Density phase separation device

[0001] The invention relates to a device and method for separating a fraction of a heavier and lighter fluid sample. In particular, the invention relates to a device and method for collecting and transmitting fluid samples, wherein the device and fluid sample are centrifuged to cause separation of the heavier fraction from the lighter fluid sample.

Description of the Related Art [0002] Diagnostic tests may require separating the entire patient blood sample into components such as serum or plasma (lighter phase component) and red blood cells (heavier phase component). Whole blood samples are typically collected by venipuncture through a tube or needle attached to a syringe or vacuum blood collection tube. After collection, separation of blood into serum or plasma and red blood cells is accomplished by rotating the syringe or test tube in a centrifuge. To maintain separation, a barrier must be placed between the components of the heavier and lighter phase. This allows you to perform subsequent component testing.

[0003] Various separation barriers are used in sampling devices to divide the area between the lighter and heavier phases of a fluid sample. The most widely used devices use thixotropic gels, such as polyester gels. However, existing polyester gel tubes for serum separation require special production equipment for both gel preparation and tube filling. In addition, the shelf life of the product is limited. Over time, globules may escape from the gel mass and may enter one or both components of the separated phases. These globules can clog measuring equipment, such as device probes used during clinical testing of a sample taken into a tube. In addition, commercially available gel barriers can chemically react with analytes. Thus, if certain drugs are present in the blood sample during its collection, an adverse chemical reaction with the gel contact surface may occur.

[0004] Certain mechanical separators have also been proposed in which a mechanical barrier between the lighter and heavier phases of the fluid sample can be used. Conventional mechanical barriers are placed between the components of the lighter and heavier phase using different hydrostatic buoyancy and increased gravity applied during centrifugation. For proper orientation with respect to plasma and serum samples, conventional mechanical separators typically require that the mechanical separator be attached to the bottom of the closure of the tube in such a way that blood filling appears in and around the device when it is coupled to the blood collection set. This connection is required to prevent premature displacement of the separator during transport, handling and blood collection. Conventional mechanical separators are attached to the tube closure with a mechanical latch between the bellows component and the closure. Exemplary devices are described in US Patent Nos. 6,803,022 and 6,479,298.

[0005] Conventional mechanical separators have some significant disadvantages. As shown in Fig. 1, conventional separators include a bellows 34 to provide a seal with the wall 38 of the tube or syringe. Typically, at least part of the bellows 34 is placed inside or in contact with the closure 32. As shown in Fig. 1, when the needle 30 is introduced through the closure 32, the bellows 34 is bent. This creates a gap 36 in which blood may spill when removing the needle 30. This may cause problems with needle passage, drawing the sample under the closure, premature start of the device, during which the mechanical separator releases prematurely during blood sampling, hemolysis, fibrin coating formation and / or poor sample quality. In addition, previous mechanical separators are expensive and complicated to manufacture due to the complicated multi-part manufacturing techniques.

[0006] Thus, there is a need for a separator that is compatible with standard sampling equipment and reduces or eliminates the previously mentioned problems of conventional separators. There is also a need for a separator device that is easy to use to separate a blood sample, minimizes cross-contamination of the heavier and lighter samples during centrifugation, is independent of temperature during storage and shipping, and is stable during radiation sterilization.

US 2002/0094305 discloses a separator device.

SUMMARY OF THE INVENTION [0007] The present invention relates to an assembly and a method for separating a fluid sample into a phase with a higher specific gravity and a phase with a lower specific gravity. Preferably, the mechanical separator of the present invention can be used with a test tube and the mechanical separator is designed to move in the tube under the influence of the centrifugal force generated to separate a portion of the fluid sample. Most preferably, the tube is a blood collection tube comprising an open end, a closed end, or an opposite end, and a side wall extending between the open end and the closed or opposite end. The sidewall includes an outer surface and an inner surface, and the tube further includes a closure positioned to fit into the open end of the tube with a septum that can be resealed. Alternatively, both ends of the tube may be open and both ends of the tube may be sealed with elastomer closures. At least one of the tube closures may contain a septum that can be resealed and can be punctured with a needle.

[0008] A mechanical separator may be placed in the tube between the upper closure and the bottom of the tube. The separator has opposite ends, upper and lower, and contains a float, ballast assembly and bellows structure. The components of the separator have dimensions and configurations to obtain a total density of the separator between the phase density of the fluid sample, such as a blood sample.

[0009] In one embodiment, the mechanical separator is adapted to separate the fluid sample into the first and second phase inside the tube. The mechanical separator comprises a float, a ballast assembly movable longitudinally relative to the float, and a bellows structure. The structure of the bellows contains the first end, the second end and a deformable bellows between them. The float may be attached to part of the first end of the bellows structure, and the ballast assembly may be attached to part of the second end of the bellows structure. The combined structure of the float and bellows also includes a separable shape connection between them. The float may have a first density and the ballast may have a second density greater than the first density of the float. The detachable contouring connection can be configured to disconnect when the float exceeds a centrifugal force of at least 250 G.

[0010] The separable shape connection of the mechanical separator can be adapted to disconnect due to the longitudinal deformation of the bellows structure. The bellows structure can also define the interior, and the float can be held detachably in part of the interior of the bellows structure. The bellows structure may also include an inner collar and at least a portion of the float may be retained within the first end of the inner collar.

[0011] The mechanical separator float may optionally include a neck, and the float may be detachably retained in a portion of the interior of the first end by a positive fit of the inner collar and neck. In another configuration, the first end of the bellows structure may include an inner engagement member facing inwardly, and the float may include an outer engagement member to obtain a mechanical interface with the outer engagement member. The first end of the bellows structure may also include a pierced head with a piercing profile such as to resist deformation when it moves the puncturing end. The float may include a head defining an opening therein to allow air to escape from the interior of the mechanical separator.

[0012] Optionally, the bellows may include a vent notation to allow air from the inside of the float to be discharged into the area outside the mechanical separator. The bellows may also include a vent to allow air to escape from the chamber defined by the bellows interior and exterior of the float, into the area outside the mechanical separator.

[0013] In another configuration, the ballast assembly includes a plurality of ballast connection sections, such as a first ballast section and a second ballast section connected to the first ballast section through part of the bellows structure. The first ballast section and the second ballast section may be oriented opposite to each other about the longitudinal axis of the mechanical separator. The mechanical separator may also contain a float made of polypropylene, a ballast assembly made of polyethylene terephthalate and a bellows structure made of thermoplastic elastomer. The separator assembly includes a movable plug located inside the float.

[0014] Another mechanical separator for separating the fluid sample into the first and second phases within the tube comprises a bellows structure having a first end, a second end, and a deformable bellows therebetween. The mechanical separator also includes a float and a ballast assembly movable longitudinally relative to the float. The ballast assembly includes a first ballast section and a second ballast section connected to the first ballast section through part of the bellows structure. The float may have a first density and the ballast assembly may have a second density greater than the first float density.

