Humidity control arrangement and / or immersion liquid removal arrangement for closed imaging compartment immersion microscopy and an arrangement and method for closed imaging compartment immersion microscopy

Abstract

The present invention refers to a humidity control arrangement (300) and to immersion liquid removal arrangement (400) both for closed imaging compartment immersion microscopy. The humidity control arrangement (300) is configured to control humidity of an atmosphere of a closed imaging compartment (110) of an immersion microscopy arrangement (1). The immersion liquid removal arrangement (400) is configured to remove purging and / or excessive immersion liquid (20) of a or in a closed imaging compartment (110) of an immersion microscopy arrangement (1). An immersion microscopy arrangement (1) as well as an operating method therefore for closed imaging compartment immersion microscopy are also proposed, wherein the arrangement comprises at least one of the humidity control arrangement (300) and the immersion liquid removal arrangement (400) which are used in the method of performing immersion microscopy.

Description

[0001] Humidity control arrangement and / or immersion liquid removal arrangement for closed imaging compartment immersion microscopy and an arrangement and method for closed imaging compartment immersion microscopy

[0002] Description

[0003] The present invention proposes means and methods of humidity control and / or of fluid disposal in closed imaging compartment immersion microscopy. In particular, the present invention refers to means and methods for controlling the humidity of the atmosphere and / or of the content and / or amount of immersion liquid in an immersion microscopy scenario involving a closed, insulated, and / or isolated imaging compartment.

[0004] More particular, the present invention relates to a humidity control arrangement and to immersion liquid removal arrangement both for closed imaging compartment immersion microscopy. An immersion microscopy arrangement as well as an operating method therefore for closed imaging compartment immersion microscopy scenarios are proposed, too.

[0005] Nowadays, in the field of immersion microscopy, long-term investigations of biological specimens become more and more important. In order to avoid an outside influence on the specimen to be investigated and on the investigation and observation conditions, the idea of using a closed imaging compartment came up.

[0006] For instance, prior art document US 2017 / 0 045 726 Al discloses a microscope observation container and an observation device, wherein a closed imaging compartment is formed by using a toroidal or ring-shaped observation container having a platelike bottom and an opening opposing the platelike bottom to which - for closing the container - a columnar housing of an objective lens of an underlying microscope is attached to with a distal conical portion thereof located at the objective’s distal end and abutted to an inside conical surface of the wall of the toroidal or ring-shaped observation container.

[0007] Although, a closed imaging space is thereby formed, this closed space is not capable of allowing a long-term observation with a high degree of control of the observation conditions, such as atmosphere and immersion liquid, without the risk of contamination and also without the likelihood of negative effects on the observation facilities. It is an object underlying the present invention to suggest arrangements for controlling the humidity and / or the liquid content and removal in closed imaging compartment immersion microscopy, a corresponding microscopy arrangement as such as well as a method for performing immersion microscopy, which are all highly suitable for and allow and enable long-term investigations of biological specimens, in particular in the field of molecular cartography and the like.

[0008] The object underlying the present invention is achieved by a humidity control arrangement according to independent claim 1, by an immersion liquid removal arrangement according to independent claim 7, by an immersion microscopy arrangement according to independent claim 12, and by a method of performing immersion microscopy according to independent claim 13. Preferred embodiments of the present invention are defined in the respective dependent claims.

[0009] According to a first aspect of the present invention, a humidity control arrangement is proposed. The present invention’s humidity control arrangement is designed for closed imaging compartment immersion microscopy. The proposed arrangement is configured to control humidity of an atmosphere of a closed imaging compartment of an immersion microscopy arrangement and it comprises at least one cooler that is configured to be arranged or that is arranged inside the closed imaging compartment and / or that is configured to remove heat from the closed imaging compartment, wherein the at least one cooler comprises at least one cooling surface that is configured to be cooled down upon operation of the at least one cooler in order to force vapor or fluid or liquid vapor contained in the atmosphere of the closed imaging compartment to condense on the cooled cooling surface in order to condense and to form a condensate. The arrangement further comprises exhaust means configured to exhaust said condensate outside the closed imaging compartment. This in particular concerns vapor generated from immersion liquid or an excessive amount thereof, the immersion liquid being water, being of aqueous nature, or being or being based on any other liquid or fluid.

[0010] According to a preferred embodiment of the present invention’s humidity control arrangement, the at least one cooler is or comprises at least one Peltier element, which is in particular formed or configured to be formed within the closed imaging compartment.

[0011] The at least one cooler may comprise at least one fan, which is in particular formed or configured to be formed within the closed imaging compartment

[0012] The humidity control arrangement may further comprise a primary condensate collecting means, which in particular is formed as a part of the exhaust means, formed as a funnel and / or formed or configured to be formed at least in part within the closed imaging compartment

[0013] In addition or alternatively, the present invention’s humidity control arrangement may further comprise a secondary condensate collecting means, which is in particular formed as a part of the exhaust means, formed as a pot and / or formed or configured to be formed outside the closed imaging compartment.

