EP1212249A1

EP1212249A1 - Method and device for picking and placing objects

Info

Publication number: EP1212249A1
Application number: EP00962366A
Authority: EP
Inventors: Kristina Schmidt; Dirk Vetter
Original assignee: Graffinity Pharmaceutical Design GmbH
Current assignee: Graffinity Pharmaceutical Design GmbH
Priority date: 1999-09-01
Filing date: 2000-08-23
Publication date: 2002-06-12
Also published as: AU7412400A; DE19941661A1; US6695369B2; US20020135190A1; DE19941661B4; WO2001016004A1

Abstract

The invention relates to a device and a method for picking individual objects (14) or particles and placing them in containers or cavities (16) filled with liquid. Prior to each transport operation for an object, an adhesive (12) is applied to one surface (10) of a transport device (2) and this surface (10) is brought into contact with the object (14), in order to transport the latter. To release the object (14) from the transport device (2), the adhesive force of the adhesive (12) is reduced, so that said adhesive becomes detached from the transport device (2).

Description

DEVICE AND PROCEDURE TO TAKE AND PLACE

OF OBJECTS

The invention relates to an apparatus and a method for picking up individual objects or particles and depositing them in containers or cavities filled with liquid.

Several methods are known for picking up, moving and placing objects or particles (pick-and-place operations).

If the objects to be picked up are comparatively large and heavy, gripping devices are often used. In EP-A-0 671 351, for example, picking up and putting down is realized with the aid of such gripping devices. A disadvantage of these devices is the enormous technical effort for their construction and their poor miniaturization.

These disadvantages are also generally evident when using suction devices. DE-A-195 12 155 describes a pick-up and arranging machine which enables the transport and pick-up of particles and their delivery in chambers by means of vacuum technology. Another disadvantage of this device is the complex and expensive equipment with vacuum-stable parts.

As an alternative to these methods, cheaper adhesive devices are usually used for transporting or picking up, in particular for light objects. A disadvantage of conventional methods according to the known prior art is that the detachment of the object from the adhesive surface after placement, for example by stripping or spinning, makes an exact placement difficult or impossible. Remaining adhesive residues on the object to be transported can also be a hindrance. If used several times, the adhesive force drops, so that it is necessary to replace the device or renew the adhesive surface. Examples of receiving and transporting devices that use adhesive surfaces are DE-A-30 10 779, GB-A-2 237 001 or US-A-5 470 116. A disadvantage of these devices is that the removal of the objects in a manual manner and Way must be made. Automation and miniaturization is therefore not possible. High demands are also placed on the adhesive, since it has to be strong enough that the object to be transported adheres during transport, but should be easily removed.

Another example is provided by US 5,553,344. This light object pickup device uses multiple removable sheets of adhesive material. After picking up the items, the contaminated leaves are removed. A disadvantage of this method is that the adhesive surface has to be renewed again and again. Removal of the objects is not intended.

US-A-5 637 395 discloses special adhesives that enable holding during the processing process (e.g. cutting) of a semiconductor wafer. The detachment is achieved by admixing compounds of the adhesive which are photopolymerizable. After exposure, the adhesive strength drops and the wafer peels off. A disadvantage of this invention is that an expensive adhesive must be used.

US-A-4 073 530 discloses a receiving device which carries an adhesive surface at a flexible end. An object is removed by reducing this adhesive surface by means of translatory movement. A disadvantage of this device is that the shape and weight of the object to be picked up must be such that a reduction in the adhesive area is possible. This is not the case with round objects. Another disadvantage is that it cannot be guaranteed that residues of the adhesive material remain on the object to be transported. If the objects to be manipulated are small spherical and light particles, in particular synthetic resin beads, which are used in combinatorial solid-phase synthesis and high-throughput screening, special methods are disclosed which in particular enable individual beads to be assigned to cavities in a microtiter plate.

WO-A-98/17383 describes a possibility of distributing a defined number of beads, which are suitable for use in combinatorial synthesis, into a microtiter plate; however, the beads to be distributed are in a suspension. It is not possible to transport individual particles with this method. The device used requires pipette-like devices whose geometry makes miniaturization difficult.

