Abstract:
A device and method for separating heavier and lighter phases of a fluid sample is described. The fluid separation device includes an elongate collection tube accommodating the fluids, and a deformable separator including a deformable bladder having a flowable substance contained therein. The deformable bladder is reconfigurable upon centrifugation to a toroidal shape allowing fluid flow therethrough. The bladder is movable along the tube during centrifugation to a position between the separated blood phase.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     This invention relates to a device and method for separating heavier and lighter fractions of a fluid sample. More particularly, this invention relates to a device and method for collecting and transporting fluid samples whereby the device and fluid sample are subjected to centrifugation in order to cause separation of a heavier fraction from a lighter fraction of a fluid sample. 
     2. Description of Related Art 
     Diagnostic tests may require separation of a patient&#39;s whole blood sample into components, such as serum or plasma, a lighter phase component, and red blood cells, a heavier phase component. Samples of whole blood are typically collected by venipuncture through a cannula or needle attached to a syringe or an evacuated collection tube. Separation of the blood into serum or plasma is then accomplished by rotation of the syringe or tube in a centrifuge. Such arrangements use a barrier for moving into an area adjacent the two phases of the sample being separated to maintain the components separated for subsequent examination of the individual components. 
     A variety of devices have been used in collection containers to divide the area between the heavier and lighter phases of a fluid sample. Many of these devices include mechanical barriers or partitions which are positioned within the lower collection tube. Upon centrifugation, the barrier becomes relocated within the tube between the separated blood phases. 
     Other separators include the use of thixotropic gel materials such as polyester gels in a tube. Such polyester gel serum tubes require special manufacturing equipment to prepare the gel and to fill the tubes. Moreover, the shelf-life of the product is limited in that, over time, globules may be released from the gel mass. These globules have a specific gravity that is less than the separated serum and may float in the serum and may clog certain measuring instruments, such as the instrument probes used during the clinical examination of the sample collected in the tube. Such clogging can lead to considerable downtime for the instrument to remove the clog. 
     No commercially available gel is completely chemically inert to all analytes. If certain drugs are present in the blood sample when it is taken, there can be an adverse chemical reaction with the gel interface. 
     Therefore, a need exists for a separator device that (i) is easily and inexpensively manufactured; (ii) is easily used to separate a blood sample; (iii) is independent of temperature during storage and shipping; (iv) is stable to radiation sterilization; (v) employs the benefits of a thixotropic gel barrier yet avoids the many disadvantages of placing a gel in contact with the separated blood components; (vi) minimizes cross contamination of the heavier and lighter phases of the sample during centrifugation; (vii) minimizes adhesion of the lower and higher density materials against separator device; (viii) is able to move into position to form a barrier in less time than conventional methods and devices; (ix) is able to provide a clearer specimen with less cell contamination than conventional methods and devices; and (x) can be used with standard sampling equipment. 
     SUMMARY OF THE INVENTION 
     The present invention provides a fluid separation device for maintaining separation of centrifuged fluids having first and second phases of respective densities. The device includes an elongate collection tube for accommodating fluids, and a deformable separator disposed within said tube. The separator is a ring-shaped bladder, having a configuration including a tubular passage for movement of the fluids therethrough. The bladder contains a flowable substance with a density intermediate the densities of the first and second phases of the fluids. The bladder furthermore is movable upon centrifugation to a position between separated first and second phases of the fluids, and is reconfigurable after centrifuge into a disk-like configuration along the tubular passage, establishing a separation between the first and second phases of the fluids. 
     The present invention also provides a method of separating and maintaining separation of fluids of first and second phases of respective densities. The method of separating collected blood fluids in heavy and light phases comprises the steps of first providing an elongate blood collection tube having a deformable separator resident therein. The deformable separator is generally toroidal in shape and contains a medium therein with a density such that the density of the bladder and medium combined is intermediate the respective densities of said heavy and light fluid phases. Collected blood fluids are placed in the tube and the tube is centrifuged to cause blood separation into said heavy and light phases. Centrifugation also causes the deformable separator to move in-between the phases and reconfigure from the generally toroidal shape having a passage therethrough for passage of fluids to a disk-like shape, which maintains separation between said separated phases of said fluids. 
     The device of the present invention is advantageous over existing separation devices in that it provides a more efficient separation of different phases of blood by the deformable bladder walking up the sides of the cylinder collection tube, while allowing flow of heavier fluids and cellular material through a central tubular passage of the separator. 
