EP2729251B1 - Microfluid structure with cavities - Google Patents

Description

The invention relates to a microfluidic structure, comprising at least one cavity with at least one inlet opening and at least one outlet opening, wherein the cavity can be filled with a liquid or flowed through by a liquid and within the cavity at least one element is provided which the liquid in the flow within the cavity stops at least temporarily and / or at least partially deflects.

Microfluidic structures are components of microfluidic platforms or microfluidic components and essentially comprise cavities and / or channels in which sample liquids to be examined or manipulated can be taken up and transported by suitable means (for example capillary forces, generated pressure differences) to correspondingly provided reaction sites ,

In particular, the present invention encompasses microfluidic platforms such as, for example, sample carriers, test strips, biosensors, or the like, which may serve to perform individual tests or measurements. For example, biological fluids (eg blood, urine or saliva) can be examined for pathogens, incompatibilities and also for their content, for example glucose (blood sugar) or cholesterol (blood fat). For this purpose, corresponding detection reactions or entire reaction cascades take place on the microfluidic platforms.

For this purpose, it is necessary that the biological sample liquid is transported to the appropriate reaction site or the reaction sites by suitable means. Such a transport of the sample liquid can take place, for example, by means of passive capillary forces (by means of appropriate capillary systems or microchannels) or else by means of an active actuator. As active actuators syringe or diaphragm pumps are used, for example, which can be located outside of the microfluidic platform or on this and build up within a micro-fluidic structure consisting of micro channels and micro cavities in particular a corresponding pressure.

In general, microfluidic platforms have a sample task on the order of a few millimeters to give up a sample liquid amount on the order of a few microliters, the sample liquid (for example, blood) must be transported via a micro-channel or via a micro-channel system to corresponding cavities, in which, for example chemical reactants are in dried form.

In order for a sample liquid to be able to perform a satisfactory detection reaction with the reactants in a cavity, the most uniform and complete possible filling of such a cavity is required.

When filling large, in particular wide and irregularly shaped cavities, for example with length and / or width dimensions of several millimeters and a resulting volume range of, for example, 10 .mu.l to about 10 ml, there is the problem that the cavity does not fill evenly and so air bubbles or air bubbles can form in the cavity. As a result, the entire volume of the cavity for the sample liquid is not available. In such a cavity, for example, stored dry substances are not sufficiently dissolved and it can lead to lump formation, whereby a desired detection reaction can be impaired.

According to the prior art, this is remedied by arranging web-like elements in the cavity such that the liquid in the cavity has to perform a meandering flow direction.

A disadvantage of this structure, however, is that volume actually consumed within the cavity is consumed by the web-like elements.

To compensate, therefore, more area must be provided on the microfluidic platform or the microfluidic component. This should be avoided in particular for microfluidic platforms because of the associated increase in manufacturing costs.

From the DE 103 60 220 A1 is a microfluidic structure or a microfluidic platform for air bubble free filling known. Concretely, there is provided a cavity, with an inlet opening and an outlet opening. In the area of the inlet opening, the Cavity microstructure elements in the form of columns on. This area forms a site with increased capillary force. Due to the increased capillary force, first a complete and air bubble-free wetting of the entrance area of the cavity with sample liquid takes place. Only then is a wetting of the outlet opening facing part of the cavity. EP 0 153 110 A2 shows a microfluidic structure with ribs. In order to accelerate the liquid transport, a ramp is provided in the cavity, which raises the level of the cavity floor to the level of the outlet opening.
Such an arrangement is unsatisfactory for the filling of large, in particular (transverse to the inflow or throughflow direction of the liquid) wide and irregularly shaped cavities.
The invention is therefore based on the object to improve a microfluidic structure according to the preamble of claim 1 such that an improved, in particular substantially air bubble-free filling, in particular of large cavities is made possible. This object is achieved with the characterizing features of claim 1. Advantageous developments of the invention can be taken from the subclaims.
The invention is therefore based on a microfluidic structure, comprising at least one cavity having at least one inlet opening and at least one outlet opening, wherein the cavity can be filled with a liquid or flowed through by a liquid and within the cavity at least one element is provided, which at the liquid whose flow within the cavity at least temporarily stops and / or at least partially deflects.
According to the invention, it is provided that the at least one element is formed by a depression formed in a wall of the cavity, which has at least one first region at which the liquid is stopped and / or at least partially deflected at least temporarily and at least one second region at which the liquid preferably flows into the depression.
In this case, the liquid runs immediately upon reaching the second region, that is, without a significant stop into the depression and pulls from a certain filling level the well also in the first area of the well first stopped liquid into the recess.