WO-A-98/32000 discloses picking up individual beads and transferring them to a microtiter plate, the beads being able to be placed in each cavity of the microtiter plate. However, the pearls are also available as a suspension and are therefore not individually controllable. The pearl is taken up by sucking up liquid until a pearl clogs the entrance of the needle. A disadvantage of this method is the high expenditure on equipment, which is caused by the pressure sensor device required.

WO-A-98/08092 describes a method which enables pearls of essentially the same size or dimensions to be arranged in a predetermined grid, such as a microtiter plate. Pearls are filled into a capillary tube. An adhesive layer is used to fix the beads. A disadvantage of this method is that after the beads have been assigned to individual fields, the excess beads have to be removed. The assignment of the pearl fields to each other is also defined. The beads in the arrays can only be transferred as a whole into the capillary system through the shadow mask. It is therefore not possible to control the beads individually to form the wells of a microtiter plate. Consequently, in principle only beads of the same size can be handled with this method. Furthermore the settling of drops of adhesive to form the adhesive layer is relatively complex, whereby the process costs are comparatively high.

The object of the invention is to create an improved device and an improved method for picking up small objects or particles and depositing them in containers or cavities filled with liquid. In particular, the disadvantages of the prior art described above are to be avoided. In particular, the device according to the invention and the method according to the invention are intended to be suitable for handling synthetic beads which are used in combinatorial solid-phase chemistry for creating combinatorial substance libraries. This object is achieved with the features of the claims.

The invention is based on the basic idea of providing a surface of a transport device with an adhesive substance of an adhesive layer or an adhesive (hereinafter referred to simply as “adhesive”) or at least increasing the adhesiveness of an adhesive that may be present, before each transport of an object, this surface is then brought into contact with the object in order to transport it. To detach the object from the transport device, the adhesive force of the adhesive is reduced or the adhesive is substantially completely removed so that it detaches from the transport device.

In the context of the present invention, the terms “transport” and “transfer” are understood to mean the repositioning of an object from a starting or receiving position to an end or placement position. These terms are not tied to any direction.

In a preferred embodiment of the present invention, a corresponding method comprises in particular the following steps: (a) One end of a means suitable for transport, such as a rod or a pen, is immersed in a liquid which is either itself is adhesive or has substances that are adhesive. The end of the object is such that it has a suitably large common surface, ie adhesive surface, when it comes into contact with the objects to be transported.

(b) After removal from the liquid, the adhesive surface is optionally subjected to drying in order to enable the adhesive substances contained in the liquid to be concentrated. This can be done, for example, by simply standing in the air.

(c) Parts of the means of transport which have an adhesive surface are brought into contact with the object to be transported in such a way that lifting and moving or transporting the object is possible.

(d) The object is deposited in a container filled with a liquid or at least one cavity filled with liquid, the adhesive surface between the object to be transported and the means of transport preferably being removed by the liquid, but at least the adhesiveness of the adhesive being considerably reduced, so that the object detaches itself from the means of transport. This can be done, for example, by creating a mixture or solution. The object is released into the container or cavity.

(e) After the item is detached, the process can be repeated any number of times.

Adhesive liquids can be, for example, viscous compounds such as polyethylene glycols or polypropylene glycols. Examples of liquids containing adhesives are aqueous sugar (e.g. glucose, sucrose, maltose) or concentrated salt solutions.

Liquids which make it possible to detach the objects can be, for example, water, aqueous buffer or salt solutions or organic solvents or a splitting reagent which, in the case of synthetic pearls as objects to be transported, at the same time makes it possible to detach compounds which are attached to the pearls. Preferred embodiments of the device according to the invention for carrying out the method according to the invention are explained in more detail below with reference to the drawings, but the invention is not restricted to these. Show it:

1a shows a schematic illustration of a transport device in the form of a pin for use in the pick-and-place device according to the invention without an adhesive layer;

1b shows a schematic illustration of a transport device in the form of a pen for use in the pick-and-place device according to the invention with an adhesive layer;

2 shows a detail of a side view of a transport device to which an object to be transported adheres;

3a shows a vertical section through part of the pick-and-place device according to the invention, in which a plurality of transport devices are arranged to be movable in an array and in the longitudinal direction;

3b shows a vertical section through a further embodiment of part of the pick-and-place device according to the invention, in which a plurality of transport devices are arranged in an array and are resiliently movable in the longitudinal direction;

4 shows a perspective view of the array arrangement shown in section in FIGS. 3a and 3b with the vertically movable transport devices provided with adhesive.

