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Title:
SYRINGE DEVICE
Document Type and Number:
WIPO Patent Application WO/2019/185122
Kind Code:
A1
Abstract:
The invention relates to a syringe device (1) comprising - a body (100), - a cylindrical retainer tube (10) coaxially comprising a wire (20) relatively moveable with respect to the retainer tube (10), - a handle means (40) configured for causing the relative movement of the retainer tube (10) and the wire (20), the retainer tube (10) and the wire (20) being separable together from the body (100).

Inventors:
REICHERT JÜRGEN (DE)
QUIRNHEIM-PAIS DAVID (DE)
THIELMANN YVONNE (DE)
WURZINGER PAUL (AT)
WOGRITSCH RAINER (AT)
GOLL HUBERT (AT)
Application Number:
PCT/EP2018/057775
Publication Date:
October 03, 2019
Filing Date:
March 27, 2018
Export Citation:
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Assignee:
MAX PLANCK GESELLSCHAFT (DE)
LEICA MICROSYSTEME GMBH (AT)
International Classes:
B01L3/02; A61B10/02; B01L3/00; C12M1/26
Domestic Patent References:
WO2013082208A22013-06-06
Foreign References:
US3720354A1973-03-13
US20160051978A12016-02-25
Attorney, Agent or Firm:
RICHARDT PATENTANWÄLTE PARTG MBB (DE)
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Claims:
Claims

1. A syringe device (1 ) comprising

- a body (100),

- a cylindrical retainer tube (10) coaxially comprising a wire (20) relatively moveable with respect to the retainer tube (10),

- a handle means (40) configured for causing the relative

movement of the retainer tube (10) and the wire (20), the retainer tube (10) and the wire (20) being separable together from the body (100).

2. The syringe device (1 ) of claim 1 , the handle means (40) comprising an operating element (41 ) configured for causing the relative movement upon operation of the operating element (41 ), the operating element (41 ) being moveable relative and parallel to the retainer tube axis and outside of the retainer tube axis.

3. The syringe device (1 ) of any of the previous claims, the inner diameter of the retainer tube (10) corresponding to the outer diameter of the wire (20).

4. The syringe device (1 ) of any of the previous claims, further comprising a base element (32), the retainer tube (10) being received in the base element (32), the handle means (40) comprising an extension (42) in operative connection with the retainer tube (10) or the wire (20) and configured for causing the relative movement.

5. The syringe device (1 ) of claim 4, the retainer tube (10), the wire (20) and the base element (32) being separable together from the body (100).

6. The syringe device (1 ) of any of the previous claims 4-5, the body (100) being adapted for supporting the handle means (40), the base element (32) and the body (100) being fixed to each other by magnetic forces.

7. The syringe device (1 ) of any of the previous claims 4 or 6, the base element (32) comprising a support tube (30), the retainer tube (10) being fixed to the base element (32) via the support tube (30), the retainer tube (10) being coaxially received in the support tube (30) and protruding the support tube (30).

8. The syringe device (1 ) of claim 7, the material of the support tube (30) being different from the material of the retainer tube (10).

9. The syringe device (1 ) of claim 8, the material of the support tube (30) comprising a metal and/or the material of the retainer tube (10) comprising glass or a polymer.

10. The syringe device (1 ) of any of the previous claims 4-9, the retainer tube (10) being fixed to the base element (32), the syringe device (1 ) further comprising a guiding element (21 ), the extension (42) being in operative connection with the wire (20) via the guiding element (21 ), the guiding element (21 ) being moveable via the handle means (40) by the element along the axis and configured for causing the relative movement of the wire (20).

11.The syringe device (1 ) of claim 10, the guiding element (21 ) comprising a recess (22) configured for receiving the extension (42).

12. The syringe device (1 ) of any of the previous claims 10-11 , the base element (32) having an interior space, the interior space comprising the guiding element (21 ), the base element (32) comprising a slot (31 ) to the interior space, the extension (42) extending though the slot (31 ) for being in the operative connection with the wire (20) via the guiding element (21 ).

13. The syringe device (1 ) of any of the previous claims 4-11 , the base element (32) or the retainer tube (10) comprising an opening (60), the base element (32) and/or the retainer tube (10) having a cylindrical wall confining an interior space, the wire (20) being at least partially received by the interior space, the opening (60) being comprised in the cylindrical wall, the wire (20) having a part protruding from the opening (60), the part of the wire (20) protruding from the opening (60) forming the operative connection with the extension (42).

14. The syringe device (1 ) of claim 13, the support tube (30) having the opening (60).

15. The syringe device (1 ) of claim 13 or 14, the part of the wire (20)

protruding from the opening (60) being fixed to the guiding element (21 ).

16. The syringe device (1 ) of claim 15, the base element (32) providing an outer sliding surface supporting the guiding element (21 ) and facing away from the retainer tube axis, the guiding element (21 ) being moveable along the sliding surface.

17. The syringe device (1 ) of claim 16, the support tube (30) providing the outer sliding surface.

18. The syringe device (1 ) of any of the previous claims 15-17, the guiding element (21 ) clutching the base element (32) with positive locking.

