The present invention relates to a microfluidic platform having at least one means for initiating a movement of a liquid, in particular a sample liquid, between at least two locations of the microfluidic platform.
The term “microfluidic platform” in the present invention is meant to encompass all objects or devices in which sample liquids that are to be investigated or manipulated can be accommodated in cavities and can be transported by suitable means (for example, capillary forces acting in microchannels) to reaction locations that are provided accordingly.
In particular, the present invention encompasses microfluidic platforms such as, for example, sample carriers, test strips, biosensors or the like, which may be used for carrying out individual tests or measurements. For example, biological liquids (e.g., blood, urine or saliva) may be investigated on the one hand for pathogens or incompatibilities but also on the other hand for their content of, for example, glucose (blood sugar) or cholesterol (blood fat). For this purpose corresponding detection reactions or whole cascades of reactions take place on the microfluidic platforms.
For these, it is necessary for the biological sample liquid to be transported by suitable means to the reaction location or locations provided for this purpose. This transporting of the sample liquid may, for example, be effected by passive capillary forces (by corresponding capillary systems or microchannels) or by an active actuating system.
The active actuating system used may be, for example, injection or diaphragm pumps which may be located outside the microfluidic platform or on said platform.
Generally, microfluidic platforms have a sample application area of the order of a few millimetres in size for the application of a quantity of sample liquid of the order of a few microlitres, the sample liquid (e.g., blood) having to be transported through a microchannel or a microchannel system to corresponding sample utilisation areas or reaction locations. This transporting or this movement of the sample liquid should take place reliably and in a simple manner.
DE 10 2004 050 062 A1 describes, for example, microfluidic platforms of this kind, while a plurality of usable platforms may be joined together as an endless strip and may be individually detached from the strip for use. The sample liquid is transported here exclusively by means of capillary forces.
DE 20 2009 008 052 U1 describes a microfluidic platform, in which both capillary forces and also an active element in the form of a pressure source are used as means for initiating a movement of a sample liquid or for transporting said liquid. The device shown is intended to be able to control transport processes in the microfluidic system precisely and safely, while the manufacturing costs for the microfluidic platform are to be kept comparatively low.
The problem of the present invention is to provide an alternative microfluidic platform of the generic type, with which at least a portion of a liquid, in particular a sample liquid, can be transported between two locations on the microfluidic platform reliably and in an easily manageable manner.
The at least two locations may be, for example, on the one hand, a sample application area in which a sample liquid is applied, and on the other hand a sample utilisation area or reaction area to which the sample liquid is to be transported and undergo a specific detection reaction therein with suitable reagents. Both the sample application area and the sample utilisation area may be embodied as cavities.
The problem stated above is solved by the characterising features of claim 1. Advantageous embodiments or further features of the invention can be inferred from the respective subclaims.
The invention starts from a microfluidic platform with at least one means for initiating a movement of a liquid, in particular a sample liquid, between at least two locations of the microfluidic platform.
It is now provided according to the invention that the at least one means comprises at least one element of changeable volume and/or shape, which is mounted on at least one component movably connected to the microfluidic platform and, by movement of the component, can be brought into a position such that the element, by changing its volume and/or shape, causes the liquid located at the at least one location to be at least partly moved from this location to the at least one other location.
By this measure it is very easy to move a liquid between two locations of a microfluidic platform without the need for external equipment (e.g., external pumps) essentially independent of the microfluidic platform. Naturally, additional capillary channels may be provided on the microfluidic platform, in which the liquid is transported purely passively by capillary forces.
It has proved very convenient if the at least one element of changeable volume and/or shape can be brought, by movement of the component, into a position such that the element, by increasing in volume, at least partly fills at least one cavity or, by decreasing in volume, at least partly re-opens at least one cavity that has previously been formed by the element or such that, as the element changes shape, the volume of at least one cavity that is at least partly delimited by the element can be changed.
An essential feature here is therefore the element of changeable volume and/or shape. When it at least partly fills at least one cavity, having increased in volume, the cavity may preferably be a sample application area of the microfluidic platform.
If this sample application area contains sample fluid that has been introduced previously, this sample liquid is displaced out of the sample application area, in accordance with the increase in the volume of the element into the sample application area, and can be transported in the direction of a sample utilisation area, for example.
The element which thus changes its volume and to a certain extent its shape as well, is thus a component for producing a kind of overpressure pump for transporting a sample from a sample application area to a sample utilisation area.
