Microscope

DE102023113324B4Active Publication Date: 2025-03-27THOMS ENG GMBH
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Patent Information

Application Number
DE102023113324
Authority / Receiving Office
DE · DE
Patent Type
Patents
Current Assignee / Owner
Filing Date
2023-05-22
Publication Date
2025-03-27
Estimated Expiration
2043-05-22

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Abstract

microscope (1) comprising arranged vertically from bottom to top in a provided setup a) a microscope base (2) with a lighting unit (3), b) a microscope slide table (4) with a support surface (5) for a microscope slide (6), wherein the support surface (5) has an opening (8) penetrating the microscope slide table (4) through which light emanating from the lighting device (3) shines from below upwards, c) a microscope objective holder (9) with at least one microscope objective (10), d) a tube lens holder (11) with a tube lens (12), e) a surface sensor holder (13) with a surface sensor (14), wherein the microscope base (2) and / or the slide stage (4), the microscope objective holder (9) and the tube lens holder (11) and / or the surface sensor holder (13) are connected to each other via a support device (15), wherein the support device (15) comprises at least three rods (16), each rod (16) connecting the microscope base (2) and / or the slide stage (4), the microscope objective holder (9), and the tube lens holder (11) and / or the area sensor holder (13) to each other, wherein a sliding device (29) for two-dimensional horizontal sliding of a microscope slide (6) on the support surface (5) of the microscope slide table (4) is arranged, wherein the sliding device (29) comprises a microscope slide frame (30) slidably arranged on the support surface (5) of the microscope slide table (4) with a continuous recess (31) for receiving the microscope slide (6), characterized by the fact that The shape and dimensions of the continuous recess (31) are adapted to the shape and dimensions of the microscope slide (6) in such a way that the microscope slide (6) always rests directly on the support surface (5) of the microscope slide table (4) within the continuous recess (31) due to gravity and can be precisely moved with the sliding device (29) over the microscope slide frame (30) without a holder for the microscope slide (6) on the sliding device (29), without any bearing play of the sliding device (29) leading to an inclination of the microscope slide (6) during movement and an associated need for refocusing.
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Description

[0001] The invention relates to a microscope, in particular a travel and / or laboratory microscope.

[0002] Microscopes are typically designed in such a way that a beam of light from a light source, viewed in transmitted light from below, is directed through a glass slide on which the flat object to be magnified is located. The light is attenuated to varying degrees by the different structures within the object, so that a transmitted image of the differently absorptive structures can be captured on the side of the object opposite the light source. This light image is conventionally projected onto a magnified intermediate image using a microscope objective, which is then viewed with further magnification through an eyepiece, which functions as a magnifying glass.

[0003] In modern microscopes, in addition to visual observation, the intermediate image can often be viewed using a digital camera, which projects the intermediate image onto an area sensor. These area sensors can be implemented as CCD or C-MOS sensors and comprise a planar matrix of individual elements (pixels), each of which can detect the light intensity at the respective individual element and, in the case of color sensors, also the light color.

[0004] Each pixel uses three subpixels, each sensitive to different wavelength ranges. Particularly advanced are the detection beam paths, in which the microscope objective projects the transmitted image behind the object to infinity, and a so-called tube lens projects this transmitted image from infinity onto the area sensor behind the microscope objective. In this arrangement, the magnification of the image on the area sensor corresponds to the ratio of the focal lengths of the tube lens and the microscope objective.

[0005] Typically, these microscopes are designed so that the microscope objective, tube lens, and area sensor are at fixed distances. A height-adjustable slide stage moves the specimen slide to the distance from the microscope objective at which the radiographic image of the specimen on the slide stage is sharply projected onto the area sensor. At this distance, the object points in the object plane of the specimen are sharply projected onto the image points of the area sensor in its image plane.

[0006] In order to capture a specific section of the object in full, the slide is moved on the slide stage. This is done using an xy translation stage into which the slide is clamped and with which even small movements can be carried out, for example at comparatively high magnifications. However, the slide is often not attached exactly at right angles to the optical axis of the microscope or is slightly uneven, so that when moved, the distance between the slide and the microscope objective changes and the image becomes blurred. At high magnifications, for example 20x or 40x, deviations in the distance between the slide and the microscope objective on the order of micrometers can already lead to a blurred image, since the depth of field of the optical image of such microscope objectives is in this order due to their numerical aperture NA.

[0007] Another problem with conventional microscopes is that the illumination, slide stage, microscope objective, tube lens, and area sensor are mechanically connected to each other by a metal column (or stand). To achieve sufficient mechanical stability against bending and twisting of the column, this column must be very solid and have a relatively large cross-section, making the microscope quite heavy overall with this type of arrangement. A typical laboratory microscope, for example, weighs approximately 7 kg.

[0008] Such microscopes are known, for example, from DE 198 61 507 B3 and DE 691 16 818 T2.

[0009] Microscopes are known from JP 2010 - 117 667 A, US 2 142 627 A, and DE 10 2014 226 942 A1 in which the microscope components are connected to one another via several rods. JP 2010 - 117 667 A shows a displacement device for a slide, in which the slide is clamped and held by a holder on its sides. In US 2 142 627 A, the slide is clamped to the slide stage by spring clamps. DE 10 2014 226 942 A1 provides a positioning section as a slide stage, so that the slide stage is positioned in its entirety.

[0010] US 5 077 620 A discloses a motor-driven positioning device in which a stage is linearly displaced along two rails. DE 10 2016 125 691 A1 discloses a holder for a specimen slide, which has a slot-shaped receptacle for the specimen slide, into which the specimen slide is automatically clamped upon insertion by means of a pressure element. US 2002 / 0 131 167 A1 discloses a holder for a specimen to be examined.

