Sample transfer device

Abstract

The invention relates to a sample transfer device (100) for receiving a sample inside the sample transfer device (100) and for transferring the sample to a processing unit or an analysis unit. The sample transfer device (100) comprises a connection opening (110) defining a transfer path (114) along which the sample is to be transferred from a loading position (120) of the sample inside the sample transfer device (100) through the connection opening (110), a shutter (130) configured to block the connection opening (110) or to unblock the connection opening (110), and a shielding member (140) configured to be arranged between the connection opening (110) and the loading position (120) to protect the sample from an incoming air flow when the shutter (130) unblocks the connection opening (110).

Description

Technical Field

[0001] This invention relates to a sample transfer device for receiving samples within a sample transfer apparatus and for transferring the samples to a processing unit or analytical unit. More specifically, the sample transfer device of this invention is used in the field of cryo-microscopy for transferring samples to be examined, for example, to a cryo-electron microscope (cryo-EM) or to a cryo-optical microscope. Alternatively, in another example, it is used for loading and / or manipulating samples, sample carriers, or sample holders within the sample transfer device, and then transferring the samples, sample carriers, or holders to another processing unit such as a FIB (Focused Ion Beam) apparatus or to an analytical unit such as a microscope. Background Technology

[0002] US 10,144,010 B2 discloses a manipulation vessel for cryogenic microscopy, which substantially corresponds to the sample transfer device of the type described above. Cryogenic microscopy particularly includes cryogenic optical microscopy and cryogenic electron microscopy.

[0003] Cryofixation is a common sample preparation method in cryo-electron microscopy. In this process, an aqueous sample is frozen (cryofixed) very rapidly to a temperature below -150°C, i.e., it is cooled very quickly to avoid the formation of ice crystals. Cryofixation has proven particularly suitable for structural biology research. The object to be studied, such as cells, enzymes, viruses, or lipid layers, is thus embedded in a thin, vitrified layer of ice. The greatest advantage of cryofixation is that biological structures can be obtained in their natural state. For example, biological processes can be stopped at any point in time by cryofixation and studied in this vitrified state, for example, in cryo-electron microscopy, or in optical microscopy with corresponding sample cooling; cryo-optical microscopy is mainly used to locate relevant regions in the sample, which can be recorded and then observed in more detail under cryo-electron microscopy.

[0004] The frozen sample is typically placed on a known electron microscope sample carrier, such as a grid or pin stub mount for scanning electron microscopy. The frozen sample must (under the aforementioned low-temperature conditions and without water) be transferred to a corresponding sample carrier holder, which can then be transferred in a suitable holder into the microscope. Typical sample carrier holders for use in conjunction with this invention have been disclosed, for example, by U.S. Patent No. 8,395,130 B2, wherein the grid constituting the sample carrier and holding the frozen sample can be secured in a corresponding holder using clamping elements.

[0005] To date, a rather temporary solution has been used, in which liquid nitrogen is stored in, for example, a polystyrene foam container, within which the necessary manipulation steps of transferring the grid to the sample carrier holder are performed. The cryogenic nitrogen gas formed by the liquid nitrogen ensures the necessary low temperature on the one hand, and creates an anhydrous atmosphere in the polystyrene foam container on the other, thereby preventing water contamination of the sample and thus preventing ice crystal contamination.

[0006] To avoid compromising the quality of frozen samples, it is crucial to transfer them in a cooled and contamination-free (especially anhydrous) manner between the processing unit used (e.g., cryo-fixation device, cryo-fracture device, or coating device) and the analytical apparatus (primarily cryo-optical microscope and cryo-electron microscope in this case). For this purpose, in routine laboratory practice, rather ad-hoc solutions have traditionally been employed, or loading and transfer systems have been specially fabricated in-house.

[0007] As noted above, the samples to be examined require continuous processing under cryogenic conditions. Contamination or devitrification can significantly reduce the success rate of the workflow. Cryo-optical microscopy is typically used to identify regions of interest before initiating time-consuming and expensive cryo-electron microscopy (cryo-EM) steps, such as scanning electron cryo-microscopy (cryo-SEM), transmission electron cryo-microscopy (cryo-TEM), or cryo-electron computed tomography (cryo-ET). By using cryo-optical microscopy, regions of interest in the nanometer range can be identified within the cell volume (millimeters). The regions of interest are then traced back in cryo-EM, greatly accelerating the analytical process. For this, an optical microscope, or at least an optical microscope stage, must be used under cryogenic conditions. Samples, typically on a sample carrier, are loaded into a sample transfer device, also known as a cryo-CLEM (“cryo-optic-electron-microscopy” shuttle), and then transferred to the cryo-stage of the optical microscope. Connecting the sample transfer device to the cryo-stage and transferring the sample to the cryo-stage involve a high risk of contamination.

