RU206470U1 - A DEVICE WITH THE POSSIBILITY OF VIDEO-FLUORESCENT AND SPECTROSCOPIC ANALYSIS FOR CONTROL AND ASSESSMENT OF THE DISTRIBUTION OF PHOTOSENSITIZERS IN BIOTISSES - Google Patents

Abstract

The utility model relates to the field of devices and equipment for therapy and diagnostics using a laser beam and is intended for research of photosensitizers in vitro, in situ and in vivo with the possibility of video fluorescence and spectroscopic analysis of the distribution of photosensitizers in the biological tissues of small laboratory animals, as well as for the implementation of controlled photodynamic impact and assessment of its effectiveness. A device with the possibility of video fluorescence and spectroscopic analysis for monitoring and assessing the distribution of photosensitizers in biological tissues, including a laser radiation generation unit with an optical filter, a module for optical switching of radiation input channels, a fiber-optic module for delivery and reception of radiation, a fiber-optic radiation delivery module with a variable aperture outgoing radiation, positioning unit, unit for recording video fluorescent images with an optical filter, unit for analyzing spectral data, unit for controlling and processing the received data. The device is made in a single housing with a completely darkened internal camera designed to accommodate the objects under study, and the video fluorescent image recording unit consists of a digital camera, an electromechanical varifocal lens and a light filter with a bandwidth in the range of recording a fluorescent signal, together with a fiber-optic radiation delivery module with a variable aperture of outgoing radiation, consisting of an optical fiber with an electromechanical varifocal lens located at the distal end, are fixed to the electromechanical slides of the positioning unit above the object under study, while the varifocal lenses of the video fluorescent image recording unit and the fiber-optic module are electrically connected to the control board connected to control and data processing unit, and the unit for generating laser radiation with a wavelength in the emission band of the photosensitizer in the red spectral range contains there is a light filter with a bandwidth in the range from 632 to 640 nm, while the blocks are controlled and controlled by specialized software, through which information about the operation of the device is displayed using LED indicators. The device improves the accuracy of determining the position of the foci of fluorescence and their geometric dimensions.

Description

The utility model relates to the field of devices and equipment for therapy and diagnostics using laser radiation and is intended for research of photosensitizers in vitro, in situ and in vivo with the possibility of video fluorescence and spectroscopic analysis of the distribution of photosensitizers in the biological tissues of small laboratory animals, as well as for the implementation of controlled photodynamic impact and assessment of its effectiveness.

AREA OF TECHNOLOGY:

The proposed utility model relates to laboratory equipment for research of photosensitizers in vitro, in situ and in vivo with the possibility of video fluorescence and spectroscopic analysis of the distribution of photosensitizers in cell cultures and biological tissues, as well as for the implementation of a controlled photodynamic effect and assessment of its effectiveness.

LEVEL OF TECHNOLOGY

A device (US 20170007192 A1) for visualizing an image of an animal, sample or phantom is known from the prior art. The device allows you to display the animal from different sides, the viewing angle is at least 360 degrees. An animal, phantom or study specimen is supported by an object holder. The object holder is an elongated tube and serves to securely fix an animal, specimen or phantom. The object holder is connected to the control motor drive. The control motor drive rotates the object holder. An image of an animal, sample, or test object is captured at each increment. X-rays are used for imaging. This device does not allow obtaining fluorescent images of an animal in the visible range, and therefore conducting fluorescence diagnostics.

An improved imaging device (US 6901279 B2) is also known, which allows a user to perform multiple imaging operations. The imaging apparatus includes several design improvements to the unit for controlling lighting within the imaging unit: improved seals and a door closing mechanism. The present invention also includes several design improvements to the imaging apparatus to facilitate image capturing, such as: auto filter selector, movable platform, auto focus control, iris and platform height control, and improved interior lighting for capturing images of an object. Several white LEDs are used as a radiation source.

Systems and methods for obtaining images of a sample are known (US 7,595,838 B2). The sample is placed in an imaging box containing a movable stage that allows the sample to be imaged from various positions and angles within the imaging box. Images are recorded by a CCD camera and processed by a computer. The acquired images from the imaging unit can be used to monitor the state of the object. This device does not allow adjusting the radiation intensity of the source and, therefore, does not allow switching between diagnostic and therapeutic modes of exposure.

