Microscope and System Comprising Such a Microscope for Examination of an Incubated Sample and Corresponding Method

Abstract

The invention relates to a microscope for microscopic examination of a sample comprising a microscope housing enclosing an illumination optics, a microscope stage and an imaging optics, an integrated sample chamber located within the microscope housing and formed by a separated housing section within said microscope housing, the housing section comprising a lid providing direct access to the microscope stage for placing the sample in the sample chamber, wherein said housing section comprises an interface for connection of an external incubation environment conditioning unit to the sample chamber, the interface being configured to provide a connection between said external incubation environment conditioning unit and the sample chamber, such that the environmental conditions in the sample chamber can be controlled when the external incubation environment conditioning unit is connected to the interface.

Claims

1. A microscope for microscopic examination of a sample comprising: a microscope housing enclosing an illumination optics, a microscope stage and an imaging optics; an integrated sample chamber located within the microscope housing and formed by a separated housing section within said microscope housing; and the housing section comprising a lid providing direct access to the microscope stage for placing the sample in the sample chamber; wherein said housing section comprises an interface for connection of an external incubation environment conditioning unit to the sample chamber, the interface being configured to provide a connection between said external incubation environment conditioning unit and the sample chamber, such that environmental conditions in the sample chamber can be controlled when the external incubation environment conditioning unit is connected to the interface.

2. The microscope of claim 1, wherein said housing section is configured such that, when the lid is closed, the sample chamber is sealed.

3. The microscope of claim 1, wherein said housing section at least partially encloses the microscope stage and a working area for placing the sample on the microscope stage.

4. The microscope of claim 3, wherein said housing section further encloses the illumination optics.

5. The microscope of claim 1, wherein said housing section is bounded by a working surface, the working surface comprising an upper side of the microscope stage.

6. The microscope of claim 1, wherein said interface further comprises at least one opening configured to receive a conduit, the conduit being connected to the external incubation environment conditioning unit, or wherein said interface comprises at least one opening including a conduit, which is connectable to the external incubation environment conditioning unit.

7. The microscope of claim 6, wherein said at least one opening is configured to be closed in a light-tight manner when the microscope is operated without the external incubation environment conditioning unit.

8. The microscope of claim 6, wherein the interface comprises a plurality of openings for respective conduits for supplying and discharging incubation atmosphere.

9. The microscope of claim 1, further comprising at least one sensor for sensing at least one parameter of the incubation atmosphere.

10. The microscope of claim 9, wherein the at least one sensor is at least partially integrated into a conduit.

11. The microscope of claim 1, wherein the interface is located at a backside of the housing section.

12. The microscope of claim 1, wherein the microscope is an inverse transmitted-light microscope, wherein the housing section at least partially encloses the microscope stage of the microscope and a transmitted-light illumination unit as the illumination optics of the microscope, and wherein a second housing section at least partially encloses the imaging optics of the microscope.

13. The microscope of claim 12, wherein the second housing section is configured to be air-conditioned and/or temperature-controlled.

14. A system for microscopic examination of a sample comprising: a microscope comprising a microscope housing enclosing an illumination optics, a microscope stage and an imaging optics; an integrated sample chamber located within the microscope housing and formed by a separated housing section within said microscope housing; the housing section comprising a lid providing direct access to the microscope stage for placing the sample in the sample chamber; and an incubation environment conditioning unit being connected to the microscope via said microscope interface; wherein said housing section comprises an interface for connecting an external incubation environment conditioning unit to the sample chamber, the interface for connection of an external incubation environment conditioning unit and the sample chamber, such that environmental conditions in the sample chamber can be controlled when the external incubation environment conditioning unit is connected to the interface.

15. The system of claim 14, wherein the incubation environment conditioning unit comprises at least one of the following connections: a connection for supplying H.sub.2O; a connection for discharging H.sub.2O and/or incubation atmosphere; a connection for supplying N.sub.2 and/or O.sub.2; a connection for supplying CO.sub.2 into the sample chamber.

16. The system of claim 14 wherein the microscope comprises a controlling unit for controlling functional components of the microscope for controlling the microscopic examination of the sample, the controlling unit being further configured to control the operation of the incubation environment conditioning unit when the external incubation environment conditioning unit is connected to the interface.

17. The system claim 16, wherein the controlling unit is configured to control at least one of the parameters being a temperature, a content of H.sub.2O, a content of CO.sub.2 and a content of O.sub.2 of the incubation atmosphere.

