nm. The data obtained are shown in Table 2. It can be seen that the DNA purified from the protein is almost completely contained in the eluate.

Example 9

Preliminarily, the capillary tip capacity for protein (BSA) was determined, which was 400 ± 10 μg. To demonstrate the effect of reversible retention of proteins, 100 μl of a BSA solution (550 μg) in TE buffer (pH 7.2) was drawn into a 5-cm multichannel tip with capillaries with a diameter of 30 μm using a mechanical dispenser. Then an aliquot was transferred to a plastic tube and analyzed spectrophotometrically, determining the protein content in the sample from the calibration curve. After that, 100 μl of TE buffer (pH 10.0) was drawn into the multichannel tip and the resulting eluate was again transferred and analyzed spectrophotometrically. The results obtained are presented in table 3. Analysis of the data indicates that the protein held at neutral pH is almost completely desorbed from the surface of the capillary with increasing pH.

When using a modified tip from 48% to 71% of the DNA is retained. The drug is significantly purified from impurities compared with the original sample. The value of 260 nm / 280 nm is on average 1.64 (1.38 for the initial preparation). The preparation of isolated DNA is very clean. It is necessary to increase the exposure time at the tip for greater cleaning.

When using the traditional technique with high purity of the extracted DNA preparation (on average, 260 nm / 280 nm is equal to 1.83), large losses of the drug were observed as a result of two washes - on average, 33% -43% of DNA is retained. In addition, the isolation procedure is longer and requires additional equipment and resources (reagents from the kit) compared to using modified MK tips.

The invention is illustrated by the following drawings.

The figure 1 shows the electrophoresis in 0.8% agarose gel. 1 - marker, 2 - initial mixture of DNA-protein, 3 - eluate from a multichannel tip without incubation (only 2-fold washing), 4 - eluate from a multichannel tip after washing and incubation (3 min).

The figure 2 shows a multi-channel array having a protective frame of several rows of glass rods.

The figure 3 shows a multi-channel array in which the protective frame can be made in the form of a tube.

The figure 4 shows a multi-channel array, in the protective frame of which three or six angular multicapillary elements in the array are replaced by glass rods.

The figure 5 shows a multi-channel array of pre-formed by laying elements of a hexagonal shape, bordering each other with a diagonal, in the corners of which are located trihedral blanks.

The figure 6 presents a fragment of a multi-channel array, showing the calculation of the elements on the side of the trihedral blanks associated with the number of elements on the diagonal in the hexagonal blanks.

The invention is illustrated in the following tables.

Table 1 shows the concentration of DNA in the eluates after isolation on a multi-channel tip.

Table 2 shows the relative content of DNA and protein in the eluates.

Table 3 shows the protein content in the obtained eluates.

Claims (5)

1. A multi-channel tip for the isolation of nucleic acids, proteins, peptides, located in the body of a polypropylene pipette tip, consisting of a glass hexagonal multi-channel array, including multi-channel elements of many parallel capillaries, on the inner surface of which a sorption layer is deposited, characterized in that the sorption layer consists of one to three polymer nanolayers resulting from the precipitation oxidative polymerization of aniline or its polymerization with 3-aminobenzoic acid and having a thickness of 3 to 10 nm, and the multi-channel element is made with a protective frame of several rows of glass rods, while a single glass hexagonal rod has a shell of low-melting glass, and the glass hexagonal multi-channel array consists of stacked repeatedly elongated single multichannel elements with capillary diameter of 1 m or more, the working surface 500 cm ^2, the volume to 500 .mu.l and additional surfaces form openings interchannel smaller diameter, wherein the protective frame is designed as a tube, the internal geometry which is formed to the size and shape of the multi-channel element. 2. The multichannel tip according to claim 1, characterized in that in the hexagonal multichannel array, from three to six angular multichannel elements are replaced by glass hexagonal rods. 3. The multichannel tip according to claim 1, characterized in that the tube, the internal geometry of which corresponds to the size and shape of the multichannel element, is obtained by melt extraction from more easily melted glass than the multichannel element, the thermal expansion coefficient of the tube corresponding to the coefficient of thermal expansion of the multichannel element. 4. A method of manufacturing a multi-channel element included in the multi-channel tip according to claim 1, comprising assembling glass tubes in a multi-channel package, securing one end thereof in a gripper of a feed unit, heating the other end in an oven with the formation of a bulb, and drawing to the desired size, characterized in that in the process of molding to obtain structures with a channel diameter of the order of and less than 1 μm, multiple stretching of multi-channel elements preformed by laying elements of a hexagonal shape is carried out s bordering each other diagonal corners which have a triangular elements, the number of capillaries on the side of the trihedron m = (n-1) / 2, where n - the number of capillaries on the diagonal of the hexagon. 5. A method of manufacturing a multi-channel element according to claim 4, characterized in that in order to prevent the capillaries from collapsing during drawing, all packets of the first or multiple drawing are insulated from one end with silicone sealant or glue, or sealed.

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