LABORATORY TEMPERING DEVICE AND METHOD

20210024871 · 2021-01-28

    Inventors

    Cpc classification

    International classification

    Abstract

    The invention relates to a laboratory tempering device for storing laboratory samples at a target temperature. It relates in particular to an incubator (1) for growing cell cultures. The invention moreover relates to a method for setting a target temperature in a laboratory tempering device that is based in particular on estimating the temperature inside the chamber.

    Claims

    1. Laboratory tempering device (1) for tempering laboratory samples at a target temperature T.sub.target, comprising: a chamber (2) for receiving laboratory samples inside chamber space (9) the outer sides of which are formed by at least one chamber wall (2a) and one chamber door (16b) that closes a chamber opening through which the inside of the chamber can be accessed by the user, a temperature control unit (6) for tempering the chamber that is attached in thermal contact to an outer side of the chamber, a temperature sensor (3) attached in thermal contact to an outer side of the chamber for recording a temperature T.sub.ak, an insulation element (4) that thermally insulates the temperature control unit, the temperature sensor and the chamber from the environment, and an electric controller (5) configured to adjust the temperature T.sub.ak by means of the temperature sensor and temperature control unit to a set-point temperature with value T.sub.x0 which is predetermined such that the temperature setting T.sub.ak=T.sub.x0 will result in the temperature T.sub.K inside the chamber being set to T.sub.K=T.sub.target.

    2. Laboratory tempering device according to claim 1 that does not comprise a temperature sensor measuring the temperature inside the chamber and serving as a measuring element for the temperature control of the electric controller that adjusts T.sub.ak to a set-point temperature having the value T.sub.x0 by means of the temperature sensor and temperature control unit.

    3. Laboratory tempering device according to claim 1 wherein the electric controller comprises a data storage unit where the at least one predetermined value T.sub.x0 is stored which is taken from the data storage unit for the purpose of setting temperature T.sub.ak=T.sub.x0.

    4. Laboratory tempering device according to claim 1, whereby the temperature control unit is operated with electric power P.sub.temp(t) during temperature setting T.sub.ak=T.sub.x0 as a function of time, and the electric controller records said power P.sub.temp(t) and the time-dependent value T.sub.ak(t) and the electric controller comprises a data processing unit configured to calculate a temperature T.sub.Kb as the temperature inside the chamber as a function of the power P.sub.temp(t) and the measured temperature T.sub.ak(t).

    5. Laboratory tempering device according to claim 4, wherein the laboratory tempering device comprises a chamber door sensor that records the opening and closing of the chamber door or the laboratory tempering device comprises an outer housing having a housing door which, when open, allows the user to access the inside of the chamber through the opened chamber door, and a housing door sensor that records the opening and closing of the housing door, whereby the electric controller is configured to record the opening and closing of the chamber door or housing door as a function of time and to calculate temperature T.sub.Kb as the temperature inside the chamber also as a function of the points in time when the chamber door or housing door is opened and closed.

    6. Laboratory tempering device according to claim 4, wherein the electric controller is configured to calculate a temperature T.sub.Kb(t) after opening and closing the chamber door or a housing door of the laboratory tempering device as a function of time t as the temperature inside the chamber pursuant to
    T.sub.Kb(t)=T.sub.ak(t)+T.sub.offset(P.sub.temp(t)P.sub.basis(t))*F with T.sub.offset being defined by T.sub.offset=T.sub.x0T.sub.target, P.sub.basis(t) being the power applied by the temperature control unit prior to opening the chamber door or housing door at steady state at a given ambient temperature and F being a scaling factor.

    7. Method (100) for setting a target temperature T.sub.target in a chamber of a laboratory tempering device according to claim 1, comprising the steps of: determining an apparatus-specific value T.sub.x0, with T.sub.x0 being predetermined such that the setting of temperature T.sub.K inside the chamber to T.sub.K=T.sub.target results from the temperature setting T.sub.ak=T.sub.x0, and setting the outside temperature T.sub.akto T.sub.ak=T.sub.x0 which results in the temperature T.sub.K inside the chamber being set to T.sub.K=T.sub.target.

