SAMPLE CARRIER INTERFACE AND METHODS - Patent application
The sample carrier interface locks microwell plates above the microscope stage, addressing interference issues with the objective lens, enabling full access and automation, and supporting incubation and sterile environments.
Patent Information
- Application Number
- JP2024544918
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2022-01-28
- Filing Date
- 2023-01-26
- Publication Date
- 2025-02-06
AI Technical Summary
Inverted microscopes face challenges in fully utilizing the capacity of microwell plates due to shelf-like structures on stage inserts that interfere with the objective lens, limiting access to samples near the inner edge of the stage insert.
A sample carrier interface with a frame that locks the microwell plate above the microscope stage, applying lateral force to prevent it from falling through the opening, allowing full access to the sample without obstruction and enabling observation from below.
The solution ensures complete utilization of the microwell plate capacity, facilitating easy loading and observation of samples without manual adjustment, improving versatility and automation, and allowing for incubation and sterile environments.
Smart Images

Figure 2025504026000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to a sample carrier interface for mounting a sample carrier on a microscope stage.The present invention further relates to a method for adapting a sample carrier to a microscope stage. [Background technology]
[0002] In an inverted microscope setup, the detection objective is placed below the microscope stage. To allow microscopic observation of a sample placed on the microscope stage, the microscope stage of the inverted microscope includes an aperture. Typically, the sample is contained in a sample carrier, e.g., a microwell plate, a petri dish or a microscope slide. The sample or samples are observed from below through a window located on the bottom side of the sample carrier.
[0003] In order to prevent the sample carrier from falling through the opening when mounting it on the microscope stage of an inverted microscope, some inverted microscopes are equipped with so-called stage inserts. The stage insert has an inner edge which fits into the opening of the microscope stage on the one hand and which matches the outer shape of the sample holder on the other hand. The inner edge has a shelf-like structure on which the micro-well plate rests. However, such a shelf-like structure collides with the objective lens when observing samples located near the inner edge of the stage insert. In particular, if the sample carrier is a micro-well plate, such a shelf-like structure obstructs the use of wells near the inner edge of the stage insert, thus significantly reducing the capacity of the sample carrier.
[0004] The use of microwell plates is well known in the fields of medical and biological analysis. The most common microwell plates are those used for high throughput screening. However, the use of microwell plates in microscopy is relatively new. Because microwell plates can hold multiple samples within individual wells and have a high sample holding capacity, they are often used in the context of high content microscopy. Summary of the Invention [Problem to be solved by the invention]
[0005] It is therefore an object of the present invention to provide a sample carrier interface for mounting a sample carrier to a microscope stage, and a method for mounting a sample carrier to a microscope stage, which allows full utilization of the volume of the sample carrier. [Means for solving the problem]
[0006] The above mentioned object is achieved by the subject matter of the respective independent claims. Advantageous embodiments are defined in the respective dependent claims and in the following description.
[0007] The proposed sample carrier interface for mounting a sample carrier on a microscope stage comprises a frame configured to receive the sample carrier and to be positioned above an aperture of the microscope stage, the sample carrier interface further comprising a locking device configured to apply a lateral force to the sample carrier when in a locked state in order to maintain the sample carrier suspended above the aperture when the sample carrier is received in the frame and the frame is positioned above the aperture of the microscope stage.
[0008] When the sample carrier is accommodated in the frame, the frame effectively increases the size of the sample carrier, which prevents the sample carrier from falling through the opening in the microscope stage. In this way, the sample carrier interface makes the sample carrier suitable for use with a microscope. The sample carrier is held above or within the opening by the sample carrier interface. A sample accommodated in the sample carrier can be viewed from below through the opening in the microscope stage.
[0009] The sample carrier accommodated in the frame is held in position only by the lateral force exerted on the sample carrier by the locking device. The sample carrier interface therefore does not require any support elements below the sample carrier. This allows unrestricted access to the bottom side of the sample carrier and thus unhindered observation of the sample accommodated in the sample carrier from below. In particular, the part of the sample carrier near the inner edge of the aperture of the microscope stage is unhindered. The proposed sample carrier interface therefore allows full utilization of the capacity of the sample carrier.
[0010] In a preferred embodiment, the locking device is configured to hold the sample in place when the sample carrier interface is moved to or from the microscope stage and when the locking device is in the locked state. This allows the sample carrier interface to be loaded with a sample carrier outside the boundaries of the microscope. This significantly facilitates the use of the sample carrier interface. In particular, multiple sample carrier interfaces can be preloaded with sample carriers in order to speed up microscopy.
[0011] In another preferred embodiment, the frame is provided with an opening at the bottom side and is configured to receive the sample carrier through said opening, in particular allowing full access to the bottom side of the sample carrier and allowing unhindered observation of the samples contained in the sample carrier from below.
[0012] In another preferred embodiment, the bottom side of the frame defines a contact surface which contacts the top surface of the microscope stage when the frame is positioned above the aperture of the microscope stage. In that embodiment, the sample carrier interface is located on the microscope stage. This means that the sample carrier interface does not have to be adapted to a specific aperture of a specific microscope stage, but can be used with several different microscopes and microscope stages. This makes the sample carrier interface much more versatile.
