RU2386970C2 - Multiplex identification system biochip (versions) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: biochip integrates a base element with a probe clusters arranged on its working surface, a surface and lower multilayer coatings, and one or two indicator cells with identifiers, and the indicator cells are series interconnected and connected to the base element either by jumpers, or by the multilayer coatings that makes it possible to separate the second indicator cell from the first indicator cell, and from the base element and to arrange the second identifier on the containers with biological samples to be analysed, and provides turnover of the first indicator cell about the surface of the base element that ensures a free access to the first identifier when the biochip is installed in temporary or persistent storage devices and provides fast-access retrieval of the biochips, including with using computer-based systems.

EFFECT: invention allows simplifying slide or biochip retrieval in temporary or persistent archives, retrieval of previous diagnostic data parametres arranged in electronic databases without additional slide or biochip retrieval in an archive.

20 cl, 8 dwg, 1 tbl, 3 ex

Description

Field of Invention

The invention relates to the field of manufacturing biochips that can be used as diagnostic tools in the field of medicine, veterinary medicine, biotechnology, forensics, environmental protection and the food industry.

State of the art

A large number of technical solutions are known regarding the use of biochips for diagnostics, in which nucleic acids, proteins, antibodies, antigens, cells and tissues are used as probes located on the surface of the biochip.

Existing diagnostic methods use both parallel analyzes of many individual biochips, for example, when analyzing the presence of genetically modified materials in food products, and sequential analyzes that are used to monitor the course of treatment in medical institutions or to monitor environmental pollution parameters. In the process of parallel and sequential analysis, it is often necessary to label those objects that are being diagnosed.

In connection with the development of computer databases that contain analysis data, there is the possibility of a long archival storage of diagnostic results in order to use these results for a long time, for example, to study the health of patients. However, due to the possibility of unauthorized access to computer databases and due to the possibility of external editing of analysis data using standard graphic programs, computer databases cannot replace the archive storage of biochips that have passed scanning. Real samples of biochips are difficult to fake, because both the substrate material and the reagents used differ from each other in different batches. Secondary scanning of biochips taken from the archive makes it possible to verify those data that are recorded in computer databases.

In addition, there are hardware capabilities for directly comparing two biochips, one of which is taken from the archive, in differential mode without using data taken from computer databases. Thus, biochips located in a temporary or permanent storage archive can be used to make decisions in especially important cases, for example, in the diagnosis of diseases or in forensics.

In most cases, biochips or diagnostic slides with one identifier in the form of a barcode are used for diagnostics [1-6]. In other embodiments, an area for applying graphical information is formed [7-9]. It is known when several identifiers of the same type are used for identification [10] or several identifiers of different types are used, which include a barcode, a magnetic element and an alphanumeric identifier [11].

Existing methods for identifying biochips contain limitations associated with the difficulty of finding biochips in known devices used to store biochips. A drawback of biochip designs using identifiers located on the front surface of biochips is the need to extract biochips from devices designed for their storage in order to carry out the process of reading identifier parameters. Typically, devices for storing slides or biochips are made in the form of boxes [12, 13] or racks [14], in which access to the biochip identifier is possible only when the biochip is removed from the storage device.

Other designs are associated with the installation of slides and biochips in flat holders or platforms [15-17]. This solution leads to a high cost of storage and transportation due to the low density of the slides or biochips and require additional tools to identify the platforms themselves and flat holders, which reduces the effectiveness of their use.

Known systems for searching for chemical components located in microplates containing barcode-based identifiers containing many cells (for example, 864 cells) that are placed on racks [18]. For identification, identifiers are used, located not only on the front surface in the auxiliary zone of the die, but also indicators located on the end surface of the dice [19]. However, the thickness of biochips made on the basis of glass slides or polymer sheets, in most cases, is in the range from 0.8 to 1.5 mm, which is insufficient to place the known types of identifiers on such a narrow end surface.

Thus, a common drawback of known identification systems is the difficulty in locating individual biochips or slides with samples after scanning and installing biochips or slides in holders for temporary or permanent storage.

An object of the present invention is to increase the efficiency of searching for slides or biochips located in temporary or permanent storages by developing a new multifunctional identification system for slides or biochips, which simplifies the search for slides or biochips in temporary or permanent archives.

Another technical objective of the invention is the development of a slide or biochip design, which further simplifies the search for samples of biomaterials that are located in temporary or permanent archives after diagnosis with improved identification of the slide or biochip.

Another technical objective of the invention is the development of a slide or biochip design, which, in addition to identifying a slide or biochip, makes it possible to simplify the search for parameters of previous diagnostics data stored in electronic databases without additional searching for slides or biochips in the archive.

SUMMARY OF THE INVENTION

One of the objects of the invention is a biochip with a multifunctional identification system for diagnostics, comprising a base element, clusters, probes, an identifier, an upper and lower multilayer coating and an additional element that is placed in the same plane with the base element and is located next to the end face of the base element, the base and additional elements are fixed relative to each other using adhesive layers, which are provided with multilayer coatings. The upper multilayer coating is placed on the surface of the base and additional elements, it is solid and clusters with probes are located on its surface, or the upper coating has through holes that form zones for the placement of clusters with probes. The identifier is glued to the upper multilayer coating or is made in the form of a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of material that allows it to be cut in the mating zone of the ends of the base and additional elements. The lower multilayer coating is made continuous or contains through holes, the location of which coincides with the position of the holes in the upper multilayer coating, while the lower multilayer coating is made of flexible material that allows the additional element to be rotated, with the identifier placed on it, relative to the base element at an angle of up to 180 degrees after cutting the upper multilayer coating, in the mating zone of the ends of the base and additional elements.

Another object of the invention is a biochip with a multifunctional identification system for diagnostics, comprising a base element, clusters, probes, an identifier, an element that is placed in the same plane as the base element, is made of a common plate with the base element and connected to it by a jumper, while the base and additional elements are fixed relative to each other with the help of the upper and lower multilayer coatings provided with adhesive layers. The upper multilayer coating is placed on the surface of the base and additional elements, it is solid and clusters with probes are located on its surface, or the coating has through holes that form zones for placing clusters with probes, while the identifier is glued to the upper multilayer coating or made in the form of a graphic image, deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of a material that allows it to be cut into e webs between the base and the additional elements. The lower multilayer coating is made continuous or contains through holes, the location of which coincides with the position of the holes in the upper multilayer coating, while the lower multilayer coating is made of flexible material that allows the additional element to be rotated, with the identifier placed on it, relative to the base element at an angle of up to 180 degrees after cutting the upper multilayer coating, in the area of the bridge between the base and additional elements and the subsequent destruction of the bridge ki.