[0011] Other microscopes in which the components are connected to one another via one or more rods are known from US 2016 / 0 041 375 A1 and US 2003 / 0 030 747 A1.

[0012] The invention is based on the object of providing a new microscope, in particular a microscope which at least partially overcomes the aforementioned disadvantages of known microscopes and / or is light compared to known microscopes of comparable object resolution.

[0013] This object is achieved by a microscope having the features of claim 1. Advantageous embodiments and further developments are specified in the dependent claims.

[0014] The microscope according to the invention comprises, in a provided setup, arranged vertically from bottom to top a) a microscope base with a lighting unit, in particular a replaceable lighting unit, b) a slide table with a, in particular horizontal, support surface for a slide, wherein the support surface has a, in particular vertical, opening penetrating the slide table, through which light emanating from the illumination device shines from bottom to top, wherein the microscope base and slide table can be separate components that can be positioned differently relative to one another, in particular also displaceable relative to one another and / or fixed in different positions relative to one another, or can also be components that are firmly connected to one another or can form a common component, c) a microscope objective holder with at least one microscope objective, d) a tube lens holder with a tube lens, e) an area sensor holder with an area sensor, wherein the microscope objective holder and the tube lens holder can be separate components that can be positioned differently relative to one another, in particular also displaceable relative to one another and / or fixable in different positions relative to one another, or can also be components that are firmly connected to one another or can form a common component, wherein on the one hand the microscope base and / or the object carrier table, on the other hand the microscope objective holder and also the tube lens holder and / or the area sensor holder are connected to one another via a carrier device.

[0015] The invention provides that the support device comprises at least three, in particular vertical, rods, each rod connecting the microscope base and / or the slide stage, the microscope objective holder, and also the tube lens holder and / or the area sensor holder. The rods can be, for example, steel rods, in particular high-strength steel rods.

[0016] The microscope according to the invention is in particular a travel and / or laboratory microscope.

[0017] The advantages of the invention lie in the fact that the massive and therefore heavy column used in the prior art for the mechanical connection of the illumination, slide stage, microscope objective, tube lens, and area sensor can be eliminated. A support system with three rods instead of just one laterally arranged column achieves the required mechanical stability with significantly less material and is therefore significantly lighter, so that the microscope as a whole can also be lighter than conventional microscopes.

[0018] One embodiment provides that the support surface of the slide table for a slide is a support surface facing away from the lighting unit, in particular a horizontal one. In this case, light emanating from the lighting device shines from bottom to top through the vertical opening penetrating the slide table in order to illuminate an area of ​​the slide arranged above the opening. Alternatively, it is also possible for the support surface of the slide table for a slide to be a support surface facing the lighting unit, in particular a horizontal one. The slide is then not held on the support surface by gravity; however, this can be achieved, for example, by clamping the slide, for example by means of a clamping device.In this case, light emanating from the illumination device first irradiates and passes through the slide containing the object and then continues to radiate from bottom to top through the vertical aperture.

[0019] One embodiment of the invention provides that the bars are arranged such that the opening in the support surface is at least substantially centered between the bars. For example, the support device comprises exactly three bars arranged in a triangular arrangement in horizontal cross-section. The support device can also comprise exactly four bars arranged in a quadrilateral arrangement in horizontal cross-section.

[0020] This design of the support structure places the center of gravity of the components between the rods, not to the side of the column, as in a conventional microscope. This load distribution allows the support structure encompassing the rods to be less massive than a column positioned to the side of the center of gravity, allowing the support structure to be significantly less massive and thus lighter than the conventional column while maintaining at least the same mechanical stability.

[0021] At high magnifications, the depth of field of the microscope in the object plane is small. This means that with conventional microscopes, refocusing is often necessary when the object is moved on the slide on the slide stage. However, with thinly sectioned samples, such as those used in histology for cancer diagnostics, the flatness of the samples is actually sufficient so that, when arranged perpendicular to the optical axis (also: beam axis) of the microscope, which corresponds to the z-direction, they can be moved in the perpendicular xy plane without a sample leaving the depth of field of the microscope objective. With conventional microscopes, however, the slide stage can be moved in the direction of the beam axis for focusing.However, due to the bearing play during this sliding movement of the slide table, the support surface of the slide table is not aligned exactly perpendicular to the z-axis in all positions; rather, the support surface can tilt during focusing.

[0022] To avoid this problem, a further development of the invention provides that the slide table and preferably also the microscope base and / or the tube lens holder and / or the area sensor holder are firmly connected to the support device, in particular to at least one or more or all of the rods of the support device. In particular, the slide table and / or the microscope base and / or the tube lens holder and / or the area sensor holder are mounted perpendicular to the rods. This does not have to be permanently the case, i.e., detaching these fixed connections may be possible. However, this fixed connection is implemented at least in one operating state of the microscope, i.e., when the microscope is used according to its intended function.

[0023] Accordingly, in the aforementioned fixed connection of the specimen slide table to the support device, it is provided that the microscope objective holder with the microscope objective is connected to the support device so as to be displaceable vertically and / or along an optical axis of the microscope for focusing.

[0024] This allows focusing without having to move the slide stage. This prevents the slide stage from tilting during focusing. Focusing is now achieved by moving the microscope objective and the microscope objective holder along the rods. Tilting of the microscope objective due to unavoidable bearing play is irrelevant, since a slight tilt of the microscope objective does not change its distance from the focal plane above the support surface of the stage support. Since the image of the microscope objective is primarily an image of the object to infinity, the image position on the area sensor does not change when the microscope objective is tilted.Thus, especially in conjunction with a very well-ground support surface of the slide table, the slide can be moved on the support surface of the slide table without the also flat object on the slide moving out of the depth of field of the microscope.

