Patent Publication Number: US-2005127215-A1

Title: Device for comminuting agglomerates, in particular by breaking up microparticles by piston movement in a container

Description:
CROSS REFERENCE  
      This application claims priority to German patent application DE 103 54 904.8, filed Nov. 24, 2003, which is incorporated by reference herein in its entirety.  
     FIELD OF THE INVENTION  
      The present invention concerns a device for comminuting agglomerates of particles present in a suspension.  
     BACKGROUND  
      Suspensions are used in diverse technical fields and in particular in the chemical field. Thus for example suspensions of microparticles, so-called beads, on whose surfaces capture molecules e.g. DNA are immobilized which can bind with certain analytes of a sample to be examined that can be detected by measuring systems are used for analytical purposes in the medical-diagnostic field. However, in these diagnostic and analytical applications and also in other application fields for suspensions, the problem occurs that the solid microparticles dispersed in the respective liquid form agglomerates. This is caused in particular by electrostatic forces and Van der Waals interactions between the microparticles. Such agglomerates may impair the optimal utilization of the suspension in the respective application.  
      Devices and methods are known which are intended to counteract the formation of agglomerates and comminute agglomerates that are already present. Conventional mixing devices are used among others for this purpose such as stirrers. Stirring the suspension exerts forces on the agglomerates of microparticles due to the stirring movement which counteract the attractive forces between the microparticles. In particular the stirring movement generates shear flows and these in turn generate shearing forces which act on the agglomerates and reduce the size of the agglomerates.  
      The previously known devices and methods have the disadvantage that they are not able to comminute agglomerates in suspensions to an adequate extent for certain applications. With the known stirring devices, either very long stirring times have to be accepted or very high stirring rates are necessary. Both of these are disadvantageous for certain applications especially because the time efficiency is low and reagents that are specific to the application which may be bound to the microparticles may become detached from the microparticles by the stirring process.  
      It is known from the article “Dispersibility of Applied Chemistry” by K. Higashitani, Proceedings of Second World Congress PARTICLE TECHNOLOGY, Sep. 19-22, 1990, Kyoto, Japan, that extensional flows and longitudinal flows with flow acceleration can be used to comminute agglomerates. The hydrodynamic forces acting on the agglomerates as a result of the extensional flows result in a substantially improved comminution of the agglomerates. In order to generate the extensional flows, the suspension should for example be passed through an opening i.e. a constriction in the flow path of the suspension.  
      Hence the object of the present invention was to provide an improved device compared to the prior art which can be used to more effectively reduce the size of agglomerates in suspensions. 
    
    
     BRIEF DESCRIPTION OF THE FIGURES  
       FIGS. 1   a  and  1   b  show two snapshots of a schematic side-view of an embodiment of the invention during operation of the device.  
       FIG. 2   a  shows a schematic side-view of a second embodiment of the device according to the invention.  
       FIG. 2   b  shows a view of the piston of the device from  FIG. 2   a  from below.  
       FIG. 3   a  shows a schematic lateral view of a third embodiment.  
       FIG. 3   b  shows a view of the piston of the device from  FIG. 3   a.    
       FIG. 4  shows a schematic lateral view of a fourth embodiment of the invention. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
      The device according to the invention for comminuting agglomerates of particles in a suspension comprises a container for receiving the suspension and at least one fluid displacement means preferably in the form of a piston which can be moved in the container in order to move a suspension between two spatial regions of a hollow space arrangement of the container, the two spatial regions being connected together by at least one flow path for the suspension which defines a constriction.  
      The displacement of the suspension caused by the piston movement results in a strong acceleration of the suspension as it flows through the constriction. In this process the hydrodynamic tensile forces and extending forces that were already mentioned above with reference to the article by K. Higashitani act on the agglomerates in the suspension. This results in an efficient comminution of agglomerates and additionally a thorough mixing of the suspension occurs. A device according to the invention enables the so-called stable state of the smallest possible agglomerates to be reached in a suspension in a relatively short time. A significant further reduction in the size of the agglomerates is then no longer possible with an acceptable amount of effort.  
