Patent Application
20100135104
The invention relates to a stirring element and to a stirring device having such a stirring element, for stirring and mixing in particular microscopically small amounts of flowable substances.
In the field of the invention, magnetic stirrers are known, for example, with magnetic stirrer bars that are driven magnetically without contact and that typically have a diameter of at least a few millimeters and a length of several millimeters to centimeters. Because of their dimension, magnetic stirrers of this kind are unsuitable in particular for use in microfluidics and biological microfluidics. Their range of use is also limited wherever magnetic fields are undesired. This can be the case, for example, when using magnetic beads, which are added to the liquid for the specific extraction of cells, DNA, proteins and the like.
The vortex mixer uses another mixing method. Here, liquids of different density are mixed together in a container as a result of inertial forces by movement of the container. In this case too, there are natural limits to miniaturization. This mixer is suitable for liquid amounts of a few tenths of a milliliter but not for less than this.
Passive diffusion mixing methods and devices are also known. However, the mixing times in diffusion mixing are relatively long.
In the article “Bubble-induced acoustic micromixing” by Robin H. Liu et al., Lab Chip, 2002, 2, 151-157, a device for mixing very small amounts of liquid (22 μl) is also proposed which comprises a chamber, filled with the liquids that are to be mixed, and cavities that are arranged peripherally and are connected to the chamber. Air bubbles trapped in the area of the cavities undergo resonant oscillation by acoustic excitation and, in so doing, also set the surrounding liquid in motion, which leads to more rapid mixing of the latter.
By contrast, the object of the present invention is to make available a stirring element and a stirring device for a flowable substance or liquid, which element and device can be used universally, in particular for mixing very small amounts of liquid.
The object is achieved by a stirring element according to claim 1, a use according to claim 16, and a stirring device according to claim 18.
The stirring element comprises a body that encloses a cavity. The cavity is connected via an opening to the area surrounding the body. According to the invention, the cavity and the opening are arranged relative to the body such that a fluid stream of the flowable substance or liquid emerging from the cavity through the opening transfers a torque to the stirring element.
The stirring device comprises a container for the flowable substance, at least one of the aforementioned stirring elements, and a sound source coupled to the container in order to generate a pressure oscillation.
Unless otherwise specified, a cavity is understood here generally as a hollow space of any desired shape. In this context, the term opening describes the outlet cross section of the cavity in a projection onto the body surface at the outlet site. The end portion or outlet channel of the cavity near the opening is referred to hereinbelow as the mouth.
The invention exploits the principle, known in fluid dynamics, whereby a fluid emerging from a tube leaves the latter in the form of a directed jet, whereas a fluid sucked into the tube enters the tube as it were from the whole of the available solid-angle range. The principle, which applies only for sufficiently high Reynold numbers, Re≧about 50, is described in the article “The ‘acoustic scallop’: a bubble-powered actuator” by Dijkink et al., Journal of Micromechanics and Microengineering, 16, 2006, 1653-1659. The article proposes using the principle as a drive for an “acoustic windmill”. A Teflon tube, closed at one end, is accordingly immersed in a container filled with water, after which an air bubble is enclosed in the capillary thereof. Sound is introduced through the water into the air bubble by means of a piezo actuator, and the air bubble is thus caused to oscillate. The alternating expansion and contraction of the volume alternately sucks liquid into the tube and ejects it again. The described asymmetry between the directed ejection and the undirected suctioning results, when seen across a complete oscillation, in a total impulse being transferred to the tube, which is used to drive the latter in the direction of its longitudinal axis.
By contrast, the use of such a tube as an independent stirring element is not known. The invention exploits this principle but, in contrast to the linearly driven Teflon tube, uses a body with a cavity, in which the cavity and the opening thereof are arranged relative to the body such that the total impulse resulting across a complete oscillation does not coincide with the direction of the longitudinal axis of the body, or to be more precise is not directed to the center of gravity, but instead generates a torque and thus causes an accelerated rotation of the body about its center of gravity.
The stirring element thus becomes an acoustic stirrer bar which, as is known from magnetic stirrer bars, is added to the liquid that is to be stirred, without a special container being needed for this. Moreover, its use is not limited by magnetic sensitivity and is therefore more universal.