[0013] In another preferred embodiment, the contact surface of the frame is flush with the bottom side of the sample carrier when the sample carrier is accommodated in the frame and the frame is positioned above the opening of the microscope stage. In this embodiment, when the sample carrier interface is placed on the top of the microscope stage, the sample carrier is positioned above the opening of the microscope stage and the bottom side of the sample carrier is flush with the top surface of the microscope stage. This allows the bottom side of the sample carrier to always be easily positioned at the reference height. Therefore, no manual adjustment is required when positioning the sample carrier interface on the microscope stage. This allows for easier automation of, for example, microscopy.
[0014] In another preferred embodiment, the sample carrier is completely housed in the frame, which surrounds the periphery of the sample carrier while leaving at least the bottom side of the sample carrier exposed, thereby protecting the sample carrier, for example, from scratches.
[0015] In another preferred embodiment, the locking device comprises an adjustment element for switching between a locked state and an unlocked state, in which the locking device exerts no lateral force on the sample carrier. The adjustment element may in particular be a slider, a button or a rotary switch. The adjustment element allows the user to quickly switch between the locked and unlocked states, which makes it easier to use the sample carrier interface.
[0016] In another preferred embodiment, the locking device comprises at least one movable engagement part configured to engage with the sample carrier when in the locked state and thereby exert a lateral force on the sample carrier. In said embodiment, the engagement part contacts the sample carrier in order to exert a lateral force on the sample carrier. The larger the contact surface between the engagement part and the sample carrier, the more securely the sample carrier is held by the sample carrier interface. It is therefore advantageous to provide a plurality of engagement parts each engaging with the sample carrier from a different side when the locking device is in the locked state.
[0017] In another preferred embodiment, the locking device comprises a wire which is wound around the circumference of the sample carrier when the sample carrier is accommodated in the frame, said wire being tightenable to apply a lateral force to the sample carrier. In particular, the wire can be tightened around one or more of the engagement parts and the circumference of the sample carrier in order to bring the engagement parts into contact with the sample carrier and apply a lateral force to the sample carrier. The use of the wire ensures that the lateral force applied to the sample carrier is uniform, which ensures a secure grip of the sample carrier.
[0018] In another preferred embodiment, the sample carrier interface comprises at least one fixing element configured to engage with a corresponding fixing element of the microscope stage. In particular, the fixing element of the sample carrier interface and the corresponding fixing element of the microscope stage are magnets. Alternatively or additionally, the corresponding fixing element of the microscope stage comprises at least one protruding element, e.g. a pin, configured to fit into a corresponding hole of the frame, which hole forms the fixing element of the sample carrier interface. The fixing element prevents the position of the sample carrier interface from changing after the sample carrier interface has been positioned on the microscope stage.
[0019] In another preferred embodiment, the sample carrier interface comprises at least one guide portion configured to engage with a microscope stage for positioning the sample carrier interface on top of the microscope stage. The guide portion ensures that the sample carrier interface is positioned at the same predefined position on the microscope stage every time the sample carrier interface is positioned on the microscope stage. This means that no additional adjustments are necessary, which allows for example easier automation of microscopy.
[0020] In another preferred embodiment, the frame is configured to form an incubation chamber when the sample carrier is accommodated in the frame. In particular, the frame is configured to form an airtight incubation chamber when the sample carrier is accommodated in the frame. In said embodiment, the sample carrier interface is used as a so-called stage-top incubator. The sample carrier interface can be used to supply an incubation atmosphere and / or a (semi-)sterile atmosphere to the samples accommodated in the sample carrier. Since the incubation chamber is formed by the sample carrier interface itself, the microscope itself does not have to be specially adapted.
[0021] In another preferred embodiment, the locking device comprises a sealing portion configured to provide an airtight seal to the incubation chamber when the sample carrier is accommodated in the frame and the locking device is in the locked state. In that embodiment, the sample carrier forms part of the wall of the incubation chamber. This makes the sample carrier interface significantly lighter and therefore easier to handle. This further saves material costs.
[0022] In another preferred embodiment, the frame comprises a gas inlet for supplying an incubation atmosphere and / or a (semi-)sterile atmosphere to the incubation chamber. In said embodiment, the gas inlet is connected to a climate control unit for controlling, for example, the temperature, humidity and CO2 content of the supplied atmosphere. This allows precise control of the environment of the samples contained in the sample carriers.
[0023] In another preferred embodiment, the sample carrier is a microwell plate or slide holder. In particular, the frame is adapted to accommodate a particular type or form factor of the sample carrier, for example a microwell plate or slide holder. By adapting the frame to a particular form factor, the sample carrier is more reliably accommodated within the frame.
[0024] The invention further relates to a method for mounting a sample carrier on a microscope stage, the method comprising the steps of providing a sample carrier interface as described above, inserting the sample carrier into a frame of the sample carrier interface, locking the sample carrier to the frame by applying a lateral force to the sample carrier, and positioning the sample carrier interface above an opening in the microscope stage to suspend the sample carrier above the opening.
[0025] The method has the same advantages as the sample carrier interface described above. In particular, the method can be complemented using the features of the respective dependent claims relating to the sample carrier interface.
[0026] In a preferred embodiment, the method comprises the additional steps of placing the sample carrier on a flat surface or on a dedicated mounting plate and lowering the sample carrier interface from above onto the sample carrier. By lowering the sample carrier interface from above onto the sample carrier, the contact surface of the frame is always positioned at the same height as the bottom side of the sample carrier. This ensures that the bottom side of the sample carrier is always easily positioned at a reference height and does not require manual adjustments when positioning the sample carrier interface on the microscope stage.