In this way, the liquid in the cavity can be controlled so that the cavity is filled evenly and substantially free of air bubbles. This is also possible with large, in particular wide and irregularly shaped cavities which, for example, have a filling volume of the order of magnitude of about 10 μl to 10 ml.

It should be noted that said wall of the cavity may be, for example, a bottom of the cavity. But there are also any other walls of the cavity conceivable. Thus, the wall, with a suitable design of the cavity-closing lid, for example, be formed by this itself. A combination of these two options is possible, for example.

According to a development of the invention, it is provided that the second region is formed by a ramp-like transition, which, starting from a bottom level of the cavity, passes over to a bottom level of the depression.

This ramp-like transition ensures in a simple manner that the sample liquid at this point runs into the depression without a stop and fills it.

It has proven to be advantageous that the ramp-like transition, starting from a boundary edge of the recess with a bottom plane of the cavity forms an angle of about 10 degrees to 60 degrees, more preferably of about 45 degrees. Experiments have shown that with the choice of such geometric parameters a desired flow behavior of the liquid is best realized.

However, instead of a ramp-like design, other embodiments of the second area would also be conceivable. Thus, the second region could also be formed by a "smooth" transition, for example by a convex or concave rounding. Also, a notch-like structure (seen in plan view of the depression) is conceivable.

By contrast, the first region is expediently formed by a boundary edge of the depression on which the converging, forming the boundary edge Walls occupy an angle which is less than 120 degrees, preferably approximately between 95 degrees and 70 degrees, more preferably at about 90 degrees.

In this way, the first region forms a capillary stop in a very reliable manner, at which the inflowing liquid is first stopped or deflected.

It has also proved to be very advantageous in experiments, if the at least one recess is elongated, wherein the at least one first region facing an inflowing liquid and the at least one second region of an inflowing liquid is remote. Thus, the inflowing liquid can be controlled such that it initially reaches the first area, is stopped there, deflected and preferably reaches the second area (without a noteworthy stop) into the depression and fills it. With a corresponding arrangement of several recesses with each other, the desired fluid control of the specific length of a cavity can be adjusted.

The recess may be formed in plan view, for example, approximately rectangular. But it can also be different in plan view, for example, be arcuate. This may be expedient, for example, if the cavity to be filled is likewise curved in its longitudinal extension.

A further advantageous embodiment of the inventive idea provides that a plurality of depressions are provided, which are arranged starting from side walls of the cavity, mutually.

In this way it is possible to emulate a meandering flow pattern of the liquid with the wells in the cavity to be filled.

It has also proved to be advantageous if the at least one first region extends approximately over the entire length of one longitudinal side of the at least one depression and the at least one second region only over a portion of the length of another longitudinal face.

This makes it possible, on the one hand to ensure a capillary stop on a wide front and, on the other hand, a time-delayed inlet of the liquid into the depression, wherein additional volume can be obtained at the location where the second area is not formed.

However, the invention also relates to a microfluidic platform with at least one microfluidic structure according to at least one of claims 1 to 7. Such a microfluidic platform can be produced inexpensively and meets high demands on a process-reliable, in particular air bubble-free filling of the existing cavities.

