RU138168U1 - STAND FOR RESEARCH ON LABORATORY ANIMALS - Google Patents

Abstract

1. Stand for research on laboratory animals, containing at least one cage for laboratory animals, a measuring platform with sensors for monitoring the vital signs of the laboratory animal, and a module for collecting, processing and transmitting data, the inputs of which are connected to the outputs of the sensors, characterized in that the measuring platform is located under the cell and contains at least two sensors that are symmetrically located along the bottom of the cell, each sensor contains a microwave oscillator, a power divider, a signal mixer, a sensing element in the form of a coplanar strip signal transmission line forming the sensor working channel, an asymmetric strip signal transmission line forming the sensor reference channel, and a dielectric substrate, while the working and reference channels are connected between the outputs of the power divider, the input of which connected to the output of the microwave oscillator, and the inputs of the signal mixer, an electrically conductive grounded layer and a printed path of the working channel are applied on one surface of the substrate, on the opposite surface of the substrate coated printing path reference channel, wherein the surface of the substrate with an electrically conductive ground plane and the working channel circuit path faces the kletke.2. The stand according to claim 1, characterized in that each sensor includes an attenuator included in the working channel between the output of the power divider and the input of the coplanar strip signal transmission line. The stand according to claim 1, characterized in that the module for collecting, processing and transmitting data contains serially connected signal amplifier,

Description

The utility model relates to medical equipment, and more specifically to technical means intended for conducting biomedical research on laboratory animals, in particular for measuring the heartbeat, respiration and movement of animals.

When conducting biomedical studies in laboratory animals for a number of applied problems that are currently being solved in medicine and pharmacology, a long non-contact monitoring of the heart rate, respiratory rate, blood pressure and motor activity of the studied laboratory animals is required. For these purposes, special stands are used, including cells for placement and spatial restriction of the movement of small laboratory animals, diagnostic equipment and communication equipment between physiological parameters sensors and an external device for collecting, processing, displaying and transmitting received data.

In the first stages of the study of the effects of drugs and their components, small laboratory animals are used to determine the effect on vital signs (respiration, heartbeat, blood pressure) and determine the toxicity of drugs. As a rule, rats are used for pharmacological studies, since the structure of their cardiovascular system is similar to that of the human cardiovascular system. The effect of drugs in the vast majority of cases is evaluated by cardiac activity, respiration, or the behavior of a laboratory animal. So, for example, to monitor the heartbeat, a miniature electrocardiograph is implanted in the body of the animal. In this case, considerable time is required for the surgical intervention and subsequent rehabilitation of the laboratory animal. More convenient, from the point of view of reducing time costs, is the method of contactless monitoring. In this case, the implantation of an electrocardiograph in the animal’s body is not required and the influence of postoperative factors on the research results is not manifested.

Known, for example, a stand designed for conducting contact electrophysiological studies in rats, which is described in patent RU 2245117 (published on 10.06.2004). This stand contains a cage for a rat, an electrode device, an auxiliary element that is fixed on a rat at the exit point of the wires of the electrode device, a reference electrode and a recording device. The auxiliary element is made in the form of a sleeve fixed to the tail of the rat with flanges at the ends. The sleeve is installed with the possibility of free rotation around the axis in the slot made in the cell wall. The electrical wires of the electrode device are passed through a sleeve-leash. Outside the cell, the ends of the electrical wires are fixed on a support located opposite the sleeve-leash. The support and the sleeve-leash are spatially separated. The electric wires of the electrode device and the reference electrode in the area between the sleeve-harness and the support sag. The reference electrode is connected to the sleeve-leash.

The closest analogue of the utility model is a stand for conducting wireless research on laboratory animals, described in patent US 8468975 (published on 06/25/2013). The stand contains a cage for accommodating a laboratory animal, two inductors mounted on the outside of the cage, and a label with an electrical circuit that includes inductively and capacitive elements connected in parallel. The mark is made in the form of an inductor L and capacitance C, which are formed on a printed circuit board. The label is fixed on the body part of the laboratory animal. In particular, the label may be glued to the paw of a laboratory animal. External inductors are connected to an alternating current signal generator and to a measuring circuit.

The stand allows you to determine the position of the laboratory animal or its specific part of the body at the current time, as well as the trajectory of the animal inside the cell. Measurements are taken without using a wired connection between the detector and the measurement system. The principle of operation of the installation is based on the excitation inside the cell of a time-varying magnetic field and the measurement of the impedance of the external electrical circuit due to the movement of the LC circuit in the cell.