    8. Method according to claim 7, with T.sub.x0 being determined in advance by means of a calibration method (200), comprising the steps of: awaiting a thermal equilibrium of the chamber; adjusting, in a verified manner, the temperature T.sub.K inside the chamber to T.sub.K=T.sub.target in a thermal equilibrium of the chamber; and determining T.sub.x0 by means of an exterior temperature sensor T.sub.ak on the outer side of the chamber of the laboratory tempering device at the now reliably set temperature inside the chamber T.sub.K=T.sub.target.

    9. Method according to claim 8, whereby T.sub.K=T.sub.target is set by connecting a mobile temperature sensor T.sub.inside that has been placed inside the chamber for calibration purposes is connected to the electric controller of the laboratory tempering device to establish a control circuit in which the mobile temperature sensor T.sub.inside inside the chamber operates as a measuring element of the control circuit and the temperature control unit(s) as a control element of the control circuit.

    10. Method (300) for estimating the temperature T.sub.K inside the chamber of a laboratory tempering device according to claim 1, comprising the steps of: determining the apparatus-specific value T.sub.x0 in particular pursuant to the calibration method described in claim 8 or claim 9, with T.sub.x0 being predetermined such that the setting of temperature T.sub.K inside the chamber to T.sub.K=T.sub.target results from the temperature setting T.sub.ak=T.sub.x0; determining an apparatus-specific value F; in particular: setting the temperature T.sub.K inside the chamber to T.sub.K=T.sub.target through temperature setting T.sub.ak=T.sub.x0; in particular: opening and closing the chamber door and/or housing door of the laboratory tempering device; and estimating the value T.sub.K inside the chamber through calculation.

    11. Method according to claim 10, whereby the value TK inside the chamber is estimated through calculation such that
    T.sub.K=T.sub.Kb=T.sub.Kb(t)=T.sub.ak(t)+T.sub.offset(P.sub.temp(t)P.sub.basis(t))*F with T.sub.offset being defined by T.sub.offset=T.sub.x0T.sub.target, P.sub.basis(t) being the power applied by the temperature control unit prior to opening the chamber door or housing door at steady state at a given ambient temperature and F being an apparatus-specific or device-specific value.

    12. Method (400) according to claim 11, whereby the value F is determined as follows: placing the laboratory tempering device in an environment having a known outside temperature T.sub.environment; setting, in a verified manner, the temperature inside the chamber T.sub.K to a value T.sub.K=T.sub.target_0 with T.sub.environment being in particular <>T.sub.target_0; opening the chamber door and/or a housing door at a certain point in time t0 and closing the same door at a later point in time t1; prior to and during opening and closing and thereafter: measuring the temperature inside the chamber T.sub.inside(t) and storing the temperature inside the chamber T.sub.inside(t) as a function of time; and using an equation, in particular equation 1 for an error compensation between the equation and measured values T.sub.inside(t) to determine factor F.

    13. Method according to claim 12, whereas setting, in a verifiable manner, the temperature inside the chamber T.sub.K to a value T.sub.K=T.sub.target_0 is done as follows: placing a mobile temperature sensor T.sub.inside inside the chamber and connecting the mobile temperature sensor T.sub.inside to the electric controller of the laboratory tempering device to establish a control circuit in which the mobile temperature sensor T.sub.inside inside the chamber operates as a measuring element of the control circuit and the temperature control unit(s) as a control element of the control circuit, wherein the control is performed with the chamber door and/or housing door.

    14. Laboratory tempering device according to claim 1 which is an incubator (1), in particular a CO2 incubator for cell cultures.

    15. Producing a laboratory tempering device according to claim 1, wherein the device-specific value T.sub.x0 is determined in advance pursuant to the calibration method described in claim 8 or 9.

    Description

    FIGURES

    [0052] FIG. 1a shows a perspective front view of an incubator according to the invention pursuant to the exemplary embodiment.

    [0053] FIG. 1b shows a perspective rear view of the incubator of FIG. 1a.

    [0054] FIG. 2 shows a schematic lateral cross-sectional view of the incubator of FIGS. 1a, 1b.

    [0055] FIG. 3 shows a diagram with the temperature top_heating circuit=T.sub.ak+T.sub.offset compared to a true chamber temperature that was measured with a mobile temperature sensor.

    [0056] FIG. 4 shows a diagram where various temperature-related parameters of the incubator are applied against time when the chamber door and housing door are first opened and then closed.