[0008] Although some applications have been discussed above, other applications that require the transfer of samples, sample carriers, or sample holders from the sample transfer device to another processing or analytical unit can be envisioned. Summary of the Invention

[0009] The purpose of this invention is to provide a sample transfer device that minimizes the risk of contamination or devitrification of samples transferred from the above-described sample transfer device to a processing unit or analysis unit.

[0010] The present invention provides a sample transfer apparatus. The sample transfer apparatus is used to receive a sample and / or a sample carrier and / or a sample holder (in this context, "sample" means including a sample carrier and / or a sample holder) inside the sample transfer apparatus, more specifically, to receive the sample and / or the sample carrier and / or the sample holder inside a chamber of the sample transfer apparatus, and to transfer the sample from inside the sample transfer apparatus to a processing unit or analytical unit outside the sample transfer apparatus. The sample transfer apparatus includes: a connecting opening defining a transfer path through which the sample is transferred from a sample loading position inside the sample transfer apparatus, particularly to a sample transfer position. In use, the sample and / or the sample carrier and / or the sample holder are first loaded into the sample transfer apparatus, more specifically, into a chamber at a predetermined location within the sample transfer apparatus, the so-called "loading position"; the chamber is typically maintained at a cryogenic temperature, for example, by filling a portion of the chamber with liquid nitrogen. The sample is then transferred from there along the transfer path through the connecting opening of the sample transfer apparatus. Upon reaching the transfer position, the sample is transferred to a processing unit or analytical unit, such as a cryogenic-optical microscope stage. Furthermore, the sample transfer device includes a baffle configured to either block or open the connection opening. The baffle serves to block the connection opening as long as the sample and / or sample carrier and / or sample holder is manipulated and / or loaded within the sample transfer device. The baffle opens the connection opening to allow sample transfer to the processing unit or analysis unit. The sample transfer device also includes a shielding member configured to be disposed between the connection opening and the loading position (in the active position) to protect the sample from incoming airflow when the baffle opens the connection opening.

[0011] When a baffle opens the connection opening to facilitate sample transfer, the sample is at high risk of contamination or devitrification at its loading position and / or en route to the transfer position. Opening the baffle, i.e., opening the connection opening, introduces an inflow of air that may directly impact the sample at its loading position and / or en route to the transfer position. For example, gaseous nitrogen from the cryogenic stage (or another unit) and / or hot air from inside the connecting tube may be pushed toward the sample, which acts as a cold trap, causing moisture to accumulate and freeze on the sample surface. A possible result is water contamination of the sample, leading to ice crystal formation or devitrification due to increased temperature. To avoid such risks, the sample transfer device of this invention includes a shielding member that protects the sample from the inflow of air when the baffle is opened to open the connection opening. The shielding member is positioned between the connection opening itself and the sample loading position. Therefore, the shielding member may or may not obstruct the transfer path of the sample and / or sample holder. On one hand, the shielding member may have a groove, which, viewed from the direction of the transfer path, is preferably precisely aligned with the cross-section of the sample holder, such that any incoming airflow is deflected by the front surface formed by the shielding member and the sample holder together. On the other hand, the shielding member in its active position may cover the sample holder and block the transfer path to protect the sample from any incoming airflow. In the first embodiment, after the incoming airflow has dissolved, the sample / sample holder can be transferred to the transfer position through the groove of the shielding member. In the second embodiment, in order to transfer the sample to the transfer position, the shielding member must be removed from the transfer path after the incoming airflow has dissolved.

[0012] In an embodiment, the shielding member is configured to present a first position and a second position. In its first position, the shielding member releases the transfer path, and in its second position, the shielding member blocks the transfer path. In this embodiment, in its second position, the shielding member blocks the transfer path and blocks any inlet to the connection opening as seen from the sample, and conversely, blocks any incoming airflow through the connection opening. This incoming airflow is deflected and directed in another direction at the surface of the shielding member facing the connection opening, preventing the airflow from directly reaching the sample. In use, after the sample has been loaded into the loading position inside the sample transfer device, the shielding member is in its second position, the baffle can be opened to open the connection opening, and then, after a short period of time, after the incoming airflow has disappeared, the sample can be transferred to its transfer position. To do this, the shielding member is brought to its first position, causing it to release the transfer path.