Registration of the spatial position of the label and, accordingly, of the part of the laboratory animal under study is determined by the change in the impedance of the circuit due to the occurrence of resonance phenomena when moving the LC circuit between the external inductance coils. The magnitude of the impedance of the external circuit depends on the resonant frequency of the LC circuit and its spatial position relative to the external inductors.

This method and the stand, designed for its implementation, provides constant non-contact control of the movement of the laboratory animal and its body parts. However, using the known device it is impossible to determine such important vital signs of the laboratory animal as the heart rate and respiratory rate. In addition, the motion sensor is mounted directly on the body of the animal, which affects the behavior of the animal.

The utility model is aimed at eliminating from the stand any means of measuring physiological parameters, including implantable implants and fixed tags that are in contact with the body of a laboratory animal. The solution to this problem provides complete non-contact control of the physiological parameters of the vital activity of the laboratory animal during biomedical research in natural behavior, including the simultaneous measurement of the following vital signs: heart rate, respiratory rate and motor activity of the animal under study.

The achievement of the specified technical result is ensured by using a stand designed for biomedical research in laboratory animals. The structure of the stand includes at least one cage for a laboratory animal, a measuring platform with sensors for monitoring the vital signs of the laboratory animal, and a module for collecting, processing and transmitting data.

The measuring platform is located under the cage for laboratory animals and contains at least two identical sensors. Sensors are symmetrically located along the bottom of the cell. Each sensor contains a microwave oscillator, a power divider, a signal mixer, a sensing element with a coplanar strip signal transmission line forming the sensor working channel, an asymmetric strip signal transmission line forming the sensor reference channel, and a dielectric substrate. The working and reference channels are connected between the outputs of the power divider and the inputs of the signal mixer. The input of the power divider is connected to the output of the microwave oscillator.

An electrically conductive grounded layer and a printed path of the working channel are deposited on one surface of the substrate. On the opposite surface of the substrate printed track of the reference channel. The surface of the substrate with an electrically conductive grounded layer and a printed track of the working channel faces the cell.

Using the sensors included in the measuring platform, simultaneous registration of the heart rate, respiratory rate and motor activity of the animal under study is provided. The performance of these functions is carried out due to the design of the sensors used.

When the sensitive elements of the sensors are located in the immediate vicinity of the laboratory animal under study (under the lower part of the cage), the influence of pulsations of the skin of the animal’s body caused by the heartbeat and respiration of the animal is manifested, as well as its movement on the propagation conditions of the generated microwave signals in the coplanar strip line of transmission of the working channel signal sensor. The pulsating movements of the skin of the animal’s body and its movement acts on the electromagnetic field of the signal, forming a signal response proportional to the change in the parameters of the external environment. This component of the signal is recorded, converted to digital form, processed using software and transmitted for further display of the received information.

The use of asymmetric strip transmission lines, which are included in the sensor’s reference channel and located on the back of the dielectric substrate, makes it possible to exclude the influence of external noise, including the influence of pulsating movements of the animal’s skin and its movement in the cage, on the reference reference signal. As a result, the propagation conditions of the microwave signal are identical in the reference channel of the sensor in the absence of environmental influences.

When changing the environmental parameters, the propagation conditions of the microwave signal in the working channel (sensitive element) of each sensor change. In this case, using the signal mixer, the deviation of the signal passing through the coplanar strip line of the working channel relative to the reference signal in the reference channel can be determined. This eliminates the influence on the reference reference signal of changes in environmental parameters. The measured deviation of the signal characterizes the changes in the parameters of the external environment, namely, the vital signs of the laboratory animal located in close proximity to the sensors.

For more precise tuning and matching of the working microwave signal with the parameters of the transmission line and the parameters of the medium being measured, an attenuator is included in the sensor. The attenuator input is connected to the output of the power divider. The attenuator output is connected to the input of the coplanar strip transmission line.

In a preferred embodiment, the data acquisition, processing and transmission module comprises a signal amplifier connected in series, to the inputs of which the sensor outputs, a low-pass filter, an analog-to-digital signal converter and a microcontroller are connected. The microcontroller may include a processor, programmable read-only memory, and random-access memory.

For complete processing of the received data, one or several personal computers can be used. In this case, data is exchanged between the computer and the data acquisition, processing and transmission module via a data line, which can be used as a USB or Wi-Fi interface.

The sensors of the measuring platform are predominantly mounted in a sealed protective case made of impact-resistant plastic, for example, acrylonitrile butadiene styrene (ABS plastic). In a particular embodiment of the design of the measuring platform, sixteen sensors mounted on one common board from the top of the cover of the split housing can be used. In order to ensure the effective operation of the measuring platform, a housing with sensors is placed under the cage in the immediate vicinity of the laboratory animal. Electronic components of the module for collecting, processing and transmitting data can be installed in the cavity of the protective sealed enclosure.