[0025] According to a further development, the displacement of the microscope objective holder with the microscope objective can be carried out manually, in particular by means of a screw drive or a spindle gear, preferably with a recirculating ball nut, or by means of a motor.

[0026] The displacement of the microscope objective holder and thus of the microscope objective can be achieved, for example, by means of a motor that is firmly connected to one or more of the rods of the support device via a holder. This motor holder can, for example, be integrated into the area sensor holder to save manufacturing costs. One embodiment of displacement by motor additionally provides a limit switch that signals when the microscope objective holder and / or the microscope objective has reached one end of a designated displacement range. If a stepper motor is used as the motor, a single limit switch at one of the two opposite end positions is sufficient. Reaching the second end position can then be determined using a step counter assigned to the stepper motor.

[0027] One embodiment provides for the rods to be guided through holes (also called bores) in the microscope base and / or the slide stage and / or the microscope objective holder and / or the tube lens holder and / or the area sensor holder. One embodiment provides for the holes for the rods to be guided through the slide stage perpendicular to the support surface of the slide stage. This should be ensured accordingly during the manufacture of the slide stage.

[0028] One embodiment provides that the rods penetrate one or more or all of the holes at least essentially without play.

[0029] According to a further development, the rods can be fixed in at least one or several or all holes by means of a fixing device and thus firmly connected to the respective component. The fixing device allows any play that may exist in the rods in the holes to be eliminated and, furthermore, a position once assumed by the respective component relative to the rods to be fixed.

[0030] For example, the fixing device comprises one or more fixing screws, each arranged in a horizontal thread in the microscope base and / or the slide stage and / or the microscope objective holder and / or the tube lens holder and / or the area sensor holder. Alternatively or additionally, the fixing device comprises a clamping device with a first clamping component and a second clamping component, wherein the second clamping component is formed around the respective hole and comprises an external thread and at least partially wedge-shaped claws, and wherein the first clamping component has a union nut with an internal thread corresponding to the external thread and an internal contour cooperating with the wedge-shaped portion of the claws such that when the union nut is tightened onto the external thread, the claws are pressed against the rod, thereby centering it and clamping it securely without play.

[0031] One embodiment of the invention provides that the microscope base and / or the slide stage and / or the microscope objective holder and / or the tube lens holder and / or the area sensor holder are designed as a lightweight component, in particular as a component with an internal hollow structure, for example a honeycomb structure and / or foam structure. These lightweight components can be manufactured, for example, using adaptive manufacturing (including 3D printing). Fiber-reinforced plastic, for example carbon fiber- or glass fiber-reinforced plastic, can be considered as a material for the lightweight components, since this material can be used to produce lightweight components with particularly high mechanical strength and low weight. These lightweight components can also be manufactured, for example, using plastic material cast, foamed, or expanded into an appropriate mold.

[0032] The slide table, manufactured, for example, as described above using adaptive manufacturing or casting, may need to be reworked to ensure the slides rest as precisely as possible on the support surface, even when moved or rotated. For this purpose, the support surface of the slide table can be ground flat, particularly with micrometer-level accuracy.

[0033] In this way, using the aforementioned lightweight components, it is possible to provide, for example, a microscope, in particular a travel and laboratory microscope according to the invention, which has a weight of only about 1.3 kg while having mechanical stability comparable to the prior art.

[0034] In conventional microscopes, an xy-translation unit is attached to the slide stage, to which the slide is clamped. In addition to the bearing play of the slide stage, the bearing play of the translation unit and the tilt-free mounting of the slide relative to the optical axis of the microscope also play a role in determining whether the specimen moves out of the microscope's focal plane. Since neither of these is sufficient for the high numerical apertures of high-magnification objectives and the associated shallow depth of field on the order of a micrometer, conventional microscopes often require refocusing after moving the slide.

[0035] In the microscope according to the invention, particularly with a slide stage permanently mounted on the support device with a support surface perpendicular to the beam axis, the flat sample does not move out of focus when moved along the support surface, i.e., in the xy plane. However, a displacement device is required to ensure that small displacements can be realized reproducibly.

[0036] The invention therefore provides that a displacement device for two-dimensional horizontal and / or vertical displacement of a specimen slide on the support surface of the specimen slide table is arranged on the slide table. The displacement device comprises a specimen slide frame arranged displaceably on the support surface of the specimen slide table and having a continuous recess for receiving the specimen slide. The shape and dimensions of the recess are adapted to the shape and dimensions of the specimen slide, in particular with little play, so that the specimen slide always rests on the support surface due to gravity. Since the specimen slide therefore always rests directly on the support surface during displacement, any bearing play of the displacement device cannot influence the position, in particular the inclination, of the specimen slide.Furthermore, since no holder for the slide is provided on the slider, but rather the slide rests directly and with play on the support surface of the slide table in the recess of the slider frame, tilting of the slide is also prevented. Thus, the proposed slider does not cause the slide to tilt, and the need for refocusing due to the slider is avoided.

