Patent Publication Number: US-2015076047-A1

Title: Particle Processing Device Using Combination of Multiple Membrane Structures

Description:
CLAIM OF PRIORITY 
     This application claims priority under 35 USC §119 to Korean Patent Application No. 2012-0037670, filed on Apr. 12, 2012 in the Korean Intellectual Property Office (KIPO), the contents of which are herein incorporated by reference in their entirety. 
     BACKGROUND 
     1. Field 
     Example embodiments relate to a particle processing device. More particularly, example embodiments relate to a particle processing device for performing multiple functions of capturing, collecting, counting and analyzing a particle in a fluid. 
     2. Description of the Related Art 
     Generally, one of technologies of detecting and capturing a micro-particle in a fluid may use a single filter layer for filtering out the particle from the fluid. However, in order to collect, count and analyze the filtered particles, additional filtering and analyzing structures and a fluid transfer therebetween may be required. During these processes, many problems such as losses of the particles may occur. 
     SUMMARY 
     Example embodiments provide a particle processing device for various functions such as sorting, counting, collecting and analyzing particles in a single analyzing device. According to example embodiments, a particle processing device includes a fluid flow path, a multi-filtering portion and a fluid transferring portion. A fluid having particles flows through the fluid flow path. The multi-filtering portion is installed in the fluid flow path. The multi-filtering portion includes at least two membrane structures. The membrane structures have different shaped openings for passing the fluid therethrough respectively. The membrane structures are arranged alone or together in the fluid flow path. The fluid transferring portion transfers the fluid forwardly or backwardly through the fluid flow path such that the fluid passes through the multi-filtering portion. 
     In example embodiments, the membrane structure of the multi-filtering portion may be detachably installed in the fluid flow path. 
     In example embodiments, the multi-filtering portion may include a first membrane structure and a second membrane structure. The first membrane structure may include a first opening of a first size and the second membrane structure may include a second opening of a second size different from the first size. The first size of the first opening may be smaller than a diameter of the particle and the second size of the second opening may be greater than the diameter of the particle. 
     In example embodiments, the multi-filtering portion may further include a third membrane structure. The third membrane structure may be detachably installed in the fluid flow path. The third membrane structure may include a third opening of a third size different from the first size. The third size of the third opening may be smaller than the first size. 
     In example embodiments, the third membrane structure may be installed in the fluid flow path, after the first membrane structure is removed from the fluid flow path. 
     In example embodiments, at least one of the membrane structures may include an electrode pattern for counting the number of the particles which pass through the opening. 
     In example embodiments, the multi-filtering portion may include a cylindrical fastening member for installing the membrane structure in the fluid flow path. 
     In example embodiments, a conductive pattern may be formed on a side surface of the cylindrical fastening member to be electrically connected to the electrode pattern 
     In example embodiments, the cylindrical fastening member may have a truncated conic shape. 
     In example embodiments, a thread groove may be formed on an inner surface or an outer surface of the cylindrical fastening member. 
     In example embodiments, the fluid may include blood, bodily fluid, cerebrospinal fluid, urine and spectrum collected from human or animal. These may be used alone or in a mixture thereof. 
     In example embodiments, the particle may include tissue, cell, protein and nucleic acid collected from human or animal. These may be used alone or in a mixture thereof. 
     In example embodiments, the effective diameter of the opening may range from about 1 μm to about 50 μm. 
     In example embodiments, the openings of the membrane structure may be arranged in a matrix form. The occupying area of the openings may range from about 5% to about 50% of the whole area of the membrane structure. 
     In example embodiments, the flow rate or direction of the fluid flowing through the multi-filtering portion in the fluid flow path may be controlled by a centrifugal force or an agitating force. 
     In example embodiments, the membrane structure may include at least two filter layers that are arranged to be overlapped with each other, the filter layers may have holes respectively that form the opening, and a shape and a size of the opening may be controlled. 
     According to example embodiments, a particle processing device may include a multi-filtering portion having at least two membrane structures which are arranged in a fluid flow path. The particle processing device may efficiently capture, collect, count and analyze particles by using bidirectional flow in the fluid flow path. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Example embodiments will be more clearly understood from the following detailed description taken in conjunction with the accompanying drawings.  FIGS. 1 to 9  represent non-limiting, example embodiments as described herein. 
         FIG. 1  is a view illustrating a particle processing device in accordance with example embodiments. 
         FIG. 2A  is a cross-sectional view illustrating a first membrane structure in the particle processing device in  FIG. 1 . 
