阅读说明：本技术 用于在显微镜中接纳样本的装置 (Device for receiving a sample in a microscope ) 是由 帕特里克·佩尔泽 克里斯蒂安·舒曼 于 2020-04-08 设计创作，主要内容包括：一种用于在显微镜中接纳样本的装置,其具有微量滴定板,该微量滴定板包括：内部部分,该内部部分带有用于样本的空穴且带有光学透明的底板,该底板从下方封闭空穴；和框架,该框架限定了支撑面并且被设计用于将所述内部部分至少保持在第一位置。所述底板在所述内部部分的第一位置布置在所述支撑面上方。所述内部部分可相对于所述框架沿垂直于所述支撑面的方向移动。(A device for receiving a sample in a microscope having a microtiter plate comprising: an inner part with a cavity for the sample and with an optically transparent bottom plate which closes the cavity from below; and a frame defining a support surface and designed to hold the inner portion at least in a first position. The base plate is arranged above the support surface in a first position of the inner portion. The inner portion is movable relative to the frame in a direction perpendicular to the support surface.)

1. A device for receiving a sample in a microscope, has

A microtiter plate (100a-100g) comprising:

an inner part (104a-104g) with a cavity (106) for the sample and with an optically transparent bottom plate (122) which closes the cavity (106) from below; and

a frame (102a-102g) defining a support surface and being designed for holding the inner portion (104a-104g) at least in a first position,

wherein the bottom plate (122) is arranged above the supporting surface in a first position of the inner portion (104a-104g), and

the inner portion (104a-104g) is movable relative to the frame (102a-102g) in a direction (A) perpendicular to the support surface.

2. The device according to claim 1, wherein the microtiter plate (100a, 100c-100g) has a locking device (124a-124c) designed for releasably interconnecting the inner portion (104a, 104c-104g) and the frame (102a, 102c-102 g).

3. The device according to claim 2, wherein the locking device (124a-124c) has a snap-in part (126a, 126b) which is connected to the frame (102c-102e) by a hinge (128) and is designed to snap into a receptacle (130) of the inner part (104c-104e), thus releasably connecting the inner part (104c-104e) and the frame (102c-102e) to each other.

4. Device according to claim 3, comprising unlocking means with a pin (132a, 132b) designed for being guided through a receptacle (130) of the inner part (104d, 104e) in order to press the catch part (126b) of the locking means (124b, 124c) out of the receptacle (130) such that the connection between the inner part (104d, 104e) and the frame (102d, 102e) is released.

5. The device according to claim 4, characterized in that the unlocking device has a motorized drive for operating the pins (132a, 132 b).

6. Device according to claim 2 or 3, comprising unlocking means designed for releasing the connection between the inner part (104a-104g) and the frame (102a-102g) by pressing the inner part (104a-104g) from above.

7. The device according to claim 2 or 3, comprising a microscope stage kit (138a, 138b) with a guide means for guiding the microtiter plate (100a-100g), wherein the guide means is designed to press the snap means (126a, 126b) of the locking device (124a-124c) out of the receptacle (130) when guiding the microtiter plate (100a-100g) such that the connection between the inner portion (104c-104e) and the frame ((102c-102e) is released.

8. The device of any one of the preceding claims, wherein the frame (102a-102g) has an opening (110) at a bottom side thereof, and the inner portion (104a-104g) is movable such that the bottom plate (122) is passable through the opening (110) of the frame (102a-102 g).

9. The device according to claim 8, wherein the frame (102a-102g) has a depth stop (120) designed for holding the inner part (104a-104g) in a second position, wherein the inner part (104a-104g) protrudes through the opening (110) of the frame (102a-102g) in the second position such that the floor (122) of the inner part (104a-104g) is arranged below the supporting surface.

10. The apparatus of claim 8 or 9, comprising a microscope stage kit (138a, 138b) designed to hold the inner portion (104f, 104g) in a second position, wherein the inner portion (104f, 104g) protrudes through the opening (110) of the frame (102f, 102g) in the second position such that the floor (122) of the inner portion (104f, 104g) is arranged below the support surface.