     A particular advantage of the device is that there is no shearing of the clot, as it is moving in the same direction as the inside of the toroidal-shaped tubular separator. The speed of the movement may be dictated by how quickly the clot separates and forms a density gradient, but can also be modified by the type of gel, or other substance used within bladder. For example, the lower the viscosity, the faster the movement of the separator, and hence the quicker the separation. 
     Furthermore, the deformable separator is advantageous to use, in that it has great tolerance variations due to its deformability. For example, it may be used with many different elongate collection tubes as it is highly tolerant to any variations between different tubes. Since it is essentially a deformable bladder, the separator adjusts easily to the collection tube, and is malleably positioned in both disk-like and toroidal configuration. 
    
    
     DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a perspective view of the fluid separation device of the present invention including a blood collection tube and deformable separator. 
     FIG. 2 is a perspective view of the separator in its resting configuration when no force is acted upon it. 
     FIG. 3 is a perspective view of the separator shown in FIG. 2 with a centrifugal force applied thereto. 
     FIG. 4 is a perspective view of the device of the present invention as centrifugal force is applied thereto. 
     FIG. 5 is a perspective view of the separation device of the present invention at rest after centrifuge. 
    
    
     DETAILED DESCRIPTION 
     The present invention may be embodied in other specific forms and is not limited to any specific embodiments described in detail, which are merely exemplary. Various other modifications will be apparent to and readily made by those skilled in the art without departing from the scope and spirit of the invention. The scope of the invention will be measured by the appended claims and their equivalents. 
     The present invention is a fluid separation device for maintaining separation of centrifuged fluids having first and second densities. Preferably the fluids are blood fluids. Blood is typically collected and separated into the lighter phase (serum or plasma) and the heavier phase (red blood cells and other cellular material) for testing and diagnoses. 
     Referring now to FIGS. 1 and 2 of the drawings, a fluid separation device  10  of the present invention is shown. Fluid separation device  10  includes an elongate collection tube  12  of generally conventional construction. Tube  12  is an elongate cylindrical member having an upper end  13 , a lower end  14 , and a cylindrical wall  15  extending therebetween. The upper end  13  includes an opening  13   a , while the lower end  14  is closed by an integrally formed bottom  14   a . A tube interior  16  is defined between upper and lower ends  13  and  14 . The opening  13   a  of upper end  13  of tube  12  may be closed by a conventional stopper  18  which is made of a suitable elastomer such as rubber. Stopper  18  may be pierceable by a needle cannula (not shown) for permitting introduction of collected blood into the interior of tube  12 . 
     Disposed within tube  12  is a deformable separator  20 . Deformable separator  20  is defined by a ring-shaped bladder  21 . The bladder  21  forming deformable separator  20  is generally in the configuration of a toroidal-shaped tube having an outer tubular wall  22  connected continuously to an inner tubular wall  24 . Inner tubular wall  24  defines an openable tubular passage  26  through bladder  21 . As will be described herein below, bladder  21  is reconfigurable to two operative shapes in the present invention. One shape maintains tubular passage  26  open so as to permit fluid flow therethrough and the other shape is in the form of a solid disk closing tubular passage  26  and preventing fluid flow therethrough. 
     Separator  20  includes a flowable substance  28  within bladder  21 . Flowable substance  28  has a density intermediate the densities of the first and second phases of the fluids being centrifuged for separation. Flowable substance  28  is preferably a thixotropic substance which is rendered flowable upon centrifuge of the fluid separation device. 
     Bladder  21  may be formed of a material having a high coefficient of friction. Such material would have a tendency to adhere to the inner wall of the collection tube. Due to this frictional adhesion and the toroidal shape taken by the bladder upon centrifugation, the bladder has a tendency to “walk” along the wall of the tube by rolling over itself rather than by sliding therealong. This provides a separation of fluids in a more proficient manner. This high coefficient of friction may be provided by selecting an appropriate material forming the bladder  21 . Also, a coating may be applied to the bladder to provide adhesion to the walls of the tube. Such a coating is inert to the blood to be separated. 
     Bladder  21  may be a flexible deformable bladder which is reconfigurable upon an application of force (e.g., centrifuge, as mentioned above). Bladder  21  may be formed from a wide variety of both elastic and inelastic materials such as polyethylene, polyurethane, or syran. The particular material which forms bladder  21  is selected so that the material does not adversely interact with the fluids (e.g., blood) which would come in contact with the bladder. The diameter of the bladder is selected such that it fits snugly within collection tube  12 . Bladder  21  is formed of a material which is sufficiently deformable, flexible, and pliable, but also has sufficient strength so as to permit bladder deformation without risk of rupturing of the bladder. Bladder  21  may be formed from polyethylene, polyurethane, syran or latex. 