[0013] The movement of the shielding member between a first position and a second position can be performed automatically and / or manually. For example, if a baffle is opened to open the connection opening, the shielding member should always be in its second position. The corresponding connection can be electromechanical or achieved by mechanical force. However, this movement can also be performed manually, for example, by a pair of tweezers. In order to move the sample from its loading position to the transfer position, the shielding member must be brought to its first position, in which the shielding member releases the transfer path. Again, this movement can be performed manually or automatically. For example, movement of the sample and / or sample holder along the transfer path can be detected, and upon detection of this movement, the shielding member can be brought into its first position by electromechanical interaction. Alternatively, force connection or manual adjustment can be used instead. However, the shielding member can also be simply pushed from its second position to its first position by applying a thrust to it, for example, by a sample holder moving along the transfer path.

[0014] The sample transfer device according to the present invention preferably has a connection opening formed within or at least part of the interior of a connecting tube, through which a transfer path extends. As discussed above, the connection opening of the sample transfer device defines a transfer path along which a sample / sample holder is transferred from its loading position to a transfer position via the connection opening. At its transfer position, the sample / sample carrier / sample holder is transferred to a processing unit or analytical unit, such as a cryogenic microscope stage. For practical reasons, the sample transfer device includes a connecting tube, the tip of which is inserted into and can be connected to a corresponding socket in the processing unit or analytical unit. Subsequently, if the shielding member is in its first position, a baffle is opened to open the connection opening and enable the transfer of the sample / sample holder along the transfer path. In such an embodiment, the connection opening is formed within or part of the interior of the connecting tube; or, in this case, the connection opening can be defined as an opening blocked or opened by a baffle. In the latter case, the connection opening is the portion of the interior of the connecting tube where the baffle is located.

[0015] In embodiments where the sample transfer apparatus includes a connecting tube, the interior of the connecting tube typically still contains an atmosphere different from that inside the sample transfer apparatus (e.g., within the chamber of the sample transfer apparatus). Within the chamber of the sample transfer apparatus, the sample is manipulated and / or loaded into its loading position. The atmosphere inside the connecting tube can have a higher temperature and higher humidity than the atmosphere within the sample transfer apparatus chamber. Therefore, upon opening a baffle, this hot and humid atmosphere can create an inflow airflow that impacts the sample, leading to a risk of contamination and devitrification. This risk can be minimized by a shielding member preferably arranged between the inner end of the connecting tube and the sample loading position. Typically, the inner end of the connecting tube is formed within the wall of the chamber of the sample transfer apparatus, where the sample is manipulated and / or loaded.

[0016] In embodiments where the shielding member is configured to present a first and a second position, it is preferred that the shielding member is configured such that, in its second position, the shielding member holds the sample in the loading position. Similarly, the term "sample" is equivalent to "sample carrier" or "sample holder." Therefore, in this embodiment, the shielding member is used to hold the sample and / or sample carrier and / or sample holder in the loading position, facilitating any manipulation of the sample or sample carrier or loading the sample holder into the loading position. This holding function was previously achieved by a pushing element or "pusher," which must be removed before transferring the sample holder to the transfer position. This pusher is located on the side of the sample holder opposite the connection opening. After loading, the sample, typically placed on a sample grid, is placed into the sample holder (typically a sample cassette) in the loading position and held in place only by the pushing element / pusher. This pusher can now be omitted as the sample holder / cassette, so the sample itself can be held in the loading position by the shielding member, which is arranged on the connection opening side such that the shielding member holds the sample holder in its loading position.

[0017] In this embodiment, the shielding member is pivotally mounted on the rotation axis. This embodiment readily allows the shielding member to present two different positions (or even more), particularly for blocking the transfer path and shielding the sample or releasing the transfer path. It is preferred if the rotation axis is oriented in a direction perpendicular to the transfer path. The corresponding embodiments will be explained in more detail below with reference to the accompanying drawings. It should be noted that the shielding member can function as a door, which can be hinged to one side to release the transfer path, or as a cover, which can be hinged vertically to release and block the transfer path respectively.