[0015] The mechanical separator float may be attached to a portion of the first end of the bellows structure, and the ballast assembly may be attached to a portion of the second end of the bellows structure. The combined bellows and float structure may further include a detachable form fit between them. In one configuration, the structure of the mechanical separator bellows defines the interior, and the float is detachably held in a part of the interior of the bellows structure.

[0016] In another configuration, the first ballast section and the second ballast section of the ballast assembly are oriented oppositely about the longitudinal axis of the mechanical separator.

[0017] Optionally, the float may include a head defining an opening therein to allow air to be drawn from the inside of the float into the area outside the mechanical separator. The bellows may include a vent to allow air from the float to be discharged into the area outside the mechanical separator. The bellows may further include a venting cut to allow air to be removed from the chamber defined by the bellows interior and exterior of the float to an area outside the mechanical separator.

[0018] In another embodiment, the separator assembly for enabling the fluid sample to be separated into the first and second phases comprises a tube having an open end and an opposite end, and a sidewall extending therebetween. A closure adapted to seal with the open end of the tube is also included. The closure defines a cavity, and the mechanical separator is releasably engaged in the cavity. The mechanical separator comprises a float, a ballast assembly movable longitudinally relative to the float, and a bellows structure. The structure of the bellows contains the first end, the second end and a deformable bellows between them. The float may be attached to part of the first end of the bellows structure, and the ballast assembly may be attached to part of the second end of the bellows structure. The combined structure of the bellows and float also includes a separable shape connection between them. The float may have a first density and the ballast may have a second density greater than the first density of the float.

[0019] The bellows structure of the separator assembly may define the interior, and the float may be detachably held in a part of the interior of the bellows structure. Release of the float from the first end of the bellows structure may release the mechanical separator from the closure cavity. Optionally, the bellows structure includes a pierceable head having a piercing profile with a structure such that it resists deformation when it moves the puncturing end. The float may also include a head defining an opening and having a circumference substantially corresponding to a portion of the piercing profile, the pierced portion of the head.

[0020] In another configuration, the ballast assembly of the separator assembly includes a first ballast section and a second ballast section connected to the first ballast section through a portion of the bellows structure. The first ballast section and the second ballast section may be oriented opposite to each other about the longitudinal axis of the mechanical separator.

[0021] Optionally, the float may include a head defining an opening therein to allow air to be drawn from the inside of the float to the area outside the mechanical separator. The bellows may include a vent to allow air from the float to be discharged into the area outside the mechanical separator. The bellows may also include a vent to allow air to escape from the chamber defined by the bellows interior and exterior of the float, into the area outside the mechanical separator. In another configuration, the separator assembly includes a movable plug positioned inside the float.

[0022] In another embodiment, the method of assembling the mechanical separator comprises the step of providing a subassembly having a first end and a second end. The subassembly contains ballast, at least partially located around the bellows structure and defining the pierceable head. The method also includes the step of introducing the first end of the subassembly into the closure cavity to provide a positive fit between the bellows structure and the closure. The method also includes the step of introducing the float to the other end of the subassembly.

[0023] In another embodiment of the present invention, the separator assembly for allowing the fluid sample to be separated into the first and second phases comprises a tube having at least one open end, a second end, and a sidewall extending therebetween. The separator assembly also includes a closure adapted to seal with the open end of the tube, the closure defining a cavity. The mechanical separator is releasably engaged in a recess. The mechanical separator comprises a float, a ballast assembly movable longitudinally relative to the float, and a bellows structure. The structure of the bellows contains the first and second ends and a deformable bellows between them. The bellows structure is based on a portion of the closure cavity, with the float being released from the bellows before the bellows are released from the cavity when subjecting the separation assembly to centrifugal forces.

[0024] Optionally, the float releases the bellows before freeing the bellows from the recess when subjecting the separator assembly to a centrifugal force of at least 250 G.

[0025] In another embodiment of the present invention, the separator assembly for allowing the fluid sample to be separated into the first and second phases comprises a tube having at least one open end, a second end, and a sidewall extending therebetween. The separator assembly also includes a closure adapted to seal against the open end of the tube, the closure defining a cavity. The mechanical separator is releasably engaged in a recess. The mechanical separator comprises a float, a ballast assembly movable longitudinally relative to the float, and a bellows structure. The structure of the bellows contains the first and second ends and a deformable bellows between them. The bellows structure is based on a part of the closure cavity, with the float being released from the bellows enabling the mechanical separator to free itself from the cavity when subjecting the separator assembly to centrifugal forces.

[0026] Optionally, the float is released from the bellows allowing the mechanical separator to free itself from the recess when subjecting the separator assembly to a centrifugal force of at least 250 G.

[0027] The assembly of the present invention is advantageous over existing separation products that use a separation gel. In particular, the assembly of the present invention does not interfere with analytes, while many gels react with body fluids. Another feature of the present invention is that the team of the present invention does not interfere with analytes for monitoring therapeutic drugs.

[0028] The assembly of the present invention also has such an advantage over existing mechanical separators that the float provides a positive fit with the bellows structure to prevent premature release of the mechanical separator from the closure. This minimizes problems with needle passage, puffing of the sample under closure, premature start of the device, hemolysis, fibrin film formation and / or poor sample quality. In addition, premature activation can be minimized by pre-increasing the puncture pressure of the bellows head relative to the inside of the stopwatch.

[0029] In addition, the assembly of the present invention does not require complicated extrusion techniques during its manufacture. The assembly of the present invention does not cause occlusion with conventional analytical probes, as is common with existing gel tubes.

[0030] Further details and advantages of the invention will become apparent from the following detailed description when read in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS [0031] Fig. 1 is a partial cross-sectional side view of a conventional mechanical separator.

[0032] Fig. 2 is an exploded perspective view of a mechanical separator assembly including a closure, bellows structure, ballast assembly, float, and collection tube according to an embodiment of the present invention.

[0033] Fig. 3 is a perspective view of the bottom surface of the closure of Fig.

2.

[0034] Fig. 4 is a cross-sectional view of the closure of Fig. 2 along line 4-4 of Fig. 3.

[0035] Fig. 5 is a perspective view of the float of Fig. 2.

[0036] Fig. 6 is a front view of the float of Fig. 2.

[0037] Fig. 7 is a cross-sectional view of the float of Fig. 2 along line 7-7 of Fig. 6.

[0038] Fig. 8 is an enlarged cross-sectional view of the float of Fig. 2 along the line VIII of Fig.

7.

[0039] Fig. 9 is a top view of the float of Fig. 2.

[0040] Fig. 10 is a perspective view of the first part of the ballast assembly with

Fig. 2.

