Sampling device

Abstract

The invention relates to a sampling device for taking a liquid sample from a container, comprising a container receiving device and a heating device, wherein the container receiving device is designed to be suitable for receiving a container, wherein the heating device is designed such that, after receiving the container, a planar partial area of ​​the container wall can be heated in the container receiving device, wherein, during heating, the planar partial area is exclusively adjacent to a gas phase in the container interior, so that when the planar partial area is heated, the gas phase is heated, causing the liquid sample to exit the outlet by heating the gas phase.

Description

[0001] The present invention relates to a sampling device for taking liquid samples from liquids from a container.

[0002] There are numerous technical solutions for extracting liquid samples from containers. Often, the liquid sample is drawn from the container using pumps. Particularly in medical diagnostics, it is essential to extract liquid samples from blood cultures in a largely automated manner. These samples are then subjected to various diagnostic procedures, such as mass spectrometry or microbiological detection methods. Blood cultures are frequently prepared in large numbers. For this purpose, blood culture bottles, which typically already contain a culture medium, are filled with a patient's blood sample. Blood cultures are used for numerous analyses, necessitating repeated extraction of liquid samples. However, sampling from blood culture containers, especially blood culture bottles, is cumbersome.

[0003] Blood culture bottles often contain added macroscopic, spherical particles intended to adsorb antibiotics. However, these particles sediment and complicate sample collection. Furthermore, blood culture samples are frequently not homogeneous liquids but rather suspensions containing, for example, cells such as red blood cells or microorganisms. These samples are also often infectious, requiring contamination-free and safe processing due to the safety risk. Therefore, single-use components that come into contact with the blood sample are often preferred. Additionally, biological samples or cultures, such as blood cultures, are heat-sensitive. Given the large number of samples in the medical diagnostic field, cost-effective sample collection devices are also preferable in practice.

[0004] Document WO2010132829A2 discloses, among other things, a device for taking blood culture samples from blood culture bottles using a robot and a (vacuum) pump, which is connected via tubing to a disposable sampling unit. The tubing also includes a filter to prevent contamination of the pump. The disposable sampling unit is also designed to penetrate the septum of the blood culture bottle.

[0005] Another common method of taking samples from a container with an outlet is to allow the liquid sample to escape from the outlet by turning the container upside down and using gravity.

[0006] However, it has been shown that using pumps to draw samples from containers, especially blood culture bottles, is disadvantageous. Besides the significant equipment costs, additional precautions are necessary to prevent contamination of the liquid sample itself and the surrounding environment.

[0007] Furthermore, it has been shown that simply inverting the container does not reliably dispense the liquid sample, particularly blood cultures, using gravity or hydrostatic pressure. Either the flow of the liquid sample is not reliably controllable, and / or it stops after a short time due to the development of a vacuum. This method is especially unreliable when the size of the outlet changes, the liquid composition and / or viscosity varies, the fill volume differs, the temperature varies, the exact orientation of the container is affected, and many other factors are present. Particularly with blood cultures, viscosity often varies, which influences the flow rate and duration of the liquid sample from the outlet.In particular, the flow of liquid blood culture samples often stops after a short time due to the development of a vacuum in the container. Therefore, this method is not suitable for reliable sample collection, especially from blood culture bottles.

[0008] The object of the invention is to overcome the described disadvantages of the prior art and, in particular, to provide an alternative sampling device for taking samples of a liquid from a container, especially blood culture samples from a blood culture bottle, which does not require a pump for sampling. Furthermore, it is an object of the invention to provide a pump-free method for taking a liquid sample from a container, especially blood culture samples from a blood culture bottle, using this sampling device, which overcomes the described disadvantages of the prior art. Finally, it is an object of the invention to provide a simple sample preparation device for preparing a liquid sample from a container for subsequent analyses, comprising this sampling device.

[0009] The problem is solved by a sampling device having the features of independent claims 1 and 3, by a method for taking a liquid sample having the features of claim 19, and by a sample preparation device having the features of claim 20. Advantageous embodiments can be found in the dependent claims.

[0010] According to the invention, a sampling device for taking a liquid sample from a container comprises a container, wherein the container has an interior space partially enclosed by a container wall, wherein the container has an outlet, wherein the interior space contains the liquid alongside a gas phase, a container receiving device, and a heating device, wherein the container receiving device is designed to accommodate the container, and wherein the heating device is designed such that, after the container has been received, a planar portion of the container wall can be heated in the container receiving device, wherein during heating the planar portion is exclusively adjacent to the gas phase on the inside of the container interior, so that when the planar portion is heated the gas phase,so that the liquid sample exits the outlet due to the heating of the gas phase.

[0011] Surprisingly, it has been shown that by heating the flat section of the container wall that borders the gas phase on the inside but not the liquid, the gas phase in the container can be selectively heated, and sufficient overpressure can be generated to allow for the controlled release of the liquid sample. Surprisingly, when the gas phase is heated, the liquid is essentially not heated, or at least not significantly. Thus, the gas phase is heated selectively. This simultaneously prevents overheating of the liquid, particularly a blood culture, allowing it to be used for further detection methods, such as AST, which requires viable microorganisms. This is particularly advantageous for the duration of the sample collection.

[0012] The liquid is in liquid communication with the outlet, especially during heating.

[0013] Preferably, the heating device is designed such that, after the container is received, only the flat portion of the container wall within the container receiving device can be heated. More preferably, the heating device heats mainly or essentially exclusively this flat portion. The container wall outside this flat portion (the surrounding area of ​​the container wall) preferably receives only indirect heat input. For this purpose, the heating device is preferably directed at the flat portion or makes contact with it on one side (the outside). Most preferably, the heating device makes contact exclusively with the flat portion during heating.Preferably, the heating device is designed such that the container wall outside the flat area (surrounding area of ​​the container wall) is essentially not heated after the container is inserted. The entire container or the entire container wall is explicitly not heated. The flat area is preferably not heated above 80°C. Preferably, the flat area is heated above 50°C. Preferably, the flat area is heated for less than 2 minutes. Particularly preferably, the flat area is heated for less than 1 minute. The heating is therefore not intended for the incubation of a liquid or culture.

[0014] During heating, only a partial area of ​​the container, in particular a partial area of ​​the container wall, especially the flat partial area of ​​the container wall, is heated by means of the heating device.

[0015] When the flat section is heated, heat is directly transferred to the gas phase. Thus, heating this flat section inside the container primarily heats the gas phase. The gas phase is preferably heated to a temperature between 50°C and 90°C. Due to the heating, the gas phase expands, creating overpressure in the container, which causes the liquid to flow out of the outlet. The flow of the liquid sample is preferably controllable by the heating process. A further advantage is that no air is introduced during sample collection because of the overpressure. This ensures that the liquid, particularly the blood culture, remains uncontaminated.

[0016] Preferably, the gas phase predominantly consists of the ambient air composition, a gas composition required for microorganism cultivation, or, in particular, a gas composition generated by microorganism cultivation. Preferably, the gas phase comprises at least 20% of the container interior. More preferably, the gas phase comprises at most 70% of the container interior.

[0017] After sampling, the liquid sample is preferably used for subsequent sample preparation and / or diagnostics – for example, for mass spectrometric measurements. The volume of the liquid sample is preferably unlimited and can comprise substantially the entire volume of the liquid. A sample volume of less than 20 mL is particularly preferred, and more preferably less than 5 mL, and furthermore, less than 2 mL. The smaller the sample volume, the gentler and faster the sampling process, since the liquid sample typically emerges from the container in the form of drops during sampling, and larger sample volumes require more time.

