Microscope
Patent Information
- Application Number
- JP2022113751
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2021-07-19
- Filing Date
- 2022-07-15
- Publication Date
- 2025-07-23
AI Technical Summary
The inefficiency of existing microscopes due to the need for manual removal of sample lids, which increases handling time and exposes samples to pollution, especially in sterile environments, reducing experimental efficiency.
A microscope with a sample handling device that automates the removal of lids from sample carriers, such as microscope slides or multiwell plates, using a flexible arm mechanism to handle lids of various sizes and shapes, integrated with a sample chamber that maintains a protected environment for samples, and includes features like a sterile atmosphere and incubation capabilities.
Enhances experimental efficiency by reducing human intervention, minimizing pollution risk, and enabling automated workflows, allowing for precise sample handling and observation in controlled environments.
Smart Images

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Abstract
Description
Technical Field
[0001] The present invention relates to a microscope for inspecting a sample received in a sample carrier having a lid.
Background Art
[0002] A sample carrier used in microscopy may have a lid for sealing the sample received in the sample carrier from the environment. When the user handles the sample, the lid prevents accidental contamination and spillage of the sample. In order to enable microscopic examination of the sample, the lid is optically transparent. However, in order to manipulate the sample, for example, by injecting a reagent into the sample, the lid must be removed, which generally requires manual work by the user. Such a need for human interaction reduces the time away from the experiment, and thus the efficiency of the experiment decreases. Furthermore, if contamination of either the sample or the environment is a serious problem, the lid needs to be removed in a sterile or semi-sterile environment such as a sterile cabinet. Such a time-consuming procedure further reduces the efficiency of the experiment.
Summary of the Invention
Problems to be Solved by the Invention
[0003] Therefore, it is an object to provide a microscope that enables more efficient experimental design and higher throughput.
Means for Solving the Problems
[0004] The above problems are achieved by the subject matter of the independent claims. Advantageous embodiments are defined in the dependent claims and the following description.
[0005] A proposed microscope for examining a sample received in a sample carrier having a lid comprises: a sample chamber configured to house the sample carrier; a microscope stage located below the sample chamber and configured to have a sample carrier placed on the microscope stage; and a sample carrier handling device. The sample carrier handling device is at least partially located within the sample chamber and is configured to remove the lid from the sample carrier to allow access to the sample.
[0006] The sample carrier may be, for example, a microscope slide, Petri dish, or multiwell plate configured to accept multiple samples. This sample carrier handling device automates the removal of the lid from the sample carrier to allow access to the sample for manipulation. This eliminates the need for human intervention and allows the microscope to be easily integrated into workflow design, particularly with software such as experimental design software. Furthermore, the sample carrier is housed in a sample chamber, thereby protecting it from the environment. This prevents contamination of the sample and / or the environment even if the lid is removed. The automation, combined with the reduced risk of contamination, allows for longer periods away from the microscope, resulting in more efficient experimental design and higher processing capacity.
[0007] In a preferred embodiment, the sample carrier handling device includes an arm positioned inside the sample chamber and configured to engage with the lid of the sample carrier. The arm is a flexible mechanism for handling the lid. In particular, the arm can be designed to engage with multiple different lids of various sizes and shapes. Thus, multiple sample carriers with different shaped elements can be used with the proposed microscope.
[0008] In another preferred embodiment, the arm has a gripper, a sliding mechanism, a key and locking mechanism, or a suction cup configured to engage with the lid. In this embodiment, the lid can be securely attached to the arm. This prevents the lid from being lost inside the sample chamber. Such loss would require the user to retrieve the lid, thereby interrupting the experiment.
[0009] In another preferred embodiment, the arm is movable along a direction perpendicular to the upper surface of the microscope stage on which the sample carrier is to be placed. In other words, the arm can move vertically. This allows the lid to be lifted from the sample carrier, without the risk of tipping over the sample carrier, which would interfere with the experiment.
[0010] In another preferred embodiment, the arm is rotatable about an axis perpendicular to the top surface of the microscope stage and / or about at least one axis parallel to the top surface of the microscope stage. This allows for finer articulation of the arm and thus for more precise handling of the lid.