[0014] Under such circumstances, an active ventilation means may be provided and arranged and configured for ventilating the secondary condensate collecting means, which may be in particular formed as a part of and / or in a vicinity of the secondary condensate collecting means, and / or formed or configured to be formed outside the closed imaging compartment

[0015] According to an alternative aspect of the present invention, an immersion liquid removal arrangement for closed imaging compartment immersion microscopy is proposed. The present invention’s immersion liquid removal arrangement is configured to remove purging and / or excessive immersion liquid of a or in a closed imaging compartment of an immersion microscopy arrangement, arranged or configured to be arranged inside the closed imaging compartment in a manner transferable to the outside of the closed imaging compartment, comprises at least one immersion liquid, general fluid or liquid, and / or vapor receiving portion that is configured (i) to at least one of receive, collect, bind, adsorb, chemisorb, physisorb, and absorb immersion fluid, any general fluid or liquid and / or vapor, in particular from the atmosphere, from and / or within the closed imaging compartment, and (ii) in particular to controllably release any immersion fluid, any general fluid or liquid or vapor carried by the liquid receiving portion when positioned outside the closed imaging compartment, in particular by evaporation.

[0016] In the present invention’s immersion liquid removal arrangement, the immersion liquid receiving portion may be or may comprise an absorptive, hydrophilic, and / or porous part or plate.

[0017] The immersion liquid receiving portion may be a microscopy slide, a part of a microscopy slide, a portion in combination with a microscopy slide, e.g. arranged side by side, a portion integrated into or a part of a holder, carrier, support, and / or transfer assembly for a microscopy slide.

[0018] The immersion liquid receiving portion may be or may comprise a hydrophilic and / or porous plate which in particular comprises a highly plan or planar surface, which is more particularly configured not to emit particle contamination and / or onto which an absorbing material for absorbing immersion liquid, any general fluid or liquid or vapor is or can be formed. Surface portions of the microscopy slide or of the plate, respectively, not covered by an absorbing material for absorbing immersion liquid, any general fluid or liquid or vapor may form or carry well and / or a well support structure.

[0019] Eventually, an immersion microscopy arrangement for closed imaging compartment immersion microscopy is proposed which comprises a closed or closable imaging compartment that is or is configured to be insulated and / or isolated from an external space regarding atmosphere, humidity, dust, light, heat and / or temperature, and a microscope that is configured for immersion microscopy, in particular for fluorescence microscopy.

[0020] Said microscope is completely or least partly contained in and surrounded by said closed or closable imaging compartment. At least one of a humidity control arrangement according to the present invention and an immersion liquid removal arrangement according to the present invention is provided formed as a portion of the microscopy arrangement.

[0021] A method of performing immersion microscopy with respect to a specimen is proposed, too, wherein an immersion microscopy arrangement for closed imaging compartment immersion microscopy according to the present invention is used and operated, and wherein at least one of a humidity control arrangement according to the present invention and an immersion liquid removal arrangement according to the present invention is controllably operated in order to control humidity and / or content of excessive immersion liquid in the closed imaging compartment of the immersion microscopy arrangement

[0022] These and further details, advantages and features of the present invention will be described based on embodiments of the invention and by taking reference to the accompanying figures.

[0023] Figure 1 is a schematic block diagram for elucidating the general configuration of an immersion microscopy arrangement according to the present invention.

[0024] Figure 2 is a schematic side view of a portion of an embodiment of the present invention’s immersion microscopy arrangement with a particular focus on the microscope’s objective in the vicinity of the specimen to be investigated.

[0025] Figure 3 is a schematic and cross-sectional side view describing an application of an embodiment of the immersion liquid removal arrangement in an immersion microscopy arrangement according to the present invention in a state before having absorbed excessive immersion liquid.

[0026] Figure 4 is a schematic and cross-sectional side view describing an application of an embodiment of the immersion liquid removal arrangement in an immersion microscopy arrangement according to the present invention in a state after having absorbed excessive immersion liquid.

[0027] Figure 5 is a schematic and cross-sectional side view describing an application of an embodiment of the immersion liquid removal arrangement in an immersion microscopy arrangement according to the present invention in a state of evaporating the absorbed amount of immersion liquid into vapor in a liquid handling compartment separated isolated from the closed imaging compartment.

[0028] Figures 6A to 6D present by means of a schematic and cross-sectional side views a processing cycle or circle of absorbing, transferring, evaporating and returning with respect to an embodiment of the present invention’s immersion liquid removal arrangement and its immersion liquid receiving portion.

[0029] Figures 7A and 7B are schematic views with respect to an embodiment of the immersion microscopy arrangement according to the present invention for elucidating the presence of the closed or closable imaging compartment, of the liquid handling compartment, and the service and control compartment with the transfer door / window for communicating between the closed / closable imaging compartment and the liquid handling compartment, without and with indication of the absorbing, transferring, evaporating and returning with respect to the present invention’s immersion liquid removal arrangement and its immersion liquid receiving portion.

