Density phase separation device

A mechanical separator for separating a fluid sample into first and second phases is disclosed. The mechanical separator includes a float having a first portion and a second portion, a ballast circumferentially disposed about a section of the float, and a deformable bellows defining an open passageway extending between a first end and a second end. The ballast is longitudinally moveable with respect to the float and engaged with the deformable bellows between the first end and the second end. At least a portion of the float is transitionable from a restraint position to a sealed position through the first end of the bellows. The first portion of the float can be positioned within the interior of the deformable bellows in the restraint position, and the first portion of the float can be positioned at an exterior location longitudinally displaced from the deformable bellows in the sealed position.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The subject 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 the heavier fraction from the lighter fraction of the fluid sample.

2. Description of Related Art

Diagnostic tests may require separation of a patient's whole blood sample into components, such as serum or plasma, (the lighter phase component), and red blood cells, (the heavier phase component). Samples of whole blood are typically collected by venipuncture through a cannula or needle attached to a syringe or an evacuated blood collection tube. After collection, separation of the blood into serum or plasma and red blood cells is accomplished by rotation of the syringe or tube in a centrifuge. In order to maintain the separation, a barrier must be positioned between the heavier and lighter phase components. This allows the separated components to be subsequently examined.

A variety of separation barriers have been used in collection devices to divide the area between the heavier and lighter phases of a fluid sample. The most widely used devices include thixotropic gel materials, such as polyester gels. However, current polyester gel serum separation tubes require special manufacturing equipment to both prepare the gel and fill the tubes. Moreover, the shelf-life of the product is limited. Over time, globules may be released from the gel mass and enter one or both of the separated phase components. These globules may clog the measuring instruments, such as the instrument probes used during the clinical examination of the sample collected in the tube. Furthermore, commercially available gel barriers may react chemically with the analytes. Accordingly, if certain drugs are present in the blood sample when it is taken, an adverse chemical reaction with the gel interface can occur.

Certain mechanical separators have also been proposed in which a mechanical barrier can be employed between the heavier and lighter phases of the fluid sample. Conventional mechanical barriers are positioned between heavier and lighter phase components utilizing differential buoyancy and elevated gravitational forces applied during centrifugation. For proper orientation with respect to plasma and serum specimens, conventional mechanical separators typically require that the mechanical separator be affixed to the underside of the tube closure in such a manner that blood fill occurs through or around the device when engaged with a blood collection set. This attachment is required to prevent the premature movement of the separator during shipment, handling and blood draw. Conventional mechanical separators are affixed to the tube closure by a mechanical interlock between the bellows component and the closure. Example devices are described in U.S. Pat. Nos. 6,803,022 and 6,479,298.

Conventional mechanical separators have some significant drawbacks. As shown inFIG. 1, conventional separators include a bellows34for providing a seal with the tube or syringe wall38. Typically, at least a portion of the bellows34is housed within, or in contact with a closure32. As shown inFIG. 1, as the needle30enters through the closure32, the bellows34is depressed. This creates a void36in which blood may pool when the needle30is removed. This can result in needle clearance issues, sample pooling under the closure, device pre-launch in which the mechanical separator prematurely releases during blood collection, hemolysis, fibrin draping and/or poor sample quality. Furthermore, previous mechanical separators are costly and complicated to manufacture due to the complicated multi-part fabrication techniques.

Accordingly, a need exists for a separator device that is compatible with standard sampling equipment and reduces or eliminates the aforementioned problems of conventional separators. A need also exists for a separator device that is easily used to separate a blood sample, minimizes cross-contamination of the heavier and lighter phases of the sample during centrifugation, is independent of temperature during storage and shipping and is stable to radiation sterilization.

SUMMARY OF THE INVENTION

The present invention is directed to an assembly and method for separating a fluid sample into a higher specific gravity phase and a lower specific gravity phase. Desirably, the mechanical separator of the present invention may be used with a tube, and the mechanical separator is structured to move within the tube under the action of applied centrifugal force in order to separate the portions of a fluid sample. Most preferably, the tube is a specimen collection tube including an open end, a closed end or an apposing end, and a sidewall extending between the open end and closed end or apposing end. The sidewall includes an outer surface and an inner surface and the tube further includes a closure disposed to fit in the open end of the tube with a re-sealable septum. Alternatively, both ends of the tube may be open, and both ends of the tube may be sealed by elastomeric closures. At least one of the closures of the tube may include a needle pierceable re-sealable septum.

The mechanical separator may be disposed within the tube at a location between the top closure and the bottom of the tube. The separator includes opposed top and bottom ends and includes a float, a ballast, and a deformable bellows. The components of the separator are dimensioned and configured to achieve an overall density for the separator that lies between the densities of the phases of a fluid sample, such as a blood sample.