Compared to the known stirring appliances and stirring elements, the acoustic stirrer bar according to the invention also has the advantage that the physical principle also functions at microscopic dimensions. With suitable miniaturization, the stirring element according to the invention can also be used in microfluidics, i.e. for stirring or mixing amounts of liquid that have a volume of a few microliters, which does not exclude the possibility of small stirring elements, suitable for this purpose, also being able to be used to effectively mix a larger amount of liquid, by addition of a suitably greater number of these small stirring elements.
The stirring elements can be used in closed sample preparation chips (known as “lab on a chip”), which are employed in particular in microfluidics, and also in open or closed “macroscopic” vessels.
According to one aspect of the invention, the preferred one-piece body has several openings, and the cavity and the openings are arranged relative to the body such that the sum of all the fluid streams emerging through the several openings transfer a torque to the stirring element.
In this case, the openings can each communicate with a separate cavity or with connected cavities or a single cavity.
Because easy to produce, the body is preferably tubular, and the interior of the tubular body forms the cavity.
This can be done, for example, by using a tube section or hose section as stirring element, in which the interior forms the cavity.
For the operating principle, it suffices that the cavity is designed, in the mouth area, in such a way that a directed jet emerges from it and ensures the aforementioned impulse transfer. The direction of flow of the emerging jet of fluid can be set, on the one hand, by the orientation of the cavity or the mouth thereof and, on the other hand, by the arrangement or shape of the opening, or by a combination of both features. In a simple configuration, the cavity, at least in the mouth area, has a tubular or channel-shaped portion (of constant cross section) and, in a complicated configuration, it has a special nozzle geometry, for example in order to increase the drive efficiency. If, for example, the opening lies in a plane oblique to the axis of a cavity that has the form of a simple bore, this will ensure a deflection of the flow away from the axis of the outlet channel or bore.
The latter principle is implemented in an advantageous development of the invention in which the tubular body is straight and, at the opening, has (at least) one end face that lies in a plane not arranged at right angles to the longitudinal axis of the body.
In a preferred embodiment of the invention, this can be done very simply, for example, by a hose section or tube section being cut with a bevel at one or both ends.
By cutting the end with a bevel, the fluid emerging from the cavity in the form of a jet is deflected away from the longitudinal axis of the body. The reason for this is that the flow along the edge of the mouth (edge of the opening) tears off at different times. In this way, the impulse transfer to the hose section or tube section will also be oblique to the longitudinal axis and therefore not in the direction of the center of gravity. A torque is exerted.
To ensure that the force components exerting the torque transverse to the longitudinal axis of the tubular body with openings at both ends do not cancel each other, the ends should not be beveled in mirror image to each other. The two end faces preferably lie in planes that are parallel to each other and not at right angles to the axis of the body. This configuration ensures a pure rotation movement of the stirring element about its center of gravity.
The stirring element according to the invention can also execute a more complex rotation about several axes (tumbling motion) by arranging the end faces preferably in planes whose normals through the respective centers of the openings are arranged askew to each other.
Of course, one of the end faces can also be arranged at right angles and the other obliquely with respect to the longitudinal axis of the hose section or tube section, or one of the two openings can be closed. In these cases, the stirring element in the form of the hose section or tube section will execute a rotation movement with a superposed linear movement.
In an alternative embodiment, the tubular body is bent and/or angled. In this way, end portions are obtained (at one end or at both ends) with a mouth that does not coincide with the longitudinal axis of he body. The emerging jet of fluid then emerges from the tubular body even with a right-angled end face to exert a torque.
The body of the tubular element is preferably provided with a cavity which is designed not to be wettable. This ensures that an air bubble enclosed in the cavity remains trapped there on account of the surface tension of the substance.
In the case of aqueous liquid, the entire body can be made, for example, of a hydrophobic material, such as polycarbonate or polytetrafluoroethylene.
The cavity is particularly preferably designed to be wettable in the area of the mouth. This ensures that some of the flowable substance flows at least into the mouth area as a result of the capillary effect and is available there as a liquid column to form the stream of fluid.
The stirring element is also preferably designed to be wettable in the area of the outer surface, such that it is ideally unwettable only in the inner area of the cavity, except for the mouth(s).
This measure also reduces the danger of the stirring element collecting on or adhering to a vessel wall.
A local wettability of the surface of the cavity in the area of the mouth and/or of the outer surface can be achieved by surface modification.
