SYSTEM FOR LOADING AND/OR MANIPULATING A SAMPLE IN A SAMPLE TRANSFER DEVICE

Abstract

A system (100) for loading a sample into and/or manipulating a sample in a sample transfer device (180) at cryogenic temperatures, comprising the sample transfer device (180) being configured to receive a sample through a receiving opening (182) of the sample transfer device (180) and configured to transfer the sample to a processing or analysing unit, and a dry box (110) having an interface opening (112) and being configured to be coupled to the sample transfer device (180) such that the interface opening (112) of the dry box (110) is located opposite the receiving opening (182) of the sample transfer device (180).

Claims

1. A system for loading a sample into and/or for manipulating a sample in a sample transfer device at cryogenic temperatures, the system comprising: the sample transfer device having a receiving opening, the sample transfer device being configured to receive the sample through the receiving opening and to transfer the sample to a processing or analysing unit; and a dry box having an interface opening, the dry box being configured to be connected to the sample transfer device such that the interface opening of the dry box and the receiving opening of the sample transfer device are facing each other to enable the sample to be transferred from the dry box into the sample transfer device.

2. The system of claim 1, wherein the dry box comprises an interface opening lid having a open state for opening the interface opening and a closed state for closing the interface opening.

3. The system of claim 2, wherein the sample transfer device comprises a receiving opening lid having an open state for opening the receiving opening and a closed state for closing the receiving opening.

4. The system of claim 3, wherein the dry box is configured to be connected to the sample transfer device when the interface opening lid is in its closed state and the receiving opening lid is in its closed state.

5. The system of claim 4, wherein a distance between the interface opening lid in its closed state and the receiving opening lid in its closed state is in a range of 0 to 10 mm when the dry box is connected to the sample transfer device.

6. The system of claim 5, wherein the distance between the interface opening lid in its closed state and the receiving opening lid in its closed state is in a range of 0 to 5 mm when the dry box is connected to the sample transfer device.

7. The system of claim 1, wherein the dry box and the sample transfer device are connectable to each other by at least one of a mechanical connection and a magnetic connection.

8. The system of claim 1, wherein, when the dry box and the sample transfer device are connected to each other, the resulting connection is a closed connection or a sealed connection.

9. The system of claim 1, wherein the dry box comprises an inlet for introducing an inert gas into an inside of the dry box.

10. The system of claim 1, wherein the dry box comprises an outlet for discharging gas out of an inside of the dry box.

11. The system of claim 1, wherein the dry box comprises a sample supply container opening configured to be connected to a sample supply container.

12. The system of claim 11, wherein the dry box comprises a sample supply container opening lid for opening and closing the sample supply container opening of the dry box.

13. The system of claim 1, wherein the dry box comprises an inert gas opening configured to be connected to an inert gas storage container.

14. The system of claim 1, wherein the sample transfer device comprises an inert gas reservoir at cryogenic temperatures.

15. The system of claim 1, wherein the dry box comprises a humidity sensor for detecting a humidity inside the dry box.

16. The system of claim 15, wherein the dry box comprises a measuring device connected to the humidity sensor for displaying humidity values.

17. The system of claim 1, wherein the dry box comprises an at least partially closable user opening providing a user access to an inside of the dry box.

18. The system of claim 17, wherein the dry box comprises a foil cover at least partially covering the user opening.

19. The system of claim 17, wherein the user opening of the dry box comprises a glove mount for mounting a glove to extend, when the glove is mounted on the glove mount, into the inside of the dry box.

20. The system of claim 1, wherein the dry box comprises a coupling mechanism for decoupling the dry box from the sample transfer device and for coupling the dry box with the sample transfer device.

21. The system of claim 20, wherein the coupling mechanism is an electromechanical coupling mechanism.

22. The system of claim 21, wherein the coupling mechanism comprises an eccentric mechanism.

23. The system of claim 22, wherein the eccentric mechanism comprises eccentric wheels at a bottom side of the dry box.

24. The system of claim 1, wherein the dry box comprises a magnifying window at a top side of the dry box.

25. A dry box for use with a sample transfer device at cryogenic temperatures, sample transfer device having a receiving opening through which the sample transfer device receives a sample, the dry box comprising an interface opening and the dry box being configured to be connected to the sample transfer device such that the interface opening of the dry box and the receiving opening of the sample transfer device are facing each other to enable the sample to be transferred from the dry box into the sample transfer device.

