Temperature control unit minimizing electrical noise in in-vitro and in-vivo experiments

Abstract

The invention relates to a temperature control unit for microscopic examination of living cells and tissues, for precisely heating both the tissue and the fluid supplying the tissue to the desired temperature, and for maintaining a constant body temperature of animals under anesthesia for prolonged periods of time, which produces electrical noise that is either completely absent from electrophysiological recordings or so minimal that it does not affect the recordings.

Description

[0001] DESCRIPTION TEMPERATURE CONTROL UNIT MINIMIZING ELECTRICAL NOISE IN In-vitro AND In-Vivo EXPERIMENTS

[0002] TECHNICAL FIELD

[0003] The invention relates to a temperature control unit for microscopic examination of living cells and tissues, for precisely heating both the tissue and the fluid supplying the tissue to the desired temperature, and for maintaining a constant body temperature of animals under anesthesia for prolonged periods of time, which produces electrical noise that is either completely absent from electrophysiological recordings or so minimal that it does not affect the recordings.

[0004] PRIOR ART

[0005] Live cell and living tissue research (In-vitro studies)

[0006] In in-vitro electrophysiological studies performed by visualization under a microscope, a special chamber with a microscope-compatible base is required on which the cell or tissue is placed. Chambers generally do not have a heating system and the heating of the cell and tissue is achieved by heating the solution that feeds the cell. Recently, an electrically heated chamber has been introduced. (https : / / science- products.com / en / shop / 321 / 45 / perfusion-recording-tissuehandling / temperature- control / thermal-stages / wp-10).

[0007] The electrical heating of the chamber may also generate electrical noise in the electrophysiological recordings taken from the tissue or cell. This is because in-vitro electrophysiological recordings are very sensitive and require recording voltages at the microvolt level. Heating the chamber electrically causes major problems in operating at sensitive voltages and even leads to inoperability. In our invention, the chamber we designed is made of Aluminum block and aluminum pipes are passed under the chamber. The chamber is heated by passing water at the desired temperature through aluminum pipes. No electrical noise is generated during recording as there are no electrical appliances in contact with the chamber. In addition, there is a sensor on the chamber that continuously measures the temperature and in case the temperature drops, the water passing through the aluminum pipe is heated and the temperature is automatically regulated to the desired temperature with an accuracy of ±0.1 oC degrees.

[0008] In studies involving the testing of different drugs and molecules on living cells or tissues to record electrophysiological changes in the cells or tissues, the solution(s) is often heated and introduced into the chamber to regulate the tissue temperature. The heating of the solutions is achieved by operating an electric heater placed in a thin tube and passing the solution through the tube. The product operating with this system is shown in the link (https: / / scienceproducts.com / en / shop / 329 / 46 / perfusion-recording- tissuehandling / temperature-control / inline-heaters / sh-27b).

[0009] However, the voltage and current used to heat the solution can also cause electrical noise in electrophysiologic recordings, which in turn can distort the recordings. In addition, multiple heaters are needed when more than one molecule or drug is to be administered. Situations requiring multiple heating also narrow the microscope area and limit or prevent working in this area with other appliances. Thanks to the chamber design of our invention, the temperature inside the chamber can be kept at the desired level even if multiple drugs or molecules are administered separately or simultaneously at 3 ml / min fluid flows. Thus, there is no need for a heating system for each solution.

[0010] Live animal research (In-vivo studies)

[0011] In live animal research, it is desirable that anesthetized animals do not lose body temperature and for this purpose, heating lamps, heating plates and electric blankets have been produced. Related products and internet addresses are:

[0012] 1 ) https: / / science-products.eom / en / shop / 294 / 128 / in-vivo / temperature-measuring- systems-1 / animal-temperature-control / hl-1

[0013] 2) https: / / science-products.com / en / shop / 297 / 128 / in-vivo / temperature-measuring- systems-1 / animal-temperature-control / hp-1 m

[0014] 3) https: / / science-products.com / en / shop / 295 / 128 / in-vivo / temperature-measuring- systems-1 / animal-temperature-control / wb-1

[0015] While these heating systems are sufficient for stages such as surgical procedures, they can cause electrical noise when electrophysiological recordings are taken from animals. Our invention has two designs. In our invention, the chamber at the end of the water heating system is removed and replaced with (1) a blanket with a water pipe passing through it or (2) copper pipes through which water passes under the metal plate in order to perform heating. Using hot water as a heater also eliminates electrical noise. The temperature setting is done automatically with the temperature measuring sensor placed on the animal's body.