In one embodiment, the mechanical separator for separating a fluid sample into first and second phases within a tube includes a float having a first portion and a second portion, and a ballast circumferentially disposed about a section of the float and longitudinally moveable with respect to the float. The mechanical separator also includes a deformable bellows defining an open passageway extending between a first end and a second end. The ballast of the mechanical separator is engaged with the deformable bellows between the first end and the second end, and at least a portion of the float transitionable from a restraint position to a sealed position through the first end of the deformable bellows. The first portion of the float may be positioned within the interior of the deformable bellows in the restraint position, and the first portion of the float may be positioned at an exterior location longitudinally displaced from the deformable bellows in the sealed position. The float may have a first density, and the ballast may have a second density greater than the first density of the float.

The mechanical separator may be oriented such that the first portion of the float may be positioned below the first end of the deformable bellows in the restraint position, and the first portion of the float may be positioned above the first end of the deformable bellows in the sealed position. Transition of the float from the restraint position to the sealed position may occur as the float and ballast exert opposing forces on the deformable bellows allowing the float to be received within the deformable bellows. The float may include an engagement protrusion, and the deformable bellows may include a restraint shoulder. The engagement protrusion of the float may be releaseably restrained within the deformable bellows by the restraint shoulder. In the sealed position, the float and the deformable bellows may form a liquid impermeable seal.

The float may also include a head portion and a body portion. The body portion of the float may include a first section having a first diameter and a second stepped section having a second diameter, the second diameter greater than the first diameter. The float may also be made of a solid material.

The ballast may include an interlock recess for accommodating a portion of the deformable bellows for attachment thereto. The ballast may also include an exterior surface and define an annular shoulder circumferentially disposed within the exterior surface.

Optionally, at least a portion of the first end of the deformable bellows may be structured for receipt within a closure. Further, at least a portion of the first end of the deformable bellows may be structured to receive a portion of the closure therein.

The float of the mechanical separator may be made of polypropylene, the ballast may be made of polyethylene terephthalate, and the deformable bellows may be made of a thermoplastic elastomer.

In another embodiment, a mechanical separator includes a float having a first portion and a second portion, and a ballast circumferentially disposed about a portion of the float and longitudinally moveable with respect to the float. The mechanical separator also includes a deformable bellows having an open first end and an open second end and defining an open passageway extending therebetween. The deformable bellows includes an exterior surface engaged with a portion of the ballast, and an interior surface releaseably engaged with a portion of the float. The float may have a first density, and the ballast may have a second density greater than the first density of the float.

Optionally, at least a portion of the float is transitionable from a restraint position to a sealed position through the first end of the deformable bellows. The first portion of the float may be positioned within the interior of the deformable bellows in the restraint position, and the first portion of the float may be positioned at an exterior location longitudinally displaced from the deformable bellows in the sealed position. Transition of the float from the restraint position to the sealed position may occur as the float and ballast exert opposing forces on the deformable bellows allowing the float to be received within the deformable bellows. The mechanical separator may be oriented such that the first portion of the float may be positioned below the first end of the deformable bellows in the restraint position, and the first portion of the float may be positioned above the first end of the deformable bellows in the sealed position. In the sealed position, the float and the deformable bellows form a liquid impermeable seal. In one configuration, the float may include an engagement protrusion and the deformable bellows may include a restraint shoulder. The engagement protrusion of the float may be releaseably restrained within the deformable bellows by the restraint shoulder.

In another embodiment, a separation assembly for enabling separation of a fluid sample into first and second phases, includes a tube having an open end, a closed end or an apposing end, and a sidewall extending therebetween. A closure adapted for sealing engagement with the open end of the tube is also included. The closure defines a recess, and a mechanical separator is releaseably engaged within the recess. The mechanical separator includes a float having a first portion and a second portion, and a ballast circumferentially disposed about a section of the float and longitudinally moveable with respect to the float. The mechanical separator also includes a deformable bellows defining an open passageway extending between a first end and a second end. The ballast of the mechanical separator is engaged with the deformable bellows between the first end and the second end, and at least a portion of the float transitionable from a restraint position to a sealed position though the first end of the deformable bellows. The first portion of the float may be positioned within the interior of the deformable bellows in the restraint position, and the first portion of the float may be positioned at an exterior location longitudinally displaced from the deformable bellows in the sealed position. The float may have a first density, and the ballast may have a second density greater than the first density of the float.

The separation assembly may be oriented such that the first portion of the float may be positioned below the first end of the deformable bellows in the restraint position, and the first portion of the float may be positioned above the first end of the deformable bellows in the sealed position. Transition of the float from the restraint position to the sealed position may occur upon longitudinal deformation of the deformable bellows.

In yet another embodiment, a separation assembly for enabling separation of a fluid sample into first and second phases includes a tube, having an open end, a closed end or an apposing end, and a sidewall extending therebetween. A closure adapted for sealing engagement with the open end of the tube is also included. The closure defines a recess, and a mechanical separator is releaseably engaged within the recess. The mechanical separator includes a float having a first portion and a second portion, and a ballast circumferentially disposed about a portion of the float and longitudinally moveable with respect to the float. The mechanical separator also includes a deformable bellows having an open first end and an open second end and defining an open passageway extending therebetween. The deformable bellows includes an exterior surface engaged with a portion of the ballast, and an interior surface releaseably engaged with a portion of the float. The float may have a first density, and the ballast may have a second density greater than the first density of the float.

