Incubator capable of avoiding condensation

Abstract

The invention relates to an incubator comprising a chamber (11) for containing a microbial culture or a cell culture, a cooling unit adapted to cool the interior of the chamber (11) and a control unit (17). The control unit (17) is configured to control the cooling unit in accordance with a value indicative of a temperature difference between the interior of the chamber (11) and the ambient environment, and to avoid condensation in the interior of the chamber (11).

Description

Technical Field

[0001] The present invention relates to an incubator and a method of operating an incubator. Background Art

[0002] In general, an incubator is a device used to grow and maintain microbial or cell cultures. Such incubators are configured to maintain optimal conditions in terms of temperature, humidity, and, advantageously, other conditions, such as the CO2 and oxygen content of the internal atmosphere (or, in other words, the air). Incubators are essential for many experimental tasks in cell biology, microbiology, and molecular biology. Incubators are used to cultivate bacteria and eukaryotic cells.

[0003] Traditional incubators include a chamber with adjustable temperature. Some also regulate humidity, gas composition, or ventilation within the chamber. For temperature regulation, traditional incubators typically incorporate heating and compressor cooling—in other words, "active cooling." These traditional incubators are suitable for so-called "stop reactions," where the culture is stopped by intense and rapid cooling, for example, from 37°C to 4°C, advantageously within 10 minutes.

[0004] Another application, known as "switching from growth to production", involves a more gentle cooling, for example from 37°C to 32°C or 28°C. In such applications, the growth of the cells is slowed down, in particular to enable a higher yield of antibodies in the cells. In such applications, avoiding contamination is crucial. Condensation must be avoided due to the risk of contamination by condensed water. However, this is difficult to achieve with conventional incubators due to their high cooling capacity, which cannot be fine-tuned. In addition, conventional incubators have the disadvantage of using too much energy due to the cooling compressor. Generally speaking, for the applications described, even if the internal temperature Ti is higher than the ambient temperature Ta, some way of cooling the chamber is required due to the heat input from the various components of the incubator, in particular the electrical components. Summary of the Invention

[0005] The problem addressed by the present invention is to provide an incubator that is particularly well-suited for "growth-to-production" applications. Therefore, an object of the present invention is to facilitate cooling while avoiding condensation within the chamber of the incubator. Furthermore, according to embodiments of the present invention, the incubator should be energy-efficient, quiet, and / or robust.

[0006] This problem is addressed by an incubator that includes the following features:

[0007] - Chamber for accommodating microbial cultures or cell cultures: Typically, the chamber is surrounded by a housing, for example a rectangular parallelepiped housing, which is suitable for being closed by a door, for example a door pivotably mounted to the housing. Advantageously, the chamber comprises smooth surfaces, which are particularly easy to clean and maintain sterility. In particular, the interior of the chamber is largely isolated from the incubator's surroundings with respect to gas, humidity, and / or temperature exchange. This facilitates the establishment of adjustable conditions in the chamber, for example with respect to atmosphere, humidity, and / or temperature. However, advantageously, the chamber is not completely airtight, but is configured to allow pressure compensation with the surrounding environment.

[0008] - A cooling unit adapted to cool the interior of the chamber: the cooling unit may comprise at least one of: a cooling compressor, a Peltier element and / or a fan.

[0009] Where the cooling unit comprises a cooling compressor, it is advantageous that the cooling side of the compressor is not in direct contact with the interior of the chamber. Instead, the cooling unit may comprise an additional circuit of the cooling unit or a heat transfer element as described below to facilitate smooth and gentle cooling while avoiding condensation.

[0010] Advantageously, the cooling unit comprises a heat transfer element comprising an inner portion facing the interior of the chamber and an outer portion facing the surroundings of the chamber: in particular, the heat transfer element passes through the housing of the chamber and facilitates increased heat transfer from the interior of the chamber to the surroundings and vice versa.