[0016] OBJECT OF THE INVENTION

[0017] Information obtained from living cells, living tissues and test animals are important experimental research in the field of health sciences. Our invention can be used in two categories.

[0018] 1 . Live cell and living tissue research (In-vitro studies)

[0019] In the examination of living cells and living tissues under the microscope, it is necessary to keep the temperature of the tissue constant for long-term preservation of viability. For this, the solution required to nourish the tissue must also be at the desired temperature. Depending on the design of the electrical appliances and devices to be used in these heating processes and the material used in their manufacture, the temperature setting accuracy and electrical noise ratio vary. Our invention will be used in temperature control processes for microscopic examination of living cells and tissues, for precisely heating both the tissue and the fluid supplying the tissue to the desired temperature, the electrical noise of which is either completely absent from electrophysiological recordings or so minimal that it does not affect the recordings.

[0020] 2. Live animal research (In-vivo studies)

[0021] In laboratory research on small live animals (mice, rats, guinea pigs, etc.) under anesthesia, the temperature of the animal must be kept constant. Our invention will be used to keep the body temperature of these animals constant for long periods of time while they are under anesthesia. Our invention will provide a working environment with no or very low electrical noise in electrophysiological recordings to be taken on live animals. In-Vitro: The reservoir we have designed in our invention is made of an aluminum block, and aluminum pipes are passed through the bottom of the reservoir. The reservoir is heated by passing water at the desired temperature through aluminum pipes. No electrical noise is generated during recording as there are no electrical appliances in contact with the reservoir. In addition, there is a sensor on the reservoir that continuously measures the temperature and in case the temperature drops, the water passing through the aluminum pipe is heated and the temperature is automatically regulated to the desired temperature with an accuracy of ±0.1 °C degrees.

[0022] Thanks to the reservoir of our invention, the temperature inside the reservoir can be kept at the desired level even if multiple drugs or molecules are administered separately or simultaneously at 3 ml / min fluid flows. Thus, there is no need for a heating system for each solution. This reduces the cost, saves space as the currently used heating systems are moved away from the microscope, and provides heating without electrical noise.

[0023] In-Vivo: At this stage, our invention has two designs. In our invention, the reservoir at the end of the water heating system is removed and replaced with a blanket with a water pipe passing through it or copper pipes through which water passes under the metal plate in order to perform heating. Using hot water as a heater also eliminates electrical noise. The temperature setting is done automatically with the temperature measuring sensor placed on the animal's body.

[0024] LIST OF DRAWINGS

[0025] Fig. 1 . Isometric view of the invention in assembled state

[0026] Fig. 2. Front view of the invention in assembled state

[0027] Fig. 3. Isometric view of the invention in assembled state

[0028] Fig. 4. Top view of the invention in assembled state

[0029] Fig. 5. Exploded view of the invention

[0030] Fig. 6. Exploded top view of the invention

[0031] Fig. 7. Exploded bottom view of the invention

[0032] Fig. 8. Bottom view of the blanket / metal plate system

[0033] Fig. 9. Top view of the blanket / metal plate system References for the numbering given in the figures:

[0034] 1 . Electronic box cover

[0035] 2. Water heating reservoir cover

[0036] 3. Water heating reservoir

[0037] 4. Water heating reservoir base

[0038] 5. Water circulation pipes

[0039] 6. Digital display screen

[0040] 7. Reservoir body

[0041] 8. Heater resistor cable and water reservoir temperature sensor cable

[0042] 9. Reservoir sensor cable

[0043] 10. Reservoir temperature sensor hole

[0044] 11 . Water circulation pump

[0045] 12. T emperature adjustment lever

[0046] 13. Power switch

[0047] 14. Heater resistor connector and water reservoir temperature sensor connector