26. The dry box of claim 25, wherein the dry box further comprises: an interface opening lid for opening and closing the interface opening; an inlet for introducing an inert gas into an inside of the dry box; an outlet for discharging gas out of the inside of the dry box; a sample supply container opening configured to be connected to a sample supply container; a sample supply container opening lid for opening and closing the sample supply container opening; an inert gas opening configured to be connected to an inert gas storage container; a humidity sensor for detecting a humidity inside the dry box; a measuring device connected to the humidity sensor for displaying humidity values; an at least partially closable user opening providing a user access to the inside of the dry box; a foil cover at least partially covering the user opening; a coupling mechanism for decoupling the dry box from the sample transfer device and for coupling the dry box with the sample transfer device, wherein the coupling mechanism comprises eccentric wheels at a bottom side of the dry box; and a magnifying window at a top side of the dry box.

Description

SHORT DESCRIPTION OF THE FIGURES

[0039] FIG. 1 schematically shows an embodiment of a system according to the present inventive concept,

[0040] FIG. 2 schematically shows a view from above of a cross section in a horizontal direction through the dry box of the system of FIG. 1,

[0041] FIGS. 3 and 4 show the system in a transparent side view in a coupled state (FIG. 3) and a decoupled state (FIG. 4), and

[0042] FIG. 5 schematically shows an embodiment of a dry box according to the present inventive concept.

DETAILED DESCRIPTION

[0043] The figures are described comprehensively, same reference signs relating to same or at least structurally equivalent elements.

[0044] FIG. 1 schematically shows an embodiment of a system according to the inventive concept in a perspective view, the dry box being shown transparently. The system is designated 100, the sample transfer device is designated 180 and the dry box is designated 110.

[0045] The sample transfer device 180 of FIG. 1 comprises a transfer rod 184 having at its other end a receiving section 186 for a sample holder/cartridge as shown in FIG. 1. In operation, the transfer rod 184 is retracted such that the receiving section 186 is positioned inside the sample transfer device 180 for being able to receive a sample holder which is typically arranged in the receiving opening 282 of the sample transfer device 180 (see also FIG. 2). Typically, the sample holder is arranged in a loading position, and a sample or a sample carrier is placed onto or into the sample holder. In a next step, the transfer rod 184 is moved in its axial direction such that the receiving section 186 of the transfer rod can receive the sample holder which is moved through the connection tube 188 and outside of the connection tube 188 when shutter 185 is in its opened position. The sample on the sample holder is then transferred to a transfer position where the sample holder as such can be transferred e.g. to the cryo-stage of a cryo-microscope. The state of the sample transfer device 180 as shown in FIG. 1 is only for illustrative purposes to better understand design and function of the sample transfer device 180.

[0046] The housing part 116 (see also FIG. 5) including the volume space of the dry box 110 can be made of a transparent or semi-transparent material and comprises in the embodiment of FIG. 1 a magnifying window 190 enabling an operator to look into the dry box 110 and to monitor its inside. As the magnifying window 190 is directed onto the interface opening 112, it is possible to view any elements in the line of sight in magnified form. The humidity of the atmosphere in the volume space of the housing part 116 can be measured by a measuring device 152 connected to a humidity sensor 250 (see FIG. 2). The dry box 110 further has an interface opening 112, the frame of which is configured such that it can be placed on top of the sample transfer device 180 as shown in FIG. 1. As the interface opening 112 is fitted onto the topside of the sample transfer device 180, a connection of the two units 180 and 110 is reached. In the connected state, the receiving opening 282 (see FIG. 2) of the sample transfer device 180 faces the interface opening 112 of the dry box 110 such that a sample and/or a sample carrier and/or sample holder can be transferred from the dry box into the sample transfer device. The connection of the two units 180 and 110 as described above does not need to be a hermetically sealed connection but needs to be a sufficiently tight connection in order to avoid excessive gas leakage.

[0047] As shown in FIG. 1, the dry box 110 further comprises two at least partly closable user openings 160 providing a user access to the inside of the dry box 110. The user openings 160 are partly closed by a foil cover 162 covering the user opening 160 and having two slits perpendicular to each other such that a user hand can enter the dry box 110 by pushing away the flexible slotted foil cover 162. Additionally, the user openings 160 may be closed by corresponding user opening doors 164.

[0048] As can be further seen in FIG. 1, the dry box 110 comprises a carrier or frame 174, which holds the interface opening 112 of the dry box 110 at a height corresponding to the height of the topside of the sample transfer device 180 as can be seen from FIG. 1. The carrier or frame 174 comprises a base part 176 which is supported by ground and comprises two eccentric wheels 172 such that an eccentric mechanism 170 is formed which will be described in connection with FIG. 3 or 4 later on. In the state showing FIG. 1, the eccentric mechanism 170 couples the dry box 110 with the sample transfer device 180 by lowering the interface opening 112 of the dry box 110 onto the topside of the sample transfer device.