19. The syringe device (1 ) of any of the previous claims 15-18, the guiding element (21 ) and the base element (32) comprising a locking against rotation of the guiding element (21 ) around the retainer tube axis.

20. The syringe device (1 ) of any of the previous claims 15-19, the guiding element (21 ) having a face side pointing in the direction of the retainer tube axis, the face side comprising a set of holes (70) distributed around the retainer tube axis, wherein in one of the holes (70) the part of the wire (20) protruding from the opening (60) is received and fixed to the guiding element (21 ).

21.The syringe device (1 ) of any of the previous claims 13-20, the opening (60) being provided by a tubular channel having a channel axis, the angle between the channel axis and the retainer tube axis being lower than 30°, preferably lower than 10°.

22. The syringe device (1 ) of any of the previous claims 4-10, the wire (20) being fixed to the base element (32), the retainer tube (10) being moveable via the handle means (40) by the element along the axis and configured for causing the relative movement of the wire (20).

23. The syringe device (1 ) of any of the previous claims, the handle means (40) further comprising a slide ring (506), the slide ring (506) clutching the body (100) with positive locking.

24. The syringe device (1 ) of claim 23, the slide ring (506) and the body (100) comprising a locking against rotation of the slide ring (506) around the retainer tube axis.

25. The syringe device (1 ) of any of the previous claims 23 or 24, the slide ring (506) and the operating element (41 ) being fixed to each other via magnetic forces.

26. The syringe device (1 ) of any of the previous claims 4-25, the body (100) comprising a movable plunger (500), the plunger (500) being configured for exerting a force onto the base element (32) upon movement of the plunger (500), the force separating the base element (32) from the body (100).

27. A syringe device (1 ) comprising a body (100), a cylindrical retainer tube (10) coaxially comprising a wire (20) relatively moveable with respect to the retainer tube (10), a handle means (40) configured for causing the relative movement of the retainer tube (10) and the wire (20), and a base element (32), the retainer tube (10) being received in the base element (32), the base element (32) or the retainer tube (10) comprising an opening (60), the base element (32) and/or the retainer tube (10) having a wall confining an interior space, the wire (20) being at least partially received by the interior space, the opening (60) being comprised in the wall, the wire (20) having a part protruding from the opening (60), the part of the wire (20) protruding from the opening (60) forming the operative connection with the handle means (40).

Description:
Syringe device

The invention relates to a syringe device.

Syringes are known in the prior art and have the capability of taking up liquids or gasses into a barrel. A plunger that fits tightly within the barrel can be linearly pulled and pushed along the inside of the barrel. The principle of taking up liquids or gasses into the barrel can be applied for holding or transferring sample material that may be sucked into the barrel for that purpose. For example, WO 2013082208 A2 discloses a method and apparatus for holding and/or transferring sample material into a second holder.

Summary of the invention

In one aspect, the invention relates to a syringe device comprising a body, a cylindrical retainer tube coaxially comprising a wire relatively moveable with respect to the retainer tube, a handle means configured for causing the relative movement of the retainer tube and the wire, wherein the retainer tube and the wire are separable together from the body.

In another aspect, the invention relates to a syringe device comprising a body, a cylindrical retainer tube coaxially comprising a wire relatively moveable with respect to the retainer tube, a handle means configured for causing the relative movement of the retainer tube and the wire, and a base element, the retainer tube being received in the base element, the handle means

comprising an extension in operative connection with the retainer tube or the wire and configured for causing the relative movement, the base element or the retainer tube comprising an opening, the base element and/or the retainer tube having a cylindrical wall confining an interior space, the wire being at least partially received by the interior space, the opening being comprising in the cylindrical wall, the wire having a part protruding from the opening, the part of the wire protruding from the opening forming the operative connection with the extension.

Brief description of the drawings

In the following embodiments of the invention are explained in greater detail, by way of example only, making reference to the drawings in which:

Fig. 1 is a schematic view of a syringe device,

Fig. 2 is a perspective view in a longitudinal cut,

Fig. 3 shows a section of Fig. 2, wherein cut out A is shown in an enlarged manner,

Fig. 4 shows a further example of a syringe device in a perspective manner in a longitudinal cut,

Fig. 5 shows a further example of a syringe device in a longitudinal cut,

Fig. 6 shows a more detailed and enlarged view of the tip area of the syringe device of Fig. 5,

Fig. 7 shows an enlarged view of a guiding element of the syringe device of Fig. 5,

Fig. 8 shows an enlarged view of an operating element together with its extension,

Fig. 9 shows an enlarged view of a support tube. Detailed description

The descriptions of the various embodiments of the present invention will be presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein is chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

Further, in the following like elements are depicted by the same reference numerals.

The term“wire” is to be understood as any elongated piece of material that is able to serve as a plunger within the retainer tube. The“wire” may be formed of a single solid material or of a set of threads that are entangled with each other. Materials may comprise a metal or a polymer like a polyamide, e.g. Nylon (e.g. Nylon 6), Kapton, PET, COC and POC.

