SU1714309A1 - Biomaterials freezing device - Google Patents

Abstract

The invention can be used in a cryogenic technique, namely in devices for software freezing of biological materials. The purpose of the invention is to increase the safety of biomaterials. The device contains a freezing chamber 1, a temperature sensor 2 installed in one of the containers with the biomaterial and connected through the differentiating unit 3 to the first input of the comparison unit 4, the master unit 5 connected to the second input of the comparison unit 4, and serially connected demodules connected to the output of the last unit 4. torus 17, divider 18, normalizing amplifier 19, second comparing unit 20, sawtooth generator 21, first comparator 15, first coincidence unit 23 and first actuator 26 connected to camera 1 blending connected to the first output of the second comparator 16 serially connected inverter 25. second block 24 matches, second actuator 27 connected to the freezing chamber 1, mode setter 10, reference signal block 13. In addition, it contains a control period formation unit, to the input of which a sawtooth voltage generator is connected, the input of the latter is connected to the output of the first master unit, and the inputs of the coincidence units are connected to the output of the control period formation unit 22, 3, etc. ^ * ^ ^ 1 ^ Cl > & Oy > &

Description

The invention relates to the field of cryogenic technology used for biological and medical research, namely, devices for programmed freezing of biological materials, such as cell cultures of gametes and zygotes of mammals, microorganisms, etc.

The aim of the invention is to increase the preservation of biomaterials during freezing by increasing the accuracy of controlling the process of program freezing.

FIG. 1 shows a device for freezing biomaterials, a block diagram; in fig. 2 and 3 are graphs illustrating the operation of the device. The proposed device contains a freezing chamber 1 with containers with a biomaterial (not shown), in one of them. temperature sensor 2 is installed, the output of which is connected through the differentiating unit 3 to the first input of the first comparison unit 4, the second input of which is connected to the output of the first master unit 5, the output of the temperature sensor 2 is connected to the input of the third comparison unit 6, the other input of which is connected to the output of block 7 integration. The output of the third comparison unit 6 through the second differentiating unit 8 and the third coincidence unit 9 is connected to the integration unit 7, another input of which is connected to the second output of the first master unit 5. The output of the mode setting unit 10 is connected to the second input of the third coincidence unit 9. The input of the initial conditions of the integration block 7 is connected to the output of the second master block 11. The other output of the third comparison block 6 is connected to the first input of the summation block 12, the other input of which is connected to the output of the reference signal block 13.

The output of the summation unit 12 through the second demodulator 14 is connected to the input of the first comparator 15 and to the input of the first target unit 5 and the second comparator 16, the first input of which is connected to the zero bus. The output of the first comparison unit 4 through the first demodulator 17 is connected to the first terminal of the divider 18, the other input of which is connected to the output of the first master unit 5. The output of the divider 18ch} 5se normalizing amplifier 19 is connected to the first input of the second block 20 equalizer. moreover, the second inputs of the normalizing detector 19 and the second comparison unit 20 are connected to the output of the first driver unit 5.

The output of the second comparator unit 20 is connected to the input of the sawtooth generator 21, the first output of which

connected to the input of the first comparator 15, and the second output of the sawtooth generator 21 to the second input of the control period formation unit 22, the first input of which is connected to the output of the first target unit 5. The output of the first comparator 15 is connected to the inputs of the first and second blocks 23 and 24 matches, the other inputs of which are connected respectively to the output of the second compyrator 16 and to the output of the inverter 25, whose input is connected to the output of the second comparator 16.3, the third inputs of the first and second blocks 23 and 24 matches are connected to move block 22 forming a control period.

The outputs of the blocks 23 and 24 coincidence are connected respectively to the inputs of the actuators 26 and 27, and the regulator in the actuator 26 may be, for example, an electromagnetic valve providing the refrigerant (liquid nitrogen) to the freezing chamber 1. In a regulatory manner, the actuator 27 can serve a heater placed in the freezing chamber 1.

The device works as follows. ..

A signal proportional to the current value of the temperature in the container is supplied from the output of temperature sensor 2 to the first input tpeTbero comparison block, to the other input of which a signal is output from the integration block 7 in the form of a linear-varying voltage, which is inclined to the set speed / back cooling the container with the biomaterial arriving in the form of a predetermined voltage from the output of the first driver unit 5 to the second input of the integration unit 7. A single signal from the output of the unit 10 mode is fed to the second input of the third block 9 matches. The signal for setting the initial value of the linearly varying voltage on you to the block of the integration block 7 comes from the output of the second master block 11 to the input of the initial conditions of the block 7 of the integration.

At the output of the comparison block b, an error signal is generated, T T, proportional to the difference between the setpoint and current temperature values. At the initial moment of time, d T 0. This signal from the first output of block 6 compare nocTynaiST "and the input of differentiating block 8," and the output of which is formed. the signal ERROR

AV d / dt (T3afl, -T), where T is the current temperature,

Tzad - Set temperature.