[0041] Fig. 11 is a front view of the first part of the ballast assembly of Fig. 2.

[0042] Fig. 12 is a cross-sectional view of the first portion of the ballast assembly of Fig. 2 along line 12-12 of Fig. 11.

[0043] Fig. 13 is a top view of the first portion of the ballast assembly of Fig. 2.

[0044] Fig. 14 is a perspective view of the bellows structure of Fig. 2.

[0045] Fig. 15 is a front view of the bellows structure of Fig. 2.

[0046] Fig. 16 is an enlarged cross-sectional view of the bellows structure of Fig. 2 along the line XV of Fig. 15.

[0047] Fig. 17 is a top view of the bellows structure of Fig. 2.

[0048] Fig. 18 is a perspective view of a composite mechanical separator comprising a float, ballast assembly, and bellows structure, according to an embodiment of the present invention.

[0049] Fig. 19 is a cross-sectional view of the mechanical separator of Fig. 18 along line 19-19 of Fig. 18.

[0050] Fig. 20 is a front view of the mechanical separator of Fig. 18.

[0051] Fig. 21 is a cross-sectional view of the mechanical separator of Fig. 18 along the lines 21-21 of Fig. 20.

[0052] Fig. 22 is a front view of an assembly containing a test tube having a closure thereon and a mechanical separator, according to an embodiment of the present invention.

[0053] Fig. 23 is a front cross-sectional view of the assembly of Fig. 22 comprising a needle reaching the interior of the tube and some fluid delivered through the needle into the interior of the tube, according to an embodiment of the present invention.

[0054] Fig. 24 is a front cross-sectional view of the assembly of Fig. 23 having the needle removed therefrom during use, and a mechanical separator spaced apart from the closure according to an embodiment of the present invention.

[0055] Fig. 25 is a front cross-sectional view of the assembly of Fig. 24 having a mechanical separator separating the less dense portion of fluid from the more dense portion of fluid, according to an embodiment of the present invention.

[0056] Fig. 26 is a front cross-sectional view of the assembly having a mechanical separator and a closure engaged in a tube, showing the needle coming into contact with the float structure according to an embodiment of the present invention.

[0057] Fig. 27 is a cross-sectional view of the assembly of Fig. 26 showing the float uncoupling needle with bellows structure, according to an embodiment of the present invention.

[0058] Fig. 28 is a cross-sectional view of the assembly of Fig. 27 showing the float detached from the bellows structure and the ballast assembly in a downward orientation according to an embodiment of the present invention.

[0059] Fig. 29 is a cross-sectional view of the assembly of Fig. 27 showing the float redirected up to a mechanical separator, according to an embodiment of the present invention.

[0060] Fig. 30 is a cross-sectional view of the assembly including the mechanical separator and closure coupled to the tube, according to an embodiment of the present invention.

[0061] Fig. 31 is a cross-sectional view of the assembly of Fig. 30 showing a needle for piercing a mechanical separator, according to an embodiment of the present invention.

[0062] Fig. 32 is a cross-sectional view of the assembly including the mechanical separator and closure coupled to the tube, according to an embodiment of the present invention.

[0063] Fig. 33 is a cross-sectional view of the assembly of Fig. 32 showing the mechanical separator partially displaced from the closure.

[0064] Fig. 34 is a partial cross-sectional view of a mechanical separator comprising a movable plug positioned in a float, according to an embodiment of the present invention.

[0065] Fig. 34A is a partial cross-sectional view of the mechanical separator of Fig. 34 in the initial position.

[0066] Fig. 34B is a partial cross-sectional view of the mechanical separator of Fig. 34A in a displaced position.

[0067] Fig. 34C is a partial cross-sectional view of an alternative mechanical separator comprising a movable plug positioned in a float, according to an embodiment of the present invention in its initial position.

[0068] Fig. 34D is a partial cross-sectional view of the mechanical separator of Fig. 34C in a displaced position.

[0069] Fig. 35 is a front cross section of the float and movable plug with part of the bellows of Fig. 34 in the initial position.

[0070] Fig. 36 is a front cross-sectional view of the float and movable plug with part of the bellows of Fig. 35 in a displaced position.

DESCRIPTION OF PREFERRED EMBODIMENTS [0071] For the purposes of the following description, the words "higher", "lower", "right", "left", "vertical", "horizontal", "upper", "lower", "transverse", " longitudinal ", etc., spatial terms, when used, refer to the described embodiments as are oriented in the drawings. However, it should be noted that many alternative variants and embodiments can be adopted except for clearly defined opposite situations. It should also be noted that the specific devices and embodiments illustrated in the accompanying drawings and described herein are simply illustrative embodiments of the invention.

[0072] As shown in the perspective view of Fig. 2, an exploded view of the mechanical separator assembly 40 of the present invention, it includes a closure 42 with a mechanical separator 44 for use in conjunction with the tube 46 for separating the fluid sample into the first and second phases in tube 46. Test tube 46 may be a sample collection tube, such as a sample collection tube used for in-vitro diagnostics, clinical trials, pharmaceutical tests, proteomics, molecular diagnostics, chemical diagnostic sample tube, blood collection tube or other fluid collection tubes body, coagulation sample tube, hematological sample tube, etc. Preferably, tube 46 is an emptied blood sample tube. In one embodiment, tube 46 may contain additional additives required in a particular test procedure, such as anti-coagulation agents, coagulation agents, stabilization additives, etc. Such additives may be in the form of particles or liquid and may be sprayed onto the cylindrical sidewall of the 52 tube 46 or located at the bottom of tube 46. Test tube 46 has a closed bottom end 48, an open top end 50 and a cylindrical side wall 52 extending between them. The cylindrical side wall 52 comprises an inner surface 54 with an inner diameter "a" extending uniformly from the open end 50 to a location substantially adjacent to the closed bottom end 48.

[0073] Test tube 46 can be made of one or more of the following representative materials: polypropylene, polyethylene teraphthalate (PET), glass or a combination thereof. The tube 46 may contain a single wall or a multiple wall configuration. In addition, tube 46 can be constructed in any practical size to obtain a suitable biological sample. For example, the tube 46 may be of a size similar to conventional high capacity tubes, low capacity tubes, or microtainer tubes as are known in the art. In one particular embodiment, tube 46 may be a standard 3 mL blood sampling tube, which is also known in the art. In another embodiment, the tube 46 can have a diameter of 16 mm and a length of 100 mm, with a blood draw capacity of 8.5 ml or 13 mm.