In one configuration, at least a portion of the float is transitionable from a restraint position to a sealed position through the first end of the deformable bellows. The first portion of the float may be positioned within the interior of the deformable bellows in the restraint position, and the first portion of the float may be positioned at an exterior location longitudinally displaced from the deformable bellows in the sealed position. Transition from the restraint position to the sealed position may occur upon longitudinal deformation of the deformable bellows.

In another embodiment, a method of separating a fluid sample into lighter and heavier phases within a tube includes the step of subjecting a separation assembly having a fluid sample disposed therein to accelerated rotational forces. The separation assembly includes a tube, having an open end, a closed end or an apposing end, and a sidewall extending therebetween. The separation assembly also includes a closure adapted for sealing engagement with the open end of the tube, with the closure defining a recess. The separation assembly further includes a mechanical separator releaseably engaged within the recess. The mechanical separator includes a float having a first portion and a second portion, a ballast circumferentially disposed about a section of the float and longitudinally moveable with respect to the float, and a deformable bellows engaged with a portion of the sidewall. The deformable bellows defines an open passageway extending between a first end and a second end, with the ballast engaged with the deformable bellows between the first end and the second end. At least a portion of the float is transitionable from a restraint position to a sealed position through the first end of the deformable bellows. The method further includes the steps of disengaging the mechanical separator from the closure, and venting air from within the mechanical separator through the open passageway of the deformable bellows until the mechanical separator is submerged within the fluid. The method also includes the steps of elongating the deformable bellows to at least partially separate from the sidewall, and transitioning the float from the restraint position to the sealed position.

The assembly of the present invention is advantageous over existing separation products that utilize separation gel. In particular, the assembly of the present invention is more favorable than gel with regard to minimizing and does not interfere with analytes resulting from sample separation. Another attribute of the present invention is that the assembly of the present invention is more favorable than prior art with regard to minimizing interference with therapeutic drug monitoring analytes.

The assembly of the present invention is also advantageous over existing mechanical separators in that the deformable bellows of the mechanical separator is snapped over a boss that protrudes from the underside of the closure, which provides retention and launch load control. As such, the deformable bellows does not directly interface with the underside of the closure in the region where the needle exits the closure. Pre-launch is therefore minimized by eliminating the deformable bellows from the path of the collection needle. This further minimizes sample pooling under the closure, hemolysis, fibrin draping, and/or poor sample quality. Additionally, the assembly of the present invention does not require complicated extrusion techniques during fabrication and may employ two-shot molding techniques.

In accordance with yet another embodiment of the present invention, a separation assembly for enabling separation of a fluid sample into first and second phases includes a tube having an open end, an apposing end, and a sidewall extending therebetween. The separation assembly also includes a closure adapted for sealing engagement with the open end of the tube and a mechanical separator disposed within the tube. The mechanical separator includes a float having a first portion and a second portion, with the float having a first density. The mechanical separator also includes a ballast disposed about a portion of the float and longitudinally moveable with respect to the float, with the ballast having a second density greater than the first density of the float. The mechanical separator further includes a deformable bellows interfaced with the float, with the bellows having an open first end and an open second end and defining an open passageway extending therebetween. The deformable bellows includes an exterior surface engaged with a portion of the ballast, and an interior surface releaseably engaged with a portion of the float, wherein centrifugal force is applied to the separation assembly when filled with fluid components of localized densities ranging from less than the density of the float and greater than the density of the ballast, and wherein sufficient centrifugal forces can seat the bellows onto the float.

Further details and advantages of the invention will become clear from the following detailed description when read in conjunction with the accompanying drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

For purposes of the description hereinafter, the words “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal” and like spatial terms, if used, shall relate to the described embodiments as oriented in the drawing figures. However, it is to be understood that many alternative variations and embodiments may be assumed except where expressly specified to the contrary. It is also to be understood that the specific devices and embodiments illustrated in the accompanying drawings and described herein are simply exemplary embodiments of the invention.

As shown in exploded perspective view inFIG. 2, the mechanical separation assembly40of the present invention includes a closure42with a mechanical separator44, for use in connection with a tube46for separating a fluid sample into first and second phases within the tube46. The tube46may be a sample collection tube, such as a proteomics, molecular diagnostics, chemistry sample tube, blood or other bodily fluid collection tube, coagulation sample tube, hematology sample tube, and the like. The tube46may also contain additional additives as required for a particular tube function. For example, the tube46may contain a clot inhibiting agent, clotting agents, and the like. These additives may be provided in particle or liquid form and may be sprayed onto the tube46or located at the bottom of the tube46. Desirably, tube46is an evacuated blood collection tube. The tube46may include a closed or an apposing bottom end48, an open top end50, and a cylindrical sidewall52extending therebetween. The cylindrical sidewall52includes an inner surface54with an inside diameter “a” extending substantially uniformly from the open top end50to a location substantially adjacent the closed bottom end48.