[0030] Figures 8A to 8D present - in a similar manner as figures 6A to 6D - by means of a schematic and cross-sectional side views a processing cycle or circle of absorbing, transferring, evaporating and returning with respect to an embodiment of the present invention’s immersion liquid removal arrangement and its immersion liquid receiving portion. Figure 9A is a schematic and cross-sectional side view of a more concrete embodiment of the immersion liquid removal arrangement for elucidating the dimensions.

[0031] Figure 9B is a schematic plan view of the more concrete embodiment as shown in figure 9A.

[0032] Figures 10 to 1 IB present schematic side and cross-sectional and plan views of still a more concrete alternative embodiment of the immersion liquid removal arrangement for elucidating the dimensions and using a microscopic slides together with well and support structures.

[0033] Figures 12 to 13B present schematic side and cross-sectional and plan views of still a more concrete alternative embodiment of the immersion liquid removal arrangement for elucidating the dimensions and using a microscopic slides together with well and support structures in combination with a microscopic slide holder.

[0034] Figure 14 is a schematic view with respect to an embodiment of a humidity control arrangement according to the present invention for elucidating the general presence of an external ventilation duct realized by a service and control compartment, the ventilation duct having an inlet and a ventilation exhaust or outlet

[0035] Figure 15 is a schematic view with respect to a more concrete embodiment of a humidity control arrangement according to the present invention, wherein a cooler is formed in the closed imaging compartment together with a cooling surface, a funnel, and an exhaust pipe leading to an external ventilation duct embedding a collecting pot via an air filter and with active ventilation in the outside portion formed by the external ventilation duct and with respect to which the closed imaging compartment is insulated.

[0036] Figure 16 is a schematic view with respect to a still more concrete embodiment of a humidity control arrangement according to the present invention, wherein - when compared to the embodiment of figure 15 - the external collecting and / or evaporating pot is substituted by or with an air filter. Figure 17 is a schematic view with respect to still a more concrete embodiment of a humidity control arrangement according to the present invention similar to that of figure 15, but plural coolers are involved.

[0037] In the following, embodiments and the technical background of the present invention are presented in detail by taking reference to accompanying figures 1 to 17. Identical or equivalent elements and elements which act identically or equivalently are denoted with the same reference signs. Not in each case of their occurrence a detailed description of the elements and components is repeated.

[0038] The depicted and described features and further properties of the invention’s embodiments can arbitrarily be isolated and recombined without leaving the gist of the present invention.

[0039] In the following and first of all, a preliminary and very general view is taken on the enclosed figures, with a particular focus on figures 1 and 2:

[0040] Figure 1 is a schematic block diagram for elucidating the general configuration of an immersion microscopy arrangement 1 according to an embodiment of the present invention. Figure 2 is a schematic side view of a portion of the present invention’s immersion microscopy arrangement 1 with a particular focus on the microscope’s objective or objective lens 2 in the vicinity of the specimen 3 to be investigated and disposed on a specimen carrier 4 or microscopy slide 4. The objective lens 2 of figure 2 shows a columnar or cylindrical portion or housing portion 2-1, a conical portion or housing portion 2-0, and a distal or front end / lens, which circumscribe a central optical axis 2-3 of the objective lens 2.

[0041] The general microscopy concept as shown in figure 1 is based on immersion of an objective or objective lens 2 of the underlying microscope 100 in an immersion liquid 20 or immersion fluids 20 embedding the specimen 3 on the specimen carrier 4 or holder 4.

[0042] In order to control the atmosphere of the closable or closed imaging compartment 110 of or for the microscope 100, according to the present invention a humidity control arrangement 300, means or device and / or an immersion liquid removal arrangement 400, means or device are provided and operated during the microscopy process.

[0043] Thereby excessive amounts of vapor - of the immersion material, liquid or fluid 20 and / or of any other general material, liquid or fluid - in the atmosphere of the closable or closed imaging compartment 110, possibly stemming from the underlying immersion fluid 20 or liquid 20, can be transferred to an outside region 120, 130 of the closable or closed imaging compartment 110.

[0044] The further optical components for detecting via detector 9 and 11 images and in particular fluorescence images of the specimen 3 under investigation may comprise a first light source 10a, a second light source 10b for bright- field observation and investigation using in the optical path mirrors 14a, 14b, beam splitters 7a, 7b, 7c, lenses 12 and 13, a filter 6, and a diffraction grating 8. an adjustment means may be used for adjusting the position of the objective 2 in the z or height direction, also for adjusting the immersion situation.

[0045] Figure 3 is a schematic and cross-sectional side view of an application of an embodiment of the immersion liquid removal arrangement 400 in an immersion microscopy arrangement 1 according to the present invention in a state before having absorbed excessive immersion liquid 20.

[0046] Figure 4 is a schematic and cross-sectional side view of an application of an embodiment of the immersion liquid removal arrangement 400 in an immersion microscopy arrangement 1 according to the present invention in a state after having absorbed excessive immersion liquid 20 which is now shown as absorbed immersion liquid or fluid 21.

[0047] Figure 5 is a schematic and cross-sectional side view of an application of an embodiment of the immersion liquid removal arrangement 400 in an immersion microscopy arrangement 1 according to the present invention in a state of evaporating the absorbed amount 21 of immersion liquid 20 into vapor 22 in a liquid handling compartment 120 separated, insulated, and / or isolated from the closable or closed imaging compartment 110.