11. The apparatus of any of claims 1 to 7, comprising a microscope stage kit (138b) designed for holding the inner portion (104g) in a third position, wherein the inner portion (104g) protrudes in the third position through an opening of the microscope stage such that a floor (122) of the inner portion (104g) is arranged below the microscope stage.

12. The device according to any one of the preceding claims, wherein the frame (102a-102g) has at least one guide member (114) designed to guide the inner portion perpendicular to the support surface.

13. The device according to any one of the preceding claims, comprising two manipulators, wherein the frame (102a-102g) comprises a grip opening and the two manipulators are designed to grip and hold the inner portion (104a-104g) through the grip opening.

14. The device according to any one of the preceding claims, wherein the cavity (106) and the frame (102a-102g) are designed as plastic injection-molded parts.

Technical Field

The present invention relates to a device for receiving a sample in a microscope.

Background

In the field of optical microscopy, a microscope should be used to examine a plurality of samples in a short time. For this purpose, so-called microtiter plates are known from the prior art. These microtiter plates consist of cavities, also called wells or wells, which are arranged in a grid in a frame. To examine the specimen using an inverted microscope or a transmitted light microscope, the cavity is closed from below with an optically transparent base. The dimensions of microtiter plates are standardized by the laboratory automation and screening institute. This standard can be seen in http:// www.slas.org/resources/information/industry-standards/http.

Especially in microscopes with an objective lens with a large light flow, i.e. a large opening angle or a large numerical aperture, and with a moderate working distance, the frame of the microtiter plate forms a mechanical obstacle. In particular, the sample-facing part of the objective may collide with the frame of the microtiter plate. This prevents those cavities that are external, i.e. arranged close to the edge, from being available for sample inspection. On the other hand, the frame cannot simply be eliminated, since it forms a support surface for the microtiter plate. If the microtiter plate is placed against an optically transparent substrate, the substrate can be scratched and the sample disposed in the cavity can be difficult to view. Devices for holding microtiter plates have also been proposed.

Disclosure of Invention

The object of the invention is to provide a device for receiving a sample in a microscope, which enables the sample arranged in a cavity of a microtiter plate to be examined microscopically, without collision occurring between the device and the objective of the microscope.

This object is achieved by a device having the features of claim 1. Advantageous developments are given in the dependent claims.

The device according to claim 1, comprising a microtiter plate having a frame and an interior portion that fits into the frame. The inner part comprises cavities which are closed from below by an optically transparent bottom plate. "below" in this application refers to the direction of gravity. This means, in particular, that the base plates are each arranged at the end of the cavity pointing in the direction of the support surface when the inner part is arranged in the first position. If the inner part is held in the first position, i.e. if the inner part is fitted into the frame, the bottom plate is arranged above the support surface of the frame. Thereby preventing the bottom plate from being scratched. The inner portion may be removed from the frame for examination using a microscope. The removed inner part can be introduced into the microscope, whereby it is possible to inspect the sample arranged in the cavity microscopically without collision between the device and the objective of the microscope.

In a preferred embodiment, the microtiter plate has a locking device which is designed to releasably connect the inner part and the frame to one another. If the inner part and the frame are connected to each other, the microtiter plate may be used in any laboratory equipment provided for the use of microtiter plates. This increases the flexibility of the device. The microtiter plate preferably comprises at least three locking means of the above-described type, whereby the inner part is held in the first position at three support points. By means of these three support points, a plane is defined which is preferably parallel to the focal plane of the objective lens. This is achieved in that the optically transparent base plate is parallel to the focal plane of the objective. This prevents aberrations caused by the tilting of the base plate relative to the focal plane.

In a further preferred embodiment, the locking device has a catch part which is connected to the frame by a hinge, in particular a solid hinge, and which is designed to snap into a receptacle of the inner part, so that the inner part and the frame are releasably connected to one another. This results in a mechanically particularly simple locking device. In particular, the catch part may be formed by a spherical protrusion on the solid hinge. Thereby, a sliding locking and/or unlocking may be achieved.