[0027] Specific embodiments will now be described with reference to the drawings. [Brief description of the drawings]
[0028] [Figure 1] FIG. 1 is a schematic cross-sectional view illustrating a sample carrier interface for mounting a sample carrier on a microscope stage according to one embodiment. [Diagram 2] FIG. 13 is a schematic top view of a sample carrier interface according to another embodiment; [Diagram 3] FIG. 3 is a schematic cross-sectional view of the sample carrier interface according to FIG. 2; [Figure 4] FIG. 4 shows a schematic top view of the sample carrier interface according to FIGS. 2 and 3; [Diagram 5] FIG. 5 is a schematic cross-sectional view showing the sample carrier interface according to FIGS. 2 to 4. [Figure 6a] FIG. 6 shows a schematic view of the locking device of the sample carrier interface according to FIGS. 2 to 5 in the unlocked state; [Figure 6b] FIG. 6 shows a schematic view of the locking device of the sample carrier interface according to FIGS. 2 to 5 in the locked state; [Figure 7a] FIG. 2 shows a schematic cross-sectional view of a sample carrier; [Figure 7b] FIG. 7b shows a schematic cross-sectional view of the sample carrier interface and the sample carrier according to FIG. 7a. [Figure 7c] FIG. 7b shows another schematic cross-sectional view of the sample carrier interface according to FIG. 7b and the sample carrier according to FIG. 7a. [Figure 7d] FIG. 7B is a schematic cross-sectional view of the sample carrier interface according to FIG. 7B and the sample carrier according to FIG. 7A. [Figure 8] FIG. 2 is a schematic cross-sectional view of a sample carrier interface according to an embodiment having an incubation chamber. [Figure 9] FIG. 9 shows a schematic top view of the sample carrier interface according to FIG. 8. [Figure 10] FIG. 2 is a schematic top view illustrating a sample carrier interface according to an embodiment. [Figure 11a] FIG. 1 is a schematic top view showing a sample carrier containing 96 wells. [Figure 11b] FIG. 2 is a schematic top view showing a sample carrier containing 24 wells. [Figure 12a] FIG. 2 is a schematic top view illustrating a sample carrier interface in a locked state according to one embodiment. [Figure 12b] FIG. 12b shows a schematic top view of the sample carrier interface according to FIG. 12a in the unlocked state. [Figure 13a] FIG. 12c shows a detailed view of the locking device of the sample carrier interface according to FIGS. 12a and 12b in the locked state; [Figure 13b] FIG. 12c shows a detailed view of the locking device of the sample carrier interface according to FIGS. 12a and 12b in the unlocked state; [Figure 14] FIG. 13 is a schematic diagram illustrating a sample carrier interface according to another embodiment. [Figure 15] FIG. 15 shows a schematic bottom view of the sample carrier interface according to FIG. 14. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0029] FIG. 1 is a schematic cross-sectional view of a sample carrier interface 100 for mounting a sample carrier 102 to a microscope stage 104, according to one embodiment.
[0030] Also shown in Figure 1 is a microscope objective 106. The optical axis O of the objective 106 is shown as a dashed vertical line. In Figure 1, the sample carrier 102 is exemplarily shown to be a microwell plate having a number of wells 108 each for containing a sample.
[0031] The sample carrier interface 100 is configured to prevent the sample carrier 102 from falling through an opening 110 in the microscope stage 104. The opening 110 in the microscope stage 104 allows the sample contained in the sample carrier 102 to be viewed from below through the objective lens 106. However, the opening 110 in the microscope stage 104 is typically larger than the dimensions of the sample carrier 102. Thus, the sample carrier interface 100 is required to fit the sample carrier 102 onto the microscope stage 104.
[0032] The sample carrier interface 100 includes a frame 112 that holds the sample carrier 102. The frame 112 is dimensioned so that it can be placed over the opening 110 of the microscope stage 104 without the frame 112 falling through the opening 110. A bottom side of the frame 112 forms a contact surface that contacts the top surface of the microscope stage 104 when the sample carrier interface 100 is placed on the microscope stage 104.
[0033] In this embodiment, the sample carrier 102 is completely accommodated in a cavity 114 formed by the frame 112. The sample carrier 102 can be inserted into the cavity 114 through an opening 116 located in the bottom side of the frame 112. In this embodiment, the frame 112 extends circumferentially around the circumference of the sample carrier 102 and is closed at the top. In other words, the frame 112 forms a downward-facing housing that can be placed above the sample carrier 102 in order to insert it into the frame 112. The cavity 114 of the frame 112 is wider at the bottom side of the frame 112 and tapers upwards. This tapered geometry of the cavity 114 guides the sample carrier 102 into position when the sample carrier interface 100 is lowered onto the sample carrier 102 in order to insert it into the frame 112. Furthermore, the tapered geometry prevents the objective lens 106 from colliding with the frame 112 when the objective lens 106 is oriented in the well 108 near the inner edge of the opening 110 of the microscope stage 104, thereby allowing greater access to the sample carrier 102 from below.