[0011] In particular, the heat transfer element is a passive heat transfer element, in that no energy is input into the heat transfer element for transferring heat. Advantageously, the heat transfer element comprises a heat pipe. In particular, a heat pipe is a heat transfer element that utilizes phase change to transfer heat between two solid interfaces. In an embodiment of the incubator, the heat pipe comprises a copper jacket and / or the heat pipe comprises water as the working fluid. For the envisioned application of the incubator, it is further advantageous that the operating range of the chamber and the heat transfer element includes a temperature of at least between 20°C and 40°C.

[0012] In the case where the cooling unit comprises a heat transfer element, it is further advantageous if it comprises a cooling element adapted to cool an outer portion of the heat transfer element: in particular, the cooling element is mounted outside the chamber. Although cooling of the interior of the chamber can be achieved by exposing the outer portion of the heat transfer element to the surrounding environment, the cooling element advantageously comprises means for regulating the heat transfer from the interior of the chamber to the surrounding environment, thereby controlling the cooling power.

[0013] In an advantageous embodiment, the cooling element comprises an external fan adapted to cool the exterior of the heat transfer element. By controlling the fan's speed, heat transfer can be controlled. However, this type of chamber cooling via a heat transfer element, particularly a heat pipe, is physically limited to situations where the chamber's internal temperature is higher than the ambient temperature. In this sense, despite the presence of a controllable cooling element, particularly an external fan, chamber cooling via the heat transfer element can be termed "passive cooling." This is in contrast to "active cooling," such as a cooling compressor that cannot function properly without energy.

[0014] The incubator further comprises a control unit configured to control the cooling unit, in particular the cooling element, in accordance with a value indicative of a temperature difference between the interior of the chamber and the surrounding environment, and to avoid condensation in the interior of the chamber. In the event that the cooling element comprises an external fan, the control unit is configured to control the rotational speed of the external fan.

[0015] This type of "passively cooled" incubator by means of heat transfer elements, in particular heat pipes, has several advantages over conventional incubators: it is energy-efficient, in particular compared to cooling by means of a cooling compressor (approximately 3 times less energy), or even more so compared to cooling by means of Peltier elements (approximately 10 times less energy).

[0016] Incubators with cooling elements or Peltier elements are robust and have few moving parts. This, in turn, contributes to a long service life and low-cost operation without requiring much maintenance. Furthermore, compared to cooling compressors, incubators are environmentally friendly by avoiding the need to use and refill hazardous coolants.

[0017] Finally, the claimed incubator facilitates gentle cooling of the chamber over a long time span, for example, gradually over 60 minutes, while strictly avoiding any condensation that could lead to contamination, such as mold, in the chamber. Thus, the incubator is particularly well-suited for the "growth-to-production switchover" application described above.

[0018] Finned Element

[0019] In an embodiment, the cooling unit includes internal fin elements mounted on the inner portion of the heat transfer element. The internal fin elements are in thermal contact with the interior of the chamber and, in particular, serve to improve heat transfer between the interior of the chamber and the inner portion of the heat transfer element. To this end, the fin elements typically have an increased surface area compared to the element to which they are mounted. They may, for example, be made of aluminum.

[0020] In a preferred embodiment, the cooling unit includes a thermal insulation layer mounted on a portion of the internal fin element positioned proximate to the heat transfer element. Due to its proximity to the heat transfer element, this portion of the internal fin element is coldest and therefore most susceptible to condensation. Thus, the thermal insulation layer further helps prevent condensation within the chamber interior. Advantageously, the thermal insulation layer includes a water-repellent or waterproof surface. This facilitates easier cleaning and keeping surfaces within the chamber interior free of contaminants.

[0021] Alternatively or additionally, the cooling unit may include an external fin element mounted on an outer portion of the heat transfer element. The external fin element is in thermal contact with the surrounding environment of the chamber and is particularly configured to improve heat transfer between the surrounding environment and the outer portion of the heat transfer element. In the event that the cooling element includes an external fan, the external fan is arranged and adapted to cool the external fin element, in particular by circulating ambient air through the external fin element.

