Incubator, sample vessel, kit and method for examining a sample material

Abstract

An incubator (1) and its use for cultivating microorganisms and/or for carrying out a chemical reaction are provided. The incubator (1) has a sample vessel holder (3) for insertion of a sample vessel (4), a heating device (5) for changing a temperature in the sample vessel holder (3) and/or in a sample vessel (4) inserted into the sample vessel holder (3), and a sample-inactivating device (6) for inactivation of a sample (7) in a sample vessel (4) that is inserted into the sample vessel holder (3).

Claims

1. An incubator (1) for at least one of cultivation of microorganisms (2) or performance of a chemical reaction, the incubator comprising: a sample vessel receiver (3) into which a sample vessel (4) is insertable; a heating device (5) for changing a temperature in at least one of the sample vessel receiver (3) or in a sample vessel (4) inserted into the sample vessel receiver (3); a sample inactivation device (6) for inactivation of a sample (7) in a sample vessel (4) inserted into the sample vessel receiver (3); an analysis unit (21), comprising at least one measurement apparatus (11) having a sensor or probe extending into the sample vessel (4), to determine if the inactivation of the sample by the sample inactivation device (6) was successful; and a closure unit (10) comprising a safety lock (9), wherein after introduction of the sample vessel (4) and closing of the sample vessel receiver (3) or after introduction of the sample (7) and closing of an incubation chamber, the closure unit (10) remains locked by the safety lock (9) until the analysis unit (21) determines that the sample inactivation was successful.

2. The incubator (1) as claimed in claim 1, further comprising a controller (8) for establishing at least one program, wherein, the closure unit (10), after introduction of the sample vessel (4) and closing of the sample vessel receiver (3) or after introduction of the sample (7) and closing of an incubation chamber, remains locked by the safety lock (9) until at least one of the established program has ended or an opening code has been input by an authorized user.

3. The incubator (1) as claimed in claim 1, wherein the at least one measurement apparatus (11) carries out a measurement of at least one experimental parameter within a sample vessel (4) inserted into the sample vessel receiver (3), the at least one measurement apparatus (11) is set up to determine at least one experimental parameter, wherein the at least one experimental parameter is at least one of: optical density, color reaction, impedance, pH, gas composition, oxygen content or CO.sub.2 content, in at least one of liquid or supernatant, spectroscopic property, electrochemical property, reaction of at least one of a substrate or a chemical, fluorescence, luminescence, nucleic acids, a nucleic acid sequence, cell mass, peptides, or proteins, and wherein the at least one measurement apparatus (11) is at least one of: a chromatography unit, a mass spectrometer, a lateral flow test unit, a spectroscopy unit, a fluorescence measurement unit, a luminescence measurement unit, a capillary electrophoresis unit, a protein characterization unit, a nucleic acid characterization unit, a immunoassay unit, or an immunobeads unit.

4. The incubator (1) as claimed in claim 1, further comprising a viewing window (14) through which optical measurement on the sample (7) is possible within at least one of the sample vessel receiver (3) or within the sample receiver, and an optical sensor (15) for performing an optical measurement on or in the sample (7).

5. The incubator (1) as claimed in claim 1, wherein the sample inactivation device (6) inactivates the sample (7) by at least one of: physical, mechanical, thermal, chemical, biological or radiation-generated inactivation, and wherein the sample inactivation device (6) is configured as at least one of: an autoclave, a hot air sterilizer, a gassing unit, a irradiation unit, a microwave unit, an electron beam unit, an ultrasound unit, a vacuum unit, a cavitation unit, a shear force unit or an inactivator release unit.

6. An incubator (1) for at least one of cultivation of microorganisms (2) or performance of a chemical reaction, the incubator comprising: a sample receiver into which a sample (7) is directly introducible; a heating device (5) for changing a temperature in the sample receiver; a sample inactivation device (6) for inactivating the sample (7) in the sample receiver; an analysis unit (21), comprising at least one measurement apparatus (11) having a sensor or probe extending into the sample receiver, to determine if the inactivation of the sample by the sample inactivation device (6) was successful; and a closure unit (10) of the incubator (1) comprising a safety lock (9) wherein after introduction of the sample (7) and closing of an incubation chamber, the closure unit (10) remains locked by the safety lock (9) until the analysis unit (21) determines that the sample inactivation was successful.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention is now described in detail with reference to multiple illustrated working examples, but is not limited to these working examples. Further working examples result from the combination of the features of individual or multiple claims with one another and/or with individual or multiple features of the working examples.