1 a shows a transport device or a transport means in the form of a pin 2, which is designed, for example, in the form of a cylindrical rod or, as shown in the figures, can have the shape of a nail. The shape of the transport device is not critical and can be chosen as long as there is sufficient surface at the end to serve as an adhesive surface. For example, the cross-sectional area of the pin 2 can be circular, oval or polygonal. The pin 2 can be guided manually or automatically, such as with the aid of a robot arm that can be moved three-dimensionally (X, Y and Z directions). In addition, the pin 2 preferably has a mounting device or a flange 6 at its upper end 4 in order to hold it on a carrier element 8 and to guide it if necessary. The mounting device 6 is preferably formed integrally or in one piece with the pin 2. Stainless steels that meet the requirement of being able to be processed very precisely (manufacture, positioning) are particularly suitable. This becomes more evident with increasing miniaturization. Another requirement is resistance to the liquids used (resistance to chemicals). A certain weight of the pins is advantageous so that they return to the original position after vertical movement out of the recess 20; alternatively, this is achieved by "pressing down" (eg using a compression spring).

1b shows a pin 2 which has an adhesive layer 12 on its “tip” or head surface 10 opposite the end 4 provided with the mounting device 6. The layer 12 is preferably only on the surface section that comes into contact with the object 14 to be transported provided in order to keep the required amount of adhesive as small as possible.

2 shows the object 14 to be picked up in the form of a polystyrene bead, as is used in chemical solid-phase synthesis, in a container or a cavity 16, which protects it against lateral displacement. The center of gravity of the object 14 is preferably below the upper edge 18 of the cavity 16. If the area of the pen tip 10 is larger than the cavity 16, the pearl 14 should partially protrude from the cavity 16 in order to be able to contact it without problems. After contacting the adhesive layer 12 provided on the top surface 10 of the pin 2, the object 14 adheres to the adhesive surface 12 and can be lifted out of the cavity by lifting the pin 2 or lowering the plate 8 carrying the cavity 16 14 taken and transported to the desired position. The cavities 14 can be arranged on a plate 8 in the form of a regular grid or array (FIG. 4), but this does not have to be identical to the grid of containers or cavities of a target plate, for example a microtiter plate. Depending on the application, this array can be designed in two or three dimensions. Possible array sizes are 12, 24, 96, 384, 1536, 9216, preferably more than 100. The pin tool preferably has 384 pins.

3a shows a row of an array consisting of pins 2, which are inserted into regularly arranged recesses 20 of the plate 8 up to the mounting device or the flange 6. The arrangement is designed such that it permits vertical movement or deflection of the pins 2, for example to be able to compensate for differences in length of the pins 2 or different object sizes when placed on the objects 14 to be transported. This embodiment is also advantageous because damage or destruction of the objects to be transported can be avoided.

Another embodiment of the storage of the pins 2 in the plate 8 is shown in Fig. 3b. There, the vertical mobility of the pins 2 is made possible by a respective spring 22, which extends over a guide section 24 formed on the pin 2 and is supported in a blind hole 26 provided in the plate 8. When a pin 2 is placed on a pearl 14 located in the cavity 16, the srift 2 can deflect according to this embodiment and thus compensate for existing length differences, handling and manufacturing tolerances, for example.

FIG. 4 shows a receiving head 28 which carries a multiplicity of pins 2. The pins 2 are received in the recesses 20 (not shown here) of the plate 8 by means of their mounting device 6. The number of pins 2 and the spacing of the rows of pins and pin columns of the array head 28 should correspond to the geometry of the supporting plate 8, in particular to the geometry of the respective with a pearl-filled cavity 16 of the plate 8, and the arrangement of the liquid-filled containers (for example a microtiter plate) into which the pearls 14 are released.