[0022] sensor

[0023] Advantageously, the incubator includes various sensors to be able to adapt to different boundary conditions, such as the ambient temperature, a first (initial) temperature in the interior of the chamber, and a first (initial) humidity in the interior of the chamber. Based on the values ​​measured by the sensors, the incubator can be controlled according to different temperature profiles over time, for example, differing in the duration of the temperature reduction or in the second (target) temperature in the chamber. Such sensors advantageously include at least one of the following:

[0024] - an internal temperature sensor adapted to measure the internal temperature of the chamber,

[0025] - an ambient temperature sensor suitable for measuring the ambient temperature,

[0026] - a humidity sensor adapted to measure the humidity in the interior of the chamber.

[0027] Any of these sensors is advantageously in communication with the control unit.Thus, the control unit may be configured to control the cooling unit, in particular the cooling element, and in particular the humidity control unit (described below), in accordance with the measured values ​​received from the sensors.

[0028] Humidity control

[0029] In an embodiment, the incubator includes a humidity control unit adapted to control the humidity within the chamber and controllable by the control unit. Advantageously, the humidity control unit includes a steam generator located outside the chamber. The steam generator may include a water reservoir and a heating element disposed at the water reservoir for generating steam. By being disposed outside the chamber, the risk of condensation within the chamber is reduced. In a second embodiment, the humidity control unit may include an open water bath located within the chamber. The water bath may include a heating element for generating steam.

[0030] Advantageously, the humidity control unit includes a pump for selectively pumping steam from the reservoir or ambient air into the chamber. Clearly, by pumping steam into the chamber, the humidity in the chamber can be increased, while by supplying ambient air into the chamber, the humidity can be reduced. The pump, in particular the steam generator, can be controlled by the control unit so that, in conjunction with the humidity sensor, the humidity in the chamber can be adjusted to a desired value, advantageously below 85%, to avoid condensation.

[0031] Other favorable features

[0032] In an embodiment, the incubator includes an internal fan arranged within the interior of the chamber. The internal fan is adapted to circulate air within the interior of the chamber. This ensures a uniform distribution of conditions, such as temperature, humidity, and gas, which is important for the reliability of growing cells.

[0033] In an embodiment, the incubator includes a HEPA filter for filtering the air within the chamber. HEPA stands for "High Efficiency Particulate Air." By filtering the air, contaminants can be removed and sterile conditions can be ensured. In this case, an internal fan is adapted to circulate air through the HEPA filter.

[0034] In an embodiment, the incubator comprises racks for static culture of cells.

[0035] In an embodiment, an incubator includes a shaker adapted to agitate a microbial or cell culture within a chamber. Advantageously, the shaker is configured to agitate one or more trays disposed within the chamber. The microbial or cell culture can be placed on the trays, for example, in test cups or Erlenmeyer flasks. Advantageously, the shaker is adapted to impart an orbital motion to the culture. This enhances the uniformity of the culture and increases the air supply between the liquid culture and the air surface.

[0036] How to operate

[0037] A second aspect of the present invention relates to a method for operating an incubator. As previously mentioned, such a method is particularly useful for performing a "switch from growth to production" application. The method comprises the following steps:

[0038] (i) Adjusting the temperature in the chamber to a first temperature value (T1) for a first time period: This first time period is typically used for cell growth. It may, for example, last several days. Advantageously, the first temperature value is between 35° C. and 40° C., in particular around 37° C.

[0039] (ii) During a transition period (tT), the temperature in the chamber is lowered to a second temperature value (T2). Advantageously, the second temperature value is between 27°C and 32°C. In a typical laboratory with an ambient temperature between 18°C ​​and 22°C, such a second temperature value can be achieved by the aforementioned "passive cooling." Advantageously, the step of lowering the temperature in the chamber is performed gradually during the transition period. The duration of the transition period can, for example, be at least 60 minutes, in particular at least 120 minutes. This ensures a smooth slowing down of the cell productivity.

[0040] (iii) During a second time period (t2), the temperature in the chamber is adjusted to a second temperature value (T2): the second time period is typically used for the cells to produce antibodies.