The present disclosure may provide for a possibility of taking up small amounts of material into the retainer tube and then detach the retainer tube from the body for further handling of the taken-up material. Thus, the retainer tube is adapted for receiving a sample material via its opening at the distal end of the retainer tube.

For example, the material may be analyzed in an X-ray machine wherein due to the possibility of removing the retainer tube together with the wire from the body the material taken up in the retainer tube can remain in the retainer tube at a position defined by the position of the wire. Further, the geometrical dimensions of the retainer tube can be kept rather small compared to the whole syringe device comprising the body such that the retainer tube can be easily transported and handled by other machines. One specific example of usage of the syringe device is crystal harvesting: the retainer tube may be configured for taking up crystals. To harvest a crystal, the cylindrical retainer tube may be inserted into the mother liquor, pointing towards a crystal. By pulling back the wire, the crystal is absorbed together with its mother liquor into the cylindrical retainer tube.

After detachment of the retainer tube and the wire from the body, the retainer tube can be inserted into a high-pressure cooler for cooling of the crystal as a preparation step for subsequent X-ray crystallography. Due to the cooling at high pressure, high-density amorphous ice is formed such that cryoprotective agents are not necessary here in order to avoid damaging of the crystals.

Another specific example of usage of the syringe device is cell and

tissue harvesting: To pick up cells, clusters of connected cells or

pieces of tissue dissolved in a storage solution, the retainer tube may be inserted in said solution, and cells, clusters of cells or pieces of

tissue may be absorbed by pulling back the wire.

In an embodiment of the invention for said example, the surface of the wire may be pretreated in a way such that targeted cells or tissues

specifically bind to the wire by biochemical or physical means.

In another embodiment of the invention, and to ease pickup of targeted material by the device, the wire may be realized as an optical fiber.

Light generated by a light source installed on the device may be coupled into the wire such that targeted material bound to the optical fiber

wire is illuminated or transformed by means of frustrated total internal reflection. As an example and to improve the optical contrast during the pickup, the targeted material may be charged with luminescent markers like fluorescent dyes

Embodiments of the invention may further have the advantage that extremely small amounts of liquid material may be sucked into the retainer tube, preferably amounts in between 50-150 nl, wherein the uptake can be made with high accuracy. Nevertheless, the mechanical setup is designed in such a manner that the syringe device can be manufactured at reasonable costs but nevertheless rather high precision.

In accordance with an embodiment of the invention, the handle means is comprising an operating element configured for causing the relative movement upon operation of the operating element, the operating element being moveable relative in parallel to the retainer tube axis and outside of the retainer tube axis. As the‘tube axis’, the present disclosure always

understands the cylinder axis of the retainer tube.

In accordance with an embodiment of the invention, the inner diameter of the retainer tube corresponds approximately to the outer diameter of the wire. The diameter difference between the wire and the retainer tube is selected such that on one hand the retainer tube and the wire are still easily moveable relative to each other and that on the other hand no air or liquids can penetrate the area between the wire and the retainer tube in which the retainer tube is in contact with the wire - this principle is known as such from standard syringes. For example, in case of a retainer tube of 250 pm inner diameter, a wire with diameter of 220 pm may be used.

In accordance with an embodiment of the invention, the syringe device is further comprising a base element, the retainer tube being received in the base element, the handle means comprising an extension in operative connection with the retainer tube or the wire and configured for causing the relative movement. It has to be noted here, that for realizing embodiments of the invention the extension is not inevitably necessary. Thus, any

embodiments of the invention may also be realized without the extension by having handle means that are in direct operative connection with the retainer tube or the wire and configured for causing the relative movement. In one embodiment, the operating element is comprising the extension, for example the extension may be protruding from the operating element. In accordance with a further embodiment of the invention, the retainer tube, the wire and the base element are separable together from the body.

The usage of the base element may have the benefit that the syringe device is easier to handle. Especially in case of extremely thin retainer tubes, attaching and detaching a retainer tube itself to and from the body may be difficult to achieve without a high risk of damaging of the retainer tube. By having a base element which has received the retainer tube, the base element may be constructed in a much larger and handy manner with good gripping capabilities such that by attaching and detaching the base element to and from the body the risk of damage to the retainer tube while performing such attachment or detachment is minimized. In the above example, the retainer tube may have an outer diameter of 300 pm, whereas the diameter of the base element may be much larger, for example 0,5-1 cm.

In accordance with a further embodiment, the body is adapted for supporting the handle means, the base element and the body being fixed to each other by magnetic forces. Thus, the separation of the base element from the body is possible by overcoming the magnetic forces of attachment. Preferably, the base element and the body are designed in such a manner that upon attachment of the base element to the body the base element is automatically forced into a desired position on the body by the magnetic forces. This may allow for a highly accurate operation of the syringe device since the handle means always have the same orientation with respect to the base element and thus the cylindrical retainer tube. Generally, the body may be reusable together with the handle means, whereas the retainer tube or the combination of base element and retainer tube are disposable elements.