[0011] In another preferred embodiment, the microscope has a stage drive device configured to move the microscope stage laterally in a plane parallel to the top surface of the microscope stage. Preferably, the microscope is an XY table. This makes it possible, for example, to select individual cavities of a multiwell plate or to select a specific important region of a single sample for observation.
[0012] In another preferred embodiment, the microscope stage is configured to move the sample carrier between at least two of the following positions: an initial position where the sample carrier is first housed in the sample chamber; a lid removal position where the lid of the sample carrier can be removed by a sample carrier handling device; an inspection position where the sample can be examined under a microscope; and an operating position where the sample can be manipulated. The sample carrier is loaded into the microscope in the initial position, either manually or automatically. The sample carrier is then moved to the inspection position or the lid removal position for examination. Once the sample carrier has been moved to the lid removal position, the lid is removed, and the sample carrier is further moved to the operating position where the sample received in the sample carrier is manipulated. Following the manipulation, the sample carrier can be moved to the inspection position for examination of the manipulated sample. In this embodiment, a number of different experiments can be automated very easily, thereby making the microscope more versatile.
[0013] In another preferred embodiment, the microscope includes a pipetting device for pipetting a sample, particularly an injector device configured to inject a liquid into the sample, and / or a micromanipulator device configured to manipulate the sample. In this embodiment, after the lid is removed, the sample can be pipetted and / or manipulated within the protected environment of the sample chamber. In particular, the sample can be pipetted and / or manipulated while it is being examined under the microscope. This allows for many experiments that would otherwise be impossible, such as tracking the neuronal activity of nerve cells activated by injected reagents.
[0014] In another preferred embodiment, the sample chamber is an incubating sample chamber containing an incubation atmosphere and / or a sterile sample chamber containing a sterile atmosphere. The protected environment of the sample chamber can be used to provide an incubation atmosphere for incubating the sample. This allows for observation of cell cultures for extended periods without the need for an external incubator. When using an external incubator, the sample must be moved through potentially undesirable environments, such as the laboratory environment. This not only stresses the sample but also requires additional time. Furthermore, the protected environment of the sample chamber can be used to provide a sterile or at least semi-sterile atmosphere. In this embodiment, even samples that are extremely sensitive to contamination can be handled under a microscope.
[0015] In another preferred embodiment, the microscope includes a first fan assembly configured to blow an atmosphere into the sample chamber through at least one first opening of the sample chamber, and a second fan assembly configured to expel the atmosphere from the sample chamber through at least one second opening of the sample chamber. This provides a directed atmosphere flow into the sample chamber. Such a flow can carry any particles, such as dust, mud, and bacteria, that enter the sample chamber and transport them to the outlet opening. This enables a sterile or semi-sterile working environment within the sample chamber. Furthermore, in the case of an incubated sample chamber, the incubation atmosphere can be recirculated. The incubation atmosphere expelled from the sample chamber can be recirculated and returned to the sample chamber by airflow. Part of the incubation atmosphere may be replaced or replenished. This saves incubation atmosphere volume and energy after opening and closing the sample chamber door.
[0016] In another preferred embodiment, at least one first opening and at least one second opening are located on opposing sides of the sample chamber, particularly on the top and bottom surfaces of the sample chamber. In such an embodiment, a laminar atmospheric flow can be generated inside the sample chamber.
[0017] In another preferred embodiment, a first fan assembly, at least one first opening, and at least one second opening are configured to generate laminar flow inside the sample chamber. The laminar flow acts like a shield or curtain, preventing the atmosphere from escaping from the sample chamber and preventing the external atmosphere from entering the sample chamber.
[0018] In another preferred embodiment, the microscope includes a sample carrier identification unit configured to identify sample carriers. The sample carrier identification unit can be used to uniquely identify sample carriers, and by extension, the samples contained within them. This allows for the automatic, sequential inspection and / or manipulation of multiple sample carriers. This further improves the amount of time that can be spent away from the microscope.
