RU115494U1 - DEVICE FOR MOVING A BIOCHIP WITH RESPECT TO THE LENS OF A MICROSCOPE SUPPORTED BY A CAMERA - Google Patents

Abstract

1. A device for moving a biochip relative to a microscope objective equipped with a camera, containing a platform with mechanisms for longitudinal and transverse movement of the biochip, a biochip attachment unit, an electric motor and a block that controls its operation, characterized in that it is equipped with a control unit for the operation of the camera, coupled with a block that controls the operation of the electric motor, and is also equipped with an additional mechanism for manual adjustment of the biochip position. ! 2. A device according to claim 1, characterized in that it is equipped with one or more removable adapters for placing the biochip or a device in which the biochip is located. ! 3. The device according to claim 1, characterized in that it is equipped with a thermoregulation system. ! 4. The device according to claim 1, characterized in that a computer acts as a control unit for the operation of the electric motor and a control unit for the operation of the camera.

Description

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

A device is known for moving a micropreparation in two mutually perpendicular directions in the plane of the microscope stage, taken as an analog. This device is the CT-12 preparation agent (see, for example, http://www.laboratorium.dp.ua/item/17), which is a removable accessory to microscopes of various models. The main parts of the CT-12 preparation agent are: base (body), longitudinal movement mechanism, lateral movement mechanism, drug attachment unit (clamping legs), device attachment unit to the microscope stage.

The CT-12 preparation can be used to move a micropreparation made on a glass slide (or another flat plate having similar dimensions) or a glass slide (plate) on which a flat object studied with a microscope is placed. Such an object may be, for example, a biochip designed to detect surface cell antigens. (For example, the biochip described in the article: A.V. Shishkin, I.I. Shmyrev, S.A. Kuznetsova, N.G. Ovchinina, A.A. Butylin, F.I. Ataullakhanov, A.I. Vorobev “Immunological biochips for the parallel determination of surface antigens and morphological studies of cells”, Journal of Biological Membranes 2008, Volume 25, No. 4, pp. 277-284). When carrying out a manual reading of the analysis result, with the help of this preparation, the biochip (placed on a slide or originally made on it) is moved across the microscope stage so that the necessary test areas (biochip spots) containing bound cells appear in the field of view of its lens. A microscopic examination and / or photographing of test areas (spots) of the biochip (for example, using a camera mounted on a microscope) is carried out, which is usually carried out alternately in a certain sequence.

The disadvantages of the device, taken as an analog, are:

manual movement of the biochip, requiring visual control (using a microscope), as well as the disconnected processes of moving the biochip and photographing its test areas (reading the analysis result). This leads to a large investment of time for this stage of the study. In addition, with the help of this device it is impossible to work with biochips, which in shape and (or) size differ significantly from the slide without placing them on the latter. For the same reason, using this device it is impossible or difficult to work with biochips located in incubation-washing cuvettes (for example, patent RU 91339), flow chambers (for example, patents RU 86750, RU 88674, RU 92196) or other similar devices (for example , patent RU 87424).

A device for moving a micropreparation relative to a microscope objective is known, which is taken as a prototype and is a motorized (scanning) stage (see, for example, the site http://www.microscope.kz/library/articles/10/1/29), for example, Prior H107 (see, for example, the website http://www.labspb.com/prior_H107.html). The main parts of a motorized (scanning) stage are: a platform equipped with a longitudinal movement mechanism, a transverse movement mechanism, a micropreparation attachment unit, an electric motor (usually one or two stepper motors) and a unit that controls its operation. The device allows you to move the micropreparation relative to the microscope objective in one plane in two mutually perpendicular directions. A biochip placed, for example, on a glass slide can act as a micropreparation. The microscope on which the scanning stage is mounted can optionally be equipped with a photo or video camera.

The disadvantage of the device taken as a prototype is the fragmentation of the processes of moving the biochip relative to the microscope objective and photographing its test areas. This leads to a significant investment of time for this stage of the study, since it does not allow it to be carried out completely in an automated mode. In addition, using this device it is difficult to work with biochips located in incubation-washing cuvettes (for example, patent for utility model RU 91339), flow chambers (for example, patents for utility model RU 86750, RU 88674, RU 92196) or other similar fixtures.