In accordance with an embodiment of the invention, the base element is comprising a support tube, the retainer tube is fixed to the base element via the support tube and the retainer tube is coaxially received in the support tube and protruding the support tube. This may permit for an easy manufacturing of the syringe device since even rather thin retainer tubes can be fixed to the base element by for example gluing the retainer tube into the support tube. The outer diameter of the support tube is rather irrelevant here since the support tube functions as a kind of adaptor through which the retainer tube can be fixed to the base element.

For example, the material of the support tube is different from the material of the retainer tube. In a further example, the material of the support tube is comprising a metal and/or the material of the retainer tube is comprising glass or a polymer. Such kind of material combinations may be beneficial since different parts of the syringe device can be designed for rather specific purposes in a free manner: a retainer tube made up from glass, especially quartz glass or a polymer like a polyimide like Kapton® are more or less transparent to many kinds of X-ray sources such that a corresponding retainer tube holding a material inside can be directly used in respective X-ray machines for X-ray analysis of the material. On the other hand, the usage of a metal for the support tube can provide a high mechanical stability to the support tube and thus a mechanically strong interface between the retainer tube and the base element. Further, the usage of a metal, especially a metal like copper, may have the advantage of an excellent heat transfer capability such that a cryocooling of a material that was sucked into and is now contained in the retainer tube can be performed in a rather efficient and quick manner.

In accordance with an embodiment of the invention, the retainer tube is fixed to the base element, wherein the syringe device further comprises a guiding element, the extension being in operative connection with the wire via the guiding element, the guiding element being moveable preferably relatively to the base element via the handle means by the element along the axis and configured for causing the relative movement of the wire. Flere, the retainer tube can either be directly or immediately fixed to the base element or it can be fixed to the base element via the above-mentioned support tube.

For example, the guiding element is comprising a recess configured for receiving the extension. Flere, the wire may be fixed to the guiding element and the extension is in operative connection with the guiding element. In the direction of the relative movement of the wire, the recess of the guiding element and the extension provide for a positive locking.

Generally, the usage of a guiding element may be beneficial since it is rather easy to mechanically contact the guiding element via the extension rather than trying to attempt to directly move the thin wire with the extension.

In one example, the base element is having an interior space, the interior space comprising the guiding element that is preferably arranged coaxially with respect to the retainer tube, the base element comprising a slot to the interior space, the extension extending through the slot for being in the operative connection with the wire via the guiding element. It has to be noted here that either the base element itself may have the slot or the support tube that optionally is attached to the base element may have the slot. In any case, the guiding element is located inside the base element and it can be moved by the extension that is extending through the slot into the guiding element within the base element. This may be beneficial since the number of mechanically moveable components which are located outside the retainer tube or the base element can be kept small. Thus, this may provide for a rather highly mechanically robust setup since it may be‘difficult’ to damage this setup since the mechanically sensible parts that have attached the thin wire are protected and shielded from the outside within the base element.

In another embodiment, the base element or the retainer tube comprise an opening, wherein the base element and/or the retainer tube have a cylindrical wall confining a material space, the wire being at least partially received by the interior space, the opening being comprised in the cylindrical wall, the wire having a part protruding from the opening, the part of the wire protruding from the opening forming the operative connection with the extension. Thus, the wire is protruding to a section of the syringe device offset to the retainer tube axis outside the base element and the retainer tube and the operative connection of the extension with the wire is in this section. This may have the advantage that the formation of the operative connection between the wire and the extension is simplified due to the open accessibility of the wire outside the base element or the retainer tube. In the above example of the base element comprising the support tube, the support tube itself may have the opening. Again this may be beneficial since providing an opening to a support tube should be typically easier than providing a respective opening especially to the retainer tube itself. For example, the support tube may be made of a metal such that this opening may be drilled in a desired manner into the support tube, which due to the choice of metal material has a sufficiently high mechanical stability to withstand the drilling. The drilling can be made in many different ways, including conventional mechanical drilling, laser drilling and water jet drilling.

In a further example, the part of the wire that is protruding from the opening is fixed to the guiding element such that in this case the syringe device additionally comprises such a guiding element. Consequently, the guiding element is outside the base element or the retainer tube and again is therefore easily accessible for forming an interconnection between the wire and the guiding element. For example, the wire can be attached to the guiding element by gluing in a manufacturing process in a rather efficient manner since outside the base element and the retainer tube both the guiding element and the wire are freely accessible for such a fixation process.

In case of making use of the guiding element, the base element is providing an outer sliding surface supporting the guiding element and facing away from the retainer tube axis, wherein the guiding element is moveable along the sliding surface. This may have the benefit that the syringe device can be designed for being operated in a‘smooth-running manner’: the sliding surface can be provided in order to minimize the friction forces due to the movement between the guiding element and the base element (that optionally has the support tube that itself may have this sliding surface). Thus, in an embodiment the support tube is providing the outer sliding surface. In accordance with an embodiment, the guiding element is clutching the base element with positive locking. Here, the only movement the guiding element can freely perform is the movement along the cylindrical axis of the retainer tube. Thus, a movement in radial direction is prohibited such that the syringe device may be mechanically more stable.

