RU103003U1 - DEVICE FOR ANALYSIS USING THE BIOCHIP - Google Patents

Abstract

 1. A device for analysis using a biochip, containing a tank, on the bottom of which is placed a biochip, characterized in that it is equipped with a device that is hermetically mounted on the surface of the biochip and dividing this tank into several containers of smaller volume, the bottom of each of which is formed by the surface area of the biochip. ! 2. The device according to claim 1, characterized in that the device dividing the container for placing the biochip into several containers of a smaller volume is made in the form of a plate with through holes. ! 3. The device according to claim 2, characterized in that the through holes have an elongated shape. ! 4. The device according to claim 1, characterized in that the device dividing the container for placing the biochip into several containers of a smaller volume is made in the form of a plate with grooves. ! 5. The device according to claim 1, characterized in that the device dividing the container for placing the biochip into several containers of a smaller volume is equipped with additional holes for introducing liquid into these containers. ! 6. The device according to claim 1, characterized in that it is equipped with a removable cover. ! 7. The device according to claim 1, characterized in that the bottom of the tank is removable. !8. The device according to claim 1, characterized in that the bottom of the tank is provided with an adhesive coating for attaching the biochip. ! 9. The device according to claim 1, characterized in that it is equipped with a device pressing to the surface of the biochip device, dividing the tank into several containers of smaller volume. ! 10. The device according to claims 1 and 7, characterized in that it is equipped with a device fixing the removable bottom of the tank. ! 11. The device according to claim 1, characterized in that the shape and dimensions are horizontal�

Description

The utility model relates to the field of medicine, but can also be used in the field of veterinary medicine and biology.

A device for incubation and washing of a biochip, designed to determine surface cell antigens, is used to incubate a biochip with a cell suspension, to wash it, and also to process a biochip with various liquids during additional studies of the cells bound to it, taken as a prototype and representing a container (for example, a Petri dish), on the bottom of which a biochip is fixed. (See, for example, A.V. Shishkin, I.I. Shmyrev, S.A. Kuznetsova, N.G. Ovchinina, A.A. Butylin, F.I.Ataullakhanov, A.I. Vorob s "Immunological Biochips for the parallel determination of surface antigens and morphological study of the cells." Biological membranes, 2008, Volume 25, №4, with 277-284).

The disadvantage of the prototype is the high consumption of reagent solutions that are used in the analysis. This is due to the fact that the solution used must cover the entire surface of the biochip located in the tank, the surface of which has not only test areas that are important for the analysis, but also background areas that separate them.

This circumstance will become especially important in cases where it becomes necessary to use solutions of expensive reagents, for example, fluorescently-labeled antibodies, used to determine coexpression of antigens on cells associated with a biochip.

The situation is further aggravated by the mismatch of the shape and size of the container in which the biochip is located, the shape and size of the biochip. This makes it necessary to bring into contact with the liquid the entire surface of the bottom, and not just the surface of the biochip. This circumstance also causes a large consumption of the studied cell suspension, washing solutions and other liquids at the stages preceding additional studies of cells bound to the biochip.

In addition, the disadvantage of the prototype is the inability to simultaneously bring into contact different parts of the surface of the biochip with solutions of different reagents without mixing them with each other. This does not allow parallel to conduct several different groups of the same type of research on the same biochip.

The disadvantage of the prototype is the need to perform accurate manipulations when securing the biochip in the container and its removal, increasing the risk of damage to the surface of the biochip.

The objective of the claimed utility model is to reduce the consumption of solutions of expensive reagents during analysis, as well as the ability to simultaneously bring into contact different parts of the surface of the biochip with solutions of different reagents without mixing them with each other.

The problem is solved due to the fact that, according to a utility model, a device for analysis using a biochip, containing a container, on the bottom of which a biochip is placed, is equipped with a device that is hermetically mounted on the surface of the biochip and dividing this container into several containers of smaller volume, the bottom of each of which is formed by the surface area of the biochip.