[0034] Additionally, the frame 112 of this embodiment includes spacer elements 118 disposed on an upper side of the frame 112 that prevent the sample carrier 102 from being inserted too deeply into the cavity 114. In particular, the sample carrier 102 is inserted into the frame 112 such that the bottom side of the sample carrier 102, the bottom side of the frame 112, and the top surface of the microscope stage 104 are all at the same height, as indicated by the dashed horizontal line H in FIG.
[0035] The frame 112 further comprises a fixing element 120a configured to engage with a complementary fixing element 120b of the microscope stage 104. The fixing element 120a of the frame 112 is arranged flush with a bottom side of the frame 112 to the left and right of the sample carrier 102 in Fig. 1. The fixing element 120b of the microscope stage 104 is arranged flush with a top surface of the microscope stage 104 to the left and right of the opening 110 of the microscope stage 104 in Fig. 1. In this embodiment, the fixing element 120a of the frame 112 and the complementary fixing element 120b of the microscope stage 104 are formed by magnets.
[0036] The sample carrier interface 100 further comprises a locking device 122 configured to lock the sample carrier 102 accommodated in the frame 112. The locking device 122 has a locked state in which the sample carrier 102 is locked in place and an unlocked state in which the sample carrier 102 is not locked in place and can for example be removed from the frame 112. Figure 1 exemplarily shows the locking device 122 in the locked state.
[0037] The locking device 122 includes movable engagement parts 124 arranged in the cavity 114 of the frame 112. The engagement parts 124 are positioned such that each engagement part 124 faces a side of the sample carrier 102. The engagement parts 124 can be moved towards the sample carrier 102 for engagement therewith. When the engagement parts 124 engage with the sample carrier 102, the engagement parts 124 exert a lateral force on the sample carrier 102 to lock the sample carrier 102 in place, and the locking device 122 is in a locked state. The bottom side of the sample carrier 102 is not disturbed at all, since the sample carrier 102 is held in place laterally only by the engagement parts 124 that engage with the sample carrier 102. This allows the objective lens 106 to be easily positioned under all wells 108 of the sample carrier 102, and the volume of the sample carrier 102 can be fully utilized.
[0038] FIG. 2 is a schematic top view of a sample carrier interface 200 according to another embodiment.
[0039] The sample carrier interface 200 according to Fig. 2 is distinguished from the sample carrier interface 200 according to Fig. 1 in that the frame 112 is open at the top, allowing access to the sample carrier 102 from above. As can be seen from Fig. 2, the frame 112 surrounds the sample carrier 102 on all four sides. In particular, the sample carrier 102 is located in the centre of the frame 112 when viewed from above. Thus, when the sample carrier interface 200 is placed on the microscope stage 104, the sample carrier 102 is located above the centre of the opening 110 of the microscope stage 104. This ensures that all wells 108 of the sample carrier 102 are equally accessible for observation using the objective lens 106.
[0040] The locking device 122 comprises an adjustment element for switching between a locked state and an unlocked state. In the embodiment, the adjustment element is exemplarily formed by a slider 202 which can be moved along the side of the frame 112, i.e. from left to right in FIG. 2 and back. The slider 202 has a first position which corresponds to the unlocked state of the locking device 122 and a second position which corresponds to the locked state of the locking device 122. When the slider 202 is moved from the first position to the second position, the engagement part 124 moves towards the sample carrier 102 and finally comes into contact with a side of the sample carrier 102. When the slider 202 is moved from the second position back to the first position, the engagement part 124 moves away from the sample carrier 102.
[0041] In Fig. 2 the locking device 122 is shown in an unlocked state, with the slider 202 in a first position. As can be seen from Fig. 2, the engagement portion 124 is therefore not in contact with the sample carrier 102. In this state the sample carrier 102 can be inserted into the sample carrier interface 200 or the sample carrier 102 can be removed from the sample carrier interface 200.
[0042] FIG. 3 is a schematic cross-sectional view of the sample carrier interface 200 according to FIG.
[0043] In Fig. 3 the locking device 122 is shown in an unlocked state. As can be seen from Fig. 3, the engagement portion 124 is located directly on the inner wall 300 of the frame 112 when the locking device 122 is in its unlocked state. The sample carrier 102 can therefore be inserted into the frame 112 without hindrance. For ease of understanding, the sample carrier 102 is not shown in Fig. 3.
[0044] FIG. 4 is a schematic top view of the sample carrier interface 200 according to FIGS.
[0045] 4 shows the locking device 122 in a locked state, with the slider 202 in a second position. The engagement portion 124 is in contact with the sample carrier 102 and applies a lateral force to the side of the sample carrier 102. In this state, the sample carrier 102 is securely held by the sample carrier interface 200 and the sample carrier interface 200 can be used to carry the sample carrier 102.
[0046] FIG. 5 is a schematic cross-sectional view of the sample carrier interface 200 according to FIGS.
[0047] Figure 5 shows the locking device 122 in a locked state. An upper portion of each of the engagement portions 124 is hinged to an inner wall 300 of the frame 112. A lower portion of each of the engagement portions 124 is moved towards the inside of the frame 112 such that the engagement portions 124 are slightly tilted. For ease of understanding, the sample carrier 102 is not shown in Figure 5.
[0048] FIG. 6a shows a schematic illustration of the locking device 122 of the sample carrier interface 200 according to FIGS. 2 to 5 in the unlocked state.