The tube46may be made of one or more than one of the following representative materials: polypropylene, polyethylene terephthalate (PET), glass, or combinations thereof. The tube46can include a single wall or multiple wall configurations. Additionally, the tube46may be constructed in any practical size for obtaining an appropriate biological sample. For example, the tube46may be of a size similar to conventional large volume tubes, small volume tubes, or microtainer tubes, as is known in the art. In one particular embodiment, the tube46may be a standard 3 ml evacuated blood collection tube, or an 8.5 ml blood draw tube having a 16 mm diameter and a length of 100 mm, as is also known in the art.

The open top end50is structured to at least partially receive the closure42therein to form a liquid impermeable seal. The closure includes a top end56and a bottom end58structured to be at least partially received within the tube46. Portions of the closure42adjacent the top end56define a maximum outer diameter which exceeds the inside diameter “a” of the tube46.

As shown inFIGS. 2-3, portions of the closure42at the top end56include a central recess60which define a pierceable re-sealable septum. Portions of the closure42extending downwardly from the bottom end58may taper from a minor diameter which is approximately equal to, or slightly less than, the inside diameter “a” of the tube46to a major diameter that is greater than the inside diameter “a” of the tube46. Thus, the bottom end58of the closure42may be urged into a portion of the tube46adjacent the open top end50. The inherent resiliency of closure42can insure a sealing engagement with the inner surface of the cylindrical sidewall52of the tube46.

In one embodiment, the closure42can be formed of a unitarily molded rubber or elastomeric material, having any suitable size and dimensions to provide sealing engagement with the tube46. The closure42can also be formed to define a bottom recess62extending into the bottom end58. The bottom recess62may be sized to receive at least a portion of the mechanical separator44. In one embodiment, the bottom end58of the closure42includes a graduated boss portion64, which extends from the bottom end58of the closure42for engagement with the mechanical separator44. The graduated boss portion64of the closure may include an outer ridge68and an inner surface70disposed within the outer ridge68. In one embodiment, the boss portion64may extend into a portion of the mechanical separator44. Additionally, a plurality of spaced apart arcuate flanges66may extend around the bottom recess62to at least partially restrain the mechanical separator44therein. In one embodiment, the flanges66are continuous about the circumference of the bottom recess62.

Optionally, the closure42may be at least partially surrounded by a shield, such as a Hemogard® Shield commercially available from Becton, Dickinson and Company, to shield the user from droplets of blood in the closure42and from potential blood aerosolisation effects when the closure42is removed from the tube46, as is known.

Referring again toFIG. 2, the mechanical separator44includes a float72, a ballast74, and a deformable bellows76such that the ballast74is engaged with a portion of the deformable bellows76and the float72is also engaged with a portion of the deformable bellows76.

Referring toFIGS. 4-5, the float72of the mechanical separator is a generally tubular body having an upper end80and a lower end82. The upper end80of the float72may include a head portion84separated from the lower end82by an engagement protrusion86. In one embodiment, the head portion84is separated from the engagement protrusion86by a neck portion88. The lower end82of the float72may include a body portion90having a first section92and a second stepped section94graduated from the first section92.

In one embodiment, the outer diameter “b” of the second stepped section94is less than the inside diameter “a” of the tube46, shown inFIG. 2. In another embodiment, the outer diameter “c” of the first section92is less than the outer diameter “b” of the second stepped section94. The outer diameter “d” of the head portion84is typically less than the outer diameter “c” of the first section92or the outer diameter “b” of the second stepped section94. The outer diameter “e” of the engagement protrusion86is greater than the outer diameter “d” of the head portion84. In one embodiment, the outer diameter “e” of the engagement protrusion86is less than the outer diameter “b” of the second stepped section94. In another embodiment, the outer diameter “b” and the outer diameter “e” are the same size.

In one embodiment, the head portion84has a generally curved shape, such as having a curvature substantially corresponding to the curvature of the boss portion64, shown inFIG. 3. In another embodiment, the head portion84has a curvature substantially corresponding to the curvature of the inner surface70of the boss portion64, also shown inFIG. 3. The curvature of the head portion84may facilitate shedding of cells or other biological material during centrifugation.

The float72can be substantially symmetrical about a longitudinal axis L. In one embodiment, it is desirable that the float72of the mechanical separator44be made from a material having a density lighter than the liquid intended to be separated into two phases. For example, if it is desired to separate human blood into serum and plasma, then it is desirable that the float72have a density of no more than about 0.902 gm/cc. In one embodiment, the float72can be made of a solid material, such as polypropylene.

As shown inFIGS. 6-9, the ballast74of the mechanical separator44includes an upper end124and a lower end126with a generally cylindrical section120extending therebetween. In one embodiment, the ballast74includes an interior surface122structured to engage at least a portion of the deformable bellows76, shown inFIG. 2. In another embodiment, the upper end124includes a recess128for receiving a portion of the deformable bellows76, also shown inFIG. 2, therein.