[0048] Figures 6A to 6D present by means of schematic and cross-sectional side views a processing scheme, cycle or circle of absorbing A, transferring B, evaporating C and returning D with respect to an embodiment of the present invention’s immersion liquid removal arrangement 400 and its immersion liquid receiving portion 410.

[0049] Figures 7A and 7B are schematic views with respect to an embodiment of the immersion microscopy arrangement 1 according to the present invention for elucidating the presence of the closed or closable imaging compartment 110, of the liquid handling compartment 120, and the service and control compartment 130 with a closable and / or openable transfer door / window 150 for controllably communicating and / or transferring between the closed / closable imaging compartment 110 and the liquid handling compartment 120, without and with indication of the absorbing, transferring, evaporating and returning with respect to an embodiment of the present invention’s immersion liquid removal arrangement 400 and its immersion liquid receiving portion 410.

[0050] Figures 8A to 8D present - in a similar manner as figures 6A to 6D - by means of a schematic and cross-sectional side views a processing scheme, cycle or circle of absorbing A, transferring B, evaporating C, and returning D with respect to an embodiment of the present invention’s immersion liquid removal arrangement 400 and its immersion liquid receiving portion 410.

[0051] Figure 9A is a schematic and cross-sectional side view of a more concrete embodiment of the immersion liquid removal arrangement 400 for elucidating the dimensions thereof.

[0052] Figure 9B is a schematic plan view of the more concrete embodiment as shown in figure 9A.

[0053] The values of the geometrical properties as depicted in figures 9A and 9B may be in the respective ranges as follows: LI = 7,5 cm / L2 = 4,0 cm / Wl = 2,5 cm / W2 = 2,0 cm / T1 = 0,12 cm / T2 = 0,90 cm - with LI, L2 denoting lengths, Wl, W2 denoting widths, and Tl, T2 denoting thicknesses. However, these values are neither mandatory nor fixed or bounded to these specific values and may be adjusted according to the particular application of the invention’s type of immersion microscopy and the underlying specimen 3 and its carrier 4.

[0054] Figures 10 to 11B present schematic side and cross-sectional and plan views of still another concrete alternative embodiment of the immersion liquid removal arrangement for elucidating the dimensions and using a microscopic slide 4 together with wells and / or well support structures 413.

[0055] The values of the geometrical properties as depicted in figures 11A and 11B may be in the respective ranges as follows: 11 = 7,5 cm / 12 = 4,0 cm / wl = 2,5 cm / w2 = 2,0 cm - with LI, L2 denoting lengths, and Wl, W2 denoting widths. Again, these values are not mandatory and not fixed and may be adjusted according to the particular application of the invention’s type of immersion microscopy and the underlying specimen 3.

[0056] Figures 12 to 13B present schematic side and cross-sectional and plan views of still a further alternative concrete embodiment of the immersion liquid removal arrangement 400 for elucidating using a microscopic slide 4 together with well and support structures 413 in combination with a microscopic slide holder 415.

[0057] Figure 14 is a schematic view with respect to an embodiment of the humidity control arrangement 300 according to the present invention for elucidating the general presence of a ventilation duct 370 realized by the service and control compartment 130 and having an inlet 371 and a ventilation exhaust 372 or outlet 372.

[0058] Figure 15 is a schematic view with respect to a more concrete embodiment of a humidity control arrangement 300 according to the present invention, wherein a cooler 310 is formed in the closed imaging compartment 110 together with a cooling surface 320, a funnel 331 as a primary condensate collecting means 330, an exhaustpipe 340 leadingto the ventilation duct370 embedding a collecting pot 342 serving as a secondary condensate collecting 341 via an air filter 344 and with active ventilation 345 in the outside portion 130 with respect to which the closed imaging compartment 110 insulated, separated and / or isolated.

[0059] Figure 16 is a schematic view with respect to an alternative more concrete embodiment of a humidity control arrangement 300 according to the present invention, wherein - when compared to the embodiment of figure 15 - the external collecting and / or evaporating pot 342 of figure 15 is substituted by or with an air filter 344.

[0060] Figure 17 is a schematic view with respect to a further alternative concrete embodiment of a humidity control arrangement 100 according to the present invention which similar to that of Figure 15, but plural coolers 310 are involved.

[0061] These and further aspects of the present invention will also be described in detail in the following passages:

[0062] The present invention is concerned with the technical field of immersion microscopy in general and in particular with immersion microscopy using a biological compatible immersion fluid 20, water as an immersion fluid, or a water based or aqueous immersion fluid 20.

[0063] Especially, the fields of (i) fluorescence immersion microscopy, (ii) immersion microscopy for investigating biological specimens, and / or (iii) immersion microscopy involving automated systems are concerned.

