DE2710702C3 - Pipette changing device - Google Patents

Description

a) a pipette insertion device (1 to 20) for inserting pipettes into a dividing and Injection device,

b) a pipette feeder device (31 to 51) for feeding the pipettes to the insertion device, and

c) a pipette transfer device arranged between the feed device and the insertion device (62) for transferring the pipettes to the insertion device arranged in the automatically operating system, wherein

a) the pipette insertion device is a guide attached to a housing (1) (3) vertically up and down displaceably guided lifting rod (4, 5), one relative to the Lifting rod rotatable and together with her up and down movable shaft (6,9), one at the lower end of the vertically displaceable shaft attached support arm (19) and a pipette holder (20) attached to one end of the support arm and having a line (21) for aspirating a sample Od. The like. Has, and the support arm for inserting a pipette (22) into the holder is guided vertically movable and rotatable,

b) the pipette feeder device has a housing (31 to 33) for the receptacle at least one holder (34) with a plurality of mutually spaced apart in one Row of pipettes (36) inserted therein, a feed device (39 to 43) for advancing the pipette holder in its longitudinal direction and a pipette ejector device (45) with an ejector plunger (47) guided vertically up and down on the housing for ejecting the Has individual pipettes, the pipette holder from the feed device can be advanced in its longitudinal direction and the ejector plunger can each be moved downwards when a pipette is in a predetermined position to the ejector, so that the pipettes are successively ejected from the holder and

c) the pipette transfer device (62) has a bottom (jib) and an outlet (7 \ a) and an inlet (76a ^ having, hollow housing (71), a support plate (74) arranged in the housing and having a guide slot (74a ) has a rotatable part (73, 75) for receiving and guided movement in each case of a pipette (70) and ₍₎ , which prevents contact between the atmosphere on the inlet side and the atmosphere on the outlet side and for moving the pipette along the _m . Guide slot can be actuated.

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50 The invention relates to a pipette changing device for use in an automatic system for the culture of biological tissues and cells.

It is closed in almost every field of medicine, biology, pharmacy, agriculture and the like For research purposes, tissue and cell cultures are inevitable.

The creation and handling of such cultures requires special care and Training, as it is important to maintain conditions that are as constant as possible in terms of ambient atmosphere, temperature, Maintain moisture and the like. It is also a disadvantage if the access from outside air possibly containing foreign bacteria to the cultures is made possible. One currently in use Process for the creation of cultures from cells, for example the liver, the nervous system, the Pituitary gland, etc. have the following disadvantages. For the microscopic examination of the culture or Cell condition, the culture container must often be removed from the incubator used and the free one Exposed to air. As a result, however, the environmental conditions of the culture are changed, which is affects the cultures that have been set. In addition, the access to air can cause an infestation with saprophytes. Another disadvantage of the known method of operation is that the handling of the cultures one Laboratory technician, so the results depend heavily on his ability or experience.

In order to avoid the above-mentioned drawbacks, an automatic device for handling has been developed created with cell cultures, which aims to reduce the dangers of air ingress as well as the processing of the Turning off cultures by hand. This automatic device includes a divider injector for Transferring the expanded cells from the culture container to a centrifugal separator to remove the supernatant liquid after centrifugation, for injecting a nutrient solution into the centrifugal separator as well as for dividing the cells into further culture containers and the like. This injector is in one arranged under a certain atmosphere held space, so that the operations described all carried out in an atmosphere conducive to the cultures. In this work however, for example, a pipette used to aspirate the supernatant liquid through the Contaminated liquid, with the result that this pipette cannot be used to introduce fresh nutrient solution or should be used to divide the cells into further culture containers.

The invention is based on the object of providing a pipette changing device of the type mentioned at the beginning To create a genus that allows the pipettes to be changed under all circumstances after each work step the cultures permitted under conducive conditions.

According to the invention, this object is achieved by the characterizing features specified in the patent claim solved.

With the help of the invention achievable technical progress, it is asserted that the pipette changing device enables automatic and sterile work under constant conditions, whereby the set cultures are not affected by external influences be affected.

To the height of the invention it is stated that the special design of the pipette changing device is not

could be suggested by the state of the art because suitable models are not known.