Fig. 1

eine mikrofluidische Struktur gemäß einem ersten, bevorzugten Ausführungsbeispiel in einer Draufsicht, prinziphaft dargestellt,

Fig. 2

eine Schnittdarstellung der mikrofluidischen Struktur gemäß Schnittverlauf II in Fig. 1,

Fig. 3

eine Detaildarstellung III aus Fig. 2,

Fig. 4a bis 4f

unterschiedliche Befüllstadien der mikrofluidischen Struktur gemäß Fig. 1 mi einer Flüssigkeit,

Fig. 5

eine mikrofluidische Struktur in einer Draufsicht gemäß einem zweiten Ausführungsbeispiel, prinziphaft dargestellt,

Fig. 6

eine mikrofluidische Struktur in einer Draufsicht gemäß einem dritten Ausführungsbeispiel, prinziphaft dargestellt,

Fig. 7

eine mikrofluidische Struktur gemäß dem Stand der Technik und

Fig. 8

eine Schnittdarstellung gemäß Schnittverlauf VIII aus Fig. 7.

Further advantages and embodiments of the invention will become apparent from embodiments, which will be explained in more detail with the aid of the accompanying figures. Mean

Fig. 1

a microfluidic structure according to a first preferred embodiment in a plan view, shown in principle,

Fig. 2

a sectional view of the microfluidic structure according to section line II in Fig. 1 .

Fig. 3

a detail III from Fig. 2 .

Fig. 4a to 4f

different filling stages of the microfluidic structure according to Fig. 1 with a liquid,

Fig. 5

a microfluidic structure in a plan view according to a second embodiment, shown in principle,

Fig. 6

a microfluidic structure in a plan view according to a third embodiment, shown in principle,

Fig. 7

a microfluidic structure according to the prior art and

Fig. 8

a sectional view according to section line VIII from Fig. 7 ,

First, on the Fig. 1 to 3 Referenced.

These figures show a microfluidic structure 1 introduced in a microfluidic component 2. The microfluidic structure 1 comprises a cavity 10, which has a filling volume of about 15 μl. The cavity 10 is unevenly shaped and provided with an inlet opening 11, which connects the cavity 10 with a filling channel 16. The filling channel 16 itself may be connected to an unspecified numbering filling opening (for example, a sample task area).

On the other side, the cavity 10 is provided with an outlet opening 12 which, for example, releases the fluidic connection to a ventilation channel 17. In the region of the outlet opening 12, a capillary stop 24 is also provided in the usual way.

Additionally or alternatively, the cavity 10 may be connected via an outlet opening to a further microchannel 18 (indicated by dashed lines) if a liquid is to be transported through the cavity 10, for example into a further cavity (not shown).

The cavity 10 is a comparatively large cavity having dimensions of about 12 mm in width, 36 mm in length and about 1.5 mm in depth.

Furthermore, it can be seen that within the cavity 10 three recesses 13 are arranged. Each recess 13 has in plan view approximately a rectangular appearance with a length L and a width B. The recesses 13, starting from longitudinal sides of the cavity 10, are mutually arranged.

It can be seen that each depression 13 has a first region 14 which faces an inflowing liquid F (cf. Fig. 4 ) and at which the inflowing liquid F is at least temporarily stopped and / or at least partially deflected.

Furthermore, each depression 13 is provided with a second region 15, at which an incoming liquid F runs into the depression 13 without stopping.

The cavity 10 is closed by a cover 21 (for example, a glued foil) and has a bottom 19. Each recess 13 has a bottom 20.

In particular, from the detailed representation according to Fig. 3 It can be seen that the first region 14 (capillary stop) is formed by a boundary edge 22 of the recess 13, at which the converging, the boundary edge 22 forming walls occupy an angle β, which is 90 degrees. Deviating from the embodiment, of course, other angles are conceivable, which may be greater or less than 90 degrees.

Furthermore, it can be seen that the second region 15 is formed by a ramp-like transition R, which, starting from the bottom level 19 of the cavity 10, to a bottom level 20 of the recess 13 passes.

In particular, it can be seen that the ramp-like transition R, starting from a boundary edge 23 of the recess 13 with the bottom plane 19 of the cavity 10 forms an angle α of approximately 45 degrees. Again, angles greater or less than 45 degrees are conceivable.

It should be noted that the second area 15 does not necessarily have to be formed by a ramp-like transition, but other configurations are also conceivable. So is in Fig. 3 indicated that the second area, for example, by a "smooth" transition, such as by a concave (15 ") or convex (15"') rounding can be formed.

