Device and method for manipulating a liquid

The invention relates to a device and method for manipulating a liquid in a channel, wherein a body, which forms a capillary intermediate space with respect to the channel wall, is moved in the channel and the channel is filled with liquid only up to the body. Preferably, the body can also bridge an area of the channel that cannot be wetted for the liquid.

The present invention relates to a device for manipulating a liquid according to the preamble of claim1, and a method for manipulating a liquid according to the preamble of claim10.

The present invention relates particularly to the manipulation of a liquid in a microfluidic system or channel. It is known to use a valve or selective venting, for example, for manipulating the liquid. In this way the liquid can be stopped in particular at a specific point. The control or manipulation of the front of the liquid, particularly in a desired region of the channel, on the other hand, is difficult or involves additional effort.

The problem on which the present invention is based is to provide a device and a method for manipulating a liquid in a preferably microfluidic channel, by which an improvement in the manipulation, particularly of the flowing front of the liquid, is made possible or facilitated.

This problem is solved by a device according to claim1or a method according to claim10. Advantageous further features are the subject of the sub-claims.

In one aspect the present invention envisages providing or moving a body in a channel for the liquid, wherein a capillary gap or intermediate space is formed between the body and the channel wall, the liquid or its front is stopped in the gap or intermediate space by capillary forces and the channel only fills up with the liquid as far as the body or only up to the end of the gap or intermediate space, while the filling of the channel with the liquid is controlled or manipulated by the position and/or movement of the body. This makes it very easy to obtain and manipulate the flowing front—hereinafter also referred to as the “front” for short—of the liquid.

Preferably, the body fills the channel by more than 60%, in particular more than 70%, particularly preferably more than 80%, of the cross-sectional area. As a result, particularly high capillary forces can be achieved between the body and the channel wall.

In another aspect of the present invention, the body is moved over a region of the channel that cannot be wetted by the liquid and this region is bridged for the liquid so that the liquid flows or is able to flow over this region. This again allows very simple control or manipulation of the liquid or its front.

According to another aspect of the present invention, the body can be moved selectively or successively into different sections of the channel or into a channel that branches off from the channel, in order to selectively control the filling with liquid.

According to another aspect of the present invention, a side channel may branch off from the channel, and the liquid only flows or is able to flow in the side channel when the body is moved, or has been moved, with the liquid in the channel at least up to the branching-off of the side channel. In this way, too, it is possible to achieve selective control of the filling with the liquid in a simple manner.

Preferably, the body is guided in or by the channel in a defined alignment. In particular, the body cannot be rotated within the channel.

Preferably, the body has a length that is greater than the maximum cross section of the channel. This allows a defined movement and/or direction of the body in the channel or microfluidic system.

Preferably, the body is dimensionally stable with a defined shape.

The present invention relates to the manipulation of a liquid, particularly in a microfluidic channel or system. By “microfluidic” are meant, according to the invention, volumes of preferably less than 10 ml, particularly preferably less than 1 ml, and/or channel liquid cross-sections (maximum diameters) of preferably less than 2 mm, particularly preferably less than 500 μm.

The above-mentioned aspects of the present invention and the aspects and features of the present invention that arise from the following description and the claims may be implemented independently of one another, or in any desired combination.

In the Figures, the same reference numerals have been used for identical or similar parts and components, producing corresponding or similar advantages and properties, even if the description is not repeated.

FIG. 1shows in schematic plan view a proposed device1for manipulating a liquid2. The device1is preferably at least substantially card-shaped, plate-shaped, flat, thin and/or planar in configuration.

The device1preferably has (at least) one in particular microfluidic channel3for receiving the liquid2. The channel3or the device1forms, in particular, a microfluidic system or a part thereof.

As shown in a schematic cross section of the device1according toFIG. 2, the device1preferably comprises a base part1A in which the channel3or the microfluidic system is or are formed in particular by one or more depressions—preferably in the form of one or more grooves—which is or are preferably closed off by a cover1B. InFIG. 2, the liquid2is not shown.

The base part1A is preferably embodied as a plastics part and/or injection moulding. The base part1A is preferably at least substantially flat, planar, plate-shaped and/or rigid in configuration.

The channel3or the microfluidic system is preferably formed in or along a flat side of the base part1A and/or open towards a flat side. The channel3or the depression or flat side is preferably at least substantially totally closed off by the cover1B. However, other design solutions are also possible.

The cover1B is preferably embodied as a film. The cover1B is preferably stuck on, laminated on and/or welded on. Preferably, the cover1B is formed by an adhesive film or heat-sealable film or the like.

The cover1B is preferably transparent, at least in parts, for example in order to permit optical detection or examination or the like.

