Abstract:
A microvalve for controlling fluid flows, and a sealing device for sealing cavities in a microfluidic system, particularly in a lab-on-a-chip system, and a method for the production thereof. A sealing surface of a valve body, or a sealing element, respectively, rests on a sealing surface of a substrate and is pressed against the sealing surface of the substrate in a fluid-tight manner by means of a clamping element. The clamping element and/or the valve body, or the sealing element, respectively, are at least partially elastic.

Description:
FIELD OF INVENTION 
     The invention concerns a microvalve for control of fluid streams and a sealing device for the sealing of cavities in a microfluidics system, especially in a lab-on-a-chip system as well as a method for its production. The microvalve has a substrate with a sealing surface and a valve body disposed movably relative to the substrate, which has a sealing surface and defines at least one channel for optional connection and/or separation of fluid lines in the substrate, wherein the sealing surface of the valve body and the sealing surface of the substrate lie against each other in a fluid-tight manner. The sealing device has a substrate with a sealing surface and a sealing element, having a sealing surface for sealing off a cavity in the substrate. The invention further relates to a sample processing chip with such a microvalve and/or such a sealing device. 
     A sample processing chip in the sense of this invention is a microfluidic system for chemical and biochemical analysis and/or synthesis, for example, for so-called point-of-care applications. These microfluidic systems are also termed lab-on-a-chip. 
     By sealing element in the sense of this invention is generally meant a nonpermeable element sealing off the cavity (channel, reservoir, chamber) from the surroundings of the substrate, or at least selectively sealing it off, e.g., for selected substances, especially a septum, a membrane, a filter element or the like. The sealing element can thus take on other functions in addition to the (selective) sealing function. For example, it can be air or gas-permeable for venting of the cavity. In contrast with the valve body, which given its function is movable relative to the substrate, the sealing element can be connected immovably to the substrate. 
     BACKGROUND OF THE INVENTION 
     Microvalves of the kind mentioned above are known. For example, reference is made to the patent application laid open DE 102 27 593 A1, the U.S. Pat. No. 6,748,975 B2 and the article “10-Way micro switching valve chip for multi-directional flow control”, Tadahiro Hasegawa et al, 7th International Conference on Miniaturized Chemical and Biochemical Analysis Systems, 5-9 Oct. 2003, Squaw Valley, Calif. USA. 
     From DE 102 27 593 A1, for example, there is known a microvalve, which has a substrate and a cover plate as valve body, which have contact surfaces lying against each other in fluid-tight contact and can be positioned relative to each other so that fluid lines can be optionally connected or separated. The microvalve is disclosed as being either a rotary valve with a cylindrical cover plate or a slide valve with a rectangular cover plate. Polymer materials and optionally composite materials are proposed preferably as the substrate and cover plate material. 
     The present invention deals with the question of how to create a simple and functionally reliable connection of the valve body and the sealing element to the substrate, as in such microvalves. Since the aforementioned microfluidics systems and especially the lab-on-a-chip systems are generally designed for onetime use, a low-cost solution is desirable. DE 102 27 593 A1 offers no clues for this. 
     In U.S. Pat. No. 6,748,975 B2 is disclosed a rotary valve, which is formed by a valve body (or rotor) which can turn relative to the substrate (or stator). The rotor can turn between two or more valve positions, in which one or more channels in the rotor optionally connects one or more inlet openings with one or more outlet openings, or separates these. The rotor lies by one contact surface on a corresponding contact surface of the stator. The position of the rotor with respect to the stator is defined by inserting the two elements in a valve housing, which besides the rotor and the stator includes various means for pressing on and activating the valve. Even though the rotor and the stator are loose parts in this case and seem suitable for onetime use, still a considerable expense is required to assembly the functional valve and thus the manipulation of the valve become more difficult. 
     A rotary valve consisting of a substrate and a rotating valve body is also pointed out in the aforementioned article by Hasegawa et al., which lie against each other by their contact surfaces. The valve body is formed from a silicone rubber ring with channels worked into it, which is pressed against the substrate by means of a mechanism consisting of at least four parts, including a pressing spring. Just how the pressing spring is buttressed against the substrate is not evident from the article. Here as well, it is to be assumed that an enclosing valve housing is provided, which receives the valve arrangement. 