(2) The figures show:

(3) FIG. 1 a schematic diagram of a working example of the incubator of the invention and of the sample vessel of the invention, with additional indication of the individual steps of the method of the invention,

(4) FIG. 2 a configuration of a sample vessel of the invention in schematic view,

(5) FIG. 3 a transfer of a sample to the sample vessel, with the sample vessel open,

(6) FIG. 4 the closed sample vessel, with the sample in a medium in the sample receiving chamber,

(7) FIG. 5 an incubation step, with incubation of the sample present in the sample receiving chamber by generation of ideal reaction and/or growth conditions,

(8) FIG. 6 the triggering of a detection reaction by actuating an opening device, such that the sample is analyzed, and

(9) FIG. 7 an inactivation step, wherein actuating an opening element releases an inactivator from an inactivation capsule into the sample receiving chamber.

DETAILED DESCRIPTION

(10) FIG. 1 shows an incubator referred to as 1 as a whole. The incubator 1 is intended for cultivation of microorganisms 2 and/or for performance of a chemical reaction. The chemical reaction may, for example, be a biochemical reaction.

(11) The incubator 1 has a sample vessel receiver 3 into which a sample vessel 4 can be inserted. The incubator 1 also has a heating device 5 that serves to change a temperature in the sample vessel receiver 3. Thus, if a sample vessel 4 has been inserted into the sample vessel receiver 3, it is also possible to change the temperature therein. In addition, the incubator 1 has a sample inactivation device 6 intended for inactivation of a sample 7 in a sample vessel 4 inserted into the sample vessel receiver 3.

(12) In a further embodiment of the incubator 1, not shown in the figures, an incubation chamber may be provided rather than the sample vessel receiver 3. A sample receiver disposed within the incubation chamber can be charged directly with a sample to be incubated. Thus, in this configuration, there is no intention to insert a sample vessel into the incubator, but rather to undertake incubation, analysis and inactivation of the sample within the sample receiver. In the description that follows, however, no further reference is made to this configuration variant. However, it is conceivable that the features described hereinafter are also employed in the embodiment with a sample receiver.

(13) By the incubator 1, it is thus possible, preferably even outside a secure laboratory specially designed for the purpose, to undertake microbiological and/or biochemical analyses on a sample since the incubator 1 creates a dedicated sealed experimental chamber for the purpose, in which incubation and inactivation of the sample 7 can be performed. For instance, the incubator 1 can especially be used to undertake analyses on foods, for example in a restaurant or a food shop.

(14) In order to be able to conduct a specific program for performance of a method by the incubator 1, preferably automatically, the incubator 1 has a controller 8. The controller 8 allows the establishment of various programs in order to be able to perform at least one incubation step and/or at least one inactivation step using an incubation and/or inactivation program. A user therefore has the opportunity to select a program for example directed specifically to a particular food and/or microorganism by the controller 8 in order thus to be able to undertake, preferably in an automated manner, incubation, analysis and inactivation of a sample 7.

(15) The incubator 1 also has a safety lock 9 set up such that a closure unit 10 of the incubator 1 is openable only when a program established via the controller 8 has ended and/or when an authorized user inputs an opening code or undertakes another release activity. It may be particularly advantageous when the safety lock 9 is set up such that the closure unit 10, after introduction of the sample vessel 4 into the sample vessel receiver 3 and closure of the sample vessel receiver 3 by the closure unit 10, remains locked until an established program has ended, such that opening is not possible prior to performance of an inactivation step for inactivation of the sample 7 present in the sample vessel 4. It is thus possible to prevent contamination from occurring outside the incubator 1.

(16) In order to be able to undertake analysis of a sample 7, the incubator 1 has at least one measurement apparatus 11. The measurement apparatus 11 is preferably set up to continuously undertake a measurement of at least one experimental parameter, especially while an established program is running. It may be particularly appropriate here when a continuous measurement is effected during an incubation program. The measurement of the at least one experimental parameter here can be effected within a sample vessel 4 inserted into the sample vessel receiver 3. This means that a measurement site is within the sample vessel 4 even though the measurement apparatus 11 is disposed outside and/or within the sample vessel 4. Moreover, it may, however, also be the case that the measurement apparatus 11 has a probe and/or sensor that extends into the sample vessel 4 in order to be able to undertake a measurement of at least one experimental parameter therein.