[0018] The container is preferably not part of the claimed subject matter. The container preferably has a pressure-resistant and / or rigid wall. This prevents significant deformation of the container at typical process pressures. In the claimed method and device, heating creates an overpressure that assists and / or causes the liquid sample to exit the container. This overpressure is therefore heat-induced. Overpressure means that the pressure inside the container is higher than the ambient pressure outside. Preferably, there is no overpressure before heating. The maximum overpressure during heating is preferably <2 bar, more preferably <0.5 bar. The minimum overpressure during heating is preferably >0.4 bar, more preferably >0.2 bar, and particularly preferably >0.1 bar. Preferably, an overpressure is present for the entire duration of the sampling process.Preferably, the container is a culture container for liquid cultures. More preferably, the container is a blood culture container. Particularly preferably, the container is a blood culture bottle. The container may contain added sedimentable macroscopic particles. In particular, the container, especially the blood culture bottle, may contain resin particles as added sedimentable macroscopic particles. Blood culture containers preferably include all containers suitable for culturing blood cultures. This includes containers made of plastics, polymers, or glass. In particular, the containers are preferably designed to be suitable for contamination-free cultivation. The container is partially filled with the liquid, such that a portion of the container's interior contains the gas phase (head region).Preferably, the container is filled with liquid to a maximum of 80%, more preferably, the container is filled with liquid to a maximum of 70%, more preferably, the container is filled with liquid to a maximum of 60%, more preferably, the container is filled with liquid to a maximum of 50%.

[0019] The heating device preferably comprises at least one heating element. The heating element can be, for example, a heating surface (e.g., a heating film), a heating block, or a directed hot air blower. Furthermore, the heating device can also include a support layer on the heating surface. It is explicitly not required that all components of the heating device (such as electrical wiring, power supply, control unit, etc.) be arranged together with the heating element within the heating device. Thus, the heating device is preferably primarily the heating element. Moreover, the heating device is explicitly not used for incubating the liquid or sample.

[0020] Preferably, only the flat area is heatable. By heating primarily or exclusively the flat area that borders the gas phase on the inside, the gas phase is primarily heated. The liquid is essentially not heated. It may only experience indirect heat input from the gas phase and / or from container wall areas outside the flat area, which are not themselves heated and only receive indirect heat input from the heated flat area. This indirect heat input into the liquid is insignificant over the duration of the sampling process. Thus, the liquid is preferably only heated insignificantly by indirect heat input during sampling. Consequently, the liquid and the gas phase in the sampling device exhibit different temperature increases during sampling.Preferably, the liquid and its constituent components, such as cells, are not damaged by any non-significant temperature increases in the liquid due to indirect heat input. Minor temperature increases in the liquid due to indirect heat input, for example from the gas phase, are preferably non-significant temperature increases that do not cause any damage to the liquid or its constituent components, such as cells. The liquid can therefore be reused for further analyses, for example in clinical blood diagnostics. For instance, it is essential not to damage blood cultures during sample collection, as they are frequently used for a number of other diagnostic procedures. This also ensures that the liquid sample remains undamaged.

[0021] The planar section comprises a portion of the container wall. Specifically, the planar section does not comprise the entire container wall or the entire container. The planar section is preferably the portion of the container wall toward which the heating element is directly directed or to which the heating element makes contact on one side (the outside). The planar section preferably extends over the entire thickness of the container wall from the outside to the inside of the planar section. Preferably, the planar section is a portion of the container wall of the blood culture bottle body. The planar section preferably has an area of ​​less than 70%, more preferably less than 50%, and most preferably less than 35% of the total surface area of ​​the container wall or the total surface area of ​​the blood culture bottle body.The flat section preferably comprises more than 5%, more preferably more than 15%, and most preferably more than 25% of the total surface area of ​​the container wall or the total surface area of ​​the blood culture bottle body. In particular, the size of the flat section is preferably selected such that the liquid does not contact the inside of the flat section during heating, i.e., for example, in a second position. Most preferably, in the second position, the inside of the flat section is bordered exclusively on the gas phase.

[0022] Preferably, the heating device is designed and arranged such that the liquid remains below a critical temperature during heating, at which, for example, microorganisms in the liquid would be damaged to such an extent that they would no longer be capable of division. This ensures that further relevant analyses, in particular blood cultures, can be performed on the liquid. Preferably, the heating device is configured such that the temperature of the liquid remains below 39°C during heating. This prevents damage to analytes, cells, viruses, and / or microorganisms.

[0023] The sampling device is a pump-free device. Furthermore, the sampling device has the advantage that no negative pressure is created when the liquid sample is dispensed during sampling, which would otherwise impede the flow of the liquid sample.

[0024] The liquid sample exits the outlet due to the overpressure generated in the container by the heating of the gas phase. This overpressure is heat-induced and can be controlled, among other things, by adjusting the heating temperature, heating time, and / or the size of the area being sampled. Preferably, the container has exactly one outlet. Furthermore, the sampling device is preferably automated or semi-automated.

[0025] Preferably, the liquid is a liquid culture, the container is a culture container, the container wall is a culture container wall, the container interior is a culture container interior, and the container receiving device is a culture container receiving device.

[0026] Particularly preferred is the liquid a liquid blood culture, the container a blood culture container, the container wall a blood culture container wall, the container interior a blood culture container interior, and the container receiving device a blood culture container receiving device.

[0027] Particularly preferred is the blood culture container a blood culture bottle, the container wall a blood culture bottle wall, the container interior a blood culture bottle interior, and the container receiving device a blood culture bottle receiving device.

[0028] Preferably, the sampling device for taking a liquid sample from a liquid blood culture from a blood culture container comprises, the blood culture container having an interior partially enclosed by a wall, the blood culture container having an outlet, the interior containing the liquid blood culture alongside a gas phase, a receiving device for the blood culture container, and a heating device, the receiving device being designed to accommodate the blood culture container, and the heating device being designed such that, after the blood culture container has been received, a flat portion of the wall of the blood culture container can be heated in the receiving device, the flat portion being adjacent to the gas phase on the inside of the blood culture container during heating.so that when the flat area is heated, the gas phase is warmed, causing the liquid sample to exit the outlet due to the heating of the gas phase.

[0029] In a preferred embodiment, the container receiving device is pivotably arranged about a pivot axis A in the sampling device. Pivoting allows for temporary and / or reversible liquid communication between the liquid and the outlet. Furthermore, if the container is pivoted such that the outlet is substantially below the liquid surface and in liquid communication with the liquid, the exit of the liquid sample is facilitated by generating a hydrostatic pressure in addition to the heat-induced overpressure, which assists the exit of the liquid sample from the outlet.

[0030] The liquid sample exits primarily due to the overpressure in the container caused by the heating of the gas phase. Additionally, the hydrostatic pressure generated by swirling also contributes to the liquid sample's exit, depending on the swirling angle. Crucially, swirling creates a connection between the liquid and the outlet, allowing the liquid sample to escape. Furthermore, swirling separates the gas phase from the outlet in the second position. This means that the overpressure generated by the heating of the gas phase can only escape, stagnate, or decrease by the release of the liquid sample. The gas phase itself cannot escape (at least not while the liquid level is high enough that the outlet is below the liquid's surface).

[0031] Alternatively, the problem is solved according to the invention by comprising a sampling device for taking a liquid sample from a container, wherein the container has an outlet and a container wall, a container receiving device for receiving the container, and a heating device for heating a planar portion of the container wall, wherein the container receiving device is pivotably arranged about a pivot axis A in the sampling device. This allows the gas phase to be selectively heated in a simple manner, while the liquid remains essentially unheated. The resulting overpressure is sufficient for the liquid sample to exit the outlet. By pivoting the container, temporary liquid communication between the liquid and the outlet can be easily established, thereby allowing for additional control of the liquid sample's exit.Furthermore, the hydrostatic pressure, in addition to the overpressure, assists in sample collection. Preferably, the sample collection device includes a heating element for heating only a specific area of ​​the container wall.

[0032] Although this is an alternative device, the described features correspond, where present, to the features of the previously described device.

[0033] In a preferred embodiment, the container has an interior space partially enclosed by a container wall. The interior space preferably contains a liquid alongside a gas phase. The container wall preferably comprises a planar portion.

[0034] Although this is an alternative device, the described features correspond, where present, to the features of the previously described device.

[0035] Preferably, the flat area does not border the liquid on its inner side during heating by the heating device, so that when the flat area is heated, the liquid is essentially not heated and / or there is essentially no direct heat input into the liquid. This prevents the liquid from heating up or heating up to the same extent as the gas phase, thus preventing damage to components of the liquid, such as cells or bacteria. Indirect heat input into the liquid is possible via heat transfer from the gas phase to the liquid and / or via areas of the container wall surrounding the flat area and / or via areas of the container wall adjacent to the flat area.However, indirect heat input does not lead to a significant increase in the temperature of the liquid, or only to a slight increase in the temperature of the liquid.

