This application claims priority under 35 U.S.C. §119 to German patent application no. DE 10 2011 007 779.0, filed Apr. 20, 2011, the disclosure of which is incorporated herein by reference in its entirety.
The present disclosure relates to a mixing chamber, cartridge, and method for mixing a first and a second component.
The document DE 30 36 538 C2, for example, describes a swivel beaker centrifuge for centrifuging blood. The purpose of such centrifuges is to separate substances in the centrifuge material space using mass inertia: particles or liquids of greater density migrate outward as a result of the greater inertia. In doing so, they displace the constituents of lower density, which in this way arrive at the center.
Compared to conventional solutions, the mixing chamber, the cartridge and the method described herein have the advantage that, instead of the known separation of two liquids of different density for example, it is possible to achieve an effective mixing of the two liquids. For this purpose, under the effect of the centrifugal force and/or magnetic force, the obstacle structure is moved through the two liquids in the container, as a result of which these liquids are mixed with each other.
Moreover, the mixing chamber comprising the container, the obstacle structure and the connection piece (which form one continuous part) can be easily mounted in a cartridge, for example.
Further advantageous embodiments of the disclosure are set forth herein.
Here, “component” means a liquid, a gas or a particle. The “first component and second component” can also just mean two different states of the same substance: for example, the first component can be an agglomerated form and the second component a liquid form of the same substance.
Here, “magnetic force” means the force acting on a conductor, through which current flows in an electrical field, or on a magnet, in particular a permanent magnet, in a magnetic field.
In one embodiment of the mixing chamber according to the disclosure, the connection piece is formed in one piece with the container and/or with the obstacle structure. Here, “in one piece” means that the connection piece, the container and/or the obstacle structure are formed from one and the same material. Thus, for example, the connection piece, the container and/or the obstacle structure can be easily produced by injection molding.
In another embodiment of the mixing chamber according to the disclosure, the connection piece is connected to a frame, which is connected, in particular adhesively bonded, to the container. This measure also allows the obstacle structure to be connected easily to the container. The frame can be connected in particular to an upper peripheral edge of the container. Instead of the frame, another structural part could also be used.
In another embodiment of the mixing chamber according to the disclosure, the connection piece is flexible or designed with a hinge. In this way, the mobility for moving the obstacle structure through the first component and second component in the container can be easily provided, and at the same time the one-part design of connection piece, container and obstacle structure is retained. Here, “one-part” means that the corresponding parts, in particular the connection piece, the container and the obstacle structure, form one continuous part.
In another embodiment of the mixing chamber according to the disclosure, the connection piece is elastic, in order to generate a restoring force that counteracts the centrifugal force and/or magnetic force. If the centrifugal force and/or magnetic force drops below a predetermined threshold value or is completely lost, this design has the effect that the obstacle structure moves automatically back out of the first component and second component in the container, and/or the obstacle structure moves through the first component and second component in the direction of the rotation point. Therefore, if a corresponding centrifuge with the mixing chamber is operated in such a way that the speed of rotation of the centrifuge oscillates around the aforementioned threshold value, the obstacle structure moves constantly in and out of the first component and second component and/or moves constantly to and fro through the first component and second component, such that the first component and second component are thoroughly mixed together.
Alternatively, the restoring force can also be generated by a further magnetic force. In this case, the connection piece does not need to be made elastic.
In another embodiment of the mixing chamber according to the disclosure, the connection piece is connected to an edge or bottom of the container. This is advantageous from the point of view of manufacturing.
In another embodiment of the mixing chamber according to the disclosure, a spike is provided on the obstacle structure and is designed such that, under the effect of the centrifugal force and/or magnetic force, it pierces a membrane closing an opening in the bottom of the container. Thus, by suitable choice of the speed of rotation of a centrifuge with the mixing chamber, a hole can be generated in the membrane, through which hole the first component and second component can flow out of the container.
In another embodiment of the mixing chamber according to the disclosure, the obstacle structure is designed as a beam, a rake, a sieve or a grid structure. All of these structures are very suitable for mixing the first component and second component together.