[0037] The displacement device can, for example, consist of parallel shafts that are attached at both ends to two clamping pieces, and a threaded rod that is also arranged parallel and rotatably mounted in the two clamping pieces. A nut is located on the threaded rod in a slide, so that the slide moves when the threaded rod rotates. The slide, in turn, is connected to the slide frame. When the threaded rod rotates, the nut, the slide, and the slide frame are then moved. By coupling two displacement stages at a right angle, so that the slide of one stage is connected to the clamping pieces of the other stage, an xy displacement of the slide frame can be achieved.The displacement device proposed by the invention uses a rectangular frame, instead of the spring clamp of a conventional microscope, arranged around the slide with a small air gap. The air gap allows the slide to move freely in the z-direction and, due to gravity, always rests flat on the slide stage. The displacement device allows the frame to be moved in the x- and y-directions. When the slide is moved, it remains flat on the slide stage without the flat object leaving the microscope's focal plane and requiring refocusing.

[0038] The movement of the slide frame and thus of the slide can be controlled manually. However, the displacement device can also have motors for moving the slide. In this case, the movement of the slide frame and thus of the slide can also be controlled using the motors via a computer program. Due to the aforementioned design of the displacement device, refocusing when moving the slide can be completely or at least significantly avoided, which results in significant processing time savings, for example, when acquiring numerous images automatically.

[0039] The microscope can comprise a programmable control device for controlling the motors of the displacement device, or such a programmable control device can be assigned to the microscope. By means of this control device, the displacement can be automated and program-controlled. The control device can additionally be connected to the area sensor and programmed such that an object on a slide is moved relative to the microscope objective by means of the displacement device, and in doing so, a plurality of partial images of the object are captured in various positions by means of the area sensor. Furthermore, the control device can have an image processing device configured such that an overall image of the object is composed from the plurality of partial images.This can also be a three-dimensional volume image if the microscope objective is positioned at multiple z-positions, thus capturing images of multiple object planes. These images of the different object planes can then be combined into a three-dimensional image by layering the individual images of the different object planes in the volume image, aligning them in the xy direction and maintaining the z-distances of the corresponding images.

[0040] Because the time required for refocusing, as explained above, is significantly reduced compared to known microscopes, the above-described configuration allows an object surface (also known as a sample surface) that is larger than the image section of the microscope to be completely scanned using the displacement unit according to the invention by taking several individual images. These individual images can then be stitched into a large overall image using digital image processing. If several overlapping individual images of the sample surface that are shifted relative to one another are acquired, they can be superimposed and combined into a large image.When overlaying the individual images in the correct position, either the displacements in the x- and y-direction of the images relative to each other can be used, or the correlation function can be calculated based on the displacements between two individual images. In the latter method, the images are then superimposed at the distance from each other at which a clear maximum of the correlation function occurs. If the images do not overlap, the value of the correlation function lies below a specified threshold, and the two images are not merged. For non-flat samples, the microscope objective can also be shifted in the z-direction, and a 3D image can be obtained by stacking the individual 2D images in the image processing device.In this case, those object areas that are blurred in the individual images can be hidden, so that in the end a sharp, two-dimensional but not necessarily flat image of the 3-dimensional surface of the object remains in the three-dimensional volume.

[0041] A further development provides that the microscope objective holder has several microscope objectives, each of which can be moved into a designated operating position by displacement and / or rotation, particularly in a horizontal plane and / or in a plane perpendicular to the optical axis of the microscope. This has the advantage that several different magnifications can be set.

[0042] For example, the microscope objectives can be arranged on a nosepiece that is rotatably mounted on the microscope objective holder. If the rotation axis of the nosepiece lies outside the rods, it can have circular cutouts through which the rods pass. The angular extent of the circular arcs of the rod passages corresponds to the rotation angle range required to position all microscope objectives on the optical axis. To ensure that the microscope objectives can be easily positioned precisely on the optical axis, a ball catch can be embedded in the microscope objective holder. This catch interacts with notches in the nosepiece at the appropriate positions for the corresponding objective positions.It is possible to arrange the objective nosepiece on the motor axis of a motor that rotates the objective nosepiece to the different angular positions at which the microscope objectives are arranged on the optical axis.

[0043] Another way to use multiple microscope objectives is to arrange them next to each other on a linear translation stage, the axis of movement of which runs perpendicular to the optical axis of the microscope. The linear translation stage is connected to the microscope objective holder and can therefore be moved in the z-direction together with the microscope objectives for focusing. A carriage of the linear translation stage can form a linear holder for the microscope objectives, which are arranged next to each other in the direction of translation. The linear holder has an opening located behind the microscope objectives in the beam path, through which the light can pass from the object to the tube lens as soon as the respective microscope objective is positioned in the beam path (or in the optical axis).Here, too, the precise positioning of a microscope objective can be achieved using a ball snap in the microscope objective holder and a notch in the movable carriage on which the microscope objectives are mounted. It is also possible to equip the linear translation stage with a screw drive for adjusting the carriage and move it using a motor and motor controller, allowing the various microscope objectives to be positioned on the optical axis of the microscope.

[0044] To minimize dust from falling onto the microscope objectives, the objective nosepiece or linear translation stage slides are embedded in the microscope objective holder in such a way that, during their rotational or linear movement, there are no, or at least no significant or large, openings to the microscope's internal light path. Any small gaps that may still exist are preferably sealed with labyrinth seals to keep dust away from the interior of the microscope through which the object is imaged.

[0045] According to one embodiment, the illumination unit comprises a light source, in particular an LED light source with adjustable intensity, and a lens arrangement that focuses light emanating from the light source onto a specimen slide lying on the support surface and thus illuminates a circular area of ​​the specimen slide. In particular, the LED light source is a planar LED light source, in particular an LED light source with a light exit diameter of more than 20 mm and / or a COB LED. The lens system can comprise a first iris diaphragm for adjusting the size of the illumination field on the specimen slide and a second iris diaphragm for adjusting the divergence of the light on the specimen slide.