      According to a preferred embodiment of the invention, the fluid displacement means is a piston forming a border between the spatial regions which can be moved axially backwards and forwards in a cylinder chamber containing the two spatial regions, which piston can displace the held suspension alternately from one spatial region into the other spatial region through the constriction as it moves backwards and forwards in the cylinder chamber. Such an embodiment of the device according to the invention can be realized and operated in a simple manner. Thus the flow path defining the constriction can be for example formed by a hole which passes axially through the piston. Then when the piston moves in the cylinder chamber, the suspension displaced from the spatial region that becomes smaller can flow through the axial hole in the piston into the expanding spatial region to produce a high flow rate in the area of the constriction and a strong acceleration of the flow having the effect that the agglomerates are torn apart. The resulting turbulence that also occurs in the suspension ensures a rapid transport of particles in the liquid and thus a good mixing or homogenization of the suspension. The reciprocating movement of the piston moves the suspension backwards and forwards between the two spatial regions during which it must each time flow through the constriction since the cylinder chamber is essentially closed towards the outside during the operation of the comminution device.  
      As a result, the large agglomerates that were originally present are comminuted as far as possible after a relatively short time and are thoroughly mixed. The suspension prepared in this manner can then be removed from the cylinder chamber or from the container through a valve that is opened or such like and provided for the intended use.  
      According to one embodiment of the invention, a small amount of the suspension is discharged from the container through a very small opening and a corresponding amount of suspension to be treated is introduced into the container through another small opening on each stroke of the piston.  
      Of course, several small axial holes or such like can be provided in the piston which can form a flow path for the displaced suspension.  
      According to another embodiment, the flow path defining the constriction is formed by an annular gap between the circumferential wall of the piston and the wall of the cylinder chamber. In such a case it is advisable to movably guide the piston in an axial manner on a piston rod which leads outwards since it is not guided by the circumferential wall of the cylinder chamber.  
      According to another embodiment, the flow path defining the constriction is formed by at least one radial recess in the circumferential wall of the piston.  
      Another embodiment of the invention provides that the two spatial regions are connected together by a fluid line forming the flow path of the suspension which runs outside the cylinder chamber. In such a case, the piston can essentially sealingly separate the two spatial regions such that the displaced suspension can only escape from the one spatial region into the other spatial region via the external fluid line.  
      According to one embodiment of the invention, the piston can be operated manually. In another embodiment of the invention, a drive motor is provided for the reciprocating movement of the piston.  
      According to a preferred embodiment of the invention, the device for comminuting agglomerates is integrated into an automated analysis system for the chemical analysis of molecules and in particular biomolecules. In such a case, the solid phase of the suspension preferably consists of beads i.e. microparticles with capture molecules immobilized thereon which can specifically bind to analytes of a sample to be analyzed that is added to the suspension e.g. a body fluid of a living being wherein this binding can be detected by technical measuring means of the analytical system such as spectroscopic means.  
      In this sense, the device according to the invention is very suitable for reducing the size of agglomerates of microparticles (beads) to which medical diagnostic reagents are attached. Especially high demands are made on the suspensions in such medical diagnostic applications, since a reduction in the bindable surface of the beads exposed to the sample material due to agglomerates has to be avoided as far as possible.  
     EXAMPLES  
      Embodiments of the invention are described in the following with reference to the figures.  
      The device for comminuting agglomerates of particles in a suspension according to  FIG. 1   a  and  FIG. 1   b  has a cylinder container  2  in whose cylinder chamber  4  a piston  6  is located such that it can be moved in a reciprocating manner. The piston  6  has a piston rod  10  which is sealingly guided through the upper front end  8  of the cylinder container  2 , which piston can be manually operated to axially move the piston  6  to and fro in the cylinder chamber  4 . In a variant of the embodiment of  FIGS. 1   a  and  1   b  a drive motor such as an electric motor can be in a driving connection with the piston rod in order to generate the stroke movements of the piston  6 .  