[0018] It is preferred that the shielding member is held in at least one of the first and second positions by magnetic force. In this embodiment, the shielding member may carry a magnet, while two other magnets may be arranged at the sample transfer device such that the corresponding magnets are operatively connected once the shielding member reaches the first and second positions, respectively. This magnetic arrangement facilitates the definition of the first and second positions of the shielding member.

[0019] In another embodiment, the shielding member includes a surface facing the connection opening of the sample transfer device, which in particular includes a flow profile for deflecting the incoming airflow. Typically, the surface facing the connection opening is used to deflect any incoming airflow by directing it in a direction different from that toward the sample itself. This effect can be improved by the flow profile of the surface impacted by the incoming airflow.

[0020] In embodiments of the sample transfer apparatus, the sample transfer apparatus includes a transfer rod configured to receive a sample holder that carries the sample and is movable in the direction of the transfer path. As discussed above, the sample holder / cassette is typically inserted into the loading position of the sample transfer apparatus. Then, according to a preferred embodiment of the invention, a shielding member moves to its second position such that the shielding member blocks the transfer path and protects the sample placed in the sample holder, while simultaneously securing the cassette in the loading position. The sample, particularly one or two sample grids, is placed on the sample holder / cassette. To move the sample holder from the loading position to a location where the sample can be transferred to a processing or analytical unit, the transfer rod is connected to the sample holder / cassette, which can be moved by the movement of the transfer rod. Typically, the transfer rod is configured to receive or be connected to the sample holder and is movable in the direction of the transfer path to move the sample holder from the loading position to the sample transfer position. To facilitate easy and precise movement of the transfer rod, the sample transfer apparatus typically includes another tube, particularly on the opposite side of the connecting tube in the above embodiments, which guides the transfer rod.

[0021] It is preferable if the tip of the transfer rod is configured to receive the sample holder. For connecting the transfer rod to the sample holder, the sample holder preferably includes a (second) bore to receive the tip portion of the transfer rod.

[0022] In another preferred embodiment, the transfer rod includes a protective shield configured to be positioned above the sample located in the sample holder when the sample holder receives or connects to the transfer rod. Preferably, the protective shield moves above the sample located in the sample holder when the transfer rod is pushed in the (second) bore of the sample holder, such that when the transfer rod is connected to the sample holder, the protective shield covers the sample or the sample in the sample holder. Therefore, the protective shield provides additional protection for the sample from any contamination. Particularly in the event of any turbulence in the incoming airflow, the protective shield prevents a portion of the incoming airflow from impacting the sample from above.

[0023] It is preferable if the height of the shielding member in the location where it protects the sample from the incoming airflow is at least equal to the height of the protective cover. Each height relates to the same substrate in the sample transfer device. This embodiment ensures that the incoming airflow is directed above the protective cover rather than below it.

[0024] In an embodiment, the sample holder includes a sample holding region for receiving a sample and / or a sample carrier, and one or more (first) boreholes extending through the sample holder aligned with the sample holding region. Thus, a sample / sample grid can be placed on the corresponding sample holding region. The corresponding (first) boreholes can enable transmission light microscopy, transmission electron microscopy, or other microscopy techniques, for example, after the sample holder has been transferred to a corresponding microscope as an analytical unit.

[0025] As discussed above, it is preferred if the sample holder includes another (second) bore. In particular, the transfer rod and / or the second bore is configured such that when the sample and therefore the sample holder are in the loading position, the transfer rod is at least partially mounted to or engaged in the second bore for moving the sample holder along the transfer path.

[0026] Furthermore, it is preferable that the second borehole of the sample holder is covered by the shielding member to protect the sample from the incoming gas flow when the shielding member is in the corresponding active position (especially in its second position). This prevents the incoming gas from entering the second borehole and dispersing from there through the interior of the sample transfer device.

[0027] It should be noted that the above features of the embodiments of the present invention can be combined in whole or in part to achieve other embodiments that still fall within the scope of the present invention.

[0028] As used herein, the term “and / or” includes any and all combinations of one or more associated listed items and may be abbreviated to “ / ”.

[0029] Although some aspects have been described in the context of the apparatus or device, it is clear that these aspects also represent a description of the method of operating such apparatus or device.