[0046] For example, the illumination unit is equipped with an LED light source whose intensity can be regulated using a power supply with current control. In a simple embodiment, the light from the LED is first shined onto a diffuser. The illuminated area of ​​the diffuser is then imaged using a condenser lens slightly in front of or slightly behind the slide. Using an iris diaphragm, which is mounted just in front of or just behind the diffuser, the diameter of the illuminated area on the slide can be adjusted. Furthermore, a second iris diaphragm can be placed just in front of or just behind the condenser lens to change the beam divergence with which the light shines through the slide.

[0047] A second embodiment of the illumination unit is based on the Köhler illumination principle. In this illumination unit, the light from the LED strikes a first lens, which, in a particularly advantageous embodiment, has an aspherical shape like the other lenses below. The LED is positioned at a distance from the first lens approximately equal to the focal length of the first lens. This approximately parallelizes the light emitted by a point on the LED. In the direction of the beam path, a second lens follows the first lens, which images the light into an intermediate image plane in which a second iris diaphragm is arranged. A first iris diaphragm is arranged between the first lens and the second lens, or shortly before the first line, or shortly behind the second lens. Behind the second iris diaphragm are a third and a fourth lens, which image the image of the first iris diaphragm onto the plane of the slide or object.If the first iris diaphragm is opened further, the circularly illuminated area on the slide increases in size due to the image from the third and fourth lenses. The focal length of the lens system consisting of the third and fourth lenses therefore determines the magnification factor with which the aperture of the first iris diaphragm is imaged onto the slide. The size of the aperture of the second iris diaphragm, on the other hand, determines the divergence with which the light passes through the slide and enters the microscope objective. The production of this illumination device is particularly cost-effective when all four lenses are of the same design.

[0048] The lenses and iris diaphragms, as well as the LED light source, can be positioned in an outer cladding tube using conical ring elements. For this purpose, the ring elements have an outer diameter that, together with the inner diameter of the cladding tube, forms a sliding fit. A nut with a hole for the beam cone to pass through can be screwed into the end of the cladding tube to secure the mounts, lenses, and iris diaphragms. The cladding tube is threaded at this end for this purpose.

[0049] So-called COB LEDs are particularly suitable as LEDs, in which a large number of LEDs are integrated on a circuit board, thus achieving a particularly large emitting area. This results in a particularly high adjustable beam divergence, or illumination aperture, with which the object is illuminated. COB LEDs are available in many different colors and in various shades of white with different color temperatures. To change the illumination unit, they can be attached to the microscope base using a screw mount or similar fastening element.

[0050] A further development provides that one or more color filters, for example for fluorescence examinations and / or polarization filters for polarization microscopic examinations, are arranged in the microscope objective holder and / or in the vertical opening in the support surface of the slide table and / or in the illumination unit and / or in front of the tube lens and / or in front of the area sensor, in particular in the beam path of the microscope.

[0051] An embodiment of the invention provides that the focal length of the tube lens is selected such that the maximum possible object resolution resulting from the numerical aperture of the microscope objective corresponds at least substantially to the image resolution of the area sensor.

[0052] A further development of the invention provides that the tube lens is selected such that the focal length f T the tube lens at least approximately corresponds to the equation fT=fi⋅BA / OA corresponds to, where f i is the focal length of the microscope objective, BA is the image resolution in the image plane of the area sensor and OA is the maximum possible object resolution of the microscope objective.

[0053] Does the microscope objective have a focal length f i and the tube lens has a focal length f T , then the magnification V i the images of the object on the area sensor by the equation V i = f T / f i .

[0054] Every microscope objective has a specific numerical aperture (NA), which corresponds to a maximum possible object resolution (OA) with which the object is captured. This object resolution (OA) should be aligned with the pixel size of the area sensor, which defines the image resolution (BA) in the image plane of the area sensor. For this purpose, the focal length of the tube lens (f) is used. T selected so that the relationship OA · V i= BA is at least approximately fulfilled. Depending on the pixel size of the area sensor, the focal length of the tube lens is, for example, in the range between 35 mm and 270 mm. The numerical aperture NA T the tube lens is preferably chosen so that it is larger than the largest numerical aperture NA M the microscope objectives used.

[0055] The invention will be explained in more detail below with regard to further features and advantages by means of the description of exemplary embodiments and with reference to the accompanying schematic drawings. Fig. 1 an embodiment of a microscope according to the invention in a lateral sectional view, Fig. 2 the microscope slide table Fig. 1 in a plan view, Fig. 3 the slide table Fig. 2 in plan view with a sliding device for the slide, Fig. 4 a movement device of a displacement device for the object carrier in plan view, Fig. 5 schematically shows the structure of an illumination unit of a microscope according to the invention, Fig. 6 schematically shows a holder for the optical elements of the Fig. 5 schematically shown lighting unit, and Fig. 7 / 8 Components of fixing devices for fixing the rods in the holes.

[0056] Corresponding parts and components are designated by the same reference numerals, even across different embodiments.

[0057] Fig. 1 shows an embodiment of a microscope 1 according to the invention comprising, in a provided setup vertically from bottom to top, a microscope base 2 with an illumination unit 3, a slide table 4 with a horizontal support surface 5 facing away from the illumination unit 3 for a slide 6 with an object 7 (see Fig. 2), wherein the support surface 5 has a vertical opening 8 penetrating the object carrier table 4, through which light emanating from the illumination device 3 radiates from bottom to top to illuminate an area of ​​the object carrier 6 arranged above the opening 8, specifically the object 7 (see Fig. 2), a microscope objective holder 9 with at least one microscope objective 10, a tube lens holder 11 with a tube lens 12, and an area sensor holder 13 with an area sensor 14. The microscope base 2, the slide stage 4, the microscope objective holder 9, the tube lens holder 11, and the area sensor holder 13 are connected to one another via a support device 15 comprising three vertical rods 16. Each rod 16 connects the microscope base 2, the slide stage 4, the microscope objective holder 9, the tube lens holder 11, and the area sensor holder 13 to one another.