(17) The measurement apparatus 11 is preferably set up to determine one or more experimental parameters selected from the group of optical density, color reaction, impedance, pH, gas composition, preferably with measurement of an oxygen content and/or a CO.sub.2 content in liquid and/or in a supernatant, spectroscopic property, electrochemical property, reaction of a substrate and/or a chemical, fluorescence, luminescence, nucleic acids and/or a nucleic acid sequence, cell mass, peptides and/or proteins. It may therefore be appropriate when the incubator 1 has one measurement apparatus 11 or multiple measurement apparatuses 11 from the group of chromatography unit, especially high-performance liquid chromatography unit and/or thin-layer chromatography unit, mass spectrometer, lateral flow test unit, spectroscopy unit, especially Raman spectroscopy and/or NIR spectroscopy unit, fluorescence measurement unit, luminescence measurement unit, capillary electrophoresis unit, protein characterization unit, nucleic acid characterization unit, immunoassay unit, especially antibody assay unit, and/or immunobeads unit.

(18) In order to be able to introduce a chemical substance and/or a biological substance into the sample vessel 4 and/or to be able to take sample material from the sample 7 present in the incubator 1 from the sample vessel 4, preferably during the performance of a program, the incubator 1 has at least one opening 12. The preferably closable opening 12 allows, by virtue of its configuration with a selection device 13, merely selective taking of sample material that does not contain microorganisms and is thus sterile. The selection device 13 may take the form, for example, of a filter. Particularly preferred filter configurations here may be a filter membrane and/or a filter resin. However, the selection device 13 may alternatively or additionally also be configured as a purifying column. Preferably, a separately configured opening 12 is provided in each case for the taking and introducing.

(19) As apparent in FIG. 1, the at least one opening 12 is disposed in the closure unit 10. Thus, the opening 12 is very easy for a user to reach if he is conducting an experiment. The opening 12 may be tightly closable, for example by a sealing device. It may be particularly appropriate when the opening 12 is closable, especially closable by a sealing device.

(20) The incubator 1 also has a viewing window 14 through which optical measurement on the sample 7 is possible. The sample 7 may be analyzed here within the sample vessel 4 inserted into the sample vessel receiver 3. For this purpose, the incubator 1 has an optical sensor 15 by which optical sensor 15 it is possible to perform an optical measurement on or in the sample 7. The optical sensor 15 may be disposed within or outside the sample vessel receiver 3 since measurements are also possible from outside the sample vessel receiver 3 via the viewing window 14.

(21) In order to enable very good mixing of a sample 7, preferably with a medium 38, the incubator 1 has a shaker and/or stirrer unit 16.

(22) In order to be able to detect a propagation process and/or biochemical activity of at least one microorganism 2 within a sample vessel 4 inserted into the sample vessel receiver 3, the incubator 1 has a detection device 17. The detection device 17 may be configured, for example, as part of the measurement apparatus 11, with a result being displayable directly to a user as to whether a propagation process is proceeding and/or biochemical activity is apparent.

(23) The incubator 1 also has an injector unit 18 intended for release of at least one substance into the sample vessel 4. A user can therefore preferably introduce a chemical substance or a biological substance into the sample vessel 4 by the injector unit 18, for example during the performance of a program, without opening the incubator 1.

(24) The controller 8 is set up to establish an establishment of one or more biological and/or chemical and/or physical incubation conditions. The controller 8 may be set up, for example, to be able to establish one or more incubation conditions from the group of temperature, pressure, radiation, electron components, current, air humidity, acceleration, rotation and/or agitation speed, atmospheric components, pH and/or conductivity. It is thus possible by the incubator 1 to conduct different chemical reactions and/or the cultivation of different microorganisms.