[0030] Further embodiments and advantages of the present invention are described below with reference to the accompanying drawings. Attached Figure Description

[0031] Figure 1 An embodiment of a sample transfer apparatus conceived according to the present invention is illustrated schematically.

[0032] Figure 2 schematically shown Figure 1 The details of the embodiment are as follows: the shielding member is in the first position.

[0033] Figure 3 Schematic illustration of the corresponding Figure 2 The details are shown, but the shielding element is in its second position.

[0034] Figure 4 A perspective view of the shielding component is schematically shown below.

[0035] Figure 5 The schematic diagram illustrates a configuration for receiving, such as Figure 4 The corresponding part of the base of the sample transfer device of the shielding component shown.

[0036] Figure 6 A perspective cross-sectional view of a sample holder that can be used in a sample transfer device according to the present invention is shown schematically.

[0037] Figure 7 Details of the shielding member in its active position and the sample holder in its loading position are schematically shown.

[0038] Figure 8 The diagram schematically shows another detail of the shielding member and sample holder in their active positions, as well as the transfer rod that is partially received by the sample holder and provides a protective cover placed above the sample holder.

[0039] Figure 9 Another embodiment of the sample transfer apparatus conceived according to the present invention is illustrated schematically.

[0040] Figure Labels

[0041] 100 Sample Transfer Device

[0042] 102 wall

[0043] 104 Inner side of the wall

[0044] 106 masks

[0045] 110 Connection opening

[0046] 112 Connecting pipe

[0047] 114 Transfer Path

[0048] 116 Inner end of connecting pipe

[0049] 118 The outer end of the connecting pipe

[0050] 120 Loading position

[0051] Area 122

[0052] Room 124

[0053] 130 baffle

[0054] 226 base

[0055] 140 Shielding components

[0056] 242 Rotation axis

[0057] 344 Magnets

[0058] 546 Magnets

[0059] 448 Magnets

[0060] 150 surface

[0061] 190 Adapter Rod

[0062] 192 Adapter tube

[0063] 660 Sample Holder

[0064] 662 Sample carrier

[0065] 664 Sample holding area

[0066] 670 First Drill Hole

[0067] 680 Second Drill Hole

[0068] 894 Protective Cover

[0069] 906 Transparent Cover

[0070] 908 Transparent Cover

[0071] 910 Supporting Leg Detailed Implementation

[0072] The accompanying drawings are described in full below, and the same reference numerals denote the same or at least structurally identical parts.

[0073] Figure 1 A sample transfer device 100 is schematically shown. The sample transfer device 100 is used to receive a sample (not shown, see below for further explanation) within itself and to transfer the sample to a processing unit or analytical unit, such as a cryogenic fixation device, cryo-fracture device, or coating device as a processing unit, or a cryo-optical microscope or cryo-electron microscope as an example of an analytical unit. It should be noted that the sample, typically a biological sample, is usually placed on a sample carrier (such as a sample grid), which is placed on a sample holder, also referred to as a sample cassette. Therefore, any reference to “sample” should be understood equivalently to references to “sample carrier” and / or “sample holder”.

[0074] Figure 1 The sample transfer device 100 includes a connection opening 110 defining a transfer path 114 along which a sample is transferred from a sample / sample holder loading position 120 inside the sample transfer device, first to the connection opening 110 and then to a transfer position, which is typically outside the sample transfer device 100. To reach the transfer position, the transfer path needs to be open, i.e., the baffle 130 needs to release the connection opening 110.

[0075] exist Figure 1 In one embodiment, the baffle 130 and the connection opening 110 are arranged near the end of the connecting tube 112. However, the baffle 130 and the connection opening 110 can be arranged anywhere along the connecting tube 112, or at the inner end 116 of the connecting tube 112, or even in the wall 102 of the sample transfer device 100 on the transfer path 114, or inside the opening 104 of the wall 102 leading to the connecting tube 112.

[0076] A shielding member 140 is arranged between the connection opening 110 and the loading position 120, more specifically, between the inner end 116 of the connecting tube 112 and the loading position 120, and even more specifically, between the inner side 104 of the opening in the wall 102 of the sample transfer device and the loading position 120, the opening being connected to the connecting tube 112 to protect the sample from the incoming airflow when the baffle 130 opens the connection opening 110. Figure 3 The corresponding arrangement of the shielding member 140 is shown in more detail so that it can function as a shield to prevent the sample from being affected by the incoming airflow. Figure 1 The embodiment shows the shielding member 140 in a first inactive position, in which the shielding member releases the transfer path 114.