[0058] Fig. 2 shows the slide table 4 of the microscope from Fig. 1 in a top view of the support surface 5. The opening 8 is not visible in this illustration, as it is covered by the object 7. Nevertheless, Fig. 2, the three rods 16 are arranged such that the undetectable opening 8, which is located below the object 7, is centered between the rods 16 in the support surface 5. Furthermore, it can be seen that the three rods 16 are arranged in a triangular arrangement.

[0059] In an embodiment of the Fig. In the microscope 1 shown in Figure 1, the slide stage 4 is rigidly connected to the rods 16 of the support device 15. The microscope objective holder 9, however, is connected to the microscope objective 10 for focusing vertically and thus displaceably along the optical axis of the microscope 1 to the rods 16 of the support device 15. The displacement of the microscope objective holder 9 with the microscope objective 10 can be performed manually, in particular by means of a screw drive or a spindle gear, preferably with a recirculating ball nut, or by means of a motor. These configurations are not shown.

[0060] Fig. 2 shows, for example, the slide table 4, that the rods are guided through holes 17 in the slide table 4. This applies analogously to the microscope base 2, the microscope objective holder 9, the tube lens holder 11, and the area sensor holder 13. The rods 16 penetrate the holes 17 at least essentially without play.

[0061] Fig. 3 shows the slide table 4 from Fig. 2 with a displacement device 29 for the specimen slide 6, with which the specimen slide can be displaced in an xy plane. The displacement device 29 comprises a specimen slide frame 30, which is displaceably arranged on the support surface 5 of the specimen slide table 4 and has a continuous rectangular recess 31 for receiving the specimen slide 6. The displacement device 29 can have motors (not shown) for displacing the specimen slide 6. In this case, a programmable control device (not shown) can be provided for controlling the motors of the displacement device 29, by means of which the displacement takes place in an automated and program-controlled manner.

[0062] The slide 6 is arranged with a small clearance (not shown), for example a small air gap around the slide 6, in the rectangular recess 31 of the slide frame 30. As a result, the slide 6 is vertically, i.e. in the z-direction, perpendicular to the plane of the drawing in Fig. 3, is freely movable and, due to gravity, always lies flat on the support surface 5 of the slide table 4. The slide frame 30 of the displacement device 29 is movable by means of further components of the displacement device 29, for example the movement devices 32 explained below (see Fig. 4), movable in the xy plane. When the slide 6 is moved, it continues to rest flat on the slide table 4, without the object 7 leaving the plane of focus of the microscope 1 and requiring refocusing.

[0063] Fig. 4 shows an example of a movement device 32 (also: sliding table) of the displacement device 29, specifically for the movement of the Fig. 3 shown slide frame 30. The displacement device 29 comprises two of the Fig. 4, one for movement in the x-direction and one for movement in the y-direction (not shown). Each movement device 32 comprises two shafts 33 arranged parallel to one another, each of which is fastened at each of its ends in a clamping piece 34, with one clamping piece 34 being provided for each of the shafts 33. The movement device 32 further comprises a threaded rod 35 arranged parallel to the shafts 33, which can be rotatably mounted in the two clamping pieces 34. The threaded rod 35 and both shafts 33 penetrate a carriage 36, wherein the carriage 36 is displaceable along the shafts 33. The threaded rod 35 is guided by an internal thread in the carriage 36, for example the internal thread of a nut arranged in the carriage 36, such that rotation of the threaded rod 35 causes a linear movement of the carriage 36 along the threaded rod 35 and the shafts 33.Thus, the slide 36 is moved linearly upon rotation of the threaded rod 35. The slide 36 is in turn connected to the slide frame 30 (not shown). Fig. 4) so ​​that the slide frame 30 is moved linearly with the carriage 36. By coupling two such movement devices 32 at right angles, specifically, for example, by connecting the carriage 36 of one movement device 32 to the clamping pieces 34 of the other movement device 32, an xy displacement of the slide frame 30 can be realized. The rotation of the threaded rods 35 of the movement devices 32 can be carried out manually or via a motor (not shown), wherein the motors can be controlled, for example, via a programmed control device.

[0064] Fig. 5 shows schematically the structure of an illumination unit 3 of a microscope 1 according to the invention, for example the one shown in Fig. 1. The illumination unit 3 has a planar LED light source 37, the intensity of which can be regulated, for example, by means of a power supply with current regulation (not shown). Suitable LED light sources 37 include, for example, so-called COB LEDs, in which a large number of LEDs are integrated on the circuit board, thus achieving a particularly large emitting area. This results in the adjustable beam divergence or illumination aperture with which the object 7 is illuminated being particularly high. The COB LEDs are available in many different colors and in various shades of white with different color temperatures.