In another embodiment of the mixing chamber according to the disclosure, the connection piece is arranged asymmetrically with respect to the obstacle structure, such that the obstacle structure twists, in particular elastically twists, the connection piece under the effect of the centrifugal force and/or magnetic force. By means of this design, the obstacle structure can rotate about an additional axis. The first axis of rotation results, for example, from the fact that the connection piece is flexible or elastic and thus bends under the effect of the centrifugal force and/or magnetic force. A further axis of rotation then results from the fact that the connection piece is arranged asymmetrically with respect to the obstacle structure, the further axis of rotation being provided by means of the twisting of the connection piece.
According to another embodiment, the cartridge according to the disclosure furthermore has: a first drum, which has a first chamber, an adjustment mechanism, which is designed to rotate the first drum about the center axis thereof when the centrifugal force exceeds a predetermined threshold value, in order thereby to connect the first chamber conductively to a second chamber, wherein the first and/or second chamber is designed as the mixing chamber. Advantageously, by suitable choice of the speed of rotation of a centrifuge with the cartridge, it is thus possible for the first and/or second component to be transferred between the first chamber and second chamber. Depending on whether the first and/or second chamber is designed as mixing chamber, the corresponding components can be effectively mixed in the first and/or second chamber. Here, “conductively” means in a manner conducting liquid, gas and/or particles.
In another embodiment of the cartridge according to the disclosure, the adjustment mechanism comprises a first bevel, which cooperates with a second bevel of the first drum in order to move the latter from a first position, in which the first drum is in form-fit engagement with a housing of the cartridge in the direction of rotation about the center axis, to a second position along the center axis and counter to the effect of a restoring means, in which second position the form-fit engagement is canceled and the first drum rotates about the center axis. Thus, a simple mechanism is made available for adjusting the first drum between at least two defined positions in the direction of rotation about the center axis.
In another embodiment of the cartridge according to the disclosure, the second chamber and/or a third chamber of the first drum is mounted upstream or downstream in relation to the center axis, wherein the first chamber can preferably be connected conductively by means of the adjustment mechanism either to the second chamber or to the third chamber. The mixing chamber can thus be mounted upstream and/or downstream from the first drum or can even be provided in the first drum itself. Moreover, the mixing chamber can preferably be optionally connected to various further chambers depending on requirements.
In another embodiment of the cartridge according to the disclosure, a second drum is provided, which has the second chamber, and/or a third drum is provided, which has the third chamber. However, it is also equally possible, for example, that the second drum has the second chamber and the third chamber. The same applies to the third drum. By providing several drums which in particular have several chambers and which are adjusted relative to one another, a wide variety of processes can be performed automatically by means of the cartridge.
Illustrative embodiments of the disclosure are explained in more detail in the following description and are shown in the figures in the drawing, in which:
Unless otherwise stated, identical reference signs in the figures designate identical elements or elements that have identical functions.
The cartridge 100 comprises a housing 102 in the form of a small tube. For example, the housing 102 can be designed as a 5 to 100 ml centrifuge tube, in particular a 50 ml centrifuge tube, a 1.5 ml or 2 ml Eppendorf tube, or alternatively as a microtiter plate (e.g. 20 μl per cavity). The longitudinal axis of the housing 102 is designated by 104.
The housing 102 accommodates, for example, a first drum 108, a second drum 106 and a third drum 110. The drums 106, 108, 110 are arranged in succession and with their respective center axes arranged coaxially with respect to the longitudinal axis 104.
The housing 102 is closed at one end 112. A restoring means, for example in the form of a spring 114, is arranged between the closed end 112 and the third drum 110 adjacent thereto. The spring 114 can be designed in the form of a coil spring or of a polymer, in particular an elastomer. The other end 116 of the housing 102 is closed by means of a closure piece 118. The closure piece 118 can preferably be taken off in order to remove the drums 106, 108, 110 from the housing 102. Alternatively, the housing 102 itself can also be dismantled in order to remove the drums 106, 108, 110 or to access the chambers, for example the chamber 136.
According to another illustrative embodiment, the spring 114 is arranged between the closure piece 118 and the second drum 106, such that the spring 114 is expanded in order to generate a restoring force. Other arrangements of the spring 114 are also conceivable.
A respective drum 106, 108, 110 can have one or more chambers:
Thus, for example, the second drum 106 comprises several chambers 120 for reagents and a further chamber 122 for receiving a sample, for example a blood sample, which has been taken from a patient.
The first drum 108, downstream of the second drum 106, comprises a mixing chamber 124 in which the reagents from the chambers 120 are mixed with the sample from the chamber 122. Moreover, the first drum 108 comprises, for example, a further chamber 126 in which the mixture 128 from the mixing chamber 124 flows through a solid phase 130. The solid phase 130 can be a gel column, a silica matrix or a filter.