The outer diameter “j” of the ballast74is less than the inside diameter “a” of the tube46, shown inFIG. 2, therefore, the ballast74may freely slide within the tube46. The inside diameter “i” of the recess128is less than the outer diameter “j” of the ballast74, and can have any dimensions suitable to receive a portion of the deformable bellows76, also shown inFIG. 2. The inner diameter “k” of the interior surface122of the ballast74is also greater than the outer diameter “b” of the second stepped section94of the float72, shown inFIGS. 4-5. Accordingly, the float72may freely move within the interior of the ballast74. In one embodiment, the ballast is circumferentially disposed about at least a portion of the float72. In yet another embodiment, the ballast74is longitudinally moveable with respect to the float72.

As shown inFIG. 7, in one embodiment, the ballast72may include a mechanical interlock recess130extending through the generally cylindrical section120, such as adjacent the upper end124. In another embodiment, the ballast72may include the mechanical interlock recess130within an interior wall131for engagement with a portion of the deformable bellows76, such as for accommodating a portion of the deformable bellows76for attachment thereto. In a further embodiment, the interlock recess130is located in recess128.

In one embodiment, it is desirable that the ballast74of the mechanical separator44be made from a material having a density heavier than the liquid intended to be separated into two phases. For example, if it is desired to separate human blood into serum and plasma, then it is desirable that the ballast74have a density of at least 1.326 gm/cc. In one embodiment, the ballast74may have a density that is greater than the density of the float72, shown inFIGS. 4-5. In another embodiment, the ballast74can be formed from PET.

As shown inFIGS. 6-9, the exterior surface of the ballast74may define an annular recess134circumferentially disposed about a longitudinal axis L1of the ballast72, and extending into the exterior surface of the cylindrical section120. In this embodiment, the annular recess134is structured to allow for an automated assembly to engage the ballast74with the deformable bellows76and/or float72, shown inFIG. 2.

As shown inFIGS. 10-13, the deformable bellows76of the mechanical separator44includes an upper first end136and a lower second end138with an open passageway142extending therebetween. The upper first end136includes a deformable sealing portion140circumferentially disposed about the open passageway142for providing sealing engagement with the cylindrical sidewall52of the tube46, shown inFIG. 2. The deformable sealing portion140can be positioned substantially adjacent the upper surface144of the upper first end136of the deformable bellows76. The deformable sealing portion140may have a generally torodial shape having an outside diameter “k” which, in an unbiased position, slightly exceeds the inside diameter “a” of the tube46, shown inFIG. 2. However, oppositely directed forces on the upper first end136and the lower second end138of the deformable bellows76will lengthen the deformable sealing portion140, simultaneously reducing the outer diameter “k” to a dimension less than “a”. Likewise, the open passageway142has an inner diameter “m” which, in an unbiased position, is smaller than the outer diameter “d” of the head portion84of the float72, shown inFIG. 5. Oppositely directed forces on the upper first end136and the lower second end138of the deformable bellows76will increase the inner diameter “m” of the open passageway to a diameter exceeding the outer diameter “d” of the head portion84of the float72, again shown inFIG. 5.

The deformable bellows76, including the deformable sealing portion140, is substantially symmetrical (with the possible exception of the placement of protrusions160) about a longitudinal axis L2, and can be made of any sufficiently elastomeric material sufficient to form a liquid impermeable seal with the cylindrical sidewall52of the tube46, shown inFIG. 2. In one embodiment, the deformable bellows76is made of a thermoplastic elastomer, such as thermoplastic polypropylene and has an approximate dimensional thickness of from about 0.020 inch to about 0.050 inch. In another embodiment, the entire bellows structure70is made of thermoplastic elastomer.

In one embodiment, the upper first end136of the deformable bellows76includes an annular shoulder146extending into the interior148of the deformable bellows76adjacent the deformable sealing portion140. In another embodiment, the annular shoulder146may be an interior surface152of the upper first end136of the deformable bellows76. Preferably, the annular shoulder146is positioned longitudinally above at least a portion of the deformable sealing portion140. Alternatively, the annular shoulder146may be an interior surface152of the upper portion of the deformable sealing portion140. In one embodiment, the deformable bellows76includes a recess150extending at least partially into the interior surface152of the upper first end136. The recess150may be circumferentially disposed about the open passageway142, and may be a continuous recess or a partitioned recess. The recess150may reduce the spring constant of the deformable bellows76, allowing the deformable bellows76to longitudinally deform with less applied force. In one embodiment, this may be accomplished by reducing the wall section of the deformable bellows76to create a hinge.

In addition, at least a portion of deformable bellows76, such as the upper first end136, can be structured for receipt within the closure42, such as the bottom recess62, also shown inFIGS. 2-3. In one embodiment, at least a portion of the deformable sealing portion140of the deformable bellows76is structured for receipt within the bottom recess62of the closure42.

The lower second end138of the deformable bellows76includes opposed depending portions154extending longitudinally downward from the upper first end136. In one embodiment, the opposed depending portions154are connected to a lower end ring156extending circumferentially about the open passageway142and below the deformable sealing portion140. In one embodiment, the opposed depending portions154include at least one ballast interlock protrusion158extending from a portion of the exterior surface160. The interlock protrusion158is engageable with the interlock recess130of the ballast74, shown inFIGS. 6-9, to secure the ballast74to a portion of the deformable bellows76between the upper first end136and the lower second end138. Optionally, the interlock recess130of the ballast74may extend completely through the opposing wall of the ballast74. In one embodiment, the exterior surface160of the deformable bellows76is secured with the interior wall131of the ballast74, shown inFIGS. 6-9. In one embodiment, two-shot molding techniques may be used to secure the deformable bellows76to the ballast74.