         FIG. 2B  is a perspective view illustrating a portion of the first membrane structure in  FIG. 2A . 
         FIG. 2C  is a plan view illustrating the first membrane structure in  FIG. 2A . 
         FIG. 3A  is a cross-sectional view illustrating a second membrane structure in the particle processing device in  FIG. 1 . 
         FIG. 3B  is a perspective view illustrating a portion of the second membrane structure in  FIG. 3A . 
         FIG. 4A  is a cross-sectional view illustrating a third membrane structure in the particle processing device in  FIG. 1 . 
         FIG. 4B  is a perspective view illustrating a portion of the third membrane structure in  FIG. 4A . 
         FIGS. 5A to 5F  are cross-sectional views illustrating a sidewall of an opening of the membrane structure in  FIG. 2A . 
         FIGS. 6A to 6C  are plan views illustrating a modification of the membrane structure in  FIG. 2A . 
         FIGS. 7A to 7D  are cross-sectional views illustrating a method of processing a particle using a combination of the membrane structures of the particle processing device in  FIG. 1 . 
         FIG. 8A  is a perspective view illustrating the membrane structure in  FIG. 7A . 
         FIG. 8B  is a perspective view illustrating the membrane structures in  FIG. 7B . 
         FIG. 8C  is a perspective view illustrating the membrane structures in  FIG. 7C . 
         FIG. 9  is a perspective view illustrating the membrane structure in  FIG. 7A . 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     Various example embodiments will be described more fully hereinafter with reference to the accompanying drawings, in which some example embodiments are shown. The present inventive concept may, however, be embodied in many different forms and should not be construed as limited to the example embodiments set forth herein. Rather, these example embodiments are provided so that this description will be thorough and complete, and will fully convey the scope of the present inventive concept to those skilled in the art. In the drawings, the sizes and relative sizes of layers and regions may be exaggerated for clarity. 
     It will be understood that when an element or layer is referred to as being “on,” “connected to” or “coupled to” another element or layer, it can be directly on, connected or coupled to the other element or layer or intervening elements or layers may be present. In contrast, when an element is referred to as being “directly on,” “directly connected to” or “directly coupled to” another element or layer, there are no intervening elements or layers present. Like numerals refer to like elements throughout. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. 
     It will be understood that, although the terms first, second, third, fourth etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present inventive concept. 
     Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “upper” and the like, may be used herein for ease of description to describe one element or feature&#39;s relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. 
     The terminology used herein is for the purpose of describing particular example embodiments only and is not intended to be limiting of the present inventive concept. As used herein, the singular forms “a,” “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. 
     Example embodiments are described herein with reference to cross-sectional illustrations that are schematic illustrations of idealized example embodiments (and intermediate structures). As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques and/or tolerances, are to be expected. Thus, example embodiments should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result, for example, from manufacturing. 
     Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this inventive concept belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. 
       FIG. 1  is a view illustrating a particle processing device in accordance with example embodiments.  FIG. 2A  is a cross-sectional view illustrating a first membrane structure in the particle processing device in  FIG. 1 .  FIG. 2B  is a perspective view illustrating a portion of the first membrane structure in  FIG. 2A .  FIG. 2C  is a plan view illustrating the first membrane structure in  FIG. 2A .  FIG. 3A  is a cross-sectional view illustrating a second membrane structure in the particle processing device in  FIG. 1 .  FIG. 3B  is a perspective view illustrating a portion of the second membrane structure in  FIG. 3A .  FIG. 4A  is a cross-sectional view illustrating a third membrane structure in the particle processing device in  FIG. 1 .  FIG. 4B  is a perspective view illustrating a portion of the third membrane structure in  FIG. 4A . 
     Referring to  FIGS. 1 to 4B , a particle processing device  10  according to example embodiments may include a fluid flow path  20  for providing a space for fluid flow, a multi-filtering portion arranged in the fluid flow path  20 , and a fluid transferring portion for transferring a fluid forwardly or backwardly through the fluid flow path  20 . 
     In example embodiments, the fluid transferring portion may include a first pump P 1  and a second pump P 2 . The first pump P 1  may be connected to a first connection flow path  12  via a first valve V 1 , and the first connection flow path  12  may be connected to a first end portion  22  of the fluid flow path  20 . The second pump P 2  may be connected to a second connection flow path  14  via a second valve V 2 , and the second connection flow path  14  may be connected to a second end portion  24  of the fluid flow path  20 . 