This signal through the third block 9 matches goes to the first input of the integration block 7, providing additional correction for the speed error signal 5 T, since the sign of the signal A V at the initial moments coincides with the signs) of the given speed VaaA generated at the output of the first master block 5 , which automatically leads to an increase in the master signal at the output of the integration blocks 7 and to an increase in the error signal b T at the time of the comparison block 6. At the same time, the signal btc of the second output of the comparison unit 6 arrives at the first input of the summation unit 12, the second input of which receives the signal Don from the output of the reference signal block 13, the value of which corresponds to the dead band size of the executive ...

 At the output of summation unit 12, a total error signal dTi defined by the expression ATi 5T + Uon is generated.

At the initial time, A Ti irp; the introduction of the Uon signal into the summation unit 12 provides for the shift of the operating range of the executive body by the value of the dead body of the executive body, which leads to a decrease in the transient time and static error in the area of the established programmatic freezing of biomaterials. The signal; l dTi from the output of summation block 12 is fed to the second demodulator 14, at the output of which a positive signal is generated, the value of which is proportional to the module:

(5T2 iaTi I..

at the initial moment of time b Ta IUon I. The signal (ZTGS of the second output of summation block 12 is fed to the input of the first driver block 5, which ensures correction of the signal (given speed) at the output of the first giving block, which leads to an increase in the speed of the transition process from small program areas scattering into areas of high program speeds. The increase in process performance occurs due to the coincidence of the characters of the signal b Ti at the output of summation unit 12 and the wedge screen at the output of master unit 5, which leads to tically to increase the gain of the entire control path.

In addition, the signal b Ti from the output of the summation block 12 is fed to the second input of the second comparator 16, ensuring the selection of the desired executive body (in, the initial moment - execute the electronic device 26). The optimal signal d Ti from the output of the second demodulator T4 is fed to the first input of the first comparator 15, to another input of which the output signal of the optimum amplitude is generated by connected to the output of the temperature sensor 2, connected in series from the output of the sawtooth generator 21 the first differentiating unit 3, the first comparing unit 4, the first demodulator 17, the divider 18, the normalizing amplifier 19, the second comparing unit 20 and the saw voltage generator 21.

The signal from the output of the temperature sensor 2, proportional to the current temperature value, is fed to the input of the first differentiating unit 3, the output

the signal of which, proportional to the rate of change of temperature, is fed to the first comparison unit 4, to another input of which a signal is transmitted from the output of the first master unit 5, which is proportional to the specified value of the cooling or heating rate. At the output of the block 4, a signal b T is defined by the expression.,

.bT Vzad-V,

where V is the current freezing rate of the biomaterial.

This signal is fed to the first demodulator 17, at the output of which a positive signal BT is generated, the value

which is proportional to the modular T. The signal b TI is fed to one input of the divider 18-, to the other. The input of which is given the signal VaaA. from the output of the master block 5. The output signal of the divider 18 is determined by the expression

I Uzad - V I

b

V

bum

This signal is fed through a normalizing amplifier 19. The gain of which is determined by the expression

KNF. KUZADCH

and 0 K 1, in the form of a signal U. calculated by the formula

I Uzad - V I

and K-Uzad.

V:

bum

is fed to one input of the second comparison unit 20, to the other input of which a signal is received. proportional to the reference signal Uzad. from the output of the master block 5., ,,,,

At the output of the comparison unit 20, a voltage Ui is formed. proportional signal difference Uzad. and U. In this case, since at the beginning of the process of program freezing V O, the signal 5 T has a maximum value close to V back1 and the signal 5 - 1, i.e. U has some maximum value. At the same time, the signal Ui at the output of the comparator block 20 is minimal, which ensures the formation at the output of the generator 21 of the sawtooth voltage of the signal with an optimal minimum amplitude. This signal arriving at the other input of the comparator 15. ensures the appearance of long duration pulses at its output.

In addition, the synchronization pulse from the second output of the sawtooth voltage generator 21 is fed to the second input of the control period formation unit 22, the first input of which receives the signal Scat., Proportional to a given speed, from the output of the master unit 5, formed at the output of the control period formation unit 22 the signal arrives at the third inputs of the blocks 23 and 24 coincidence, ensuring the connection of the selected executive body at certain times Nnep., set by the control period formation unit 22 and multiples of the period generator 21, a sawtooth voltage.

From the output of the comparator 15 pulses of optimal long duration; arrive at the first inputs of blocks 23 and 24 of coincidence, which ensures that at the initial moments the output pulses are supplied to the executive unit 26, which supplies refrigerant, for example nitrogen, to the freezing chamber 1. The chamber begins to cool, and the cooling rate increases. The 5 T signal at the output of the comparison unit 4 begins to decrease, which ultimately leads to an increase in the signal Ui at the output of the comparison unit 20 and an increase in the amplitude of the output signal of the sawtooth voltage generator 21. The signal d T at the output of the comparison unit 6 at this time increases, resulting in an increase in the 5T2 signal at the first input of the comparator 15.