The objective of the claimed utility model is to accelerate the process of reading the result of the analysis carried out using a biochip, as well as increasing the versatility of the device.

The problem is solved due to the fact that, according to a utility model, a device for moving a biochip relative to a microscope objective equipped with a camera, containing a platform with mechanisms for longitudinal and transverse movement of the biochip, a biochip attachment unit, an electric motor and a unit controlling its operation, is equipped with a camera operation control unit, coupled with the unit that controls the operation of the electric motor, and is also equipped with an additional mechanism for manual adjustment of the position of the biochip.

The device is equipped with one or more removable adapters to accommodate the biochip or device in which the biochip is located.

The device is equipped with a thermoregulation system.

A computer acts as a control unit for the operation of the electric motor and a control unit for the operation of the camera.

Using the claimed utility model, it is possible to automatically move the biochip relative to the microscope objective for subsequent photographing of its test areas using a digital camera mounted on the microscope (or other device that allows microphotography), that is, reading the analysis result. At the same time, due to the presence of one or several removable adapters, it is possible to work with biochips of various shapes or sizes, or with various devices (for example, incubation-washing cuvettes, flow chambers, platforms, slide glasses) in which biochips are fixed. Thanks to this, the device is highly versatile. The device can be mounted on most models of light microscopes. The presence of an additional device for manual adjustment of the position of the biochip facilitates the setup of the device. Pairing the unit that controls the operation of electric motors with the unit that controls the operation of the camera mounted on a microscope allows photographing as soon as the biochip is moved a predetermined distance relative to the lens and the required area is in its field of view. After this, the biochip immediately moves to the next required position. Performing a series of images of various sections of the biochip in a fully automatic mode leads to a significant reduction in labor intensity and dramatically increases the reading speed of the analysis result. The presence of a temperature control system (thermostating) allows you to conduct research at the required temperature conditions, which is required to solve some research problems.

The utility model is illustrated in the drawing, where

figure 1 presents a General view of the device (top);

figure 2 presents a section aa in figure 1;

figure 3 presents a removable adapter in which is mounted a flow chamber with a biochip;

figure 4 presents a General view of the biochip.

The utility model contains a base (platform) 1 (Fig. 1) on which a movable section 2 is located, to which a movable section 3 is connected. The movement of section 2 relative to the base 1 provides a lateral movement mechanism, which includes a rack and pinion gear consisting of gears 4 and racks 5. The rails 5 are fixedly mounted on the base 1. One gear 4 is fixed on the shaft 6, and the second gear 4 is fixed on the shaft 7. The shafts 6 and 7 are placed in the holes 8 of the movable section 2. The shafts 6 and 7 are tubes, inside of which passes shaft 9 mechanisms of longitudinal movement. When the gears 4 rotate, the section 2 moves relative to the base 1 along the transverse axis. The ability to move the movable section 2 relative to the base 1 only along the transverse axis is provided by the strips 10 (fixedly attached to the section 2), which are placed in the grooves 11 made in the base 1. This forms a dovetail connection.

The movement of section 3 relative to section 2 provides a mechanism of longitudinal movement, which includes a gear plate 12 and a shaft 9, which is a cylinder with a thread. The gear plate 12 (figure 2) is attached to the movable section 3. When the shaft 9 rotates, section 3 moves relative to section 2 along the longitudinal axis. In this case, the toothed plate 12 moves along the groove 13 of the section 2. With the movable section 3 there is a bracket 14 having protrusions 15. In the protrusions 15 there are threaded holes in which the clamping screws 16 are located. The bracket 14 with the protrusions 15 and the screws 16 form a fastening assembly adapter 17. The mount of the adapter 17 is removable. This allows you to replace it with another mount, in cases where it is necessary to place in the device an adapter 17 having a different shape or size. This increases the versatility of the device. In the adapter 17 (Fig. 3), a biochip 18 (Fig. 4) or a device 19 (Fig. 3) is attached (for example, a flow chamber (for example, patents for utility model RU 86750, 88674, 92196), a section of the incubation-washing container ( for example, a utility model patent RU 87424), a platform for placing a biochip (for example, a utility model patent RU 90213), a cuvette (for example, a utility model patent RU 91339), a glass slide or other device) in which the biochip 18 is placed. Depending on this, different adapters 17 are used, designed to accommodate one or more of separately taken biochips 18 or fastenings of the above or similar devices. Figure 3 presents the adapter 17, intended for mounting the device 19, which in this case is a flow chamber (patent for utility model RU 88674) in which the biochip is located 18. The adapter 17 is equipped with removable clamping bars 20, which fix the device 19 vertically.