[0049] FIG. 2 schematically shows a perspective view from above through the system 100 onto the topside of the sample transfer device 180 and onto elements arranged in the floor area of the volume space of the dry box 110.

[0050] The elements shown in FIG. 2 are now described from left to right. On the left there is a sample supply container opening 230 to which a sample supply container 232 can be connected, for instance, magnetically. As can be seen from FIG. 2, the sample supply container 232 comprises a perforated plate typically located above a bath of liquid cryogenic gas, the perforated plate comprising small sample transfer containers loaded with grids or sapphire plates. The sample supply container opening 232 can be opened and closed by a sample supply container opening lid 234. The next element shown in FIG. 2 is an interface opening lid 214 for opening and closing the interface opening 112. The interface opening of the dry box 110 allows access to the sample transfer device 180 which is arranged below interface opening 112. The next element shown in FIG. 2 is an inert gas opening lid 242 shown in its closed state covering an inert gas opening 240. Such an inert gas opening 240 serves the purpose of allowing cold inert gas streaming inside the dry box 110. The inert gas opening 240 can be connected to an inert gas storage container 344 (see FIG. 3). Alternatively, 240 can designate another sample supply container opening to which a sample supply container can be connected, which sample supply container opening 240 is closable by a sample supply container opening lid 242.

[0051] Reference sign 220 designates another inlet or quick connector or valve for introducing an inert gas into the inside of the dry box. For instance, gaseous nitrogen from a gas cylinder may be introduced through a quick connector 220 for efficiently generating a dry atmosphere of sufficiently low humidity within a small amount of time.

[0052] Depending on the specific application, it might be sufficient to only use the sample supply container 232 and/or the sample transfer device 180 as a source of cold inert gas streaming into the dry box 110. However, in order to achieve an even less humid atmosphere inside the dry box 110 in a smaller time interval, another source of inert gas like a nitrogen gas cylinder or the inert gas storage container 344 is useful.

[0053] In operation, the dry box 110 is placed by means of its frame or carrier 174 in relation to the sample transfer device 180 such that interface opening 112 is positioned above the receiving opening 282 of the sample transfer device 180. If the receiving opening 282 is closed by a receiving opening lid 284, the interface opening 112 is placed above the receiving opening lid 284 as shown in FIG. 2. By the eccentric mechanism 170 which will be described in further detail in connection with FIGS. 3 and 4 below, the interface opening 112 is lowered onto the top surface of the sample transfer device 180 (see also FIG. 1) in order to achieve an essentially closed system of the two units 180 and 110. Next, an inert gas is introduced into the dry box 110, preferably by opening the inert gas inlet 220. Instreaming inert gas displaces the air inside the dry box 110, and the humidity of the cryogenic atmosphere is measured by the measuring device 152 connected to the humidity sensor 250. As the system 100 is not hermetically sealed, humid air can be displaced through existing air leaks. A relative humidity of less than 5% can be achieved and is desirable. It is noted that introduction of inert gas into the dry box 110 can be automized by means of a control unit (which may be part of the measuring device 152) and a valve controlling the amount of instreaming inert gas by means of the humidity sensor 250 or by simply adjusting the amount of gas released from a gas cylinder.

[0054] It is preferred to keep the dead volume between the closed interface opening lid and the (transparent) receiving opening lid 284 as small as possible in order to reduce the amount of humid air inside this dead volume to a minimum. First, the interface opening lid 214 is opened such that air from said dead volume flows into the dry box 110. Then, if present, the receiving opening lid 284 of the sample transfer device 180 is removed. Typically, the inside of the sample transfer device 180 also is under cryogenic atmosphere. It is, however, also conceivable to use a sample transfer device 180 without a receiving opening lid 284 such that the cryogenic atmosphere inside the sample transfer device 180 is completed by cryogenic gas from the dry box 110.

[0055] In a next step, a sample supply container is connected to the sample supply container opening 230 of the dry box. The sample supply container opening lid 234 is opened when the inert atmosphere inside the dry box 110 has the desired low humidity. Samples can now be transferred from the sample supply container 232 onto e.g. a smaller sample carrier/grid and/or onto a sample holder/cartridge inside the receiving opening 282 of the sample transfer device 180. Also, other kinds of manipulation of samples/sample carriers/sample holders including unloading are possible without any risk of contamination or devitrification.