[0049] The slider 202 is connected to the engagement part 124 by a rod and joint arrangement 600. The first rod 602 is horizontally movable in FIG. 6a and is connected to the second rod 604 by a first joint 606. The second rod 604 is connected to the engagement part 124 by a second joint 608. The movement of the second rod 604 is limited by a guide element 610. In the first position, the second rod 604 is arranged such that the first rod 602 and the second rod 604 form an angle of less than 90°. When the locking device 122 is in the unlocked state, the second rod 604 is in the first position.
[0050] FIG. 6b shows a schematic illustration of the locking device 122 of the sample carrier interface 200 according to FIGS. 2 to 5 in the locked state.
[0051] In the second position, the second rod 604 is positioned such that the first rod 602 and the second rod 604 are perpendicular to each other. As can be seen by comparing Figures 6a and 6b, this means that when the second rod 604 is in the second position, the engagement portion 124 is located further away from the first rod 602 than when it is in the first position.
[0052] By horizontally moving the first rod 602 to the left in Figures 6a and 6b, the second rod 604 is moved from the first position to the second position. Similarly, by horizontally moving the first rod 602 to the right in Figures 6a and 6b, the second rod 604 is moved from the second position back to the first position. Thus, the rod and joint arrangement 600 forms a lever, which presses the engagement portion 124 towards the top in Figures 6a and 6b and thus towards the sample carrier 102 housed in the frame 112.
[0053] Figures 7a-7d are schematic cross-sectional views of a sample carrier 700 and a sample carrier interface 702, according to one embodiment. With joint reference to Figures 7a-7d, these figures show how the sample carrier 700 fits onto a microscope stage 704.
[0054] FIG. 7 a is a schematic cross-sectional view of a sample carrier 700 .
[0055] The sample carrier 700 is exemplarily formed as a microwell plate having a number of wells 108 for accommodating the samples. The sample carrier 700 is arranged on top of a flat surface 706, e.g. a table surface or a dedicated mounting plate. Figure 7a corresponds to a first step in the method of adapting the sample carrier 700 to a microscope stage 704.
[0056] FIG. 7 b is a schematic cross-sectional view of the sample carrier interface 702 and the sample carrier 700 .
[0057] In Fig. 7b, the sample carrier 700 is accommodated inside the sample carrier interface 702 and the locking device 122 of the sample carrier interface 702 is in an unlocked state. Fig. 7b corresponds to a second step in the method for adapting the sample carrier 700 to the microscope stage 704. In the second step, the sample carrier 700 is inserted into the frame 112 of the sample carrier interface 702 by lowering the sample carrier interface 702 from above onto the sample carrier 700.
[0058] FIG. 7 c is another schematic cross-sectional view of the sample carrier interface 702 and the sample carrier 700 .
[0059] In Fig. 7c, the sample carrier 700 is accommodated inside the sample carrier interface 702 and the locking device 122 of the sample carrier interface 702 is in a locked state. Fig. 7c corresponds to a third step in the method of adapting the sample carrier 700 to the microscope stage 704. In the third step, the sample carrier 700 is locked to the frame 112 by applying a lateral force to the sample carrier 700. The lateral force is applied by an engaging portion 124 of the locking device 122 contacting a side of the sample carrier 700.
[0060] FIG. 7 d is another schematic cross-sectional view of the sample carrier interface 702 and the sample carrier 700 .
[0061] In Fig. 7d, the sample carrier 700 is accommodated inside the sample carrier interface 702, and the locking device 122 of the sample carrier interface 702 is in a locked state. The combination of the sample carrier interface 702 and the sample carrier 700 is positioned on top of the microscope stage 704 such that the sample carrier 700 is suspended above the opening 110 of the microscope stage 704. In the suspended state, the samples accommodated in the wells 108 of the sample carrier 700 can be observed through the objective lens 708 of the microscope. Fig. 7d corresponds to a fourth step in the method of adapting the sample carrier 700 to the microscope stage 704. In the fourth step, the sample carrier interface 702 is positioned on top of the opening 110 of the microscope stage 704 in order to suspend the sample carrier 700 above the opening 110.
[0062] FIG. 8 is a schematic cross-sectional view of a sample carrier interface 800 according to an embodiment having an incubation chamber 802 .
[0063] The sample carrier interface 800 according to FIG. 8 differs from the sample carrier interface 100 according to FIG. 1 in that it comprises an incubation chamber 802 and has means for supplying this incubation chamber 802 with an incubation atmosphere.
[0064] An incubation chamber 802 is formed above the sample carrier 102. The incubation chamber 802 is defined by the frame 112 of the sample carrier interface 800 and the sample carrier 102 itself. The frame 112 is closed by a lid 804 which is placed on top of the frame 112 and provides an airtight seal. The engagement parts 124 each include a sealing part 806 which is configured to provide an airtight seal for the incubation chamber 802 when the sample carrier 102 is accommodated in the frame 112 and the locking device 122 is in the locked state. This means that in this embodiment the incubation chamber 802 is only formed when the sample carrier 102 is accommodated in the frame 112 and the locking device 122 is in the locked state.
[0065] A gas inlet 808 is located to the right of the incubation chamber 802 in Figure 8. The gas inlet 808 can be connected to, for example, a climate control unit to supply the incubation chamber 802 with an incubation atmosphere.
[0066] FIG. 9 is a schematic top view of the sample carrier interface 800 according to FIG.