It is not necessarily necessary here that the number of cavities 16 of the plate 8 for receiving the objects 14 corresponds to the number of pins 2 or the number of filled containers. There can also be an integer multiple of cavities 16 of the starting plate, which can be accommodated and placed several times in a microtiter plate format, for example, or several microtiter plates. The number of filled containers (the target plate) can also be an integer multiple of the number of pins 2 or the plate or plates intended for lifting the objects 14 out. The use of a robot, on the arm of which the array head 28 made of a plurality of pins 2 is attached, is advantageous here. With a large number of pins 2, a regular arrangement in rows and columns or in a concentric geometry is advantageous. When using a computer-assisted camera, the adjustment of the array head 28 and the entire process can be automated with the aid of suitable software. This achieves a high degree of parallelism in the process and enables an efficient pick-and-place procedure.

Claims

PATENT CLAIMS

1. Method for picking up and placing objects (14) with the method steps: a) immersing at least one section (10) of a transport device (2) in a first liquid which is itself adhesive and/or has adhesive substances in order to form an adhesive layer ( 12) to be formed on the section (10) of the transport device (2); b) removing the section (10) from the first liquid; c) bringing the adhesive layer (12) formed on the transport device (2) into contact with the object (14) to be transported; d) transferring the object (14); and e) depositing the object (14) to be transported by immersing the adhesive layer (12) in a second liquid in order to reduce the adhesive force of the adhesive layer (12) at least to the extent that the object (14) moves away from the section (10) of the transport device (2) replaces.

2. Method for picking up and placing objects (14) with the method steps: a) providing a transport unit (28) for several objects (14) to be transferred with several protruding sections (10), on each of which an adhesive layer (12) is formed ; b) bringing a projecting section (10) of the transport unit (28) into contact with a single object (14) to be transported; c) transferring the objects (14) adhering to the respective adhesive layers (12) by moving the transport unit (28); and d) putting down the objects (14).

3. Method for picking up and placing objects (14) with the

Method steps: a) providing a transport device (2) with an end section (10) for at least one object (14) to be transferred, on which an adhesive layer (12) is formed; b) bringing the adhesive layer (12) formed on the transport device (2) into contact with the object (14) to be transported; c) transferring the object (14); and d) depositing the object (14) to be transported by immersing the adhesive layer (12) in a second liquid in order to reduce the adhesive force of the adhesive layer (12) at least to the extent that the object (14) moves away from the section (10) of the transport device (2) replaces.

4. Method for picking up and placing objects (14) with the method steps: a) providing a transport unit (28) for several objects (14) to be transferred with several transport devices (2) arranged in an array, each with excellent sections (10 ), on each of which an adhesive layer (12) is formed; b) bringing the transport unit into contact with the objects (14) to be transported, the individual transport devices (2) being guided in an axially movable manner in order to grip objects (14) of different sizes; c) transferring the objects (14) adhering to the respective adhesive layers (12) by moving the transport unit (28); and d) putting down the objects (14).

5. A method for picking up and placing objects (14), which is a combination of at least two of the methods described in claims 1 to 4.

6. The method according to any one of claims 2 to 5, wherein the formation of the adhesive layer (12) is formed by immersion in a first liquid which is itself adhesive and/or has adhesive substances.

7. The method according to claim 1, 4 or 5, wherein after forming the adhesive layer (12), the section (10) is subjected to a drying step in order to concentrate the adhesive substances contained in the first liquid.

8. The method according to any one of claims 1 to 7, wherein the transport unit (28) and / or transport device (2) is moved manually or automatically.

9. The method according to claim 8, wherein the transport unit (28) and / or transport device (2) is moved automatically by attaching it to a robot.

10. The method according to any one of claims 1, 3 and 5 to 9, wherein several transport devices (2) are arranged as a transport unit (28) in an array in order to transfer several objects (14) at the same time.

11. The method according to any one of claims 2 and 4 to 10, wherein the object (14) to be transported is deposited by immersing the adhesive layer (12) in a liquid in order to reduce the adhesive force of the adhesive layer (12) at least to the extent that the object (14) detaches from the section (10) of the transport device (2).

12. The method according to any one of claims 1, 3 and 5 to 11, wherein the object to be transported (14) is deposited by dissolving the adhesive layer (12).

13. The method according to any one of claims 1, 3 and 5 to 12, wherein the object (14) to be transported is deposited by immersing the adhesive layer (12) in a mixture or solution.

14. The method according to any one of claims 1 and 5 to 13, wherein the self-adhesive liquid has viscous compounds.

15. The method according to claim 14, wherein the viscous compounds are polyethylene glycols or polypropylene glycols.

16. The method according to any one of claims 1 and 5 to 15, wherein the liquid containing adhesive substances is aqueous sugar solutions or concentrated salt solutions.