    [0057] FIG. 5 shows a diagram where the curve of the true chamber temperature T.sub.K, as applied against time, is shown that was measured with a mobile temperature sensor and a fit curve that was calculated based on error compensation.

    [0058] FIGS. 6, 7, 8, 9 and 10 show exemplary embodiments of methods according to the invention.

    [0059] FIG. 1a shows the laboratory tempering device configured as incubator 1 for growing cell cultures, in this case a CO2 incubator for growing eukaryotic cells. The incubator has an incubator chamber (see FIG. 2) for receiving at least one cell culture container comprising a cell culture that grows therein and a temperature sensor 3 attached in thermal contact to the outer side of the upper chamber wall 2a. The incubator comprises: [0060] a chamber 2 for receiving laboratory samples inside chamber space 9 the outer sides of which are formed by at least one chamber wall 2a and one chamber door 16b that closes a chamber opening 2b through which the inside of the chamber can be accessed by the user, [0061] a temperature control unit 6 for tempering chamber 2 that is attached in thermal contact to an outer side 2a of the chamber formed by the upper chamber wall 2a, [0062] a temperature sensor 3 attached in thermal contact to the same outer side 2a of the chamber 2 for recording a temperature T.sub.ak, [0063] an insulation element (4, 16) comprising an insulation layer 4 and the housing door 16 that thermally insulate the temperature control unit, the temperature sensor and the chamber from the environment, and [0064] an electric controller 5 configured to adjust the temperature T.sub.ak by means of the temperature sensor and temperature control unit to a set-point temperature with value T.sub.x0 which is predetermined such that the temperature setting T.sub.ak=T.sub.x0 will result in the temperature T.sub.K inside the chamber to be set to T.sub.K=T.sub.target.

    [0065] The incubator 1 comprises a display of the user interface unit 8 through which the electric controller 5 outputs information to the user and through which the user may make inputs. The information displayed includes in particular the estimated temperature T.sub.Kb inside chamber space 9. The incubator does not comprise a sensor with which the temperature inside the chamber T.sub.K could be measured with on-board means. The electric controller 5 is positioned in an electronics compartment 14 of the housing 7, whereas the compartment 14 outside the insulation layer 4 arranged between chamber 2 and housing 7 is arranged on the rear side of the incubator which is arranged. Compartment 14 also comprises the voltage supply 6a of the incubator. In addition, gas connections 17 for N2 and CO2 are provided on the rear side of the incubator.

    [0066] FIG. 3 shows that the chamber temperature T.sub.K which can be measured in the inside space 9 of chamber 2 by means of a verified mobile temperature sensor (measured temperature) drops from 37 C. to approx. 26 C. after the housing door 16 and the chamber door 16b are opened and that the chamber temperature slowly goes back to the initial value of 37 C. once the doors are closed again. This is done by adjusting the temperature T.sub.ak (top heating circuit) of the temperature sensor 3 arranged on the outer side to the predetermined, in this case device-specific value T.sub.x0. Said value T.sub.x0 may, and will normally, differ from the target temperature, but not necessarily. In the particular case of the exemplary incubator, said value was below 37 C. which is due to the fact that the temperature sensor used that measures T.sub.ak is not calibrated; such sensor calibration is not necessary because calibration of the laboratory tempering device's temperature accuracy is done by predetermining value T.sub.x0. One can see that the value top_heating circuit=T.sub.ak+T.sub.offset varies only slightly. However, according to the teaching of the invention this value is firmly linked to the chamber temperature T.sub.K.