[0019] In another preferred embodiment, the sample carrier identification unit comprises a camera, a barcode reader, and / or an RFID reader. The camera can be used to uniquely identify the sample carrier based on a tag such as a barcode or QR code, or based on a handwritten label. The barcode reader can be used to uniquely identify the sample carrier based on a barcode. The RFID reader can be used to uniquely identify the sample carrier based on an RFID tag.
[0020] In another preferred embodiment, the microscope comprises a box-shaped microscope housing that defines a sample chamber, and the housing has a door to provide access to the sample chamber. The box-shaped microscope comprises a housing within which all microscope components are arranged. The housing typically has one or more openings for accessing the inside of the microscope. Due to the closure or sealing of the housing, the box-shaped microscope is particularly suitable for precise control of the environment of the sample, for example by a climate control unit. In this embodiment, the sample chamber is located inside the box-shaped microscope housing. This means that the environment of the sample chamber can be precisely controlled.
[0021] In another preferred embodiment, the box-shaped microscope housing defines a component space below the microscope stage, and the component space contains a plurality of microscope components. The component space may include the power supply of the microscope, imaging optics, illumination system, filter, environmental control unit, or incubation control unit.
[0022] Specific embodiments will be described below with reference to the drawings.
Brief Description of the Drawings
[0023] [Figure 1] It is a schematic diagram of a microscope having a sample carrier handling device. [Figure 2] It is a plan view showing the sample chamber of the microscope according to FIG. 1, where the arm of the sample carrier handling device is in the rest position. [Figure 3] It is a plan view showing the sample chamber of the microscope according to FIG. 1, where the arm of the sample carrier handling device is in the lid gripping position. [Figure 4] It is a plan view showing the sample chamber of the microscope according to FIG. 1, where the arm of the sample carrier handling device is in the lid holding position. [Figure 5] It is a plan view showing the sample chamber of a microscope having a pipette handling device according to one embodiment. [Figure 6]A plan view showing a sample chamber of a microscope having a sample carrier identification unit according to one embodiment. [Figure 7] A side view of a sample chamber of a microscope according to one embodiment. [Figure 8] A side view showing a sample carrier handling device having a lock and key mechanism according to one embodiment. [Figure 9] A side view showing a sample carrier handling device having a suction cup according to one embodiment. [Figure 10] A side view schematically showing a microscope according to one embodiment. [Figure 11] A perspective view schematically showing the microscope according to FIG. 10. [Figure 12] A flowchart showing a method of inspecting a sample using a microscope.
Best Mode for Carrying Out the Invention
[0024] FIG. 1 is a schematic view of a microscope 100. The microscope 100 is exemplarily formed as a box-type microscope.
[0025] Conventional microscopes include a microscope stand that holds all microscope components. The openness of conventional microscopes allows easy access to all of their components. However, due to the openness, the samples placed in conventional microscopes are exposed to the environment. Furthermore, the microscope stand typically blocks access to the sample from one side.
[0026] In contrast, the box microscope 100 shown in Figure 1 is completely enclosed inside a microscope housing 102. Specifically, the microscope housing 102 forms a sample chamber 104 configured to house a sample carrier 106 in which one or more samples are placed, and has an optically transparent lid 400 (see Figure 4). The lid 400 protects the sample contained within the sample carrier 106 from the environment, thereby preventing contamination and preventing the sample from drying out. The lid 400 also prevents the sample carrier 106 from spilling when handled by the user. By enclosing the sample carrier 106 inside the microscope housing 102, precise control of the sample environment is possible, for example by an incubation control unit 1002 (see Figure 10) to control the temperature, humidity, and gaseous composition of the sample chamber 104. Since the enclosed sample remains protected from the environment even when the lid 400 is removed, both the sample and the environment are protected from accidental contamination. Furthermore, if necessary for the experiment, the sample chamber 104 can be easily transformed into an incubation chamber and / or a sterile environment.