Conversely, however, it is also possible that the element decreases in volume and at least partly frees up at least one cavity that has previously been at least partly filled by the element. In this case, a vacuum is formed by the volume that has been freed up in the cavity. If the cavity is fluidically connected (for example, via corresponding microchannels) to a sample utilisation area and the latter is in turn connected to a sample application area, this initiates transfer of a sample liquid that has been delivered to the sample application area, in the direction of the sample utilisation area or in the direction of the said freed-up cavity.
In this case the element of changeable volume and/or shape thus serves as a kind of vacuum pump for transporting the sample liquid.
Finally, it is also possible for the element to be changeable only in its shape and for it to at least partially define a cavity in a specific position. A sample application area may, for example, be part of the cavity, which is at least partially delimited by the element of changeable shape. If the element of changeable shape, which may, for example, be configured as a membrane, is then pushed into the cavity, the volume of the cavity bounded by the element of changeable shape is reduced.
This produces a kind of manual diaphragm pump, which is integrated in the microfluidic platform and in turn is able to initiate transport of the sample liquid to a sample utilisation area that is fluidically connected to the sample application area.
With the reduction in pressure on the membrane-like element that is changeable in shape, the volume of the cavity that is at least partly bounded by this element is increased again, so that it is possible to transport a liquid in the opposite direction, i.e., back towards the cavity that is at least partly bounded by the element. Corresponding applications may be envisaged.
It has proved very advantageous if the component is embodied as a cover and in at least one position covers at least one cavity. Expediently, the cover-like component may be arranged to cover the microfluidic platform at least from two opposite sides.
If the cavity is a sample application area, for example, the movement of the cover-like component triggers a dual function, so to speak. On the one hand, the transporting of a sample solution applied to the sample application area is brought about by the element of changeable volume and/or shape, and on the other hand at the same time the sample application area is covered and in this way subsequent contamination of the sample liquid, for example, by the user or by contamination of the environment by the sample liquid, is reliably prevented.
The microfluidic platform can be configured to be particularly easy to handle if the cover-like component is connected to the microfluidic platform so as to be slidable or pivotable therewith.
Expediently, at least one sealing means may be provided such that, in the at least one position of the cover-like component that covers at least one cavity, the covered cavity is outwardly sealed off. This reinforces the effect of the element of changeable volume and/or shape.
It is very useful if the sealing means is provided on the cover-like component on the side facing the at least one cavity that is to be covered. Alternatively, the sealing means could also be provided on the microfluidic platform, specifically around the cavity that is to be covered. The sealing means used may be, for example, a film-like seal which can correspondingly be adhered to the area that is to be sealed off. However, other shapes of seal are also possible, such as, for example, lip-like seals.
According to an advantageous further feature of the invention, it is envisaged that the cover-like component has at least one cavity or opening, in which the at least one element of changeable volume and/or shape is at least partially held. In this way, the element can easily be carried with it during movement of the cover-like component.
In particular, it is expedient if the element of changeable volume and/or shape is compressed in a first position of the cover-like component that opens up the cavity and the cover-like component can be moved into a second position in which the cavity is sealingly covered and the element of changeable volume and/or shape has relaxed into the cavity, the cavity being fluidically connected to at least one other cavity, particularly a sample utilisation area.
The cavity may advantageously be embodied as a sample application area of a technical medical measuring instrument, for example, a biosensor, a test strip or the like. When the element of changeable volume and/or shape expands into the sample application area after corresponding movement of the cover-like component, the sample liquid is forced in the direction of the sample utilisation area.
It may be envisaged according to another embodiment of the invention that, in a first position of the cover-like component, the element of changeable volume and/or shape is relaxed into a cavity of the microfluidic platform and the cover-like component can be brought into a second position, sealingly covering the cavity, in which the element of changeable volume and/or shape has opened up the cavity and has been compressed, while the cavity of the microfluidic platform is fluidically connected to at least one other cavity, particularly to a sample utilisation area and a sample application area.
According to this further feature, during the movement of the cover-like component, a sample liquid applied to the sample application area is transported towards the cavity that has been opened up, i.e., therefore towards the sample utilisation area as well.
In order to ensure easy movement of the cover-like component it is expedient that the element of changeable volume and/or shape should have bevels on the side facing the cavity. According to yet another further feature of the invention, the element of changeable volume and/or shape is of membrane-like configuration and the cover-like component can be brought into a position, in which at least one cavity is sealingly covered and in which the membrane-like element at least partly defines a cavity, while by applying pressure to the membrane-like element it is possible to reduce the volume of the cavity which is thereby at least partly restricted. This further feature makes it possible in particular to produce a diaphragm pump which is virtually integrated in the cover-like component.
