Patent Publication Number: US-9409171-B2

Title: Microfluidic structure having recesses

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, the cavity being adapted to be filled with a liquid or have a liquid flow through it, and at least one element being provided within the cavity which at least temporarily stops and/or at least partly diverts the liquid as it flows within the cavity. 
     Microfluidic structures are components of microfluidic platforms or microfluidic components and essentially comprise cavities and/or channels in which sample liquids that are to be investigated or manipulated can be held and transported by suitable means (e.g. by capillary forces, pressure differences created) to reaction sites 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 and 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 entire reaction cascades take place on the microfluidic platforms. 
     For this it is necessary for the biological sample liquid to be transported by suitable means to the reaction site or sites provided for this purpose. This transporting of the sample liquid may be carried out for example by passive capillary forces (using corresponding capillary systems or microchannels) or by means of active actuating elements. Injection or membrane pumps, for example, may be used as the active actuating elements and may be located outside the microfluidic platform or on the platform and produce a corresponding pressure within a microfluidic structure consisting in particular of microchannels and microcavities. 
     In general, microfluidic platforms comprise a sample input region of the order of a few millimeters in size for introducing a quantity of sample liquid of the order of a few microliters, while the sample liquid (such as blood) has to be transported through a microchannel or through a microchannel system to corresponding cavities containing for example chemical reagents in dried form. 
     In order that a sample liquid can undergo a satisfactory detection reaction with the reagents in a cavity, it is essential that the cavity is filled as completely and uniformly as possible. 
     When filling large cavities, particularly those that are broad and irregularly shaped, for example with lengths and/or width dimensions of several millimeters and a resulting volume range from for example 10 μl to about 10 ml, there is the problem that the cavity does not fill uniformly and thus air inclusions or air bubbles may form in the cavity. As a result, the whole of the volume of the cavity is not available for the sample liquid. Dry substances stored in such a cavity, for example, are thus not sufficiently dissolved and the formation of clumps may occur, thus adversely affecting a desired detection reaction. 
     According to the prior art, a remedy is offered by providing bar-like elements in the cavity arranged in such a way that the liquid in the cavity has to flow in a meandering direction. 
     However, a disadvantage of this structure is that the bar-like elements take up space within the cavity which is actually needed. 
     Therefore, to compensate, more space has to be provided on the microfluidic platform or microfluidic component. This should be avoided in particular for microfluidic platforms, on account of the associated increase in manufacturing costs. 
     A microfluidic structure or a microfluidic platform for filling without any air bubbles is known from DE 103 60 220 A1. Specifically, a cavity is provided having an inlet opening and an outlet opening. In the region of the inlet opening the cavity comprises microstructural elements in the form of pillars. This region forms an area of increased capillary force. The increased capillary force initially causes total wetting, free from air bubbles, of the entry region of the cavity with the sample liquid. The part of the cavity facing the outlet opening is only wetted subsequently. 
     In order to accelerate the transporting of liquid, a ramp is provided in the cavity which raises the level of the cavity base to the level of the outlet opening. 
     An arrangement of this kind is unsatisfactory for filling cavities that are large, particularly broad (at right angles to the direction of inflow or throughflow of the liquid) and irregularly shaped. 
     The invention is therefore based on the problem of improving a microfluidic structure according to the preamble of claim  1  so as to allow improved filling, particularly of large cavities, particularly substantially free from air bubbles. 
     The problem is solved with the charactering features of claim  1 . Advantageous further features of the invention can be found in the subclaims. 
     The invention therefore starts from a microfluidic structure comprising at least one cavity having at least one inlet opening and at least one outlet opening, the cavity being adapted to be filled with a liquid or have such a liquid flow through it and within the cavity is provided at least one element which at least temporarily stops and/or at least partially deflects the liquid as it flows within the cavity. 
     According to the invention it is envisaged that the at least one element is formed by a recess provided in a wall of the cavity, which has at least one first region at which the liquid is at least temporarily stopped and/or at least partially deflected and at least one second region at which the liquid preferably flows into the recess. 
     On reaching the second region the liquid flows immediately, i.e. without any appreciable stop, into the recess and, beyond a specified fill level of the recess, also draws the liquid that has initially stopped in the first region of the recess into the recess with it. 
     In this way the liquid in the cavity can be controlled such that the cavity is filled uniformly and substantially free from air bubbles. This is possible even with cavities that are large, particularly wide and irregular in shape which have, for example, a fill volume of the order of about 10 μl to 10 ml. 
     It should be noted that the above-mentioned wall of the cavity may be, for example, a base of the cavity. However, any other walls of the cavity are also conceivable. Thus, in a suitable configuration of a lid closing of the cavity, the wall may also be formed by the latter, for example. A combination of these two possibilities is also possible, for example. 
     According to a further feature of the invention, it is envisaged that the second region is formed by a ramp-like transition which starts from a base level of the cavity and extends to a base level of the recess. 
     This ramp-like transition ensures, in a simple manner, that the sample liquid flows into the recess at this point, without stopping, and fills the recess. 
     It has proved advantageous if the ramp-like transition, starting from a boundary edge of the recess, forms an angle of about 10° to 60°, most preferably about 45°, with a base plane of the cavity. Tests have shown that the desired flow characteristics of the liquid can best be achieved by such a choice of geometric parameters. 
     However, instead of a ramp-like configuration, other configurations of the second region would also be possible. Thus the second region could also be formed by a “soft” transition, for example by a convex or concave rounded portion. A notch-like structure (looking at the recess in plan view) is also conceivable. 
     The first region, by contrast, is expediently formed by a boundary edge of the recess at which the convergent walls that form the boundary edge enclose an angle of less than 120°, preferably approximately between 95° and 70°, most preferably about 90°. 
     In this way the first region reliably forms a capillary stop at which the inflowing liquid is initially stopped or deflected. 
     It has also proved highly advantageous in tests if the at least one recess is of elongate configuration, the at least one first region facing an incoming liquid and the at least one second region being remote from an incoming liquid. Thus the incoming liquid can be controlled so that initially it reaches the first region, is stopped there, deflected and on reaching the second region preferably runs into the recess (without any appreciable stop) and fills it. With a corresponding arrangement of a plurality of recesses with one another, the desired control of the liquid can be adapted to the specific length of a cavity. 
     The recess may be approximately rectangular, for example, in plan view. However, it may also be of a different shape in plan view, for example arcuate. This may be expedient, for example, when the cavity that is to be filled is also of arcuate configuration in its longitudinal extent. 
     According to another expedient embodiment of the inventive concept, a plurality of recesses are provided which are arranged alternately, starting from the side walls of the cavity. 
     In this way it is possible to create a meandering flow path for the liquid with the recesses in the cavity that is to be filled. 
     It has also proved advantageous if the at least one first region extends substantially over the entire length of a longitudinal side of the at least one recess and the at least one second region extends over only part of the length of another longitudinal side. 
     In this way it is possible on the one hand to ensure a capillary stop over a wide front while on the other hand ensuring a time-delayed inflow of liquid into the recess, while additional volume can be obtained at the point where the second region is not formed. 
     However, the invention also relates to a microfluidic platform having at least one microfluidic structure according to at least one of claims  1  to  7 . A microfluidic platform thus configured can be manufactured cheaply and meets high demands for a reliable, particularly bubble-free filling of the cavities present. 
    