     The first valve V 1  may be connected to a first fluid supply portion (not illustrated), and a fluid may be supplied from the first fluid supply portion to the first end portion  22  of the fluid flow path  20  by the first pump P 1 . The second valve V 2  may be connected to a second fluid supply portion (not illustrated), and a fluid may be supplied from the second supply portion to the second end portion  24  of the fluid flow path  20  by the second pump P 2 . For example, the first pump and the second pump may operate on the basis of mechanical principles (e.g. external syringe pumps, pneumatic membrane pumps, vibrating membrane pumps, vacuum devices), electrical or magnetic principles (e.g. electrohydrodynamic pumps, magenetohydrodynamic pumps), thermodynamic principles, etc. 
     Accordingly, the fluid transferring portion may transfer a fluid in a first direction (forwardly) from the first end portion  22  of the fluid flow path  20  to the second end portion portion  24  of the fluid flow path  20 . Additionally, the fluid transferring portion may transfer a fluid in a second direction (backwardly) from the second end portion  24  to the first end portion  22 . 
     In another example embodiment, a separation container for centrifugation or agitation may be used to function as the fluid flow path  20 . In this ease, the separation container used for the fluid flow path  20  may include a cylindrical tube, which contains the fluid therein. The separation container may be connected to a fluid transferring portion such as a rotor of a centrifuge or an agitating means of an agitator such that the separation container may rotate or move in curved trajectories to separate desired particles in the fluid flow path  20 . 
     Accordingly, the fluid transferring portion may rotate or agitate the separation container such that the fluid may flow bidirectionally (forwardly or backwardly) along the fluid flow path  20 . Thus, the flow rate or direction of the fluid flowing through the multi-filtering portion in the fluid flow path  20  may be controlled by a centrifugal force or an agitating force. 
     For example, the fluid may be a bodily fluid such as blood including cells of different types and biological particles. The fluid may include a target particle having information about the health of an organism. The target particle may be a biological micro-particle such as cancer cell, bacteria, virus, etc. 
     In particular, the fluid collected from human or animal sample may include blood, bodily fluid, cerebrospinal fluid, urine, spectrum, a mixture thereof, a diluted solution thereof, etc. The particle in the fluid may include tissue, cell, protein, nucleic acid, a mixture thereof. 
     The multi-filtering portion may include at least two membrane structures which have different shaped openings for filtering the fluid respectively. The two membrane structures may be arranged alone or together in the fluid flow path  20  to perform at least one of separating, collecting and counting particles. 
     In example embodiments, the multi-filtering portion may include a first filter structure  30 , a second filter structure  40  and a third filter structure  50  which are detachably installed in the fluid flow path  20 . The first to third filter structures may be arranged alone or together in the fluid flow path  20 . 
     As illustrated in  FIGS. 2A to 2C , the first filter structure  30  may include a first membrane structure  32  and a first cylindrical fastening member  34  for installing the first membrane structure  32  in the fluid flow path  20 . The first cylindrical fastening member  34  may include a connection portion  36 , which is fixed to the first end portion  22  of the fluid flow path  20 . 
     In example embodiments, the first membrane structure  32  may include a plurality of first openings  33  for filtering the fluid. For example, a diameter of the first opening  33  may have a first size smaller than a diameter of a target particle. The first cylindrical fastening member  34  may have a truncated conic shape. The inner area of the first cylindrical fastening member  34  may be gradually decreased in a forward direction along the fluid flow path  20 . 
     For example, the effective diameter of the first opening may range from about 1 μm to about 50 μm. The first openings may be arranged in a matrix form. The occupying area of the first openings may range from about 5% to about 50% of the whole area of the first membrane structure  32 . 
     As illustrated in  FIGS. 3A to 3B , the second filter structure  40  may include  30  may include a second membrane structure  42  and a second cylindrical fastening member  44  for installing the second membrane structure  42  in the fluid flow path  20 . The second cylindrical fastening member  44  may include a connection portion  46 , which is fixed to the first end portion  22  of the fluid flow path  20 . 
     In example embodiments, the second membrane structure  42  may include a plurality of second openings  43  for filtering the fluid. The second opening  43  may have a different shape from the first opening  33 . For example, a diameter of the second opening  43  may have a second size greater than the diameter of the target particle. 