A system for imaging small laboratory animals is also known (WO 2008/142593 A2). The system includes a docking station and at least one method for imaging small animals using it. The docking station provides a workspace and docking ports for preparing and anesthetized animals awaiting imaging. To duplicate the position of the research object, a holder is provided that holds the object in a reproducible position on the object tray. Monitoring of the main vital signs of the objects of research is carried out. The object tray includes fiducials to help align images of the same modality and images of different modalities. The disadvantages of the system include the fact that it is not protected from external light exposure, which can negatively affect the quality of the resulting images.

The closest analogue of the proposed device (prototype) is a device for obtaining fluorescent tomographic images (RF patent 2368306). The device contains a laser radiation source, modulated in amplitude and equipped with at least one fiber-optic output, a radiation receiver equipped with at least one fiber-optic input, installed with the ability to scan radiation over the area of interest of the object under study, and a unit signal processing and visualization. The fiber-optic inputs and outputs are equipped with systems of electromechanical movements of the input and output, connected to the motion control unit, made with the possibility of moving the fiber-optic input and output independently of each other, with a given step and spatial shift. The signal processing and visualization unit provides the construction of a three-dimensional image of the area of interest of the object under study with a flat scanning model. EFFECT: use of the invention makes it possible to increase the spatial resolution of the tomography device and to simplify its design. However, this device does not have diode lasers with a high radiation power sufficient for photodynamic therapy. This does not allow using this device for effective controlled photodynamic therapy and evaluating the effectiveness of pharmaceuticals for photodynamic therapy.

USEFUL MODEL DISCLOSURE

The task to be solved by this utility model is to ensure the implementation of a precision controlled photodynamic effect and assess its effectiveness using video fluorescence diagnostics and local spectroscopic analysis of the distribution of photosensitizers in biological tissues in vitro, in situ and in vivo.

The problem is solved by the fact that the proposed device with the possibility of video fluorescence and spectroscopic analysis for monitoring and assessing the distribution of photosensitizers in biological tissues, including a unit for generating laser radiation with an optical filter, a module for optical switching of radiation input channels, a fiber-optic module for delivering and receiving radiation, fiber an optical radiation delivery module with a variable aperture of outgoing radiation, a positioning unit, a video fluorescent image recording unit with an optical filter, a spectral data analysis unit, a control and processing unit for the received data, characterized in that the device is made in a single housing with a completely darkened internal camera designed for placement of the objects under study, and the unit for recording video fluorescent images, consisting of a digital camera, an electromechanical varifocal lens and a light filter with a passband in the fluorescent recording range rescent signal, together with a fiber-optic radiation delivery module with a variable aperture of outgoing radiation, consisting of an optical fiber with an electromechanical varifocal lens located at the distal end, are fixed on the electromechanical movements of the positioning unit above the object under study, while the varifocal lenses of the video fluorescence image recording unit and fiber -optical modules are electrically connected to the control board connected to the control and data processing unit, and the unit for generating laser radiation with a wavelength in the emission band of the photosensitizer in the red spectral range contains a light filter with a passband in the range from 632 to 640 nm, while the units controlled and controlled by specialized software, through which information about the operation of the device is displayed using LED indicators.

Also, this problem is solved by the fact that the unit for analyzing the spectral composition of radiation with a fiber-optic system for delivering and receiving radiation is included in the module for determining the rate of decrease in fluorescence intensity as a feedback link for automatically adjusting the power of laser radiation during photodynamic exposure.

The problem is also solved by the fact that the unit for recording video fluorescent images is included in the module for determining the rate of decrease in fluorescence intensity as a feedback link for automatically adjusting the power of laser radiation during photodynamic exposure.

The technical result of the claimed utility model is to improve the accuracy of determining the position of the foci of fluorescence and their geometric dimensions. The device also allows the rate of change of fluorescence intensity in the far red visible range to be used as feedback for adjusting the power of the laser source.

The claimed device solves the following technical problems:

- determination of the localization of the photosensitizer in biological tissues in situ, in vivo in the near red range of the spectrum

- registration of the dynamics of photobleaching in areas of interest

- comparison of the measured spectral data with the measurement sites on experimental samples, animals.

BRIEF DESCRIPTION OF DRAWINGS

The essence of the utility model is illustrated by drawings, which are included in the present description. The drawings illustrate an embodiment of the utility model and together with the above general description of the utility model and the following detailed description of the implementation serve to explain the principles of operation of the present utility model.