[0074] The open upper end 50 is constructed so as to at least partially receive the closure 42 therein to form a liquid-tight seal. The closure includes an upper end 56 and a lower end 58 structured to at least partially receive in tube 46. Closure portions 42 adjacent to upper end 56 define a maximum outer diameter that exceeds the inner diameter "a" of tube 46. As shown in Fig. from 2 to 4, the closure parts 42 at the upper end 56 comprise a central recess 60 that defines a pierceable septum that can be resealed. The closure portions 42 extending downward from the lower end 58 may taper from a smaller diameter that is approximately equal to or slightly smaller than the inner diameter "a" of the tube 46 to a larger diameter that is larger than the inner diameter "a" of the tube 46 at upper end 56. In this way, the bottom end 58 of the closure 42 can be pressed into a portion of the tube 46 adjacent to the open end 50. The natural elasticity of the closure 42 can provide sealing engagement with the inner surface of the cylindrical side wall 52 of the tube 46.

[0075] In one embodiment, the closure 42 may be formed of a uniformly formed rubber or elastomeric material and may be of any suitable size and dimensions to provide sealing engagement with the tube 46. The closure 42 may also be formed to define a lower stretching cavity 62 bottom end 58. The bottom recess 62 may be of a size suitable to receive at least a portion of the mechanical separator 44. In addition, a plurality of spaced arcuate flanges 64 may extend around the lower recess 62 to at least partially hold the mechanical separator 44 therein.

[0076] Referring again to Fig. 2, the mechanical separator 44 includes a float 66, ballast assembly 68 and bellows structure 70 such that the float 66 is coupled to a portion of the bellows structure 70, and the ballast assembly 68 is also coupled to a portion of the structure 70 lives.

[0077] Referring now to Figs. 5 to 9, the mechanical separator float 66 is generally a cylindrical body 72 having an upper end 74, a lower end 76 and a channel 78 extending longitudinally between them. The upper end 74 may include a head 80 separated from the generally cylindrical body 72 by the neck 82. The float 66 is substantially symmetrical about the longitudinal axis L. In one embodiment, the outer diameter "b" of the cylindrical body 72 is smaller than the inner diameter "a" of the tube 46, shown in Fig. 2. The outer diameter "c" of the head 80 is typically smaller than the outer diameter "b" of the cylindrical body 72. The outer diameter "d" of the head portion 82 is smaller than the outer diameter "b" of the cylindrical body 72 and is also smaller than the outer diameter "c" of the head 80.

[0078] The head 80 of the float 66 comprises an upper surface 84 defining therein an opening 86 for allowing air to be evacuated. In one embodiment, a plurality of openings, such as, for example, four openings 86a, may be arranged at an angle of 90 ° to each other to allow air to escape. As shown in the enlarged view of Fig. 8 formed along the intersection VIII in Fig. 7, the hole 86 may include a recess extending into the upper surface 84, or a protrusion extending upward from the upper surface 84. Part 86 may be substantially square or round and may be continuous around the float 66. Part 86 is typically recessed inward from the outside diameter "c" of head 80. In addition, opening 86 of head 80 of float 66 may be structured to allow passage of the puncturing end shown in Fig. 2526.

[0079] Referring again to Figs. 5 to 9, the upper surface 84 of the head 80 may also include a diagonal circumference area 88 adjacent the outer diameter "c" of the head 80, with an angle of inclination A. In one embodiment, the angle of inclination A about 15 degrees to about 25 degrees, e.g. 20 degrees. In another embodiment, the head 80 may also include a bottom surface 90 adjacent to the neck 82. The bottom surface may also include an angle of inclination B of from about 8 degrees to about 12 degrees, e.g. 10 degrees.

[0080] The cylindrical body 72 of the float 66 may include a fret area 94 adjacent to the neck 82. The fret area 94 may include a slope angle C of from about 15 degrees to about 25 degrees, e.g. 20 degrees. The lower end 76 of the float 66 may include a stepped portion 96 with an outer diameter "e" that is smaller than the outer diameter "b" of the cylindrical body 72. In an alternative embodiment, the lower end 76 may be a mirror image of the head 80, so that the float is symmetrical along the longitudinal axis.

[0081] In one embodiment, preferably the float 66 of the mechanical separator 44 is made of a material with a density less than the fluid to be separated into two phases. For example, if it is desired to separate human blood into serum and plasma, preferably float 66 has a density not greater than about 0.902 g / cm³. In another embodiment, the float 66 may be formed of polypropylene.

[0082] As shown in Fig. 2, the ballast assembly 68 of the mechanical separator 44 may include a plurality of ballast portions, such as the first ballast portion 98 and the second ballast portion 100. The first ballast portion 98 and the second ballast portion 100 may be oriented oppositely about the longitudinal axis L1 of the mechanical separator 44. In one embodiment, the first ballast portion 98 and the second ballast portion 100 are symmetrical to each other and are their mirror image. Hence, although in Fig. from 10 to 13 only the first ballast portion 98 is shown, it should be understood that the second ballast portion 100 is a mirror image of the first ballast portion 98. Taken together in an opposite orientation, the first ballast portion 98 and the second ballast portion 100 of the ballast assembly 68 are generally cylindrical. Alternatively, it is anticipated that the ballast assembly 68 may consist of more than two connecting parts, i.e., first ballast portion 98 and second ballast portion 100. In one embodiment, the ballast assembly may comprise three joining ballast portions or four joining ballast portions.

[0083] As shown in Figs. 10 to 13, the first ballast portion 98 of the mechanical separator 44 includes a bent side wall 102 having an inner surface 104 and an outer surface 106. The bent side wall 102 has an arch and dimensions substantially corresponding to the arch and dimensions of the inner surface 54 tube 46, shown in Fig. 2, so that the first ballast portion 98 can slide inside the tube 46. The first ballast portion 98 has an upper end 108 and a lower end 110 and an arcuate body 111 extending between them. At the upper end 108 of the first ballast portion 98, there is a receiving recess 112 located on the outer surface 106 of the first ballast portion 98. The receiving recess 112 may extend along the entire arch of the upper end 108 of the outer surface 106. In one embodiment, the receiving recess 112 may be provided as a bonding surface between the float and the first ballast portion 98 and / or the second ballast portion 100 in dual injection molding techniques. Optionally, a second receiving recess 114 may be included at the lower end 110 of the first ballast portion 98. The first ballast portion 98 also has an outer diameter "h" of the upper end 108 which is smaller than the outer diameter "g" of the arch body 111.

[0084] Referring again to Figs. 10 to 13, the first ballast portion 98 may include an inner boundary 118 extending from the inner surface 104 into the interior defined by the arch of the inner surface 104. The inner boundary 118 may have an arc angle D extending along the inner surface 104 of the first ballast portion 98. In one embodiment, the arc angle D is from about 55 degrees to about 65 degrees, e.g. 60 degrees. In another embodiment, the internal constraint 118 is oblique upwards at an angle E or from about 40 degrees to about 50 degrees, e.g. 45 degrees.