17. The method according to claim 16, wherein the aqueous sugar solutions contain glucose, sucrose or maltose.

18. The method according to any one of claims 1, 3 and 5 to 17, wherein the liquid into which the adhesive layer (12) is immersed to deposit the object (14) is water, aqueous buffer or salt solutions, organic solvents and / or Has elimination reagents.

19. The method according to claim 18, wherein the cleavage reagents simultaneously cause the cleavage of compounds hanging on the object (14).

20. The method according to any one of claims 1 to 19, wherein the objects to be transported (14) are synthesis beads which are used in combinatorial solid-phase chemistry to create combinatorial substance libraries.

1. The method according to any one of claims 1 to 20, wherein the transfer of the object (14) to be transferred is carried out by transporting it through the transport device (2) and / or transport unit (28).

22. The method according to claim 21, wherein the transfer of the object (14) to be transferred is realized in that it is raised and lowered by the transport device (2) and / or transport unit (28) and the transfer is carried out by at least one change between an object -Receiving device and an object placement device takes place.

23. Device for picking up and placing objects (14) with a transport device (2) which has an adhesive layer (12) on its free end section (10) in order to hold an object (14) to be transported, the adhesive layer (12 ) is designed in such a way that when the object (14) is placed down by immersing it in a liquid, its adhesiveness is reduced at least to such an extent that the object (14) detaches itself from the end section (10) of the transport device (12).

24. Device for simultaneously picking up and placing several objects (14) with several transport devices (2) arranged in an array in a transport unit (28), which have an adhesive layer (12) on their respective end section (10), each to be transported Object (14) is assigned exactly one transport device (2).

25. Device for simultaneously picking up and placing several objects (14) with several transport devices (2) arranged in a transport unit (28), which have an adhesive layer (12) on their respective end section (10), the transport devices (2) are guided axially movably in the transport unit (28) in order to grip objects (14) of different sizes.

26. Device for picking up and placing objects (14), which is a combination of at least two of the devices described in claims 23 to 25.

27. Device according to one of claims 23 to 26, wherein the adhesive layer (12) is an adhesive layer formed by immersing at least the end section (10) of the transport device (2) in a liquid, the liquid itself being adhesive and/or having adhesive substances .

28. Device according to one of claims 23 to 27, wherein the transport unit (28) and / or transport device (2) is provided on a robot in order to be moved automatically.

29. Device according to one of claims 23 and 25 to 28, wherein a plurality of transport devices (2) are arranged as a transport unit (28) in an array in order to transfer several objects (14) at the same time.

30. Device according to one of claims 24 to 29, wherein the adhesive layers (12) are designed in such a way that, in order to deposit the objects (14), they reduce their adhesiveness at least to the extent that the objects (14) move away from them by immersing them in a liquid Detach the respective end section (10) of the transport devices (12).

31. Device according to one of claims 23 and 26 to 30, wherein the adhesive layer (12) is designed such that the object (14) to be transported is deposited by dissolving the adhesive layer (12).

32. Device according to one of claims 23 and 26 to 31, wherein the liquid into which the adhesive layer (12) is immersed to reduce its adhesive force is a mixture or solution.

33. Device according to one of claims 27 to 32, wherein the self-adhesive liquid has viscous compounds.

34. The device according to claim 33, wherein the viscous compounds are polyethylene glycols or polypropylene glycols.

35. Device according to one of claims 27 to 34, wherein the liquid containing adhesive substances is aqueous sugar solutions or concentrated salt solutions.

36. The device according to claim 35, wherein the aqueous sugar solutions comprise glucose, sucrose or maltose.

37. Device according to one of claims 23 and 26 to 36, wherein the liquid into which the adhesive layer (12) is immersed to deposit the object (14) is water, has aqueous buffer or salt solutions, organic solvents and / or release reagents .

38. The device according to claim 37, wherein the cleavage reagents simultaneously cause the cleavage of compounds hanging on the object (14).

39. Device according to one of claims 23 to 38, wherein the objects to be transported (14) are synthesis beads which are used in combinatorial solid-phase chemistry to create combinatorial substance libraries.