[0064] In the sense of the present invention the terms water, aqueous solution, and biological compatible fluid are used as synonyms in the sense of the present invention and throughout the present disclosure for characterizing an immersion fluid to be used in the context of the present invention. Inter alia, the following corresponding requirements may at least in part play an important role:

[0065] - Long term investigation and / or long maintenance intervals - e.g. several weeks or months - are envisaged in biologically relevant immersion microscopy, during which no active air exchange with an external or outside space or atmosphere is or shall be possible, namely due to danger of contamination of the biological specimen and / or of the environment to be investigated.

[0066] - A dedicated imaging compartment is required that is isolated from the outside space to a certain degree or extent, namely in order to provide (i) isolation from external light impact or incidence, (ii) isolation from mechanical vibration, and / or (iii) a thermal insulation or isolation in order to allow temperature control for repeatable imaging conditions. These aspects are also important in order to protect the nature and properties of the biological specimen under investigation.

[0067] As a consequence, the present invention in particular refers to an immersion microscopic situation, wherein the imaging compartment is closed, insulated, and / or isolated from an outside space and / or atmosphere over a comparable long time, for instance - but not only - for several weeks or months.

[0068] Under such circumstances, the following challenges and / or problems may occur at least partially or in an arbitrary combination and are to be solved by the means and measures according to the present invention:

[0069] 1. During water immersion microscopy, water vapor or in general vapor of the biologically compatible immersion fluid 20 is generated, for instance from the wet track of an immersion droplet that evaporates with time. The vapor content leads to or may tend to form a saturated vapor atmosphere in the closed, isolated and insulated imaging compartment 110. With the vapor content rising towards saturation increases the risk of uncontrolled condensation and / or precipitation in the imaging compartment 110. As a consequence, numerous negative effects may arise, including damage of the microscope and its components or of any other, for instance electrical facilities.

[0070] 2. During immersion microscopy, purging of immersion lines is necessary in order to remove bubbles from the immersion liquid or fluid, such bubbles deteriorating the imaging quality. The conventionally taken measure of placing a purging droplet on a microscopy slide outside the sample area where the droplet shall evaporate is not feasible in a closed compartment 110 and its environment with the saturated vapor atmosphere.

[0071] 3. After conventionally purging an immersion droplet in order to remove bubbles from the underlying field of view or FoV, the droplet may e.g. be absorbed by one or plural porous rings formed on or in a region of the underlying objective lens 2 for being evaporated. This does not work in the case of the present invention’s situation with a closed imaging compartment 110. Additionally under such conditions a microbiological growth for instance of fungi, bacteria, etc. will occur on the continuously wet surfaces and / or parts of the microscope and other facilities, thereby leading to microbiological contamination.

[0072] 4. Conventional disposal removal solutions or facilities may include a water trap and / or a pump and they are complicated and do not solve the problem as mentioned above under subsection 1 above.

[0073] According to the present invention, inter alia the following solutions for the underlying problems are proposed, which may be combined with each other in an arbitrary manner.

[0074] Aspects of humidity control in closed imaging compartment immersion microscopy

[0075] According to a first aspect or solution principle of the present invention and for controlling humidity of an atmosphere of a closed imaging compartment 110 of an immersion microscopy arrangement 1 or device 1, one or plural coolers 310 are used in order to control the temperature within the closed imaging compartment 110 and / or of the atmosphere of the closed imaging compartment 110, namely by removing heat generated by the microscope 100, its components, and / or other facilities from the closed imaging compartment 110.

[0076] Such a cooler 310 maybe formed by or may comprise a Peltier element 350, and / or coolers 310 with one or plural fans 360 may be used. The immersion fluid vapor 22 or water vapor will - under operation of the cooler 310 - condense on cold cooling surfaces 320 of the cooler 310 and form droplets of immersion fluid 20 or water which then may drop down as a condensate.

[0077] A funnel 331 as a primary condensate collecting means 330 may be located below the cooler 310 in order to collect the immersion fluid 20 or water condensate and may also lead the thereby collected liquid out of the closed imaging compartment 110 and / or to an evaporation pot 342 which may be positioned outside the closed imaging compartment 110 and which may also be referred to as a secondary condensate collecting means 341.

[0078] The collecting pot 342 may also be located in an area 130 with an active ventilation 345 and with an exhaust means 370 or exhaust or ventilation line 370 leading to the outside of the closed imaging compartment 110 and / or the microscope or instrument area 130.

[0079] By adaptation and / or manipulation of the number of the coolers 310, of the operation and / or of the airflow generated, the humidity and / or other parameters of the atmosphere of the closed imaging compartment 110 can be controlled and adjusted.

[0080] Thereby, the required configuration and the operation of the involved components are simple, and no additional active components are necessary.

[0081] Aspects of the removal of excessive purging and / or immersion liquid in closed imaging compartment immersion microscopy

[0082] On the other hand, in view of a required removal of purging liquid 20, and according to the present invention’s additional or alternative solution principle, excessive immersion liquid 20 can be removed from the closed or closable imaging compartment 110 by using an adhesive and / or absorptive part 410 also referred to as an immersion liquid receiving part or portion 410, which is capable of receiving and / or absorbing excessive amounts of purging liquid 20 and / or immersion liquid 20 and which can be transferred into the vicinity of the microscope 100 and into the closed imaging compartment 110, in particular in an unloaded state, and away from the closed imaging compartment 110 and the microscope 100, in particular in a loaded state. After removal from the closed imaging compartment 110 and the microscope 100, the excessive immersion liquid 21 loaded to the adhesive and / or absorptive part 410 can be evaporated in an outside space 120 of the closed imaging compartment 110 in order to form vapor 22, thereby unloading the adhesive and / or absorptive part 410.