Another object of the invention is a biochip with a multifunctional identification system for diagnostics, containing a base element, clusters, probes, an identifier and provided with upper and lower multilayer coatings, a second identifier and two additional elements, for accommodating the first and second identifiers, respectively. Additional elements are placed in the same plane with the base element and are arranged one after another so that the end face of the base element abuts the first end of the first additional element, and the end face of the second additional element abuts the second end of the first additional element, while the base element, the first and second additional the elements are placed between the upper and lower multilayer coatings and are fixed relative to each other using adhesive layers, which are provided with multilayer coatings. The upper multilayer coating is placed on the upper surface of the base, first and second additional elements, it is solid and clusters with probes are located on its surface, or the coating has through holes that form zones for the placement of clusters with probes. The first and second identifiers are glued to the upper multilayer coating or made in the form of a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of material that allows it to be cut in the mating zone of the ends of the base and first additional elements and in the mating zone of the ends first and second additional elements. The lower multilayer coating is made continuous or contains through holes, the location of which coincides with the position of the holes in the upper multilayer coating, while the lower multilayer coating is made of flexible material, which enables cutting of the lower multilayer coating in the mating zone of the ends of the first and second additional elements, with the possibility of disconnection the second element from the biochip and the subsequent rotation of the first additional element with the identifier relative to it tion of the base member at an angle of 180 degrees, after cutting the upper multilayer coating zone interfacing ends of the base member and the first element.

Another object of the invention is a biochip with a multifunctional identification system for diagnostics, containing a base element, clusters, probes, an identifier and equipped with a second identifier and two additional elements, for placing the first and second identifiers, respectively, additional elements are placed in the same plane as the base element, made of the common plate together with the base element, are located one after another, connected to each other using jumpers, while the end face of the base element Erez jumper end connected to the first additional element, second additional element end connected to the second end of the first additional element, wherein the base member, first and second additional elements is further attached to each other via adhesive layers that are provided with upper and lower multilayer coating. The upper multilayer coating is placed on the surface of the base, first and second additional elements, it is solid and clusters with probes are located on its surface, or the coating has through holes that form zones for placing clusters with probes, and the identifiers are glued to the upper multilayer coating or are made in the form a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of a material that allows cutting in the areas of jumpers. The lower multilayer coating is glued to the rear surfaces of the base element and the rear surfaces of the first and second additional elements, made in the form of a continuous array or contains through holes, the location of which coincides with the position of the holes in the upper multilayer coating, while the lower multilayer coating is made of material, providing the ability to cut the coating in the zone of the bridge between the first and second additional element, with the possibility of subsequent destruction of the slipping and disconnecting the second element with the identifier from the first element connected to the base element, where the ability to rotate the first additional element with the identifier placed on it relative to the base element to an angle of up to 180 degrees is provided due to the flexible properties of the lower multilayer coating after cutting the upper multilayer coating in the zone jumpers between the base and the first additional elements and the destruction of this jumper.

The upper and lower multilayer coatings are made of materials included in the group consisting of: i) opaque materials, ii) translucent materials, iii) reflective materials, iv) light absorbing materials. The base element and additional elements are made of polymers, metals, ceramics, glass or a combination thereof from a thickness of 0.5 mm to 10 mm. As the material of a flexible multilayer, polymers, metals, or a combination of them, with a thickness of 0.05 to 1.0 mm are used. The reflective surface is made of a mirror or retroreflective and applied to the surface of a self-adhesive film or metal film.

The sticker-identifier is made in the form of a graphic identifier, a magnetic medium, or a combination thereof.

List of figures

Figure 1 shows a fragment of a cross section of a biochip containing a base element and an additional element, where a) the base and additional elements are made of separate flat elements, b) the base and additional elements are made of a single solid base, which contains a recess between the base and indicator elements.

In figure 2. a fragment of a cross-section of a biochip containing a base element and first and second additional elements is shown, the base and additional elements being made of a single solid base and connected in series with each other using the first and second jumpers.

In figure 3. a diagram of the transformation of the biochip at the stages of diagnosis and storage.

Figure 4 shows an isometric projection of the components of the biochip containing two identifiers and two working areas, made on the basis of three planar elements connected to each other by jumpers to which the upper and lower multilayer coatings are attached.

5. a variant of a multichip that can be used to make individual biochips is given.

Figure 6 presents the options for the formation of fluorescent signals using a reflective surface, where a) the reflective surface is made mirrored, b) the reflective surface is made of retroreflective material.

Figure 7 shows the results of amplification of a fluorescent signal depending on the distance between the fluorescent label and the mirror surface, where a) the image of clusters without a mirror surface; b), c), d) image of clusters using a mirror layer placed respectively at a distance of 1 mm, 3 mm and 6 mm from the working surface of the biochip.

Fig. 8 shows cross sections of biochip fragments for different versions of the upper and lower multilayer coatings, where a) the upper multilayer coating contains a reflective surface, b) the lower multilayer coating contains reflective surfaces located under the working areas of the biochip, c) the upper multilayer coating contains a polymer, adapted to immobilize proteins.

Description

Description of terms

The term "biochip" means a device that includes the base and first additional elements or the base and first and second additional elements made on the basis of a solid carrier and at least one flexible multilayer coating provided with an adhesive layer that combines the base element and the first additional element or basic element, the first and second additional elements in a single multilayer structure. Moreover, the basic element and additional elements can be made: a) from a single solid carrier and connected by a jumper or b) made of separate elements. Clusters with probes are formed on the surface of the working area located on the base element. Within the boundaries of the first and second additional elements, the first and second identifiers are placed that characterize the parameters of an individual biochip. Identifiers are made in the form of separate multi-parameter identifiers, for example barcodes or magnetic tapes. It is possible to additionally apply code, digital or alphabetic identifiers on the auxiliary surface of the base element near the work area or near clusters.

The term "solid support" means a solid planar element, mainly rectangular in shape. As the materials from which the solid supports are made, polymers, glass, metal, mica, ceramics, or combinations thereof can be used.

The choice of material of the slide is influenced by the physicomechanical properties of the slides: thermoplasticity, the possibility of stamping and formation in the molten state, the ability to withstand temperature cycles during hybridization, and the resistance to chemical reagents that are part of the hybridization mixture and washing solutions. Thermoplastic plastics provide the ability to stamp and form the selected shape of the slide from the polymer melt. The polymers are selected from the group consisting of polymethyl methacrylate, polybutyl methacrylate, polyvinyl chloride, polycarbonate, copolymers of methyl methacrylate and / or copolymers of butyl methacrylate with other monomers, such as styrene, acrylonitrile and others. Using the thermoplastic properties of the polymers on the surface of the slide, protrusions can be formed grooves.