[0065] The Fig. The illumination unit 3 shown in Figure 5 is based on the Köhler illumination principle in terms of its construction. In this illumination unit 3, the light from the LED light source 37 strikes a first lens L1. The distance between the LED light source 37 and the first lens L1 roughly corresponds to the focal length of the first lens L1. As a result, the light emitted from a point on the LED light source 37 is approximately parallelized. In the direction of the beam path, there are a first iris diaphragm I1 and a second lens L2, which images the light into an intermediate image plane in which a second iris diaphragm I2 is arranged. The first iris diaphragm I1 is thus arranged between the two lenses L1 and L2. In the direction of the beam path, the second iris diaphragm I2 is followed by two further lenses: a third lens L3 and a fourth lens L4, which image the image of the first iris diaphragm I1 into the plane of the specimen slide 6 or the specimen 7.If the first iris diaphragm I1 is opened further, the circularly illuminated area on the specimen slide 6 increases in size due to the imaging of the third lens L3 and the fourth lens L4. The focal length of the lens system comprising the third lens L3 and the fourth lens L4 determines the magnification factor with which the aperture section of the first iris diaphragm I1 is imaged onto the specimen slide 6. The size of the aperture section of the second iris diaphragm I2, on the other hand, determines the divergence with which the light passes through the specimen slide 6 and then enters the microscope objective.

[0066] Fig. 6 shows schematically a holder for the optical elements of the Fig. 5 schematically shown illumination unit 3, exemplified by the first lens L1, the second lens L2, and the first iris diaphragm I1. The first lens L1, the second lens L2, and the first iris diaphragm I1 are positioned in an outer cladding tube 39 by means of conical ring elements 38. The other optical elements and also the LED light source can be positioned in the cladding tube 39 in a similar manner. The ring elements 38 have an outer diameter which, together with the inner diameter of the cladding tube 39, forms a sliding fit. At the end of the cladding tube 39, a nut with a bore for the passage of the beam cone can be screwed in to fix the elements (not shown). In this case, the cladding tube 39 is provided with a thread at its end.

[0067] Fig. 7 and Fig. 8 show components of fixing devices 18 for fixing the rods 16 in the holes 17. With these fixing devices 18, the rods are firmly connected to the respective component, in Fig. 8 to the slide table 4. The fixing device 18 can be a component in which Fig. 8 the slide table 4, inserted horizontal thread 19, which extends to one of the holes 17. Two such threads 19 are in Fig.8. A fixing screw 28 can be screwed into each of these threads 19 and press against the rod 16 inserted into the hole 17, thereby fixing it in place. The fixing device 18 can also be a clamping device 20 with a first clamping component 21 and a second clamping component 22. The second clamping component 22 is formed around the respective hole 17 and comprises an external thread 23 and at least partially wedge-shaped claws 24. The first clamping component 21 is a union nut 25 with an internal thread 26 corresponding to the external thread 23 and an internal contour 27 interacting with the wedge-shaped section of the claws 24 such that when the union nut 25 is tightened onto the external thread 23, the claws 24 are pressed against the rod 16, thereby centering it and clamping it securely without play. List of reference symbols 1 microscope 2 microscope base 3 lighting unit 4 slide table 5 Support surface of the slide table 4 6 slides 7 Object 8 vertical opening in the support surface 5 9 Microscope lens holder 10 microscope objective 11 Tube lens holder 12 tube lens 13 Area sensor holder 14 Area sensor 15 Carrier device 16 bars 17 Hole in the slide table 4 18 Fixing device 19 horizontal thread 20 clamping device 21 first clamping component 22 second clamping component 23 external threads 24 claws 25 union nut 26 internal threads 27 Inner contour 28 Fixing screw 29 Shifting device 30 slide frames 31 Recess of the slide frame 30 32 Movement device of the shifting device 29 33 Wave 34 clamping piece 35 threaded rod 36 sleds 37 LED light source 38 conical ring element 39 Sheath tube I1 first iris diaphragm I2 second iris diaphragm L1 first lens L2 second lens L3 third lens L4 fourth lens