[0027] The sample carrier 106 is placed on a microscope stage 108 located below the sample chamber 104. The microscope stage 108 is movable along two orthogonal directions; that is, the microscope stage 108 is a so-called XY table. Therefore, by moving the microscope stage 108, it becomes possible, for example, to select individual cavities or wells of the sample carrier 106, or to select a specific important region of a single sample for observation.
[0028] The microscope 100 shown in Figure 1 is exemplary, configured as a transmitted light microscope 100. The imaging optical system 110 for imaging the sample is exemplary located below the microscope stage 108 in the component space 112, and the illumination system 114 for illuminating the sample is located above the microscope stage 108 in the sample chamber 104. The optical axes of the imaging optical system 110 and the optical axes of the illumination system 114 are aligned. Thus, the illumination light emitted by the illumination system 114 passes through the sample before entering the imaging optical system 110. In an alternative embodiment, the positions of the imaging optical system 110 and the illumination system 114 can be reversed. In another alternative embodiment, both the imaging system and the illumination system 114 are located on the same side of the microscope stage 108. Additional components, such as power supplies or various filters, may be located in the component space 112.
[0029] To remove the lid 400 from the sample carrier 106 and to allow access to the sample from above for handling, the microscope 100 is equipped with a sample carrier handling device 116. The sample carrier handling device 116, exemplary, comprises a base 118 positioned adjacent to the microscope stage 108 within the sample chamber 104, and an arm 120 connected to the base 118. In the embodiment shown in Figure 1, the arm 120 has a gripper 122 for engaging with the lid 400 of the sample carrier 106. However, other elements such as a key and locking mechanism or a suction cup 902 (see Figures 8 and 9) for engaging with the lid 400 are also possible. The arm 120 can be rotated around the base 118 and moved along the vertical axis A. This is indicated by two bidirectional arrows P1, P2 in Figure 1 and will be described in more detail later with reference to Figures 7-9. Additional components of the sample carrier handling device 116, such as one or more motors for moving the arm 120 and gripper 122, and a control unit for controlling the arm 120, can be arranged in the component space 112 below the sample chamber 104. The sample carrier handling device 116 will be described in more detail later with reference to Figures 2 to 9.
[0030] Figure 2 is a plan view of the sample chamber 104 of the microscope 100 according to Figure 1. In Figure 2, the arm 120 of the sample carrier handling device 116 is in a resting position and rotated away from the sample carrier 106.
[0031] The sample carrier 106 is exemplary formed as a multiwell plate having 24 wells arranged in 4 rows and 6 columns. To uniquely identify each well, the rows are labeled A-D and the columns are labeled 1-6. In Figure 2, the lid 400 is placed on top of the sample carrier 106.
[0032] As can be seen in Figure 2, the arm 120 has an arm joint 200, which allows the gripper 122 to rotate around this arm joint. This provides the arm 120 with a joint for finer control. The gripper 122 has two L-shaped gripper arms 202, each gripper arm having a gripping portion 204, which can engage with the lid 400 of the sample carrier 106 from the side facing it, thereby gripping the lid 400. The process of gripping the lid 400 will be described in more detail later with reference to Figure 3.
[0033] Figure 3 is another plan view of the sample chamber 104 of the microscope 100 according to Figure 1. In Figure 3, the arm 120 of the sample carrier handling device 116 is rotated in the lid gripping position so that the gripper arm 202 can engage with the lid 400 of the sample carrier 106. The gripping portions 204 of the gripper arm 202 are moved toward each other to grip the lid 400 of the sample carrier 106. In the next step, the arm 120 is lifted upward to lift the lid 400 from the sample carrier 106.
[0034] Figure 4 is another plan view of the sample chamber 104 of the microscope 100 according to Figure 1. In Figure 4, the arm 120 of the sample carrier handling device 116 holds the lid 400 of the sample carrier 106 in the lid holding position and is rotated away from the sample carrier 106. In the lid holding position, the lid 400 is not located above the sample carrier 106. Therefore, the sample placed in the sample carrier 106 is accessible from above for manipulation. The manipulation of the sample will be described in more detail later with reference to Figure 5.