A device dividing a container for placing a biochip into several smaller containers is made in the form of a plate with through holes.

Through holes are elongated.

A device dividing a container for placing a biochip into several containers of a smaller volume is made in the form of a plate with grooves.

The device dividing the container for placing the biochip into several containers of a smaller volume is equipped with additional holes for introducing liquid into these containers.

The device is equipped with a removable cover.

The bottom of the tank is removable.

The bottom of the tank is provided with an adhesive coating for attaching the biochip.

The device is equipped with a device pressing to the surface of the biochip device, dividing the capacity into several containers of smaller volume.

The device is equipped with a device fixing the removable bottom of the tank.

The shape and dimensions of the horizontal section of the tank, on the bottom of which the biochip is placed, correspond to the shape and dimensions of the biochip.

Using the claimed utility model allows to reduce the consumption of solutions of expensive reagents during the analysis, while allowing the simultaneous contacting of different parts of the biochip surface with solutions of different reagents without mixing them with each other. This is achieved due to the presence of a removable device, hermetically mounted on the surface of the biochip and dividing the container in which the biochip is placed into several containers of smaller volume, the bottom of each of which is formed by the surface sections of the biochip.

Correspondence of the shape and size of the internal horizontal section of the tank, on the bottom of which the biochip is placed to the shape and size of the biochip, allows to reduce the consumption of cell suspension and solutions used at those stages of the analysis when the device dividing the tank for placing the biochip into several smaller containers is not installed .

The presence of a removable bottom, as well as the presence of an adhesive coating on it, can reduce the risk of damage to the biochip when it is fixed in the device and removed from it. The bottom can be made of adhesive film, which makes it easy to separate and replace it after analysis. This makes using the device more convenient. The bottom of the tank can be made transparent, which also allows you to control the process of some stages of the analysis analysis (for example, washing the biochip from non-specifically bound cells), as well as reading the analysis result using microscopy in transmitted light.

Due to the use of a removable cover, liquid splashing is eliminated and its evaporation is reduced.

The presence of a device fixing the removable bottom of the tank makes its fastening reliable and eliminates the separation of the bottom during the analysis.

The presence of an additional device that presses a device to the biochip, dividing the container for placing the biochip into several containers of a smaller volume, eliminates the possibility of depressurization of this compound.

The presence of additional holes in the device dividing the container for placing the biochip into several containers of smaller volume, allows you to enter the necessary solutions into these containers using an automatic micropipette, a Hamilton syringe or other similar device.

The device can be equipped with several types of removable devices, dividing the container (cuvette) into several containers of smaller volume. This increases the versatility of the device, because it allows you to work with biochips of different designs.

The presence of a removable cover allows you to reduce the evaporation of liquid from the device during the analysis. In the presence of a hermetically sealed lid, the device can also be used as a container, allowing for long-term storage of the biochip before use. (In this case, the device intended for dividing the container for placing the biochip into several containers of smaller volume should be removed).

The utility model is illustrated by the drawing, in which Fig. 1 shows a general view of the device (top) with an installed device dividing the container (cuvette) into several containers of a smaller volume, which is made in the form of a plate with parallel through slots.

figure 2 presents a section aa in figure 1

figure 3 presents a section bb in figure 1

Figure 4 presents a General view of the device (top) with a biochip installed and a removable transparent cover and a removed device designed to separate the container (cuvette) into several smaller containers.

Figure 5 presents a section CC in figure 4

Figure 6 presents a cross section of a device in which a device is installed, designed to divide the cell into several containers, made in the form of a plate with parallel grooves.

Figure 7 presents a top view of the device in which the device is installed, designed to divide the cuvette into several containers, made in the form of a plate with through holes.

On Fig presents a biochip, test sections of which are made in the form of parallel stripes.

Figure 9 shows the biochip, the test sections of which are made in the form of areas of a round shape.