Further, the utility model is illustrated by a description of a specific example of the implementation of the stand, designed for biomedical research of laboratory animals. The explanatory drawings show the following:

in FIG. 1 - general view of the stand;

in FIG. 2 is a sectional view of the protective sealed housing of the measuring platform in the area of the board with sensors;

in FIG. 3 is a block diagram of electronic components of the stand.

The stand shown in FIG. 1 ÷ 2 drawings, designed for biomedical research in a laboratory rat. The stand contains cage 1 for the maintenance of a laboratory animal. A protective sealed housing 2 is installed under the lower part of cage 1. A removable cover 3 is installed on the upper part of the detachable housing 2. Housing 2 is made of shockproof dielectric, which is used acrylonitrile butadiene styrene (ABS plastic). The material used is transparent to electromagnetic radiation.

In the cavity of the housing 2 near its upper cover 3 there is a measuring platform, which is a common board 4, on which sixteen printed circuit boards 5 are installed symmetrically along the bottom of the cell 1, which serve as sensors. Each circuit board 5 contains a sensing element and other electronic components. Together with the measuring platform, the electronic components of the module for collecting, processing and transmitting data (MD) are located in the cavity of the housing 2. The sealed housing 2 provides the placement of sensors (printed circuit boards 5) in the immediate vicinity of the laboratory animal, while excluding the contact of electronic components with the waste products of the animal.

Each sensor (D1 ÷ D16) 6 contains a microwave oscillation generator (GC) 7, a power divider (DM) 8, an attenuator (AT) 9, a coplanar strip signal transmission line (CL) 10, an asymmetric strip signal transmission line (NL) 11 and signal mixer (CM) 12 (see. Fig. 3 drawings). Coplanar strip line 10 serves as a sensitive element of the sensor and forms together with the attenuator 9 a working channel of the sensor. The attenuator 9 is included in the working channel between the output of the power divider 8 and the input of the coplanar strip line 10. The asymmetric line NL 11 forms the reference channel of the sensor. The working and reference channels of the sensor are connected between the outputs of the power divider 8 and the inputs of the signal mixer 12. The input of the power divider 8 is connected to the output of the microwave oscillator 7.

The electronic components of the sensor are located on a dielectric substrate. An electrically conductive grounded layer and a printed path of the working channel are deposited on one surface of the substrate. On the opposite surface of the substrate printed track of the reference channel. The surface of the substrate with an electrically conductive grounded layer and a printed track of the working channel faces the cell 1.

The module (MD) 13 contains a series-connected signal amplifier (US) 14, a low-pass filter (LPF) 15, an analog-to-digital signal converter (ADC) 16 and a microcontroller (MK) 17. The US amplifier 14 is made with sixteen channels. The outputs of the sensors 6 are connected to the inputs of the US 14 amplifier. The low-pass filter 15 is made with a cutoff frequency of 20 Hz. The ADC converter 16 is also made with sixteen channels.

The output channels of the ADC converter 16 are connected to the MK 17 microcontroller, consisting of a central processor (PR) 18, programmable read-only memory (ROM) 19 and random access memory (RAM) 20. The processor 18 is connected via a personal data line (LP) 21 to a personal computer (PC) 22. The line LP 21 uses the USB or Wi-Fi interface.

Power supply nodes and blocks of the stand is carried out from a power source with galvanic isolation (not shown in the drawing). The power supply converts an alternating mains voltage of 220 ± 22 V into a constant voltage of 3.3 V.

Biomedical research on a laboratory animal (rat) is carried out using the stand as follows.

The following characteristics recorded over a long period of time were chosen as indicators of the vital activity of a laboratory rat: heart rate, respiratory rate, and motor activity, as measured by the movement of the laboratory rat across cell 1 (along the surface of measuring platform 2). The measurement of these characteristics is carried out non-contact using a measuring platform 2, which is a common board 4, on which sixteen printed circuit boards 5 of the sensors are symmetrically located. Platform 2 is installed under cage 1, in which the laboratory rat is located, and covers the surface of the bottom of the cage.

When you turn on the power of the stand in each of the sixteen sensors 6 (see. Fig. 3 drawings) using the generator GK 7 creates harmonic microwave oscillations. As working signals, narrow-band microwave signals are used. The working signal is transmitted to the input of the divider DM 8, which divides the input signal into two equal output power signals. From the first arm (output) of the DM 8 divider, the signal enters the working channel of the sensor, which contains the attenuator AT 9 and the coplanar line KL 10. The amplitude of the working signal is pre-adjusted without distortion of the waveform using the attenuator AT 9. From the second arm (output) the divider DM 8 signal enters the reference channel of the sensor with an asymmetric line NL 11.