[0067] As can be seen in Fig. 9, the sealing portion 806, which ensures an airtight seal, extends circumferentially around the circumference of the sample carrier 102. Said sealing portion 806 provides a reliable airtight seal for the incubation chamber 802. The position of the gas inlet 808 is indicated by a dotted line in Fig. 9.
[0068] FIG. 10 is a schematic top view of a sample carrier interface 1000 according to one embodiment.
[0069] The sample carrier 1002 accommodated in the sample carrier interface 1000 is formed as a microwell plate with 96 wells 108, for example. In FIG. 10, the position of the objective lens 106 of the microscope relative to the sample carrier 1002 is shown. The position of the optical axis O of the objective lens 106 is indicated by a black circle 1004 in FIG. 10. The objective lens 106 is arranged below the wells 108 of the sample carrier 1002, which is located in the upper left corner. The position of the aperture 110 of the microscope stage 704 is indicated by a dashed rectangular box 1006 in FIG. 10. As can be seen from FIG. 10, there is a large gap between the objective lens 106 and the inner edge of the aperture 110 of the microscope stage 704. Therefore, there is no risk of the objective lens 106 colliding with the microscope stage 704, even when observing samples located in wells 108 near the inner edge of the aperture 110 of the microscope stage 704.
[0070] FIG. 11 a is a schematic top view of a sample carrier 1100 containing 96 wells 108 .
[0071] The dotted rectangular box 1102 in Fig. 11a shows the area accessible to the objective lens 106 when a sample carrier interface according to any of the embodiments described above is used to mount the sample carrier 1100 on the microscope stage 704. The dashed rectangular box 1104 in Fig. 11a shows the area accessible to the objective lens 106 when a prior art stage insert is used to mount the sample carrier 1100 on the microscope stage 704. As can be seen from Fig. 11a, when the known stage insert is used, only 80 of the 96 wells 108 are accessible.
[0072] FIG. 11b is a schematic top view of a sample carrier 1106 containing 24 wells 108.
[0073] The dotted rectangular box 1108 in Fig. 11b shows the area accessible to the objective lens 106 when a sample carrier interface according to any of the embodiments described above is used to mount the sample carrier 1106 on the microscope stage 704. The dashed rectangular box 1110 in Fig. 11b shows the area accessible to the objective lens 106 when a prior art stage insert is used to mount the sample carrier 1106 on the microscope stage 704. As can be seen from Fig. 11b, when the known stage insert is used, only 8 of the 24 wells 108 are fully accessible, and for the remaining 16 wells 108 only 1 / 2 of the area of the wells 108 is accessible.
[0074] 11a and 11b, which illustrate that when known stage inserts are used, the volume of the microwell plate is limited to about 60%-80% of the total volume, with the remaining volume inaccessible for viewing.
[0075] 12a and 12b each show a schematic top view of a sample carrier interface 1200 according to one embodiment.
[0076] The sample carrier interface 1200 according to Fig. 12a and 12b is distinguished from the sample carrier interface 200 according to Fig. 2 to 5 by the locking device 1202. The locking device 1202 according to Fig. 12a and 12b comprises a contact pin 1204 arranged at one of the corners of the frame 112. In Fig. 12a and 12b, the contact pin 1204 is exemplarily arranged at the upper left corner. The contact pin 1204 has a dovetail-shaped end 1206 which can contact a corresponding corner of the sample carrier 102. The contact pin 1204 is therefore oriented towards the upper right corner of the sample carrier 102 in Fig. 12a and 12b. By directly contacting the contact pin 1204 with the corner, the contact pin 1204 has the function of a form-fitting device.
[0077] The sample carrier interface 1200 according to Figures 12a and 12b is further distinguished from the sample carrier interface 200 according to Figures 2 to 5 in that the frame 112 is provided with ledges 1208 arranged at the four corners of its bottom opening 116. Said ledges 1208 prevent the sample carrier 102 from falling through the opening 116 when the sample carrier is arranged in the sample carrier interface 1200 and the locking device 1202 is in the unlocked state.
[0078] In figure 12a the sample carrier interface 1200 is shown in a locked state.
[0079] In the locked state, the contact pin 1204 has been moved towards the corresponding upper left corner of the sample carrier 102 in Fig. 12a. The dovetail end 1206 is pressed from the upper left against the corner of the sample carrier 102, exerting a lateral force on the sample carrier 102 against the frame 112, i.e., the lower right corner of the opening 116 in the frame 112. Thus, in the locked state, the sample carrier 102 is clamped between the dovetail end 1206 and the lower right corner of the opening 116, which fixes the sample carrier 102 in place.
[0080] FIG. 12b shows the sample carrier interface 1200 in an unlocked state.
[0081] In the unlocked state, the contact pin 1204 has been moved towards the top left in Fig. 12b. The dovetail end 1206 is no longer pressed against a corner of the sample carrier 102 and no lateral force is applied to the sample carrier 102 by the locking device 1202. The opening 116 in the frame 112 is slightly larger than the sample carrier 102, which allows the sample carrier 102 to move freely in the opening 116 in the unlocked state. This allows the sample carrier 102 to be removed from the sample carrier interface 1200.
[0082] In figures 13a and 13b a detailed view of the locking device 1202 of the sample carrier interface 1200 according to figures 12a and 12b is shown, respectively.