[0035] Figure 5 is a plan view of the sample chamber 104 of a microscope 500 according to one embodiment. The microscope 500 according to Figure 5 is distinguished from the microscope 100 according to Figure 1 in that it has a pipetting device 502 for pipetting the sample. Pipetting the sample may include, for example, introducing various liquid reagents into the sample.
[0036] The pipetting apparatus 502 has a rectangular frame 504 positioned parallel to the top surface of the microscope stage 108. The frame 504 holds one or more injection nozzles 506, of which only two are shown in Figure 5. Each injection nozzle 506 is connected to a liquid reservoir outside the sample chamber 104 via a fluid line 508. The frame 504 is movable within the sample chamber 104 by an injector drive. Thus, the injection nozzles 506 can target individual wells of the sample carrier 106 for pipetting.
[0037] Figure 6 is a plan view of the sample chamber 104 of a microscope 600 according to another embodiment. The microscope 600 according to Figure 6 is distinguished from the microscope 500 according to Figure 5 in that it has a sample carrier identification unit 602.
[0038] In Figure 6, the illustrated lid 400 has a handwritten label 604, an RFID tag 606, a QR code 608, and a barcode 610, each of which constitutes a unique identifier that uniquely identifies the sample carrier 106. The sample carrier identification unit 602 is configured to read at least one of these unique identifiers. The sample carrier identification unit 602 may include, for example, a camera and a control unit. The camera is configured to capture an image of the lid 400 when the arm 120 is in the lid holding position and to transmit the image to the control unit. The control unit is configured, for example, for handwritten text recognition. Thus, the control unit can convert the handwritten label 604 into machine-readable text, thereby identifying the sample carrier 106. Alternatively or additionally, the control unit is configured to convert the QR code 608 and / or barcode 610 into machine-readable text to identify the sample carrier 106. The sample carrier identification unit 602 may also include a dedicated barcode reader or RFID reader, which is configured to identify the sample carrier 106 based on the RFID tag 606.
[0039] Figure 7 is a side view of the sample chamber 104 of a microscope 700 according to one embodiment.
[0040] The arm 120 of the sample carrier handling device 116 has an arm drive unit 702 wrapped around a base 118. The arm drive unit 702 has a first motor that engages with a rail 704 on the base 118 to move the arm 120 along a vertical axis A. The arm drive unit 702 further includes a second motor configured to rotate the arm drive unit 702, and by extension the entire arm 120, around the base 118. A cable 706 connects the arm drive unit 702 to a component space 112 below the sample chamber 104. The cable 706 has electrical and control lines for supplying power and control signals to the two motors of the arm drive unit 702, as well as to the actuators of the arm joint 200 and the gripper 122.
[0041] Figure 8 is a side view of a sample carrier handling device 800 according to one embodiment. The sample carrier handling device 800 shown in Figure 8 is distinguished from the sample carrier handling devices 800 shown in Figures 1 to 7 by having a lock and key mechanism 802 for engaging with the lid 400 of the sample carrier 106.
[0042] The locking and keying mechanism 802 includes a first holding mechanism 804 positioned on the lid 400 of the sample carrier 106, and a second holding mechanism 806 positioned on the underside of the arm 120 of the sample carrier handling device 800. The second holding mechanism 806 is configured to be attached to and detached from the first holding mechanism 804. When the second holding mechanism 806 is attached to the first holding mechanism 804, the arm 120 can be moved upward to lift the lid 400 from the sample carrier 106.
[0043] Figure 9 is a side view of a sample carrier handling device 900 according to another embodiment. The sample carrier handling device 900 shown in Figure 9 is distinguished from the sample carrier handling devices 900 shown in Figures 1 to 8 by having an adsorption cup for engaging with the lid 400 of the sample carrier 106.
[0044] The adsorption cup is positioned on the underside of the arm 120 of the sample carrier handling device 116. When the adsorption cup is in contact with the upper surface of the lid 400, air can be removed from the center of the adsorption cup in order to adsorb the lid 400 to the adsorption cup, and thus to the arm 120. Air can be removed by moving the arm 120 downward, thereby pressing the adsorption cup against the upper surface of the lid 400 and pushing the air out from the center of the adsorption cup. Alternatively, air can be removed from the center of the adsorption cup by a small pump. Once the air is again reintroduced to the center of the adsorption cup, for example by a controllable valve, the lid 400 is removed from the arm 120 again.