The lower second end138of the deformable bellows76may also include a restraint shoulder162extending into the interior148of the deformable bellows76. The restraint shoulder162may be positioned at the bottom end163of the opposed depending portions154. In one embodiment, the interior148of the deformable bellows76is structured to releaseably retain at least a portion of the float72, shown inFIGS. 4-5, therein. In another embodiment, the restraint shoulder162is structured to restrain the engagement protrusions86of the float72thereagainst, and dimensioned to allow a portion of the float72, such as the head portion84to pass into the interior148of the deformable bellows76. The inner diameter “n” of the deformable bellows adjacent the lower second end138, such as extending between the restraint shoulder162, is dimensioned to be greater than the inner diameter “m” of the open passageway142, but smaller than the outer diameter “e” of the engagement protrusion86of the float72, shown inFIG. 5. Therefore, a portion of the float72, such as the head portion84, may be received and retained within the interior148of the deformable bellows76.

As shown inFIGS. 14-15, in the restraint position, the assembled mechanical separator44of the present invention includes a deformable bellows76engaged with the ballast74. A portion of the float72, such as the head portion84, is engaged within the interior148of the deformable bellows76. The float72may be secured at least partially within the interior148of the deformable bellows76by the mechanical engagement of the engagement protrusion86of the float72and the restraint shoulder162of the deformable bellows76.

As shown inFIG. 15, the mechanical separator44can be engaged with a portion of the closure42in the restraint position. As shown, a portion of the closure42, such as the boss portion64, is received at least partially within the open passageway142of the deformable bellows76. In one embodiment, the boss portion64is received within the open passageway142at the upper first end136of the deformable bellows76forming a liquid impermeable seal therewith.

A portion of the float72, such as the head portion84, may also be received within the open passageway142in the restraint position. In one embodiment, the head portion84of the float72is received within the open passageway142at the lower second end138of the deformable bellows76. The float72is dimensioned such that the head portion84, having an outer diameter “d”, is greater than the inner diameter “m” of the open passageway142of the deformable bellows76at the upper first end136, as shown inFIG. 13. Accordingly, the head portion84of the float72cannot pass through the open passageway142of the deformable bellows76in the restraint position.

Referring again toFIG. 15, the assembled mechanical separator44may be urged into the bottom recess62of the closure42. This insertion engages the flanges64of the closure42with the upper first end136of the deformable bellows76. During insertion, at least a portion of the upper first end136of the deformable bellows76will deform to accommodate the contours of the closure42. In one embodiment, the closure42is not substantially deformed during insertion of the mechanical separator44into the bottom recess62.

As shown inFIGS. 16-18, the mechanical separation assembly40includes a mechanical separator44and a closure42inserted into the open top end50of the tube46, such that the mechanical separator44and the bottom end58of the closure42lie within the tube46. The mechanical separator44, including the deformable bellows76, will sealingly engage the interior of the cylindrical sidewall52and the open top end of the tube46.

As shown inFIG. 17, a liquid sample is delivered to the tube46by the puncture tip164that penetrates the septum of the top end56and the boss portion64of the closure42. For purposes of illustration only, the liquid is blood. Blood will flow through the pierced boss portion64of the closure, through the open passageway142of the deformable bellows76, shown inFIGS. 11 and 13, over the head portion84of the float72, and through the space between the float72and the opposed depending portions154of the lower second end138of the deformable bellows76. As shown inFIGS. 10 and 13, the opposed depending portions154define a fluid access area166, therebetween to allow fluid received from the puncture tip164to pass between the float72and the deformable bellows76and into the closed bottom end48of the tube46as shown by the arrows B, reducing pre-launch of the mechanical separator.

As shown inFIG. 18, once a sufficient volume of fluid has been delivered to the tube46, through the puncture tip164as above-described, the puncture tip164can be removed from the closure42. In one embodiment, at least a portion of the closure42, such as the boss portion64, is made of a self-sealing material to form a liquid impermeable seal once the puncture tip164is removed. The mechanical separation assembly40may then be subjected to accelerated rotational forces, such as centrifuge, to separate the phases of the fluid.

Referring again toFIGS. 16-17, in use, the mechanical separator44, particularly the deformable bellows76, is intended to be restrained with the closure42until the mechanical separator44is subjected to accelerated rotational forces, such as within a centrifuge.

As shown inFIG. 18, upon application of accelerated rotational forces, such as centrifugation, the respective phases of the blood will begin to separate into a denser phase displaced toward the closed bottom end58of the tube46, and a less dense phase displaced toward the top open end50of the tube46, with the separated phases shown inFIG. 22. During centrifugation, the mechanical separator44experiences a force sufficient to disengage it from the closure42. Once disengaged, the mechanical separator44travels down the tube46toward the fluid interface. Transition of the float72from the restraint position to the sealed position occurs as the mechanical separator44contacts and submerges in the fluid. As air trapped within the mechanical separator44vents through the open passageway142of the deformable bellows76, the float72begins to move up within the mechanical separator44as soon as the mechanical separator44contacts the fluid interface and begins to submerge in the fluid. As the float72may be formed of a solid material, air is not trapped within the float72and thus, no additional venting mechanism is included within the float72. As a result, leakage between the float72and the deformable bellows76is minimized.