The device is attached to the microscope stage (not shown in the drawing) using screws passing through the holes 21 (Fig. 1) made in the base 1. In the base 1 and the movable section 2, the holes 22, 23 are made, which are necessary for the passage of light from the illuminator a microscope (not shown) to illuminate the biochip 18. A gear 24 is attached to the shaft 6 of the lateral movement mechanism. The action of the lateral movement mechanism is provided by an electric motor 25, on the shaft 26 of which the gear 27 is fixed, coupled to the gear 28, fixed on the shaft 29. On the shaft 29 is also fixed gear 30, coupled with the gear 24, mounted on the shaft 6.

A gear 31 is fixed on the shaft 9 of the longitudinal movement mechanism. The rotation of the gear 31 (together with the shaft 9) provides an electric motor 32, on the shaft 33 of which a gear 34 is fixed, coupled to the gear 31. The electric motors 25 and 32 are connected to the tachometers 35. A mechanism containing parts 24 -35, placed in the housing 36, which is attached to section 2.

It is also possible to design a device containing one electric motor and a transmission mechanism that is switched to transmit torque either to the longitudinal movement mechanism or to the transverse movement mechanism.

The device is also equipped with piezoelectric sensors (not shown), which wires (not shown) are connected to a unit 37 that controls the operation of electric motors 25 and 32.

The movement of sections 2 and 3 along the respective axes at predetermined distances is due to the operation of electric motors 25 and 32. The number of revolutions and the sequence of switching on the operation of electric motors 25 and 32 are set by the control unit 37. The control unit 37 of the operation of the electric motors is coupled to the camera control unit 38 (or another a similar device that allows microphotography of areas of the surface of the biochip 18). The control unit 38 is connected to the camera (not shown) by a cable 39. When the biochip 18 moves to a predetermined position, a signal is sent to the camera to take photographs.

The electric motor operation control unit 37 is capable of urgently blocking their operation if the rotation of the shafts encounters significant resistance (for example, when sections 2 and 3 reach extreme positions or if there is an obstacle to their movement).

In addition to the automated movement of the biochip 18 to predetermined positions, the possibility of manual movement is provided, which may be necessary to adjust the initial position of the biochip 18 before reading the result. For this purpose, it is possible to rotate the shafts 7 and 9 manually using the handles 40 and 41. The handle 40 is mounted on the shaft 7, and the handle 41 on the shaft 9. The device is equipped with coordinate scales with noniuses (not shown in the drawing) that facilitate manual adjustment.

The rotation of the handles 40 and 41 is permissible only when the electric motors 25 and 32 are turned off. To prevent accidental rotation of the handles 40 and 41 during operation of the electric motors 25 and 32, a protective cap 42 is used, which is attached to section 2. The ability to turn on the electric motors 25 and 32 only with the screwed cap 42 provides a contact sensor 43, which is connected by wires 44 to the control unit 37. A device for moving a biochip can be installed on a microscope stage (not shown in the drawing) only if it is not and EET of fixed protruding parts. In other cases, it is possible to install the device instead of the stage. For this, the device is equipped with a removable strap 45 (figure 2), which is attached to the base 1 with bolts 46. The strap 45 has a connector 47 for connecting to a typical mounting unit, originally intended for mounting the stage to the microscope body. Since these attachment nodes are different for different models of microscopes, the device can be equipped with different versions of the mounting strips 45. In cases where the microscope is rigidly mounted on the desktop, the device can be mounted not on the microscope body, but mounted on the desktop. To do this, it is equipped with a removable stand (not shown in the drawing), which is mounted instead of the strap 45.

The electric motors 25 and 32 are connected to the block 37 (controlling their operation) by wires 48. The tachometers 35 are connected to the block 37 by wires, which are not shown in the drawing.