(25) In order to be able to reliably inactivate a sample 7 present in a sample vessel 4 by the incubator 1, the sample inactivation device 6 may be set up to inactivate the sample 7 by one type or multiple types of inactivation method. The inactivation can be effected here preferably by physical, mechanical, thermal, chemical, biological and/or radiation-generated inactivation. The term “inactivation” may relate to killing of microorganisms, inactivation of viruses and/or rendering a chemical substance harmless.

(26) The sample inactivation device 6 may be configured, for example, as at least one device selected from the group of autoclave, hot air sterilizer, gassing unit, irradiation unit, microwave unit, electron beam unit, ultrasound unit, vacuum unit, cavitation unit, shear force unit and/or inactivator release unit, especially for release of a chemical and/or biological substance.

(27) In order to enable particularly uniform heating of a sample vessel 4 inserted into the sample vessel receiver 3, the heating device 5 has a heating sleeve 19 that lines the inside of the sample vessel receiver 3. The heating sleeve 19 therefore surrounds the sample vessel 4 in the inserted state, such that uniform release of heat is possible.

(28) The heating device 5 also has a hotplate 20 that may be disposed in a base region of the sample vessel receiver 3 and/or in the closure unit 10 of the sample vessel receiver 3.

(29) The incubator 1 has an analysis unit 21. The analysis unit 21 enables performance of an analysis as to whether an inactivation of the sample by the sample inactivation device 6 was successful. It may be particularly appropriate here when the analysis unit 21 is electronically coupled to the controller 8 and/or the safety lock 9, such that opening of the sample vessel receiver 3 is possible only in the case of successful inactivation. The safety lock 9 therefore remains closed until it has been detected by the analysis unit 21 that inactivation of the sample was successful.

(30) If a sample vessel 4 is inadvertently damaged within the sample vessel receiver 3 of the incubator 1 in such a way that sample material 7 escapes, it is possible by a sealing element that enables watertight and/or vapor-tight and/or airtight and/or pressure-tight closing of the sample vessel receiver 3 with the closure unit 10 to prevent contamination of the surrounding space and of the personnel in the vicinity.

(31) The incubator 1 has a recognition device 22 that recognizes when a sample vessel incompatible with the incubator 1 has been inserted into the sample vessel receiver 3 or a compatible sample vessel 4 has been inserted wrongly aligned. The recognition device here is thus able to prevent closure of the closure unit 10 and/or activation of the incubator 1. It is thus possible to avoid the risk of damage through the use of incompatible sample vessels or improper use of the incubator 1.

(32) The incubator 1 has an actuator device 23 that can interact with an opening element 34 and/or an opening device 37 in the sample vessel 4. The actuator device 23 may therefore be operated from the outside in order to open an inactivation capsule 34 and/or a detection capsule 25 in the sample vessel 4 when the incubator 1 is closed and/or in operation.

(33) FIG. 1 indicates a working example of a method of the invention for analysis of a sample material 7, wherein, in a first step, a sample 7 to be analyzed is transferred in a sample vessel 4. Subsequently, the sample vessel 4 is closed and introduced into the sample vessel receiver 3 of the incubator 1. The sample vessel receiver 3 of the incubator 1 is then closed by the closure unit 10 and locked by the safety lock 9. By the controller 8, it is then possible to perform an incubation program, the incubation conditions being freely adjustable or predefinable.

(34) During the performance of the incubation program, the sample 7 within the sample vessel 4 can be analyzed by a measurement apparatus 11, 28. This can serve, for example, to detect growth of microorganisms 2 in the sample 7. If, for example, the growth of the microorganisms 2 exceeds a particular limit, it is necessary to dispose of a food from which the sample has been taken.

(35) During the performance of the incubation step, it is possible to take sample material 7 from the sample vessel 4 in order to be able to undertake further analyses on a sample material 7 taken.

(36) During the performance of the incubation program and a subsequent inactivation program, the sample vessel receiver 3 of the incubator 1 is locked, such that it is not openable by a user. After the performance of the incubation step, an inactivation program is conducted in order to achieve inactivation of the sample material 7 present in the sample vessel 4.

(37) After the inactivation program has ended, the incubator 1 is unlocked, such that access to the sample vessel 4 in the sample vessel receiver 3 is possible and the sample vessel 4 can be removed.

(38) Subsequently, the sample vessel 4 can be disposed of together with the sample 7 present therein. Owing to the inactivation of the sample 7 present, the sample vessel 4 can be disposed of in domestic refuse.