     The inventor itself has already presented microvalve arrangements with a substrate  210  and a valve body  212  of the aforementioned kind at the conference “MipTec—The 9th International Conference and Exhibition on Drug Discovery” on 9 May 2006, as described hereafter by means of  FIG. 1 . The valve body  212  is in the form of an elastomer seal and is pressed by its contact or sealing surface  214  against a corresponding contact or sealing surface  216  of the substrate  210  via a valve cylinder  218 . The valve cylinder  218  is fashioned in the form of a plunger and has a pressing force applied to it by means of a compression spring  220 . The compression spring  220  in turn thrusts against a housing  222 , which is screwed directly onto the substrate  210  by means of a screw connection  224 . The microvalve arrangement of  FIG. 1  is of simple construction when compared to the aforesaid prior art, yet still a multitude of different materials and components are needed and the onetime assembly is still too elaborate in practice for a mass production. 
     SUMMARY OF THE INVENTION 
     The problem of the present invention, accordingly, is to improve a microvalve as well as a sealing device of the aforementioned kind so that it can be produced with low effort and thus with low costs. Accordingly, the problem of the invention is to provide a method for the production of such a microvalve or a corresponding cover device that is more economical and thus suited for the mass production of disposable products. 
     The problem is solved by a microvalve for control of fluid streams in a microfluidics system, especially in a lab-on-a-chip system, with a substrate, having a sealing surface, and a valve body disposed movably relative to the substrate, which has a sealing surface and defines at least one channel for optional connection and/or separation of fluid lines in the substrate, wherein the sealing surface of the valve body and the sealing surface of the substrate lie against each other in a fluid-tight manner, wherein the valve body is pressed by its sealing surface against the sealing surface of the substrate by means of a clamping element connected to the substrate in form-fitting manner and the clamping element and/or the valve body is at least partly elastic, a sealing device for sealing of cavities in a microfluidics system, especially in a lab-on-a-chip system, with a substrate, having a sealing surface, and a sealing element, having a sealing surface for sealing a cavity in the substrate, wherein the sealing element is pressed by its sealing surface against the sealing surface of the substrate by means of a clamping element connected in form-fitting manner to the substrate and the clamping element and/or the sealing element is at least partially elastic, as well as a method for production of a microvalve or a sealing device in a microfluidics system, especially in a lab-on-a-chip system, wherein a valve body or a sealing element with a sealing surface is placed on a sealing surface of a substrate, the valve body or the sealing element is pressed by means of a clamping element by its sealing surface fluid-tight against the sealing surface of the substrate, and the clamping element is connected by form-fit to the substrate. Advantageous modifications of the invention are the subject of the subclaims. 
     In the microvalve according to the invention, the valve body is pressed by its sealing surface against the sealing surface of the substrate by means of a clamping element connected to the substrate in form-fitting manner and the clamping element and/or the valve body is at least partly elastic. 
     The inventors have discovered that the construction of the microvalve according to the invention is likewise suitable for simple and economically favorable assembly of other sealing elements with sealing function. In a sealing device according to the invention for the sealing of cavities with a sealing element of the kind described above, the sealing element is pressed by its sealing surface against the sealing surface of the substrate by means of a clamping element connected in form-fitting manner with the substrate, while the clamping element and/or the sealing element are at least partially elastic. 
     The method according to the invention for production of the microvalve or the sealing device in a microfluidics system, especially in a lab-on-a-chip system, calls for placing a valve body or a sealing element with a sealing surface on a sealing surface of a substrate and connecting a clamping element in form-fitting manner to the substrate, wherein the clamping element presses the valve body or the sealing element by its sealing surface fluid-tight against the sealing surface of the substrate. 