[0077] Figure 1Also shown is a transfer rod 190, which will be discussed further below, and serves as a means of transferring a sample holder loaded in loading position 120 along transfer path 114 to the outer end 118 of connecting tube 112. For this purpose, transfer rod 190 is mounted in transfer rod tube 192, in which transfer rod 190 can move axially.

[0078] An internal forming chamber 124 of the sample transfer device, including the loading position 120, is included. A cryogenic atmosphere is preferably present in chamber 124 when the sample / sample carrier / sample holder is manipulated and / or mounted in the loading position and / or transferred to the transfer position. The cryogenic atmosphere inside chamber 124 can be generated by filling a portion of chamber 124 with liquid nitrogen. The liquid nitrogen level typically reaches below the base of the sample transfer device, on which the loading position 120 is located. This base is designated as 226 and... Figure 2 , Figure 3 and Figure 5 It is shown in more detail below.

[0079] Reference numeral 122 depicts an area on the sample carrier / grid where the sample can be manipulated or where the sample carrier / grid can be removed and placed on the sample holder / cassette. However, it can also be an area where the sample holder / cassette can be placed and where the sample / sample carrier can be transferred from outside the sample transfer device 100 to the sample holder located in area 122. To allow this type of operation, a preferred transparent cover to the chamber 124 (more detailed as...) Figure 9 (As shown) or a portion of such a cover is partially opened by moving it aside to expose the corresponding proximity area. Users should always take care to keep the exposed area as small as possible to avoid disrupting the cryogenic atmosphere.

[0080] Figure 2 schematically shown Figure 1 Details of the interior of the sample transfer device 100. From Figure 2 As can be seen, the shielding member 140 is in its first position on the release transfer path 114. In this position, the sample holder / cassette can be transferred along the transfer path 114 through the connection opening 110 from the loading position 120 to a sample transfer position outside the sample transfer device 100. The shielding member 140 is pivotally mounted on the rotation shaft 242, such that the shielding member 140 can pivot from the inactive (first) position to... Figure 3 The activity shown is in the second position.

[0081] Figure 3 It shows the relationship with Figure 2 The same details apply, wherein the shielding member 140 is in its active (second) position. In this position, the shielding member 140 blocks the transfer path 114, as from... Figure 3As can be seen. Furthermore, in the indicated position, the shielding member 140 secures the sample holder / cassette in the loading position 120, thereby also securing the sample in the loading position 120. It is preferable that the shielding member 140 is held in its active and inactive positions by magnetic force, respectively. For this purpose, a magnet 344 is disposed in the base 226 of the sample transfer device 100. Another magnet 546 (see...) Figure 5 It is placed at a position corresponding to the movable position of the shielding member 140 in the base 226 of the sample transfer device 100. This will combine... Figure 4 and Figure 5 Describe the operation of the magnet.

[0082] Figure 4 The shielding member 140 is schematically shown from a bottom perspective. The shielding member 140 has a surface 150 facing the inner side 104 of the wall 102 of the sample transfer device 100, thereby facing the incoming airflow. Furthermore, the shielding member 140 includes a drilled hole in the direction of the rotation axis 242 for mounting the shielding member 140 to the base 226 of the sample transfer device 100. Further, from... Figure 4 As can be seen, the shielding member 140 includes a magnet 448, which can be magnetically connected to each of the two magnets 344 and 546 in the substrate 226 of the sample transfer device 100. Figure 5 The two magnets 344 and 546 are shown. When the shielding member 140 is pivoted in its first position, the shielding member 140 is secured by the magnetic force between magnet 448 and magnet 344. When the shielding member 140 is pivoted in its second position, the shielding member 140 is secured by the magnetic force between magnet 448 and magnet 546. Surface 150 may have a profile for guiding the airflow impacting surface 150 in a preferred direction away from the sample behind it.