In the framework of the present invention, the term “base element” is understood to mean a separate solid flat element or element made of a single preform together with the first and second additional elements in the manufacture of a biochip. On the surface of the working area of the base element in the process of manufacturing the biochip, clusters are formed with probes characterizing an individual biochip. As a structural element of the biochip, the basic element performs two functions. In accordance with the main function, the base element is a carrier of probes that are immobilized on the surface of the base element or on the surface of the upper multilayer coating within the boundaries of the working areas located on the surface of the base element during the formation of the biochip. The second function that the base element performs as a structural element of the biochip is the function of attaching a multilayer coating on the surface of the base element to create hybridization volumes. In this case, the base element performs the auxiliary function of a solid carrier for a flexible multilayer coating.

Depending on the diagnostic tasks, the dimensions of the base element on which the probes are placed may be smaller or larger than standard glass slides. The base element may be a structural element, which includes the holder of the base element. When choosing the sizes of the base element, it is more preferable to use not only the standard sizes of individual slides, equal to 25 mm × 75 mm, but also other sizes [20]. For example, to reduce the cost of preparing individual biochips, it is possible to use the sizes of the base element, the dimensions of which are 12.5 mm × 75 mm, or mini-basic elements with a size of 25 mm × 37.5 mm, or 12.5 mm × 37.5 mm You can use other sizes of the base element more than 4 mm × 4 mm and less than 120 mm × 120 mm.

One aspect of the invention includes the selection of the material from which the biochip is made. The choice of optical properties of the material of the base element of the biochip depends on the method of recording diagnostic data. Different types of labels are recorded by different physical methods. The most widely used methods of measuring transmittance [21, 22], measuring reflected signals [23, 24], or measuring fluorescent signals [25, 26].

Based on the selected type of label and the registration method, the material from which the slide is made can be a uniform solid material, for example glass, mica, polymer, metal, ceramics. In the manufacture of slides from polymers, they can be transparent, matte, white, black or color. To measure diagnostic results in transmission mode, the slide material must have a light transmission of at least 80-90%. When measuring a reflected, for example colorimetric, signal, the requirements for the material of the slide are related to the quality of formation of the white reflective surface. When measuring signals in fluorescence mode, it is necessary that the material of the slide or the outer surface of the multilayer coating has a minimum intrinsic fluorescence.

Depending on the method for detecting fluorescence, the material may be transparent, made of glass or transparent plastic, for example polymethylmethacrylate, or made in the form of an opaque material, for example black, having a minimum reflectivity, made, for example, of polyvinyl chloride.

Diagnostic results reflecting the interaction between the test sample and the probe are detected using labels. Any labels selected from the group consisting of fluorescent, colorimetric, enzyme, radioactive labels, labels associated with resonant energy transfer (FRET, BRET), labels emitting a luminescence signal (chemiluminescent or bioluminescent labels) can be used within the framework of this invention.

Biochips with immobilized oligonucleotides and proteins are most widely used. Depending on the type of label that is immobilized with the studied DNA or antibody fragment, catalytic, ligand, fluorescent or radioactive labels are used. As catalytic labels, hemin, cyancobalamin or flavin are used. As ligand labels, biotin, dioxigenin or dinitrobenzene are used. Su3, Su5, Su7, FAM, TAMRA, R6G, R110, ROX or JOE are used as fluorescent labels. The tag lists provided include, but are not limited to, other tag options that can be used to detect a signal.

The term "additional element" means a solid planar planar element, which is mainly made in the form of a rectangular shape. The additional element can be made in the form of a separate solid flat element or in the form of an element made of a single workpiece in the manufacture of a biochip together with the base element. The first and second additional elements of the biochip are intended for fastening the first and second identifiers placed on the surface of the upper multilayer coating or on the surface of the additional elements in the form of labels provided with an adhesive layer. The second additional element is equipped with at least one technological hole, which allows you to provide: a) fastening the biochip in the space of the washing and drying chambers, b) attaching the second element, equipped with a second identifier, to the storage device of the test sample made, for example, in the form packages, boxes, or for fixing the identifier on storage devices of volumetric objects used for forensic research, or for storing identifiers in medical records.

The first and second additional elements can provide the possibility of installing additional protective elements in the form of films, sheets or plates on the surface of the biochip to protect the surface of individual chips during storage or during hybridization.

Additional technological holes in the second additional element (see figure 2) allow: a) to group several biochips in the form of notebooks. The material of the additional element may be similar or different from the material of the base element in physicochemical properties or in color.

As the material of the first and second additional elements, it is preferable to use polymers. The polymers are selected from the group consisting of polymethyl methacrylate, polybutyl methacrylate, polyvinyl chloride, polycarbonate, copolymers of methyl methacrylate and / or copolymers of butyl methacrylate with other monomers, such as styrene, acrylonitrile, etc. The thickness of the additional element should preferably be the same with the thickness of the base element used or installed in the frame, and lie in the range from 0.5 mm to 10 mm.

The term "multilayer coating" means a node that is the main element for the formation of a biochip. A multilayer coating contains at least two flexible layers with different physicochemical properties. The multilayer coating may contain a composition of at least two layers included in the group consisting of: i) a flexible polymer layer, ii) an adhesive layer, iii) a reflective layer, iv) a translucent layer, v) an opaque layer, vi) absorbent a layer, vii) a layer for displaying biochip identifiers selected from a group of barcodes, magnetic tape, inductive sensors, and combinations thereof.

The term "flexible layer" in the framework of this invention refers to a polymer layer that is used to form layers or in which through holes are formed to create hybridization volumes. The flexible layer can additionally carry out the bearing function of the biochip elements when connecting the base element and the first and second additional elements and may have a thickness of more than 0.05 mm or more than 0.1 mm, 0.3 mm, 1.0 mm. Adhesive layers have a thickness of more than 0.01 mm. The reflective layer has a thickness of more than 0.001 mm. The translucent layer has a thickness of more than 0.01 mm. The opaque layer has a thickness of more than 0.01 mm The absorbent layer has a thickness of more than 0.001 mm. Modifying and / or absorbing layers are applied to the active surfaces of biochips during the manufacturing process.

The list of layers used to create biochips oriented to the analysis of proteins, antibodies, enzymes, as a layer material for immobilization of probes, may include such polymeric materials as nylon, nitrocellulose, PVDF, and other polymers.