[0041] According to the present invention, during steps (i), (ii), and (iii) above, the temperature and / or humidity in the chamber are regulated such that the humidity does not reach 100%, and in particular does not exceed 85%. In other words, the temperature in the chamber must always be above the dew point. To meet this criterion, a reduction in humidity may or may not be necessary, depending on the first humidity value during the first time period and the desired second (target) temperature value. However, a reduction in humidity is often necessary, particularly when it is desired to achieve a second (target) humidity value similar to the first humidity value (e.g., between 75% and 85%). As previously mentioned, the reduction in humidity can be achieved by pumping ambient air, which is typically cooler and less humid, into the chamber.

[0042] In various embodiments, the humidity may be reduced by continuously controlling and adjusting the humidity during the transition period according to the aforementioned criteria, or by reducing the humidity in the chamber to a transition humidity value (RHT) before reducing the temperature in step (ii). In the latter case, the transition humidity value needs to satisfy the criterion that the second temperature value (T2) is greater than the dew point of air having the first temperature value (T1) and the transition humidity value (RHT).

[0043] By the above method of operation, a gentle temperature reduction can be achieved without causing any harmful condensation in the incubator.

[0044] In an advantageous embodiment of the incubator, the control unit is configured to control the cooling unit, in particular the cooling element, and the humidity control unit, if present, to perform the method.

[0045] Furthermore, it will be appreciated from the foregoing that the incubator and method of operation may be advantageously used to grow or maintain microbial cultures or cell cultures.

[0046] Further advantageous embodiments are listed in the dependent claims and in the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] The present invention will be better understood from the following detailed description thereof, and other objects besides the above objects will also become clear. Such description refers to the accompanying drawings, in which:

[0048] Figure 1 shows a schematic diagram of an incubator according to an embodiment of the present invention;

[0049] Figure 2 A block diagram illustrating control in an incubator according to an embodiment of the present invention is shown;

[0050] Figure 3 Schematic time series of temperature (T) and humidity (RH) are shown for a method of operating an incubator according to an embodiment of the present invention. DETAILED DESCRIPTION

[0051] Figure 1 The schematic diagram illustrates an embodiment of an incubator 1 as described above. The incubator 1 comprises a chamber 11 in which a cell culture is placed for the purpose of growing, maintaining and / or producing, for example, antibodies. In order to provide optimal conditions for the cells, the atmosphere in the chamber 11 can be controlled, for example, in terms of temperature Ti, humidity RHi and / or its gas composition.

[0052] For certain applications, such as the aforementioned "stop reaction" and "growth-to-production switch" applications, the interior of the chamber 11 requires cooling. Cooling of the chamber 11 is necessary not only to achieve temperatures below the ambient temperature Ta, but also within a certain temperature range above the ambient temperature. This is due to the heat input from various components of the incubator 1, such as the internal fan 16 and the shaker motor (not shown). In a typical laboratory with an ambient temperature of approximately 20°C, cooling may already be required to achieve temperatures of 30°C or 35°C or below.

[0053] Gentle cooling of the chamber 11, which does not fall below the ambient temperature Ta, can be achieved by a cooling unit 13, which includes a passive heat transfer element 13c, such as a heat pipe, connecting the interior of the chamber 11 to the surrounding environment. Although a piece of thermally conductive material (e.g., copper) can alternatively be used as the passive heat transfer element 13c, the effective thermal conductivity of a heat pipe can be two to three orders of magnitude higher, making it the preferred passive heat transfer element.

[0054] In order to improve the thermal coupling with the interior of the chamber 11 and with the surrounding environment, an internal heat sink with fins 13b and an external heat sink with fins 13a can be mounted on the heat pipe. In addition, the cooling unit 13 can include a cooling element 14 for adjusting the cooling power, the cooling element 14 being arranged to cool the external part, in particular the external fins 13a. The cooling element 14 can be implemented as a fan 14, such as a common computer fan, which cools air having an ambient temperature Ta (e.g., Figure 1 ) blows onto the external fins 13a. Such cooling elements 14 are advantageously controlled according to the temperature difference Ti-Ta between the interior and the surrounding environment. To this end, the incubator 1 advantageously comprises sensors for the internal temperature Ti and the ambient temperature Ta.