[0036] In a further preferred embodiment, the planar section borders the gas phase on the inside of the container during heating by means of the heating device. Preferably, the planar section borders exclusively on the gas phase on the inside of the container.

[0037] This allows the gas phase to be selectively heated in a simple manner. Furthermore, the liquid sample can then exit the outlet by heating the gas phase.

[0038] Preferably, heating the flat section results in a direct heat input into the gas phase. The liquid itself does not heat up significantly. The heating device is preferably designed to ensure that this direct heat input into the gas phase occurs as quickly as possible. The temperature is selected, among other things, to prevent damage to the container wall. During heating, the gas phase is heated to a temperature that creates an overpressure in the container, causing the liquid to drip from the outlet. The dimensions of the heating device and the heating temperature can depend on factors such as the thickness of the container wall, the size of the gas phase, the container wall material, and / or the temperature sensitivity of the liquid. Preferably, the container wall outside the flat section is not heated, or only minimally heated, by indirect heat input from the flat section.The heating process preferably comprises only the direct heat input from the heating device into the gas phase via the flat section. Preferably, the flat section is designed such that the directly surrounding area of ​​the container wall, for example up to a distance of 0.5–5 cm from the flat section, also borders the gas phase on the inside. This prevents the liquid from being heated by an unintentional indirect heat input from the container wall outside the flat section, which borders the liquid on the inside.

[0039] In a further preferred embodiment, the heating device is configured such that, after the container has been received, it can make contact with the flat portion of the container, particularly in a second position. In this configuration, the heating device is preferably only able to make contact with the flat portion of the container after the container has been received, particularly in the second position. It is particularly preferred that the heating surface is essentially completely in contact with the flat portion of the container wall, particularly in the second position.

[0040] This means that the heating device preferentially heats the flat area via direct contact – for example, by means of a heating surface. This has the advantage that areas outside the flat area and any liquid adjacent to the gas phase do not receive direct heat input and are therefore essentially not heated, or only heated to a negligible degree. This, in turn, ensures that essentially only the gas phase is heated by direct heat input. The liquid does not receive any direct heat input.

[0041] In a further preferred embodiment, the heating device comprises a heating surface for heating the planar portion of the container. A heating film is particularly preferred. By heating over a larger area, the gas phase can be heated particularly efficiently. Preferably, the heating surface has a low heat capacity. This results in fast response times, which simplifies sample extraction. For example, by using a heating film, the heat storage capacity can be reduced due to its thinness. The heating surface and / or the heating film thus have the advantage that the required heating temperature is reached quickly and dissipates rapidly after being switched off. Preferably, the heating surface has a thickness of less than 5 mm, or particularly preferably less than 2 mm.

[0042] In a further advantageous embodiment, the heating element, particularly when in contact with the flat area, can be designed to be essentially form-fitting to that flat area. This has the advantage that the heat transfer from the heating element to the flat area is particularly efficient.

[0043] Preferably, the heating device includes a heating surface that is designed to be flexible in shape. This allows the heating device to easily adapt to the shape of the container wall when pressed against it.

[0044] The heating device preferably comprises at least two layers, wherein a first layer is a flexible heating surface, and wherein a second layer is a support layer that is particularly autoreversible and compressible. The heating surface can be, for example, a heating film or another heating element. The support layer preferably has a heat capacity that is lower than that of metals. Preferably, it has heat-insulating properties. Preferably, the support layer consists of a polymer, such as neoprene. A low heat capacity is advantageous for easy temperature control during heating.

[0045] According to an advantageous embodiment of the invention, the container receiving device can be pivoted about the pivot axis A into a first position suitable for inserting and removing the container and into a second position suitable for removing the liquid sample. Preferably, the outlet is in liquid communication with the liquid in the second position. This allows the container to be easily inserted or removed in the first position, and simplifies the removal of the liquid sample in the second position. Preferably, the outlet, in particular a sample outlet device forming the outlet, is in liquid communication with the liquid in the second position, and the liquid sample can exit the outlet, especially during heating.

[0046] Preferably, in the second position, no liquid borders the flat area on the inside. Preferably, the sampling device is configured and the heating device is arranged such that the flat area of ​​the container wall, particularly exclusively, can be heated by the heating device in the second position.

[0047] Furthermore, it is preferred that the container receiving device is designed such that the container cannot be removed from the receiving device in the second position. This enables contamination-free and safe use of the device.

[0048] The sample outlet device serves to extract the sample, i.e., a portion of the liquid, from the container. Preferably, the sample outlet device is reversibly arranged on the container. This allows the sample outlet device to be attached and removed as needed. Preferably, the sample outlet device includes the outlet, or more preferably, the sample outlet device is the outlet itself. Furthermore, the sample outlet device preferably penetrates a septum. The septum preferably closes an opening in the container. The septum is preferably part of a container closure.

[0049] Preferably, the pivot axis A runs horizontally. Furthermore, it is preferred that in the first position, a longitudinal axis a of the container receiving device is aligned at a first pivot angle to the horizontal. Preferably, this first pivot angle is negative.

[0050] Preferably, in the second position, the longitudinal axis a of the container receiving device is aligned at a second pivot angle to the horizontal. Preferably, the second pivot angle is positive.

[0051] In a further preferred embodiment, the heating device is arranged such that it contacts the container in the second position. Preferably, the heating device contacts the container exclusively in the second position. In a further preferred embodiment, the heating device is arranged such that it contacts the flat portion of the container wall in the second position. Particularly preferably, the heating device contacts the flat portion of the container wall exclusively in the second position.

[0052] This allows the liquid sample to exit the outlet only in the second position after heating. Swiveling the device into the first position disconnects it from the container. In particular, this arrangement ensures that the flat section never comes into contact with the liquid on the inside during heating, and / or not in the first position. Heating is thus interrupted by swiveling the device into the first position.

[0053] In a further advantageous embodiment, the heating device is arranged on the container receiving device. This ensures that the heating device, in particular the heating surface, is securely positioned on the container, especially the flat section, before, for example, the outlet comes into contact with the liquid.

[0054] This simplifies the heating of the flat sub-area.

[0055] In a further preferred embodiment, the container receiving device has a longitudinal axis a. In the first position, the longitudinal axis a of the container receiving device preferably has a first pivot angle about the pivot axis A, wherein the first pivot angle is selected such that the liquid cannot escape from the outlet. In the second position, the longitudinal axis a of the container receiving device preferably has a second pivot angle about the pivot axis A, wherein the second pivot angle is selected such that the liquid can escape from the outlet. This allows the release of the liquid sample to be easily controlled, and also enables the safe insertion and removal of the container, i.e., for example, without unintentional leakage of the liquid.Furthermore, it is preferred that the container receiving device is pivotable to at least the two pivot angles (α, β) about the pivot axis A and that the pivot axis A runs in the horizontal, wherein in the first position the longitudinal axis a of the container receiving device is aligned in the first pivot angle to the horizontal, wherein in the second position the longitudinal axis a of the container receiving device is aligned in the second pivot angle to the horizontal.

[0056] Preferably, in the first position, the liquid is not in contact with the outlet, and in the second position, it is in contact with the outlet. In particular, the first swivel angle is chosen such that the liquid is not in contact with the outlet. This prevents liquid from escaping and potentially contaminating the container when it is inserted or removed. In particular, the second swivel angle is chosen such that the liquid is in contact with the outlet. This allows the liquid sample to exit the outlet during heating.

[0057] Preferably, the second swivel angle is selected such that any potentially present added sedimentable macroscopic particles in the liquid settle in the container in such a way that the added sedimented macroscopic particles do not impede the liquid's exit from the outlet. Preferably, the macroscopic particles settle particularly in the blood culture bottle body and / or in the shoulder of the blood culture bottle and / or in a container body, so that they do not impede the liquid's exit from the outlet. This ensures reliable sample collection, especially with blood culture bottles. Preferably, the first swivel angle is between 0° and -180°, more preferably between -30° and -90°, and most preferably between -60° and -70°.Preferably the second swivel angle is between +1° and +90°, more preferably between +10° and +89°, more preferably between +10° and +40°, and particularly preferably between +15° and +25°.