The device is equipped with a temperature control (temperature control) system containing devices 49 (Fig. 3) that change the temperature, a temperature sensor 50, and a temperature control unit 51 (Fig. 1). Devices 49 (figure 3) are installed on removable adapters 17, but can be placed in other parts of the device. In this case, devices 49 are Peltier elements capable of providing both heating and cooling, but other devices capable of changing the temperature can also be used. The temperature sensor 50 mounted on the device 19, which houses the biochip 18, but it can be placed in other places, for example on the adapter 17 of the device. The temperature changing devices 49 and the temperature sensor 50 are connected to the thermoregulation control unit 51 by wires, which are not shown in the drawing.

Adapters 17 (or other parts of the device) in which temperature-changing devices 49 are installed are made of metal or other materials having high thermal conductivity.

Blocks 37, 38, 51 together form a control system for the operation of the device. It can be interfaced with a computer (not shown in the drawing), with the help of which the operation algorithm is set. At the same time, it is possible to operate the device independently of a computer. In this case, the operation algorithm of the device is set using the control panel (not shown in the drawing).

Perhaps the execution of the device, in which the function of the control system instead of blocks 37, 38, 51 completely performs the computer.

Possible execution of the device, in which the mechanisms of longitudinal and lateral movement are equipped with anti-backlash devices (not shown in the drawing).

Biochip 18 (Fig. 4) is a transparent substrate 52 on which test sections 53 (“spots” of the biochip) containing immobilized antibodies, as well as background sections 54 that do not contain immobilized antibodies, are located in strictly defined places. Antibodies immobilized in test sites 53 are specific for cell surface antigens. The principle of operation of such biochips is based on the specific binding (in the area of test sites) of cells having detectable antigens. At that stage of the analysis performed using biochip 18, where the use of the claimed device may be required, in the area of test sections 53 there are bound cells.

In addition to biochips 18 of the described design, the device can be used to work with other types of biochips.

The claimed device operates as follows.

The device is mounted on a microscope stage. In cases where the microscope’s construction does not allow this, the stage is removed, and a strap 45 is attached to its attachment site. Screws 46 to the strap 45 attach a device for moving the biochip. Screws 16 secure the adapter 17 and place the biochip 18 or the device 19 with the biochip 18 inside it. The safety cap 42 is removed from the correction device and, turning the handles 40 and 41, the biochip 18 is moved to its original position. In most cases, this position will be the position of the biochip 18, when the area from which the reading begins is located in the field of view of the microscope objective. The safety cap 42 is returned to its original position. The microscope is focused. A digital camera mounted on a microscope is connected by a cable 39 to a unit 38 that controls its operation. Turn on the power to the device. If the device is used independently of the computer, the algorithm of its operation is set using the control panel. If the device is used in conjunction with a computer, the operation algorithm is set via the computer.

In the process of operation of the device in automatic mode, it sequentially moves the biochip 18 to predetermined positions. In this case, the necessary sections of its surface fall into the field of view of the microscope objective. When moving the biochip 18 to a predetermined position, the control system sends a signal to the camera for shooting. Then the control system gives a signal to resume operation of the electric motor 25 and (or) 32 to move the biochip 18 to the next position.

Depending on the operating mode of the device, the obtained images are saved in the digital camera memory, or are immediately saved in the computer's memory for further processing. After all the necessary parts of the biochip are photographed, if necessary, the process can be repeated using a lens with a different magnification or using the necessary filter.

Claims (4)

1. A device for moving a biochip relative to a microscope objective equipped with a camera, comprising a platform with mechanisms for longitudinal and transverse movement of the biochip, a biochip mount, an electric motor and a unit that controls its operation, characterized in that it is equipped with a camera operation control unit paired with a unit that controls the operation of the electric motor, and is also equipped with an additional mechanism for manually adjusting the position of the biochip. 2. The device according to claim 1, characterized in that it is equipped with one or more removable adapters for accommodating a biochip or device in which the biochip is located. 3. The device according to claim 1, characterized in that it is equipped with a thermoregulation system. 4. The device according to claim 1, characterized in that the computer acts as the control unit for the operation of the electric motor and the control unit for the operation of the camera.