[0055] Advantageously, the incubator 1 further comprises a HEPA filter 15 arranged to filter the air in the interior of the chamber 11. By means of an internal fan 16 a good circulation of the air in the chamber 11 and through the HEPA filter can be achieved.

[0056] Figure 2 Shows such as Figure 1 The control unit 17 receives as input the values ​​of the internal temperature Ti, the ambient temperature Ta and the internal humidity RHi measured by corresponding sensors, e.g. Figure 1 Based on the measured values, the control unit 17 controls the cooling element 14 and the humidity control unit 18 ( Figure 1 (not shown in the figure, see the section “Humidity Control” above) so that the internal temperature Ti and the internal humidity RHi follow the desired course of change over time.

[0057] The desired course of the internal temperature Ti is determined primarily by the intended application, see for example Figure 3 In turn, the humidity RHi is regulated to remain below 100% at all times in order to avoid condensation. Since some components in the interior of the chamber 11, such as the interior portion of the heat pipe 13c, can (and usually will) be cooler than the measured internal temperature Ti, the humidity RHi is advantageously controlled to never exceed 85%. This also avoids condensation on the cooler components.

[0058] Figure 3 A schematic time series of internal temperature Ti and internal humidity RHi is illustrated for a gentle cooling action, such as in a "switch from growth to production" application. In such an application, cells being grown are typically subjected to a first temperature T1, e.g., approximately 37°C, for a first time period t1. During the same time period, humidity is controlled to a first humidity value RH1, e.g., between 75% and 85%.

[0059] Then, a slow and gentle transition from the first temperature T1 to the second temperature T2 occurs, for example, to around 32°C or 28°C. Such a temperature T2 is ideal for stopping cell growth but increasing its productivity, for example, antibody production. This slow and gentle temperature reduction from T1 to T2, over a transition period tT of, for example, one or two hours, is advantageously performed by a passive heat transfer element 13c, as it is robust and energy-efficient.

[0060] In order to avoid condensation in the chamber 11 during the temperature reduction, the humidity in the chamber can be reduced to a transition humidity value RHT. This can be achieved by the humidity control unit 18. Figure 3 As shown in , if humidity reduction is already initiated and completed before the temperature reduction begins, the transition humidity value RHT is determined, for example, by the control unit 17 based on the temperatures T1 and T2, such that the following criterion is met: the second temperature value T2 is greater than the dew point of the air having the first temperature value T1 and the transition humidity value RHT. Advantageously, a safety margin is again incorporated, for example by requiring that the second (target) humidity value RH2 also not exceed, for example, 85%. Alternatively, the humidity can be continuously controlled and adjusted during the transition period tT so that it never reaches 100%, and in particular does not exceed 85%. This reliably prevents condensation within the chamber 11, thereby preventing contamination of the chamber 11.

Claims

1. An incubator comprising - a chamber (11) for accommodating a microbial culture or a cell culture, - a cooling unit adapted to cool the interior of the chamber (11), - a control unit (17) configured to control the cooling unit according to a value indicative of a temperature difference between the interior of the chamber (11) and the surrounding environment and to avoid condensation in the interior of the chamber (11).

2. The incubator according to claim 1, The cooling unit includes at least one of the following: - Cooling compressor, - Peltier elements, -fan.

3. An incubator according to any one of the preceding claims, The cooling unit includes - a heat transfer element (13c) comprising an inner portion facing the interior of the chamber (11) and an outer portion facing the surroundings of the chamber (11), - a cooling element (14) adapted to cool the outer portion of the heat transfer element (13c), The control unit (17) is configured to control the cooling element (14) according to a value indicative of a temperature difference between the interior of the chamber (11) and the surrounding environment and to avoid condensation in the interior of the chamber (11).

4. An incubator according to any claim 3, wherein the heat transfer element (13c) comprises a heat pipe, In particular, wherein the heat pipe comprises a copper jacket, and / or In particular, the heat pipe comprises water as the working fluid.

