Adapter for Use with a Sample Holder, and Method for Arranging a Sample in a Detection Beam Path of a Microscope

Abstract

An adapter is useful with a sample holder of a microscope. The adapter has at least one support region for reproducibly orienting the adapter in a mounted state in a sample holder support. The adapter also has a first coupling point for detachable connection to a coupling structure of a sample holder on one side, and a second coupling point for detachable connection to a coupling structure of a sample manipulator on a side of the adapter opposite to the first coupling point. The adapter is useful with the sample holder, a sample chamber, a microscope and a method for arranging a sample in a detection beam path of a microscope.

Claims

1: An adapter for a sample holder of a microscope, the adapter comprising: at least one support region for reproducibly orienting the adapter in a mounted state in a sample holder support, a first coupling point for detachable connection to a coupling structure of a sample holder on one side of the adapter and a second coupling point for detachable connection to a coupling structure of a sample manipulator on a side of the adapter opposite to the first coupling point.

2: A sample holder for receiving and holding a sample to be observed, the sample holder comprising: a coupling structure, which is compatible with a first coupling point of an adapter, which comprises at least one support region for reproducibly orienting the adapter in a mounted state in a sample holder support a first coupling point for detachable connection to a coupling structure of a sample holder on one side of the adapter, and a second coupling point for detachable connection to a coupling structure of a sample manipulator on a side of the adapter opposite to the first coupling point, wherein the coupling structure facilitates a detachable connection of the sample holder to the adapter by the coupling structure and the first coupling point.

3: The sample holder as claimed in claim 2, comprising the adapter connected by the coupling structure and the first coupling point.

4: A sample chamber for a microscope comprising a sample holder support and an adapter, wherein the adapter comprises at least one support region detachably mounted or mountable in the sample holder support.

5: A microscope comprising the sample chamber as claimed in claim 4.

6: A method for arranging a sample in a detection beam path of a microscope, the method comprising: providing the sample chamber as claimed in claim 4, inserting a sample to be observed, which is held on a sample holder, into an interior of the sample chamber, wherein the sample holder comprises a coupling structure connected to a first coupling point of the adapter and the adapter with the at least one support region, is detachably mounted in the sample holder support of the sample chamber with predefined positioning, connecting the adapter to a sample manipulator by a second coupling point of the adapter and a coupling structure of the sample manipulator, and moving the sample holder with the sample manipulator in the detection beam path of the microscope.

7: The sample holder of claim 2, further comprising: a sample stage or sample cage, and a carrier portion.

8: The sample holder of claim 7, wherein the carrier portion is fastened to only one side of the sample stage, and wherein the sample holder comprises no barrier to observation on any other side of the sample stage.

9: The sample holder of claim 7, wherein the carrier portion comprises at least one aperture.

10: The sample holder of claim 7, wherein the sample stage or sample cage is configured to support a sample having a width of more than 5 mm.

11: The sample holder of claim 3, wherein the first coupling point is a dovetail guide.

12: The microscope of claim 5, wherein the microscope is a light sheet microscope.

13: The microscope of claim 12, configured to receive a sample having a width of more than 5 mm.

14: The method of claim 6, wherein the microscope is a light sheet microscope, and wherein the sample has a width of more than 5 mm.

Description

[0030] The invention will be explained in more detail below on the basis of schematic figures and exemplary embodiments. In the figures:

[0031] FIG. 1 shows a first exemplary embodiment of a coupling piece or adapter according to the invention;

[0032] FIG. 2 shows a first exemplary embodiment of a sample chamber according to the invention;

[0033] FIG. 3 shows a second exemplary embodiment of a sample chamber according to the invention;

[0034] FIG. 4 shows a first exemplary embodiment of a sample manipulator with an open gripper;

[0035] FIG. 5 shows the first exemplary embodiment of the sample manipulator with a closed gripper;

[0036] FIG. 6 shows a first exemplary embodiment of a sample holder according to the invention;