[0056] FIG. 3 schematically shows an embodiment of the system 100 in a transparent side view. Again, the sample transfer device is depicted 180, the dry box 110 and the frame or carrier of the dry box 174. As can be seen from FIG. 3, an inert gas storage container 344 is received inside the carrier or frame 174 of the dry box 110. This inert gas storage container 344 can be connected to the inert gas opening 240 as discussed in connection with FIG. 2. Alternatively, according to the embodiment shown in FIG. 2, instead of or in addition to an inert gas storage container, a sample supply container 232 may be included into the lower part of the carrier or frame 174. In this respect, reference is made to the explanations in connection with FIG. 2.

[0057] The carrier or frame 174 comprises a bottom part or base part 176 essentially extending parallel to the ground onto which the sample transfer device 180 is placed. The base part 176 of the carrier or frame 174 comprises an eccentric mechanism 170 which comprises an eccentric wheel 172 on the left and another one on the right side of the base part 176 of the carrier or frame 174 (as also shown in FIG. 1). In the position of the eccentric wheel 172 as shown in FIG. 3, the frame or carrier 174 is in a lowered position to enable coupling of the dry box 110 and the sample transfer device 180.

[0058] FIG. 4 shows the system 100 of FIG. 3 with the only difference that the eccentric wheel 172 is in another position where the base part 176 of the carrier or frame 174 is lifted up such that the dry box 110 takes a slightly tilted position and is decoupled from the sample transfer device 180.

[0059] FIG. 5 schematically shows an embodiment of a dry box 110 according to the inventive concept in a perspective view similar to that in FIG. 1 but without a sample transfer device.

[0060] The housing part 116 including the volume space of the dry box 110 can be made of a transparent or semi-transparent material. The dry box 110 has an interface opening 112 (see FIG. 1), the frame of which is configured such that it can be placed on top of the sample transfer device 180 as shown in FIG. 1. As shown in FIG. 5, the dry box 110 further comprises two at least partly closable user openings providing a user access to the inside of the dry box 110, which user openings may be closed by corresponding user opening doors 164 (shown in the closed state). As can be further seen in FIG. 5, the dry box 110 comprises a carrier or frame 174, which holds the housing part 116 of the dry box 110 including the interface opening 112 at a height corresponding to the height of the topside of the sample transfer device 180 as shown in FIG. 1. The carrier or frame 174 comprises a base part 176 which is supported by ground and comprises two eccentric wheels 172 such that an eccentric mechanism 170 is formed which has been described in connection with FIG. 3 or 4 above. In the state of FIG. 5, the eccentric mechanism 170 couples the dry box 110 with the sample transfer device 180 by lowering the interface opening 112 of the dry box 110 onto the topside of the sample transfer device.

[0061] A measuring device 152 having a display for operating the device and/or for displaying relative humidity values of the inside of the housing part 116 of the dry box 110 measures the relative humidity of the atmosphere inside the housing part 116 by humidity sensor 250. A relative humidity of less than 5% can be achieved and is desirable. It is noted that introduction of inert gas into the dry box 110 can be automated by means of a control unit and/or the measuring device 152 and a valve controlling the amount of instreaming inert gas by means of the humidity sensor 250 or by simply adjusting the amount of gas released from a gas cylinder.

[0062] Further features of the dry box 110 have been discussed in connection with FIGS. 1 to 4 and may be individually or jointly additionally implemented in the dry box 110 of FIG. 5.

LIST OF REFERENCE SIGNS

[0063] 100 system

[0064] 110 dry box

[0065] 112 interface opening

[0066] 116 housing part

[0067] 152 measuring device

[0068] 160 user opening

[0069] 162 foil cover

[0070] 164 user opening door

[0071] 170 eccentric mechanism

[0072] 172 eccentric wheel

[0073] 174 carrier, frame

[0074] 176 base part

[0075] 180 sample transfer device

[0076] 184 transfer rod

[0077] 185 shutter

[0078] 186 receiving section for sample holder

[0079] 188 connection tube

[0080] 190 magnifying window

[0081] 214 interface opening lid

[0082] 220 inlet for inert gas

[0083] 230 sample supply container opening

[0084] 232 sample supply container

[0085] 234 sample supply container opening lid

[0086] 240 inert gas opening

[0087] 242 inert gas opening lid

[0088] 250 humidity sensor

[0089] 282 receiving opening

[0090] 284 receiving opening lid

[0091] 344 inert gas storage container