[0083] According to a first aspect of immersion or purging liquid disposal, a purging droplet or a droplet of immersion fluid 20 (for instance for purging) may be transferred onto an underlying microscopy slide 4 serving as a specimen carrier from the closed imaging compartment 110 by a robot, namely in order to be evaporated outside the closed imaging compartment 110.

[0084] Additionally or alternatively, a plate part or means which is absorptive with respect to the purging liquid 20 and / or the immersion fluid 20 and which may be e.g. hygroscopic, hydrophylic and / or porous and / or formed as a plate part may be transferred to the microscope 1 to perform the required purging, for instance instead of a microscopy slide 4 serving as a specimen carrier. After transferring the absorptive part 410, 411, 412 out of the closedimagingcompartment 110, the absorbed excessive immersion fluid 21 or water evaporates in an area 120 that is separated and isolated from the imaging compartment 110 thereby in a noncritical area.

[0085] Further alternatively or additionally an underlying microscopy slide 4 may be fixed to an assembly 415 which is used in general in order to transfer any slide 4 (e.g. a slide 4 serving as a specimen carrier during the microscopy process) to the microscope 1 and thus into the closed imaging compartment 110 and out of it. The configuration of the microscopy slide 4 comprises an adhesive and / or adoptive absorptive (e.g. hydrophilic porous) plate and / or part 411 which is configured and comprises means for absorbing the purging immersion fluid 20 and / or water. After transfer of the modified microscopy slide 4 out of the closed imaging compartment 110, the loaded absorbed fluid 21 and / or water evaporates in an area that is uncritical for the closed imaging compartment 110.

[0086] The absorptive part 411 can alternatively be a plate placed next to a microscopy slide 4 in a horizontal plane where the bottoms of the slide 4 and of the plate 411 are aligned.

[0087] Otherwise the absorptive part 411 can be integrated into an underlying slide holder 415 or slide carrier 415 which is used for transferring an underlying microscopy slide 4 into and out of the closed imaging compartment 110 and to and from, respectively, the underlying microscope 1 as such.

[0088] The present invention and its embodiments may further be understood based on the following items:

[0089] (1) A humidity control arrangement 300 according to the present invention is configured and designed for closed imaging compartment immersion microscopy. It is configured to control humidity of an atmosphere of a closed imaging compartment 110 of an immersion microscopy arrangement 1. It comprises at least one cooler 310 that is configured to be arranged or that is arranged inside the closed imaging compartment 110 and / or that is configured to remove heat from the closed imaging compartment 110. The at least one cooler 310 comprises at least one cooling surface 320 that is configured to be cooled down upon operation of the at least one cooler 310 in order to force vapor contained in the atmosphere of the closed imaging compartment 110 to condense condensate on the cooled cooling surface 320 in order to form a condensate. The arrangement 300 further comprises exhaust means 340 configured to exhaust said condensate to an outside 130 of the closed imaging compartment 110.

[0090] (2) In the humidity control arrangement 300 according to item (1), the at least one cooler 310 may be or may comprise at least one Peltier element 350, which is in particular formed or configured to be formed within the closed imaging compartment 110.

[0091] (3) In the humidity control arrangement 300 according to any one of the preceding item (1) and (2), the at least one cooler 310 may comprises at least one fan 360, which may be in particular formed or maybe configured to be formed within the closed imaging compartment 110.

[0092] (4) In the humidity control arrangement 300 according to any one of the preceding items (1) to (3), a primary condensate collecting means 330 may further ne comprised, which in particular may be formed as a part of the exhaust means 340, formed as a funnel 331 and / or formed or configured to be formed at least in part within the closed imaging compartment 110.

[0093] (5) In the humidity control arrangement 300 according to any one of the preceding items (1) to (4), a secondary condensate collecting means 341 may further be comprised, which in particular may be formed as a part of the exhaust means 340, formed as a pot 342 and / or formed or configured to be formed outside the closed imaging compartment 110.

[0094] (6) In the humidity control arrangement 300 according to item (5), an active ventilation means 345 may further be comprised which may be arranged and configured for ventilating the secondary condensate collecting means 341, which in particular may be formed as a part of and / or in a vicinity of the secondaiy condensate collecting means 341, and / or formed or may be configured to be formed outside the closed imaging compartment 110.