(39) FIGS. 2 to 7 show a working example of a sample vessel 4 of the invention. The sample vessel 4 is intended for cultivation of microorganisms 2 and/or for performance of the chemical reaction, especially a biochemical reaction, in an incubator 1.

(40) The sample vessel 4 has a safety closure 27 by which a sample receiving chamber 26 is closable in a non-openable manner. This means that the sample receiving chamber 26, after closure by the safety closure 27, is openable only by destruction of the sample vessel 4 since opening of the sample vessel 4 after closure thereof is not envisaged. It is thus possible to prevent improper use by a user, such that compliance with the requisite safety standards is easier and the risk of contamination of man and the environment is distinctly reduced.

(41) In order to be able to use the sample vessel 4 in a maximum number of different incubation and/or inactivation programs, the sample vessel 4 is closable in a watertight and/or vapor-tight and/or airtight and/or pressure-resistant manner by the safety closure 27.

(42) The sample vessel 4 may have a stirrer apparatus, for example in the form of a magnetic stirrer bar 41. It is thus more easily possible, for example, to dissolve a dried medium 38 held in the sample vessel 4 by addition of water or another solvent.

(43) The sample vessel 4 may have a dedicated measurement apparatus 28, preferably set up for continuous performance of a measurement of at least one experimental parameter. The measurement apparatus 28 may be set up, for example, to determine one or more experimental parameters selected from the group of optical density, color reaction, impedance, pH, gas composition, especially oxygen content and/or CO.sub.2 content in liquid and/or supernatant, spectroscopic property or electrochemical property, reaction of a substrate and/or a chemical, fluorescence, luminescence, nucleic acids and/or a nucleic acid sequence, cell mass, peptides and/or proteins. The sample vessel 4 may therefore have a measurement apparatus 28 or multiple measurement apparatuses 28 from the group of lateral flow test unit, capillary electrophoresis unit, protein characterization unit, nucleic acid characterization unit, immunoassay unit, especially antibody assay unit, and/or immunobeads unit.

(44) In order to be able to introduce a chemical substance and/or a biological substance into the closed sample vessel 4, for example by an injector unit 18 of the incubator 1, the sample vessel 4 has a lock opening 29. In order to be able to prevent microorganisms from being able to escape inadvertently from the sample receiving chamber 26, the lock opening 29 has a selection device 30 for separation of microorganisms. The selection device 30 may be configured, for example, as a chemical and/or biological and/or physical selection device 30. It may be particularly appropriate when the selection device 30 takes the form of a filter, preferably a filter membrane and/or a filter resin. However, the selection device 30 may also be configured as a purifying column. The lock opening 29 is disposed in the safety closure 27 of the sample vessel 4. As apparent in FIG. 1, the lock opening 29 may be configured as a stub 42. A lock opening 29 in the form of a stub 42 may have the advantage of being guidable through an opening 12 formed in the closure unit 10 of the incubator 1 and hence, in use position, at least part of the stub 42 projects out of the sample vessel receiver 3 and/or is outside the sample vessel receiver 3. It is thus easier to perform the sample introduction and/or taking via the lock opening 29. The lock opening 29 may be closable, for example, by a seal. Alternatively or additionally, the lock opening 29 may be set up to perform a pressure equalization in the sample vessel 4. For this purpose, the lock opening 29 may have a valve, for example, especially a pressure relief valve.

(45) The sample vessel 4 has a shape adapted to the sample vessel receiver 3 of the incubator 1. It may be particularly appropriate here when the sample vessel 4 has an at least partly cylindrical configuration. The sample vessel 4 has at least one transmissive viewing window 32, such that optical measurement is possible on or in a sample material 7 present in the sample vessel 4 by a measurement apparatus 11, 28 disposed outside the sample vessel 4. The viewing window 32 is preferably formed in an outer shell 31 of the sample vessel 4.

(46) The sample vessel 4 has an inactivation capsule 24 disposed within the sample receiving chamber 26. The inactivation capsule 24 contains an inactivator 31 that may take the form, for example, of a sterilizing reagent. As a result of the actuation of an actuation device 23 in the incubator and/or an opening element 34 in the sample vessel 4, the inactivator 33 can be released from the inactivation capsule 24. The actuator device 23 here can actuate the opening element 34, such that it penetrates a capsule wall and/or opens a capsule closure 35. The opening element 34 is preferably configured as a bolt or a pin disposed within the inactivation capsule 24. The capsule wall is of flexible configuration, such that it establishes a certain puncture resistance on the one hand and easy opening is achievable by the opening element 34 on the other hand.