     While thus far the only valve arrangements known are those assembled from at least six individual parts and needing to be assembled in a corresponding number of individual steps, only three parts are provided for the microvalve of the invention or for the sealing device of the invention, namely, the substrate, the valve body and the clamping element. These three elements are put together in a simple work step, in which they are stacked one on the other and fixed by form fitting between the clamping element and the substrate. Here, the clamping element and/or the valve body or the sealing element functionally replace the spring. The clamping element, which supports the valve body or the sealing element relative to the substrate on its side away from the sealing surface, also functionally replaces the much more complicated to fabricate housing. The clamping element can be made as a simple injection molded, metal or stamped part (e.g., from spring plate) or a combination of the two, a plastic extrusion-coated stamped part. The valve body can also be made as a simple part, such as a disk-shaped part, in one or at least a few work steps. The microvalve of the invention and the sealing device of the invention totally do without the use of a spring to generate the pressing force. For this purpose, the invention makes use of the (partial) elasticity of the valve body or sealing element and/or the clamping element. For this there needs to be a suitable choice of material for the valve body or the sealing element and/or the clamping element, taking into account the geometry of the particular structural part, so that a sufficient elasticity and, thus, pressing force is assured for the sealing. 
     In one advantageous modification, the valve body or the sealing element is compressive-elastic. Alternatively or additionally, the clamping element is flexural-elastic, at least for a segment. 
     The former can be achieved preferentially in that the valve body or the sealing element consists at least partly of an elastomer. Especially suitable materials are thermoplastic elastomers, silicones, fluoroelastomers such as Viton®, ethylene-propylene-diene rubber, styrene-butadiene rubber (SBR), ethylene-propylene rubber (EPM) or nitrile rubber. 
     The latter can be achieved preferentially in that the clamping element consists of spring steel, an injection-molded partly elastic plastic, or a plastic extrusion-coated spring steel. Specially suitable plastics are thermoplasts and duroplasts, especially acrylonitrile-butadiene-styrene copolymerizate (ABS), polyoxymethylene (POM), polyether ketones (PEEK). 
     In one preferred modification of the invented microvalve or the invented sealing device, the clamping element and the substrate engage with each other by means of a snap connection. 
     The snap connection is preferably provided by a locking pawl or a snap hook formed on the clamping element, which locks into a corresponding opening in the substrate. However, the flexural elasticity of the clamping element can be utilized for this. 
     Especially preferably, the valve body has a shape-stable part and an elastomer seal, on which the sealing surface is formed, whereby a pressing force from the pressing ring acts across the shape-stable part on the elastomer seal. 
     The shape-stable part ensures a uniform distribution of the pressing force over the entire sealing surface of the elastomer seal, while the latter due to its elasticity is compressed and provides a sufficient sealing. 
     In one advantageous modification, the shape-stable part together with the elastomer seal is produced by two-component injection molding. 
     In this way, the shape-stable part, which in this embodiment preferably consists of a shape-stable plastic, and the elastomer seal are combined into a single valve body, which reduces the assembly expense. Also, the production of a two-component injection-molded part is relatively economical. 
     Advantageously, the at least one channel in the elastomer seal is formed as a through opening. 
     This embodiment of the invention has the advantage of easy workmanship. Channels in the form of depressions or grooves, if the valve body is not finished by injection molding, are produced or added subsequently in familiar fashion by etching, laser ablation, spray engraving, hot engraving, milling or the like. On the other hand, the channel in the form of a through opening can be produced in a single stamping process and a valve body with such an elastomer seal is therefore more favorable. 
     The microvalve can preferably be fashioned as a rotary valve or a slide valve. 
     In an especially preferred embodiment of the microvalve or the sealing device, the sample processing chip forms the substrate. 
     The microvalve or the sealing device on account of their makeup are easy to miniaturize. The functional components of valve and/or sealing device can therefore be arranged with higher density on the microfluidic chip. It is also possible to use both sides of a chip for mounting. In this way, even higher integration densities and more complex channel structures and thus an improved functionality can be achieved for the same footprint on a chip. 