[0058] The choice of the optimal first and second swivel angles depends in particular on the fill level of the container, whether the container contains added sedimentable macroscopic particles that could impede the flow of the liquid sample from the outlet, and / or on the arrangement and / or design of the heating device. For the two standard types of blood culture bottles commonly used, with added sedimentable macroscopic particles (see...), Fig. 6a and Fig. 6d) The preferred swivel angle range for the second swivel angle is +15° to +25°. This is advantageous because, particularly within this swivel angle range, the added macroscopic particles sediment so reliably that the flow of the liquid sample from the outlet is not obstructed. The second swivel angle can therefore also depend on the size and shape of the blood culture bottle, the length of the outlet extending into the blood culture bottle, and the amount of added sedimentable macroscopic particles. Furthermore, a swivel angle range of -30° to -90° for the first swivel angle is preferred, as the blood culture bottle can be easily and safely inserted into and removed from the container holding device (blood culture bottle holding device) within this swivel angle range.

[0059] In a further preferred embodiment, the container receiving device comprises a first and a second element. The first element is pivotably arranged about the pivot axis A for pivoting the container receiving device about the pivot axis A, and the second element is movably arranged on the first element. Thus, this preferred embodiment represents at least a two-part container receiving device. This allows for the simple implementation of a locking mechanism. This has the advantage that the container can be easily inserted and removed while still being secured. Furthermore, the heating device can thus easily make positive contact with the container.

[0060] In a further advantageous embodiment, the second element is movably arranged on the first element by pivoting it about a pivot axis B on the first element. This is a particularly simple and stable way to implement a locking mechanism. The pivot axis B can be located on the first element.

[0061] In a further advantageous embodiment, the container can be inserted into and removed from the container receiving device by moving the second element into an open position, whereas the container cannot be removed by moving the second element into a closed position. This prevents the container from being removed from the container receiving device, for example during sampling, and thus prevents the surrounding area from being contaminated with liquid.

[0062] According to a further advantageous embodiment of the invention, the sample outlet device, which forms the outlet for the liquid sample from the container, can be arranged on the container. Particularly preferably, the sample outlet device is arranged reversibly on the container. This allows the outlet to be removed from or attached to the container as needed. This is advantageous for contamination-free operation. Furthermore, blood culture bottles, in particular, can be incubated without an outlet and only equipped with one for sample collection.

[0063] In a further preferred embodiment, the container receiving device includes a centering device which aligns the container and / or the sample outlet device, particularly in the closed position. This ensures that the sample exiting the sample outlet and / or the sample outlet device is reliably received in an interchangeable sample container and does not miss the interchangeable sample container and contaminate the surroundings.

[0064] According to a further advantageous embodiment, the centering device can be configured such that the pivot axis B is displaceable and shifts during pivoting. This shift allows the container receiving device to accommodate containers of different dimensions. Preferably, the pivot axis is displaceable such that a radial pivoting movement is superimposed on a lateral shift. The alignment of the container is further supported by the additional lateral movement of the second element during radial pivoting. The centering device preferably includes a sliding arrangement for this purpose. This sliding arrangement is preferably located on the second element and / or is part of the second element. It is particularly preferably arranged in close proximity to the underside of the container base.Preferably, the centering device is arranged such that closing the container receiving device by pivoting the second element about the movable pivot axis results in a lateral displacement of the sliding assembly and thus a lateral displacement of the container. Preferably, the centering device also includes an alignment arrangement. This is preferably arranged on the first element. The alignment arrangement can serve as a counterpiece. Preferably, it is arranged such that when the container receiving device is closed and the container is subsequently laterally displaced, it is pressed into the alignment arrangement, aligning the container and / or the sample outlet device, and thus, in particular, the outlet. The centering device therefore preferably comprises the movable pivot axis B, the sliding assembly, and the alignment arrangement.

[0065] In a further preferred embodiment, the sampling device comprises a sample receiving unit for accommodating the exchangeable sample container. The exchangeable sample container is preferably configured to receive the liquid sample from the outlet. The sample receiving unit is preferably arranged and configured such that the exchangeable sample container is positioned and oriented to receive the liquid sample from the sample outlet and / or the outlet. By aligning the exchangeable sample container, the sample receiving unit ensures that the opening of the exchangeable sample container is always located in the same position. The exchangeable sample container can be, for example, an Eppendorf cup or a comparable vessel, a Falcon tube, or a 96-well plate. The exchangeable sample container can also be a mass spectrometric sample carrier.Preferably, the sample receiving device includes a level sensor for determining the fill level of the interchangeable sample container. This level sensor can be, for example, a photoelectric sensor, a weight sensor, or a capacitive sensor.

[0066] The problem is further solved by a method for taking a liquid sample from a container using the sampling device, wherein the container has an interior space partially enclosed by a container wall, wherein the container has an outlet, and wherein the interior space contains the liquid alongside a gas phase, comprising a first step in which the container is positioned in the container receiving device of the sampling device such that the container is oriented at a first pivot angle to the horizontal such that the liquid cannot escape from the outlet; a further step in which the container receiving device of the sampling device is pivoted about a pivot axis A to a second pivot angle to the horizontal such that the liquid has contact with the outlet in such a way that the liquid can escape from the outlet;a subsequent step in which the heating device of the sampling device heats a flat section of the container wall, wherein the flat section on the inside of the container is exclusively adjacent to the gas phase, so that the gas phase is heated and the liquid sample exits from the outlet.

[0067] The process allows for pump-free extraction of the liquid sample from the container. Furthermore, the process is controllable and reliable.

[0068] Preferably, the process is carried out semi-automatically or fully automatically by the sampling devices described above. Preferably, the container has an opening which is closed with a septum. Preferably, to create the outlet on the container, the septum is pierced by the sample outlet device, or more precisely, by a part of the sample outlet device. This allows the liquid sample to be easily extracted, and the container to be resealed by removing the sample outlet device. The liquid sample exits primarily due to the overpressure in the container caused by the heating of the gas phase. Furthermore, the hydrostatic pressure generated by swiveling also contributes to the exit of the liquid sample, depending on the swivel angle.Crucially, the swiveling action requires two key elements: first, it creates a liquid-to-speech connection between the liquid and the outlet, allowing the liquid sample to flow out. This ensures the container can be inserted into or removed from the sample receiving device without contamination, as liquid-to-speech communication only occurs in the second swivel position. Second, the second swiveling action is crucial because the liquid separates the gas phase from the outlet. This prevents the overpressure generated by heating the gas phase from escaping, stagnating, or decreasing through the release of the liquid sample. The gas phase itself cannot escape. Preferably, the heating of the flat section can only occur after the container receiving device has been swiveled to a second angle.The sampling device preferably comprises a control unit and a measuring device, wherein the measuring device detects the second swivel angle and the control unit enables the heating of the flat sub-area. Preferably, the liquid is not substantially heated during the heating of the flat sub-area.

[0069] The problem is further solved by a sample preparation device for preparing a liquid sample from a container comprising one of the sample extraction devices described here, a pipetting device, a control device for controlling the pipetting device, and a device for receiving further sample containers.

[0070] The pipetting device can thus receive the liquid sample taken from the sampling device and pipette it into further sample containers for further processing.

[0071] Preferably, the sample preparation device is automated or semi-automated. Preferably, the sample preparation device is configured to process blood culture samples from blood culture bottles. Additionally, the sample preparation device preferably includes a device for receiving mass spectrometric sample carriers. Preferably, the sample preparation device provides mass spectrometric sample carriers with processed samples, in particular extracted and processed blood culture samples, for measurement with a MALDI-TOF mass spectrometer.

[0072] The problem is further solved alternatively by an alternative device for the controllable release of a liquid from a container, wherein the container is configured to receive and hold the liquid, and the container has a fill level such that the container has a gas phase in the form of a head region above the surface of the liquid, and the container has a sample outlet device with an outlet for the liquid to escape from the container, comprising a container receiving device for receiving, holding and positioning the container, wherein the container is oriented in the container receiving device such that the liquid is arranged between the gas phase in the form of a head region and the outlet and there is liquid communication between the liquid and the outlet;A heating device configured and arranged such that it transfers heat to the container in such a way that the heat is substantially received by the gas phase of the head region of the container, and the heat is substantially not received by the liquid, causing the gas phase of the head region of the container to expand and create an overpressure in the container relative to the ambient pressure outside the container, the overpressure forcing the liquid out of the outlet.