An embodiment of the invention is shown in the drawing and will be described in more detail below described. It shows

F i g. 1 is a sectional view of an inventive Pipette inserter,

2 shows a partial view of a pipette holder of the Device according to the invention and an enlarged sectional view of a pipette,

F i g. 3 shows a plan view of a pipette feeder device,

Fi g. 4 is a view in section along the line H-II in Fig. 3,

4 is an enlarged partial sectional view of a Pipette holding part,

F i g. 6 shows a schematic representation of the mode of operation of a pipette triggering device,

F i g. 7 shows a sectional view of a pipette transfer device and FIG

F i g. 8 is a series of sectional views along the line "1-" in FIG. 7th

A pipette insertion device shown in Fig. 1 has a housing 1 in which a pinion 2 which can be set in rotation by a drive source is mounted. A guide 3 fastened to the housing 1 contains a vertically displaceable lifting rod 4. This is composed of a sleeve 5, which has a toothed rack 5a in engagement with the pinion 2 on one side and a longitudinal groove 5b opposite it, and a shaft 6 rotatably mounted therein. This has a stop head 7 at the upper end. With the longitudinal groove 5b there is a guide 3 seated guide pin 8 in engagement. A further shaft 9 with a guide groove 9a is attached to the lower end of the shaft 6 the groove 9a of the shaft 9 in engagement guide pin 14. At the upper end of the hollow shaft 12, a gear 15 meshing with the drive pinion 11 is attached. A microswitch 16 is attached to a support plate 17 and works together with an actuator 18 attached to the gear 15 . Like. is connected. As in FIG. 2 shows a conical mouthpiece 20a, onto which a pipette 22 with a funnel-shaped mouth 22a can be placed.

If the pinion 2 is set in rotation, the toothed rack 5a which is in engagement therewith moves vertically upwards or downwards. As a result, the whole of the sleeve 5, the shaft 6 and the shaft 9 moves composite lifting rod 4 together with the support arm 19 attached to the lower end of the shaft 9 with the bracket 20 up or down. When the pinion 11 is driven by the motor 10, the hollow shaft 12 becomes Set in rotation via the gear 15 and thereby takes the shaft 9 with the support arm 19 with it.

The following is the operation of the pipette inserter as an example when dividing a cell culture contained in a centrifuge tube according to the centrifugation of the same explained. A pipette supplied by a transfer device (not shown) is held in a certain position.

The motor 10 of the insertion device is set in motion around the hollow shaft 12 and thus the support arm 19 to turn. If the holder 20 sitting on the support arm 19 comes into a position above the held one Pipette, the rotation comes to a standstill, for example by actuating the microswitch 16. Then the Drive of the pinion 2 set in motion to lower the lifting rod 4 from the position shown. Through this also lowers the arm 19 with the holder 20 sitting at its end, so that its mouthpiece 20a in the pipette 22 is inserted and wedged therein. Then the pinion is driven in the opposite direction to lift the lifting rod 4 with the support arm 19 again. Under the drive of the motor 10 is now the Support arm 19 with the pipette attached to it rotated over a centrifugation tube (not shown) whereupon the support arm is lowered again in the manner described above, so that the end of the pipette 22 is inserted into the centrifuge tube. A suction device connected to the line 21 sucks now remove the supernatant liquid from the tube. Then the support arm 19 is again like as described above and rotated further so that the pipette contaminated by suction on can be removed from a designated point. A new pipette is then added using the Transfer device supplied and held at the place provided for the transfer. After this Inserting this pipette in the manner described above will put it back into the centrifuge tube introduced to supply this with a nutrient solution and the cell culture by repeated suction and Injecting to float.

After sucking off the supernatant liquid and resuspending the cell culture A new nutrient solution can be injected into the culture, which has been divided into individual cells Any amounts or the like on prepared Petri dishes. In the same way, a Culture can also be divided into several centration tubes.

F i g. 3 shows a feeder device for supplying the pipettes to a dividing and injecting device in FIG an automatic device for processing

4 ^r > of cell cultures and the like.