In an example, the guiding element is a cylindrical inner wall that is supported by the sliding surface that may also have such kind of cylindrical shape.

In accordance with an embodiment of the invention, the guiding element and the base element are comprising a locking against a rotation of the guiding element around the retainer tube axis. For example, a slot or multiple slots may be provided in the base element or the support tube, wherein the slots are provided in the axial direction, wherein a pin of the guiding element is engaging with the slot. The locking against the rotation may be beneficial since an unintended movement of the wire due to a rotation only of the guiding element is avoided. Thus, the only possibility of moving the wire is a movement of the guiding element by the handle means in the axial direction of the cylindrical retainer tube.

In accordance with an embodiment of the invention, the guiding element is having a face side pointing in the direction of the retainer tube axis, the face side comprising a set of holes distributed around the retainer tube axis, wherein in one of the holes the part of the wire protruding from the opening is received and fixed to the guiding element. Provision of a set of holes instead of only a single hole may allow for an easier manufacturing of the syringe device since even in case the fixation of the wire to one of the holes fails, a set of further holes are still available that can be used for the fixation purpose.

In accordance with an embodiment of the invention, the opening is provided by a tubular channel having a channel axis, wherein the angle between the channel axis and the retainer tube axis is lower than 30°, preferably lower than 10°. Such small angles may be beneficial since any frictional forces between the wire and the base element or the retainer tube have this opening is minimized due to only a rather small bending of the wire when running over the edges of the opening.

In accordance with a further embodiment of the invention, the wire is fixed to the base element, wherein the retainer tube is moveable via the handle means by the element along the axis and configured for causing the relative movement of the wire. While the above examples were based on the principle that the base element and the retainer tube are provided in a fixed position relative to the body and the wire is moveable, this embodiment vice versa now assumes that the wire and the base element are provided in a position fixed with respect to the holder while the retainer tube itself is moveable via the handle means along the axis. For example, the base element may again carry the support tube such that the retainer tube is moveable via the handle means within the support tube.

In accordance with an embodiment of the invention, the handle means are further comprising a slide ring, wherein the slide ring is clutching the body with positive locking. Thus, in radial direction with respect to the axis of the retainer tube there is no freedom of movement given to the slide ring. The holder may again provide a respective sliding surface for the slide ring such that the slide ring can slide along this surface in the axial direction of the retainer tube.

For example, the slide ring and the body are comprising again a locking against a rotation of the slide ring around the retainer tube axis. Regarding possible advantages reference is made to the above discussion regarding the guiding element which advantages can be applied here in an analogous manner.

In accordance with an embodiment of the invention, the slide ring and the operating element are fixed to each other via magnetic forces. Thus, the slide ring may comprise a magnet and the operating element may comprise a metallic material that is magnetically attachable to this magnet of the slide ring. Thus, the operating element is reversibly detachable from the slide ring such that the operating element may be removed from the syringe device after performing the desired suction process, i.e. after pulling back the operating element and thus moving back the wire and sucking in material into the retainer tube. Since thereafter the operating element can be removed from the syringe device, the extension is not anymore in a positive locking with the wire or the guiding element. Therefore, the syringe device is free of any parts that could prohibit or disturb a subsequent separation of the retainer tube and wire from the body. A further benefit may be that accidental operation of the syringe device in terms of moving the wire is prohibited.

In accordance with an embodiment of the invention, the body is comprising a moveable plunger, the plunger being configured for exerting a force onto the base element upon movement of the plunger, the force separating the base element from the body. This may provide for an easy one-handed possibility of removing the base element and thus the retainer tube from the body. For example, while the retainer tube and the base element are still connected to each other, the syringe device may be moved to a respective transfer unit that can receive the base element together with the retainer tube. When the base element and the retainer tube are at a respective correct position in the transfer unit, the plunger may be pressed or moved such that thereupon the base element is separated from the holder and remains in the transfer unit for further usage.

In another aspect, the invention relates to a syringe device comprising a body, a cylindrical retainer tube coaxially comprising a wire relatively moveable with respect to the retainer tube, a handle means configured for causing the relative movement of the retainer tube and the wire, and a base element. The retainer tube is received in the base element and the base element or the retainer tube are comprising an opening. The base element and the retainer tube are having a wall confining an interior space, wherein the wire is at least partially received by the interior space and the opening is comprised in the wall, wherein the wire is having a part protruding from the opening. The part of the wire protruding from the opening is forming the operative connection with the handle means. It has to be noted that the above described embodiments can be freely combined with each other as long as the combinations do not exclude each other.

Fig. 1 shows a schematic view of a syringe device 1 which comprises a body 100 and a cylindrical retainer tube 10 that is coaxially comprising a wire 20 moveable with respect to the retainer tube 10. Further, a handle means 40 is provided that is configured for causing the relative movement of the retainer tube and the wire. By moving the handle 40 forth and back, material can be moved in and out of the tip of the retainer tube.

