Mixing deivce and mixing method for mixing small amounts of liquid

Abstract

The invention relates to a mixing method for mixing at least one small quantity of liquid, in which a quantity of liquid is applied in a reaction region and at least one surface sound wave is reacted with the quantity of liquid. The invention relates further to a mixing device for mixing at least one quantity of liquid for performing the method of the present invention, a use of the device, and a method of analysis for bond strengths on surfaces.

1 . A mixing method for mixing at least a small quantity of liquid, in which at least one quantity of liquid ( 53 ) is applied to a reaction region ( 3 ,  23 ,  43 ,  63 ,  83 ,  93 ,  103 ,  204 ) of a solid body surface, preferably of a chip, and at least one surface sound wave is brought into a reaction with the at least one quantity of liquid ( 53 ,  73 ), in order to mix it.  
     
     
         2 . The mixing method according to  claim 1 , in which the at least one quantity of liquid ( 53 ) is applied to a part ( 23 ,  43 ,  103 ) of the surface, on which a production device ( 25 ,  45 ,  105 ) for the at least one surface sound-wave is located.  
     
     
         3 . The mixing method according to one of claims  1  or  2 , in which the at least one quantity of liquid is applied in a depression ( 3 ,  23 ,  204 ) in the solid body surface.  
     
     
         4 . The mixing method according to one of claims  1  through  3 , in which the at least one quantity of liquid ( 53 ,  73 ) is applied on a part ( 43 ,  63 ,  83 ,  93 ,  103 ) of the surface, which has different wetting characteristics than its lateral surrounding area, such that the liquid preferably is retained thereon.  
     
     
         5 . The mixing method according to one of claims  1  through  4 , in which the surface sound wave is pulsed.  
     
     
         6 . The mixing method according to  claim 5 , in which the pulse frequency of the surface sound wave is selected, such that it is in resonance with an eigenfrequency of the small quantity of liquid ( 53 ) on the reaction region ( 3 ,  23 ,  43 ,  63 ,  83 ,  93 ,  103 ,  204 ).  
     
     
         7 . The mixing method according to one of claims  1  through  6 , in which the at least one surface sound wave is sent decentralized onto the quantity of liquid ( 73 ).  
     
     
         8 . The mixing method according to one of claims  1  through  7 , in which at least two surface sound waves are sent onto the quantity of liquid ( 73 ), whose phase displacement (ΔΦ) is unequal by a multitude to its wave length (λ), preferably is equal to half the wave length.  
     
     
         9 . The mixing method according to one of claims  1  through  8 , in which the at least one surface sound wave is produced with an interdigital transducer ( 5 ,  25 ,  45 ,  65 ,  66 ,  67 ,  68 ,  85 ,  95 ,  105 ,  206 ).  
     
     
         10 . The mixing method according to one of claims  1  through  9 , in which the at least one surface sound wave is produced with a surface sound wave generating device with a preferably biocompatible coating.  
     
     
         11 . The mixing method according to  claim 10 , in which an insulating coating of the surface sound wave generating device is used.  
     
     
         12 . The mixing method according to one of claims  10  or  11 , in which a coating is used with a higher dielectrical constant on the surface sound wave generating device.  
     
     
         13 . The mixing method according to one of claims  1  through  12 , in which the quantity of liquid is disposed in an area, in which a resonator ( 86 ) for a surface sound wave is located, which is sent out from a surface sound generating device ( 85 ) spaced from the resonator region.  
     
     
         14 . The mixing method according to one of claims  1  through  13 , in which the quantity of liquid is located in a region, in which interference elements ( 101 ,  104 ) are located for generating turbulence in the quantity of liquid.  
     
     
         15 . The mixing method according to one of claims  1  through  14 , in which multiple quantities of liquid are applied for mixing on the reaction region ( 3 ,  23 ,  43 ,  63 ,  83 ,  93 ,  103 ,  204 ).  
     
     
         16 . The mixing method according to one of claims  1  through  14 , in which a material to be released on the reaction region ( 3 ,  23 ,  43 ,  63 ,  83 ,  93 ,  103 ,  204 ) is brought into contact with a liquid and by action of a surface sound wave, is released into the liquid.  
     
     
         17 . The mixing method according to one of claims  1  through  16 , in which the at least one quantity of liquid ( 53 ,  73 ) additionally is headed.  
     
     
         18 . The mixing device for mixing at least one small quantity of liquid by performing a method according to  claim 1 , with a t least one surface sound wave generating device ( 5 ,  25 ,  45 ,  65 ,  66 ,  67 ,  68 ,  85 ,  95 ,  105 ,  206 ) on a solid body surface and a reaction region ( 3 ,  23 ,  43 ,  63 ,  83 ,  93 ,  103 ,  204 ), which is arranged to the at least one surface sound wave generating device, such that it is deformed in operation of the at least one surface sound wave generating device from the generated surface sound wave.  
     
     
         19 . The mixing device according to  claim 18 , in which the reaction region is formed as a depression ( 3 ,  23 ,  204 ) and the depth of this depression is small relative to the wave length of a surface sound wave, which can be produced with the surface sound wave generating device ( 5 ,  206 ).  
     