[0095] (7) An immersion liquid removal arrangement 400 according to the present invention is configured and designed for closed imaging compartment immersion microscopy. The arrangement 400 is configured to remove purging and / or excessive immersion liquid 20 of a or in a closed imaging compartment 110 of an underlying immersion microscopy arrangement 1. It is arranged or configured to be arranged inside the closed imaging compartment 110 in a manner transferable to an outside 120 of the closed imaging compartment 110. It comprises at least one immersion liquid receiving portion 410 that is configured (i) to at least one of receive, collect, bind, adsorb, chemisorb, physisorb, and absorb immersion liquid 20 or fluid 20, in particular from the atmosphere, from and / or within the closed imaging compartment 110 and (ii) in particular to controllably release any immersion liquid 20 or fluid 20 carried by the liquid receiving portion 410 when positioned outside the closed imaging compartment 110, in particular by evaporation.

[0096] (8) In the immersion liquid removal arrangement 400 according to item (7), the immersion liquid receiving portion 410 may be or may comprise an absorptive, hydrophilic, and / or porous part or plate 411.

[0097] (9) In the immersion liquid removal arrangement 400 according to any one of items (7) and (8), the immersion liquid receiving portion 410 may be a microscopy slide 4, a part of a microscopy slide 4, a portion in combination with a microscopy slide 4, a portion integrated into or a part of a holder 415, carrier 415, support 415 and / or transfer assembly 415 for a microscopy slide 4.

[0098] (10) In the immersion liquid removal arrangement 400 according to any one of items (7) to (9), the immersion liquid receiving portion 410 may be or may comprise a hydrophilic and / or porous plate 411 which in particular may comprise a highly plan or planar surface 411a, that is more particularly configured not to emit particle contamination and / or onto which an absorbing material 412 for absorbing immersion liquid 20 is or can be formed.

[0099] (11) In the immersion liquid removal arrangement 400 according to any one of items (9) and (10), surface portions of the microscopy slide or of the plate 411, respectively, not covered by an absorbing material 412 for absorbing immersion liquid 20 may form or may carry a well and / or a well support structure 413.

[0100] (12) An immersion microscopy arrangement 1 according to the present invention is configured and / or designed for closed imaging compartment immersion microscopy. The arrangement 1 comprises a closed or closable imaging compartment 110 that is or is configured to be insulated and / or isolated from an external space or compartment 120, 130 regarding atmosphere, humidity, dust, light, heat and / or temperature, and a microscope 100 that is configured for immersion microscopy, wherein said microscope 100 is completely or least partly contained in and surrounded by said closed or closable imaging compartment 110, and at least one of a humidity control arrangement 300 according to any one of items (1) to (6) and an immersion liquid removal arrangement 400 according to any one of items (7) to (11) is provided and / or formed.

[0101] (13) In a method of performing immersion microscopy, in particular with respect to a specimen 3 according to the present invention, an immersion microscopy arrangement 1 for closed imaging compartment immersion microscopy according to item (12) is used and operated, and at least one of a humidity control arrangement 300 according to any one of items (1) to (6) and an immersion liquid removal arrangement 400 according to any one of items (7) to (11) is controllably operated in order to control humidity and / or content of purging liquid 20 and / or excessive immersion liquid 20 in the closed imaging compartment 110 of the immersion microscopy arrangement 1. List of Reference Signs immersion microscopy arrangement objective, objective lens -0 conical part or portion -1 columnar or cylindrical part or portion -2 distal or front end or lens -3 central optical axis specimen specimen carrier, microscopic / microscopy slide adjustment means in the height or z direction filter a beam splitter b beam splitter c beam splitter diffraction grating detector 0a light source 0b light source bright- field observation 1 (2-dimensional) detector 2 lens 3 lens 4a mirror 4b mirror 0 immersion / purgingliquid / fluid (before absorption)1 immersion / purging liquid / fluid (after absorption)2 immersion / purgingliquid / fluid (evaporated outside) 00 (immersion) microscope 10 closed / closable imaging compartment 20 liquid handling compartment 21 liquid handler, liquid handling device 30 service and control compartment 50 transfer door / window 300 humidity control arrangement, means or device

[0102] 310 cooler

[0103] 320 cooling surface

[0104] 330 (primary) condensate collecting means

[0105] 331 funnel

[0106] 340 exhaust means, exhaust line, exhaust pipe

[0107] 341 (secondary) condensate collecting means

[0108] 342 (collecting and / or evaporating) pot

[0109] 344 air filter

[0110] 345 active ventilation means

[0111] 350 Peltier element

[0112] 360 fan

[0113] 370 ventilation duct

[0114] 371 inlet

[0115] 372 ventilation exhaust

[0116] A direction of approaching

[0117] B direction of retraction

[0118] 400 Immersion liquid removal arrangement, means or device

[0119] 410 immersion liquid receiving portion

[0120] 411 absorptive, hydrophilic, and / or porous part / plate

[0121] 411a (highly plan / planar) surface

[0122] 412 Immersion liquid absorbing material

[0123] 413 well and support structure

[0124] 415 holder, support, carrier, and / or transfer assembly for a microscopy slide

[0125] 11 length

[0126] LI length

[0127] 12 length

[0128] L2 length

[0129] T1 thickness wl width

[0130] W1 width w2 width

[0131] W2 width x spatial direction

[0132] X direction of the 1stlongitudinal extension y spatial direction

[0133] Y direction of the 2ndlongitudinal extension z spatial direction

[0134] Z direction of the height extension

Claims

Claims1. Humidity control arrangement (300) for closed imaging compartment immersion microscopy,- configured to control humidity of an atmosphere of a closed imaging compartment (110) of an immersion microscopy arrangement (1),- comprising at least one cooler (310) that is configured to be arranged or that is arranged inside the closed imaging compartment (110) and / or that is configured to remove heat from the closed imaging compartment (110),- wherein the at least one cooler (310) comprises at least one cooling surface (320) that is configured to be cooled down upon operation of the at least one cooler (310) in order to force vapor contained in the atmosphere of the closed imaging compartment (110) to condense on the cooled cooling surface (320) in order to form a condensate, and- further comprising exhaust means (340) configured to exhaust said condensate to an outside (130) of the closed imaging compartment (110).