In all the plan views of the device1, the cover1B has been omitted for illustration purposes.

The device1has at least one body4that is movable in the channel3or system and/or in the liquid2.

The body4is movable in the channel3, in particular along the channel3. The plan view of the device1according toFIG. 1shows the body4in a first position. The plan view according toFIG. 3shows the body4in a second or other position.

The proposed device1and the proposed method provide that the liquid2and, particularly preferably, the front2A thereof (flowing front) and/or the filling of the channel3with the liquid2can be manipulated or controlled by means of the movement of the body4in the channel3, particularly depending on the position and/or movement of the body4. This is particularly made possible or achieved, according to the proposal, by the fact that the liquid2does not automatically fill the channel3, particularly as a result of capillary forces. In particular, the cross section of the channel3is chosen to be such (so great) and/or the wettability is chosen to be such (so little) that there is no, or in any case only marginal, flow of the liquid2, for example starting from a reservoir5connected to the channel3, into the channel3by capillary forces, over the relevant period of time. Particularly preferably, the angle of contact of the liquid2with the channel wall, formed here by the base part1A and the cover1B and optionally also with the body4or its surface, is less than 90°.

When the locally variable or movable body4is moved into the region of the front2A in the channel3, in particular moves out of the liquid2beyond the front2A into the not yet filled channel3, or is brought into contact for the first time with the liquid2, starting from the channel3which has not yet been filled, the liquid2flows into the gap or intermediate space6that is present between the channel wall and the body4. This intermediate space6is very narrow or slot-like, in particular. This geometric change to the channel cross section for the liquid2in the region of the body4leads to an increased pressure gradient within the liquid2or to an increased capillary force or to an outflow of the liquid2into the intermediate space6. In particular, such high capillary forces are at work in the intermediate space6that the desired outflow of the liquid2into the intermediate space6takes place in particular relatively or sufficiently rapidly.

If the body4in the channel3is moved away from the reservoir5or from the inflow end of the liquid2or from the part of the channel3that has already been filled with liquid2, i.e. to the right, as indicated by the arrow, in the representation inFIG. 1, so that the body4remains in contact with the liquid2or its front2A, the liquid2streams or flows constantly into the intermediate space6that is moving or being formed, and thus into the channel3. This provides a controlled transporting of the liquid into the channel3or permits controlled manipulation of the liquid2. In particular, the filling of the channel3with the liquid2or the position and/or movement of the front2A of the liquid2can thus be controlled or manipulated very simply.

FIG. 1shows the device1in a still moving state. The liquid2has not yet completely filled the intermediate space6, but has filled it only partially. The liquid2is thus still flowing into the intermediate space6, in particular, as indicated by the arrow. Alternatively or additionally, this may show that the body4itself is still being moved in the direction of the arrow, i.e. into the part of the channel3that is not yet filled with liquid2.

Particularly preferably, the maximum speed of movement of the body3is limited so that it is at least not substantially greater than the speed at which the liquid2fills the intermediate space6. In this way it can be ensured that even during a longer movement of the body4the contact of the body4with the liquid2or its front2A is not broken. However, it is also possible to move the body4temporarily faster. However, care must be taken to ensure that this movement does not last too long, so as to avoid the above-mentioned loss of contact with the liquid2. This can be done for example by correspondingly limiting the maximum travel distance at high speed and/or the maximum time taken for the travel at high speed.

FIG. 3shows the body4in another position. In particular, the intermediate space6here is completely full of liquid2. This is, in particular, a stationary state which is occupied when the body4is no longer being moved and the intermediate space6has been completely filled with the liquid2. In this state, the liquid2or its front2A terminates at least substantially with the end of the body4that is at the front in the direction of movement, or with the end of the narrow gap or intermediate space6for the liquid2that is formed between the body4and channel wall.

The body4has a preferably at least substantially sharp edge or a sharp step at least at its front end in the direction of movement, in order to generate by means of an increase in cross-section that is as abrupt or sharp as possible and thus produce a capillary stop for the liquid2or its front2A, so that the liquid2stops in a defined or reliable manner when the intermediate space6is completely full. This is to avoid, in particular, the liquid flowing out beyond the body into the channel3, particularly as a result of capillary forces, and thereby flowing completely around the body4. Even if this is preferably unwanted, this effect may nevertheless be utilised if necessary, for example if the body4is moved up to a corresponding projection, stop or other cross-section of the channel3or up to another body4in the channel3or brought into contact therewith.

The proposed device1and the proposed method may also be used to manipulate the liquid2, particularly by moving the body4within the liquid2and/or by moving the body4out of the liquid2and/or moving the body4into the liquid2. Thus, for example, it is possible to mix the liquid2or to transfer a specified amount of the liquid2or a constituent of the liquid2.