[0085] In one embodiment, preferably the ballast assembly 68 of the mechanical separator 44 is made of a material with a density greater than the fluid to be separated into two phases. For example, if it is desired to separate human blood into serum and plasma, preferably the ballast assembly 68 has a density of at least 1.326 g / cm³. The ballast assembly 68, comprising the first ballast portion 98 and the second ballast portion 100, may have a density greater than the density of the float 66 shown in Figs. 5 to 9. In one embodiment, the ballast assembly 68 may be formed of PET material. The first ballast part 98 and the second ballast part 100 can be formed or extruded as separate parts, but manufactured at the same time in one mold.

[0086] As shown in Figs. 14 to 17, the bellows structure 70 of the mechanical separator 44 includes an upper first end 120, a lower second end 122, and a deformable bellows 124 circumferentially therebetween. The upper first end 120 and bellows structure 70 comprise a pierceable head 126, comprising a substantially flat portion 128, surrounded by a generally bent threshold 130, for a suitable connection with the shape of the lower recess 62 of the closure 42, shown in Figs. 2 to 4. In one embodiment, the substantially flat portion 128 may be bent with a nominal radius of about 0.750 inches. In one embodiment, the generally bent threshold 130 has an arc angle F from about 35 degrees to about 45 degrees, e.g., about 40 degrees. The substantially flat surface 128 may have any suitable dimensions, however, preferably the substantially flat portion 128 has a diameter of from about 0.285 inches to about 0.295 inches. The substantially flat portion 128 of the pierceable head 126 has a structure allowing it to pass through the puncturing end shown in Figs. 25-26, such as the tip of a needle, a needle tube, or probe. In one embodiment, the pierceable head 126 has a sufficient thickness to allow the entire penetrating portion of the puncture end to be placed therein prior to penetration. When withdrawing the piercing end from the flat portion 128 of the pierceable head 126, the pierced head 126 has a resealable structure to provide a liquid tight seal. Piercing head 126 of mechanical separator 44 may be extruded and / or formed from an elastically deformable, self-sealing material, such as a thermoplastic elastomer. Optimally, the pierced head 126 can be vented by a plurality of incisions, such as incisions formed in the post-molding operation, for venting the mechanical separator 44.

[0087] Referring now to Fig. 19, in one embodiment, the deformable bellows 124 may include vent slits 131 for venting two places, such as a chamber formed by the interior of float 66 and a chamber formed by the interior of deformable bellows 124 and the outer portion of float 66. These incisions can be created in the procedure after forming. During centrifugation, when the mechanical separator 70 is released from the closure 42 and the mechanical separator 70 is immersed in the fluid, the air is then discharged through the cuts. The cuts 131 may be located radially around the deformable bellows 124 and may have a length of from about 0.05 inches to about 0.075 inches, measured on the inner surface of the deformable bellows 124.

[0088] As shown in the enlarged cross-section in Fig. 16 along line XV of Fig. 15, the upper first end 120 of the bellows structure 70 defines the interior 132 and the inner surface 134 of the upper first end 120 at the piercing portion 126 of the head, and the inner surface 134 of the upper first end 120 at the pierced head portion 126 includes an inner engaging portion 136 extending into the interior 132 of the upper first end 120. In one embodiment, the inner engaging portion 136 has a structure for engaging with the inner diameter of the float 66. Coupling the inner engaging portion 136 of the bellows structure 70 and the inner diameter of the float, shown in Fig. 8, provides a reinforcing structure for the piercing head 126 of the bellows structure 70. In one embodiment, the circumference 92 of float float 66 shown in Fig. 6 to 9 generally corresponds to the piercing profile of pierceable head 126 of the bellows structure 70. Therefore, the upper first end 120 of the bellows structure 70 may include a pierceable head 126 having a piercing profile with a structure substantially opposed to deformation when it moves the piercing end through it, as shown in Figs. 25-26. Corresponding profiles of piercing head 126 of bellows structure 70 and heads 80 of float 66 make piercing head 126 of the present invention more stable and less susceptible to "expansion" from the pierced area of ​​existing mechanical separators. For additional support in limiting sample puffing and premature release of the separator 44 from the bottom recess 62 of the closure 42, the flat portion 128 of the pierceable head 126 may optionally include a thickened area, e.g. from about 0.02 inches to about 0.08 inches thicker with other upper parts first end 120 of the structure of 70 lives. In this way, the premature activation of the mechanical separator 44 is further minimized by pre-compressing the pierceable head relative to the interior of the closure 42.

[0089] Referring again to Figs. 14 to 17, the inner surface 134 of the upper first end 120 of the bellows structure 70 also includes an inner flange 138 extending into the interior 132 and positioned between the piercing head portion 126 and the deformable bellows 124. Inner flange 138 may hold detachably at least part of the float 66 shown in Figs. 5 to 9 in the interior 132 of the bellows structure 70. In another embodiment, the inner flange 138 may detachably hold at least a portion of the float 66, again shown in Figs. 5 to 9, inside the upper first end 120 of the structure 70 by means of a mechanical contact surface. The attached float 66 shown in Figs. 5 to 9 and the upper first end 120 of the bellows structure 70 provide a releasable form engagement between them to maintain the float 66 in a fixed relationship to the bellows structure 70. In one embodiment, the neck 82 of the float 66 and the inner collar 138 of the bellows structure 70 hold the float 66 mechanically adjacent to the bellows structure 70.

[0090] Referring to Figs. 14-15, the deformable bellows 124 is longitudinally spaced from the upper first end 120 of the bellows structure 70. The deformable bellows 124 may be located at the inner flange 138 but extending laterally outwardly from the outer surface 144 of the bellows structure 70. The deformable bellows 124 is symmetrical about the longitudinal axis L2 and includes an upper end 146, a lower end 148 and an empty interior extending between them. The deformable bellows 124 provides sealing engagement with the structure 70 of the bellows with the cylindrical lateral wall 52 of the tube 46, as shown in Fig. 2. The deformable bellows 124 can be made of any suitable elastomer material sufficient to form a liquid tight seal with the cylindrical lateral wall 52 of the test tube 46 . In one embodiment, the bellows is a thermoplastic elastomer and has a suitable dimension thickness from about 0.015 inches to about 0.025 inches. In another embodiment, the entire bellows structure 70 is made of a thermoplastic elastomer.

[0091] The deformable bellows 124 may generally have a toroidal shape with an outer diameter "i" which, in an undeformed position, slightly exceeds the inner diameter "a" of the tube 46, shown in Fig. 2. However, opposing forces acting on the upper end 146 and lower end 148 will lengthen the deformable bellows 124, while reducing the outer diameter "i" to a dimension smaller than "a".