A multilayer coating may include: a) flexible layers provided with one adhesive layer, b) flexible layers provided with two adhesive layers and applied to the upper and lower surfaces of the flexible layer, c) flexible layers not provided with an adhesive layer, d) combination of layers included in paragraphs a), b), c). The flexible layers forming the multilayer coatings are arranged one above the other and connected in such a way that one of the surfaces of the upper or lower multilayer coatings contains a self-adhesive layer that is glued to the upper and / or lower surfaces of the supporting elements of the biochip or slide, for example by applying pressure.

An adhesive or adhesive layer should create a strong bond between the surface of the slides, the surface of the supporting element and the multilayer coating. This connection should be stable and should not be broken when the temperature of the external environment changes in the range from -20 to 60 ° C. The adhesive layer must retain its adhesive parameters under the conditions of the action of the reagents used to wash the surface of the slides or during the formation of the modifying layer on the surface of the slides, or the reagents involved in the formation of the hybridization solution.

By the term “probe” is meant one of two binding molecules that interact with each other through a specific non-covalent interaction. The probe molecule is immobilized on the working surface of the biochip, and the quality of binding is determined by the choice of probe structure. The group of typical pairs of molecules that are used in the manufacture of protein and DNA chips may include oligonucleotides, proteins, antigens, antibodies, enzymes. An analyte includes one or more types of molecules that need to be diagnosed.

The term "cluster" means a part of the active working surface of the biochip, on which probes of the same type are immobilized. Up to 500 clusters are placed on the working surface of biochips with an average density level, in which from 2 to 20 types of probes are placed. Clusters can be in the form of a rectangle, square, circle, ellipse, polygon, triangle, or represent a linear structure expressed by a linear sequence of points. Clusters can be applied on a modified surface of slides [21] or fixed on an unmodified surface [27].

The term "auxiliary surface" refers to the surface of the biochip located outside the working zones on which the clusters with probes are located.

Description

In the process of studying the properties of polymeric materials, with an adhesive layer deposited on their surface, under conditions of changing temperature in the range from -10 ° С to + 60 ° С, as well as in buffer solutions for hybridization or in solutions for modifying the surface of polymers, it was found that flexible polymeric materials with adhesive layers deposited on them, for example, made in the form of self-adhesive films, allow you to create many options for inexpensive multi-chips.

Known technical solutions in which self-adhesive films are used to perform only one function in the manufacture of biochips. Such functions, for example, include: creating hybridization volumes [28, 29], attaching solid slides with a modified surface [30] to the surface of a flexible base [30], attaching solid slides to a solid substrate surface [31], and gluing flexible slides onto a solid surface polymer films to form an active surface [32]. It is known to use PVC as a structural element of biochips. However, the known solutions use one function of PVC, for example, to create a surface layer [33] or for use as an adhesive base for gluing the outer layer onto a slide [32].

A similar analogue of the symmetric arrangement of two layers of polymer material above the upper and lower surfaces of an individual slide used in spectroscopy is known [34]. This device contains only four working areas on the surface of the glass slide, and the square shape of the slide holder is not intended for the use of these structures in widely known scanners working with biochips and placed on rectangular plates 25 × 75 mm in size. In addition, the device is not intended for hybridization on the surface of the slide, since the materials do not contain data on the possibility of the structure working with the applied solutions at elevated temperatures required for hybridization. The present invention eliminates all of the above disadvantages of analogues.

The proposed technical solution establishes a different approach in the design of biochips or slides, since it involves the use of a transformable design that changes its configuration during the diagnostic process.

In addition, in this invention, to increase the efficiency and reduce the cost of production of biochips, the materials of the flexible layers included in the multilayer coating are selected so that they can simultaneously perform at least several independent functions.

The first, structural, function is associated with the support and fastening of the base element and the first and second additional elements relative to each other at all stages of biochip production, from the stage of processing the surface of the slides to the stage of diagnosis.

The second function that the material of the flexible layers included in the multilayer coating can perform is the creation of hybridization zones separated from each other on the surface of the base element that is part of the biochip. Hybridization zones are formed by making through holes in the material of the flexible base.

The third function of the flexible layers is related to the choice of the material of the flexible layer and its physicochemical surface properties. Such properties include: a) the possibility of immobilization of probes on a modified or unmodified surface of a flexible layer, b) the possibility of forming a reflective surface to enhance fluorescence signals, c) the ability to select a flexible layer with a surface that performs quenching of fluorescence.

The fourth function of a flexible layer located on the outer surface of a multilayer coating can be attributed to the possibility of applying on its surface a graphic image of a barcode or other graphic digital or alphabetic information identifying both individual biochips and clusters.

The fifth function that the flexible layer in the biochip design can perform is the ability to easily separate the second additional element from the biochip for identification of the studied samples for subsequent storage in the archive and the possibility of forming a flexible hinge to allow the first additional element to rotate relative to the base element from 0 to 180 degrees or 90 degrees.

As an additional informative parameter when constructing a biochip, it is possible to use the color of the polymer, which is part of the upper or lower flexible layer, which allows you to bind the color of the biochips to the diagnostic function they perform.

It is possible to perform an auxiliary zone of the base element in a color scheme different from the color schemes of the first and second additional elements. Selecting a specific color for the base element, the first and second identifiers allows you to simplify the work of the operator during hybridization and when scanning results, since it can be additional information that allows you to determine the type of biochips that is associated with a specific color of the auxiliary zone or the color of the first or second identifiers.

The combination of more than five technical functions of the flexible layers allows you to get a synergistic positive effect, which was not obtained earlier, since no more than two functions of the flexible layer were used to create biochips.

In the framework of this invention to create a multilayer coating, it is possible to use a wide range of polymers. The material from which the flexible multilayer coating is made can be made of transparent or colored flexible polymers, polymers that are equipped with a reflective layer, polymers with a low level of autofluorescence, polymers capable of modifying the surface or directly immobilizing oligonucleotide or protein probes on its surface.

These materials include polyethylene, polypropylene, polyvinyl chloride (PVC). Most preferred is a polymeric carrier made of polyvinyl chloride with a layer of glue applied to it. For example, 3M (USA) [35] and Orafol (Germany) produce a wide range of self-adhesive materials based on transparent, white and colored polyvinyl chloride, as well as self-adhesive materials containing a reflective layer made in the form of a mirror or reflective surface.

In the present invention, the technical problem is solved with the help of materials that can eliminate thermal expansion and layering of layers in the manufacturing process of a multilayer coating based on it. As an example that includes, but does not limit the scope of the invention, polyvinyl chloride is preferably used as the material from which the flexible layers of the multilayer coating are made.