     Flowable substance  28  is contained within bladder  21  in sealed containment. Substance  28  may preferably be a gel introduced into bladder  21  upon evacuation of bladder  21 . Flowable substance  28  is a thixotropic medium which may be subject to fluid flow upon introduction of a force thereto. Generally, contact between substance  28  and the blood is prevented by bladder  21 , but it is still preferred that substance  28  be substantially water insoluble and be inert to components of the blood. 
     Substance  28  is selected so that it becomes resident between the separated blood phases. Thus, substance  28  is selected to have a specific gravity when combined with the bladder, intermediate the specific gravities of the separated lighter serum or plasma phase, and the heavy cellular phase. When separating phases in blood, it is preferable to use a substance  28  with a density of between 1.030 g/cc and 1.06 g/cc, and it is most preferable to use a substance with a density of 1.045 g/cc, which is intermediate the densities of red blood cells and serum. Substance  28  is generally fluid in nature. However, at rest and under normal handling and shipping conditions, it may be semi-solid or resistant to flow. When subjected to forces such as centrifugal forces, substance  28  becomes flowable. Upon cessation of such centrifugal forces however, substance  28  may return to its more solid or non-flowable state. 
     Substance  28  may be selected from the group consisting of gels, oils, silicones, and combinations thereof. Substance  28  may be a single component gel or may be formed of various combinations of gels and fluids. Examples include mixtures of silicon and hydrophobic silicon dioxide powders, or mixtures of liquid polybutane polymer and silicon dioxide powder. The gels may also contain a flow-promoting substance mixed therein. The gel may also contain particulate matter mixed in combination therewith, particularly beads. 
     With reference to FIGS. 2 and 3 of the drawings, ring-shaped bladder  21  is shown at rest in FIG. 2, and is shaped as a flat annular disk-shape with tubular passage  26  closed, or obstructed. In this configuration, it may serve as a barrier through which fluids may not flow. Upon application of a centrifugal force however, bladder  21  reconfigures into a toroidal-shaped tube as shown in FIG. 3, with tubular passage  26  defined by inner tubular wall  24 . 
     Prior to use of the fluid separation device  10 , the deformable separator  20  is inserted into tube  12 . The gel containing bladder is positioned in the lower end  14  of tube  12 . After withdrawal of blood, the blood is then injected into tube  10 . With reference now to FIGS. 4 and 5 of the drawings, the tube is then subjected to centrifuge. Upon centrifuge, bladder  21  reconfigures to a toroidal shaped tube with outer tubular wall  22  continuously connected to inner tubular wall  24 , defining a tubular passage  26  therethrough. The toroidal tube contains an upper end  34  and a lower end  36  and a center of gravity  38  in the middle therebetween. Separator  20  moves up through collection tube  12  from lower end  14  towards upper end  13  in a direction indicated by directional arrow  32 . As separator  20  moves upward within tube  12 , the more dense red blood cells flow through tubular passage  26  in a direction as indicated by directional arrows  39 . As noted above, bladder  21  preferably moves within tube  12  by a frictionless, rolling mechanism. In rolling the toroidal tube up the cylindrical walls of tube  12 , the outer tubular wall  22  rolls to the lower end  36  of separator  20  to replace inner tubular wall  24  similar to a mobius strip. The direction of the rolling movement of the wall is indicated by directional arrows  40 . Preferably the movement is accompanied by the absence of sliding between outer wall  22  and cylindrical walls  15  of collection tube  12 . This provides a more efficient migration of separator  20 , and, subsequently, a more efficient separation of fluids. 
     This rolling mechanism coupled with a slight adhesion of outer wall  22  to the cylindrical walls of tube  12  provide an efficient “walking” migration of the separator up the tube, with the more dense red blood cells flowing through the tube&#39;s center to the bottom of the tube. Bladder  21  substantially clings to the sides of the tube, which provides tubular passage  26  as the only alternative downward direction where the clot is able to flow. The central aperature in the bladder provides a funnel like entrance for the higher density clot and cellular material to flow. 
     Upon cessation of the centrifuge process, bladder  21  then reverts to its disk-like configuration with tubular passage  26  being obstructed as seen in FIG.  5 . Separator  20  is now at rest between the red blood cells of lower density, and the serum of higher density, and provides a barrier therebetween by obstruction of tubular passage  26 .