For moving the body4, the device1preferably comprises a manipulating device7, as shown inFIG. 2. However, the manipulating device7may only be associated with the device1, in particular it may form part of a separate device.

The movement of the body4preferably takes place in contactless manner and more particularly magnetically in the embodiment shown, particularly preferably by the variation of a magnetic field acting on the body4. In particular, the magnetic field is generated externally. In the embodiment shown, the manipulating device7comprises for this purpose at least one external magnet and/or electromagnet or a plurality of electromagnets.

Moreover, the body4is preferably produced at least partly from magnetic or magnetisable material, or provided therewith, the material in particular forming a magnet. In particular, a paramagnetic, superparamagnetic or ferromagnetic material is used.

The magnetic material or the magnet may for example be accommodated in the body4or glued therein or mounted or glued therein or, for example, cast therein. However, the body4may also be made essentially from magnetic or magnetisable material. If necessary, several or different magnetic materials or magnets may also be mounted or used on the body4, for example spatially distributed or spaced from one another, in particular so as to achieve a certain controllability or mobility of the body4.

The use of the magnetic material or the magnet may ensure for example that the body4is also movable along a gradient of the magnetic field acting on the body4, i.e. in particular a magnetic field generated by the manipulating device7, also in particular in an area of high magnetic field strength.

The body4can also be moved in a specified direction, into a specified area and/or optionally also in opposite directions, by suitably changing the magnetic field or the gradient of the magnetic field. Correspondingly rapid changes, particularly a change in the direction of the gradient of the magnetic field, can also provide a back and forth motion or reciprocating movement of the body4or oscillation of the body4which may be very rapid.

Alternatively or additionally, the body4can also be moved by any other method, for example by the action of gravity, for example during pivoting or rotation, or by the effect of some other force or acceleration, for example during rotation of the device1, by electrical attraction or repulsion, by frictional or interlocking engagement on the body4, for example by means of a filament or other tensioning or compression means, by ultrasound or the like.

The body4is preferably movable in the longitudinal direction or along the channel3at least or optionally only in one direction or in both directions.

In order to achieve or assist an easy and/or defined movement of the body, particularly in the channel3or along the channel3or on the bottom of the channel3or on the base part1A, the body4optionally comprises at least one guide means4A which, in the embodiment shown, may be formed by, in particular, a plurality of projections or runners, as indicated inFIG. 2. The guide means4A or the projections or runners may for example assist with the sliding of the body4on the base part1A or on the bottom of the channel3, i.e. may reduce the sliding resistance. The guide means4A may guide or hold the body4in particular at a spacing from the bottom of the channel3, the side walls of the channel3and/or the cover1B.

As required, the guide means4A may be provided on only one side, particularly on the bottom of the body4, or on several or all of the sides of the body4facing the channel wall. As required, differently configured guide means or projections, runners or the like may also be provided or formed on the various side faces.

To achieve the least possible contact of the body4with the channel wall or to achieve the least possible friction, particularly flat and/or calotte-shaped projections are particularly preferred.

Alternatively or additionally, the body4may also be guided laterally by the liquid2in the channel3. In particular, it is possible for the liquid2to tend to fill the intermediate space6between the body4and the channel wall, over the entire periphery of the body4, or towards all the channel walls. This filling may in particular take place automatically, as a result of capillary forces. This filling may for example take place automatically after the body4first comes into contact with the liquid2. As the body4then continues to move within the channel3, the intermediate space6then remains at least sufficiently filled with liquid to ensure that the body4is preferably guided laterally solely by the liquid2and in particular without making contact with the channel wall.

The above-mentioned filling of the intermediate space6with the liquid2and, in particular, the general lateral filling of the body4in the channel3with the liquid2and/or the rapid filling of the intermediate space6with the liquid2or rapid advance of the front2A in the intermediate space6may be assisted or achieved by a plurality of measures, in particular by a narrow size or flat configuration of the intermediate space6and/or by good or increased wettability of the body4.

The intermediate space6is preferably very thin or narrow or tight in configuration. This produces relatively high capillary forces in the intermediate space6which ensure that the liquid2fills the intermediate space6very quickly and/or preferably on every side around the circumference of the body4.

To increase or improve the wettability, the body4may be correspondingly partially or completely structured, particularly preferably microstructured, treated and/or coated, in particular at least or only on its surfaces and side faces facing the channel wall. In this way it is possible for example to ensure that the side faces of the body4are of correspondingly hydrophilic configuration, in the case of a hydrophilic liquid2, whereas the channel3or its channel wall is then of particularly hydrophobic configuration.