     The microvalve or sealing device of the invention, especially when combined with a recessed seat, can be integrated almost fully in the sample processing chip when the valve seat or the seat for the sealing element is worked so deep in the form of a recess into the sample processing chip that the valve body can be set fully in the processing chip. Moreover, the clamping element can also be integrated in the sample processing chip, at least partly, by suitable depressions or recesses in it. In this way, the integration density of the functional components is further increased and the chip is given a flat profile, even when the functional components of valve and/or sealing device are mounted on both sides. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Further problems, features and benefits of the invention will now be explained more closely by means of sample embodiments with the help of the drawings. These show: 
         FIG. 1 , a microvalve of familiar design; 
         FIG. 2 , a perspective view of a first embodiment of the invented microvalve on a sample processing chip; 
         FIG. 3 , the sample processing chip with microvalve per  FIG. 2  in exploded view; 
         FIG. 4 , the sample processing chip with microvalve per  FIG. 2  in perspective partial section, and 
         FIG. 5 , the sample processing chip with microvalve per  FIG. 2  in another perspective and 
         FIG. 6 , a sectional view through a sample processing chip with a second embodiment of the invented microvalve. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     A first embodiment of the microvalve of the invention with sample processing chip is shown in perspective view from various directions and partly sectioned in  FIGS. 2 to 5 , to which we shall refer in what follows. 
     The microvalve is designed as a rotary valve  2  and has an essentially cylindrical valve body  10  and a clamping element  12  that supports it. The valve body  10  consists of a shape-stable part  14  and an elastomer seal  16 , on whose bottom side a sealing surface  18  is formed. The valve  2  is arranged in the manner described hereafter on a substrate in the form of a sample processing chip  20  and secured. By its sealing surface  18 , the valve lies on a corresponding sealing surface  22  of the substrate  20 . 
     The clamping element  12  in this embodiment is stamped out from a plate of spring steel and bent into the three-dimensional shape depicted. The clamping element  12  has an annular segment  24  for pressing on the valve body  10  and three downward bent anchor elements  26 , each with an arrow-shaped pawl  32  at its lower end for form-fitting connection to the sample processing chip  20 . From the annular segment  24 , three bending elements  28  emerge radially inwards and rest against the top side of the shape-stable part  14  of the valve body  10 . The height of the anchor elements  26  is designed as a function of the height of the valve body  10  so that the bending elements  28  are tensioned in desired degree and press the valve body  10  against the substrate  20  when the valve is mounted on the substrate  20 . The bending elements  28  have the shape of triangular brackets that pass into the annular segment  24  on one side and by their opposite corner  30 , pointing radially inwards, rest against the shape-stable part  14  of the valve body  10 . By a small contact surface between the bending elements  28  and the shape-stable part  14  the rotating of the valve body  10  is opposed by only a slight frictional force in this place when the rotary valve is activated. The spring force by which the bending elements  28  press the valve body  10  against the substrate  20  is determined, for a given basic material (spring steel plate) by the geometry of the clamping element  12 . It is designed so that the pressure ensures a seal for the least possible frictional resistance. One must take into account the coefficient of friction between the sealing surface  18  of the elastomer seal  16  and the sealing surface  22  of the substrate  20 , as well as the size of the surface. 
     The substrate  20  is two-piece. It has a support  34 , in which fluid lines are made in the form of boreholes  36  and/or groovelike channels  38  on the lower side, i.e., the side away from the microvalve. The substrate  20 , moreover, has on its lower side a cover film  42 , by which the fluid lines  36 ,  38  of the lower side of the substrate are closed. The boreholes  36  open the channels  38  through the support  34  upward to the valve. 
     The elastomer seal has, for an optionally adjustable fluidic connection of two or more boreholes  36  and fluid lines  38 , one or more channels. The channels are fashioned either as a through opening  40 , passing entirely through the elastomer seal  16 , see  FIG. 3 . In this case, the elastomer seal  16  can be made as a stamped part and the channels  40  are punched out. In another embodiment, the channels are groovelike depressions  40 ′ worked into the elastomer seal  16 ′ from the side of the sealing surface  18 ′, see  FIGS. 4 and 5 . 
     On the top side of the support  34  is provided an annular groove  44  surrounding the sealing surface  22 . As can be seen in  FIGS. 4 and 5 , the shape-stable part  14  of the valve body  10  has a coaxial, cylindrical hollow on its lower side to accommodate the elastomer seal  16 ,  16 ′. This hollow is deeper than the thickness of the elastomer seal, so that a ring-shaped edge  46  of the shape-stable part  14  sticks out axially above the sealing surface  18  of the elastomer seal  16 . The edge  46  engages with the annular groove  44  in the substrate  20  and acts together with the annular groove  44  as a rotary guide for the microvalve  2 . 