[0037] FIG. 7 shows a second exemplary embodiment of a sample holder according to the invention;

[0038] FIG. 8 shows a detailed view of an adapter in the mounted state;

[0039] FIG. 9 shows a sample chamber according to the invention, equipped with a sample holder and a sample;

[0040] FIG. 10 shows an exemplary embodiment of a sample chamber with a sample holder, adapter and sample manipulator in a detection beam path of a microscope;

[0041] FIG. 11 shows a sectional illustration of a light sheet microscope with an inserted sample chamber and a sample manipulator in a coupling position;

[0042] FIG. 12 shows a schematic section of a light sheet microscope with illumination objectives;

[0043] FIG. 13 shows a schematic sectional illustration of a light sheet microscope with illustrations of a coupling position and a loading position of the sample manipulator; and

[0044] FIG. 14 shows a schematic illustration of a sample chamber with a sample holder, adapter and sample manipulator, and exemplary movement dimensions.

[0045] The drawings are schematic. Identical technical elements are provided with the same reference signs.

[0046] A first exemplary embodiment of a coupling piece 1 or adapter 1 according to the invention, illustrated schematically in FIG. 1, comprises an elongate form that is flattened on both sides. At the end regions, support regions 2 are present in each case on one side. These are situated on a side face of the adapter 1 that faces a sample chamber 3 (see FIGS. 2, 8) in a mounted state of the adapter 1. A first coupling point 1.1, configured as a so-called dovetail guide in the exemplary embodiment, is situated on the same side. A second coupling point 1.2 in the form of an aperture is situated on the opposite side face, which faces away from the sample chamber 3 in the mounted state of the adapter 1. The latter can be embodied as a blind hole or as a passage opening. In further embodiments, the second coupling point 1.2 can be embodied, for example, as a dovetail guide, hook, funnel, sphere, etc.

[0047] FIG. 2 shows a first exemplary embodiment of a sample chamber 3 according to the invention. At its upper edge, it comprises a sample holder support 4 in the form of respectively one groove or cutout in two mutually opposing walls of the sample chamber 3. The walls of the sample chamber 3 comprise windows 5 and enclose an interior 6 of the sample chamber 3. In order to introduce, for example, a desired medium, for example a culture medium, into the interior 6 or in order to let said medium flow through the interior 6, ports 7 for supply and/or removal are present (see also FIG. 3).

[0048] FIG. 3 shows a further embodiment of the sample chamber 3 with viewing windows 5 and ports 7. The upper edge of the sample chamber 3 comprises the sample holder support 4 in the form of a cutout, into which a sample holder 8 with an adapter 1 detachably fastened thereto engages or is able to engage.

[0049] Furthermore, a sample manipulator 12 is present with a gripper as a coupling structure 13. The latter serves to grip and hold the sample holder 8. To this end, the sample manipulator 12 is detachably connected to the second coupling point 1.2 of the adapter 1 by means of the coupling structure 11. The sample manipulator 12, more particularly the gripper, is movable in controlled fashion by means of a drive 17, which in turn has established a connection with a control unit 18, said connection being suitable for transmitting control commands.

[0050] The gripper (coupling structure 13) as part of the sample manipulator 12 is shown in an open state in FIG. 4.

[0051] In FIG. 5, the sample manipulator 12 is illustrated with a closed gripper.

[0052] An exemplary embodiment of a sample holder 8 is illustrated in FIG. 6. The sample holder 8 holds the sample P on a sample stage 9. It comprises a coupling piece 1, which is embodied as a flat rod in this example. In different variants, the sample holder 8 can be embodied to receive various samples P. A carrier portion 10 between the sample stage 9 and coupling structure 11 is laterally connected to the sample stage 9 and embodied in an offset or angled fashion such that the center of gravity of the sample holder 8 is located below the coupling structure 11 and the sample holder 8 hangs out vertically, even with a sample P.