The non-obviousness of the technical solution is additionally associated with the simultaneous use of all the technological capabilities of PVC. A variety of known types of PVC allows you to create a biochip with new advanced features.

These PVC options for building biochips include: a) choosing the color of the auxiliary surface of biochips to create a multi-chip color gamut, b) using a self-adhesive film with a reflective surface, for example, made with a sprayed layer of aluminum or made in the form of a retroreflective surface, c) selection of different layer thicknesses PVC to control the volume of the hybridization mixture, d) the ability to effectively modify the surface of PVC to activate the surface and immobilize the probes, e) application to the outer layer is flexible th basics of graphic images, for example, in the form of bar codes or other alphanumeric identifiers.

The analysis of the prior art showed that none of the inventions known from the prior art solved the complex task of simplifying the procedure for searching biochips in archives.

When developing the biochip design with multifunctional identifiers, it was found that the introduction of the first additional element into the biochip design based on the base element with the possibility of its rotation relative to the surface of the base biochip element in the angle range from 0 to 180 degrees or 90 degrees allows data reading from the first identifier when it is installed in the storage device without additional extraction of the biochip from the storage device, as shown in figure 3. Introduction to the design of the second additional element and the placement on it of a second identifier, which preferably has the same code combination as the first identifier, allows you to identify objects of research placed in separate devices (boxes, bags, bags, bottles, test tubes). This combination of the functions of the first and second identifiers allows, in modern clinics provided with computer systems, to provide a quick search according to the first and second identifiers of both digital diagnostic data located in the database and a quick search of real samples of biochips that have passed the scanning stage to various time and placed in temporary and permanent archives, as well as carry out a quick search for samples of the studied material in the case when it is necessary to conduct additional diagnostics.

This achieves a positive effect associated with a reduction in the search time for a given biochip in a large array of biochip archives. This function is especially necessary in hospitals to compare research data during the treatment of the patient.

Another non-obvious function of the first and second additional element is the possibility of attaching a protective film to their surface to protect the surface of the formed biochips during transportation and as covering elements protecting the evaporation of the hybridization liquid during hybridization. Thus, all the listed additional opportunities associated with the introduction of the first and second additional elements into the biochip, with the possibility of disconnecting the second additional element from the biochip and with the possibility of placing the first additional element in an upright position, provide a general synergistic positive result associated with convenience, simplicity, high efficiency and reliability of the search for biochips or diagnostic objects located in permanent or Yemen archives.

Figure 1-4 and figure 7 shows examples of designs for different variants of biochips. Figure 5 presents an embodiment of a multichip, with which several individual biochips are manufactured simultaneously. On figa and 1b shows options for the simplest designs of biochips containing a base element and an additional element. The biochip (10) contains a base element (1) and an additional element (2), as well as upper (5) and lower (6) multilayer coatings. In the first embodiment, shown in figa, the base and additional elements are made of separate flat elements. The upper (5) multilayer coating is placed on the upper surface of the base (1) element and the first (2) additional element. At least one hole (7) is made in the upper multilayer coating, the position of which coincides with the working area of the biochip. Clusters (3) with probes (4) are placed on the upper surface of the biochip within the working area. During hybridization, the walls of the holes (7) formed in the upper (5) multilayer coating limit the spreading of the hybridization liquid. The thickness of the upper multilayer coating can adjust the volume of the hybridization fluid. To eliminate the drying of the hybridization liquid, a cover element (not shown in Fig. 1) is applied to the surface of the upper (5) multilayer coating, which is removable and whose edges abut against the auxiliary surface of the biochip, fixing a constant volume of the hybridization mixture. The lower multilayer coating (6) is attached to the lower surfaces of the base (1) element and the first (2) additional element. The lower multilayer coating, depending on the choice of the type of biochip and methods for scanning the results of hybridization, can be distributed over the entire surface of the base element or contain holes located above the holes in the upper multilayer coating, or occupy part of the surface located in the auxiliary zone of the base element. This design allows the passage of light flux through a transparent solid carrier of the base element and is used to measure the transmission of light flux through the test substance. In other embodiments, which are described in more detail in the examples, the lower multilayer coating may be opaque or contain a reflective surface. After hybridization and scanning of diagnostic results, the operator, before installing the biochip in a temporary or permanent storage device, divides the upper multilayer coating into parts mated to the base (1) element and the additional (2) element in the interface zone (8) of the end surfaces of the base and additional elements. Moreover, due to the flexible properties of the lower multilayer coating, which performs the function of a hinge (in the zone (9) between the base element and the first additional element), the additional element (2) can be rotated relative to the horizontal surface of the base (1) element by an angle of 90 degrees and in this form is installed in the storage device. This arrangement of the additional element allows free access to the data recorded on the identifier (14), mounted on the additional element, for example, in the form of a barcode, and enables the data to be scanned without removing the biochip or slide from the storage device (11). The storage unit (11) may contain an additional identifier (11) (see figure 3) and may, depending on size, contain from 10 to 1000 biochips. The installation of blocks on top of each other in the vertical and horizontal plane along the XY coordinates allows you to significantly expand the number of stored biochips and allows you to use automated search systems similar to those used to search for dies with biomaterials placed.

In cases where it is necessary to provide temporary storage and separation of surfaces superimposed on each other biochips or slides with samples, the additional element is rotated 180 degrees relative to the upper surface of the base element. Thus, it is possible to form a double thickness on one side of the biochip, which allows you to separate the working surfaces of the biochips from the rear non-working surfaces due to the space created by the thickness of the additional element.

In the second version of the biochip, shown in Fig.1b, the base and additional elements are made of a single solid base, which contains a recess (15) between the base (1) and additional (2) elements, a jumper (16) is formed in the recess between the base and additional elements. As in the first embodiment, the upper multilayer coating (5) is located on the front surfaces of the base and additional elements of the biochip, and the second multilayer coating (6) is located on the common back surface, including surfaces related to the base and additional elements, and the surface related to jumper. After hybridization and scanning, the operator disconnects the upper multilayer coating (5), separating the base and additional parts of the upper multilayer coating (5) from each other in the mating zone (8) of the side surfaces of the base element and the additional element. By pressing the additional element (2), the operator destroys the jumper (16), thereby making it possible for the lower (6) flexible layer to function as a hinge connecting the base (1) and additional (2) elements. As in the first version of the biochip, shown in figa, the first additional element (2) is automatically installed in a vertical position relative to the horizontal position of the base element (1), then the biochip is placed in a storage device (11), providing access to information placed on the identifier (14).

Figure 2 shows a variant of the biochip (20), which contains the base element (21), the first additional element (22) and the second (28) additional element made of a single solid base, which contains the first (30) and second (31) the recesses, respectively, between the base (21) and the first (22) additional element and between the first (22) additional element and the second (28) additional element.