     
         20 . The mixing device according to  claim 18 , in which the reaction region ( 23 ) is designed as a depression and the at least one surface sound wave generating device ( 25 ) is arranged at least partially in the depression.  
     
     
         21 . The mixing device according to one of claims  19  or  20 , in which the depression includes a recess ( 204 ) in a coating ( 202 ) on a solid body.  
     
     
         22 . The mixing device according to  claim 21 , in which the coating ( 202 ) includes silicon dioxide.  
     
     
         23 . The mixing device according to  claim 18 , in which the reaction region includes preferably a holding region ( 43 ,  63 ,  83 ,  93 ,  103 ) on the solid body surface, whose wetting characteristics differ from its lateral surrounding area, such that the quantity of liquid preferably is retained thereon.  
     
     
         24 . The mixing device according to  claim 23 , in which the at least one surface sound wave generating device ( 45 ,  105 ) and the preferred holding region ( 23 ,  103 ) overlap at least partially.  
     
     
         25 . The mixing device according to one of claims  23  or  24 , in which the surrounding area of the preferred holding region ( 43 ,  63 ,  83 ,  93 ,  103 ) is silanisized.  
     
     
         26 . The mixing device according to one of claims  18  through  25 , in which the reaction region ( 63 ) and the at least one surface sound wave generating device ( 65 ,  66 ,  67 ,  68 ) are arranged relative to one another, such that a surface sound wave, which is generated with the at least one surface sound wave generating device ( 65 ,  66 ,  67 ,  68 ) acts decentrally on the reaction region ( 63 ).  
     
     
         27 . The mixing device according to one of claims  18  through  26 , with at least two surface sound wave generating devices ( 65 ,  66 ,  67 ,  68 ) for producing surface sound waves, which are phase-displaced to one another in the reaction region ( 63 ).  
     
     
         28 . The mixing device according to one of claims  18  through  27 , with interference elements ( 101 ,  104 ) in the reaction region ( 93 ,  103 ).  
     
     
         29 . The mixing device according to  claim 28 , in which the interference elements ( 101 ) include etched regions in a non-etched or only minimally etched surrounding area or non-etched or only minimally etched regions in an etched surrounding area.  
     
     
         30 . The mixing device according to  claim 28 , in which the interference elements ( 101 ) include regions, which are coated differently from its surrounding area.  
     
     
         31 . The mixing device according to  claim 28 , in which the interference elements are formed by a non-uniform definition ( 104 ) of the reaction region ( 103 ).  
     
     
         32 . The mixing device according to one of claims  18  through  31 , with a preferably biocompatible coating ( 33 ,  43 ) on the surface sound wave generating device ( 25 ,  45 ).  
     
     
         33 . The mixing device according to  claim 32 , in which the coating ( 33 ,  43 ) has different wetting characteristics from its lateral surrounding area, such that the liquid preferably stops thereon.  
     
     
         34 . The mixing device according to one of claims  18  through  33 , in which the at least one surface sound wave generating device ( 5 ,  25 ,  45 ,  64 ,  66 ,  67 ,  68 ,  85 ,  95 ,  105 ,  206 ) includes an interdigital transducer.  
     
     
         35 . The mixing device according to one of claims  18  through  34 , with a resonator ( 86 ) in the reaction region ( 83 ), which is designed, such that a surface sound wave, which is produced with the at least one surface sound wave generating device ( 85 ), resonates.  
     
     
         36 . The mixing device according to claims  34  and  35 , in which the resonator ( 86 ) includes periodically arranged metal coatings, whose distance corresponds to the finger distance of the interdigital transducer ( 85 ).  
     
     
         37 . The mixing device according to one of claims  35  or  36 , with a coating on the resonator.  
     
     
         38 . The mixing device according to one of claims  18  through  37 , with a coating on the at least one surface sound wave generating device.  
     
     
         39 . The mixing device according to one of claims  37  and  38 , in which the coating is insulating.  
     
     
         40 . The mixing device according to one of claims  37  through  39 , in which the coating has a high dialectric constant.  
     
     
         41 . The mixing device according to one of claims  37  through  40 , with a thickness, which is smaller or essentially the same as the wave length of the surface sound wave produced by the at least one surface sound wave generating device.  
     
     
         42 . The mixing device according to one of claims  18  through  41 , with a heating device in the region of the reaction region ( 2 ,  23 ,  43 ,  63 ,  83 ,  93 ,  103 ,  204 ).  
     
     
         43 . A use of a device according to one of claims  18  through  42  as a cell adhesion assay.  
     
     
         44 . A method of analysis for analyzing the bond strength of objects on surfaces using a method according to one of claims  1  through  17 , in which as the quantity of liquid, a solution with microscopically small objects is used and during or after the reaction of the surface sound wave with the quantity of liquid in dependence on the current produced by the surface sound wave in the quantity of liquid, the objects adhered to the quantity on the surface is analyzed.  
     
     
         45 . The method of analysis according to  claim 44 , in which, as the solution, a nutritive solution is used and the objects are biological objects, in particular, cells or bacteria.  
     
     
         46 . The method of analysis according to one of claims  44  or  45 , in which the surface is functionalized in at least one sub-area.