[0048] 15. Reservoir sensor connector

[0049] 16. Electronic control unit box base

[0050] 17. Control unit vents

[0051] 18. Power cable clip

[0052] 19. Water heating reservoir cover holder

[0053] 20. Reservoir sample reservoir glass base

[0054] 21 . Reservoir heating aluminum pipe

[0055] 22. Reservoir temperature sensor

[0056] 23. Toroid transformer

[0057] 24. EMI / RFI line filter

[0058] 25. Rectifier, regulator, filters, data acquisition, and main control circuit board

[0059] 26. Pump and resistor drive

[0060] 27. Sensor and resistor cable housing

[0061] 28. Sensor and resistor cable inlet hole

[0062] 29. Water inlet and outlet nipples

[0063] 30. Heating resistors

[0064] 31 . Water reservoir heating resistors

[0065] 32. Water reservoir temperature sensor 33. Blanket / metal plate system

[0066] 34. Hot water outlet

[0067] 35. hot water Inlet

[0068] 36. Pipe line

[0069] DETAILED DESCRIPTION OF THE INVENTION

[0070] The temperature control unit minimizing electrical noise in in vitro and in-vivo experiments subject to the invention comprises electronic box, water reservoir, reservoir, water circulation pump (11 ), water circulation pipes (5) and blanket / metal plate system (33) units.

[0071] Electronic control unit comprises electronic box cover (1), digital display screen (6), temperature adjustment lever (12), power switch (13), heater resistor connector and water reservoir temperature sensor connector (14), reservoir sensor connector (15), electronic control unit box base (16), control unit vents (17), power cable clip 18), toroid transformer (23), EMI / RFI line filter (24), rectifier, regulator, filters, data acquisition and main control circuit board (25), pump, and resistor driver (26) parts. The temperature adjustment lever (12) is used to adjust the temperature on the digital display. The power switch (13) is used to switch on and off the supply of electric current to electronic systems. The heater resistor connector and the water reservoir temperature sensor connector (14) is where the temperature sensor is inserted and where the connecting cables for the resistance and sensor enter. The reservoir sensor connector (15) is where the cable for the temperature sensor in the reservoir enters. The control unit vents (17) provide conventional transfer of the temperature that may occur inside the control unit while it is operating to the room environment. The power cable clip (18) prevents the power cable from snapping under the strain of being pulled. The toroid transformer (23) provides the conversion of the energy required for the device. The EMI / RFI line filter (24) ensures that sensitive electronic components operate correctly without being affected by external signals. The rectifier, regulator, filters, data acquisition and main control circuit board (25) is the circuit board containing the electronic components required for the operation of the system. The pump and resistor driver (26) sets the electrical input required for pump and resistor operation. Water reservoir comprises water heating reservoir cover (2), water heating reservoir (3), water heating reservoir base (4), water heating reservoir cover holder (19), sensor and resistor cable slot (27) which is the room where the sensor is located and the resistor connection cables are located, sensor and resistor cable inlet hole (28) which ensures that the water hoses are tightly connected and the water enters and exits the reservoir without leaking from the connection point, water inlet and outlet nipples (29), heating resistors (30) for heating the water, water reservoir heating resistors (31 ) indicating the points where the ends of the resistors enter and exit, and water reservoir temperature sensor (32) parts.

[0072] The reservoir comprises the reservoir body (7), reservoir temperature sensor hole (10), reservoir sample reservoir glass base (20), reservoir heating aluminum pipe (21), and reservoir temperature sensor (22) parts.