Thus, an increase in the amplitude of the output signal of the generator 21 of the saw-tooth voltage supplied to the second bypass of the comparator 15. and an increase in the signal d Ta to the comparator 15 fed to the first input causes an additional one.

by increasing the steepness of the sawtooth voltage of the sawtooth generator 21, reducing the pulse duration at the output of the comparator 15, and thus further reducing the refrigerant supply to the freezing chamber 1. Upon reaching and then exceeding the current freezing rate of a given programmed freezing rate, the 5T signal at the output of comparison unit 6 will change sign to the opposite. This will cause the block 23 to turn off, since the second input has a zero signal, and the appearance of a single signal at the second input of the block 24, ensuring the connection of the actuator 27, i.e. connecting the heater to the freezing chamber ..

The camera will begin to warm up, while the cooling rate of the containers with the biomaterial will begin to decrease and, under the action of the heater, will again reach the specified program value. From the moment a given program freezing speed is set in the container, the error signals d T and (5 T at the outputs of comparison unit 6 and comparison unit 4, respectively, under the influence of the optimal algorithm, devices are installed such that provide freezing of the material at a given speed. If during the adjustment the freezing rate is deviate from the preset, this will cause a change in the sign of the error signal (ST at the output of the comparison unit 6, ensuring the selection and connection of the necessary executive body to eliminate this deviation.

Thus, in the proposed mouth; The controller gain is not only a function of the error signals dt and dt, but also on the steepness of the saw voltage, the duration of the control period and the error in the freezing rate. In the temperature stabilization mode, the same device is used without introducing new features. In order for this device to be used in the temperature stabilization mode at a given point of the temperature field, it is necessary from the output of the master unit 5 to the second input of the integrating unit 7 to submit a programmed speed value equal to zero, and from the output of the second master unit 11 to the initial value unit 7 of the integration signal of setting the desired stabilization temperature, and at the output of the mode control 10 set a zero signal for disconnecting the differentiating unit 8 from the first input of the integration unit 7.

The signal generated at the output of the control period formation unit 22 is fed to the third inputs of the coincidence units 23 and 24, ensuring the connection of the selected executive unit at certain times specified by the control period formation unit 22. In the temperature stabilization mode, all processes in the device proceed in the same way as with the stabilization of the rate of change of the biomaterial temperature.

Improving the quality of stabilization in the sections of the transition and steady-state process in the temperature stabilization mode provides for the expense of shifting the operating range of the executive body by the value of the dead body of the executive body and the optimal algorithm of the device, ensuring that the current temperature deviates from the set value in the overshoot area of no more than 3%, and mode no more than 2%. The high level of optimization of the CTC programs for the freezing of bio-materials in a wide range of speeds of 0.1-100 ° C / min in the speed stabilization sections and in the temperature stabilization sections at any given point of the temperature field (from -160 ° C) makes it possible to use a software freezing device biomaterials both in real conditions and for research purposes, and to increase the safety of biomaterials during freezing,.:

Claims (1)

Invention Formula A device for freezing biomaterials comprising a freezing chamber with a temperature sensor connected to serially connected first differentiating unit, first comparison unit, first demodulator, divider normalizing amplifier, second comparison unit, sawtooth generator, lervo ± the comparator, the first block of matches, the first actuator, the output of which is connected to the freezing chamber, as well as the first master unit, the output of which is connected to the first comparison unit, the inputs of the divider, the normalizing amplifier and the second comparison unit, the second comparator connected in series, the first input of which is connected to the zero bus, and the output is connected to the second input of the first block of matches, the inverter, the second block of matches, the second input of which is connected to the output of the first comparator, the second actuator, the output of which is connected to the freezing power, is so that in order to increase the preservation biomaterials when frozen by improving the accuracy of controlling the process of software freezing, it is equipped with a comparison unit connected in series by a child, the first input of which is connected to a temperature sensor, a summation unit whose output is connected to the first master unit and the second input of the second comparator, a second demodulator whose output is connected to the second input the first comparator, as well as serially connected by the second differentiating unit, the input of which is connected to the second output of the third comparison unit, the third unit m coincidence integration unit, whose output is connected to a second input of the third block comparison, the second input with the output of the first master unit, the reference signal block, the second master block, mode adjuster, the outputs of which are connected respectively to the second input of the summation unit, the third input of the integrator, the second input of the third coincidence unit, and the control period generation unit, the first input which is connected to the output of the first master block, the second input is with the second output of the sawtooth generator, and the output is with the third inputs of the first and second comparison blocks.