The device comprises a housing 1 (Fig. 1), which is a plate in which a hole 2 is made (Fig. 2). A removable bottom 3 is attached to the housing 1 (Figs. 3, 5, 6) made of a transparent material. When attaching the bottom 3 (figure 5) to the body 1, a container 4 is formed. The bottom 3 has an adhesive coating (not shown in the drawing). The bottom 3 can be made in the form of an adhesive film glued to the housing 1. A biochip 5 is attached to the bottom 3 (by gluing to the adhesive coating) 5. Other design options for the removable bottom are possible, for example, in the form of a solid plate, as well as other methods of attachment biochip 5. It is also possible to implement a device with a fixed bottom, but in this case it will be much less convenient to use.

The stiffness of fixation of the removable bottom 3 (Fig. 5) to the housing 1 is provided by the pressing frame 6. The pressing frame 6 has a hole closed by a transparent insert 7, which, when assembling the device, is located under the bottom 3 of the tank 4.

The shape and dimensions of the horizontal cross section of the tank 4 (FIG. 1) correspond to the shape and dimensions of the biochip 5 (FIGS. 8, 9). The device is equipped with a removable device 8 (Fig. 1, 3, 6, 7) installed on the surface of the biochip 5 (Fig. 3, 6) (located in the tank 4) and dividing the tank 4 into several containers 9 having smaller sizes.

The device 8 is made in the form of a plate 10 having a coating 11, a sealing connection with a biochip 5. To be able to work with biochips of 5 different types (Figs. 8, 9), the device is equipped with different types of removable devices 8 (Figs. 1, 3, 6, 7 ), differing in design. In the device 8 (1, 3) of the 1st type, in the plate 10 there are made through holes (slots) 12 of an elongated shape, arranged in parallel. When installing the device 8 on the surface of the biochip 5 are formed parallel to each other capacitance 9 (figure 3). Through-holes 13 are made in the plate 10 (FIG. 1) of the device 8, each of which is connected to one of the holes (slots) 12. The holes 13 are used to fill the containers 9 with liquid using an automatic micropipette, a Hamilton syringe, or other similar device. (When liquid is introduced, a micropipette tip or a Hamilton syringe needle is inserted into hole 13).

In the device 8 (Fig.6) of the 2nd type, instead of through the slots, grooves 14 are made of an elongated shape, which are also located in parallel. The device 8 of this type also has holes (similar to the holes 13 shown in FIG. 1), which communicate with the grooves 14. When a device of the 2nd type 8 is installed on the surface of the biochip (6), several containers 9 are also formed, which are in In this case, they look like capillaries.

Devices 8 of the 1st and 2nd type allow working with biochips (Fig. 8), in which test sections 24 containing immobilized substances are made in the form of parallel strips. In this case, it is possible to install this device so that the slots 12 (or grooves 14) are perpendicular to the test sections of the biochip and each groove 14 (slot 12), when the device 8 is installed on the surface of the biochip 5, forms a container 9, at the bottom of which several fragments were located different test sections 24. In addition, it is possible to install the device 8 so that the grooves 14 (slots 12) are located along the test sections 24 of the biochip 5. In this case, when the device 8 is installed on a turn In the biochip 5, containers 9 are formed, the bottom of each of which is formed by only one of the test sections 24. This allows you to bring into contact with the solution of each reagent used, introduced into the tank 9, either only one test section 24 of the biochip 5, or several fragments of different test sections 24. When installing the device 8, related to the 1st or 2nd type, on the surface of the biochip, shown in Fig.9, at the bottom of each of the tanks 9 is a group of several test sections 24.