    
     
       Further advantages and embodiments of the invention will become clear from embodiments by way of example, as will be explained with the aid of the accompanying drawings, wherein: 
         FIG. 1  shows a microfluidic structure according to a first preferred embodiment in plan view, in schematic form, 
         FIG. 2  is a sectional view of the microfluidic structure along section line II in  FIG. 1 , 
         FIG. 3  is a detailed view III from  FIG. 2 , 
         FIGS. 4 a  to 4 f    show different stages of filling the microfluidic structure according to  FIG. 1  with a liquid, 
         FIG. 5  shows a microfluidic structure in plan view according to a second embodiment, in schematic form, 
         FIG. 6  shows a microfluidic structure in plan view according to a third embodiment, in schematic form, 
         FIG. 7  shows a microfluidic structure according to the prior art and 
         FIG. 8  shows a sectional view along section line VIII in  FIG. 7 . 
     
    
    
     First of all, reference will be made to  FIGS. 1 to 3 . 
     These figures show a microfluidic structure  1  introduced into a microfluidic component  2 . The microfluidic structure  1  comprises a cavity  10  which has a fill volume of about 15 μl. The cavity  10  is irregularly shaped and is provided with an inlet opening  11  which connects the cavity  10  to a fill channel  16 . The fill channel  16  itself may be connected to a fill opening (for example a sample input region) which is not specifically designated. 
     On the other side the cavity  10  is provided with an outlet opening  12  which for example opens up the fluidic connection to a venting channel  17 . In the region of the outlet opening  12  a capillary stop  24  is also provided in conventional manner. 
     Additionally or alternatively the cavity  10  may be connected through an outlet opening with another microchannel  18  (shown by dashed lines) if a liquid is to be transported through the cavity  10  into another cavity, for example (not shown). 
     The cavity  10  is a comparatively large cavity measuring about 12 mm wide, 36 mm long and about 1.5 mm deep. 
     It should also be noted that there are three recesses  13  within the cavity  10 . Each recess  13  is substantially rectangular in appearance, in plan view, with a length L and a width B. The recesses  13  are arranged alternately, starting from longitudinal sides of the cavity  10 . 
     It can be seen that each recess  13  comprises a first region  14  which faces an incoming liquid F (see  FIG. 4 ) and at which the incoming liquid F is at least temporarily stopped and/or at least partly deflected. 
     Moreover, each recess  13  is provided with a second region  15  at which an incoming liquid F flows into the recess  13  without being stopped. 
     The cavity  10  is closed off by a cover  21  (for example a film attached by adhesion) and comprises a base  19 . Each recess  13  comprises a base  20 . 
     The detailed view in  FIG. 3 , in particular, shows that the first region  14  (capillary) is formed by a boundary edge  22  of the recess  13  at which the convergent walls forming the boundary edge  22  make an angle β which is 90°. In a departure from the embodiment shown, other angles are naturally possible and may be greater than or less than 90°. 
     It can also be seen that the second region  15  is formed by a ramp-like transition R which, starting from the base level  19  of the cavity  10 , extends to a base level  20  of the recess  13 . 
     In particular it can be seen that the ramp-like transition R, starting from a boundary edge  23  of the recess  13 , forms an α of about 45 degrees with the base plane  19  of the cavity  10 . Here, too, angles greater than or less than 45° are possible. 
     It should be noted that the second region  15  does not necessarily have to be formed by a ramp-like transition but that other embodiments are also possible. Thus,  FIG. 3  shows that the second region may for example also be formed by a “soft” transition, for example a concave  15 ″ or convex  15 ′″ rounded portion. 
     With reference to  FIGS. 4 a  to 4 f    it will now be described how the flow characteristics of a liquid F flowing into the cavity  10  are controlled by the recesses  13 : 
     Thus, the inflowing liquid F first of all flows onto the first of the cavities  13  in a direction of flow S ( FIG. 4 a   ). 
     The liquid F is initially stopped and deflected at the first region  14  or at the boundary edge  22  ( FIG. 4 b   ). 
     The liquid F continues on to the first region  14  of the second recess  13  and again to the second region  15  of the first recess  13 , as a result of which the liquid F fills the first recess  13  through the second region  15  (cf. the dashed arrow in  FIG. 4 c   ). 