[0092] As shown in Figs. 14-15, the lower second end 122 of the bellows structure 70 comprises oppositely downward extending portions 140 extending longitudinally downward from the upper first end 120. In one embodiment, the opposing downward extending portions 140 are connected to the lower end ring 142, extending circumferentially around the structure of 70 bellows. In one embodiment, the opposing downwardly extending portions 140 define a receiving space 150 with a structure to receive portions of the ballast assembly 68 therein. In one embodiment, the opposing downward extending portions 140 define receiving spaces 150. The first ballast portion 98 has a structure for receiving and attaching in the first receiving space, and the second ballast portion 100 has a structure for receiving and attachment in the second receiving space 150. In one embodiment, the downward extending portions 140 have an outer arc G corresponding to the outer arc of the first ballast part 98 and ballast part 100. Downward extending portions 140 of the bellows structure 70 may also be designed to be molded with a ballast assembly 68, e.g., in two-injection molding techniques. This may allow bonding between the ballast assembly 68 and bellows 70 along the hanging surfaces of the portions 140. This may allow the ballast assembly 68 to open flexibly when the bellows 70 extends and then allow the float 66 to enter the ballast assembly 68.

[0093] As shown in Figs. 18 to 21, when assembled, the mechanical separator 44 comprises a bellows structure 70 having an upper first end 120, a lower second end 122, and a deformable bellows 124 therebetween. The float 66 is attached to a portion of the upper first end 120 of the bellows structure 70 and the ballast assembly 68, comprising the first ballast portion 98 and the second ballast portion 100, is attached to the second lower end 122 of the bellows structure 70. The first ballast part 98 and the second ballast part 100 can be connected to each other by means of a bellows structure part 70, e.g. by means of a downwardly extending part 140.

[0094] As shown in Fig. 21, in one embodiment, the receiving recess 112 of the first ballast portion 98 may be mechanically engaged with the corresponding projection 152 of the lower ring 142 of the bellows structure 70. Similarly, a corresponding receiving recess 112 of the second ballast portion 100 may be mechanically coupled to the corresponding projection 152 of the lower end ring. As shown in Fig. 20, the second receiving recess 114 of the first ballast portion 98 may also be mechanically coupled to the bottom end 154 of the downwardly extending portion 140 of the bellows structure 70. Therefore, the first ballast portion 98, the second ballast portion 100 and the opposing downwardly extending portions 140 of the bellows structure 70 form a cylindrical outer portion with a diameter "j" that is smaller than the diameter "a" of the interior of the tube 46 shown in Fig. 2.

[0095] In this configuration, the float 66 provides reinforcing support for the piercing head 126 of the bellows structure 70 to minimize deformation and expansion. The float 66 is delimited in the interior 132 of the bellows structure 70 by the mechanical contact surface of the inner collar 138 of the bellows structure 70 with the neck 82 of the float 66.

[0096] As shown in Fig. 19, the composite mechanical separator 44 can be pressed into the lower recess 62 of the closure 42. This insertion engages the flanges 64 of the closure 42 with the upper end 120 of the bellows structure 70. During insertion, at least part of the upper end 120 of the bellows structure 70 will deform to accommodate the closure contours 42. In one embodiment, the closure 42 is not substantially deformed when introducing the mechanical separator 44 into the lower recess 62. In one embodiment, the mechanical separator 44 is coupled to the closure 42 by a shape fit of the pierceable head 126 of the upper end 120 of the bellows structure 70 and the lower recess 62 closing 42. Optionally, a latch ring (not shown) may be used at the upper end 120 of the bellows structure 70 for additional mechanical integration of the separator 44 with the closure 42.

[0097] Referring again to Fig. 21, in use, the float 66 of the mechanical separator 44 is to be held within the structure 132 of the bellows 70 by the mechanical contact surface of the inner flange 138 of the structure 70 with the neck 82 of the float 66 until the mechanical separator is exposed centrifugal forces such as in a centrifuge. The presence of the float 66 prevents deformation of the upper part of the bellows structure 70 and thereby prevents the mechanical separator 44 from releasing from the closure 42. The mechanical separator 44 is "locked" in the closure 42 until a force g is generated during spinning, sufficient to pull out and release the float 66 from bellows 70 and releasing the mechanical separator 44 from closure 42.

[0098] When centrifugal forces are applied, the bellows structure 70, in particular the deformable bellows 124, are adapted to longitudinal deformation due to the force exerted on the ballast 68. Ballast 68 exerts a force on the bellows 70 due to overloading during spinning. The inner collar 138 is bent longitudinally due to the centrifugal force exerted on it by the float 66, thereby allowing the neck 82 of the float 66 to be released. When the float 66 is released from the bellows structure 70, it can move freely in the mechanical separator 44. However, at least a portion of the float 66 can be prevented from moving through the bottom end 156 of the mechanical separator 44 by contact with the internal restraint 116 of the first ballast portion 98 and internal restriction 116 of the second ballast portion 100. In one embodiment, the stepped portion 96 of the float 66 may move through the lower end 156 of the mechanical separator 44, however, the cylindrical float body 72 is restrained within the mechanical separator 44 by an internal boundary 116 of the first ballast portion 98 and an internal boundary 116 of the second ballast portion 100. After the mechanical separator 44 is released from the closure 42, the mechanical separator 44 moves towards the fluid interface in the tube 46. After the mechanical separator 44 is in the fluid contained in the tube 46, the float 66 moves back and is attached. in bellows 70.

[0099] In one embodiment, the ballast assembly 68 and bellows structure 70 may be molded together or extruded as a subassembly, e.g., in a double injection molding. The subassembly may comprise a ballast assembly at least partially disposed around the bellows structure 70 comprising pierceable head 126. In another embodiment, the ballast assembly 68 and bellows structure 70 may be co-molded or co-extruded, e.g. in dual injection molding, in part of the closure 42, as shown in Fig. 19. Co-forming the ballast assembly 68 and bellows structure 70 reduces the number of manufacturing steps required to manufacture the mechanical separator 44. Alternatively, the ballast assembly 68 and bellows structure 70 can be molded together or coextruded together, e.g. in double injection molding, and then introduced into closure 42. The float 66 can then be inserted separately into the subassembly to move the mechanical contact surface between the bellows structure 70 and the closure 42. Alternatively, the float 66 can be inserted into the subassembly and the combined float and subassembly can then be introduced into the closure 42.

[0100] As shown in Figs. 22-23, the mechanical separation assembly 40 includes a mechanical separator 44 and a closure 42 inserted into the open end 50 of the tube 46, such that the mechanical separator 44 and the bottom end 58 of the closure 42 are inside the tube 46. Optionally, the closure 42 may be at least partially surrounded by a shield, such as Hemogard® Shield commercially available from Becton, Dickinson and Company to shield the user from blood droplets in the closure 42 and from potential aerosolization of the blood when the closure 42 is removed, as is known. During insertion, the mechanical separator 44, comprising structure 70, engages sealingly with the interior of the cylindrical side wall 52 and the open top end of the tube 46.