[0073] For In-vitro Experiments: The electronic control unit, the water reservoir and the water circulation pump (11 ) are connected by water circulation pipes (5) and reservoir temperature sensors (22). The temperature of the water can be adjusted to the desired degree by the user through the temperature adjustment lever (12) and digital display screen (6) on the electronic control unit. After this adjustment, electricity is sent to the water reservoir and the water in the water reservoir starts to heat up through the water reservoir heating resistors (31 ). The water circulation pump (11 ) is also energized via the electronic box and when the water circulation pump (11) operates, the water in the water heating reservoir (3) circulates first to the water circulation pump (11), then to the reservoir body (7) and then back to the water heating reservoir (3). The water passing through the chamber heating aluminum pipes (21) inside the reservoir body (7) transfers its temperature to the reservoir body (7) and heats the reservoir. When the reservoir temperature sensor (22) on the reservoir body (7) indicates the desired temperature, the electronic box stops supplying energy to the water heating reservoir (3). However, the water circulates continuously. When the temperature of the reservoir body (7) falls below the desired temperature, the water heating reservoir (3) is energized and the water is heated. The water heating process is controlled with an accuracy of 0.1 °C. Both the temperature of the water in the water heating reservoir (3) and the temperature of the reservoir body (7) can be displayed separately on the digital display screen (6) on the electronic box. For In-vitro experiments: The electronic control unit, water reservoir, water circulation pump (11 ), and blanket / metal plate system (33) are connected to each other by water circulation pipes (5) and reservoir temperature measurement sensors (22). When the desired water temperature is set on the digital display screen (6) of the electronic control unit, electricity is sent to the water heating reservoir (3) and the water in the water heating reservoir (3) starts to heat up. The water circulation pump (11 ) is also energized via the electronic control unit, and when the water circulation pump (11) operates, the water in the water heating reservoir (3) circulates by first going to the water circulation pump (11), then to the blanket / metal plate system (33), and then back to the water heating reservoir (3). A plastic pipe line (36) passes through the blanket / metal plate system (33). Water passes through this plastic pipe line (36) and heats the blanket / metal plate system (33). The reason for using plastic pipe line (36) is to make the blanket / metal plate system (33) bendable and foldable. In the blanket / metal plate system (33), metal pipes (preferably aluminum or copper) pass underneath the flat metal plate and water passes through these metal pipes to heat the blanket / metal plate system (33). The metal plate is stainless steel.

[0074] The water passing through the plastic / metal pipe line (36) inside the blanket / metal plate system (33) transfers its temperature to the blanket / metal plate system (33), thereby heating the blanket / metal plate system (33). In the in-vivo system, the reservoir temperature sensor (22) is a portable sensor to be placed on the test animal. When the temperature sensor (22) on the test animal indicates the desired temperature, the electronic control unit stops supplying energy to the water reservoir (3), but the water circulation continues continuously. When the temperature of the test animal falls below the desired temperature, energy is supplied to the water reservoir (3) and the water is heated. The water heating process is performed by being controlled with an accuracy of 0.1 °C. Both the temperature of the water in the water reservoir (3) and the temperature of the test animal can be displayed separately on the digital display screen (6) on the electronic control unit.

Claims

CLAIMS1. A temperature control unit minimizing electrical noise in in vitro experiments, characterized by comprising an electronic control unit, a water heating reservoir cover (2), a water heating reservoir (3), a water heating reservoir base (4), and a water circulation pump (11 ) connected to each other by water circulation pipes (5) and reservoir temperature sensors (22), a digital display screen (6) allowing the user to adjust the water temperature to the desired degree and display the temperatures, water reservoir heating resistors (31 ), a water reservoir temperature sensor (32), a reservoir body (7) in which the sample is placed, reservoir heating aluminum pipes (21 ), a reservoir temperature sensor (22) for detecting when the desired temperature has been reached and when the temperature has dropped below the desired temperature.

2. A temperature control unit minimizing electrical noise in in vivo experiments, characterized by comprising a blanket / metal plate system (33) comprising an electronic control unit, a water heating reservoir cover (2), a water heating reservoir (3), a water heating reservoir base (4), water reservoir heating resistors (31 ), a water reservoir temperature sensor (32), a water circulation pump (11 ), and a pipe line (36); and water circulation pipes (5), a digital display screen (6) and reservoir temperature measurement sensors (22) that allow the user to adjust the water temperature to the desired degree and display the temperatures.

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