     The liquid F is then stopped and deflected again at the first region  14  of the second recess  13  and the cavity  10  is filled completely, initially leaving the second recess  13  free (cf.  FIG. 4 d   ). 
     As soon as the liquid F reaches the second region  15  of the second recess  13 , the second recess  13  is also filled through the second region  15  (ramp-like transition (R)). The liquid front of the liquid F then extends to the first region  14  of the last recess  13  ( FIG. 4 e   ). 
     At the first region  14  the liquid F is again initially stopped and deflected until it then reaches the second region  15  of the last recess  13  and, proceeding from that point, fills the latter. 
     The filling process extends as far as the capillary stop  24  in the region of the outlet opening  12  and proceeds with substantially no air inclusions (air bubbles) (cf.  FIG. 4 f   ). 
     As a result of the alternating arrangement of the recesses  13 , the liquid F is directed in a substantially meandering configuration through the cavity  10 . 
       FIGS. 1 to 4  show that the second region  15  does not extend over the entire length L of a recess  13  but makes up only part of this length. Moreover, the region  15  also occupies a width which is significantly less than the width B of the recess  13  as a whole. In particular, the width of the region  15  is preferably less than half the width B of the recess  13 . As a result it is possible to make good use of the volume of the recess  13  with an adequate fill function of the region  15 . 
     In a departure from the embodiment shown, in which the regions  15  are positioned on the longitudinal sides of the recesses  13  remote from the incoming liquid F, it is also possible, however, to provide such regions at least partly on the transverse sides of the recesses  13  (cf. the dashed lines  15 ′ in  FIG. 1 ). It is also possible to provide a plurality of such regions on a recess (cf. also reference numerals  43  in  FIG. 6 ). 
       FIG. 5  now shows a second embodiment  3  of a microfluidic structure of a microfluidic component  4 . In contrast to the microfluidic structure  1  according to  FIGS. 1 to 4 , the microfluidic structure  3  comprises a cavity  30  with slightly differently configured recesses  31 . Each recess  31  is in turn provided with a first region  32  in the form of a stop edge (capillary stop) which faces the direction of flow S of an incoming liquid. On the longitudinal side of the recess  31  remote away from the incoming liquid there is in turn a second region  33  in the form of a ramp, the region  33  extending over an entire length L of the recess  31 . The width of the region  33  in turn amounts to at most only half a width B of the recess  31 . In this embodiment as well, a meandering flow is created for an incoming liquid by the alternating arrangement of the recesses  31 . 
     With reference to  FIG. 6 , a third embodiment of the invention will now be described. A microfluidic structure  5  on a microfluidic component  6  is shown which (in contrast to the preceding embodiments) has a cavity  40  which is curved, viewed in the direction of inflow S of a liquid. 
     Seven recesses  41  are provided in the cavity  40 , each recess  41  having a longitudinal extent L and being of a curved configuration over this length L. Moreover it is apparent that each recess  41  is in turn provided with a first region  42  in the form of a stop edge (comparable with region  14  of the first embodiment) and, at the longitudinal side remote from the incoming liquid, comprises two regions  43  in the form of a ramp (comparable with the region  15  in the first embodiment). 
     An incoming liquid is initially stopped and deflected at the regions  42  and after reaching the regions  43  the process of filling each recess  41  begins until the liquid runs right on to the next recess  41 . Thus the cavity  40  is filled step by step without any appreciable air inclusions. 
     Finally, with reference to  FIGS. 7 and 8 , the prior art will be briefly discussed. 
     These Figures show a microfluidic structure  7  of a microfluidic component  8  in which, in contrast to the embodiments according to the invention, a cavity  50  comprises not recesses but bars  51 . The bars  51  are arranged alternately, starting from longitudinal sides of the cavity  50 , and are intended to allow a meandering flow of an incoming liquid (not shown) and hence filling of the cavity  50  substantially free from air bubbles. The bars  51  start from a base  53  of the cavity  50  and extend to a cover  52  which closes off the cavity  50  at the top. 
     It is readily apparent that the inserted bars  51  significantly restrict the useful volume of the cavity  50 . 
     LIST OF REFERENCE NUMERALS 
     