     The second cylindrical fastening member  44  may have a truncated conic shape. The inner area of the second cylindrical fastening member  44  may be gradually decreased in a forward direction along the fluid flow path  20 . Accordingly, the first cylindrical fastening member  34  and the second cylindrical fastening member  44  may be inserted with interference fit into each other such that the first membrane structure  32  and the second membrane structure  42  may be arranged to be spaced apart from each other (See  FIG. 7B ). For example, the second membrane structure  42  may be installed in front of the first membrane structure  32 , that is, upstream in the fluid flow path  20 . 
     In example embodiments, the second membrane structure  42  may include an electrode pattern  41  for counting the number of the particles which pass through the second opening  43 . The electrode pattern  41  may be formed on the second member structure  42  to surround the second opening  43 . The electrode pattern  41  may have various shapes for counting the number of the particles which pass through the second opening  43 . 
     The electrode pattern  41  may be electrically connected to a conductive pattern  45  on the second cylindrical fastening member  44 . Accordingly, the electrode pattern  41  may be electrically connected to an external device such as a counter (not illustrated) through the conductive pattern  45 . 
     As illustrated in  FIGS. 4A and 4B , the third filter structure  50  may include a third membrane structure  52  and a third cylindrical fastening member  54  for installing the third membrane structure  52  in the fluid flow path  20 . 
     In example embodiments, the third membrane structure  52  may include a plurality of third openings  53  for filtering the fluid. For example, a diameter of the third opening  53  may have a third size smaller than the first size. 
     The third cylindrical fastening member  54  may have a truncated conic shape. The inner area of the third cylindrical fastening member  54  may be gradually decreased in a forward direction along the fluid flow path  20 . Accordingly, the first to third cylindrical fastening members may be inserted with interference fit. For example, the third membrane structure  52  may be installed in the fluid flow path  20  instead of the first membrane structure  32 . That is, after the first membrane structure  32  is removed, the third membrane structure  52  may be installed in rear of the second membrane structure  42 , that is, downstream in the fluid flow path  20 . 
     In example embodiments, a biochemical material layer may be coated on the cylindrical fastening member of the multi-filtering portion or surface treatment may be performed on the cylindrical fastening member, in order to increase or decrease the adhesive strength with the particle. 
       FIGS. 5A to 5F  are cross-sectional views illustrating a sidewall of an opening of the membrane structure in  FIG. 2A . 
     Referring to  FIG. 5A to 5F , the opening formed in the membrane structure may have various profiles. As illustrated in  FIGS. 5A and 5B , the sidewall profile of the opening may have a linear shape. As illustrated in  FIGS. 5C and 5D , the sidewall profile of the opening may have a curved shape. As illustrated in  FIGS. 5E and 5F , the middle portion of the opening may have a relatively smaller diameter. Alternatively, the opening may have a constant diameter in an extending direction of the opening. 
     Although it is not illustrated in the figures, the opening of the membrane structure may have various shapes. As seen in plan view, the opening may have a circular or polygonal shape. 
       FIGS. 6A to 6C  are plan views illustrating a modification of the membrane structure in  FIG. 2A . 
     Referring to  FIGS. 6A to 6C , a first membrane structure  32  may include at least two filter layers that are arranged to be overlapped with each other. The first membrane structure  32  may include a first filter layer  34   a  and a second filter layer  34   b.  The first filter layer  34   a  may include a plurality of first holes  36   a  and the second filter layer  36   b  may include a plurality of second holes  36   b.  The first filter layer  34   a  and the second filter layer  34   b  may be arranged to be overlapped with each other. 
     As illustrated in  FIGS. 6B and 6C , the first and second filter layers  34   a  and  34   b  may move (translate or rotate) relatively to each other to control the size of the first openings  33  that are formed by the first and second holes  36   a  and  35   b.  Accordingly, the first membrane structure  32  may serve as a filter for selectively passing a particle in fluid. Although it is illustrated in the figures, the second and third membrane structures  42  and  52  may include filter layers that are arranged to be overlapped with each other to control the size and the area of the opening. 
     Hereinafter, a method of collecting a particle from a fluid using the particle processing device in  FIG. 1  will be explained. 
       FIGS. 7A to 7D  are cross-sectional views illustrating a method of processing a particle using a combination of the membrane structures of the particle processing device in  FIG. 1 .  FIG. 8A  is a perspective view illustrating the membrane structure in  FIG. 7A .  FIG. 8B  is a perspective view illustrating the membrane structures in  FIG. 7B .  FIG. 8C  is a perspective view illustrating the membrane structures in  FIG. 7C .  FIG. 9  is a perspective view illustrating the membrane structure in  FIG. 7A . 