While in Fig. 1 a the body 100 and the retainer tube 10 were fixed to each other, in Fig. 1 b the retainer tube 10 is separated from the body 100. This separated cylindrical retainer tube 10 may then be used for further purposes, like for example for analysis of the material that was sucked into the retainer tube by retracting the wire 20.

Fig. 2 schematically shows a further example of a syringe device 1 for receiving a sample or holding a sample (not shown). A retainer tube 10, for example a small capillary is held by a support tube 30. It is also possible that the retainer tube and the support tube form a single element of a single material. Coaxially to the cylindrical axis of the retainer tube a wire 20 is provided, for example a nylon thread, a wire or a thin needle. The retainer tube 10 and the wire 20 are moveable relative to each other. An enlarged version of the tip area of Fig. 2 is shown in Fig. 3.

The syringe device further comprises a handle means 40 in order to achieve the above mentioned relative movement of the retainer tube 10 and the wire 20. Therefore, the handle comprises an operating element 41 that is operable in order to cause the relative movement. This could be done manually by for example pushing on one distal end of the operating element 41 , or by means of a mechanical drive that for example makes use of an electrical motor. In the example shown in Fig. 2 an operation of the operating element against the restoring force of the spring element 43 causes a movement of the extension 42. The extension 42 is part of the handle means and extends perpendicularly from the operating element. In the given example, the extension 42 is fixed to the operating element 41 by means of a bolted connection. The operating element 41 is moveable parallel to the axis of the retainer tube 10 and laterally offset to the retainer tube axis.

The lower end of the extension 42 is clutching a guiding element 21 with positive locking. For that reason, the guiding element 21 comprises a recess 22 that is receiving the extension 42 - the extension 42 extends through the recess 22 into the guiding element 21. The guiding element 21 is located in the rear part of the support tube 30 and is moveable along the axis of the retainer tube 10. The wire 20 is fixed to the guiding element 21.

The support tube 30 comprises a slot, like for example an elongated hole, through which the lower part of the extension 42 can extend. In case the extension 42 is moving parallel to the axis of the retainer tube 10, the guiding element 21 and thus the wire are moved. Consequently, the wire 20 is moved in axial direction within the retainer tube 10.

The slot 31 thereby limits the way of movement. Expediently this way of movement is chosen in such a manner that in case of a pressed operating element 41 the front end of the wire 20 is at a level with the distal front end (the opening) of the retainer tube 10, or even that in this case the wire slightly extends out of the front end of the retainer tube.

Releasing the pressure acting onto the operating element 41 leads to a restoring force by the spring element 43 and thus to a backwards directed movement of the extension 42 and consequently a backward movement of the wire 20 within the port tube 30 and the retainer tube 10.

As shown in Fig. 1 , the support tube is fixed to a base element 32. It is also possible, that the support element and the base element form a single element, i.e. the support tube is integrally formed with the base element. The above-mentioned slot 31 can also be part of the base element 32 or, as shown in Figs. 2 and 3, it can be part of the support tube 30.

In the example of Fig. 2, the base element 32 is coupled to a tube holder 50 of the syringe device 1 in a magnetic manner, such that the base element 32 together with the support tube 30, the wire 20 and the retainer tube 10 is reversibly attachable and detachable from the tube holder 50. The tube holder 50 is fixed to the body 100 of the syringe device 1. It is also the body 100 that carries at least partially the operating element 41 , the spring element 43 and at least part of the mechanism that permits for a movement of the guiding element and thus the extension 42.

It may be advantageous in case only the support tube 30 is detachable together with the wire 20 and the retainer tube 10 from the tube holder 50. Further possible is that the retainer tube 10 is detachable from the tube holder 50 together with the wire 20. In case of the presence of the base element 32 and the support tube 30, the retainer tube 10 may be detachable from the support tube 30 together with the wire 20. In case of the presence of the base element 32, the support tube 30 and the retainer tube 10, the retainer tube 10 may be fixed to the support tube 30 and the support tube 30 may be detachable from the base element 32.

Generally, any of the above-mentioned components may be attached to each other in a form locking or force locking way in order to reversibly permit the attachment and detachment of these elements. The usage of a magnetic coupling, especially between the tube holder 50 and the base element 32 may be especially advantageous.

Instead of having a mechanism of the handle means for which pushing of the operating element 42 causes a movement of the extension 42 towards the tip direction, it is also possible to reverse the operation of the handle means such that pushing of the operating element causes a retraction of the wire 20 within the support tube 30 and the retainer tube 10. A respective inverse setup of the mechanics of the handle means is within the capabilities of a skilled person. For example, the outer diameter of the wire 20 corresponds more or less to the inner diameter of the retainer tube 10 which maximizes the suction effect when retracting the wire within the retainer tube.

Using the syringe device 1 of Fig. 2 it is possible for example to receive a protein crystal that is located in a fluid inside the retainer tube 10. For this purpose, the operating element 41 is operated and the retainer tube is moved to the crystal that is to be taken up. By slowly losing the operating element 41 and thus retracting the wire 20, the crystal is sucked into the interior of the retainer tube. In this manner it is possible to suck one or more crystals together with the fluid surrounding the crystals by operating the operating element into the interior of the retainer tube 10 in a controlled manner.