Accordingly, when used in an aqueous solution, the body is either made of a hydrophobic material and rendered hydrophilic in the area of the mouth and/or of the outer surface, or the body is made of a hydrophilic material and rendered hydrophobic in the area of the cavity (cavities), if appropriate except for the mouth (mouths).
It can ideally be rendered hydrophilic or hydrophobic in a known manner by an immersion method, as is described in DE 100133111C2, or by a coating. Polycarbonate, for example, as a weakly hydrophobic material can be rendered hydrophilic by O2 plasma treatment on the surface.
In an alternative construction, the stirring element is composed of two tube sections or hose sections lying one inside the other, of which the inner one is non-wettable (hydrophobic) and the outer one is wettable (hydrophilic). The outer hose section can also be longer, in order to form wettable mouth areas. Such a construction can be obtained, for example, by simply pushing the tubes or hoses one over the other or by co-extrusion. Instead of the outer hose section or tube section, it is also possible to provide a kind of net or film covering.
When the stirring elements are used in apolar organic liquids, lipophilic surfaces can accordingly be used in the area of the outer surface and/or of the mouth, and lipophobic surfaces can be used in the area of the cavity (cavities), if appropriate except for the mouth (mouths).
Alternatively or in addition, it is possible to provide a pressure-increasing means which is connected to the container of the stirring device and by means of which the flowable substance is subjected to a pressure and therefore penetrates into the mouth area of the cavity upon compression of the gas bubble enclosed in the cavity. The flowable substance is then once again available as a liquid column for forming the stream of fluid.
In an advantageous development, the stirring element comprises a spacer, which is designed to prevent direct adherence of the body, in particular at one of the end faces, to a container wall.
In the stirring device according to the invention, the container can be formed by a chamber in a sample preparation chip.
To ensure that the stirring element or stirring elements remain in the container (or in the chamber of the sample preparation chip) and are not transported away with the liquid, the container is delimited by retainer elements or by narrowed areas with opening cross sections that are smaller than the smallest dimension of the stirring elements.
The sound source used is, for example, a loudspeaker or the like, preferably a piezo actuator coupled to a container wall.
The sound field is preferably introduced into the gas bubble via a container wall and the substance to be stirred, in order to minimize losses caused by any substantial impedance differences. The sound source is therefore preferably connected to the container wall in an area which is in contact with the flowable substance during operation of the stirring device.
In order to optimize the introduction of sound into the gas bubbles contained in the cavities of the stirring elements, gas cushions with a large surface area and large volume on a liquid surface should also be avoided. This can be done by providing the container with a cover or lid which is flexible or fits as tightly as possible and which can be adapted to the liquid level, or by ensuring the smallest possible interface between the liquid and the environment, for example by a constriction of the container in the filling area.
The stirring device preferably has a control system which is designed to set a frequency on the sound source that corresponds to the resonant frequency of a gas bubble enclosed in the cavity of the stirring element.
Further objects, features and advantages of the invention are explained in more detail below on the basis of illustrative embodiments and with reference to the drawings, in which:
The stirring element 100 according to the illustrative embodiment shown in
If the stirring element 100 is immersed in a liquid or a flowable substance, interfaces 122, 124 form between the enclosed gas bubble 114 and the liquid passing through the end openings into the mouth areas of the cavity 112. In the illustrative embodiment shown, the cavity 112 is wettable in the mouth areas thereof, for which reason a liquid column 126, 128 forms in each case in the mouth area as a result of the capillary effect alone. To trap the gas bubble 114 safely in the cavity 112, the rest of the cavity is advantageously designed to be non-wettable by the liquid. When used in aqueous liquids, it is recommended that the body be made of a hydrophobic material, and that the hydrophobic property be cancelled out in the mouth areas of the cavity 112 by one of the surface modifications discussed above. Polycarbonate and polytetrafluoroethylene have proven to be suitable materials.
In addition to the embodiment shown, a dividing wall can be incorporated in the center of the stirring element. This would result in two cavities that were separated from each other and that were each closed at one end (also called blind bores), by means of which the position of the gas bubble would be stabilized.