18. A method for microscopic examination of a sample comprising: equipping a microscope with an external incubation environment conditioning unit for incubating a sample chamber of the microscope, said microscope comprising: a microscope housing enclosing an illumination optics, a microscope stage and an imaging optics; an integrated sample chamber located within the microscope housing and formed by a separated housing section within said microscope housing; the housing section comprising a lid providing direct access to the microscope stage for placing the sample in the sample chamber, said housing section comprising an interface for connecting the external incubation environment conditioning unit to the sample chamber; configuring the interface to provide a connection between said external incubation environment conditioning unit and the sample chamber, such that the environmental conditions in the sample chamber can be controlled when the external incubation environment conditioning unit is connected to the interface; and connecting the incubation environment conditioning unit to the microscope via the interface.

19. An incubated system comprising: a microscope for microscopic examination of a sample comprising: a microscope housing enclosing an illumination optics, a microscope stage and an imaging optics; an integrated sample chamber located within the microscope housing and formed by a separated housing section within said microscope housing; and the housing section comprising a hinged lid providing direct access to the microscope stage for placing the sample in the sample chamber; wherein said housing section comprises an interface for connection of an external incubation environment conditioning unit to the sample chamber, the interface being configured to provide a connection between said external incubation environment conditioning unit and the sample chamber, such that environmental conditions in the sample chamber can be controlled when the external incubation environment conditioning unit is connected to the interface; and an external incubation environment conditioning unit comprising at least one protruding conduit for insertion into an at least one opening of the interface, the external incubation environment conditioning unit configured to be coupled to an outside of the interface and serving to provide at least one conduit incubation atmosphere into the sample chamber.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] FIG. 1 schematically shows a perspective view of an embodiment of a system according to the inventive concept,

[0029] FIG. 2 schematically shows a perspective view of assembling a microscope with an incubation atmosphere conditioning unit, and

[0030] FIG. 3 schematically shows a side view of the situation in FIG. 2.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] FIG. 1 schematically shows in a perspective view an embodiment of a microscope 100 for microscopic examination of a sample 120 arranged on a microscope stage 116. A microscope housing 102 encloses an illumination optics 118, the microscope stage 116 and an imaging optics 124. An integrated sample chamber 106 is located within the microscope housing 102 and formed by a separated housing section 104 within said microscope housing 102. The housing section 104 comprises a hinged lid 109 which provides direct access to the microscope stage 116 for placing the sample 120 in the sample chamber 106 onto the microscope stage 116 and for exchanging samples 120 and/or manipulating samples 120 when the lid is opened. The embodiment shown in FIG. 1 is an inverse transmitted-light microscope 100 where the transmitted-light illumination optics 118 is arranged within the housing section 104, while the imaging optics is located below the microscope stage 116 in a second housing section 122. The imaging optics 124 typically includes a microscope objective and an image detector as the main components. The image detector usually comprises a camera which generates microscopic images which are typically displayed on a display screen 142 outside the microscope housing 102.

[0032] The construction of the microscope housing section 104 allows—after closing the lid 109—to form a dedicated sample chamber 106 which constitutes a preferably sealed space which can be incubated such that during microscopic examination/imaging of living samples 120 like cells, the sample can be kept under favorable and stress-free environmental conditions. To this end, the housing section 104 comprises an interface 108 for connection of an external incubation environment conditioning unit 110 to the sample chamber 106. The interface 108 is configured to provide a connection between the conditioning unit 110 and the sample chamber 106, such that environmental conditions in the sample chamber 106 can be controlled when the conditioning unit 110 is connected to the interface 108.

[0033] In the embodiment shown, the interface 108 as a part of the housing section 104 comprises two openings 112 in the backside of the housing section 104, each opening 112 being configured to receive a conduit 114 (see also FIGS. 2 and 3). Incubation atmosphere can be introduced through at least one of the conduits 114 into the sample chamber 106. Depending on the leakage of the sample chamber 106, a part of the incubation atmosphere is allowed to escape the sample chamber 106. On the other hand, a part of the incubation atmosphere can be withdrawn from the sample chamber 106 via another one of the conduits 114.