    [0067] FIG. 4 shows a diagram where various temperature-related parameters of the incubator are applied against time when the chamber door and housing door are first opened (first vertical line at t.sub.0=70s) and then closed (second vertical line at t.sub.1=370s). At time point t.sub.0=70s, a base performance value P.sub.basis(t) (PWM_basis) characterizing the power input of temperature control units 6 (heating circuit) is recorded which is calculated as the moving average of here 30 values for P.sub.basis(t) (which at that point in time have already passed but are stored in a memory of the electric controller). The curve P.sub.basis(t) of the temperature control's power input is called PWM and the scale is located on the right vertical axis. Those are values around 0.01 to 0.3 indicating the time-dependent duty cycle of the power supply of the temperature control unit controlled by means of pulse width modulation. The true chamber temperature T.sub.K measured by means of a verified mobile temperature sensor that is placed in the inside space 9 of the incubator for testing is also shown for purposes of explanation and better understanding. The temperature of the temperature sensor 3 on the outer side of the chamber wall 2a is shown as curve T_mess. The curve T_top circle follows from a value T.sub.offset(T_offset) as T_top circle =T.sub.ak(t)+T.sub.offset. Curve T.sub.Kb(t) is also entered, namely as T_anz. The temperature values T.sub.Kb that vary according to this curve are shown as the calculated chamber temperature in display 8. Value T.sub.K in the inside space 9 of the chamber is estimated by calculation pursuant to equation 1 applied in this example:


    T.sub.K=T.sub.Kb=T.sub.Kb(t)=T.sub.ak(t)+T.sub.offset(P.sub.temp(t)P.sub.basis(t))*F.

    [0068] Here, the apparatus-specific value T.sub.x0=T.sub.target+T.sub.offset. Here, T.sub.target=37 C.

    [0069] FIG. 5 shows a diagram (temperature against time) to explain how the apparatus-specific value F is determined. Again, the true chamber temperature T.sub.K (18/50-10 min-ACTUAL) is applied, as measured by means of a verified mobile temperature sensor that is placed in the inside space 9 of the incubator for testing purposes. The ambient temperature was 18 C. and the temperature inside the chamber was set to 50 C. The chamber temperature T.sub.K dropped after the door was opened. The fit curve is applied ideally to the curve T.sub.K (t) (18/50-10 min-calculated) in the period between opening and closing the door(s) through parameter variation (error compensation). In this example, the fit curve follows equation 1 from which factor F can be derived which is defined for the incubator. Both apparatus-specific values T.sub.x0 and F are deposited in a data storage unit. The temperature inside the chamber can be set by means of T.sub.x0 and the temperature control of the temperature sensor T.sub.ak. The temperature profile inside the chamber after opening the door can be estimated by means of scaling factor F.

    [0070] FIG. 7 shows one example of method 100 according to the invention for setting a target temperature T.sub.target in a chamber of a laboratory tempering device, in particular in a laboratory tempering device according to the invention pursuant to FIGS. 1 to 5, comprising the steps of: [0071] Determining an apparatus-specific value T.sub.x0 in particular by means of calibration method 200, with T.sub.x0 being predetermined such that the setting of temperature T.sub.K inside the chamber to T.sub.K=Ttarget results from the temperature setting T.sub.ak=T.sub.x0. (101) [0072] Setting the outside temperature T.sub.ak to T.sub.ak=T.sub.x0 which results in the temperature T.sub.K inside the chamber being set to T.sub.K=T.sub.target. (102)

    [0073] FIG. 6 shows one example of calibration method 200 according to the invention for calibrating a laboratory tempering device, in particular a laboratory tempering device according to the invention pursuant to FIGS. 1 to 5, comprising the steps of: [0074] Awaiting a thermal equilibrium of the chamber; (201) [0075] Adjusting, in a verified manner, the temperature T.sub.K inside the chamber to T.sub.K=T.sub.target in a thermal equilibrium of the chamber; (202) [0076] Determining T.sub.x0 by means of an exterior temperature sensor T.sub.ak on the outer side of the chamber of the laboratory tempering device at the now reliably set temperature inside the chamber T.sub.K=T.sub.target. (203) [0077] Storing T.sub.x0 in the laboratory tempering device or in its data storage unit. (204)

    [0078] Here, the temperature T.sub.K inside the chamber is set to T.sub.K=T.sub.target in a verifiable manner by controlling T.sub.K=T.sub.target which is done by connecting a mobile temperature sensor T.sub.inside placed inside the chamber for calibration purposes to the electric controller of the laboratory tempering device to establish a control circuit in which the mobile temperature sensor T.sub.inside inside the chamber operates as a measuring element of the control circuit and the temperature control unit(s) as a control element of the control circuit.