In the process of propagation of the microwave signal along the coplanar line 10, used as a sensitive element of the sensor, most of the electric field lines are concentrated in the dielectric substrate between the printed track of the sensor working channel and the electrically conductive grounded layer. A smaller part of the electric field lines is concentrated in the surrounding airspace above the electrically conductive grounded layer and the printed path of the working channel.

Since the dielectric constant of the body of the laboratory animal is much higher than the dielectric constant of air, when the animal approaches the sensitive element of the sensor 6, the conditions for the propagation of the microwave signal in the coplanar line CL 10 change. animal. Such pulsations lead to a decrease in the amplitude of the signal and to the appearance of a phase delay of the signal.

The selection of a useful signal directly related to changes in the amplitude and phase of the transmitted signal when the laboratory animal approaches a certain sensor 6 is made by comparing the signal transmitted through the working channel with the reference signal that is transmitted through the reference channel. To do this, from the second arm of the DM 8 divider, an equal-in-power signal is transmitted to the reference channel of the sensor containing an asymmetric NL line 11.

In the NL 11 asymmetric line, most of the electromagnetic signal propagates in the dielectric substrate between the printed track of the reference channel and the electrically conductive grounded layer. Due to the fact that the printing track of the reference channel is located on the opposite side of the dielectric substrate with respect to the printing track of the working channel and the electrically conductive grounded layer, which together form the KL 10 coplanar line, the environmental impact, in particular, the movement of the body of the laboratory animal, on the reference reference signal of the sensor.

Due to the reduction of the influence of external factors on the propagation of electromagnetic signals in the reference channel of the sensor 6 and the coordination of the transmitted signals with the input characteristics of the CM 12 signal mixer, identical conditions for the propagation of microwave signals in the working and reference channels of the sensors 6 are ensured (in the absence of environmental influences). Under these conditions, reliable and accurate selection of signals characterizing the change in the position of the studied object, heart rate and respiratory rate of the laboratory animal is ensured. This principle of non-contact measurements of the characteristics of the external environment was previously implemented using the example of a device for recording the propagation velocity of a pulse wave. The device described in patent RU 126257 (published March 27, 2013) is used to study the cardiovascular system of living organisms.

Next, the microwave signals from the working and reference sensors are fed to the input of the mixer CM 12, with which the input signals are multiplied. At the output of the mixer SM 12, a resulting microwave signal is formed with a quasi-constant component, which depends on the amplitude of the compared signals and the phase difference between the signals. Conversion, pre-processing and data transfer to a computer for subsequent processing and visualization of signals is carried out using the module MD 13.

Common to all sixteen sensors 6, the MD 13 module sequentially performs the following functions:

- amplifies the input signals of the sensors in a sixteen-bit amplifier US 14;

- selects using the low-pass filter 15 quasiconstant components of the signal of each sensor, depending on the amplitude of the compared signals and the phase difference between the signals;

- carries out synchronous analog-to-digital conversion with a frequency of 1 kHz of sensor signals using a sixteen-channel ADC converter 16;

- provides the transmission of information in digital form to the microcontroller MK 17 via the SPI bus;

- generates information packets in accordance with the data transfer protocol, agreed with the software part of the hardware-software complex of the stand, using the microcontroller MK 17, consisting of a processor PR 18 and memory devices PRZU 19 and RAM 20.

The transfer of information packets in real time from the MD 13 module to the personal computer PC 22 is carried out through the data line of the LP 21. For the transmission of information packets using one measuring platform (one cell 1), the USB interface is used as the LP 21 line. If it is necessary to control several cells 1 with laboratory animals, the LP line 21 is used in the form of a Wi-Fi interface to transfer information packets from the MD 13 modules to a common PC 22 computer.

PC 22, representing the programmable part of the hardware-software complex of the stand, performs the following functions:

- receiving information packets in accordance with the data transfer protocol;

- processing of received data;

- visualization of the signal from each sensor;

- selection of the spectrum of the signal from each sensor;

- determination of the dependence of changes in recorded parameters over time and the construction of time dependencies;

- formation of a report on research;

- preservation of research results.

Based on the processed information received from each sensor, the software calculates the heart rate, respiratory rate, speed and trajectory of the laboratory animal. Moreover, the accuracy of determining the location of a laboratory animal in a cage depends on the number of sensors used in the measuring platform. The more sensors located under the cage, the higher the resolution of the measuring platform and, accordingly, the higher the accuracy of determining the location of the animal at a given point in time.