[0045] Figure 10 is a schematic side view of a microscope 1000 according to one embodiment, which has means for controlling the atmosphere inside the sample chamber 104.
[0046] The front door 1004 for accessing the sample chamber 104 is located on the right side of the sample chamber 104 in Figure 10. Other doors or additional doors may be provided as desired.
[0047] On the upper side of the sample chamber 104 is a first fan assembly 1006, which includes two fans, for blowing an atmosphere into the sample chamber 104 through a first opening 1008 of the sample chamber 104. The opening is formed to accommodate a filter system, which may be a filter 1010 extending across the entire opening. However, a single opening may be provided for each fan of the first fan assembly 1006, and filters may be optionally placed in each of these openings. Multiple second openings 1100 (see Figure 11) are located on the lower surface of the sample chamber 104, allowing the atmosphere from inside the sample chamber 104 to flow out of the sample chamber 104 (also called "outlet openings").
[0048] When the first fan assembly 1006 is activated, a directional atmospheric flow is generated that flows downward from the top surface of the sample chamber 104 to the outlet opening in the bottom wall. The atmosphere that is released from inside the sample chamber 104 at the bottom surface of the sample chamber 104 passes through the inside of the microscope housing 102, is drawn in by the first fan assembly 1006, and is blown back into the sample chamber 104. Thus, a steady flow of atmosphere is formed, as shown by the set of white arrows in Figure 10. Preferably, the directional atmospheric flow is laminar.
[0049] The microscope 1000 further has an optional second fan assembly 1012 located on the underside of the sample chamber 104. The second fan assembly 1012 includes one single fan for drawing in the atmosphere flowing through at least one second opening 1100. Thus, the second fan assembly 1012 assists in the circulation of the atmosphere through the inside of the microscope housing 102 and the inside of the sample chamber 104.
[0050] The second filter system 1014 is located in an opening or leak hole of the microscope housing 102. Such an opening / leak hole allows fresh air from outside the microscope 1000 to be introduced into the inside of the microscope housing 102. This air is filtered by the second filter system and drawn into the second fan assembly 1012, as indicated by a single dotted arrow P4.
[0051] The microscope 1000 shown in Figure 10 further includes an incubation control unit 1002 for controlling and adjusting the parameters of the incubation atmosphere circulating between the inside and outside of the sample chamber 104 within the microscope housing 102, as indicated by a set of white arrows.
[0052] A suitable incubation atmosphere contains air with a predetermined content of H2O (relative humidity) and a predetermined content of CO2 (carbon dioxide). It is also desirable to perform hypoxic experiments with insufficient oxygen in the atmosphere. Typically, the temperature of the incubation atmosphere can be set in a range between the ambient temperature and up to 50°C, the CO2 range is typically set to 0.5-20%, and the O2 range is set to 1-18%. Humidity needs to be balanced to ensure that potential condensation is avoided or at least not damaged by any of the components of the microscope 1000 or the sample itself. Preferably, at least the temperature, humidity, and CO2 content are controlled. In hypoxic experiments, the O2 content is controlled by the introduction of N2 (nitrogen). These parameters of the incubation atmosphere can be controlled and adjusted by the incubation control unit 1002. To control the above parameters, it is preferable to place corresponding sensors in the sample chamber 104 and / or in the microscope housing 102 and / or on the microscope stage 108, preferably near the sample.
[0053] The control unit can be used to adjust its output in order to control the suction pressure of the second fan assembly 1012. For best results in this regard, the control unit can be connected to the incubation control unit 1002.
[0054] Figure 11 is a schematic perspective view of the microscope 1000 as shown in Figure 10.