[0073] The problem is further solved alternatively by an alternative device for the controlled discharge of a liquid from a container, wherein the container is configured to receive and hold the liquid, and the container has a fill level such that the container has a head region in the form of a gas phase above the surface of the liquid, and the container has a sample discharge device with an outlet for the liquid to discharge from the container, comprising a container receiving device for receiving, holding and positioning the container, wherein the orientation of the container can be changed by means of the container receiving device such that in a first position the head region with its gas phase is arranged between the liquid and the outlet and there is no liquid communication between the liquid and the outlet.and such that in a second position the liquid is arranged between the head region with its gas phase and the outlet, and liquid communication exists between the liquid and the outlet; a heating device configured and arranged such that it transfers heat to the container in such a way that, in the second position, the heat is substantially received by the gas phase of the head region of the container, and substantially not received by the liquid, causing the gas phase in the head region of the container to expand and generate an overpressure in the container relative to the ambient pressure outside the container, the overpressure forcing the liquid out of the outlet.

[0074] Definitions: • The gas phase is located above the liquid. Preferably, the gas phase is the air space above the liquid in the container. The gas phase thus preferably forms a headspace in the container. The headspace is therefore a liquid-free space. The gas phase is not part of the liquid, culture, or blood culture. • The liquid is the liquid phase in the container – preferably with its components. The liquid may contain dissolved and undissolved components. The liquid may be a suspension. The liquid may contain microscopic and / or macroscopic particles. Preferably, macroscopic particles are visible to the naked eye. Furthermore, the liquid may, in particular, contain cells, microorganisms, and / or viruses. Preferably, the liquid is a liquid culture medium, preferably containing cells. Particularly preferably, the liquid is a blood culture. The terms liquid blood culture and blood culture are used interchangeably here. Solid culture media are excluded according to the invention. The (liquid) blood culture comprises a mixture of culture medium and a blood sample. The blood sample may, for example, be a whole blood sample. The blood sample preferably originates from patients.It should not be confused with the liquid sample taken from the container. Preferably, the blood culture has been incubated before the liquid sample is taken, for example, in an external incubator. The blood sample is preferably added to the blood culture container before cultivation / incubation, particularly before sampling. This allows any microorganisms potentially present in the blood sample to multiply before sampling. Alternatively, the blood sample can also be a prepared or pre-processed blood sample. Alternatively, a cerebrospinal fluid sample, biopsy sample, wound exudate sample, or tissue sample can be added to the culture medium instead of the blood sample. The blood culture does not include the gas phase in the blood culture container. Added sedimentable macroscopic particles are preferably not part of the liquid.For the purposes of this application, added sedimentable macroscopic particles preferably do not include components of the blood sample, such as cells, but rather, in particular, polymer or resin particles that have been added alongside the blood sample, for example, for the adsorption of antibiotics into the blood sample, or that were already present in the container. Specifically, added sedimentable macroscopic particles are particles that can obstruct or clog the outlet of the container. Specifically, added sedimentable macroscopic particles are artificial particles, for example, made of resin or a polymer. • The liquid sample is a sample taken from the container. The liquid sample is a subset of the liquid. Therefore, the liquid sample is preferably a portion of the liquid that is extracted from the liquid in the container. For this purpose, the liquid sample exits the outlet (due to the generated overpressure and / or hydrostatic pressure). The liquid sample can thus comprise dissolved and undissolved components, in particular cells or viral particles. Specifically, it can contain dissolved and undissolved components of the blood sample and / or microorganisms. Preferably, the liquid sample is a suspension. The liquid sample is preferably largely liquid. Preferably, it does not include any added sedimentable macroscopic particles. • Sampling is preferably synonymous with sample dispensing. Sampling is particularly preferably the discharge of the liquid sample from the outlet. The discharge of the liquid sample occurs due to the overpressure in the container, preferably supported by hydrostatic pressure in the container due to its orientation. Sampling therefore does not include sampling using a vacuum. For example, sampling using syringes and pumps is excluded. The sampling device is preferably designed without a vacuum and / or without a pump. The liquid sample remains in a liquid state at all times during sampling. It does not evaporate. • The expression “liquid alongside a gas phase” preferably means that both phases, the liquid and the gas phase, are in the same container and adjacent to each other. It preferably does not mean that the two phases are positioned laterally relative to each other (side by side). Instead, both phases are preferably always arranged one above the other. Due to density and gravity, the gas phase is always positioned above the liquid. • The liquid communication is preferably a flow connection. It is particularly preferred that it be a flow connection between the liquid and the outlet. Thus, the liquid communication is also preferably a flow connection between the liquid in the container and the environment outside the container. • Direct heat input preferably involves heat transfer from and / or across the heated flat section(s) of the container to the respective phase (liquid or gas) that is adjacent to – i.e., in contact with – the heated flat section of the container wall on the inside. Thus, heat transfer occurs from the outside of the flat section of the container wall to the inside of the flat section of the container wall, and from there into the adjacent phase (liquid or gas). This phase is specifically the gas phase when the container receiving device is in the second position. Direct heat transfer to the gas phase therefore occurs through heat transfer via the material of the adjacent container wall. • Indirect heat input is preferably a heat transfer from the heated area to the surrounding container wall. Furthermore, indirect heat input is preferably a heat transfer from the phase heated by direct heat input (gas phase) to the adjacent phase (liquid). Additionally, indirect heat input is preferably a heat transfer from the container wall surrounding the heated area to the liquid. Indirect heat input is significantly less than direct heat input. Moreover, the temperature in the container wall decreases with increasing distance from the heated area. Thus, the temperature in the surrounding container wall is inhomogeneously distributed. The liquid heats up only minimally due to indirect heat input. Indirect heat input is not considered heating. • The terms “non-significant heating” and “non-significant temperature increases” are synonymous and equivalent within the scope of this application. A “non-significant heating” preferably corresponds, for example, to a temperature increase of the liquid that is below the temperature of the gas phase. Preferably, the temperature of the liquid during non-significant heating remains closer to room temperature than to the temperature of the heated gas phase. Preferably, the temperature of the liquid is only no more than 10°C, and particularly preferably no more than 5°C above the ambient temperature and / or its initial temperature before the heating of the gas phase. The non-significant heating preferably has no effect on the subsequent usability of the liquid or sample.In particular, during non-significant heating, the temperature of the liquid is preferably increased only to the extent that no adverse effects occur on components of the liquid and / or the liquid sample (such as damage to contained microorganisms), so that the further use of the sample and / or the liquid in clinical diagnostic procedures in blood analysis (such as mass spectrometric methods) is not impaired. Non-significant, minor, negligible, and insignificant are interchangeable, identical terms used within the scope of this application. • When the container holding device is pivoted, the orientation of the container holding device and / or the direction of the container's longitudinal axis b relative to the direction of gravity preferably changes. When pivoting about the pivot axis A, the angle between the longitudinal axis a of the container holding device and the horizontal preferably changes. Preferably, the container is at least partially inverted within the container holding device when pivoting about the pivot axis A. The pivoting is not a complete rotation or a periodically repeated shaking motion, such as for the purpose of mixing (as, for example, in a piston shaker or in incubators for cell cultures).