Further, it is possible, that fluid and/or crystals can be ejected from the retainer tube 10 by pushing the operating element 41 , in case for example the desired crystal was missed or was located within the retainer tube 10 at an undesired position. By repeatedly sucking in and ejecting liquid the desired crystals can be selected and positioned within the retainer tube 10. Similarly, it is possible to optimize the amount of liquid that is located within the retainer tube 10 in a similar manner. This may permit a later investigation of the crystal or the crystals in a highly qualitative manner since the amount of liquid that could be disturbed can be accordingly minimized. For later experiments on the crystals and investigations of the crystals the retainer tube can be detached together with the wire and optionally together with the support tube and the optional base element 32 from the body 100.

Fig. 3 is an enlarged view of the tip area of the syringe device 1 of Fig. 2 in a slightly modified manner. Similar elements are designated with the same reference numerals as in Fig. 2. Compared to Fig. 2 the tube holder 50 is modified. The base element 32 is also magnetically attachable to the tube holder 50 of the syringe device 1 in order to permit for a reversible removal of the retainer tube, optionally together with the support tube and the base element. Clearly visible is the wire 20 within the retainer tube 10, wherein the retainer tube 10 is received within the support tube 30.

Fig. 4 shows a further example of a syringe device 1 , wherein in this example the support tube 30 is fixed to the retainer tube 10 and moveable together with the retainer tube 10 along the axis of the cylindrical retainer tube 10. The wire 20 is stationary, i.e. it cannot move. As was described above with respect to Fig. 2, the handle means 40 comprises an extension 42 which extension is moveable by the operating element 41. Flowever, compared to the example of Fig. 2, the extension 42 engages with the support tube 30 in a positive locking manner, in order to move the support tube 30 relative to the stationary wire 20.

All the further technical details of Fig. 4 are similar or identical to the respective technical details of Fig. 2, such that the discussion regarding Fig. 2 can be applied in an analogous manner to Fig. 4.

Fig. 5 shows a further example of a syringe device in a cross-sectional view. The syringe device 1 has a tip region that is shown in an enlarged manner in Fig. 6. Generally, the syringe device 1 comprises a body 100 which carries a base element 32. The base element 32 is magnetically attached to the body 100. For example, a tube holder 50 that is part of the holder 100 comprises one or several magnets, wherein the base element 32 is magnetically attracted by these magnets.

The base element 32 comprises a recess 62 in which a support tube 30 is received. The support tube 30 has a cylindrical shape and has itself received a retainer tube 10. Typically, the support tube 30 is made of a mechanically stable material like a metal and the retainer tube 10 is made of a material like a polymer, for example Kapton. Different materials are also possible like PC, COC, POC and PET.

The cylindrical retainer tube 10 coaxially comprises a wire 20 like for example a nylon wire. Movement of the wire 20 relative to the retainer tube 10 permits for sucking or expelling material into and from the tip of the retainer tube 10. Here, the general principles apply as discussed above with respect to Figs. 2- 4.

The syringe device 1 further comprises a guiding element 21 which is sliding on an outer sliding surface of the support tube 30. Attached to the guiding element 21 is an end portion of the wire 20. The end portion of the wire 20 is protruding from an opening 60 of the support tube 30. Thus, the wire 20 extends from within the retainer tube 10 into the support tube 30, then through the opening 60 and then to the guiding element 21 , which holds the wire. Therefore, by movement of the guiding element 21 in the axial direction of the retainer tube and the support tube, the wire is moved in the axial direction within the retainer tube 10. This movement leads to a change of the free volume within the retainer tube 10 which is used to take up material.

Fig. 7 shows an enlarged version of the guiding element 21. The guiding element 21 also has a tube shape and a tubular passage 71 which is adapted to slide on the outer surface of the support tube 30. This leads to a clutching of the guiding element 21 with the support tube 30 with positive locking. Thus, any movement in radial direction of the tube of the guiding element is impossible.

The guiding element 21 has a face side pointing in the direction of the retainer tube axis towards the tip end of the retainer tube, wherein the face side comprises a set of holes 70 that are distributed around the retainer tube axis. The holes can be used to take up the wire 20 thus permitting an easy way of assembly of the wire and the guiding element. Any one of these holes 70 can be used to take up the end of the wire 20 that is protruding from the opening 60, wherein thereupon this end of the wire can be permanently fixed to the guiding element by for example adding glue to the hole 70 that has taken up the end of the wire.

In order to avoid an unintentional rotation of the guiding element 21 around the retainer tube axis, the guiding element 21 and the support tube 30 may comprise a locking against said rotation. The locking is for example realized via a protrusion 72 of the tubular passage 71 that engages with a respective notch on the outer surface of the support tube 30.

In order to permit for a movement of the guiding element 21 on the support tube 30, a handle means 40 as perspectively shown in Fig. 8 is provided. The handle means 40 comprises an extension 42 that can be brought in operative connection with the guiding element 21.