(47) The sample vessel 4 also has a detection capsule 25 disposed within the sample receiving chamber 26. The detection capsule 25 contains a detection device 36 for detecting a chemical and/or biological substance. It may be particularly appropriate here when the detection capsule 25 is intended for detection of an antigen and/or a nucleic acid and/or a nucleic acid sequence. The detection capsule may be openable by actuating an actuator device 23 and/or an opening device 37. By actuating the actuation device 23, it is also possible to actuate the opening device 37, such that the detection device 36 is releasable into the sample receiving chamber 26. The detection capsule 25 here has been produced from a flexible material. This has the advantage that it is puncture-resistant on the one hand and is easily openable by the opening device 37 on the other hand. The opening device 37 is preferably configured as a bolt and/or pin. It may be particularly appropriate when the detection capsule 25 includes a lateral flow test that can be introduced at least partly into the sample receiving chamber 26 by actuating the opening device 37. The detection device 36 may alternatively or additionally also be a chemical that starts a detection reaction. A detection reaction may relate here, for example, to a detectable color change.

(48) FIGS. 1 to 7 show individual method steps performable using the sample vessel 4.

(49) In FIG. 3, sample material 7 is first introduced into the sample receiving chamber 26 of the sample vessel 4.

(50) After the sample material 7 has been introduced into the sample vessel 4, the safety closure 27 is closed and locked, such that subsequent opening is no longer possible (cf. FIG. 4).

(51) As shown in FIG. 5, there is subsequently an incubation step in which ideal reaction and/or growth conditions can be established by a controller 8.

(52) FIG. 6 shows a detection step. By actuating the opening device 37, a detection device 36, especially a lateral flow assay, is initially released into the medium 38, with opening of a capsule closure 35 by actuation of the opening device 37.

(53) After performance of the detection that may result, for example, in a color change, as shown in step 7, an inactivation step is undertaken. By actuation of the opening element 34, this opens the inactivation capsule 24 at its capsule closure 35 in that the opening device 34 penetrates the capsule wall. Subsequently, the inactivator 33 present in the inactivation capsule 24 can be released into the sample receiving chamber 26 in order to inactivate the sample 7 present therein and the microorganisms 2 present therein.

(54) Subsequently, the entire sample vessel 4 can be disposed of.

(55) In order to be able to prevent the introduction of an incompatible sample vessel 4 or a compatible sample vessel 4 in the wrong alignment into the sample vessel receiver 3 of the incubator 1, the sample vessel receiver 3 has a guiding device 39, and the sample vessel 4 a compatible counterpart guiding device 40. By the guiding device 39 and the counterpart guiding device 40, it is possible to define a particular alignment of the sample vessel 4 on introduction into the sample vessel receiver 3. Thus, incorrect insertion of the sample vessel 4 into the sample vessel receiver 3 is ruled out. Especially in the case of performance of a sample vessel movement within the incubator 1, in the event of improper insertion of the sample vessel 4 into the sample vessel receiver 3, there may be damage to the sample vessel 4 and hence escape of sample material.

LIST OF REFERENCE NUMERALS

(56) 1 incubator 2 microorganism 3 sample vessel receiver 4 sample vessel 5 heating device 6 sample inactivation device 7 sample/sample material 8 controller 9 safety lock 10 closure unit 11 measurement apparatus 12 opening 13 selection device 14 viewing window 15 optical sensor 16 shaker/stirrer unit 17 detection device 18 injector unit 19 heating sleeve 20 hotplate 21 analysis unit 22 recognition device 23 actuator device 24 inactivation capsule 25 detection capsule 26 sample receiving chamber 27 safety closure 28 measurement apparatus 29 lock opening 30 selection device 31 outer shell 32 viewing window 33 inactivator 34 opening element 35 capsule closure 36 detection device 37 opening device 38 medium 39 guiding device 40 counterpart guiding device 41 magnetic stirrer bar 42 stub