[0075] The present invention is explained in more detail below with reference to exemplary embodiments illustrated in the drawings. In all the examples and figures in this document, the container is a blood culture bottle and the liquid is a liquid blood culture. Although the invention is particularly advantageous in this embodiment, it is not limited to this container and this liquid. The figures show: Fig. 1 a schematic perspective view of a sample preparation device with a sample extraction device; Fig. 2 an embodiment of the sampling device made of Fig. 1, namely in (a) a schematic side view; and in (b) a schematic perspective view with a container shown; Fig. 3 an embodiment of the container receiving device from Figure 2, namely in (a) in a first schematic perspective view; in (b) in a second schematic perspective view; Fig. 4 an embodiment of the sampling device from the Fig. 1 and Fig. 2 with the container and a centering device in a schematic cross-sectional side view, namely in (a) the container receiving device in a first position with a second element in an open position; in (b) the container receiving device in the first position with the second element in a partially closed position; in (c) the container receiving device in the first position with the second element in a closed position and in (d) the container receiving device in a second position; in (e) a detail enlargement (dashed oval) of the container receiving device from Figure 4d showing a planar section of the container and a heating device; Fig. 5 a schematic side view of the container receiving device from Figure 3 comprising a centering device and a movable pivot axis B, namely in (a) with the second element in the open position and in (b) with the second element in the closed position; schematically shown are the positions of guide pins in guide grooves in the open position and in the closed position; Fig. 6 schematic views of different blood culture bottles and of a sample outlet device, namely in (a) a blood culture bottle in a first form made of the Fig. 4a-e containing liquid, closed with a septum in side view; in (b) a blood culture bottle of the same shape and a sample outlet device in perspective view; in (c) a blood culture bottle of the same shape with the arranged sample outlet device in a side view and in (d) another blood culture bottle in a second shape; Fig. 7 an embodiment of the heating device from the Fig. 4a-e, namely in (a) in a schematic perspective view without a support layer; in (b) in a schematic cross-sectional view with the support layer; Fig. 8 an embodiment of the container made from the Fig. 4D-E in a cross-sectional view; Fig. 9 a second embodiment of the sampling device in a schematic perspective view, namely in (a) with the container receiving device in the first position and in (b) with the container receiving device in the second position; Fig. 10 An illustration of a swivel angle division in relation to the horizontal in the form of a coordinate system.

[0076] Fig. Figure 1 schematically shows a perspective view of a sample preparation device 1. It comprises a sample collection device 2. The sample collection device 2 has a container 3. The container 3 is preferably a blood culture bottle 4. The sample preparation device 1 further comprises a pipetting device 5 for mixing and / or transferring defined quantities of liquid and a control device 6 for controlling the pipetting device 5. The sample preparation device 1 also includes several devices 7 for receiving additional sample containers. These additional sample containers are, for example, Eppendorf cups. ®, centrifuge tubes or reaction vessels. Furthermore, the sample preparation device 1 can include other devices such as centrifuges, oscillating shakers, thermocyclers. The sample preparation device 1 can also include a robot that, for example, transports an interchangeable sample container 16 (not shown) and / or the other sample containers between the devices in the sample preparation device 1.

[0077] The sampling device 2 serves to receive the container 3 and to dispense a liquid sample 36 of a liquid 24, in particular the liquid sample 36 of a blood culture 25, into an exchangeable sample container 16 (partially not shown here; see Fig. 4a-d).

[0078] Fig. Figure 2a schematically shows an embodiment of the sampling device 2 in a side view. A container receiving device 8 is shown, which is pivotably arranged about a pivot axis A in the sampling device 2. In this example, the container receiving device 8 is arranged on a base 10 of the sampling device 2. The sampling device 2 also has a sample receiving device 11, which can receive the interchangeable sample container 16 (not shown) and is arranged on the base 10. The container receiving device 8 has a first element 12 and a second element 13. The first element 12 is pivotably arranged about the pivot axis A, thus making the container receiving device 8 pivotable about the pivot axis A. This allows a container 3 held in the container receiving device 8 to be pivoted about the pivot axis A. The longitudinal axis b (see Figure 2a) is pivoted in this process. Fig. 6a) of the container 3 and the longitudinal axis a of the container receiving device 8 are pivoted about the pivot axis A. The second element 13 is pivotably arranged on the first element 12. Furthermore, the first element 12 has an alignment arrangement 14 for aligning the container 3 as part of a centering device 15.

[0079] Fig. Figure 2b schematically shows the embodiment of the sampling device 2. Fig. Figure 2a shows a perspective view. Additionally, the container 3, in this example a blood culture bottle 4, is shown. A sample outlet device 17 is arranged on the container 3. The remaining features are already described in the section on Fig. 2a described.

[0080] Fig. Figure 3a schematically shows the embodiment of the container receiving device 8. Fig. Figure 2 shows a perspective view. A heating device 18 is arranged on the container receiving device 8. The heating device 18 is designed as a heating surface 32, in particular as a heating film 19. The heating device 18 is arranged on the inside of the second element 13. A compressible support layer 20 of the heating device 18 is arranged between the heating surface 32 and the second element 13. The longitudinal axis a of the container receiving device 8 is also shown. It runs essentially centrally through a container-compatible recess 31 in the container receiving device 8. In this example, the longitudinal axis a is also largely congruent with the longitudinal axis b of a container 3 held in the container receiving device 8 (not shown; see Figure 2). Fig. 4a-d and Fig. 6a). The pivot axis A runs in a vertically offset parallel plane and at a right angle to the longitudinal axis a.

[0081] Fig. Figure 3b schematically shows the embodiment of the container receiving device 8. Fig. 3a in a different perspective view. The alignment arrangement 14 of the centering device 15 is designed such that the sample outlet device 17 is supported (see ). Fig. 2b). Furthermore, the alignment arrangement 14 of the centering device 15 is designed such that the alignment arrangement 14 acts as a feed limiter in the centering device 15.

[0082] Fig. Figures 4a-d show schematic cross-sectional views of the sampling device 2 from the Fig. 1-2 with container 3 in different phases of sampling and positions 21, 22, 33, 34 of the container receiving device 8 in the sampling device 2.

[0083] This shows Fig. 4a the received container 3 in the container receiving device 8, after it has been inserted. The container receiving device 8 is in a first position 21 for inserting and removing the container 3. The second element 13 of the container receiving device 8 is also in an open position 22. The container 3 is not in contact with the heating device 18 in this position. The container 3 can be inserted and removed in the open position 22. The sample outlet device 17 arranged on the container 3 forms an outlet 23 on the container 3. The container 3 has a container wall 29 which partially encloses a container interior 30. The container interior 30 is enclosed except for an opening 42 (see ). Fig. 6 a,d) completely enclosed by the container wall 29. The opening 42 of the container 3 is closed with a septum 43 (see. Fig. 6 a, b, d). The septum 43 is pierced by means of the sample outlet device 17. The interior of the container 30 contains the liquid 24, preferably the blood culture 25, and a gas phase 26. The gas phase 26 is located above the liquid 24 relative to the horizontal h. The gas phase 26 forms a head region of the interior of the container 30. In the first position 21, the liquid 24 is not in liquid communication with the outlet 23. In the first position 21, the gas phase 26 separates the liquid 24 from the outlet 23.

[0084] The sample outlet device 17 is only partially located within the alignment arrangement 14 in the first position 21. An edge 27 of the sample outlet device 17 is spaced apart from the alignment arrangement 14. The second element 13 has a sliding arrangement 28. In this example, the container 3 rests on the sliding arrangement 28 in the first position 21. The longitudinal axis a of the container receiving device 8 has a first pivot angle α with respect to the horizontal h in the first position 21. Within the scope of the invention, it is also conceivable that the sample outlet device 17 is arranged on the container 3 after the container 3 has been inserted into the container receiving device 8. In particular, it is conceivable that the arrangement takes place during the subsequent alignment or advancement of the container 3. The longitudinal axis a of the container receiving device 8 intersects the horizontal h at a first intersection point S1 in the first position.

[0085] Fig. Figure 4b schematically shows the container receiving device 8 with a partially closed container receiving device 8 in the first position 21. Before the container receiving device 8 can be pivoted into a second position 34 (see Figure 4b). Fig. 4d), the second element 13 is pivoted into a closed position 33 (see. Fig. 4c). Closing the container receiving device 8 causes the container 3 to shift and be aligned within the container receiving device 8 by the centering device 15. Furthermore, in this example, the heating device 18, here a heating surface 32 designed as a heating film 19, is brought into contact with the container wall 29 by the closing action. The centering device 15 comprises the sliding assembly 28 and the alignment assembly 14. Upon closing, the sliding assembly 28 pushes the container 3 with the sample outlet device 17 into the alignment assembly 14. This aligns the sample outlet device 17 and / or the container 3. The alignment assembly 14 acts as a counter-element to the sliding assembly 28.