Claims

[1] Microscope (1) comprising arranged vertically from bottom to top in a designated setup a) a microscope base (2) with a lighting unit (3), b) a slide table (4) with a support surface (5) for a slide (6), the support surface (5) having an opening (8) penetrating the slide table (4) through which light emanating from the illumination device (3) radiates from bottom to top, c) a microscope objective holder (9) with at least one microscope objective (10), d) a tube lens holder (11) with a tube lens (12), e) an area sensor holder (13) with an area sensor (14), wherein on the one hand the microscope base (2) and / or the object carrier table (4), on the other hand the microscope objective holder (9) and furthermore the tube lens holder (11) and / or the area sensor holder (13) are connected to one another via a carrier device (15), wherein the support device (15) comprises at least three rods (16), each rod (16) connecting the microscope base (2) and / or the object carrier table (4) on the one hand, and the microscope objective holder (9) and also the tube lens holder (11) and / or the area sensor holder (13) to one another, wherein a displacement device (29) for two-dimensional horizontal displacement of a specimen slide (6) on the support surface (5) of the specimen slide table (4) is arranged on the specimen slide table (4), wherein the displacement device (29) comprises a specimen slide frame (30) displaceably arranged on the support surface (5) of the specimen slide table (4) with a continuous recess (31) for receiving the specimen slide (6), characterized by , that The shape and dimensions of the continuous recess (31) are adapted to the shape and dimensions of the specimen slide (6) in such a way that the specimen slide (6) always rests directly on the support surface (5) of the specimen slide table (4) within the continuous recess (31) due to the force of gravity and can be moved precisely with the displacement device (29) over the specimen slide frame (30) without any holder for the specimen slide (6) on the displacement device (29), without any possible bearing play of the displacement device (29) leading to an inclination of the specimen slide (6) during displacement and the associated need for refocusing. [2] Microscope (1) according to claim 1, characterized by , that the microscope objective holder (9) and the tube lens holder (11) are separate components that can be positioned differently relative to one another, or that the microscope objective holder (9) and the tube lens holder (11) are components that are firmly connected to one another, or that the microscope objective holder (9) and the tube lens holder (11) form a common component. [3] Microscope (1) according to claim 1 or 2, characterized by that the bars (16) are arranged such that the opening (8) in the support surface (5) is arranged at least substantially centered between the bars (16). [4] Microscope (1) according to claim 3, characterized by that the support device (15) has exactly three bars (16) which are arranged in a triangular arrangement in the horizontal cross-section, or exactly four bars (16) which are arranged in a quadrilateral arrangement in the horizontal cross-section. [5] Microscope (1) according to one of the preceding claims, characterized bythat the specimen slide table (4) is fixedly connected to the carrier device (15) at least in one operating state of the microscope (1), and that the microscope objective holder (9) with the microscope objective (10) is connected to the carrier device (15) so as to be displaceable vertically and / or along the optical axis of the microscope (1) for focusing. [6] Microscope (1) according to claim 5, characterized by that the displacement of the microscope objective holder (9) with the microscope objective (10) is carried out manually or by means of a motor. [7] Microscope (1) according to one of the preceding claims, characterized by that the rods (16) are guided through holes (17) in the microscope base (2) and / or the slide table (4) and / or the microscope objective holder (9) and / or the tube lens holder (11) and / or the area sensor holder (13). [8] Microscope (1) according to claim 7, characterized bythat the rods (16) penetrate one or more or all of the holes (17) at least substantially without play. [9] Microscope (1) according to claim 7 or 8, characterized by that the rods (16) can be fixed at least in one or several or all holes (17) by means of a fixing device (18) and can thus be firmly connected to the respective component. [10] Microscope (1) according to claim 9, characterized by that the fixing device (18) comprises one or more fixing screws (28) each arranged in a horizontal thread (19) in the microscope base (2) and / or the object carrier table (4) and / or the microscope objective holder (9) and / or the tube lens holder (11) and / or the area sensor holder (13). [11] Microscope (1) according to claim 9 or 10, characterized byin that the fixing device (18) comprises a clamping device (20) with a first clamping component (21) and a second clamping component (22), wherein the second clamping component (22) is formed around the respective hole (17) and comprises an external thread (23) and at least partially wedge-shaped claws (24), and wherein the first clamping component (21) has a union nut (25) with an internal thread (26) corresponding to the external thread (23) and an internal contour (27) cooperating with the wedge-shaped section of the claws (24) in such a way that when the union nut (25) is tightened on the external thread (23), the claws (24) are pressed against the rod (16) and thereby center the rod and clamp it securely without play. [12] Microscope (1) according to one of the preceding claims, characterized bythat the microscope base (2) and / or the slide table (4) and / or the microscope objective holder (9) and / or the tube lens holder (11) and / or the area sensor holder (13) are designed as a lightweight component. [13] Microscope (1) according to claim 12, characterized by that the or each lightweight component is a component with an internal hollow structure. [14] Microscope (1) according to claim 13, characterized by that the internal cavity structure is a honeycomb structure and / or a foam structure. [15] Microscope (1) according to one of claims 12 to 14 characterized by that the or each light component is made of a fibre-reinforced plastic. [16] Microscope (1) according to claim 15, characterized by that the fibres reinforcing the plastic are or comprise carbon fibres or glass fibres. [17] Microscope (1) according to one of the preceding claims, characterized bythat the displacement device (29) has motors for displacing the object carrier (6). [18] Microscope (1) according to claim 17, characterized by that a programmable control device is provided for controlling the motors of the displacement device (29), by means of which the displacement takes place in an automated and program-controlled manner. [19] Microscope (1) according to claim 18, characterized by that the control device is additionally connected to the area sensor (14) and is programmed such that an object (7) of a specimen slide (6) is moved relative to the microscope objective (10) by means of the displacement device (29) and in this case a plurality of detail images of the object (7) are recorded in different positions by means of the area sensor (14). [20] Microscope (1) according to claim 19, characterized bythat the control device has an image processing device which is set up in such a way that an overall image of the object (7) is composed from the plurality of detail images. [21] Microscope (1) according to one of the preceding claims, characterized by that the microscope objective holder has a plurality of microscope objectives, wherein each microscope objective can be brought into a designated use position by displacement and / or rotation, in particular in a horizontal plane and / or in a plane perpendicular to the optical axis of the microscope. [22] Microscope according to one of the preceding claims, characterized by that the lighting unit includes: a light source, in particular an LED light source with adjustable intensity, and a lens arrangement that focuses light emanating from the light source onto a slide lying on the support surface and thus illuminates an area of the slide. [23] Microscope according to claim 22, characterized by that the LED light source is a planar LED light source, in particular an LED light source with a light exit diameter of more than 20 mm and / or a COB LED. [24] Microscope according to claim 22 or 23, characterized by that the lens system comprises a first iris diaphragm for adjusting the size of the illumination field on the slide and a second iris diaphragm for adjusting the divergence of the light on the slide. [25] Microscope according to one of the preceding claims, characterized by that one or more color filters and / or polarization filters are arranged in the microscope objective holder and / or in the vertical opening in the support surface of the slide table and / or in the illumination unit and / or in front of the tube lens and / or in front of the area sensor. [26] Microscope according to one of the preceding claims, characterized bythat the focal length of the tube lens is selected such that the maximum possible object resolution resulting from the numerical aperture of the microscope objective corresponds at least substantially to the image resolution of the area sensor. [27] Microscope according to one of the preceding claims, characterized by , that the tube lens is chosen such that the focal length of the tube lens at least approximately corresponds to the equation f T = f i · BA / OA corresponds to, where f i is the focal length of the microscope objective, BA is the image resolution in the image plane of the area sensor and QA is the maximum possible object resolution of the microscope objective.

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