In another preferred embodiment, the device comprises an unlocking device with a pin which is designed to be guided through a receptacle of the inner part in order to press the catch part of the locking device out of the receptacle, so that the connection between the inner part and the frame is released. Thereby preventing accidental loosening of the connection between the inner part and the frame. Furthermore, the release of the inner part from the frame can easily be automated by means of pins. In particular, the unlocking device has a motorized drive for actuating the bolt.

In an advantageous embodiment, the device comprises unlocking means which are designed to release the connection between the inner part and the frame by pressing the inner part from above. This allows the operator to simply manipulate the unlocking device, whereby the device can be used more efficiently. The unlocking device may comprise, in particular, a lever mechanism.

In an advantageous embodiment, the device comprises a microscope stage kit with a guide part for guiding the microtiter plate, wherein the guide part is designed to press the catch part of the locking device out of the receptacle when guiding the microtiter plate, so that the connection between the inner part and the frame is released. Thus, when the microtiter plate is loaded into the microscope, the inner part is released from the frame and can be moved in a direction perpendicular to the support surface. This allows a particularly efficient use of the device.

In another advantageous embodiment, the frame has an opening at its bottom side and the inner part is movable such that the bottom plate can pass through the opening of the frame. The inner part can thereby be positioned such that the bottom plate is arranged below the support surface defined by the frame. The inner part preferably protrudes through an opening in a microscope stage of the microscope, while the support surface rests on the microscope stage. The objective for examining the sample can then be positioned close to the base plate without the objective colliding with the frame of the microtiter plate. In particular, no additional components are required in this embodiment to arrange the inner part in the microscope.

Advantageously, the frame has a depth stop which is designed to hold the inner part in the second position, wherein the inner part in the second position protrudes through the opening of the frame such that the floor of the inner part is arranged below the supporting surface. The depth stop prevents the inner portion from moving relative to the frame. This prevents, in particular, a displacement of the base plate relative to the focal plane of the objective. The frame preferably has at least three depth stops, the respectively assigned support points of which, which are the points at which the inner part rests on the respective depth stop, define a plane parallel to the focal plane of the objective. This prevents aberrations caused by the tilting of the base plate relative to the focal plane.

It is particularly advantageous if the device comprises a microscope stage kit designed for holding the inner part in the second position, wherein the inner part in the second position protrudes through the opening of the frame such that the floor of the inner part is arranged below the support surface. For this purpose, the microscope stage kit has, for example, a depth stop which positions the inner part such that the base plate is parallel to the focal plane of the objective lens. The microscope stage assembly preferably has three depth stops, the respectively assigned support points of which define a plane parallel to the focal plane of the objective.

In a preferred embodiment, the apparatus comprises a microscope stage kit designed for holding the inner part in a third position, wherein the inner part in the third position protrudes through an opening of the microscope stage such that a floor of the inner part is arranged below the microscope stage. In particular, the inner part is held by means of a depth stop. Thus, for examining the sample, the microtiter plate can be moved relative to the objective without the objective colliding with the frame of the microtiter plate.

In a further preferred embodiment, the frame has at least one guide element which is designed to guide the inner part perpendicularly to the supporting surface. It is thereby ensured that the base plate remains parallel to the support surface and the focal plane of the objective lens even when the inner part is moved.

In another preferred embodiment, the device comprises two manipulators, wherein the frame comprises a grip opening and the two manipulators are designed for gripping and holding the inner portion via the grip opening. By means of the manipulator, the inner part can be positioned particularly precisely in order to prevent aberrations caused by the tilting of the base plate relative to the focal plane.

The cavity and the frame are preferably designed as plastic injection-molded parts. This makes it possible to produce the microtiter plate of the device particularly inexpensively.

Drawings

Additional features and advantages are derived from the following description, which explains the several embodiments in more detail, with reference to the drawings.