2. Humidity control arrangement (300) according to claim 1, wherein the at least one cooler (310) is or comprises at least one Peltier element (350), which is in particular formed or configured to be formed within the closed imaging compartment (110).

3. Humidity control arrangement (300) according to any one of the preceding claims, wherein the atleast one cooler (310) comprises atleast one fan (360), which is in particular formed or configured to be formed within the closed imaging compartment (110).

4. Humidity control arrangement (300) according to any one of the preceding claims, further comprising a primary condensate collecting means (330), which in particular is formed as a part of the exhaust means (340), formed as a funnel (331) and / or formed or configured to be formed at least in part within the closed imaging compartment (110).

5. Humidity control arrangement (300) according to any one of the preceding claims, further comprising a secondary condensate collecting means (341), which is in particular formed as a part of the exhaust means (340), formed as a pot (342) and / or formed or configured to be formed outside the closed imaging compartment (110).

6. Humidity control arrangement (300) according to claim 5, further comprising an active ventilation means (345) which is arranged and configured for ventilating the secondary condensate collecting means (341), which is in particular formed as a part of and / or in a vicinity of the secondary condensate collecting means (341), and / or formed or configured to be formed outside the closed imaging compartment (110).

7. Immersion liquid removal arrangement (400) for closed imaging compartment immersion microscopy,- configured to remove purging and / or excessive immersion liquid (20) of a or in a closed imaging compartment (110) of an immersion microscopy arrangement (1),- arranged or configured to be arranged inside the closed imaging compartment (110) in a manner transferable to an outside (120) of the closed imaging compartment (110),- comprising at least one immersion liquid receiving portion (410) that is configured (i) to at least one of receive, collect, bind, adsorb, chemisorb, physisorb, and absorb immersion liquid (20), in particular from the atmosphere, from and / or within the closed imaging compartment (110) and (ii) in particular to controllably release any immersion liquid (20) carried by the liquid receiving portion (410) when positioned outside the closed imaging compartment (110), in particular by evaporation.

8. Immersion liquid removal arrangement (400) according to claim 7, wherein the immersion liquid receiving portion (410) is or comprises an absorptive, hydrophilic, and / or porous part or plate (411) or plate (411).

9. Immersion liquid removal arrangement (400) according to any one of claims 7 and 8, wherein the immersion liquid receiving portion (410) is a microscopy slide (4), a part of a microscopy slide (4), a portion in combination with a microscopy slide (4), a portion integrated into or a part of a holder (415), carrier (415), support (415) and / or transfer assembly (415) for a microscopy slide (4).

10. Immersion liquid removal arrangement (400) according to any one of claims 7 to 9, wherein the immersion liquid receiving portion (410) is or comprises a hydrophilic and / or porous plate (411) which in particular comprises a highly plan or planar surface (411a), that is more particularly configured not to emit particle contamination and / or onto which an absorbing material (412) for absorbing immersion liquid (20) is or can be formed.

11. Immersion liquid removal arrangement (400) according to any one of claims 9 and 10, wherein surface portions of the microscopy slide or of the plate (411), respectively, not covered by an absorbing material (412) for absorbing immersion liquid (20) forms or carries a well and / or a well support structure (413).

12. Immersion microscopy arrangement (1) for closed imaging compartment immersion microscopy, comprising:- a closed or closable imaging compartment (110) that is or is configured to be insulated and / or isolated from an external space or compartment (120, 130) regarding atmosphere, humidity, dust, light, heat and / or temperature, and- a microscope (100) configured for immersion microscopy, wherein:- said microscope (100) is completely or least partly contained in and surrounded by said closed or closable imaging compartment (110), and at least one of a humidity control arrangement (300) according to any one of claims 1 to 6 and an immersion liquid removal arrangement (400) according to any one of claims 7 to 11 is provided.

3. Method of performing immersion microscopy, in particular with respect to a specimen (3), wherein:- an immersion microscopy arrangement (1) for closed imaging compartment immersion microscopy according to independent claim 12 is used and operated, and- at least one of a humidity control arrangement (300) according to any one of claims 1 to 6 and an immersion liquid removal arrangement (400) according to any one of claims 7 to 11 is controllably operated in order to control humidity and / or content of purging liquid (20) and / or excessive immersion liquid (20) in the closed imaging compartment (110) of the immersion microscopy arrangement (1).

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