To assist or permit the guidance of the body4in the channel3by means of the liquid2and/or to assist or permit the filling of the intermediate space6at the bottom, the body4preferably has a density that at least substantially corresponds to the liquid2.

Preferably, the liquid2thus forms a film between the body4and the channel wall, i.e. in the intermediate space6, thus enabling the body4to be guided laterally.

The body4preferably has a cross-section which is at least substantially geometrically similar to the channel cross-section. The optional guide means4A are preferably not taken into consideration. Thus, a very small intermediate space6or one that is uniform over the circumference or cross-section can be achieved or ensured between the body4and the channel wall, particularly if the body4is at least substantially centrally arranged or guided in the channel3.

In the embodiment shown, the channel is at least substantially rectangular or square in cross-section. The body4is then preferably at least substantially correspondingly configured. However, other cross-sectional shapes may also be used. For example, it is also possible for the channel3and the body4to have an at least substantially round, oval or flat cross-section.

The body4is preferably of elongate configuration. This helps to ensure good guidance in the channel3.

The body4preferably has an at least substantially constant cross-section over its entire length or at least over a large left-hand region thereof.

In the embodiment shown, the body4is preferably at least substantially cuboid and/or prism-shaped.

The body4preferably comprises at least substantially flat or planar side faces that face the corresponding side walls of the channel wall.

The average or maximum distance of the body4or its surface from the channel wall, i.e. the average or maximum height or thickness of the intermediate space6, is preferably less than 1 mm, more particularly less than 500 μm, particularly preferably approximately 200 μm or less.

The body4is preferably guided in a defined alignment in the channel3or by means of the channel3.

Preferably, the body4has a length that is greater than the maximum cross-section of the channel3. Accordingly, the body4is guided at least in the lengthwise direction through the channel3.

Particularly preferably, the body4fills the cross-section of the channel3by more than 60% in terms of area, more particularly by more than 70% or 80%, as schematically shown in the cross-section according toFIG. 2. This ensures that the intermediate space6is very small in cross-section, which is advantageous particularly for filling it with liquid2.

The body4is preferably of dimensionally stable configuration with a defined shape.

The body3is preferably made of plastics or is a plastics component. This is favourable in terms of its manufacture or permits the use of a material having the desired properties. For example, the body4is made at least substantially of PMA or PE.

The body3is preferably an injection moulded part or is produced by injection moulding. This allows cheap and easy manufacture and/or shaping.

If required, the body4or at least its surface is made from a luminescent or fluorescent material or is, for example, partially coated therewith. This assists with detection of the body4.

The body4is preferably movable at least substantially in a straight line in the channel3and/or movable back and forth in the channel3. However, it is also possible that the channel3does not extend in a straight line but is coiled or meandering or is bent or extends in some other way. The body4may then preferably be moved along the channel3or in a section or region of the channel3.

Preferably, only a single movable body4is provided in the device1or channel3or in the system. This contributes to a defined movement. However, it is also possible to provide a plurality of bodies4in the channel3, which are in particular movable independently of one another and allow corresponding manipulation of the liquid2. For example, the bodies4may also be configured differently, for example they may have different cross-sections or sizes and/or be movable in different sections or channels and/or may also be movable together or cooperate with one another, so that for example the intermediate spaces6between the bodies4and the channel wall can be brought into communication with one another and the liquid2can be conveyed or transferred from one intermediate space6to another intermediate space6.

The body4may also be movable into different regions or sections of the channel3or microfluidic system and/or into different liquids2.

Particularly preferably, according to the proposal, the body4is always moved or manipulated with the front2A of the liquid2or, conversely, the front2A of the liquid2is always moved or manipulated together with the body4or by the body4.

The proposed device1and the proposed method can be used for different purposes. Thus, for example, a certain volume of liquid can be placed in the channel3. Alternatively or additionally, the wetting of the channel3can be influenced by the position of the body4.

Some other embodiments of the proposed device1and methods and uses will be described in more detail hereinafter by means of the additional Figures. The previous remarks and explanations apply accordingly and in a supplementary manner, even though the corresponding description has not been included, to avoid repetition.

FIGS. 4 and 5each show a plan view of the proposed device1according to a second embodiment, the body4being shown in various positions.

The channel3in the second embodiment comprises at least one non-wettable region3A which can be bridged for the liquid2by means of the body4.

In the embodiment shown the channel3has two or more branches or channel sections3B and/or two or more non-wettable regions3A. Preferably, the body4is selectively movable into one of the two channel sections3B and/or over at least one of the two regions3A. In the embodiment shown the channel sections3B are connected to a main section of the channel3for example by means of a branch connecting them to one another, the body4being selectively movable into one of the channel sections3B, as shown inFIG. 5.