Based on the data obtained in real time, the state of the cardiovascular and respiratory systems of the laboratory animal and its motor activity are evaluated. A test bench for laboratory animal studies provides continuous contactless monitoring of several physiological parameters of the vital activity of a laboratory animal. Measurements can be carried out for the purpose of a comprehensive biomedical study of animals in the conditions of their natural behavior. This does not require fixation of the body of the animal and / or implantation of diagnostic devices into the body of the animal.

The above-described example of the implementation of the utility model is based on a specific form of execution of the stand, designed for research on laboratory animals, but this does not exclude the possibility of achieving a technical result in other special cases of the implementation of the utility model. In particular, design options are possible without the use of attenuators as part of the working channels of the sensors. Depending on the tasks and the requirements, the device may vary the number of cells for laboratory animals, the number and configuration of modules for collecting, processing and transmitting data, the number of sensors that are part of each measuring platform. It should be noted that the number of sensors in each measuring platform cannot be less than two. This restriction of the smallest possible number of sensors symmetrically installed along the bottom of the cage is introduced in order to perform the function of the sensor associated with the determination of the motor activity of a laboratory animal. In the case of using cages for laboratory animals with a protected bottom, the measuring platform can be used without a protective sealed enclosure.

The stand can be used to solve a wide range of applied problems in medicine and pharmacology, for example, for testing and laboratory studies of side effects of pharmacological agents.

The list of digital and abbreviated letter designations of the elements of the stand for conducting research on laboratory animals depicted in FIG. 1 ÷ 3 drawings:

1 - a cage for keeping a laboratory animal;

2 - protective sealed housing;

3 - removable housing cover;

4 - the total board of the measuring platform;

5 - sensor circuit board;

6 - sensor (D1 ÷ D16);

7 - generator of microwave oscillations (HA);

8 - power divider (DM);

9 - attenuator (AT);

10 - coplanar strip signal transmission line (CL);

11 - asymmetric strip signal transmission line (NL);

12 - signal mixer (SM);

13 - module for the collection, processing and transmission of data (MD);

14 - signal amplifier (US);

15 - low-pass filter (low-pass filter);

16 - analog-to-digital Converter (ADC);

17 - microcontroller (MK);

18 - microcontroller processor (PR);

19 - programmable read-only memory device (EEPROM);

20 - random access memory (RAM);

21 - data transmission line (LP);

22 - personal computer (PC).

Claims (9)

1. Stand for research on laboratory animals, containing at least one cage for laboratory animals, a measuring platform with sensors for monitoring the vital signs of the laboratory animal, and a module for collecting, processing and transmitting data, the inputs of which are connected to the outputs of the sensors, characterized in that the measuring platform is located under the cell and contains at least two sensors that are symmetrically located along the bottom of the cell, each sensor contains a microwave oscillator, a power divider, a signal mixer, a sensing element in the form of a coplanar strip signal transmission line forming the sensor working channel, an asymmetric strip signal transmission line forming the sensor reference channel, and a dielectric substrate, while the working and reference channels are connected between the outputs of the power divider, the input of which connected to the output of the microwave oscillator, and the inputs of the signal mixer, an electrically conductive grounded layer and a printed path of the working channel are applied on one surface of the substrate, on the opposite surface of the substrate coated printing path reference channel, wherein the surface of the substrate with an electrically conductive ground plane and the working channel circuit path faces the cell. 2. The stand according to claim 1, characterized in that each sensor includes an attenuator included in the working channel between the output of the power divider and the input of the coplanar strip signal transmission line. 3. The stand according to claim 1, characterized in that the data acquisition, processing and transmission module comprises serially connected signal amplifier, to the inputs of which the sensor outputs, a low-pass filter, an analog-to-digital signal converter and a microcontroller are connected. 4. The stand according to claim 3, characterized in that the microcontroller includes a processor, programmable read-only memory and random access memory. 5. The stand according to claim 1, characterized in that it contains at least one personal computer and a data transmission line that provides data exchange between the computer and the data acquisition, processing and transmission module. 6. The stand according to claim 1, characterized in that the measuring platform contains sixteen sensors. 7. The stand according to claim 1, characterized in that it contains at least one protective sealed housing, in the cavity of which the sensors of the measuring platform are installed, while the housing is located under the cage. 8. The stand according to claim 7, characterized in that the electronic components of the module for collecting, processing and transmitting data are located in the cavity of the housing. 9. The stand according to claim 7, characterized in that the housing is made of acrylonitrile butadiene styrene.

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