FIG. 1 shows a block diagram of the device and the following designations are adopted:

1 - housing with complete darkening of the inner chamber, 2 - housing door with a handle, 3 - emergency shutdown button, 4 - radiation source control key, 5 - radiation source operation switching key, 6 - unit activation button, 7 - USB interfaces, 8 - connector with HDMI interface, 9 - Ethernet connector, 10 - indicators, 11 - control and data processing unit, 12 - laser radiation generation unit, 13 - optical filter, 14 - module for optical switching of radiation input channels, 15 - fiber-optic module for delivery and reception of radiation, 16 - fiber-optic module for delivery of radiation with a variable aperture of outgoing radiation, 17 - unit for recording video fluorescent images, 18 - varifocal lens, 19 - optical filter, 20 - lens control board, 21 - positioning unit, 22 - block for analyzing the spectral composition of radiation, 23 - optical filter.

FIG. 2 shows a general view of the product and the following designations are adopted:

1 - housing with full darkening of the inner chamber, 2 - housing door with a handle, 3 - emergency shutdown button, 4 - radiation source control key 6 - unit start button, 7 - connectors with USB interfaces, 8 - connector with HDMI interface, 9 - Ethernet connector, 10 - indicators

FIG. 3 is a left side view

FIG. 4 shows a view from the right and the following designations are adopted:

1 - housing with full darkening of the inner chamber, 2 - housing door with a handle, 3 - emergency shutdown button, 4 - radiation source control key 6 - unit start button, 7 - connectors with USB interfaces, 8 - connector with HDMI interface, 9 - Ethernet connector.

FIG. 5 shows a diagram of a specialized software device and the following designations are adopted: 25 - control module of the radiation generation unit, 26 - control module of the spectral data analysis unit, 27 - lens control module, 28 - control module of the video-fluorescent image recording unit, 29 - control module of the positioning unit ...

FIG. 6 shows the algorithms for the operation of the device and the following designations are adopted: 6A - obtaining video fluorescent images, 6B obtaining spectral data, 6B - carrying out the process of photodynamic exposure.

DEFINITIONS AND TERMS (optional)

The term "tissue site under study" in this document means a body area within which surgery is performed, as well as any other object, for example, an experimental sample with an unknown concentration of a photosensitizer, subject to fluorescence study in order to assess the accumulation of a photosensitizer or other phosphor.

IMPLEMENTATION OF THE USEFUL MODEL

The device works as follows:

Inside the case (1) with a door (2) there is a completely darkened chamber for placing experimental objects (24), with the help of a specialized software module (25) of the control and data processing unit (11), a laser radiation generation unit (12) is switched on, in which on the front panel of the case, its controls are displayed: an emergency shutdown button (3), a key for controlling the radiation source (4), a key for switching the operation of the radiation source (5). Laser radiation passing through a light filter (13) is delivered to the module for optical switching of radiation input channels (14) with a button (5) which has one connector for input and two for outputting radiation. A fiber-optic module for delivery and reception of radiation (15) and a fiber-optic module for delivery of radiation with a variable aperture of outgoing radiation (16) are connected to two connectors at the output. Further operation of the device depends on the position of the radiation switch. When inserted into a fiber-optic module for delivery and reception of radiation (15), which has a Y-shape and is equipped with two optical connectors on the side of two branches for connection to an optical switch (14) and a unit for analyzing the spectral composition of radiation (22), and with the other side is equipped with a tip for contacting with experimental objects, the radiation is delivered to the investigated objects. The scattered laser radiation and the excited fluorescence of the photosensitizer are collected by the receiving fibers of the module (15) and delivered through them to the spectral data analysis unit (22), having previously passed through a light filter (23) to attenuate the laser radiation. The radiation is decomposed into a spectrum for further analysis. The obtained data is transmitted to the control and information processing unit (11), using the module (26) of specialized software, the spectra are analyzed: the intensity of the laser line, the intensity of fluorescence, the difference in the intensities of laser and fluorescent radiation, with subsequent display on the screen of the data monitor in the form of graphs and histograms, which makes it possible to determine the rate of decrease in the fluorescence intensity and allows the module to be used as a feedback link for automatic adjustment of the laser radiation power during photodynamic exposure. When radiation is injected from an optical switch into a fiber-optic radiation delivery module with a variable aperture (16), the radiation is delivered to the objects under study. An electromechanical varifocal lens (18) is placed at the distal end of the module (16), which is connected by electrical contacts to the control board (20), and it is connected to the control and information processing unit (11). The objective (18) is controlled by the module (27) of specialized software, which sends a series of electrical pulses to the motors to change the aperture in order to form a laser spot with a given diameter in the area where the experimental objects are located. The generated radiation is intended to excite fluorescence, and at high values of the power density, a photodynamic effect on experimental objects is achieved. The fluorescent signal passes through a light filter (19) and is collected by a video fluorescent image recording unit (17) with a varifocal lens (18), which is connected by electrical contacts to the control board (20). The information received from the unit for recording video fluorescent images enters the control and data processing unit (11), using the module (28) of specialized software, images are analyzed: brightness at a point, average brightness in a rectangle, horizontal brightness profile, vertical brightness profile, brightness profile an arbitrary segment, the average brightness in an arbitrary polygon, followed by displaying data on the monitor screen in the form of graphs and 2D images with the distribution of the fluorescent signal in experimental objects, which makes it possible to determine the rate of decrease in the fluorescence intensity and use the module as a feedback link for automatic adjustment of the laser power radiation under photodynamic exposure.