[0055] Figure 11 shows the distribution of the second (outlet) openings 1100 along the two lower edges of the sample chamber 104. The laminar flow acts as a shield or curtain around one side of the microscope stage 108. This atmospheric shield / curtain prevents bacteria-containing particles from entering the sample chamber 104, particularly the sample itself, while simultaneously preventing the atmosphere inside the sample chamber 104 from escaping and preventing the atmosphere outside the sample chamber 104 from entering the sample chamber 104.
[0056] When the user places their arm into the sample chamber 104 through the door 1004, the laminar flow is blocked only in a small area around the user's arm, so the remaining atmospheric flow still acts as a protective shield. Furthermore, any contamination brought in by the user's arm can be carried away by the atmospheric flow and transported to the outlet opening in the lower wall of the sample chamber 104.
[0057] Figure 12 is a flowchart showing the method for inspecting a sample using the microscope 100 described above.
[0058] In step S1200, the process is initiated. In step S1202, the sample chamber 104 is opened and the sample container with the lid 400 is placed inside the microscope stage 108. The sample chamber 104 is then closed. In step S1204, incubation for the sample chamber 104 is started or restarted. Once the sample chamber 104 is sterile or semi-sterile as desired by the user, step S1206 is performed. In step S1206, a lid removal command is given to the microscope 100, either by user input or by a control unit, such as a computer, that implements an automated workflow. The microscope stage 108 then moves the sample carrier 106 to a predetermined lid removal position. Next, the arm 120 of the sample carrier handling device 116 is moved to the lid gripping position, engages with the lid 400, and lifts the lid 400 from the sample carrier 106. The arm 120 is then moved to the lid holding position.
[0059] In step S1208, the sample carrier 106 is moved to an inspection position where the sample can be examined under a microscope, or to an operating position where the sample can be manipulated. The inspection position and the operating position may be the same. Following the manipulation and / or inspection of the sample, step S1210 is performed. In step S1210, a lid attachment command is given to the microscope 100, either by user input or by the control unit. The microscope stage 108 then moves the sample carrier 106 to the lid removal position. Next, the arm 120 of the sample carrier handling device 116 is moved to the lid gripping position, lowering the lid 400 onto the sample carrier 106, and then disengaging from the lid 400. The arm 120 is then moved to the resting position. The process then ends in step S1212, or steps S1202 through S1210 are repeated for additional sample carriers 106s.
[0060] Elements that function identically or similarly are indicated by the same reference numeral in all figures. As used herein, the term "and / or" includes all possible combinations of one or more of the related items and may be abbreviated as " / ".
[0061] While several embodiments have been described in the context of the apparatus, it is clear that these embodiments also represent descriptions of the corresponding methods, where blocks or apparatus correspond to steps or features of steps. Similarly, embodiments described in the context of steps also represent descriptions of the corresponding blocks, items, or features of the corresponding apparatus. [Explanation of symbols]
[0062] 100 Microscopes 102 Microscope Housing 104 Sample Chamber 106 Sample carrier 108 Microscope Stages 110 Imaging Optical System 112 component spaces 114 Lighting Systems 116 Sample Carrier Handling Device 118 base 120 Arm 122 Grippa 200 Arm Joints 202 Gripper Arm 204 Gripping part 400 lids 500 Microscopes 502 Pipette Processing Unit 504 Frame 506 Injection nozzle 508 Fluid Line 600 Microscopes 602 Sample carrier identification unit 604 Labels 606 RFID tags 608 QR code 610 barcodes 700 Microscopes 702 Arm drive unit 704 Rail 706 Cable 800 Sample Carrier Handling Device 802 Locking and Key Mechanism 804,806 Retention mechanism 900 Sample Carrier Handling Device 902 Suction Cup 1000 Microscopes 1002 Incubation Control Unit 1004 Door 1006 Fan Assembly 1008 Aperture 1010 Filter 1012 Fan Assembly 1014 Filter System A axis P1, P2, P3, P4 Arrows
Claims
1. A microscope (100, 500, 600, 700, 1000) for inspecting a sample received in a sample carrier (106) having a lid (400), wherein the microscope (100, 500, 600, 700, 1000) comprises: A sample chamber (104) configured to accommodate the sample carrier (106); A microscope stage (108) disposed below the sample chamber (104), the microscope stage (108) being configured to have the sample carrier (106) disposed thereon; A sample carrier handling device (116) at least partially disposed within the sample chamber (104), the sample carrier handling device (116) being configured to remove the lid (400) from the sample carrier (106) to provide access to the sample; The microscope (100, 500, 600, 700, 1000) comprising the above.