[0034] Suitable incubation atmospheres comprise air with a predefined content of H.sub.2O (relative humidity) and a predefined content of CO.sub.2 (carbon dioxide). It is also desirable to conduct hypoxia experiments with a deficiency of oxygen in the atmosphere. Typically, the temperature of the incubation atmosphere can be set in a range between ambient temperature up to 50° C., the CO.sub.2-range is set between 0.5 to 20%, and the O.sub.2-range is between 1 to 18%. The humidity must be balanced to ensure that potential condensation is avoided or at least does harm neither the microscope 100 nor the conditioning unit 110 nor the sample itself. It is preferred to control at least the temperature, the humidity and the CO.sub.2-content on its own. In hypoxia experiments, the O.sub.2-content is controlled by N.sub.2-input.

[0035] In order to control the above parameters, it is preferred to arrange sensors in the conduits 114 and/or in the sample chamber 106 and/or at the microscope stage 116 close to the sample 120. In a preferred embodiment, at least some of the sensors are integrated into a conduit 114 for supplying incubation atmosphere to the sample chamber 106.

[0036] As shown in FIG. 1, the housing section 104 is bounded downward by a working surface 107 including an upper side of the microscope stage, in other words the microscope stage tabletop. This construction provides a user-friendly access to the working area for placing and manipulating the sample 120. To the other sides, the housing section is bounded by the inner sides of the lid 109 and the backside of the housing section 104 itself.

[0037] For increasing the live span of the imaging optics 124 and in case of using immersion objectives, it is preferred to air condition and/or temperature-control the second housing section 122. This can either be done by the same conditioning unit 110 and a correspondingly enlarged interface 108 or, more preferred, by a separate air conditioning unit.

[0038] In a preferred embodiment, the microscope 110 comprises a controlling unit 140 that controls functional components like the illumination optics 118, the microscope stage 116 and the imaging optics 124 of the microscope 100 for controlling the microscopic examination/imaging of the sample 120. Typically, a graphical user interface (GUI) is displayed on the display screen 142 for a user-friendly operation of the microscope 100. The controlling unit 140 is further configured to control the operation of the incubation environment conditioning unit 110 when the conditioning unit 110 is connected to the interface 108. Cables and lines for communication between the microscope controlling unit 140 and a conditioning unit controller (not shown) can be guided through one or more of the above openings/conduits of the interface 108. In this case, the same GUI may display corresponding buttons for setting desired values for the incubation atmosphere parameters as mentioned above. After confirmation that the lid 109 is closed and the sample to be examined is placed on the table of the microscope stage 116, generation of the user-defined incubation atmosphere automatically starts and, once the desired atmosphere is established and the sample 120 is in the right position, examination/imaging of the sample is carried out.

[0039] As already mentioned above, FIG. 2 shows an assembling process of equipping a microscope 100 with an incubation environment conditioning unit 110 resulting in a system 130. Same reference signs as in FIG. 1 designate the same components. As shown in FIG. 2, interface 108 also comprises mounting sites for fixing the conditioning unit 110 at its corners to the backside of the microscope 100. The interface 108 further comprises openings 112 configured for receiving two conduits 114 of the conditioning unit 110, the two conduits 114 providing respective ducts through which incubation atmosphere is fed into the sample chamber 106. In this embodiment, the conduits 114 are connected to the conditioning unit 110 e.g. by welding or by a flanged connection. The assembling process shown in FIG. 2 is particularly suitable for retrofitting a microscope 100 with a conditioning unit 110.

[0040] FIG. 3 schematically shows a cross-section of the components shown in FIG. 2 in a side view. Again, same reference signs refer to same components. In order to avoid repetitions, reference is made to the descriptions of FIGS. 1 and 2. As can be seen from FIG. 3, the opening 112 has the form of a duct for receiving a conduit/tube/pipe 114, which is part of the conditioning unit 110. In another embodiment, the conduit 114 may be part of the interface 108 such that the end of the conduit would have to be connected to the conditioning unit 110.

REFERENCE SIGNS

[0041] 100 microscope [0042] 102 microscope housing [0043] 104 housing section [0044] 106 sample chamber [0045] 107 working surface [0046] 108 interface [0047] 109 lid [0048] 110 incubation environment conditioning unit [0049] 112 opening [0050] 114 conduit [0051] 116 microscope stage [0052] 118 illumination optics [0053] 120 sample [0054] 122 second housing section [0055] 124 imaging optics [0056] 130 system [0057] 140 controlling unit [0058] 142 display screen