    [0079] FIG. 10 shows one example of method 300 according to the invention for estimating the temperature T.sub.K inside the chamber of a laboratory tempering device, in particular in a laboratory tempering device according to one of FIGS. 1 to 5, comprising the steps of: [0080] Determining the apparatus-specific value T.sub.x0 in particular pursuant to the calibration method described in claim 8 or claim 9, with T.sub.x0 being predetermined such that the setting of temperature T.sub.K inside the chamber to T.sub.K=T.sub.target results from the temperature setting T.sub.ak=T.sub.x0; (301) [0081] Determining an apparatus-specific value F; (302) [0082] in particular: Setting the temperature T.sub.K inside the chamber to T.sub.K=T.sub.target through temperature setting T.sub.ak=T.sub.x0; (303) [0083] in particular: Recording the opening and closing of the chamber door and/or housing door of the laboratory tempering device; (304) [0084] Estimating the value T.sub.K inside the chamber through calculation such that


    T.sub.K=T.sub.Kb=T.sub.Kb(t)=T.sub.ak(t)+T.sub.offset(P.sub.temp(t)P.sub.basis(t))*F [0085] with T.sub.offset being defined by T.sub.offset=T.sub.x0T.sub.target, P.sub.basis(t) being the power applied by the temperature control unit prior to opening the chamber door or housing door at steady state at a given ambient temperature. (305)

    [0086] FIG. 9 shows one example of method 400 according to the invention for determining the apparatus-specific value F, comprising the steps of: [0087] Placing the laboratory tempering device in an environment having a known outside temperature T.sub.environment. (401) [0088] Setting, in a verified manner, the temperature inside the chamber T.sub.K to a value T.sub.K =T.sub.target_0 with T.sub.environment being in particular <>T.sub.target_0; (402) [0089] Opening the chamber door and/or a housing door at a certain point in time t0 and closing the same door at a later point in time t1; (403) [0090] Prior to and during opening and closing and thereafter: Measuring the temperature inside the chamber T.sub.inside(t) and storing the temperature inside the chamber T.sub.inside(t) as a function of time; (404) [0091] Using a calculation rule, preferably an equation, in particular equation 1 for an error compensation between the equation and measured values T.sub.inside(t) to determine factor F. (405)

    [0092] Here, the temperature T.sub.K inside the chamber is set to a value T.sub.K=T.sub.target_0 in a verifiable manner by placing a mobile temperature sensor T.sub.inside inside the chamber and connecting the mobile temperature sensor T.sub.inside to the electric controller of the laboratory tempering device to establish a control circuit in which the mobile temperature sensor T.sub.inside inside the chamber operates as a measuring element of the control circuit and the temperature control unit(s) as a control element of the control circuit. The control is performed with the chamber door and/or housing door.

    [0093] FIG. 8 shows one example of a method (500) according to the invention for performing a diagnosis to a laboratory tempering device for storing laboratory samples at a temperature T.sub.target, the laboratory tempering device comprising: [0094] a chamber for receiving laboratory samples inside chamber space the outer sides of which are formed by at least one chamber wall and one chamber door that closes a chamber opening through which the inside of the chamber can be accessed by the user, [0095] a temperature control unit for tempering the chamber that is attached in thermal contact to an outer side of the chamber, [0096] an exterior temperature sensor attached in thermal contact to an outer side of the chamber for recording a temperature T.sub.ak, [0097] an interior temperature sensor attached in thermal contact to the inside of the chamber for recording a temperature T.sub.inside which is in particular positioned inside, [0098] an insulation element that thermally insulates the temperature control unit, the temperature sensor and the chamber from the environment, and [0099] an electric controller configured to adjust the temperature T.sub.ak to a set-point temperature with the value T.sub.target by means of the interior temperature sensor and the temperature control unit, with the apparatus-specific value T.sub.x0 being stored in a data storage unit,
    the method comprising the steps of: [0100] Adjusting the temperature inside the chamber to the value T.sub.target; (501) [0101] Measuring the temperature T.sub.ak when the temperature inside the chamber is adjusted to the value T.sub.target and a stationary equilibrium exists, (502) [0102] Comparing T.sub.ak with T.sub.x0, (503) [0103] Preferably: Storing the results of the comparison of T.sub.ak with T.sub.x0 in a data storage unit of the laboratory tempering device; (504) [0104] Preferably: Outputting an error message by means of the user interface unit of the laboratory tempering device if the comparison shows that T.sub.ak<>T.sub.x0. (505)