The body4may for example be moved temporarily or permanently over or onto a non-wettable region3A, as shown inFIG. 5. In this way the corresponding region3A is preferably bridged, so that the liquid2can flow, in particular, over the body4or through the intermediate space6over the non-wettable region3A into the adjoining channel or channel section3B, as shown inFIG. 5.

In order to bridge the non-wettable region3A by means of the body4, the body4is preferably moved over or onto the non-wettable region3A, so that the liquid2can flow through the intermediate space6over the region3A into the adjoining channel3or channel section3B.

Preferably, the body4has a longer length in the longitudinal direction of the channel than the non-wetting region3A, so that the body4is preferably able to cover the region3A completely and in particular can project on both sides into the adjoining channel region, in order to bridge the region3A fluidically—i.e. for the liquid2—in such a way that the liquid2is able to flow away over the region3A.

The non-wettable region3A may if necessary be formed only on the bottom of the channel3or optionally over the entire cross-section or circumference of the channel3, i.e. also on the side walls and on the lid1B, for example, in addition to the bottom.

The non-wettable region3A is particularly preferably formed by a corresponding coating and/or treatment of the respective material.

By the term “non-wettable” is meant, in particular, according to the proposal, that the wetting of the region3A by the liquid2is so poor or the contact angle is so small that the liquid2does not flow away over this region3A into the adjoining channel3or channel section3B. Rather, it requires bridging by the body4.

Depending on the configuration, it may be such that after a first wetting or bridging of the region3A, a permanent fluid connection or flow over the region3A is made possible, even if the body4no longer bridges the region3A. However, it is also possible for this fluid connection or flow over the region3A to be maintained only when, or as long as, the body4also bridges this region.

When the body4is moved away again, for example moved on, as shown inFIG. 5, or moved back again, for example into the section of the channel3that has already been filled with liquid2, the fluid connection over the region3A may also be interrupted directly again or may be broken automatically. This depends particularly on the capillary forces or on the wettability and dimensions, for example of the region3A.

If necessary, in the second embodiment the body4may also be moved back into the main section of the channel3and then into the other channel section3B, in this case into the upper channel section3B, so as to bridge the other non-wettable region3A (too) for the liquid2.

It is also possible that a plurality of non-wettable regions3A are arranged or formed one behind the other, at a spacing from one another, in the channel, and can be bridged for the liquid2by means of the body4, particularly one after the other. Thus, for example, a correspondingly controlled or manipulated forward flow of the liquid2in the channel3can be achieved, in order, for example, to carry out and/or run various reactions, detections or the like one after the other in channel sections3A located behind one another.

In the second embodiment, the body4is preferably selectively or successively movable into at least one or into several regions or sections3B of the channel3.

In the third embodiment, explained hereinafter with reference toFIGS. 6 to 8, the device1comprises at least one, preferably several side channels3C, which branch off, in particular, laterally from the channel3and/or preferably have a smaller cross-section in relation to the channel3. By corresponding positioning or movement of the body4along the channel3it is possible to supply, or fluidically connect, a desired side channel3C or the side channels3C with the liquid2.

In the plan view according toFIG. 6, the body4with the front2A is still at a distance from the first side channel3C, so that the liquid cannot flow into this side channel3C.

In the plan view according toFIG. 7, the body has been moved further forwards and has reached the first side channel3C, so that it is now fluidically connected or the liquid2is able to flow, or has flowed, into the side channel3C, as shown inFIG. 7.

In the plan view according toFIG. 8, the body4is in a further advanced position, adjacent to the next side channel3C, so that this is now also connected to the liquid2or is being filled with the liquid2or has already been filled, as shown inFIG. 8.

The influx of liquid2into a side channel3C of the channel3is thus controlled by the body4, while the liquid2only flows into the side channel3C when the body4is being moved or has been moved with the liquid2in the channel3at least up to the point where the side channel2C branches off from the channel3.

Thus, by means of the proposed device1and the proposed method, it is possible selectively to supply individual channel portions3B or side channels3C or the like with the liquid2. This can be done in particular by selective attachment or connection and/or bridging of a non-wettable region3A, or the like.

Alternatively or additionally, the proposed device1and the proposed method may also be used to meter the liquid2, particularly by corresponding movement of the body4and/or by selective filling of corresponding metering regions or chambers.

Individual features of the different embodiments and the embodiments themselves may be combined with one another as desired, but may also be implemented or used independently of one another.

LIST OF REFERENCE NUMERALS