     To activate the rotary valve  2 , this has a manipulating element in the form of two cylinder boreholes  48  on its top side. Instead of two boreholes, a slot or some other recess or a projecting shoulder can be provided, with which a complementary tool can engage in form-fitting manner to activate the valve. 
     In the support  34  of the substrate  20 , three installation openings  50  are made on a circle with a 120° partition for the form-fitting connection to the anchor elements  26  of the clamping element  12 . The installation openings  50  each have the shape on the top side of a staggered oblong hole with a radially inward lying segment  52 , long in the tangential direction, and a radially outward lying segment  54 , short in the tangential direction. The direction indications are each referred to the axis of rotation of the valve. The long segment  52  serves to guide the arrow-shaped pawl  32  on the anchor element  26 , the short segment  54  serves to receive the anchor elements  26  in the area of their narrower leg above the arrow-shaped pawls  32 . From the lower side, the installation openings  50  have a hollow  56  with greater width in the radial direction. In this way, a shoulder  58  is formed in the installation opening. 
     The diameter of the partial circle on which the long segments  52  of the installation openings  50  are situated is smaller than the diameter of the partial circle on which the anchor elements  26  are arranged. For this reason, the anchor elements  26  must be radially tensioned inwards during the assembly, in order to be threaded into the long segments  52  of the installation openings  50  with the pawls  32 . When the clamping element  12  is then lowered until the bending elements press the valve body  10  against the substrate  20  in the desired degree, the axial end position of the clamping element  12  is achieved, in which the pawls  32  snap radially outwards and engage the shoulders  58  in form-fitting manner, so that a pulling of the anchor elements out from the openings  34  is prevented. Thanks to the hollow  56 , the arrow-shaped pawls  32  after being installed do not stick out from the substrate  20  at the lower side. 
     Another embodiment of the invented microvalve is shown in  FIG. 6 . The microvalve, again, is fashioned as a rotary valve  102  with an essentially cylindrical valve body  110  and a clamping element  112  to support it. The valve body  110  consists of a shape-stable part  114  and an elastomer seal  116 , on whose lower side a sealing surface  118  is formed, lying on a corresponding sealing surface  122  of the substrate  120 . The substrate  120  is likewise two-piece, but only the support  134  is shown in  FIG. 6 . In the support  134 , fluid lines are made in the form of boreholes  136  and/or groovelike channels  138  on the lower side, i.e., the side away from the microvalve. The boreholes  136  open the channels  138  through the support  134  upward to the valve. 
     The elastomer seal  116  has, for optionally adjustable fluidic connection of two or more boreholes  136  or fluid lines  138 , one or more channels in the form of a through opening  140 . 
     On the top side of the support  134  is once again provided an annular groove  144  surrounding the sealing surface  122 , with which the ring-shaped edge  146  of the shape-stable part  114  engages to form a rotary guide. 
     The manipulation element for activation of the rotary valve  102  in this embodiment has the shape of a polygonal inner profile  148 . 
     The microvalve in the embodiment of  FIG. 6  differs from the previously described one mainly in that an injection-molded plastic part is used as the clamping element  112 . The clamping element  112 , like the clamping element  12 , is a single piece. It has a cylindrical housing segment  124  with several, preferably three, elastic bending elements  128 , pointing radially inwards on its top side. The bending elements  128  are connected at their radially inner end  130  to an annular segment  131  for stabilization and adjustment of the elasticity-related pressing force. By this em annular segment  131 , the clamping element  112  lies on the top side of the shape-stable part  114  of the valve body  110 . The spring force by which the bending elements  128  press the valve body  110  against the substrate  120  is once again dictated by the geometry of the clamping element  112  for a given base material (plastic or plastic extrusion-coated spring steel plate). 