[0083] Figure 6 An embodiment of a sample holder 660 is schematically shown, the sample holder 660 being configured to be placed as... Figure 1The sample transfer device 100 is shown in loading position 120. The sample holder 660 or sample cassette in this embodiment includes two sample holding regions 664 configured to receive the sample carrier 662, in this case, a sample grid. The sample is placed on the sample grid 662. Two first boreholes 670 extend through the sample holder 660 aligned with the corresponding sample holding regions 664, allowing the sample to be examined to be imaged using a transmission light microscope or a transmission electron microscope. In addition to the two first boreholes 670, a second borehole 680 extends through the sample holder 660 perpendicular to the two first boreholes 670. The borehole 680 is configured to receive the tip portion of a transfer rod 190. The transfer rod 190 can be connected to the sample holder 660 such that, through axial movement of the transfer rod 190, the sample holder 660 moves along a transfer path 114. This allows the sample on the sample carrier 662 to move from loading position 120 through connection opening 110 to a transfer position outside the sample transfer device 100.

[0084] Figure 7 The diagram illustrates the shielding member 140 relative to the sample holder 660 (e.g., Figure 6 An embodiment of the arrangement of the sample holder 660. Figure 7 In the arrangement shown, the shielding member 140 is in its active (second) position, and the shielding member 140 is configured such that when the shielding member 140 is positioned in its active (second) position, the shielding member 140 can cover the second borehole 680 of the sample holder 660. In this embodiment, the shielding member 140 not only protects the sample on the sample carrier 662 from the incoming airflow, but also prevents the incoming airflow from entering the borehole 680, which would otherwise pass through the borehole 680 to the first borehole 670, thereby reaching the interior of the sample and / or sample transfer device 100.

[0085] In an exemplary operation, the shielding member 140 is in its inactive (first) position, and the sample holder 660 can be inserted into the loading position 120. For example, using a tool such as a pair of tweezers, the shielding member 140 is moved to its active (second) position to the right, where it is held magnetically, as described above. In this position, the sample holder 660 is secured in the loading position (see...). Figure 3Samples can be inserted. The sample transfer device 100, also known as a shuttle, can now be attached to a processing unit or analysis unit, such as a cryogenic stage of a cryogenic microscope. Next, the baffle 130 is opened to open the transfer path 114. Opening the baffle 130 allows any gas present in the connecting lines to be drawn into the interior of the sample transfer device 100. However, the shielding member 140, in its active position, protects the sample on the sample holder 660 by deflecting the incoming airflow. Meanwhile, as Figure 7 As shown, the shielding member 140 prevents gas from entering. Figure 6 and Figure 7 The sample holder 660 is shown with a drilled hole 680. Using the shielding member 140 of the present invention, moisture in the incoming airflow cannot condense on the sample, thus preventing any contamination. After a predetermined period of time, for example by moving the sample holder 660 toward the connection opening 110 via a transfer rod 190, the shielding member 140 is moved to its inactive (first) position, thereby pushing the shielding member 140 into the first position where it is held magnetically.

[0086] Figure 8 Another preferred embodiment is shown, illustrating the position where the transfer rod 190 is connected to the sample holder 660, and the shielding member 140 is positioned as follows: Figure 7 The location shown. From Figure 8 As can be seen, the transfer rod 190 (shown in its longitudinal section) includes a protective cover 894, which is configured to be positioned above the sample carried by the sample holder 660 when the transfer rod is received by the sample holder 660. When the transfer rod 190 is moved into the second bore 680 of the sample holder 660, the protective cover 894 moves above the sample holder 662 located within the sample holder 660. The protective cover 894 provides additional protection to the sample from any airflow from above. Figure 8 As shown, it is preferred if the height of the shielding member 140 is at least equal to or greater than the height of the protective cover 894, with each height relating to the same substrate 226 in the sample transfer device 100. In this way, even the protective cover 894 is protected by the shielding member 140, so that any incoming airflow is directed in the area above the protective cover 894.

[0087] Figure 9 Another embodiment of the sample transfer device 100 is shown, which substantially corresponds to Figure 1 The embodiments shown above. Therefore, referring to the above... Figure 1 The following discussion will only cover the differences from this embodiment. Figure 9 It can be seen that, Figure 1The sample transfer device 100 includes a transparent cover 906 mounted on a frame of the sample transfer device 100 via four support legs 910. Vaporized inert gas / nitrogen can escape from the interior of the sample transfer device 100 through the gap between the frame and the transparent cover 906, thereby maintaining the interior under a slight overpressure and preventing external air from entering the interior.