[0101] As shown in Fig. 23, the liquid sample is delivered to the tube 46 through the piercing end 160 which penetrates the septum of the upper end 56 of the closure 42 and the piercing head 126 of the bellows structure 70. For illustrative purposes only, the liquid is blood. Blood will flow through the central channel 78 of the float 66 to the closed bottom end 48 of the tube 46. The piercing end 160 will then be withdrawn from the assembly. After removing the piercing end 160, the closure 42 will seal automatically. Piercing head 126 also seals in a manner that it is substantially impermeable to fluid.

[0102] As shown in Fig. 24, when the mechanical separator assembly 40 is subjected to a rotational force, as during centrifugation, the respective blood phases will begin to separate into a higher density phase displaced towards the closed lower end 58 of tube 46 and a smaller phase density, displaced towards the upper open end 50 of tube 46.

[0103] In one embodiment, the mechanical separator assembly 40 is adapted such that when it is subjected to centrifugal force, the float 66 is released from engagement with the bellows structure 70 before the bellows structure 70 is released from the lower recess 62 of the closure 42. Accordingly, the inner flange 138 of the bellows structure 70, shown in Fig. 16, may deform sufficiently to allow release of at least part of the float 66 from the bellows structure 70, while the bellows structure 70 is coupled to the bottom recess 62 of the closure 42. The detachable form connection of the float 66 with the bellows structure 70 may be adapted to release the float 66 from structure 70 lives when the mechanical separator assembly 40 is subjected to centrifugal forces exceeding the spin threshold. In one embodiment, the centrifugation threshold is at least 250 G. In another embodiment, the centrifugation threshold is at least 300 G. When the mechanical separator assembly 40 is subjected to centrifugal force exceeding the centrifugation threshold and the separable shape connection of float 66 and bellows structure 70 disconnected, the mechanical separation assembly 40 may disengage, e.g. by means of a release release coupling from the bottom recess 62 of the closure 42 as shown in Fig. 24. Optionally, the release of the float 66 from the bellows structure 70 allows the mechanical separator assembly 40 to release from the bottom recess 62 of the closure 42.

[0104] The mechanical separator assembly 40 is adapted to be held in the lower cavity of the closure during preparatory procedures, such as when inserting a non-patient needle through the piercing head 126 of the bellows structure 70. In another embodiment, the mechanical separator assembly 40 is also adapted in such a way that the float 66 is held in a detachable form fit with the bellows structure 70 when inserting a non-patient needle by the piercing head 126 of the bellows structure 70. Accordingly, the releasable form fit of float 66 and bellows structure 70 is sufficient to resist an axial force prior to actuation, applied substantially along the longitudinal axis L of float 66, as shown in Fig. 6 and / or substantially along the longitudinal axis L2 of the bellows structure 70, as shown in Fig. 15. The detachable form fit of float 66 and bellows structure 70 may be sufficient to resist a force of at least 0.5 pounds (2.22 N). In another embodiment, the detachable form fit of float 66 and bellows structure 70 may be sufficient to resist a force of at least 2.5 pounds (11.1 N). The detachable shape connection of the float 66 and the bellows structure 70 of the mechanical separator assembly 40 is therefore sufficient to maintain the connection of the float 66 and the bellows structure 70 and the mechanical separator assembly 40 in the lower recess 62 of the closure 42 when inserting a needle not intended for the patient through the piercing head 126 structure of 70 apartments. The detachable form connection of float 66 and bellows structure 70 is also adapted to detach float 66 from bellows structure 70 and mechanical separator assembly 40 from lower recess 62 of closure 42 when applying centrifugal force exceeding the spin threshold.

[0105] In use, the centrifugal force applied will push the mechanical ballast assembly 68 of the separator 44 towards the closed lower end 58 of the tube 46. The float 66 is pushed towards the upper end 50 of the tube 46 only after the mechanical separator 44 has been released from the closure 42 and the mechanical separator will be immersed in the fluid. While the mechanical separator 44 is still attached to closure 42, both float 66 and ballast assembly 68 experience a force acting to pull them toward the bottom end of tube 46. Accordingly, ballast assembly 68 is movable longitudinally relative to float 66. This longitudinal movement generates longitudinal deformed structures 70 bellows. As a result, the bellows structure 70, and in particular the deformable bellows 124, become longer and narrower and are concentrically inwardly spaced from the inner surface of the cylindrical side wall 52. The force exerted by the float 66 on the inner collar 138 of the bellows structure 70 deflects the bellows structure 70 and in this situation, the float neck 66 is released. When the float 66 is detached from the inner flange 138 of the bellows structure 70, the upper end 120 of the bellows structure 70 is elastically deformable in the longitudinal direction when applying centrifugal force. Accordingly, the upper end 120 of the bellows structure 70 will detach from the closure 42. In one embodiment, the closure 42, in particular flanges 64, are not dimensionally changed by applying centrifugal force and as a result do not deform.

[0106] As shown in Fig. 24, in one embodiment, the negative buoyancy of the ballast assembly 68 defies the positive buoyancy of the float 66 by creating a differential force that causes the bellows structure 70 to compress and move away from the inner surface of the side wall of the tube 46. This elongation of the bellows structure 70 opens a venting slit 131 when loaded. Once the venting slits have been opened, air trapped in the mechanical separator assembly 40 may be discharged through the venting slots 131 into the tube at a location above the mechanical separator assembly 40. After centrifugation, the structure 70 of the bellows resiliently returns to its undeformed position, and the vent notches 131 seal automatically to the closed position.

[0107] The present structure reduces premature actuation by preventing the mechanical separator 44 from detaching from the closure 42 due to the interaction of the needle with the head of the bellows structure 70. The mechanical separator 44 cannot separate from the closure 42 until the float 66 is activated during centrifugation. In addition, the closure structure 42 generates a pre-load in the target area of ​​the bellows structure 70, which helps minimize bellows expansion.

[0108] When the mechanical separator 44 is detached from the closure 42 and the diameter of the deformable bellows 124 is reduced, the components of the lighter blood phase will be able to slide through the deformable bellows 124 and move upwards, and similarly, the components of the heavier blood phase will be able to slide. through deformable bellows 124 and moving downwards. As noted above, the mechanical separator 44 has a total density between the densities of the separated blood phases.

[0109] As a result, as shown in Fig. 25, the mechanical separator 44 will stabilize in position in the tube 46 of the mechanical separator device such that the heavier phase components 162 will be between the mechanical separator 44 and the closed lower end 58 of tube 46, while the lighter phase ingredients 164 will be between the mechanical separator 44 and the upper end of tube 50. Once this stabilized state is reached, the centrifuge will be stopped and the deformable bellows 124 will resiliently return to the non-displaced state and to seal against the inside of the cylindrical side wall 52 of tube 46. The formed liquid phases may then be available separately for analysis.