Based on Fig. 4a to 4f It will now be described how a liquid F flowing into the cavity 10 is controlled by the depressions 13 in its flow path:
Thus, the inflowing liquid F first flows toward the first of the cavities 13 with a flow direction S ( Fig. 4a ).

In this case, the liquid F is first stopped at the first region 14 or the boundary edge 22 and deflected ( Fig. 4b ).

The liquid F continues to the first region 14 of the second recess 13 and thereby also to the second region 15 of the first recess 13, whereby the liquid F via the second region 15, the first recess 13 fills (see dashed lines indicated arrow in FIG Fig. 4c ).

The liquid F is then stopped and deflected again at the first region 14 of the second depression 13 and a complete filling of the cavity 10 takes place, first leaving the second depression 13 (see FIG Fig. 4d ).

As soon as the liquid F also reaches the second region 15 of the second depression 13, the second depression 13 is also filled via the second region 15 (ramp-like transition R). The liquid front of the liquid F now extends to the first region 14 of the last depression 13 (FIG. Fig. 4e ).

At the first region 14, the liquid F is again initially stopped and deflected until it subsequently reaches the second region 15 of the last depression 13 and, starting there, fills it.

The filling process extends to the capillary stop 24 in the region of the outlet opening 12 and essentially takes place without air inclusions (air bubbles) (cf. Fig. 4f ).

Due to the mutual arrangement of the depressions 13, a meandering control of the liquid F takes place through the cavity 10.

It is at the Fig. 1 to 4 it can be seen that the second region 15 does not extend over the entire length L of a depression 13, but only constitutes part of this length. Furthermore, the region 15 also assumes a width which is significantly smaller than the width B of the entire depression 13. In particular, the width of the region 15 is preferably less than half the width B of the depression 13. This makes it possible, with sufficient filling function Area 15 well exploit the volume of the recess 13.

Notwithstanding the embodiment shown, in which the regions 15 are positioned on the longitudinal sides of the depressions 13 facing away from the inflowing liquid F, it is also conceivable to provide such regions at least partially on the transverse sides of the depressions 13 (cf. dashed lines 15 'in FIG Fig. 1 ). It is also conceivable to provide several such areas at one depression (see also paragraphs 43 in FIG Fig. 6 ).

In Fig. 5 Now, a second embodiment 3 for a microfluidic structure of a microfluidic component 4 is shown. In contrast to the microfluidic structure 1 according to the Fig. 1 to 4 , The microfluidic structure 3 comprises a cavity 30, with Each recess 31 is in turn equipped with a first region 32 in the form of a stop edge (capillary stop), which faces the flow direction S of an inflowing liquid. A second region 33 in the form of a ramp is again provided on the longitudinal side of the depression 31 facing away from an inflowing liquid, the region 33 extending over an entire length L of the depression 31. The width of the region 33 is in turn only about a maximum of half a width B of the recess 31. Also in this embodiment, a meandering flow of an incoming liquid is modeled by the mutual arrangement of the recesses 31.

Referring to the Fig. 6 Now, a third embodiment of the invention will be described. There, a microfluidic structure 5 can be seen on a microfluidic component 6, which (in contrast to the preceding exemplary embodiments) has a curved cavity 40 viewed in the inflow direction S of a liquid.

In the cavity 40 seven recesses 41 are provided, each recess 41 has a longitudinal extent L and extends over this length L curved. Furthermore, it can be seen that each depression 41 is in turn provided with a first region 42 in the form of a stop edge (comparable to region 14 of the first embodiment) and on the longitudinal side facing away from an inflowing liquid, each having two regions 43 in the form of a ramp (comparable to FIG the area 15 in the first embodiment).

An inflowing liquid will now be stopped and deflected first at the regions 42 and, after reaching the regions 43, begin the filling process of each depression 41 until the liquid continues to run completely up to the next depression 41. Thus, it is thus also a gradual filling of the cavity 40 without appreciable air pockets possible.

Finally, referring to the FIGS. 7 and 8 briefly again on the state of the art will be discussed.