[0053] Thus, a sample holder 8 according to the further exemplary embodiment illustrated in FIG. 7 comprises a sample stage 9, a carrier portion 10 and the coupling structure 11 of the sample holder 8 situated thereon. By way of example, the coupling structure 11 is embodied in such a way that the latter fits into the first coupling point 1.1 of the adapter 1 illustrated in FIG. 1 in detachably interlocking fashion. The carrier portion 10 comprises vertically extending slots.

[0054] FIG. 8 shows, in a magnified detailed illustration, the sample chamber 3 with an inserted sample holder 8 and a gripper of the sample manipulator 12, said gripper being in contact with the sample holder 8. The adapter 1 has been inserted into the sample holder support 4 such that the sample holder 8 is held with a defined position relative to the sample chamber 3 in the interior 6 thereof. The sample chamber 3 can be moved together with the sample holder 8, for example be inserted into a microscope 16 (see, e.g., FIGS. 10,11) or removed therefrom, for as long as the sample manipulator 12 has not yet been connected to the second coupling point 1.2 (covered by the sample manipulator 12). In the illustrated exemplary embodiment, a part of the sample manipulator 12 situated at the second coupling point 1.2 engages around the adapter 1.

[0055] The sample chamber 3 with the inserted sample holder 8 and the sample P are shown in perspective fashion in FIG. 9.

[0056] FIG. 10 shows an exemplary embodiment of a sample chamber 3 with a sample holder 8 (not shown), adapter 1 and sample manipulator 12 in a detection beam path 15 of a microscope 16. A light sheet 19 only indicated here can be generated along an illumination beam path 14 in the interior 6 of the sample chamber 3. The sample P is illuminated by the light sheet 19, in each case in one plane. Image data of the sample P are captured by means an objective 20 along the detection beam path 15.

[0057] FIG. 11 shows a microscope 16 with an inserted sample chamber 3, illustrated in a section. The sample holder 8 with adapter 1 and sample P were equipped outside of the microscope 16 and inserted into the microscope 16 as a unit. There, the adapter 1 is contacted by, and detachably connected to, the sample manipulator 12, which has been displaced into a coupling position 21 in controlled fashion. The sample holder 8 is shown in the work direction 23, which allows an illumination of the sample P for both objectives 20 (one of which is illustrated) of the illumination beam path 14 and an image capture along the detection beam path 15.

[0058] The sample chamber 3 and objectives 20 of the microscope 16 can be seen in FIG. 12. The objectives 20 serve to generate the light sheet 19 in the interior 6 of the sample chamber 3.

[0059] A loading position 22 and the coupling position 21 of the sample manipulator 12 are shown in a further sectional illustration of the microscope 16 (FIG. 13).

[0060] Exemplary dimensions of a sample P to be observed by means of the invention can be gathered from FIG. 14. The dimensions specified in exemplary fashion simultaneously specify possible distances through which a sample P is movable in controlled fashion by means of the sample manipulator 12 that has been coupled at the second coupling point 1.2. Rotations about the longitudinal axis (z-axis) are not illustrated. The movements of the sample manipulator 12 and the movements of the sample P resulting therefrom are prompted, and optionally also monitored, by the control unit 18.

REFERENCE SIGNS

[0061] 1 Adapter, coupling piece [0062] 1.1 First coupling point [0063] 1.2 Second coupling point [0064] 2 Support region [0065] 3 Sample chamber [0066] 4 Sample holder support [0067] 5 Window [0068] 6 Interior [0069] 7 Port [0070] 8 Sample holder [0071] 9 Sample stage [0072] 10 Carrier portion [0073] 11 Coupling structure (of the sample holder) [0074] 12 Sample manipulator [0075] 13 Coupling structure (of the sample manipulator) [0076] 14 Illumination beam path [0077] 15 Detection beam path [0078] 16 Microscope [0079] 17 Drive [0080] 18 Control unit [0081] 19 Lightsheet [0082] 20 Objective [0083] 21 Coupling position [0084] 22 Loading position [0085] 23 Work direction [0086] P Sample