Figure 3 is a diagram explaining the sequence of transformation of the shape of the biochip (20) at different stages of diagnosis and storage. Before or after hybridization, the operator disconnects the upper (25) multilayer coating in the area located above the second (31) jumper, and separates the lower (26) multilayer coating under the second (31) jumper, separating the multilayer coating between the first (22) and the second ( 28) additional elements. Then the operator destroys the second jumper (31) and separates the second (28) additional element from the biochip (20). Using the technological hole (38), the second additional element (28) with the identifier installed on it can be installed on the container with samples of the test material, which can be placed in bags and / or in test tubes, or embedded in research materials or in the patient’s card, thus identifying the diagnostic results with the object of study in the case of their search in electronic databases or in the case of a search for a sample of the studied material from the data recorded in the databases for secondary oh diagnostics.

Then the operator scans the biochip using a scanner (35), processes the diagnostic results using software using a computer (36), and transfers the analysis data via a communication line (37) to the central data bank, which stores images and diagnostic data that can be identified in accordance with the codes of the first and second identifiers.

At the final stage, the operator cuts the upper (25) multilayer coating of the biochip (20), separating the base (21) and additional (22) parts of the upper multilayer coating from each other, and pressing the additional element (22) destroys the jumper (30), thereby making it possible to install the first additional element (22) in a vertical position due to the flexible properties of the lower multilayer coating (26) for subsequent installation of the biochip (20) in the storage device (11).

The examples cited include, but are not limited to, other biochip options, a common feature of which is that the first identifier is located on the side opposite to the flexible multilayer coating, which makes it possible to rotate the first additional element.

Figure 4 shows an isometric projection of a biochip containing two working areas on the base element. The base (40) element is connected using the first (41) jumper with the first (42) additional element, which in turn is connected using the second (43) jumper with the second (44) additional element. The first (47) and second (48) identifiers are graphically applied or placed on the upper multilayer coating (45) in a graphical manner or placed on separate labels provided with an adhesive layer, and a section line of the upper multilayer coating in the area between the first additional and a base element and a second (49) cut line between the first additional element and the second additional element. In the above embodiment, the upper multilayer coating (45) is made of a self-adhesive film. The lower multilayer coating (50) contains three layers. The first layer (51) acts as a gasket provided with a double-sided adhesive layer. The first adhesive layer is glued to the back side of the biochip, the reflective layer (52) is glued to the second adhesive layer, which is protected on the back side with an additional layer (53) of self-adhesive film. On the back surface of the last layer, a graphic image of the cut line between the first and second additional elements is preliminarily applied for their subsequent separation. Openings (55) are formed in the upper (45) multilayer coating and in the gasket (51), which coincide with the position of the working areas of the base element (40).

Figure 5 shows a variant of a multichip, which includes, but is not limited to other options and can be used for the manufacture of individual biochips. The structure of the biochips that make up the multichip can be similar to the structure of the biochip shown in Fig. 4.

The multichip contains a carrier element common to all biochips (61), which is connected to each biochip by an individual jumper (68). Jumpers serve as an intermediate supporting element and make it possible to carry out structural functions when working with a multi-chip at different stages of manufacture, including washing, drying, printing clusters on a work surface. Technological holes (63) can be formed in the carrier element, allowing additional fastening of the multi-chip or the connection of several multi-chips in the form of folders or notepads for transportation or storage. Solid media in the form of slides (64) and the supporting element (61) are planar, in the same plane, and form a planar layer to which at least one flexible multilayer coating is attached.

Individual biochips are separated relative to each other along lines (65) graphically displayed on the upper and lower multilayer coatings of the multichip. In the upper multilayer coating (66) of the multichip, holes (68) can be formed that coincide with the position of the working zones of individual biochips. Similar holes can be made in the gasket (69). One of the intermediate layers (70), as part of the lower multilayer coating of the multichip, contains a reflective surface. The bottom layer (71) protects the reflective layer (70).

Telechem International Inc. is known to [36] produces biochips with a mirror surface located on the back surface of slides, from which biochips are formed. However, this solution is quite expensive, because it uses spraying technology. Known technical solutions for placing a mirror or retroreflective surface on the front surface of biochips [37] or multilayer structures containing optical elements inside the layers [38]. However, for the manufacture of simple and cheap mass chips, it is more preferable to use reflective surfaces made on the basis of self-adhesive films.

It is preferable to use coatings developed by 3M as reflective materials. The company offers a wide range of multilayer retroreflective coatings, which are made using spheres [39] or microstructured surfaces [40, 41, 42]. The most promising retroreflective films of diamond type. For example, 3M Series 3990 VIP Series film is a microprism based material that provides higher retroreflectivity. Films coated with a retroreflective layer are provided with a self-adhesive composition and are glued at room temperature. The retroreflective surface of materials based on the use of cubic angle prisms is made by casting or molding prismatic elements on the lower surface of a very thin substrate. Depending on the type of material, 7300 to more than 15500 prisms are placed on one square centimeter of the surface (3M technical description).

On figa presents a reflection of the incident light (75) on the reflective mirror surface (78) of the biochip (80), located behind the rear surface of the base element (81) of the biochip, on the front surface of which there are clusters (82) with probes (83), equipped with fluorescent dyes. The light flux (75) falls on the surface of the biochip, on which clusters (82) with probes (83) are placed, causing the first fluorescence flux of sample S1, which arrives at the input of the reader optical system (35). Further, the light flux (75) passes through the transparent layer (81) of the base element carrier and is reflected from the mirror surface (78). The mirror surface (78) is pressed against the back surface of the base element using a protective layer (79) provided with an adhesive layer. The reflected signal (76) passes through a transparent carrier (81) and excites the second fluorescence stream S3, acting on the next cluster (84), probes (85) equipped with fluorescent labels emit fluorescence fluxes in different directions, including in the direction opposite to the input of the optical system. In this case, the fluorescence flux is reflected from the mirror layer (78) and returns to the input of the optical system in the form of flows S2, S4. Thus, from one incident flux (22), four fluorescence fluxes S sum. = S1 + S2 + S3 + S4 are formed.