      The diameter of the piston  6  which is essentially radially centered in  FIGS. 1   a  and  1   b  is slightly less than the inner diameter of the cylinder chamber  4  such that a small annular gap  12  is present between the piston circumference and the inner circumferential surface of the cylinder chamber  4 . This annular gap  12  is a flow path defining a constriction for the suspension  14  held in the cylinder chamber  4 . Hence the suspension  14  can flow through the annular gap  12  between the two spatial regions  16  and  18  of the cylinder chamber  4  that are partitioned by the piston  6 .  
       FIG. 1   a  shows a snapshot of a downwards movement of the piston  6 . In this process the piston  6  displaces the suspension from the spatial region  18  through the annular gap  12  into the spatial region  16 . The drive force exerted on the piston  6  is of such a magnitude that the suspension fluid passes the constriction  12  at a high flow rate, the flow of the suspension being greatly accelerated immediately before entering the constriction  12 . The greatly accelerated elongation flow exerts stretching forces on agglomerates in the suspension that may be present in this area which leads to a break up of the agglomerates.  
      As shown by the flow arrows  20  that are drawn as a simplified qualitative representation of the flow behavior, the high flow rate of the suspension when it enters the expanding spatial region  16  generates turbulence. This has a mixing effect and contributes to the desired homogenization of the suspension.  
       FIG. 1   b  shows a snapshot as the piston  6  is moved upwards during which the suspension  14  is displaced from the spatial region  16  which is now contracting through the constriction  12  into the expanding spatial region  18 . On entry and passage through the annular gap  12 , agglomerates that may be present in the suspension are subjected to the aforementioned stretching forces in the accelerated elongation flow.  
      Once the suspension  14  is sufficiently finally dispersed after an appropriate number of axial reciprocating movements of the piston  6 , the check valve  22  located in an outlet line can be opened in order to provide the suspension for the intended further use.  
       24  refers to a check valve in a line leading to the cylinder  2 . After this check valve  24  is opened, new suspension can thus be fed into the cylinder chamber  4  for treatment in the device according to the invention.  
      Elements which correspond to functional or/and constructional elements of the first embodiment are labeled with the same reference numerals in order to elucidate the other embodiments of the invention in the relevant figures.  
      The second embodiment of the invention according to  FIG. 2   a  and  FIG. 3   a  only differs from the first embodiment in that the piston  6  of the second embodiment has a larger diameter D such that it is slidingly guided directly on the inner wall of the cylinder chamber  4  during its axial reciprocating movement. As shown in particular in  FIG. 2   b , the piston  6 , however, has radial and axial through-grooves  12  which together with the inner wall of the cylinder chamber  4  form a narrowed flow path for the suspension as it is forced to flow backwards and forwards between the spatial regions  16  and  18  by the reciprocating movement of the piston  6 .  
      The third embodiment of  FIG. 3   a  and  FIG. 3   b  is also a modification of the first embodiment which was already elucidated with reference to  FIGS. 1   a  and  1   b . In the third embodiment the circumferential wall of the piston  6  is slidingly guided against the inner wall of the cylinder chamber  4 . Axial through-holes  12  in the piston  6  serve as a flow path for the suspension when it is displaced between the two spatial regions  16  and  18 . In the example of  FIG. 3   b  four through-holes  12  are shown. Of course fewer through-holes can be present depending on the particular application.  
      The fourth embodiment of  FIG. 4  has a piston  6  which essentially sealingly separates the two spatial regions  16  and  18  from one another. An external fluid line  12  which connects the spatial regions  16  and  18  of the cylinder chamber  4  is provided as a flow path with a constriction or large flow resistance.