In these figures, a microfluidic structure 7 of a microfluidic component 8 can be seen, in which, within a cavity 50 unlike the embodiments according to the invention, no depressions, but webs 51 are attached. The webs 51, starting from longitudinal sides of the cavity 50, are mutually arranged and intended to meander a flow of an inflowing liquid (not shown) and thus enable a largely bubble-free filling of the cavity 50. The webs 51 extend from a bottom 53 of the cavity 50 starting up to a cavity 50 upwards final cover 52 zoom.

It is readily apparent that the useful volume of the cavity 50 is significantly limited by the introduced webs 51.

LIST OF REFERENCE NUMBERS

1

microfluidic structure

2

microfluidic component

3

microfluidic structure

4

microfluidic component

5

microfluidic structure

6

microfluidic component

7

microfluidic structure

8th

microfluidic component

10

cavity

11

inlet port

12

outlet

13

deepening

14

first area of the depression (stop edge)

15

second area of the depression (ramp)

15 '

alternatively trained second area

15 "

alternatively formed second area (concave rounding)

15 " '

alternatively formed second area (convex rounding)

16

filling channel

17

vent channel

18

another microchannel

19

Bottom of the cavity

20

Bottom of the depression

21

cover

22

Bounding edge of the depression

23

Bounding edge of the depression

24

capillary

30

cavity

31

deepening

32

first area of the depression (stop edge)

33

second area of the depression (ramp)

40

cavity

41

deepening

42

first area of the depression (stop edge)

43

second area of the depression (ramp)

50

cavity

51

web

52

cover

53

Bottom of the depression

α

angle

β

angle

B

Width of the recess

F

liquid

L

Longitudinal extension of the depression

R

ramp-like transition area

S

Flow direction of an inflowing liquid

Claims (6)

1. Microfluidic structure (1, 3, 5) comprising at least one cavity (10, 30, 40) with at least one inlet opening (11) and at least one outlet opening (12), wherein the cavity (10, 30, 40) is fillable with a fluid (F) or a fluid can flow through said cavity and an element (13, 31, 41) is provided inside the cavity (10, 30, 40) which at least temporarily stops and at least in sections deflects the fluid (F) upon its flow (S) inside the cavity (10, 30, 40), characterised in that the at least one element (13, 31, 41) is formed by an indentation (13, 31, 41) introduced into a wall (19) of the cavity (10, 30, 40), the indentation (13, 31, 41) having at least one first region (14, 32, 42) which is formed by a boundary edge (22) of the indentation (13), at which the converging walls forming the boundary edge (22) form an angle (β) which is smaller than 120°, particularly preferably approximately 90°, and the first region (14, 32, 42) forms a capillary stop at which the fluid (F) is at least temporarily stopped and is deflected at least in sections and the at least one element (13, 31, 41) has at least one second region (15, 15', 15", 15"', 33, 43) which is formed by a ramp-like transition (R) which, proceeding from a ground level (19) of the cavity (10), merges up to a ground level (20) of the indentation (13), at which the fluid (F) runs into the indentation (13, 31, 41).
2. Microfluidic structure (1, 3, 5) according to claim 1, characterised in that the ramp-like transition (R), proceeding from a boundary edge (23) of the indentation (13), forms an angle (α) of approximately 10° to 60°, particularly preferably approximately 45°, with the ground level (19) of the cavity (10).
3. Microfluidic structure (1, 3, 5) according to any one of the preceding claims 1 or 2, characterised in that the at least one indentation (13, 31, 41) is formed longitudinally, wherein the at least one first region (14, 32, 42) is facing an inflowing fluid (F) and the at least one second region (15, 33, 43) is facing away from an inflowing fluid (F).
4. Microfluidic structure (1, 3) according to any one of the preceding claims 1 to 3, characterised in that a plurality of indentations (13, 31, 41) are provided which, proceeding from side walls of the cavity (10, 30, 40), are arranged alternatingly.
5. Microfluidic structure (1, 5) according to any one of the preceding claims 1 to 4, characterised in that the at least one first region (14, 32, 42) extends approximately over the entire length (L) of a longitudinal side of the at least one indentation (13, 31, 41) and the at least one second region (15, 33, 43) only extends over a part of the length (L) of another longitudinal side.
6. Microfluidic platform (2, 4, 6) with at least one microfluidic structure (1, 3, 5) according to at least one of claims 1 to 5.

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