On figb presents a variant of the conversion of incident light (86) on a biochip (81), as the reflective surface of which is used a retroreflective surface (89) made of a self-adhesive film. The luminous flux (86), incident at an angle to the axis of the optical system of the scanner (35), causes the fluorescence flux R1 of the labels contained in the cluster (82). Fluorescence fluxes propagate in different directions, including falling toward the reflective surface (89). The incident fluorescence flux is twice refracted on the triangular surface of the reflector (89) and returns to the optical receiving surface in the form of flux R2. The incident stream (86), passing through the transparent carrier of the base element (90) and the cluster (82) located on its surface (91), is also refracted on the retroreflective surface (89) and returns back to the light emitter. Passing a second time through cluster (82), the reflected light excites a second fluorescence flux R3. Part of the fluorescence flux is reflected from the retroreflective surface (89) and enters the input of the optical system (35) in the form of fluorescence flux R4. The total fluorescence flux arriving at the input of the optical system (35) is equal to the sum of the four fluxes Rsum. = R1 + R2 + R3 + R4. The total fluorescence signal can theoretically be four times larger than when scanning conventional biochips. However, taking into account the absorption and scattering of light on the sample carrier and taking into account the efficiency of the retroreflective surface, which decreases with increasing angle of incidence of the incident flux (86), type and quality of the reflective surface, distance H from the working surface (91) with immobilized clusters (82) to the retroreflective surface (89), this technical solution makes it possible to ensure the return of the light flux and increase the additional illumination of the object not more than four times, as in the case of a mirror, but from two three times, depending on the type of retroreflective material and the angle of inclination of the incident light. It should be noted that a retroreflective coating produced on an industrial scale is significantly cheaper than reflective surfaces that perform not a retroreflection, but a concentration of a fluorescent signal [43]. Known technical solutions for the development of retroreflective films [42] with increased efficiency of retroreflective structures at low angles of inclination of the incident light, which makes the use of reflective surfaces even more attractive.

An example is shown below that confirms the capabilities of biochips equipped with a mirror surface. The dependence of the brightness of the glow of clusters located in the cell on the distance between the rear surface of the cell and the mirror is measured.

Table Dependence of the brightness of the clusters in a cell 1.0 mm thick on the distance between the back surface of the cell and the mirror, which has a light reflection coefficient k = 0.87 Registration Terms The distance from the working surface of the biochip to the mirror (mm) The average brightness of clusters (conventional units) Brightness increase Without mirror - 41.8 one With a mirror 1,1 143.6 3.44 2 123.6 2.96 3 114.0 2.73 6 92.0 2.20 eleven 70.0 1,67

The experiment shows that the design of the device described in the description allows working not only with good and expensive mirrors (for k> 0.95), but also with medium quality mirrors (for example, with k = 0.87). In the latter case, the decrease in brightness relative to the theoretically achievable value (for k = 0.87), equal to 3.5, is several percent (the measured value of the increase in brightness is 3.44).

Figure 7 presents photographs of clusters at various distances from the rear surface of the cell to the mirror at which measurements were taken (column 2 of the table).

As can be seen from the experimental results, even at a distance of 11 mm, the brightness of the cluster points increases by 1.67 times.

Examples

Below are examples of the use of self-adhesive films for the manufacture of various types of biochips.

Example 1. Biochip with a reflective surface and a hybridization volume

On figa shows a variant of the biochip (93), which, in contrast to the known solution [37] contains hybridization volumes (94), formed due to the thickness of the upper multilayer coating (95), glued to a reflective layer (96), glued to the upper surface base (97) element and the first (98) and second (99) additional elements, which are made in the form of independent elements and are attached to each other due to the upper (100) and lower (101) multilayer coatings.

Example 2. A biochip with a reflective surface located on the back surface of a transparent base element

On figb shows a variant of the biochip (102), in which the reflective surface (103) is placed behind the rear surface of the base element (104). In this embodiment, the reflective surface is not located over the entire surface of the biochip, but is located under the working areas (105), which allows reducing the level of reflecting light fluxes from the auxiliary surface and lowering the background level.

Example 3. Protein chip

On figv shows a variant of the protein chip (106), which differs from the known options [32, 44] in that it has hybridization volumes (107) made using the upper layer (108), which is part of the upper multilayer coating (109) comprising a polymer layer (110) and a gasket (111) provided with a double-sided adhesive layer for fixing the layer (110) relative to the surface of the base element (112), the first additional element (114) and the second additional element (115), to the reverse surface which attached the lower multilayer coating ( 116). The difference is that the protein chip has a multifunctional identification system made using the first and second additional elements that are disconnected and provide an overview of the identifiers in accordance with the previously given description.

Industrial applicability

The biochip (options) has a simple design, is inexpensive to manufacture, and may be available for medical, veterinary, and other types of diagnostics in small laboratories.

The biochip provides the ability to separate the second additional element from the first additional element and the base element and place the second identifier on containers containing biological samples for analysis, and also provides the ability to rotate the first additional element 90 degrees from the surface of the base element, which provides free access to the first identifier when placing the biochip in devices for temporary or permanent storage and ensure flushes the ability to quickly search for biochips, including with automatic systems.

Thus, the combination of introduced new structural elements and the possibility of transforming the position of the individual nodes of the biochip relative to each other can improve the efficiency of the search for biochips and test samples during permanent or temporary storage.

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Claims (20)