Once the mechanical separator44is fully submerged, the float72and the ballast74exert opposing forces on the deformable bellows76. As a result, the deformable bellows76, and particularly the deformable sealing portion140, become longer and narrower and become spaced concentrically inward from the inner surface of the cylindrical sidewall52.

Referring toFIGS. 18-22, after the mechanical separator44has disengaged from the closure42and is submerged in the fluid, the outer diameter “n” (shown inFIG. 13) of the deformable sealing portion140is lessened, allowing the lighter phase components of the blood to slide past the deformable sealing portion140and travel upwards. Likewise, heavier phase components of the blood may slide past the deformable sealing portion140and travel downwards. As noted above, the mechanical separator44has an overall density between the densities of the separated phases of the blood. Upon application of applied centrifugal acceleration, the inner diameter “m” of the open passageway142of the deformable bellows76also deforms as a result of the opposing forces exerted upon it by the float72and the ballast74. This deformation increases the inner diameter “m” of the open passageway142, shown inFIG. 13, to a dimension greater than the outer diameter “d” of the head portion84of the float72, shown inFIG. 5, thereby allowing the head portion84of the float72to pass through the open passageway142. Accordingly, during centrifuge, the mechanical separator44is transitioned from a restraint position, shown inFIGS. 14-15, to a sealed position, shown inFIGS. 19-21.

Referring toFIGS. 19-21, the mechanical separator44, including the deformable bellows76, ballast74, and float72, is shown in the sealed position. As the inner diameter “m” of the open passageway142of the deformable bellows76of the mechanical separator44is increased during centrifuge, the head portion84of the float72may pass therethourgh. Preferably, the inner diameter “m” of the open passageway142of the deformable bellows76does not exceed the outer diameter “e” of the engagement protrusion86of the float72during deformation. Even more preferably, the inner diameter “m” of the open passageway142does not exceed the outer diameter “b” of the second stepped section94of the float72during deformation. Because the float72is made of a naturally buoyant material, the float72is urged upwardly as indicated by the arrow A.

Once centrifuge is ceased, the inner diameter “m” of the open passageway142returns to the unbiased position and engages the float72about the neck portion88in the sealed position. In one embodiment, the deformable bellows76form a liquid impermeable seal about the neck portion88of the float72through the open passageway142in the sealed position. In the sealed position, at least a portion of the float72, such as the head portion84, is positioned at a location exterior168to the deformable bellows76, such as at a location exterior168to the interior148of the deformable bellows76. In this embodiment, the head portion84may be positioned at an exterior location168that is longitudinally displaced from the deformable bellows76along the longitudinal axis L3of the mechanical separator44in the sealed position. Because the float72of the mechanical separator44is buoyant in fluid, when the mechanical separator44is oriented as shown inFIGS. 16-18, the head portion84of the float72may be positioned below the upper first end136of the deformable bellows76, shown inFIG. 15, in the restraint position, and positioned above the upper first end136of the deformable bellows76, shown inFIGS. 19-21, in the sealed position.

Referring toFIG. 22, after centrifuge and the transition of the mechanical separator44from the restraint position to the sealed position, the mechanical separator44will stabilize in a position within the tube46of the mechanical separation device40, such that the heavier phase components170will be located between the mechanical separator44and the closed bottom end58of the tube46, while the lighter phase components172will be located between the mechanical separator44and the top end of the tube50. After this stabilized state has been reached, the centrifuge will be stopped and the deformable bellows76, particularly the deformable sealing portion140, will resiliently return to its unbiased state and into sealing engagement with the interior of the cylindrical sidewall52of the tube46. The formed liquid phases may then be accessed separately for analysis.

Although the above invention has been described with specific reference to certain configurations, it is contemplated herein that various alternative structures may be employed without departing from the spirit of the claims herein. For example, as shown inFIGS. 23-24, although the previous description of the invention was made with reference to a closure having a bottom recess and/or a boss portion, the mechanical separator244can be configured to include a standard closure242having a conventionally sloped bottom surface246. In this configuration, the deformable bellows276, having an open passageway243, is held in position adjacent the standard closure242by an interference fit between the interior wall250of the tube252and the outer surface254of the deformable bellows276. Optionally, a small annular protrusion258in the interior wall250of the tube252may be employed to further increase the interference between the deformable bellows276and the tube252. The ballast290is engaged with at least a portion of the deformable bellows276. Also shown inFIGS. 23-24, it is contemplated herein that various configurations of the float272may also be employed, provided at least a portion of float272, such as a head portion280, is transitioned from a position within the interior of the deformable bellows276in restraint position, shown inFIG. 23, to a position exterior to the deformable bellows276in the sealed position, shown inFIG. 24.