The third drum 110, arranged in turn downstream from the first drum 108, comprises a chamber 132 for receiving a waste product 134 from the chamber 126. Moreover, the third drum 110 comprises a further chamber 136 for receiving the desired end product 138.
The cartridge 100 has an outer geometry such that it can be placed in a seat of a centrifuge, in particular in a seat of a swinging-bucket rotor or fixed-angle rotor of a centrifuge. During the centrifuging procedure, the cartridge 100 is rotated at high speed about a rotation point 140 indicated schematically in
The aim now is to control various processes inside the cartridge 100 by means of suitably controlling the speed of rotation. Thus, for example, the mixing chamber 124 is first of all intended to be brought into fluidic communication with the chamber 122, in order to receive the sample from the chamber 122. Thereafter, the mixing chamber 124 is to be connected to the chambers 120 in order to receive the reagents from these. The reagents and the sample are then to be mixed in the mixing chamber 124 at a controlled speed of rotation. Similarly, the processes in the chambers 126, 132 and 136 are also intended to take place at a controlled speed of rotation.
As is shown in
The projections 200, the slits 204, the bevels 206, the projections 212, the bevels 218, 220, the projections 240 and the bevels 242 form, together with the restoring spring 141, the aforementioned adjustment mechanism 300 for defined rotation of the first drum 108 relative to the second drum and third drum 110 about the longitudinal axis 104.
If the speed of rotation is now reduced again, which is associated with a corresponding reduction in the centrifugal force, the spring 114 presses the first drum 108 back in the direction of the rotation point 140 by means of the third drum 110. In this way, the second drum 106 and its bevels 220 are likewise moved back in the direction of the rotation point 140, as a result of which the bevels 242 of the first drum 108 come to lie against the bevels 206 of the housing 102 and, performing a further rotation movement of the first drum 108, slide along these to a third position, as is shown in
The process described above can be repeated as often as required in order to rotate the first drum 108 in a defined manner relative to the second drum 106 and third drum 110.
The mixing chamber 124 comprises a container 500 for receiving at least two components. These are preferably components that are supplied by means of the second drum 106. For example, the components can be in the form of reagents or samples, in particular blood samples.
The mixing chamber 124 also has an obstacle structure 506, which is designed to move through the liquids 502, 504 under the effect of a centrifugal force (i.e. if the speed of rotation of the centrifuge exceeds a predetermined threshold value) in order to mix these liquids together.
Moreover, a connection piece 508 is provided, which connects the obstacle structure 506 to the container 500. The obstacle structure 506 thus forms, together with the connection piece 508 and the container 500, a single part that is easy to handle, in particular easy to assemble. At the same time, however, the obstacle structure 506 is provided to be movable relative to the container 500 in order to perform its mixing function.
For example, the obstacle structure 506 and the connection piece 508 and container 500 can be made from one piece, that is to say produced from the same material. This can be easily achieved, for example, by injection molding of the obstacle structure 506, the connection piece 508 and the container 500.
Alternatively, the connection piece 508, at its container-side end, can be connected to a frame 510 (since this is another illustrative embodiment, the frame 510 is shown by broken lines). The frame 510 is in turn connected, in particular adhesively bonded, to the container 500, in particular to an upper peripheral edge 512 of the container 500. According to one embodiment, the obstacle structure 506 can be produced in one piece with the connection piece 508 and the frame 510, in particular by injection molding.
In the illustrative embodiment according to
The mixing is effected in the first instance by the movement of the obstacle structure 506. In addition, when the mixing chamber 124 is used with the above-described cartridge 100, the mixing chamber 124 itself moves along the longitudinal direction 104 away from and toward the rotation point 140, as has been described above. This provides a further mixing effect.
According to an alternative embodiment, instead of an elastic connection piece 508 it would also be possible to use a stiff connection piece, which is connected to the container 500 by means of a hinge. Restoring could then be provided by a separate spring.
Moreover, the mixing chamber 124 can be designed such that further process steps and structures are integrated, e.g. sedimentation structures or channel or siphon structures for conveying and switching the liquids 502, 504.