It is naturally also possible for the microfluidic platform advantageously to comprise a plurality of cavities and for a plurality of elements that are changeable in volume and/or shape to be provided, which are mounted on the at least one component that is movably connected to the microfluidic platform. In this way, for example, a plurality of (possibly different) sample liquids can be applied, for example, to several sample application areas and with a movement of the component a movement of the sample liquid in the manner described previously can be initiated.
However, the invention does not relate only to a microfluidic platform as described, but also to a method of initiating a movement of a liquid, particularly a sample liquid, between at least two locations of a microfluidic platform, in particular using a microfluidic platform according to the invention.
According to the invention the method comprises at least the following steps:
The method according to the invention very reliably allows the initiation of a movement of a liquid between at least two locations of a microfluidic platform.
In an advantageous embodiment of the method, it may be envisaged, for example, that the at least one element of changeable volume and/or shape is brought, by the movement of the component, into a position such that, with an increase in volume, the element at least partly fills the at least one cavity, or, with a decrease in volume, at least partly frees up the at least one cavity which has previously been at least partly filled by the element or, with a change in the shape of the element, the volume of at least one cavity at least partly defined by the element is changed.
In particular, three further features of the method according to the invention may advantageously be envisaged.
It may be envisaged that the element of changeable volume and/or shape is compressed in a first position of the cover-like component that opens up the cavity, and the cover-like component is brought into a second position in which the cavity is sealingly covered and the element of changeable volume and/or shape relaxes into the cavity, the cavity being fluidically connected to at least one other cavity, particularly a sample utilisation area.
However, the method may advantageously be embodied so that the element of changeable volume and/or shape in a first position of the cover-like component is relaxed into a cavity of the microfluidic platform and the cover-like component is brought into a second position that sealingly covers the cavity, in which the element of changeable volume and/or shape has freed up the cavity again and has been compressed, the cavity of the microfluidic platform being fluidically connected to at least one other cavity, particularly to a sample utilisation area and a sample application area.
A third advantageous embodiment of the method may provide that the element of changeable volume and/or shape is of membrane-like configuration and the cover-like component is brought into a position, in which at least one cavity is sealingly covered and in which the membrane-like element delimits the at least one cavity at least partly, while as a result of pressure on the membrane-like element the volume of the at least one cavity that is thereby limited at least in parts is reduced.
Further advantages and embodiments of the invention will be illustrated by means of embodiments by way of example, which are described in more detail with the aid of the accompanying drawings, wherein
b is a plan view of the microfluidic platform according to
c is a view of the microfluidic platform according to
d is another view according to
a is a second embodiment of a microfluidic platform according to the invention in a diagrammatic sectional view along section line A in
b is a plan view of the microfluidic platform according to
c is a representation of the microfluidic platform according to
d is also a representation according to the view in
e is a view of the microfluidic platform in the position shown in
a is a third embodiment of a microfluidic platform according to the invention in a lateral sectional view along section line A from
b is a view of the microfluidic platform according to
c is a view of the microfluidic platform according to
d is a view of the microfluidic platform according to the view in
e is a plan view of the microfluidic platform in the position according to
Reference will be made first to
The sample application area 100 serves for the application of a sample liquid P (shown by dashed lines) which is connected via a microchannel 102 to the sample utilisation area 101. The sample utilisation area 101 may, for example, contain reagents, so that sample liquid P entering the sample utilisation area 101 causes corresponding detection reactions for detecting a particular analyte. The sample utilisation area 101 in turn may be provided, via a microchannel 103, with other cavities or venting means (not shown in detail).
The cavity of the sample application area 100 is opened upwards to receive the sample P. The sample utilisation area 101 and also the microchannels 102, 103 are covered at the top by a thin cover film 14 which may, for example, be adhered to the base member 10. On the left hand side, the base member 10 is movably connected to a movable cover 11 which is substantially rectangular in outline, in plan view. The cover 11 has an upper cover part 110, a lower cover part 111 and a rear cover wall 112. The above-mentioned parts of the cover 11 may be both connected to one another in multiple sections and also formed in one piece.
It can be seen that the left-hand end of the base member 10 is accommodated between the upper part 110 and the lower part 111 of the cover 11. In
It is also apparent that a substantially circular recess 113 has been provided in the upper cover part 110, in which an element 12 of changeable volume and/or shape is held. The element 12 may be adhesively attached to the upper cover part 110 on its upper side, for example. Preferably, the element 12 of changeable volume and/or shape is made of compressible or deformable synthetic material, for example, foam or rubber.