FIG. 1a is a top view of a microtiter plate of a device for receiving samples in a microscope according to one embodiment;

fig. 1b is a perspective view of a frame of a microtiter plate of a device for receiving samples in a microscope according to the embodiment of fig. 1 a;

fig. 1c is a perspective view of an interior portion of a microtiter plate of a device for receiving samples in a microscope according to the embodiment of fig. 1 a;

FIG. 2 is a cross-sectional view of a microtiter plate according to one embodiment in an assembled state;

FIG. 3a is a cross-sectional view of a locking device of a microtiter plate according to one embodiment, wherein the inner portion is held in a first position;

fig. 3b is a cross-sectional view of a locking device of the microtiter plate according to the embodiment of fig. 3a, wherein the inner portion is held in a second position;

FIG. 4 is a cross-sectional view of a locking device of a microtiter plate according to an alternative embodiment;

FIG. 5 is a cross-sectional view of a locking device of a microtiter plate according to another alternative embodiment;

FIG. 6 is a cross-sectional view of a device for receiving a sample in a microscope, the device having a microscope stage kit, according to one embodiment; and

fig. 7 is a cross-sectional view of a device for receiving a sample in a microscope having a microscope stage kit according to an alternative embodiment.

Identical or identically functioning parts are denoted by the same reference numerals in the following figures.

Detailed Description

Fig. 1a shows a top view of a microtiter plate 100a of a device for receiving samples in a microscope according to an embodiment.

The microtiter plate 100a includes a frame 102a and an interior portion 104a, which are shown separately in fig. 1b or 1c, respectively. The inner portion 104a has a plurality of cavities 106 for receiving a sample. The cavities 106 are arranged in a grid and are indicated by the letters a to H from top to bottom and the numbers 1 to 12 from left to right, respectively. Thus, each cavity 106 may be uniquely identified by a combination of letters and numbers. The microtiter plate 100a shown in FIG. 1a has, for example, 96 cavities 106 arranged in a grid. Alternatively, other arrangements of the cavities 106 are envisioned, particularly those described by standards promulgated by the society for laboratory automation and screening.

Fig. 1b shows a perspective view of the frame 102a of the microtiter plate 100a of the device for receiving samples in a microscope according to the embodiment of fig. 1 a.

The frame 102a includes a wall 108a bounding an opening 110 extending through the frame 102a in a vertical direction. The opening 110 is designed to receive the interior portion 104a of the microtiter plate 100 a. On the underside of the wall 108a, a circumferential foot 112 is provided, which defines a support surface of the frame 102a and thus of the microtiter plate 100 a. Four projections 114 are provided on the top side of the frame 102a, which projections are designed to project into holes 116 of the inner part 104a shown in fig. 1c, so that the inner part 104a is prevented from sliding off vertically relative to the frame 102 a. The projection 114 is part of a locking device which will be described further below with the aid of an embodiment and with reference to fig. 3a to 5 and is denoted there by reference numerals 124a to 124 c.

Fig. 1c shows a perspective view of an inner part 104a of a microtiter plate 100a of a device for receiving samples in a microscope according to the embodiment of fig. 1 a.

The inner portion 104a includes a structural member 118a that includes voids 106 arranged in a grid. On the top side of the structural part 118a, a hole 116 for the projection 114 of the frame 102a is formed.

Fig. 2 shows a cross-sectional view of a microtiter plate 100b according to one embodiment in an assembled state. The cutting plane extends perpendicular to the longitudinal direction of the walls 108b, 118b of the frame 102b and the inner portion 104 b.

Only one of the voids 106 of the inner portion 104b is exemplarily shown in fig. 2. In the embodiment shown, the cavity 106 is formed by a cylindrical recess of the structural part 118b of the inner part 104b, which extends in a direction a perpendicular to the support surface and is closed at its lower end by an optically transparent bottom plate 122. Alternatively, the cavity 106 can also be formed by a rectangular recess of the structural part 118b, in particular also with rounded edges.