The in F i g. The feeder device shown in FIG. 3 has a base plate 31 with a frame 32 which is subdivided by a partition 33 and which contains a number of pipette holders 34. Each holder 34 has the shape of a parallelogram in plan view and is delimited by two side walls 34a, 34b. The brackets are open at the top and bottom and have a one in FIG. 5 illustrated annular part 35 or a series of such annular parts 35, in each of which a pipette is held in a resilient manner. One side wall 34b has a step 34c on the upper part, which is a step shown in FIG. 6 has cam profile 37 shown. In the space 31a delimited by the frame 32 and the partition 33 are several, in

In the embodiment shown, four pipette holders 34 are accommodated and driven by a thrust plunger 38 in the direction of the in FIG. 3 is loaded by the arrow shown in FIG. 3 also shows a feed spindle 39, a feed web 40 with an integral nut 40a seated on the spindle 39, a motor 41 for driving the spindle 39 via toothed belts 42, 43, and a pipette ejector 45 in Fig. 4 recognizes, together from one on the frame 32

attached, overhead standing L-shaped guide part 46, an ejector plunger 47 guided in it so as to be vertically displaceable, an ejector plunger 47 connected to the plunger and in the position shown in FIG. 6 shown way with the cam profile 37 of the side wall 346 cooperating Rciektivenstci! 4H and a spring 49 that loads the ejector plunger 47 downwards. Perpendicularly below the plunger 47 of the pipette ejector 45, the base plate 31 is penetrated by an opening 31c, the diameter of which is somewhat larger than that of a pipette. In FIG. 3 one can also see a stamp 50 for hooking the pipette holders after all the pipettes have been ejected.

The feeder device described above operates as follows. First of all, one or more pipette holders 34 equipped with sterilized pipettes are inserted into the space 31a delimited by the frame 32 and the partition 33. The motor 41 is then switched on in order to set the feed spindle 39 in rotation, so that the nut 40a moves together with the feed web 40 in the direction of the arrow shown in FIG. The feed web 40 engages the one side wall 34a of the foremost pipette holder 34 and pushes it in front of it until the first pipette 36 seated in the holder 34 in the direction of movement reaches a position below the ejector 45. Simultaneously with this, a recess 376 of the cam profile 37 at the step 34c of the other side wall 346 reaches the actuating part 48 of the ejector 45, so that the plunger 47 suddenly moves downwards under the load of the spring 49 and pushes the pipette in question out of its retaining ring 35 . In this way, when the holder 34 is moved in the direction of the arrow, the pipettes seated in the holding rings 35 are ejected one after the other through the opening 31c in the base plate 31. This is done in that the cam profile 37 of the step 34c on the side wall 346, the depressions 37b of which correspond to the position of the individual pipettes in the holder 34, moves in the direction of the arrow shown in Figure 6 under the actuating part 48 of the ejector 45 Actuating part 48 is permanently loaded by the spring 49 in contact with the cam profile 37 and, as it moves, slowly runs up against a flank emanating from the respective recess 37b until it reaches the highest point of the respective following elevation 37a and then jerks into the next recess 376 occurs. As a result, the plunger 47 also moves jerkily downwards and in the process ejects the respective pipette 36 from the retaining ring 35, which only holds it loosely, downwards through the opening 31c. Each time the actuating part 48 is lowered into a recess 37b of the cam profile 37, a pipette is located just below the plunger 47 and is ejected from the holder 34 by this.

These processes are repeated until all pipettes have been ejected from the respective holder 34, the latter moving through a passage between the frame 32 and the partition wall 33 into a second space 316 and then held between the plunger 50 and the frame 32 therein will. The motor 41 is then reversed in order to return the feed web 40 counter to the direction of the arrow into the starting position, whereupon the second pipette holder 34 is brought into the feed position by the plunger 38. The pipettes are then ejected from the second holder one after the other in the manner described above and introduced. In the movement caused thereby <i'jr second holder 34 in the direction of the arrow ir Andean space 31 b of the Zubiingereinrichtung already therein first bracket is displaced due to the mutually complementary Parallclogrammfonn the brackets against its loading by the ram 50 to the left in Fig. 3 , until then the two brackets are now running parallel to each other in the room

ίο 3161iegen. This way, everyone will be in the first Barely 31a housed holders 34 contained pipettes successively fed and the empty Mounts transferred into the second space 316. The empty brackets can then be removed from the second space 3ίσ removed and newly filled brackets inserted into the first space 31a, whereupon the supply of pipettes can be continued in the manner described above.