In order to move the sample liquid P applied to the sample application area 100, or at least some of said liquid P, towards the sample utilisation area 101, the biosensor 1 shown operates as follows:
After the sample liquid P has been placed in the sample application area 100 (
In the position shown in
If the cover 11 is now pushed further to the right (
Depending on the dimensions of the cavities of the sample application area 100, sample utilisation area 101 and the microchannels 102, 103, the sample liquid P′ displaced into the sample utilisation area 101 also passes through the microchannel 103 into other cavities (not shown in detail) which in some cases may also be needed for other subsequent reactions. Also, as the sample liquid P is displaced by the element 12 expanding into the cavity of the sample application area 100, the additional seal 13 essentially prevents sample liquid P from escaping outwards from the cover 11.
In the embodiment shown the cover 11 is designed so that it is held in the opened position (
In the embodiment shown in
a to e now show a second embodiment of a microfluidic platform according to the invention in the form of a biosensor 2. The biosensor 2 also comprises a base member 20 comparable in shape to the base member 10, and provided at its left-hand end with a substantially circular cavity 200. The cavity 200 is connected via a microchannel 202 with the substantially circular cavity of a sample utilisation area 201. The sample utilisation area 201 is in turn connected via a microchannel 203 to the substantially circular cavity of a sample application area 204. The sample application area 204 is upwardly open and allows a sample liquid P to be introduced (cf.
However, for this purpose the microchannels 202, 203 and also the sample utilisation area are closed off at the top by a cover film 24 which is, for example, adhered to the base member 20. On the left-hand side of the base member 20 a cover 21 is movably connected thereto. The cover 21 is in an extended position, in the position shown in
It is also apparent that the element 22 has a bevel 220, which is provided on the side facing the cavity 200 and in the direction of movement, i.e., on the right (cf. the arrows) in the Figures.
In the embodiment shown in
As in the embodiment according to
In the embodiment shown in
Also provided in the embodiment shown in
a to e show a third embodiment of a microfluidic platform according to the invention. A biosensor 3 is shown which in turn shows a base member 30 comparable in shape with the base members 10 and 20 and a cover 31 that is movably connected thereto. The base member 30 of the biosensor 3 is in turn shown only partly (in the region of the cover 31) and comprises there a sample application area 300 for the application of a sample liquid P which is fluidically connected through a microchannel 302 to a sample utilisation area 301. From the sample utilisation area 301 runs another microchannel 303 which is able to connect the sample utilisation area 301 to other cavities or venting devices (not shown in detail). The sample utilisation area 301 and the microchannels 302 and 303 are covered at the top by a suitable cover film 34.
The cover 31 comprises an upper part 310, a lower part 311 and a rear wall 312, similarly to the other embodiments.
Also provided in the upper cover part 310 is a substantially circular through-opening 313. An element 32 of changeable volume and/or shape in the form of a membrane-like part is mounted in the upper part of the through-opening 313, preferably by adhesive bonding or welding.
Moreover, on the underside of the upper cover part 310 there is also provided a film-like seal 33 which surrounds the opening 313. In this embodiment as well, suitable means (not shown in detail) are provided which secure the cover 31, preferably by latching, in its open position shown in
If the cover 31 is now pushed to the right, in the direction of the base member 30, until it reaches the end stop, by the application of a releasing force (step S1″,
At the same time the volume V is sealed off to the outside by the cover 31, the sealing action being further reinforced by the above-mentioned seal 33.
If in a further step the membrane-like element 32 is pressed down (S2″, 32′,
In the embodiment shown in
Finally it should be pointed out that the embodiments shown in
Thus
Moreover, a cover 41 is slidably connected to the base member 40 and has a plurality of elements 42 of changeable volume and/or shape which may, for example, be configured in the manner of the element 12 shown in
It is, of course, possible to provide a movable connection of the above-mentioned covers with the base members of the microfluidic platforms by some other method. For example, instead of a sliding movement, a rotary or hinged movement may also be provided.
The microfluidic platforms 1 to 4 described are preferably made of plastics, using the known plastics processing methods, particularly injection moulding. The films 14, 24, 34 and 403 that cover the cavities and microchannels formed in the base members 10 to 40 may be, for example, self-adhesive films or films provided with hot-melt adhesives which are laminated onto the surface of the base members. Alternatively it is also possible, of course, to use fixed covers for the covering, attached to the base members for example by UV adhesion, ultrasound welding, laser welding or high frequency welding.
Number | Date | Country | Kind |
---|---|---|---|
10186837.0 | Oct 2010 | EP | regional |
Filing Document | Filing Date | Country | Kind | 371c Date |
---|---|---|---|---|
PCT/EP2011/067340 | 10/4/2011 | WO | 00 | 11/15/2013 |