[0086] The process of closing the container receiving device 8 is described in Fig. 4c is completed. The second element 13 is in the closed position 33. The container receiving device 8 remains in the first position 21. The sliding arrangement 28 presses the container 3 with the sample outlet device 17 into the alignment arrangement 14. The container 3 and / or the sample outlet device 17 are thereby aligned. The container 3 is also thereby fixed. The sliding arrangement 28 includes a compressible contact point (not shown) so that containers 3 of different shapes can be reliably pressed into the alignment arrangement 14. The heating device 18 contacts the container wall 29. The heating device 18 is not switched on in the first position 21. The heating device 18 is arranged such that it contacts the container 3 on one side and substantially in the lower half of the container 3, which adjoins the container bottom 45. The second element 13 locks in the closed position 33.

[0087] Fig. Figure 4d schematically shows the container holding device 8 with the container holding device 8 closed in the second position 34. The container holding device 8 secures the container 3 in its position so that it does not fall out of the sampling device 2 when swiveled. In the second position 34, the longitudinal axis a of the container holding device 8 has a second swivel angle β with respect to the horizontal h. The container holding device 8 is reversibly locked in this second position 34. The longitudinal axis a of the container holding device 8 intersects the horizontal h at a second intersection point S2.

[0088] In this second position 34, the liquid 24 is in liquid communication with the outlet 23. The heating device 18 now contacts the container wall 29 in a planar section 35. The planar section 35 borders, preferably exclusively, on the gas phase 26 on the inside. (Note: Since the planar section 35 extends in a second dimension over a part of the container wall 29 visible in cross-section on the inside, a precise representation of the planar section 35 would also have to extend over this part. For the sake of clarity and comprehensibility, the planar section 35 is shown in the...) Fig. However, 4 is only shown schematically in the cross-sectional area. For a more precise representation of the planar sub-area 35, see below. Fig. 6b and Fig. (Referring to Figure 8). Preferably, the flat section 35 is contacted externally by the heating device 18. The position and extent of the flat section 35 on the container 3 are complementary to the heating device 18, which is designed as a heating surface 32. The heating device 18 heats the flat section 35. In this example, the heating device 18 heats the flat section 35 in the second position 34. The heating phase lasts between 10 seconds and 2 minutes. This heats the gas phase 26. The gas phase 26 expands as a result. This creates an overpressure in the container 3. In the case of blood culture bottles 4, the overpressure during sampling and heating is preferably between 0.1 bar and 2.0 bar. As a rule, the overpressure increases during heating. Due to the overpressure and the hydrostatic pressure, the liquid sample 36 exits from the liquid 24 through the outlet 23.Due to the prior alignment of the container 3 and / or the sample outlet device 17, the outlet 23 is aligned, and the liquid sample 36 reliably drips into the exchangeable sample container 16 in the sample receiving device 11. A photoelectric sensor 37 detects the fill level of the exchangeable sample container 16 and interrupts the sampling process when a defined fill level is reached in the exchangeable sample container 16. The heating process is then stopped. By using a thin heating film 19 as the heating element 18, the heat capacity of the heating element 18 is minimal. As a result, the direct heat input stops essentially immediately after heating ceases. The overpressure decreases. Typically, the liquid sample 36 stops flowing from the outlet 23 shortly after heating ceases. Thus, the cessation of heating stops the liquid sample 36 from the outlet 23.The locking mechanism of the container holding device 8 is released, preferably automatically. The container holding device 8 pivots back to the first position 21. For this purpose, the container holding device 8 has a pivoting mechanism (not shown). This includes a locking mechanism for reversibly locking the container holding device 8 in the second position 34 and a damping mechanism. The damping allows the pivoting back to the first position 21 to be gravity-driven while still remaining damped. After returning to the second position 34, the liquid communication between the liquid 24 and the outlet 23 is interrupted again. Egress of the liquid sample 36 is no longer possible. The container 3 can be safely removed.

[0089] Fig. Figure 4e schematically shows a close-up of the heating device 18 and the container wall 29 with the planar section 35 in cross-section from Figure 4d. The planar section 35 is part of the container wall 29. The heating device 18, here the heating surface 32 designed as a heating film 19, contacts the container wall 29 of the container 3 at the planar section 35. The planar section 35 is contacted on the outside by the heating device 18. On the inside, the planar section 35 borders the gas phase 26, which is located in the interior of the container 30.

[0090] The planar section 35 extends over the entire thickness d of the container wall 29. A support layer 20 is arranged against the heating surface 32. The support layer 20 consists, for example, of a heat-resistant foam. This allows the heating device 18, designed here as a heating film 19, and the support layer 20 to adapt to the shape of the container 3 when the heating film 19 comes into contact with it. For this purpose, the support layer 20 is designed to be compressible. Since it automatically returns to its original shape after contact with the container 3, it is designed to be autoreversibly compressible.

[0091] Fig. 5a and Fig. Figure 5b schematically shows a closing mechanism 50 of the container receiving device 8 in the open position 22 and the closed position 33, and thus simultaneously another part of the centering device 15 of the container receiving device 8. Fig. 1-4. The locking mechanism 50 is shown in a cross-sectional view of the second element 13. The second element 13 is pivotally arranged about a pivot axis B on the first element 12. The first element 12 has a first guide pin 38 and a second guide pin 39, while the second element 13 has a first guide groove 40 and a second guide groove 41. However, for the function, it is largely irrelevant which of the elements 12, 13 has guide pins 38, 39 or guide grooves 40, 41. Other configurations of guide elements (39-41) are also conceivable. The first guide pin 38, which is further away from the pivot axis A, is simultaneously the pivot axis B. In the open position 22 ( Fig. 5a) Each guide pin 38,39 has different positions in the associated guide groove 40,41 than in the closed position 33 ( Fig. 5b). The pivot axis B thus shifts during the pivoting of the second element 13 about the pivot axis B in relation to the pivoting second element 13. The pivot axis B is therefore displaceable. A radial pivoting movement of the second element 13 is superimposed on a lateral displacement. As a result, when the second element 13 pivots about the pivot axis B, the sliding arrangement 28 (not shown; see Fig. 4a-d) additionally moves laterally in the direction of the alignment arrangement 14. This presses or shifts the received container 3 with the sample outlet device 17 into the alignment arrangement 14. The container 3 with the sample outlet device 17 is thereby aligned. Thus, the locking mechanism 50 is also part of the centering device 15. Furthermore, the container receiving device 8 can receive containers 3 with different circumferences u for sample extraction due to the movable pivot axis B. The second guide pin 39 and the second guide groove 41 primarily serve to stabilize and guide the locking mechanism 50. The second guide pin 39 also moves within its guide groove 41 (second guide groove 41) during the pivoting of the second element 13 about the pivot axis B.This ensures, in particular, that the heating surface 32 is aligned in the closed position 33 such that the entire heating surface 32 contacts the container wall 29. Furthermore, the closing mechanism 50 includes a locking device (not shown) that locks the second element 13 in the closed position 33.

[0092] Fig. Figure 6 shows various schematic views of different containers 3, in particular of different blood culture bottles 4, and of the sample outlet devices 17. Thus, it shows Fig. 6a a side view of container 3 designed as a first typical form of a blood culture bottle 4, as in the Fig. Figures 4a-e show the liquid 24 and the gas phase 26 in the interior of the container 30. Furthermore, the container in this illustration contains added sedimentable macroscopic particles 47 (in the Fig. (Figures 4a-e have been omitted for clarity). These serve, among other things, for the adsorption of antibiotics in the blood culture. The liquid 24 is the blood culture 25. The interior of the container 30 is partially enclosed by the container wall 29. The opening 42 is closed. Preferably, the opening 42 is closed by the septum 43. The septum 43 is preferably enclosed in a container closure 44. The container 3 has a base 45 on its underside. The base 45 is preferably arranged opposite the opening 42. The container 3 has a longitudinal axis b, which extends centrally from the base 45 to the opening 42.