1. A biochip with a multifunctional identification system for diagnostics, containing a base element, clusters, probes, an identifier, an upper and lower multilayer coating, characterized in that it is equipped with an additional element for placing an identifier, which is located in the same plane with the base element and is paired with an end face the base element, while the base and additional elements are placed between the upper and lower multilayer coatings and are fixed relative to each other using adhesive layers, which are equipped with ogosloynye coating
moreover, the upper multilayer coating is placed on the surface of the base and additional elements, it is solid and clusters with probes are located on its surface or the coating has through holes forming zones for the placement of clusters with probes, while the identifier is glued to the upper multilayer coating or made in the form of a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of a material that makes it possible to cut in the interface zone of the ends of the base and additional elements,
where the lower multilayer coating is made continuous or contains through holes, the location of which coincides with the location of the holes in the upper multilayer coating, while the lower multilayer coating is made of flexible material, allowing rotation of the additional element with the identifier placed on it relative to the base element at an angle of up to 180 ° after cutting the upper multilayer coating in the mating zone of the ends of the base and additional elements,
moreover, the upper and lower multilayer coatings are made of materials included in the group consisting of: i) opaque materials, ii) translucent materials, iii) reflective materials, iv) light-absorbing materials. 2. The biochip according to claim 1, characterized in that the base element and the additional element are made of polymers, metals, ceramics, glass, or a combination thereof and have a thickness of from 0.5 to 10 mm. 3. The biochip according to claim 1, characterized in that the flexible multilayer coatings are made of polymers, metals or a combination thereof and have a thickness of 0.05 to 1.0 mm. 4. The biochip according to claim 1, characterized in that the reflective material is made with a mirror or retroreflective surface. 5. The biochip according to claim 1, characterized in that the glued identifier is made in the form of a graphic image, a magnetic medium, or a combination thereof. 6. A biochip with a multifunctional identification system for diagnostics, containing a base element, clusters, probes, an identifier, an upper and lower multilayer coating, characterized in that it is equipped with an additional element, which is located in the same plane with the base element, made in the form of a common plate together with the base element and connected to it by a jumper, while the base and additional elements are fixed relative to each other using the upper and lower multilayer coatings provided with adhesive layers,
moreover, the upper multilayer coating is placed on the surface of the base and additional elements, it is solid and clusters with probes are located on its surface or the coating has through holes forming zones for the placement of clusters with probes, while the identifier is glued to the upper multilayer coating or made in the form of a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of a material that makes it possible to cut in the jumper zone between the base and additional elements,
where the lower multilayer coating is made continuous or contains through holes, the location of which coincides with the location of the holes in the upper multilayer coating, while the lower multilayer coating is made of flexible material, allowing rotation of the additional element with the identifier placed on it relative to the base element at an angle of up to 180 ° after cutting the upper multilayer coating in the jumper zone between the base and additional elements and the subsequent destruction of the jumper ,
moreover, the upper and lower multilayer coatings are made of materials included in the group consisting of: i) opaque materials, ii) translucent materials, iii) reflective materials, iv) light-absorbing materials. 7. The biochip according to claim 6, characterized in that the base element and the additional element are made of polymers, metals, ceramics, glass, or a combination thereof and have a thickness of from 0.5 to 10 mm. 8. The biochip according to claim 6, characterized in that the flexible multilayer coatings are made of polymers, metals or a combination thereof and have a thickness of 0.05 to 1.0 mm. 9. The biochip according to claim 6, characterized in that the retroreflective material is made with a mirror or retroreflective surface. 10. The biochip according to claim 6, characterized in that the glued identifier is made in the form of a graphic image, a magnetic medium, or a combination thereof. 11. A biochip with a multifunctional identification system for diagnostics, containing a base element, clusters, probes, an identifier, upper and lower multilayer coatings, characterized in that it is equipped with a second identifier and two additional elements, which serve to place the first and second identifiers, respectively, additional elements placed in the same plane with the base element and are arranged one after another so that the end face of the base element is adjacent to the first end face of the first additional element, and the torus n second additional element is adjacent to the second end of the first additional element, wherein the base member and first and second additional elements are placed between upper and lower multilayer coatings and secured relative to each other via adhesive layers that are provided with the multilayer coating,
moreover, the upper multilayer coating is placed on the upper surface of the base element and the first and second additional elements, is continuous and clusters with probes are located on its surface or the coating has through holes forming zones for the placement of clusters with probes, while the first and second identifiers are glued to the upper multilayer coating or made in the form of a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of material, providing the possibility of its cutting in the mating zone of the ends of the base and first additional elements and in the mating zone of the ends of the first and second additional elements,
where the lower multilayer coating is attached with an adhesive layer to the surfaces of the base element and the first and second additional elements and is continuous or contains through holes, the location of which coincides with the location of the holes in the upper multilayer coating, while the lower multilayer coating is made of a flexible material that allows cutting of the lower a multilayer coating in the mating zone of the ends of the first and second additional elements with the possibility of detaching the second element of the biochip and the subsequent rotation of the first additional element, placed on it with respect to the identifier of the base member at an angle of 180 ° after the cutting of the upper multilayer coating interface zone ends of the base member and the first element,
moreover, the upper and lower multilayer coatings are made of materials included in the group consisting of: i) opaque materials, ii) translucent materials, iii) reflective materials, iv) light-absorbing materials. 12. The biochip according to claim 11, characterized in that the base, first and second additional elements are made of polymers, metals, ceramics, glass, or a combination thereof and have a thickness of 0.5 to 10 mm. 13. The biochip according to claim 11, characterized in that the flexible multilayer coatings are made of polymers, metals or a combination thereof and have a thickness of from 0.05 to 1.0 mm. 14. The biochip according to claim 11, characterized in that the retroreflective material is made with a mirror or retroreflective surface. 15. The biochip according to claim 11, characterized in that the glued identifier is made in the form of a graphic image, a magnetic medium, or a combination thereof. 16. A biochip with a multifunctional identification system for diagnostics, containing a base element, clusters, probes, an identifier, an upper and lower multilayer coating, characterized in that it is equipped with a second identifier and two additional elements to accommodate the first and second identifiers respectively, additional elements are placed in one plane with the base element, made in the form of a common plate with the base element, arranged one after another, connected to each other using jumpers so that the end face of the base element is connected via a jumper to the end face of the first additional element, and the end face of the second additional element is connected to the second end face of the first additional element, while the base element, the first and second additional elements are additionally bonded to each other using adhesive layers, which are provided with the upper and lower multilayer coatings,
moreover, the upper multilayer coating is placed on the surface of the base, first and second additional elements, is solid and clusters with probes are located on its surface or the coating has through holes forming zones for the placement of clusters with probes, while the identifiers are glued to the upper multilayer coating or are made in a graphic image deposited on the surface of the upper multilayer coating, while the upper multilayer coating is made of a material that provides Nost cutting it in the areas of bridges,
where the lower multilayer coating is attached with an adhesive layer to the surfaces of the base element and the first and second additional elements and is continuous or contains through holes, the location of which coincides with the location of the holes in the upper multilayer coating, while the lower multilayer coating is made of material that allows it to be cut into the jumper zone between the first and second additional elements for the subsequent destruction of the jumper and disconnecting the second element with the identifier torus first element connected to the base member, as well as providing the ability to rotate the first additional element placed thereon identifier relative to the base member at an angle of 180 ° after the cutting of the upper multilayer coating headroom between the base and the first additive elements and fracture of said bridges,
moreover, the upper and lower multilayer coatings are made of materials included in the group consisting of: i) opaque materials, ii) translucent materials, iii) reflective materials, iv) light-absorbing materials. 17. The biochip according to claim 16, characterized in that the base element and the additional element are made of polymers, metals, ceramics, glass, or a combination thereof and have a thickness of 0.5 to 10 mm. 18. The biochip according to claim 16, characterized in that the flexible multilayer coatings are made of polymers, metals or a combination thereof and have a thickness of 0.05 to 1.0 mm. 19. The biochip according to clause 16, wherein the reflective material is made with a mirror or retroreflective surface. 20. The biochip according to clause 16, wherein the glued identifier is made in the form of a graphic image or magnetic medium.

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