[0088] While, in principle, a user access to the interior can be provided by at least partially opening / removing the transparent cover 906, it is preferred if the transparent cover 906 includes a transparent cap 908 that can be at least partially opened to provide such a user access. In the illustrated embodiment, the transparent cap 908 is pivotally mounted to one of the support legs 910. Thus, atmospheric interference can be minimized when loading / manipulating samples from outside the sample transfer device 100.

[0089] like Figure 9 As shown, the shielding member 140 is arranged between the connection opening 110 and the loading position 120, more specifically between the inner end 116 of the connecting tube 112 and the loading position 120, and even more specifically between the inner side 104 of the opening in the wall 102 of the sample transfer device and the loading position 120, to protect the sample from the incoming airflow when the baffle 130 opens the connection opening 110. Figure 9 The embodiment shows the shielding member 140 in its second active position. For more details regarding the components and functions of the sample transfer device 100, refer to the above. Figure 1 .

Claims

1. A sample transfer device (100) for receiving a sample inside the sample transfer device (100) and for transferring the sample to a processing unit or an analysis unit, the sample transfer device (100) comprising: A connection opening (110) defines a transfer path (114) through which the sample is transferred from the sample loading position (120) inside the sample transfer device (100) along the transfer path (114) through the connection opening (110). A baffle (130), the baffle (130) being configured to block the connection opening (110) or to allow the connection opening (110), and A shielding member (140) is configured to be disposed between the connection opening (110) and the loading position (120) to protect the sample from the incoming airflow when the baffle (130) opens the connection opening (110).

2. The sample transfer device (100) according to claim 1, wherein the shielding member (140) is configured to present a first position and a second position, wherein in the first position of the shielding member (140), the shielding member (140) releases the transfer path (114), and in the second position of the shielding member (140), the shielding member (140) blocks the transfer path (114).

3. The sample transfer device (100) according to claim 1 or 2, wherein the connection opening (110) is formed by at least a portion of the interior of the connecting tube (112) or at least a portion of the interior of the connecting tube (112), and the transfer path (114) extends through the connecting tube (112).

4. The sample transfer device (100) according to claim 3, wherein the shielding member (140) is arranged between the inner end (116) of the connecting tube (112) and the loading position (120) of the sample, or is arranged between the inner side (104) of the opening in the wall (102) of the sample transfer device (100) leading to the connecting tube (112) and the loading position (120) of the sample.

5. The sample transfer device (100) according to claim 2, wherein the shielding member (140) is configured such that, at the second position of the shielding member (140), the shielding member (140) secures the sample in the loading position (120).

6. The sample transfer device (100) according to claim 1, wherein the shielding member (140) is pivotally mounted on the rotation shaft (242).

7. The sample transfer device (100) according to claim 2, wherein the shielding member (140) is held magnetically in at least one of the first position and the second position.

8. The sample transfer device (100) according to claim 1, wherein the shielding member (140) includes a surface (150) facing the connection opening (110) of the sample transfer device (100).

9. The sample transfer device (100) according to claim 1, wherein the sample transfer device (100) includes a transfer rod (190) configured to receive a sample holder (660) carrying the sample, the transfer rod (190) being movable in the direction of the transfer path (114).

10. The sample transfer device (100) according to claim 9, wherein the transfer rod (190) includes a protective cover (894) configured to be placed above the sample carried by the sample holder (660) when the sample holder (660) receives or is connected to the transfer rod (190).

11. The sample transfer device (100) according to claim 10, wherein the height of the shielding member (140) is at least equal to the height of the protective cover (894), each of the heights being related to the same substrate (226) in the sample transfer device (100).

12. The sample transfer device (100) according to any one of claims 9 to 11, wherein the sample transfer device (100) includes the sample holder (660) for receiving the sample.

13. The sample transfer device (100) according to claim 12, wherein the sample holder (660) includes a sample holding region (664) for receiving the sample and / or sample carrier (662) and a first borehole (670) extending through the sample holder (660) aligned with the sample holding region (664).

14. The sample transfer device (100) according to claim 12, wherein the sample holder (660) includes a second bore (680) configured to receive the transfer rod (190) when the sample holder (660) is in the loading position (120).

15. The sample transfer device (100) according to claim 14, wherein the second borehole (680) is covered by the shielding member (140) when arranged between the connection opening (110) and the loading position (120) to protect the sample from the incoming airflow.

16. The sample transfer device (100) according to claim 8, wherein the surface (150) has a flow profile for deflecting the incoming airflow.

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