[0083] The locking device 1202 includes a switch 1300 that holds the contact pin 1204 so that it can be moved from left to right and back relative to the switch 1300 in Figs. 13a and 13b. A spring 1302 pushes the contact pin 1204 to the right in Figs. 13a and 13b, so that the contact pin 1204 contacts a corner of the sample carrier 102 when the sample carrier 102 is placed on the sample carrier interface 1200. A stopper 1304 of the contact pin 1204 prevents the contact pin 1204 from being pushed out of the switch 1300. The switch 1300 of the locking device 1202 is located at the top of the frame, which makes it easy to quickly access the switch 1300 from above. This allows the user to quickly switch between the locked and unlocked states even when the sample carrier interface 1200 is placed on the microscope stage.
[0084] In figure 13a the sample carrier interface 1200 is shown in a locked state.
[0085] In the locked state, the switch 1300 is moved to the right in Fig. 13a and abuts against a first stopper 1306. Magnets 1308, 1310 are arranged on the switch 1300 and on the stopper 1306 respectively and prevent the switch 1300 from moving. The spring 1302 allows the contact pin 1204 to move slightly to the left in Fig. 13a in order to compensate for the tolerance when the contact pin 1204 is pressed against the sample carrier 102.
[0086] In figure 13b the sample carrier interface 1200 is shown in an unlocked state.
[0087] In the unlocked state, the switch 1300 has been moved to the left in Fig. 13b and abuts against a second stopper 1312. The magnet 1308 of the switch 1300 interacts with the magnet 1314 of the second stopper 1312 to prevent the switch 1300 from moving in the unlocked state. The distance between the first stopper 1306 and the second stopper 1312 is such that the contact pin 1204 can move far enough away from the sample carrier 102 but is not pressed against it in the unlocked state.
[0088] FIG. 14 shows a schematic diagram of a sample carrier interface 1400 according to another embodiment.
[0089] The sample carrier interface 1400 according to Fig. 14 is distinguished from the sample carrier interface 1200 according to Fig. 12a to 13b by the position of the locking device 1202. The locking device 1202 of the sample carrier interface 1400 is arranged on the left side of the frame 112 in Fig. 14.
[0090] The sample carrier interface 1400 according to Fig. 14 is furthermore distinguished from the sample carrier interface 1200 according to Fig. 12a-13b in that the frame 112 is provided with a leaf spring 1402. The leaf spring 1402 is arranged on the inner side of the frame 112 facing the opening 116. When the sample carrier 102 is accommodated in the sample carrier interface 1400, the leaf spring 1402 abuts against the sample carrier 102. This positions the sample carrier 102 in the opening 116 and loosely holds it. Only when the locking device 1202 is switched into the locked state is the sample carrier 102 fixed in place.
[0091] The frame 112 of the sample carrier interface 1400 further has four recesses 1404 arranged facing the inside of the opening 116. These recesses 1404 allow a user to grasp the sample carrier 102 when the sample carrier 102 is accommodated in the sample carrier interface 1400. This allows the sample carrier 102 to be easily removed from the sample carrier interface 1400.
[0092] In FIG. 15 a schematic bottom view of the sample carrier interface 1400 according to FIG. 14 is shown.
[0093] As can be seen from Fig. 15, the sample carrier interface 1400 comprises a cover panel 1500 disposed on the bottom side of the frame 112. The cover panel 1500 has an opening 1502 which leads to the opening 116 of the frame 112, allowing a sample disposed in the sample carrier 102 to be observed from below when the sample carrier 102 is disposed in the sample carrier interface 1400. Furthermore, the cover panel 1500 forms a ledge 1208 which is disposed at the corner of the opening 116.
[0094] Although all embodiments show the use of the sample carrier interface in combination with an inverted microscope, the use of the sample carrier interface is not limited to inverted microscopes: the sample carrier interface can for example also be used in upright microscopes.
[0095] Elements having the same or similar function are provided with the same reference numerals in all figures. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items and may be abbreviated as " / ". The individual features of each embodiment and all combinations thereof with each other, as well as combinations with individual features or groups of features in the above description and / or claims, are considered to be disclosed.
[0096] Although some aspects have been described in the context of an apparatus, it will be apparent that these aspects also represent a description of a corresponding method, where a block or apparatus corresponds to a step or feature of a step, and similarly, aspects described in the context of a step also represent a description of a corresponding block or item or feature of a corresponding apparatus. [Explanation of symbols]
[0097] 100 Sample Carrier Interface 102 Sample Carrier 104 Microscope Stage 106 Objective Lens 108 wells 110 Aperture 112 frames 114 Cavity 116 Aperture 118 Spacer Element 120a,120b Fixed element 122 Locking device 124 Engagement part 200 Sample Carrier Interface 202 Slider 300 Inner wall 600 equipment 602,604 Rod 606,608 Joint 610 Guide Element 700 Sample Carrier 702 Sample Carrier Interface 704 Microscope Stage 706 faces 708 Objective Lens 800 Sample Carrier Interface 802 Incubation Chamber 804 Lid 806 Seal part 808 Gas inlet 1000 Sample Carrier Interface 1002 Sample carrier 1004 Circle 1006 Rectangular Enclosure 1100 Sample Carrier 1102,1104 Rectangular box 1106 Sample Carrier 1108,1110 Rectangular box 1200 Sample Carrier Interface 1202 Locking device 1204 Contact pin 1206 End 1208 Ledge 1300 Switch 1302 Spring 1304,1306 Stopper 1308,1310 Magnets 1312 Stopper 1314 Magnet 1400 Sample Carrier Interface 1402 Leaf spring 1404 Recess 1500 cover panel H line O optical axis
Claims
1. A sample carrier interface (100, 200, 702, 800, 1000) for mounting a sample carrier (1002) on a microscope stage (104, 704), comprising: The sample carrier interface (100, 200, 702, 800, 1000) a frame (112) configured to receive the sample carrier (102, 700, 1002, 1100, 1106) and to be positioned over an opening (110) in the microscope stage (104, 704); a locking device (122) configured to apply a lateral force to the sample carrier (102, 700, 1002, 1100, 1106) when in a locked state to maintain the sample carrier (102, 700, 1002, 1100, 1106) suspended above the opening (110) when the sample carrier (102, 700, 1002, 1100, 1106) is housed in the frame (112) and the frame (112) is positioned over the opening (110) of the microscope stage (104, 704); Equipped with Sample carrier interface (100, 200, 702, 800, 1000).