The container 500, the obstacle structure 506 and/or the connection piece 508 can be produced from the same polymer or from different polymers. The one or more polymers are, in particular, thermoplastics, elastomers or thermoplastic elastomers. Examples are cyclo-olefin polymer (COP), cyclo-olefin copolymer (COC), polycarbonates (PC), polyamides (PA), polyurethanes (PU), polypropylene (PP), polyethylene terephthalates (PET) or polymethyl methacrylates (PMMA).
The obstacle structure 506 and the connection piece 508 can each have a cross section that varies in its respective longitudinal direction. Here, “longitudinal direction” means in particular a direction away from the container 500.
Moreover, at its freely oscillating end, the obstacle structure 508 can have an additional mass, for example in the form of a thickened area or a metallization, in order to increase the inertia effect and therefore the oscillation amplitude upon variation of the speed of rotation.
In a further embodiment, the obstacle structure 508 has at least one magnet, which can be moved by means of an in particular electrical or magnetic field. The magnet, e.g. a metallization or a permanent magnet, for example of iron, is mounted on the obstacle structure 508. The means, in particular coils or permanent magnets, for generating the field are accommodated in the centrifuge housing, for example. The obstacle structure 508 is then deflected counter to the centrifugal force 142, and the centrifuge rotor together with the mixing chamber 124 moves through the field. In this way, the obstacle structure 508 can also be moved, in order thereby to mix the liquids 502, 504 together, when the speed of rotation of the centrifuge is kept constant. Alternatively or in addition, the field itself can also be controlled in terms of its strength and orientation, in order to move the obstacle structure 508. In this case, mixing can even take place without centrifuge.
Whereas, in the illustrative embodiment according to
In one embodiment, the free end of the obstacle structure 506 can have a spike 516. An opening 518 is provided in the bottom 514 of the container 500, which opening 518 is closed by a membrane 520 in order to prevent the liquids 502, 504 from flowing out of the container 500.
When the speed of rotation exceeds a predetermined threshold value, the pivoting of the obstacle structure 506 about the attachment point 522 causes the spike 516 to move into the membrane 520 and thereby destroy the latter. The liquids 502, 504 can thus flow out of the container 500. The threshold value is preferably above the threshold value for the mixing of the liquids 502, 504 by means of the obstacle structure 506. This ensures that the liquids 502, 504 are first mixed together, and only then is the membrane 520 pierced.
For example, the opening 518 can be connected to a downstream chamber, for example the chamber 126 of the first drum 108 (see
In the illustrative embodiment according to
The beams 506 according to the illustrative embodiments 6A and 6B have, for example, a width of 0.1 to 3 mm. The distance between the beams 506 (illustrative embodiment according to
In the illustrative embodiment according to
In the illustrative embodiment according to
In the illustrative embodiment according to
Moreover, in the illustrative embodiment according to
Although the disclosure has been described here on the basis of preferred illustrative embodiments, it is not in any way limited to these, and instead it can be modified in many ways. It will be noted in particular that the designs and illustrative embodiments described here for the mixing chamber according to the disclosure can be applied accordingly to the cartridge according to the disclosure and to the method according to the disclosure for mixing a first component and second component, and vice versa. It is also possible for more than two components to be processed. It will further be noted that “a” or “one” in this text does not preclude a multiplicity.
Number | Date | Country | Kind |
---|---|---|---|
10 2011 007 779 | Apr 2011 | DE | national |
Number | Name | Date | Kind |
---|---|---|---|
3384354 | Migule et al. | May 1968 | A |
4732487 | Pollard | Mar 1988 | A |
5360410 | Wacks | Nov 1994 | A |
6386751 | Wootan et al. | May 2002 | B1 |
20030179647 | Simba | Sep 2003 | A1 |
20050184012 | Coull | Aug 2005 | A1 |
20090129973 | Emerson | May 2009 | A1 |
20100261595 | Schaefer et al. | Oct 2010 | A1 |
20110013474 | Ludwig et al. | Jan 2011 | A1 |
Number | Date | Country |
---|---|---|
1627985 | Jun 2005 | CN |
970 926 | Nov 1958 | DE |
74 35 369 | Feb 1975 | DE |
30 36 538 | May 1982 | DE |
1 106 253 | Jun 2001 | EP |
1 533 024 | May 2005 | EP |
2011117148 | Sep 2011 | WO |
Number | Date | Country | |
---|---|---|---|
20120269030 A1 | Oct 2012 | US |