5. The incubator according to any one of claims 3 to 4, The operating range of the chamber (11) and the heat transfer element (13c) includes a temperature between at least 20°C and 40°C.

6. An incubator according to any one of claims 3 to 5, The cooling unit includes - an internal fin element (13b) mounted on the inner portion of the heat transfer element (13c) and in thermal contact with the interior of the chamber (11).

7. The incubator according to claim 6, The cooling unit includes - a heat insulating layer mounted on a portion of the internal fin element (13b) positioned adjacent to the heat transfer element (13c), Especially wherein the thermal insulation layer comprises a water repellent or waterproof surface.

8. An incubator according to any one of claims 3 to 7, The cooling unit includes - External fin elements (13a) mounted on the outer portion of the heat transfer element (13c) and in thermal contact with the surroundings of the chamber (11).

9. An incubator according to any one of claims 3 to 8, wherein the cooling element (14) comprises an external fan adapted to cool an outer portion of the heat transfer element (13c), in particular adapted to cool the outer fin element (13a), The control unit (17) is configured to control the rotation speed of the external fan.

10. An incubator according to any one of the preceding claims, comprising - an internal temperature sensor adapted to measure the internal temperature (Ti) of the chamber (11), and - an ambient temperature sensor suitable for measuring the ambient temperature (Ta), The internal temperature sensor and the ambient temperature sensor are in communication with the control unit (17).

11. An incubator according to any one of the preceding claims, comprising a humidity control unit (18) adapted to control the humidity in the interior of the chamber (11) and controllable by the control unit (17), and - a humidity sensor adapted to measure the humidity (RHi) in the interior of the chamber (11) and to communicate with the control unit (17).

12. The incubator according to claim 11, The humidity control unit (18) comprises a steam generator, which is located outside the chamber (11) and includes a water reservoir and a heating element arranged at the water reservoir, wherein the humidity control unit (18) comprises a pump for selectively pumping steam or ambient air into the chamber (11), The pump, in particular the steam generator, can be controlled by a control unit (17).

13. An incubator according to any one of the preceding claims, comprising - an internal fan (16) arranged inside the chamber (11) and adapted to circulate air inside the chamber (11).

14. An incubator according to any one of the preceding claims, comprising - a HEPA filter (15) for filtering the air in the interior of the chamber (11), An internal fan (16) is adapted to circulate air through the HEPA filter (15).

15. An incubator according to any one of the preceding claims, comprising - a shaker suitable for shaking the microorganism culture or cell culture in the interior of the chamber (11), In particular, a shaker is suitable for imparting orbital motion to the culture.

16. A method of operating an incubator according to any one of the preceding claims, the method comprising the steps of: (i) regulating the temperature in the chamber (11) to a first temperature value (T1) during a first time period (t1), (ii) during a transition period (tT), lowering the temperature in the chamber to a second temperature value (T2), (iii) regulating the temperature in the chamber (11) to a second temperature value (T2) during a second time period (t2), During the above steps (i), (ii) and (iii), the temperature and / or humidity in the chamber (11) is adjusted so that the humidity does not reach 100%, in particular does not exceed 85%.

17. The method according to claim 16, further comprising the following steps before step (ii): Lowering the humidity in the chamber (11) to the transition humidity value (RHT), The second temperature value (T2) is greater than the dew point of air having the first temperature value (T1) and the transition humidity value (RHT).

18. The method according to any one of claims 16 to 17, wherein the first temperature value (T1) is between 35°C and 40°C, in particular 37°C, and / or The second temperature value (T2) is between 27°C and 32°C.

19. The method according to any one of claims 16 to 18, The duration of the transition time period (tT) is at least 60 minutes, in particular at least 120 minutes.

20. The incubator according to any one of claims 1 to 15, The control unit (17) is configured to control the cooling unit, in particular the cooling element (14), in particular the humidity control unit (18), to perform the method according to any one of claims 16 to 19.

21. Use of an incubator according to any one of claims 1 to 15 or 20 for growing or maintaining microbial cultures or cell cultures.

22. Use of a method according to any one of claims 16 to 19 for growing or maintaining a microbial culture or a cell culture.

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