2. the locking device (122) is configured to hold a sample in place when the sample carrier interface (100, 200, 702, 800, 1000) is moved to or from the microscope stage (104, 704) and when the locking device (122) is in a locked state. The sample carrier interface (100, 200, 702, 800, 1000) of claim 1.
3. the frame (112) has an opening (116) on a bottom side and is configured to receive the sample carrier (102, 700, 1002, 1100, 1106) through the opening (116); A sample carrier interface (100, 200, 702, 800, 1000) according to claim 1 or 2.
4. a bottom side of the frame (112) defining a contact surface that contacts a top surface of the microscope stage (104, 704) when the frame (112) is positioned over the opening (110) of the microscope stage (104, 704); A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 3.
5. a contact surface of the frame (112) is flush with a bottom side of the sample carrier (102, 700, 1002, 1100, 1106) when the sample carrier (102, 700, 1002, 1100, 1106) is accommodated in the frame (112) and the frame (112) is positioned above the opening (110) of the microscope stage (104, 704); A sample carrier interface (100, 200, 702, 800, 1000) according to claim 4.
6. The sample carrier (102, 700, 1002, 1100, 1106) is completely contained within the frame (112). A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 5.
7. the locking device (122) comprises an adjustment element (202) for switching between a locked state and an unlocked state in which the locking device (122) does not exert a lateral force on the sample carrier (102, 700, 1002, 1100, 1106); A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 6.
8. the locking device (122) comprises at least one movable engagement portion (124) configured to engage the sample carrier (102, 700, 1002, 1100, 1106) when in a locked state, thereby exerting a lateral force on the sample carrier (102, 700, 1002, 1100, 1106); A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 7.
9. the locking device (122) comprises a wire that is wound around the sample carrier (102, 700, 1002, 1100, 1106) when the sample carrier (102, 700, 1002, 1100, 1106) is received in the frame (112); the wires are tightenable to apply a lateral force to the sample carrier (102, 700, 1002, 1100, 1106); A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 8.
10. the sample carrier interface (100, 200, 702, 800, 1000) comprises at least one fixing element configured to engage with a corresponding fixing element of the microscope stage (104, 704); A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 9.
11. the sample carrier interface (100, 200, 702, 800, 1000) comprises at least one guide portion configured to engage with the microscope stage (104, 704) to position the sample carrier interface (100, 200, 702, 800, 1000) on top of the microscope stage (104, 704); A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 10.
12. the frame (112) is configured to form an incubation chamber (802), in particular an airtight incubation chamber (802), when the sample carrier (102) is accommodated in the frame (112), The sample carrier interface (800) according to any one of claims 1 to 11.
13. the locking device (122) includes a sealing portion (806) configured to provide an airtight seal to the incubation chamber (802) when the sample carrier (102) is received in the frame (112) and the locking device (122) is in a locked state. The sample carrier interface (100) of claim 12.
14. the frame (112) is provided with a gas inlet (808) for supplying an incubation atmosphere and / or a (semi-)sterile atmosphere to the incubation chamber (802); A sample carrier interface (800) according to claim 12 or 13.
15. The sample carrier (102, 700, 1002, 1100, 1106) is a microwell plate or a slide holder; A sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 14.
16. A method for adapting a sample carrier (102, 700, 1002, 1100, 1106) to a microscope stage (104, 704), said method comprising the steps of: a) providing a sample carrier interface (100, 200, 702, 800, 1000) according to any one of claims 1 to 13; b) inserting said sample carrier (102, 700, 1002, 1100, 1106) into a frame (112) of said sample carrier interface (100, 200, 702, 800, 1000); c) locking the sample carrier (102, 700, 1002, 1100, 1106) to the frame (112) by applying a lateral force to the sample carrier (102, 700, 1002, 1100, 1106); d) positioning the sample carrier interface (100, 200, 702, 800, 1000) above an opening (110) in the microscope stage (104, 704) to suspend the sample carrier (102, 700, 1002, 1100, 1106) above the opening (110); The method includes:
17. The method further comprises the following additional steps: placing the sample carrier (102, 700, 1002, 1100, 1106) on a flat surface or on a dedicated mounting plate; lowering the sample carrier interface (100, 200, 702, 800, 1000) from above onto the sample carrier (102, 700, 1002, 1100, 1106); Including, 17. The method of claim 16.