At the shoulder of the projection 114, the frame 102b forms a support surface 120 on which the inner portion 104b can rest. The inner part 104b can thereby be held in a first position in which the bottom plate 122 is arranged above the support surface formed by the feet 112. The inner portion 104b may be moved along the projection 114 in a direction a perpendicular to the support surface to separate the inner portion 104b from the frame 102 b. Thus, the protrusion 114 forms a guide member for guiding the inner portion 104 b.

Fig. 3a shows a cross-sectional view of a locking device 124a of a microtiter plate 100c according to one embodiment. In fig. 3a, the inner portion 104c is held in the first position.

The locking device 124a includes a spherical snap member 126a that is connected to the frame 102c by a solid hinge 128. The catch part 122a is designed to snap into the receptacle 130 of the structural part 118c of the inner part 104c and thus releasably connect the inner part 104c and the frame 102c to one another. By the spherical shape of the catch part 126a, it is achieved that the catch part 126a is slidingly snapped into and out of the receptacle 130 of the structural part 118c of the inner part 104 c. In fig. 3a, the snap member 122 snaps into the receptacle 130 and thereby securely holds the inner portion 104c in the first position.

Fig. 3b shows a cross-sectional view of the locking means 124a of the microtiter plate 100c according to the embodiment of fig. 3 a. In fig. 3b, the inner part 104c is held in a second position in which the base plate 122 is arranged below the support surface, so that the frame 102c does not form a mechanical obstacle for the microscope objective.

In fig. 3b, the snap member 126a is not snapped into the receptacle 130. Furthermore, the inner portion 104c is displaced downwards in a direction a perpendicular to the support surface with respect to the view in fig. 3 a. In fig. 3b, the inner portion 104c rests on a support surface 120 formed by the wall 108c of the frame 102c and is thereby held in the second position.

Fig. 4 shows a cross-sectional view of the locking device 124b of the microtiter plate 100d according to an alternative embodiment. The locking device 124b according to fig. 4 differs from the locking device 124a according to fig. 3a and 3b in that the catch part 126b is not spherical. Thus, the catch member 126b does not slidably disengage from the receptacle 130 of the structural member 118d of the inner portion 104d to release the connection between the inner portion 104d and the frame 102 d. To release the connection between the inner portion 104d and the frame 102d, the pin 132a is required. The pin 132a is designed to be guided through the receptacle 130 of the inner part 10dc in order to press the catch part 126b of the locking device 124b out of the receptacle 130. The unlocking means are thus formed by the pin 132 a.

Fig. 5 shows a cross-sectional view of a locking device 124c of a microtiter plate 100e according to another alternative embodiment. The locking device 124c according to fig. 5 differs from the locking device 124b according to fig. 4 in that above the receptacle 130 of the inner part 104e there is additionally provided a guide rail 134 which guides the pin 132b in a direction a perpendicular to the support surface. Thereby preventing the inner portion 104e from slipping vertically relative to the frame 102 e. The projection 114 may be omitted in this alternative embodiment. Furthermore, the pin 132b has a guide part 136, which prevents the pin 132b from slipping out of the guide rail 134 when the pin 132b is guided in the direction a perpendicular to the support surface. The shape of the guide part 136 also prevents the snap part 126b from snapping into the receptacle 130 of the structural part 118e of the inner part 104 e.

Fig. 6 shows a cross-sectional view of a microtiter plate 100f having a microscope stage kit 138a according to one embodiment.

The microscope stage kit 138a has a depth stop 140a, against which a projection 142 formed on the structural part 118f of the inner part 104f can rest. When the projection 142 rests on the depth stop 140a, the inner portion 104f is held in the second position. In the embodiment according to fig. 6, the support surface 120 formed by the wall 108c of the frame 102c may be omitted. In particular, the embodiment according to fig. 6 can be advantageously improved by the components of the locking devices 124a to 124c according to fig. 3a, 3b, 4 and 5.

Fig. 7 shows a cross-sectional view of a device for receiving a sample in a microscope having a microtiter plate 100g and a microscope stage kit 138b according to an alternative embodiment.