[0093] Fig. Figure 6b shows the same first typical shape of a blood culture bottle 4 in a perspective view. The sample outlet device 17 is also shown (not yet attached to the container 3). In addition, the planar section 35 is shown schematically in its entirety, which in Fig. 4d-e can be seen in cross-section. Fig. Figure 6c shows the first typical form of a blood culture bottle 4 with an attached sample outlet device 17. A typical total container volume (empty volume) of blood culture bottles 4 is less than 100 mL, preferably 70 mL. Typically, this blood culture bottle is filled with 20 to 50 mL, preferably 35 mL, of liquid culture medium. This is then typically mixed with up to 10 mL of blood, preferably whole blood. The liquid culture medium together with the blood, preferably whole blood, are the main components of the blood culture 25. Manufacturers of these blood culture bottles 4 include, for example, Biomérieux.

[0094] Fig. Figure 6d shows a second typical form of a blood culture bottle 4 with a sample outlet device 17 not yet arranged. A typical total container volume (empty volume) of blood culture bottles 4 is less than 100 mL, preferably 70 mL. Typically, this blood culture bottle is filled with 20 to 50 mL, preferably 35 mL, of liquid culture medium. This is then typically also mixed with up to 10 mL of blood, whole blood, or a separated component of blood. Manufacturers of these blood culture bottles 4 include, for example, Becton Dickinson.

[0095] Based on this second typical shape of the blood culture bottle 4, the following structural areas 46 are identified. These also apply analogously to the first shape of the blood culture bottle 4. Where applicable, these areas also apply to other container shapes. Extending from the container base 45 (blood culture bottle base) to the opening 42 in the following order: a blood culture bottle body 46a, a blood culture bottle shoulder 46b, and a blood culture bottle neck 46c. The blood culture bottle body 46a has a circumference u. Similarly, containers 3 have a circumference u. The container receiving device 8 is designed to receive at least both of the depicted shapes of blood culture bottles 4 (Type 1: Fig. 6c and Type 2: Fig. 6d).

[0096] Fig. Figure 7a schematically shows a perspective view of the heating device 18, which is designed as a heating surface 32. Here, the heating surface 32 is designed as a heating film 19. It has an electrical heating resistance. In this example, the heating resistance is designed as a wire or conductor 51. The heating resistance is arranged on a film 52. The heating resistance is also arranged over a surface. The film 52 is electrically insulating and heat-resistant. It consists, for example, of Kapton. ® Applying a voltage and conducting current through the heating element generates heat due to the high resistance of the element. In this example, the heating surface 32 heats the flat area 35 by means of contact. The heating surface 32 is flexible in shape, allowing it to adapt to the container wall 29 and make full contact with it. Fig. Figure 7b schematically shows a cross-sectional view of the heating device 18. The heating device 18 comprises two layers 53 and 54. The heating surface 32 forms a first layer 53. It is designed as a heating film 19. The heating surface 32 is flexible and pliable. Thus, it adapts to its substrate and / or to the container 3 when it makes contact with the container 3. A second layer 54 is arranged on the back of the first layer 53. In particular, the first layer 53 is arranged almost entirely against the back of the second layer 54. The second layer 54 therefore contacts the first layer 53 on the side facing away from the container 3. The second layer 54 is the support layer 20 for the first layer 53 (the heating surface 32). In particular, the support layer 20 is compressible, so that when pressure is applied to the heating surface 32, the support layer 20 adapts to the shape of the container wall 29.After removal of container 3, the compressible support layer 20 returns to its original shape on its own. It is therefore autoreversibly compressible. Likewise, the arranged first layer 53 returns to its original shape.

[0097] Fig. Figure 8 schematically shows an embodiment of the container 3 in a cross-sectional view. This cross-section is shown at the level of a body of the container 3, in particular at the level of the blood culture bottle body 46a. The thickness d of the container wall 29 is shown. In addition, the planar section 35 is shown. Fig. Figure 4d-e is shown schematically. The planar section 35 is heated along its entire thickness d. The planar section 35 extends over part of the circumference u of the container 3 or the body of the blood culture bottle 46a. Furthermore, the planar section 35 extends over the entire thickness d of the container wall 29. An inner surface 56 and an outer surface 57 of the planar section 35 are also shown. The inner surface 56 faces the interior of the container 30. The outer surface 57 faces in the opposite direction. The heating element thus makes direct contact with the outer surface of the planar section.

[0098] Fig. Figure 9 schematically shows an alternative embodiment of the sampling device 2 in a perspective view. Fig. Figure 9a shows the container receiving device 8 in the first position 21 and Fig. Figure 9b shows the container receiving device 8 in the second position 34. The container receiving device 8 comprises only the first element 12. The first element 12 is also pivotably arranged in the sampling device 2.

[0099] The heating device 18 is designed as a heating surface 32. In this embodiment, the heating device 18 is arranged outside the container receiving device 8. For example, the heating device 18 can be arranged at the base 10. Here, the heating device 18 is not pivotable but remains in its position – regardless of the position 21, 34 of the container receiving device 8. In this embodiment, the heating device 18 is arranged such that it contacts the container 3, in particular the planar section 35, in the second position 34 (see Fig. 9b).

[0100] In this embodiment, the container receiving device 8 is in the first position 21 also simultaneously in an open position and in the second position 34 simultaneously in a closed position ( Fig. 9a). Apart from the aforementioned differences and the resulting differences, this alternative embodiment is essentially identical to the previous embodiment.

[0101] Further embodiments which use the concept of selective heating of the gas phase 26 for sampling, in particular in combination with a swiveling device for the container 3, are conceivable and are included in the set of claims.

[0102] Fig. Figure 10 schematically shows a gradation of the swivel angle ranges of the first and second swivel angles with respect to the horizontal h to illustrate the two swivel angles α,β in both positions (21,34) in the previously shown embodiments (see Figure 10). Fig. 4 ad). The longitudinal axis a of the container receiving device 8 intersects the horizontal h in the first position at the first intersection point S1 at an angle α and in the second position at the second intersection point S2 at an angle β. It can be seen that swivel angles above the horizontal h are positive swivel angles and swivel angles below the horizontal h are negative swivel angles. In the examples shown, each swivel angle α, β is defined to the left of the respective intersection points S1, S2 by the longitudinal axis a and the horizontal h. In the present example, the first swivel angle α is defined below the horizontal h. The second swivel angle β is defined above the horizontal h. With the viewing direction and arrangement shown, the two swivel angles α, β are defined according to the Fig.4. The angle is preferably measured on the left side of the intersection points (S1, S2), starting from the horizontal h. In the example shown, the first swivel angle is approximately α = -58° and the second swivel angle is approximately β = +36°. Reference symbol list 1 Sample preparation device 2 Sampling device 3 containers 4 blood culture bottles 5 Pipetting device 6 Control device 7 Devices for holding additional sample containers 8 Container receiving device 10 Base 11 Sample Receiving Unit 12 First element 13 Second Element 14 Alignment arrangement 15 Centering device 16 Interchangeable sample container 17 Sample outlet device 18 Heating system 19 Heating film 20 Support layer 21 First position 22 Disclosure 23 Outlet 24 Liquid 25 Blood culture 26 Gas phase 27 Edge of the sample outlet device 28 Sliding arrangement 29 Container wall 30 container interior 31 recess 32 heating surface 33 Closed position 34 Second position 35 Area section 36 Liquid Sample 37 Light barrier sensor 38 First guide pin 39 Second guide pin 40 First Leading Nut 41 Second guide groove 42 Opening the container 43 Septum 44 Container closure 45 Container bottom 46. ​​Section of the blood culture bottle 46a Section: Blood culture bottle body 46b Section: Blood culture bottle shoulder 46c Section: Blood culture bottle neck 47 Added sedimentable macroscopic particles 50 Locking mechanism of the container receiving device 51 conductor track 52 slides 53 First shift 54 Second shift 56 Inside of the flat sub-area 57 Outside of the flat sub-area A Swivel axis A a longitudinal axis a of the container receiving device h Horizontal α First swivel angle of the longitudinal axis a in the first position β Second swivel angle of the longitudinal axis a in the second position B Swivel axis B b Longitudinal axis b of the container u circumference of the blood culture bottle body or container body d thickness of the container wall S1 First intersection of the longitudinal axis a with the horizontal h S2 Second intersection of the longitudinal axis a with the horizontal h QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature

[0000] WO 2010132829A2

[0004]

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