The guiding element 21 that is of cylindrical shape comprises a

circumferential notch 22 into which the element 42 can engage. Upon the engagement, the guiding element and the handle means are coupled to each other in a positively locked manner such that a movement of the handle means 40 in the axial direction of the retainer tube 10 will cause for a sliding movement of the guiding element 21 along the surface of the support tube 30.

The handle means 40 comprises an operating element 42 that is moveable relative and parallel to the retainer tube axis and outside of the retainer tube axis. The operating element carries the extension 42.

As can be seen in Fig. 5, the handle means further comprises a slide ring 506 which is adapted to clutch the body 100 with positive locking such that the slide ring 506 can slide in axial direction of the retainer tube 10. The slide ring 506 and the operating element 41 can be fixed to each other via magnetic forces. For that purpose, the slide ring 506 may comprise for example a magnet, wherein a contact area 800 of the operating element 41 (see figure 8) can be magnetically attached.

In order to remove the retainer tube from the body 100, in a first step the operating element 41 may be detached from the slide ring 506. For example, the operating element 41 may just be pulled away perpendicularly to the retainer tube axis. A disengagement of the extension 42 from the notch 22 is easily achievable since the positive locking between the extension 42 and the notch 22 is only in the direction of the retainer tube axis. After removal of the operating element 41 , the base element 32 may be detached from the holder 50 and therefore from the tube 100. For that purpose, a plunger 500 may be used that is located on the rear side of the syringe device 1. The plunger is moveable in the axial direction of the retainer tube axis and configured for exerting a force onto the base element 32 upon movement of the plunger towards the base element 32. A spring element 502 is provided that serves the purpose of providing a restoring force onto the plunger 500 when the pressing of the plunger 500 is released. Thus, by means of the spring element 502 the plunger is moved back into its initial position.

A piston 504 is mechanically attached to the plunger 500 such that a movement of the plunger 500 leads to a movement of the piston 504. The distal end of the piston 504 is mounted within the ring-shaped holder 50 and can get into contact with the rearward face of the base element 32. Thus, by exerting a force by pushing the plunger 500 towards the base element 32, the distal end of the piston 504 is pushed through the holder 50 onto the base element 32. Due to this exerted force, the magnetic force currently acting in between the base element 32 and the holder 50 is overcome such that the base element 32 is thereby detached from the holder 50 and thus the body 100.

It has to be noted here that this mechanism comprising the plunger 500 and the piston 504 together with the spring element 502 is only optional. It may also be possible to manually detach the base element 32 from the holder 50 by for example pulling the base element 32 away from the holder 100. A pair of scissors may be used for that purpose, wherein the scissors may grip the outer surface of the part of the base element that forms the recess 62.

Fig. 9 schematically shows an example of a support tube 30. The support tube 30 comprises the above-mentioned opening 60. The opening 60 is provided by a tubular channel having a channel axis, wherein the angle between the channel axis and the retainer tube axis is lower than 30°. Preferably, the angle is lower than 10°. This may permit for a smooth sliding of the wire from outside into the interior space of the support tube 30 and from there into the retainer tube 10.

In an example, the above described syringe device may be suitable for example for high pressure cooling of protein crystals. To fit the needs of the high-pressure cooler, crystals may be harvested with specially fabricated sample units like the retainer tube discussed above. The retainer tube may be comprised in the base element together with or without the support tube. A polyimide capillary (retainer tube) with 250 pm inner diameter is for example used. The capillary is cut to form an angled tip and to a length of 5 mm. A nylon thread (i.e. wire) with diameter of 220 pm is inserted into the polyimide capillary. The capillary is attached to a copper pin (support tube). The nylon thread may protrude up to 1 mm out of the copper and within the polyimide capillary.

The copper pin itself may be mounted to a pin holder (base element). This assembly may altogether be termed a“sample unit”. It can be extended after the cooling process to fit a SPINE standard for automated sample mounting (sample unit together with the extension is called sample holder).

The sample units may be pre-treated with 80 % (v/v) ethanol in an ultrasonic bath and dried on a heat plate. This may change the wettability of the polyimide capillary remarkably. To harvest a crystal, the capillary may be inserted into the mother liquor, pointing towards a crystal. By retracting the wire, the crystal is absorbed together with its mother liquor. Absorbing of the crystal together with the mother liquor may also be due to capillary forces - here, the tip of the wire inside the capillary forms a stop for the crystal and the liquor inside the capillary.

A high-pressure cooler e.g. based on the Leica EM ICE system may be used modified to fit the needs of protein crystallography. Sample units may be inserted into a cylindrical cartridge in the loading station. When a cooling cycle is started, the sample unit together with the cartridge may be transferred to a high-pressure chamber, where the sample may then be cooled with pressurized liquid nitrogen.

List of reference numerals

syringe device

retainer tube

wire

guiding element

notch

support tube

slot

base element

handle means

operating element

extension

spring element

tube holder

opening

recess

hole

passage

protrusion

body

plunger

spring element

piston

slide ring

contact area