The microscope stage kit 138b has a depth stop 140b against which the projection 123 of the base plate 122 can rest. When the protrusion 123 rests on the depth stop 140b, the inner portion 104f is held in the third position. In the third position, the inner portion 104g protrudes through an opening in the microscope stage such that the floor 122 of the inner portion 104g is disposed below the microscope stage. Thus, neither the microscope stage nor the frame 102g is a mechanical obstacle for the microscope objective, and the support surface 120 formed by the wall 108c of the frame 102c can be omitted in the embodiment according to fig. 7.

Different embodiments of a device for receiving a sample in a microscope have already been shown by means of fig. 1a to 7, which enable a sample arranged in a cavity to be examined by means of a microscope without collisions occurring in this case between the frame of the microtiter plate and the microscope objective.

Although some aspects within the scope of the described apparatus have been described, it is clear that these aspects are also a description of a corresponding method, wherein a block or an apparatus corresponds to a method step or a function of a method step. Similarly, aspects described in the context of method steps are also a description of the respective block or component or of a characteristic of the respective device. Some or all of the method steps may be performed by (or using) hardware devices, such as processors, microprocessors, programmable computers, or electronic circuits. In some embodiments, one or more of the most important method steps may be performed by such an apparatus.

Embodiments of the invention may be implemented in hardware or software, depending on certain implementation requirements. Implementation can be via a non-volatile storage medium, such as a floppy disk, DVD, blu-ray, CD, ROM, PROM and EPROM, EEPROM or flash memory, on which electronically readable control signals are stored, which cooperate (or can cooperate) with a programmable computer system such that the respective method is performed. Accordingly, the digital storage medium may be computer-readable.

Some embodiments according to the invention comprise a data carrier having electronically readable control signals, which can cooperate with a programmable computer system so as to carry out one of the methods described herein.

Generally, embodiments of the invention can be implemented as a computer program product having a program code, which is effective to perform one of the methods when the computer program product runs on a computer. The program code may be stored, for example, on a machine-readable carrier.

Other embodiments include a computer program stored on a machine-readable carrier for performing one of the methods described herein.

In other words, an embodiment of the invention is thus a computer program having a program code for performing one of the methods described herein, when the computer program runs on a computer.

Thus, another embodiment of the invention is a storage medium (or data carrier or computer-readable medium) comprising a computer program stored thereon for performing one of the methods described herein when it is executed by a processor. The data carrier, the digital storage medium or the recording medium is typically tangible and/or not seamless. Another embodiment of the present invention is an apparatus as described herein that includes a processor and a storage medium.

Thus, another embodiment of the invention is a data stream or a signal sequence forming a computer program for performing one of the methods described herein. The data streams or signal sequences may be configured, for example, in such a way that they are transmitted via a data communication connection, for example via the internet.

Another embodiment includes a processing mechanism, such as a computer or programmable logic device, configured or adapted to perform one of the methods described herein.

Another embodiment comprises a computer on which a computer program for performing one of the methods described herein is installed.

Another embodiment according to the present invention comprises an apparatus or system configured to transmit a computer program (e.g., electronically or optically) for performing one of the methods described herein to a receiver. The receiver may be, for example, a computer, a mobile device, a storage device, etc. The apparatus or system may comprise, for example, a file server for transmitting the computer program to the receiver.

In some embodiments, programmable logic devices (e.g., field programmable gate arrays, FPGAs) may be used to perform some or all of the functions of the methods described herein. In some embodiments, a field programmable gate array may cooperate with a microprocessor to perform one of the methods described herein. In general, the methods are preferably performed by any hardware device.

List of reference numerals

100a-100g microtiter plate

102a-102g frame

104a-104g inner part

106 cavities

108a-108g wall

110 opening

112 foot

114 projection

116 holes

118a-118g structural component

120 bearing surface

122 base plate

123 projection

124a-124c locking device

126a, 126b snap member

128 solid hinge

130 jack

132a, 132b pin

134 guide rail

136 guide member

138a, 138b microscope stage kit

140a, 140b depth stops

142 are raised.