The fixture 8 of the 3rd type (Fig. 7) is a plate in which the holes are made 15. The holes 15 are arranged so that when the fixture 8 of this type is installed on the surface of the biochip, shown in Fig. 9, containers are formed at the bottom each of which is located on one test site, and when installing the device 8 on the surface of the biochip, shown in Fig. 8, several separate containers are formed for each of the test sites. It should be noted that the diameter of the holes 15 should be large enough (1-3 mm optimally) so that there would be no difficulties when filling the tanks with liquid 9. Therefore, the device of the 3rd type can be used to work with biochips 5, (shown on 9), the test sections 24 of which are located at a sufficiently large distance from each other and have dimensions close to the diameter of the holes 15. The use of biochips with such characteristics is advisable for solving a fairly limited number of tasks.

The walls of the slots 12 (Fig. 3), the grooves 14 (Fig. 6), the holes 15 (Fig. 7) of the fixtures 8 can have a coating (not shown in the drawing), which provides an increase or decrease in their hydrophilicity (hydrophobicity). For the same purpose, instead of coating, chemical or physico-chemical modification of the surface of these areas can be used.

The device 8 (Figs. 3, 6) is pressed to the surface of the biochip 5 using a plate 16, which is movably mounted in the grooves 17 made in the frame 6. The pressing plate 16 has an opening 18 (Fig. 5), which is located above the tank 4 when it is installed .

With the removed device 8, the container 4 can be hermetically closed by a lid 19 (Fig. 5), which is fixed on the housing 1 by means of a pressing plate 16. In this form, the device can be used as a container for storing a biochip. In addition, the cover 19 can be installed during the analysis at those stages when the device 8 is not used. In the latter case, the presence of the lid 19 prevents splashing and reduces the evaporation of liquid from the tank 4.

When the fixture 8 of the 1st or 3rd type is installed during the analysis, a removable cover 20 (Fig. 3) can be used to reduce the evaporation of liquid from the containers 9. This is especially important since small volumes of solutions are used, and the evaporation of the liquid can lead to quick drying of the biochip surface and distortion of the analysis results.

The biochip 5 (Fig. 8, 9) is a solid flat substrate 21 on which there is a working area 22 and edges 23. In the working area 22 on the surface of the biochip are test sections 24, in each of which molecules of substances capable of specifically binding to strictly defined molecules present in the test sample. For example, in test sites 24, antibody molecules specific for cell surface antigens can be immobilized. Moreover, the test sites differ from each other by the type of molecules immobilized in them, for example, they contain immobilized antibodies having different specificities. Test sections 24 are separated from each other by background sections 25 that do not contain molecules of these substances. The substrate 21 may be made of a transparent material. In this case, during the analysis, it is possible to conduct a microscopic examination of the biochip in transmitted light.

Test sections can be made in the form of parallel stripes (Fig. 8) or in the form of areas ("spots") round (Fig. 9) or another shape.

The device is used as follows.

A removable bottom 3 is attached to the housing 1 and this connection is fixed using a removable frame 6. A biochip 5 is fixed in the tank 4. When using a biochip 5 designed to detect cell surface antigens and containing immobilized antibodies specific for their surface antigens, during analysis perform the following manipulations. If necessary, block the sites of nonspecific binding of the substrate 21, for example, by incubating the biochip 5 with a solution of bovine serum albumin or another protein. Then, the biochip is washed with a detergent solution, after which the biochip 5 is incubated with a suspension of the studied cells. The corresponding liquids are introduced into the container 4 by means of an automatic pipette or other similar device. During prolonged incubation of the biochip, for example, with a blocking solution or suspension of cells, to prevent spatter and reduce evaporation of the liquid, the container 4 can be closed by a removable cover 19, which is fixed by a pressing strip 16 inserted into the grooves 17 of the removable frame 6. When changing liquids, the cover 19 take off.