While the feed web 40 is continuously moved forward as described above, In view of the safe ejection of the pipettes, it is advantageous to briefly pull the feed bar each time stop when a pipette is in position on the ejector. to For this purpose, a microswitch can be attached in a position denoted by 51 in FIG be, which is always via an actuator connected to the traveling nut 40a of the feed web 40 can then be actuated when a pipette is in the ejector to switch off the motor 4i and thus to stop the feed web 40. A timing element is preferably also provided, which switches the motor on again with a certain delay after the feed bar has stopped. This delay is preferably set to the cycle with which the pipettes one after the other should be supplied.

F i g. 7 and 8 show a transfer device for transferring the pipettes to a dividing and injecting device in an automatic device for processing cell cultures and the like.

In Fig. 7 a pipette feed device can be seen 61, a transfer device 62 to be described below and one by means of a shaft 63a

• »5 rotatably mounted support arm 63, which together with the various parts of the splitting and injection device are accommodated in a closed space 64 is in which an atmosphere conducive to cultures is maintained.

jo The transfer device 62 has an essentially cylindrical housing 71 with a space 64 that is open to contain the culture atmosphere Window or outlet 71a and a floor 716, one in the center of the housing 71 mounted shaft 72 and a rotatable on the shaft, a one-sided flat 73 * having sluice body 73. At the upper end of the fixed shaft 72 is a guide slot 74a having support plate 74 attached. The upper end of the lock body 73 is fixed to a

w »connected to it rotatable cleat 75, which has a cutout 75a in which a pipette can be accommodated. The housing 71 has furthermore a cover 76 with an inlet opening for inserting one pipette at a time.

The described transfer device 62 works as follows: From the feeder device 61 arranged above the cover 76, in each case a pipette 70 into the inlet port 76a of the lid

• introduced so that they can with their thinner lower Tci! 70j through Jen guide slot 74; .- the Traepiaue M through the same and with one ..: .. * eri: n KopHeii 706 an the Ti, igpiatie gets stuck. The lower part 70;) hang! then in the flattening 73a of the lock body 73 down. Then the Schii ^ utie 75 and the Sciiii-usenkkörpertr 73 together clockwise in F i g. 8 set in rotation, an edge -es cutout 75a engages the pipette 70 and it is in the Slide along guide slot 74a. During the rotation of the sliding plate 75 and the lock body 73 of the in F i g. 8A into the one shown in FIG. The position shown in FIG. 8B is previously closed by the lock body 73 held window 71a of the housing 71 completely released, so that the meanwhile also in Dn i.ung offset support arm 63 inserted into the window 71a and in a cutout 746 of the support plate 74 on the open End of the guide slot 74a can be aligned. As the lock body continues to rotate 73 and the push plate 75 in the position shown in Fig.8C, the pipette is from the guide slot 74a of the Support plate 74 pushed into a recess 63b of the support arm 63 so that it now hangs on this. Thereupon the support arm can then be turned back in order to remove the attached pipette from a (not shown) Insertion device to be handed over.

In the position of the lock body shown in Fig. 8A 73 and the push plate 75, the opening 76a of the cover 76 is released, while the window 71a of the housing 71 is kept completely closed by the lock body 73. Will then if the slide body 73 and the thrust plate 75 are rotated together, the thrust plate first closes 75 the opening 76a of the cover before the lock body 73 closes the window 71a of the housing 71 opens (Fig.8B). After turning back the bracket 63 from the window 71a of the housing the shooting body 73 and the thrust plate 75 are rotated back into the position shown in FIG they remain there until a further pipette is supplied from the feeder device 61. First of all the opening or the window 71a of the housing 71 is completely closed by the lock body 73, before the push plate 75 again releases the opening 76a in the cover 76 and a further pipette is supplied can be.

In addition 5 sheets of drawings

Claims (1)

Claim: Ns
f'l 10 15th Pipette changing device for use in an automatically operating system for the Culture of biological tissues and cells, characterized by