As shown inFIGS. 25-26, the mechanical separator344can be engaged with a closure342having a luer collar320, which may be engaged into the underside of the closure342. In one embodiment, the luer collar320may be snap-engaged into the underside370of the closure342. In use, when the mechanical separator344including a deformable bellows376, a ballast390engaged with a portion of the deformable bellows376, and a float372also engaged with a portion of the deformable bellows376, is subject to centrifuge, the luer collar320may release from the underside370of the closure342along with the mechanical separator344. Upon transition from the restraint position, shown inFIG. 25, to the sealed position, shown inFIG. 26, the head portion384of the float372of the mechanical separator344transitions from a position at least partially interior to the deformable bellows376to a position exterior to the deformable bellows376and into the luer collar320.

As shown inFIG. 27, the mechanical separator444, including a deformable bellows476, a ballast490engaged with a portion of the deformable bellows476, and a float472also engaged with a portion of the deformable bellows476, may be inserted into a tube446having a tube insert450. The tube insert450can be any appropriate device inserted into the tube446, such as circumferentially disposed about a portion of the mechanical separator444, to prevent premature release of the mechanical separator444from the tube insert450of the closure442. In one embodiment, the tube insert450can be circumferentially disposed about a portion of the deformable bellows476to provide additional interference with the tube476.

Alternatively, as shown inFIG. 28, the mechanical separator544, including a deformable bellows576, a ballast590engaged with a portion of the deformable bellows576, and a float572also engaged with a portion of the deformable bellows576may be engaged with a retaining collar550that is permanently affixed to the underside of the closure542. In one embodiment, the deformable bellows576is held fixed relative to the closure542during shipping and handling. The interior diameter “r” of the retaining collar550is sufficiently sized to allow access of a puncture tip for closure sampling after centrifugation (not shown), therethrough.

As shown inFIGS. 29-30, the mechanical separator644may also include a deformable bellows676, a ballast690engaged with a portion of the deformable bellows676, and a float672also engaged with a portion of the deformable bellows676. In this embodiment, the deformable bellows676are biased over a boss portion646of the closure642. In the restraint position, as shown inFIG. 29, the inner diameter “s” of the open passageway652of the deformable bellows676is enlarged to accommodate the boss portion646. In the sealed position, shown inFIG. 30, the head portion684of the float672passes through the open passageway652to a location exterior to the deformable bellows676and is sealed therein by the unbiased diameter of the passageway652. Optionally, the ballast690may include a shoulder630and the float672may include an engagement protrusion632for restraining the float672within the mechanical separator644during shipment in the restraint position.

As shown inFIGS. 31-32, the mechanical separator744may include a deformable bellows776, a ballast790engaged with a portion of the deformable bellows776, and a float772also engaged with a portion of the deformable bellows776. The closure742may include a ring750adjacent the contact surface752to further secure the deformable bellows776to the closure742in the restraint position, shown inFIG. 31. In this configuration, introduction of fluid, such as blood, causes the float772of the mechanical separator744to rise, and centrifugation causes the deformable bellows776to separate from the closure742and transitioning the mechanical separator744from the restraint position, shown inFIG. 31, to the closed position, shown inFIG. 32.

Alternatively, as shown inFIGS. 33-34, the mechanical separator844may include a deformable bellows876, a ballast890engaged with a portion of the deformable bellows876, and a substantially spherical float872. In this embodiment, the open passageway870of the deformable bellows876includes protrusions882substantially corresponding to the outer diameter of the spherical float872. In the restraint position, shown inFIG. 33, the spherical float872is positioned within the interior840of the mechanical separator844. In the sealed position, shown inFIG. 34, the spherical float872includes a first portion835transitioned at least partially exterior to the interior840of the mechanical separator844. In one embodiment, the spherical float872forms a seal with the protrusions882of the deformable bellows876.

The mechanical separator of the present invention includes a float that is transitionable from a restraint position to a sealed position as the float and ballast exert opposing forces on the deformable bellows, thereby allowing the float to be received within the deformable bellows. Thus, in use, the mechanical separator of the present invention minimizes device pre-launch and reduces sample pooling under the closure by providing an open passageway within the bellows. Additionally, the reduced clearance between the exterior of the float and the interior of the ballast minimizes the loss of trapped fluid phases, such as serum and plasma.

Although the present invention has been described in terms of a mechanical separator disposed within the tube adjacent the open end, it is also contemplated herein that the mechanical separator may be located at the bottom of the tube, such as affixed to the bottom of the tube. This configuration can be particularly useful for plasma applications in which the blood sample does not clot, because the mechanical separator is able to travel up through the sample during centrifugation.

While the present invention is described with reference to several distinct embodiments of a mechanical separator assembly and method of use, those skilled in the art may make modifications and alterations without departing from the scope and spirit. Accordingly, the above detailed description is intended to be illustrative rather than restrictive. For example, while the assembly described above relates to a biological sample tube, other types of sample containers may be used. In addition, while various configurations of the components have been provided above, it should be noted that other shapes and dimensions may be implemented.