         
           1  Microfluidic structure 
           2  Microfluidic component 
           3  Microfluidic structure 
           4  Microfluidic component 
           5  Microfluidic structure 
           6  Microfluidic component 
           7  Microfluidic structure 
           8  Microfluidic component 
           10  Cavity 
           11  Inlet opening 
           12  Outlet opening 
           13  Recess 
           14  First region of the recess (stop edge) 
           15  Second region of the recess (ramp) 
           15 ′ Second region of alternative design 
           15 ″ Second region of alternative design (concave rounded portion) 
           15 ′″ Second region of alternative design (convex rounded portion) 
           16  Fill channel 
           17  Venting channel 
           18  Further microchannel 
           19  Base of cavity 
           20  Base of recess 
           21  Cover 
           22  Boundary edge of recess 
           23  Boundary edge of recess 
           24  Capillary stop 
           30  Cavity 
           31  Recess 
           32  First region of recess (stop edge) 
           33  Second region of recess (ramp) 
           40  Cavity 
           41  Recess 
           42  First region of recess (stop edge) 
           43  Second region of recess (ramp) 
           50  Cavity 
           51  Bar 
           52  Cover 
           53  Base of recess 
         α Angle 
         β Angle 
         B Width of recess 
         F Liquid 
         L Longitudinal extent of recess 
         R Ramp-like transition region 
         S Direction of flow of an incoming liquid