[0110] In an alternative embodiment, shown in Figs. 26 to 29, the displacement of the piercing end 160 by the closure 42 of the mechanical separator assembly 40a comes into direct contact with the float 66a. In this embodiment, the bellows structure 70a may be oriented to circumferentially surround a portion of the float 66a to provide sealing engagement with the closure 42 and the side wall of the tube 46. As shown in Fig. 27, the force of the piercing end 160 disconnects the detachable form fit connection between float 66a and bellows structure 70a, as previously described above, thereby allowing fluid, such as blood, to fill mechanical separator 44a around float 66a. As shown in Fig. 28, when the float 66a is extended from the bellows structure 70a, the mechanical separator 44a is free to get out of the closure 42 during accelerated rotation, such as during spinning. As shown in Fig. 29, when the mechanical separator 44a is detached from the closure, the natural buoyancy of the float 66a pushes the float 66a back to the bellows structure 70a as soon as the mechanical separator 44a is introduced into the fluid in the tube.

[0111] In yet another alternative embodiment shown in Figs. 30-31, similar to the description of Figs. 26 to 29, the bellows structure 70b may include a piercing head 126b, as in the configuration described previously, except that the piercing head 126b has a thickness sufficient to immerse the entire piercing end 200 of the needle 202 in the pierceable head portion 126b before coming into contact with float 66b. By allowing the piercing end 200 to fully immerse in the pierceable portion 126b of the head, expansion of the bellows or drawing of the sample in the deformable bellows is minimized. The float 66b can be made of a compact, rigid material. As the needle 202 is moved further, the float 66b is moved allowing fluid such as blood to flow around the float 66b into the tube 204. During centrifugation, the float 66b will again engage with bellows 70b.

[0112] In yet another embodiment, shown in Figs. 32-33, similar to the description of Figs. 26 to 29, the bellows assembly 70c may include a piercing head 126c having a target area 71c thickened to resist expansion or deformation during movement by him piercing end (not shown). By minimizing bellows expansion, premature disconnection of the mechanical separator from the closure is also minimized. Accordingly, the use of centrifugal force, but without engaging the piercing end with the mechanical separator, causes longitudinal displacement of the ballast assembly 68c, allowing the mechanical separator 44c to free from the closure 42c. Optimally, the latch ring may be positioned around the bellows assembly 70c at the closure 42c to hold the mechanical separator 44c in place.

[0113] According to yet another example of the present invention, shown in Fig. 34, the mechanical separator 600 may include float 668, bellows 670, ballast 672 as described herein. In one configuration, float 668 may be equipped with a movable plug 620 located in the inner portion of float 668. In one embodiment, the movable plug 620 may be formed of the same material as the float 668, and in another embodiment the movable plug 620 may be formed of a material having substantially the same density as the float density 668. In yet another embodiment, the movable plug 620 may be introduced into the inner portion 622 of float 668 after forming float 668.

[0114] In certain situations, a mechanical separator 600 comprising a float 668 having a movable stopper 620 may be preferred. For example, certain test procedures require that the sample is placed in a sample collection container and this sample collection container is subjected to centrifugal force to phase separation of the lighter and heavier in the sample as described here. After separating the sample, the sample collection container and the samples placed therein can be frozen, e.g. at about -70 ° C and then thawed. During the freezing process, the heavier sample phase may expand by forcing the sample column upwards in the sample collection container and through the inner portion 622 of float 668, thereby colliding with a barrier placed between the lighter and heavier phases. To minimize this effect of volumetric expansion, the movable plug 620 may be equipped with an inner portion 622 of float 668, as shown in Fig. 34A.

[0115] Once the sample has been split into lighter and heavier phases in the sample collection container (not shown) the sample may be frozen. During the freezing process, a portion of the sample with a higher density may expand upwards. In order to prevent the higher density portion displaced from coming into contact with the lighter phase and to prevent leakage of the higher density portion of the sample from the float 668, the movable plug 620 moves upwards as the higher density phase expansion, as shown in Fig. 34B.

[0116] The movable plug 620 may be adapted to move with the expanded column of higher density material present in the inner portion 622 of the float 668 during freezing. It is envisaged here that the movable plug 620 can be held in the upper limit by the upper portion 671 of bellows 670, shown in Figs. 34C-34D. In this configuration, the elasticity of the upper portion 671 of the bellows 670 can act as an extensible balloon to hold the movable plug 671 in the mechanical separator 600.

[0117] According to yet another embodiment, the movable plug 620 may be provided with a transverse hole 623 which is substantially in line with the transverse hole 624 provided in the float 668 in the initial position shown in Fig. 35 and is substantially blocked by the blocking part 625 of float 668 in the displaced position shown in Fig. 36. In one embodiment, the transverse opening 624 of the movable plug 620 is located substantially perpendicular to the longitudinal axis R of the movable plug 668.

[0118] In this configuration, after sampling and when applying centrifugal force in the mechanical separator, air captured in the inner portion 622 of float 668 can be discharged through transverse hole 623 of movable cork and transverse hole 624 of float 668 and released from mechanical separator 600 In particular, air may be evacuated from the space between float 668 and bellows 670 as described herein. When the movable plug 620 is moved upward, the transverse opening 623 of the movable plug 620 aligns with the blocking portion 625 of the float 668, which prevents the sample from escaping from the movable plug 620 and the inner portion 622 of the float 668 through the transverse hole 623.

[0119] The movement of the movable cork 620 can be fully passive and reactive to the externally applied sample freezing conditions. In some cases, the movable stopper 620 may also be adapted to return to its starting position after subsequent thawing of the sample.

[0120] Although the present invention has been described in the context of a mechanical separator placed in a test tube at an open end, it is also envisaged here that the mechanical separator may be located at the bottom of the tube, e.g. attached to the bottom of the tube. This configuration can be particularly useful in plasma applications where the blood sample does not clot because the mechanical separator is able to move up the sample during centrifugation.

[0121] The mechanical separator according to the present invention comprises a float which is coupled or locked to a part of the bellows structure until the separator is subjected to centrifugal force. Hence, in use, the mechanical separator of the present invention minimizes premature commissioning of the device and provides a more stable target area in the interface of the piercing end to reduce sample puffing under confinement. In addition, the reduced clearance between the outside of the float and the inside of the ballast minimizes the loss of captured fluid phases such as serum and plasma.

[0122] Although the present invention has been described with reference to several separate embodiments of the mechanical separator assembly and method of use, those skilled in the art can make modifications and changes without departing from the scope limited by the appended claims. Accordingly, the above detailed description is intended to be illustrative rather than limiting.

Becton, Dickinson and Company, USA Agent:

EP 2 326 422 B1

Z-11195/13