2. The microscope (100, 500, 600, 700, 1000) according to claim 1, wherein the sample carrier handling device (116) comprises an arm (120) disposed inside the sample chamber (104) and configured to engage the lid (400) of the sample carrier (106). The microscope (100, 500, 600, 700, 1000) according to claim 1.
3. The microscope (100, 500, 600, 700, 1000) according to claim 2, wherein the arm (120) has a gripper (122), a slide mechanism, a lock and key mechanism (802), or a suction cup (902) configured to engage the lid (400). The microscope (100, 500, 600, 700, 1000) according to claim 2.
4. The microscope (100, 500, 600, 700, 1000) according to claim 2, wherein the arm (120) is movable along a direction orthogonal to the upper surface of the microscope stage (108) on which the sample carrier (106) is to be disposed. The microscope (100, 500, 600, 700, 1000) according to claim 2.
5. The microscope (100, 500, 600, 700, 1000) according to claim 2, wherein the arm (120) is rotatable about an axis orthogonal to the upper surface of the microscope stage (108) and / or rotatable about at least one axis parallel to the upper surface of the microscope stage (108). The microscope (100, 500, 600, 700, 1000) according to claim 2.
6. The microscope (100, 500, 600, 700, 1000) has a stage driving device configured to move the microscope stage (108) laterally in a plane parallel to the upper surface of the microscope stage (108). The microscope (100, 500, 600, 700, 1000) according to claim 1.
7. The microscope stage (108) is at the following positions, namely, an initial position where the sample carrier (106) is first accommodated in the sample chamber (104), a lid removal position where the lid of the sample carrier (106) can be removed by the sample carrier handling device (116), an inspection position where the sample can be examined microscopically, an operation position where the sample can be manipulated, and is configured to move the sample carrier (106) between at least two of these positions. The microscope (100, 500, 600, 700, 1000) according to claim 1.
8. The microscope (500, 600) includes a pipetting device (502) for pipetting the sample, in particular an injector device configured to inject liquid into the sample, and / or a micromanipulator device configured to manipulate the sample. The microscope (500, 600) according to claim 1.
9. The sample chamber (104) is an incubated sample chamber (104) containing an incubation atmosphere and / or a sterile sample chamber (104) containing a sterile atmosphere. The microscope (1000) according to claim 1.
10. The microscope (1000) includes a first fan assembly (1006) configured to blow an atmosphere into the sample chamber (104) through at least one first opening (1008) of the sample chamber (104), a second fan assembly (1012) configured to discharge the atmosphere from the sample chamber (104) through at least one second opening of the sample chamber (104), and has. The microscope (1000) according to claim 1.
11. The at least one first opening (1008) and the at least one second opening are arranged on opposite sides of the sample chamber (104), in particular on the upper and lower surfaces of the sample chamber (104). The microscope (1000) according to claim 10.
12. The first fan assembly (1006), the at least one first opening (1008), and the at least one second opening (1100) are configured to generate a laminar flow inside the sample chamber (104). The microscope (1000) according to claim 10.
13. The microscope (600) includes a sample carrier identification unit (602) configured to identify the sample carrier (106). The microscope (600) according to claim 1.
14. The sample carrier identification unit (602) includes a camera, a barcode reader, and / or an RFID reader. The microscope (600) according to claim 13.
15. The microscopes (100, 500, 600, 700, 1000) include a box-shaped microscope housing (102) that defines the sample chamber (104), and the box-shaped microscope housing (102) has a door (1004) for accessing the sample chamber (104). The microscopes (100, 500, 600, 700, 1000) according to claim 1.