     Referring to  FIGS. 7A and 8A , after a first filter structure  30  is installed in a fluid flow path  20 , a fluid F may flow in a first direction (forward direction) from a first end portion  22  of the fluid flow path  20  to a second end portion  24  of the fluid flow path  20  by a fluid transferring portion such that the fluid F may pass through a first membrane structure  32  of the first filter structure  30 . 
     A diameter of a first opening  33  of the first membrane structure  32  may have a first size smaller than a diameter of a micro-particle T. Accordingly, the first membrane structure  32  may filter out the micro-particle T from the fluid F. Particles having a diameter smaller than the first size may pass through the first membrane structure  32 . 
     Referring to  FIGS. 7B and 8B , a second filler structure  40  may be installed in the fluid flow path  20 . The first and second filter structures  30  and  40  may have a truncated conic shape. As illustrated in  FIG. 9 , a thread groove may be formed on an inner surface of a first cylindrical fastening member  34  of the first filter structure  30  and a thread may be formed on an outer surface of a second cylindrical fastening member  44  of the second filter structure  40  to be inserted into the thread groove. Alternatively, a thread groove may be formed on the outer surface of the second cylindrical fastening member  44  of the second filter structure  40  and the thread may be formed on the inner surface of the first cylindrical fastening member  34  of the first filter structure  30 . 
     Accordingly, the second cylindrical fastening member  44  of the second filter structure  40  may be inserted with interference fit into the first cylindrical fastening member  34  of the first filter structure  30  such that the first membrane structure  32  and the second membrane structure  42  may be arranged in the fluid flow path  20  to he spaced apart from each other. For example, the second membrane structure  42  may be installed in front of the first membrane structure  32 , that is, downstream of the fluid flow. 
     The fluid transferring portion may change a flow direction and transfer a fluid in a second direction (backward direction) opposite to the first direction from the second end portion  24  of the fluid flow path  20  to the first end portion  22  such that the fluid may pass through the first membrane structure  32  of the first filter structure  30  and the second membrane structure  42  of the second filter structure  40 . 
     A diameter of a second opening  43  of the second membrane structure  42  may have a second size greater than the diameter of the micro-particle T. The second membrane structure  42  may include an electrode pattern  41  for counting the number of the micro-particles T passing through the second opening  43 . The electrode pattern  41  may be formed to surround the second opening  43 . Accordingly, the second membrane structure  42  may be used to count and analyze the micro-particles. 
     Referring to  FIGS. 7C and 8C , a third filter structure  50  may be installed in the fluid flow path  20 . The third filter structure  50  may be installed in the fluid flow path  20  instead of the first filter structure  30 . Accordingly, after the first membrane structure  32  is removed, a third membrane structure  52  may be installed in rear of the second membrane structure  42 , that is, upstream of the fluid flow. 
     The fluid transferring portion may change a flow direction again and transfer a fluid in the first direction (forward direction) from the first end portion  22  of the fluid flow path  20  to the second end portion  24  such that the fluid may pass through the second membrane structure  42  of the second filter structure  40  and the third membrane structure  52  of the third filter structure  50 . 
     The third membrane structure  52  may include a plurality of third openings  53  for filtering the fluid. For example, a diameter of the third opening  53  may have a third size smaller than the first size of the first opening  32 . Accordingly, the micro-particle T may be filtered out to remain on the third membrane structure  52 . 
     Referring to  FIG. 7D , the second filter structure  40  may be removed from the fluid flow path  20  and the micro-particles T filtered by the third filter structure  50  may be collected. 
     As mentioned above, a particle processing device according to example embodiments may perform various functions such as sorting, counting, collecting and analyzing particles from a fluid using a combination of the different membrane structures. 
     At least two membrane structures and a combination thereof may be used to provide a particle processing device where various functions of sorting, counting, collecting and analyzing particles may be performed in one device, thereby minimizing loss of micro-particles and miniaturizing the entire analyzation system. 
     The foregoing is illustrative of example embodiments and is not to be construed as limiting thereof. Although a few example embodiments have been described, those skilled in the art will readily appreciate that many modifications are possible in the example embodiments without materially departing from the novel teachings and advantages of the present inventive concept. Accordingly, all such modifications are intended to be included within the scope of the present inventive concept as defined in the claims. In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures. Therefore, it is to be understood that the foregoing is illustrative of various example embodiments and is not to be construed as limited to the specific example embodiments disclosed, and that modifications to the disclosed example embodiments, as well as other example embodiments, are intended to be included within the scope of the appended claims.