During the incubation of the biochip 5 with a cell suspension, the cells settle to its surface. In the presence of detectable surface antigens, cells bind in the region of those test sites 24 of biochip 5, where specific antibodies to them are immobilized. Unbound cells are eliminated by rinsing the biochip 5 with a wash solution, which is also poured into a container 4. The quality of washing the biochip is evaluated, for example, by microscopic examination. In this case, the device is placed on a microscope stage. The quality criterion for washing the biochip 5 is the absence of cells in the region of the background areas 25. If necessary, the biochip is incubated with a solution that increases the binding strength of the remaining cells to the substrate. The intermediate result is read out, for example, by microphotographing the test sections 24 using a camera mounted on an inverted microscope. Liquid is drained from tank 4 and its excess is carefully removed. After that, a fixture 8 is installed in the tank 4, which is pressed against the surface of the biochip 5 using the clamping strip 16. Sealing of the connection of the fixture 8 with the surface of the biochip 5 is provided by the coating 11. When the fixture 8 is installed, several small containers 9 are formed, the bottom of which is formed by the surface areas of the biochip 5. Depending on the design of the biochip 5 (Fig. 8 or Fig. 9), as well as depending on the type of device 8 and the position in which it is installed, at the bottom of each of the containers 9 may be located either one test section 24, or several test sections 24 or fragments thereof. Moreover, in test sites 24 with immobilized antibodies are bound cells. The containers are filled with 9 solutions of reagents used for additional studies of bound cells, for example, solutions of fluorescently-labeled antibodies when determining antigen coexpression on cells. This manipulation is carried out using a Hamilton syringe, an automatic micropipette, or other similar device. When using device 8 of the 3rd type, these solutions are introduced directly into containers 9, and when using device 8 of the 1st or 2nd type - into openings 13. When using device 8 of the 2nd type, the greatest savings are made in the reagent solutions introduced into capacity 9. Incubate the biochip with these solutions. At the same time, to reduce the evaporation of liquid from the containers 9 when using the device 8 of the 1st or 2nd type, a removable cover 20 is installed on the device. After incubation, a liquid can be introduced into the container 9, which inactivates the reagent contained in them. Then, the biochip is washed. When this device 8 is removed. The result of an additional study of bound cells is read, for example, in the case under consideration, microphotography of test sections 24 using a camera mounted on a luminescent microscope. Disassemble the device, separate the biochip from the removable bottom 3. After washing and treating with a disinfectant solution, the device can be reused.

With the help of this device, many other additional studies of biochip-bound cells can be performed using nutrient media, dye solutions, antibody solutions conjugated to enzymes, as well as solutions of other substances that are introduced into tanks 9 during the analysis. the sequence of performed manipulations will be different.

In addition, the device can also be used to work with other types of biochips intended for research of other objects. The nature and sequence of the manipulations performed will also differ.

Claims (11)

1. A device for analysis using a biochip, containing a tank, on the bottom of which is placed a biochip, characterized in that it is equipped with a device that is hermetically mounted on the surface of the biochip and dividing this tank into several containers of smaller volume, the bottom of each of which is formed by the surface area of the biochip. 2. The device according to claim 1, characterized in that the device dividing the container for placing the biochip into several containers of a smaller volume is made in the form of a plate with through holes. 3. The device according to claim 2, characterized in that the through holes have an elongated shape. 4. The device according to claim 1, characterized in that the device dividing the container for placing the biochip into several containers of a smaller volume is made in the form of a plate with grooves. 5. The device according to claim 1, characterized in that the device dividing the container for placing the biochip into several containers of a smaller volume is equipped with additional holes for introducing liquid into these containers. 6. The device according to claim 1, characterized in that it is equipped with a removable cover. 7. The device according to claim 1, characterized in that the bottom of the tank is removable. 8. The device according to claim 1, characterized in that the bottom of the tank is provided with an adhesive coating for attaching the biochip. 9. The device according to claim 1, characterized in that it is equipped with a device pressing to the surface of the biochip device, dividing the tank into several containers of smaller volume. 10. The device according to claims 1 and 7, characterized in that it is equipped with a device fixing the removable bottom of the tank. 11. The device according to claim 1, characterized in that the shape and dimensions of the horizontal section of the tank, on the bottom of which the biochip is placed, correspond to the shape and size of the biochip.