     The housing segment  124  has the shape of a hollow cylinder, which encloses the valve cylinder  110  and sits on the top side of the substrate  120 . Several, preferably three, anchor elements  126  emerge downward in the axial direction from the cylinder wall of the housing segment  124 . The anchor elements  126  each have at their free end a pawl or a snap hook  132  for form-fitting connection to the sample processing chip  120 . In the support  134  of the substrate  120  there are three installation openings  150  arranged on a circle with a 120° division. The installation openings  150  have an undercut  158  pointing radially inward from the lower side of the support  134 . The clamping element  112  and the installation openings  150  are shaped or dimensioned so that the anchor elements  126  move radially inwards by virtue of the elasticity of the material when the snap hooks  132  are introduced into the corresponding installation openings  150  and become tensioned in this way. When the clamping element  112  is further lowered until the bending elements  128  press the valve body  110  against the substrate  120  in the desired degree, the axial end position of the clamping element  112  is reached, in which the snap hooks  132  snap radially inward and thereby engage in form-fitting manner with the undercuts  158 , so that a pulling of the anchor elements  126  out from the openings  150  is prevented. 
     The height of the anchor elements  126  is designed as a function of the thickness of the substrate  120  or the height of the undercut  158  so that the bending elements  128  are tensioned to the desired degree and press the valve body  110  against the substrate  120  when the valve is mounted on the substrate  120 . 
     As regards the providing of the pressing force, all sample embodiments shown are identical in that the elasticity is provided by the valve body and more precisely by the elastomer seal on the one hand and by the clamping element and more precisely by the bending elements on the other hand. The shape-stable part of the valve body is rigid enough to distribute the pressing force uniformly over the elastomer seal. 
     As a departure from this, it is possible and also preferred from the aspect of the invention having a sealing device with a sealing element, to configure the valve body or the sealing element as a single-piece element. In the form of a septum, the sealing element can be fully elastic, thereby ensuring that it has sufficient stability on its own to fulfill the desired sealing function. For example, in the form of a ceramic filter, the sealing element is inelastic. In this case, the required elasticity to generate a sufficient pressing force comes solely from the clamping element. The same holds in principle for the valve body as well. 
     The shape-stable part and the elastomer seal can basically be joined by form-fit; friction connection, and intimate material connection. As already mentioned, both parts of the valve body are produced in a joint two-component injection molding. Alternatively, they can be produced separately and glued together. In departure from the sample embodiments depicted, a form fit can also be achieved by dogs in the form of projections on the shape-stable part, which engage with corresponding recesses in the elastomer seal or vice versa. 
     LIST OF REFERENCE NUMBERS 
     
         
           2  Rotary valve 
           10  Valve body 
           12  Clamping element 
           14  Shape-stable part 
           16 , 16 ′ Elastomer seal 
           18 , 18 ′ Sealing surface of elastomer seal 
           20  Sample processing chip/substrate 
           22  Sealing surface of substrate 
           24  Annular segment 
           26  Anchor element 
           28  Bending element 
           30  Corner of bending element 
           32  Pawl 
           34  Support 
           36  Fluid line, borehole 
           38  Fluid line, groovelike channel 
           40 , 40 ′ Channel 
           42  Cover film 
           44  Annular groove 
           46  Ring-shaped edge 
           48  Cylinder borehole 
           50  Installation opening 
           52  Long segment 
           54  Short segment 
           56  Hollow 
           58  Shoulder 
           102  Rotary valve 
           110  Valve body 
           112  Clamping element 
           114  Shape-stable part 
           116  Elastomer seal 
           118  Sealing surface of elastomer seal 
           120  Sample processing chip/substrate 
           122  Sealing surface of substrate 
           124  Cylindrical housing segment 
           126  Anchor element 
           128  Bending element 
           130  Inner end of bending element 
           131  Annular segment 
           132  Pawl, snap hook 
           134  Support 
           136  Fluid line, borehole 
           138  Fluid line, groovelike channel 
           140  Channel 
           144  Annular groove 
           146  Ring-shaped edge 
           148  Profile 
           150  Installation opening 
           158  Undercut 
           210  Substrate 
           212  Valve body 
           214  Sealing surface 
           216  Contact or sealing surface 
           218  Valve cylinder 
           220  Compression spring 
           222  Housing 
           224  Screw connection