When the gas bubble 114 is made to oscillate by application of sound, it will alternately contract and expand. The moment of expansion is indicated in
The forces acting on the stirring element from the impulses of the fluid streams are preferably considered in the center of gravity system of the stirring element. The center of gravity is identified by 134. The force components acting from the centers of the openings in the direction of the center of gravity 134 cancel each other out. This results in a force couple composed of opposite and equal forces 136, 138, which act at the center points of the outlet openings. These cause a torque, identified by the arrow 140, which sets the stirring element 100 in a pure rotation movement.
Overall, there is therefore an asymmetry between the suction movement and the ejection movement, which ensures that across a complete oscillation of the gas bubble (expansion and compression), a net overall impulse is transferred which sets the stirring element according to the invention in a rotation movement.
When the gas bubble 214 is again caused to oscillate by application of an acoustic field, the liquid column 228 is forced out through the opening of the cavity, as has been described before, at an oblique angle to the longitudinal axis 220 of the body during expansion of the gas bubble 214. The resulting impulse of the fluid stream is identified by an arrow 232. The force acting on the stirring element 200 is divided in the center of gravity system (the center of gravity is at 234) into a component 238, which acts perpendicular to the longitudinal axis 220 of the body at the center of the opening, and a component 242, which extends parallel to the longitudinal axis. This results, on the one hand, in a torque 240 that acts on the stirring element, and, on the other hand, in an acceleration in the direction of the longitudinal axis 220 of the body. The stirring element 200 according to
The illustrative embodiments according to
When the stirring element according to the invention is used in a vessel, the problem can arise that, if it makes contact with the wall, it is prevented from moving, in particular from rotating, or may even adhere to the wall as a result of adhesion forces. If a wettable outer surface of the stirring element does not adequately eliminate this problem, it is solved by a development according to
The stirring device according to the invention is shown schematically in
The piezo actuator 630 is connected to an alternating voltage source 640, which excites it to oscillation. By setting a suitable frequency, the coupled-in sound can be adapted to the resonant frequency of the gas bubbles enclosed in the cavities of the stirring elements. This ensures an increase in amplitude of the oscillation in the cavity and, therefore, an efficient utilization of the coupled-in sound.
After thorough mixing, the liquid or the flowable substance can be removed, for example by being poured out of the container 600, in which case the stirring elements 620 are held back in the container 600 with the aid of a suitable retainer element 650, for example in the form of a grid (illustrated only in
Although the stirring elements according to the invention can also be used in such a container, a primary interest is to use them for stirring and mixing particularly small amounts of liquid. The operating principle is largely independent of the scale of the stirring elements, for which reason it is possible to use them in very much smaller vessels, for example in titer plates, Eppendorf capsules or in a chamber of a sample preparation chip. The latter use is illustrated in
In the manner described above, the sound source causes an acoustic oscillation of the liquid in the chamber 710 and, therefore, of the air bubbles present inside the stirring elements 720. By means of the periodic movement of fluid that is generated in this way, the stirring elements are moved and the liquid is thoroughly mixed. Retainer elements 750 in the admission line 712 and also in the discharge line 714 ensure that the stirring elements 720 are held back in the chamber during delivery and discharge of the liquid.
In contrast to the illustrative embodiment according to
As can be seen from the view in
This preferably also applies to the cavity of the stirring element according to the invention, which cavity has a mouth in the form of a nozzle, with a mouth cross section that narrows in the direction of the opening to promote flow, and with a sharp tear-off edge in the plane of the opening.
As has been explained, the stirring elements can be used in a wide range of applications. In the configuration particularly suitable for mixing or stirring microscopic amounts of liquid, the stirring elements preferably have a length of 0.1 mm to 10 mm. The internal diameter of the cavity is preferably less than 1 mm and particularly preferably 0.1 mm to 1 mm. However, the principle of acoustic operation according to the invention also functions at the macroscopic level. Therefore, stirring elements in which the cavity has an internal diameter of up to about one centimeter and a length of up to several centimeters can also be used according to the invention.
Reference is once again expressly made to the fact that the exact number and shape of the cavities is not important. One, two or more cavities can be provided. It is possible for two, more and/or all cavities to be separate from one another or connected to one another. In particular, the cavities can be connected to one another by a common hollow space in the body.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2007 020 244.1 | Apr 2007 | DE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP2008/003163 | 4/19/2008 | WO | 00 | 10/23/2009 |