The lenses (18) of the blocks (16, 17) are fixed on the electromechanical slides of the positioning unit (21), which is controlled by the specialized software module (29) of the control and data processing unit (11), over the experimental object and operate in a synchronous mode, which makes it possible to irradiate the area falling into the field of view of the unit for recording video fluorescent images (17). The positioning unit (21) allows you to move the image registration unit (17) for a detailed analysis of individual sections of experimental objects.

On the case (1) are brought out to the right side panel from the control and data processing unit (11) interface connectors: USB (7), HDMI (8), Ethernet (9), for connecting input and output devices, such as a keyboard, computer mouse and monitor, as well as for connecting the device to the Internet. The front panel displays indicators (10), reporting on the state of operation of the device blocks, a button to turn on the device (6).

Design features of the utility model:

- the built-in unit for controlling the device and analyzing the diagnosed data inside the case allows achieving portability of the device, reducing the number of interface cables connecting functional modules and the number of external units of the product;

- the completeness of the installation allows the use of one source of laser excitation radiation for video fluorescence, fiber spectral diagnostics, as well as for photodynamic impact on the objects under study, including those with hard-to-reach localization, using additional fiber-optic radiation delivery devices.

Thus, the totality of all essential features makes the proposed device a multifunctional instrument, the presence in which of a high-intensity laser source of radiation in the far red range of the spectrum, allows for video fluorescence diagnostics, tissue analysis with spectral resolution, using fiber instruments, including the sounding depth, as well as carries out a photodynamic effect on the objects of research, which facilitates the use of the device in preclinical studies of biomarkers in situ and in vivo.

The proposed utility model can be serially manufactured from materials approved for medical use, some parts of which can be manufactured using the technology of printing on a 3D printer from polymer materials.

Claims (3)

1. A device with the possibility of video fluorescence and spectroscopic analysis for monitoring and assessing the distribution of photosensitizers in biological tissues, including a unit for generating laser radiation with an optical filter, a module for optical switching of radiation input channels, a fiber-optic module for delivering and receiving radiation, a fiber-optic module for delivering radiation with variable aperture of outgoing radiation, a positioning unit, a unit for recording video fluorescent images with an optical filter, a unit for analyzing spectral data, a unit for controlling and processing the received data, characterized in that the device is made in a single housing with a completely darkened internal camera designed to accommodate the objects under study, and the unit for recording video fluorescent images consists of a digital camera, an electromechanical varifocal lens and a light filter with a bandwidth in the range of recording a fluorescent signal, together with a fiber-optic them with a radiation delivery module with a variable aperture of outgoing radiation, consisting of an optical fiber with an electromechanical varifocal lens located at the distal end, are fixed on the electromechanical movements of the positioning unit above the object under study, while the varifocal lenses of the video fluorescent image recording unit and the fiber-optic module are electrically connected to a control board connected to the control and data processing unit, and the unit for generating laser radiation with a wavelength in the emission band of the photosensitizer in the red spectrum range contains a light filter with a passband in the range from 632 to 640 nm, while the blocks are controlled and controlled by specialized software, through which information about the operation of the device is displayed using LED indicators. 2. The device according to claim 1, characterized in that the system for analyzing the spectral composition of radiation with a fiber-optic system for delivering and receiving radiation is included in the unit for determining the rate of decrease in fluorescence intensity as a feedback link for automatically adjusting the power of laser radiation during photodynamic exposure. 3. The device according to claim. 1, characterized in that the system for recording video fluorescent images is included in the unit for determining the rate of decrease in fluorescence intensity as a feedback link for automatically adjusting the power of laser radiation during photodynamic exposure.

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