Patent Publication Number: US-2023138146-A1

Title: Biological Fluid Collection and Stabilization System

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. patent application Ser. No. 16/967,315 entitled “Biological Fluid Collection and Stabilization System” filed Feb. 4, 2019, which is the United States national phase of International Application No. PCT/US2019/016520 filed Feb. 4, 2019, and claims priority to U.S. Provisional Application Ser. No. 62/626,904 entitled “Biological Fluid Collection and Stabilization System” filed Feb. 6, 2018, the disclosures of which are hereby incorporated by reference in their entirety. 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Disclosure 
     The present disclosure relates generally to a biological fluid collection system. More particularly, the present disclosure relates to a biological fluid collection device with flow-through blood stabilization and precise sample dispensing of a portion of the sample into a device for analyzing the sample such as a point-of-care or a near-patient-testing device. 
     2. Description of the Related Art 
     Blood sampling is a common health care procedure involving the withdrawal of at least a drop of blood from a patient. Blood samples are commonly taken from hospitalized, homecare, and emergency room patients either by finger stick, heel stick, or venipuncture. Once collected, blood samples may be analyzed to obtain medically useful information including, for example, chemical composition, hematology, and coagulation. 
     Blood tests determine the physiological and biochemical states of the patient, such as disease, mineral content, drug effectiveness, and organ function. Blood tests may be performed in a clinical laboratory or at the point-of-care near the patient. 
     SUMMARY OF THE INVENTION 
     The present disclosure provides a biological fluid collection system that receives a sample and provides flow-through blood stabilization technology and a precise sample dispensing function for point-of-care and near patient testing applications. A biological fluid collection system of the present disclosure is able to effectuate distributed mixing of a sample stabilizer within a blood sample and dispense the stabilized sample in a controlled manner. In this manner, a biological fluid collection system of the present disclosure enables blood micro-sample management, e.g., passive mixing with a sample stabilizer and controlled dispensing, for point-of-care and near patient testing applications. 
     In accordance with an embodiment of the present invention, a biological fluid collection system adapted to receive a sample includes a mixer having a first mixer end and a second mixer end; a sample stabilizer disposed within the mixer; and a syringe assembly having a collection chamber, the syringe assembly removably connectable with the second mixer end, the syringe assembly creates a vacuum that draws the sample through the mixer and into the collection chamber. 
     In one configuration, the biological fluid collection system includes a closure removably connectable with the first mixer end. In another configuration, the closure includes a cap having a first cap end, a second cap end, and defining a cap channel therein, the cap having a pierceable self-sealing stopper within a portion of the cap channel and a cap connection portion at the second cap end; and an adapter having a first adapter end, a second adapter end, and defining an adapter channel therein, the adapter having an adapter connection portion at the first adapter end, the cap connection portion removably connectable with the adapter connection portion. In yet another configuration, with the cap connected to the adapter, the closure is connectable to a first blood collection device via the cap, and with the cap disconnected from the adapter, the closure is connectable to a second blood collection device via the adapter. In one configuration, the first blood collection device is a tube holder. In another configuration, the second blood collection device is a line ending in a Luer connector. In yet another configuration, the syringe assembly includes a barrel defining a collection chamber and having a first end, a second end, and a sidewall therebetween; a stopper slidably disposed within the collection chamber of the barrel, the stopper sized relative to the collection chamber to provide sealing engagement with the sidewall of the barrel, the stopper transitionable between a first stopper position, in which the stopper is a first distance from the first end of the barrel, and a second stopper position, in which the stopper is a second distance from the first end of the barrel, the second distance greater than the first distance; and a plunger having a first plunger end and a second plunger end, a portion of the first plunger end engaged with the stopper, wherein movement of the plunger away from the first end of the barrel moves the stopper to the second stopper position thereby creating the vacuum that draws the sample through the mixer and into the collection chamber. In one configuration, with the syringe assembly connected to the mixer, the barrel is in fluid communication with the mixer. In another configuration, the mixer effectuates distributed mixing of the sample stabilizer within the sample. In yet another configuration, the mixer includes a material including pores; and a dry anticoagulant powder within the pores of the material. In one configuration, the sample dissolves and mixes with the dry anticoagulant powder while passing through the material. In another configuration, the material is an open cell foam. In yet another configuration, the sample stabilizer is the dry anticoagulant powder. In one configuration, the sample is a blood sample. 
     In accordance with another embodiment of the present invention, a biological fluid collection and testing system adapted to receive a sample includes a biological fluid collection device comprising a mixer having a first mixer end and a second mixer end; a sample stabilizer disposed within the mixer; a syringe assembly having a collection chamber, the syringe assembly removably connectable with the second mixer end, the syringe assembly creates a vacuum that draws the sample through the mixer and into the collection chamber; and a closure removably connectable with the first mixer end; and a testing device having a receiving port adapted to receive a portion of the syringe assembly for closed transfer of at least a portion of the sample from the syringe assembly to the testing device. 
     In one configuration, the closure includes a cap having a first cap end, a second cap end, and defining a cap channel therein, the cap having a pierceable self-sealing stopper within a portion of the cap channel and a cap connection portion at the second cap end; and an adapter having a first adapter end, a second adapter end, and defining an adapter channel therein, the adapter having an adapter connection portion at the first adapter end, the cap connection portion removably connectable with the adapter connection portion. In another configuration, with the cap connected to the adapter, the closure is connectable to a first blood collection device via the cap, and with the cap disconnected from the adapter, the closure is connectable to a second blood collection device via the adapter. In yet another configuration, the first blood collection device is a tube holder. In one configuration, the second blood collection device is a line ending in a Luer. In another configuration, the syringe assembly includes a barrel defining a collection chamber and having a first end, a second end, and a sidewall therebetween; a stopper slidably disposed within the collection chamber of the barrel, the stopper sized relative to the collection chamber to provide sealing engagement with the sidewall of the barrel, the stopper transitionable between a first stopper position, in which the stopper is a first distance from the first end of the barrel, and a second stopper position, in which the stopper is a second distance from the first end of the barrel, the second distance greater than the first distance; and a plunger having a first plunger end and a second plunger end, a portion of the first plunger end engaged with the stopper, wherein movement of the plunger away from the first end of the barrel moves the stopper to the second stopper position thereby creating the vacuum that draws the sample through the mixer and into the collection chamber. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above-mentioned and other features and advantages of this disclosure, and the manner of attaining them, will become more apparent and the disclosure itself will be better understood by reference to the following descriptions of embodiments of the disclosure taken in conjunction with the accompanying drawings, wherein: 
         FIG.  1    is an exploded view of a biological fluid collection system in accordance with an embodiment of the present invention. 
         FIG.  2    is an assembled view of a biological fluid collection system in accordance with an embodiment of the present invention. 
         FIG.  3    is a cross-sectional view of the biological fluid collection system of  FIG.  2    with a blood sample drawn within a syringe assembly in accordance with an embodiment of the present invention. 
         FIG.  4    is a cross-sectional view of the syringe assembly of  FIG.  3    with a mixer and a closure removed from the syringe assembly in accordance with an embodiment of the present invention. 
         FIG.  5    is a cross-sectional perspective view of a syringe assembly in a first position with a blood sample contained therein adjacent a point-of-care testing device in accordance with an embodiment of the present invention. 
         FIG.  6    is a cross-sectional perspective view of a syringe assembly in a second position with a blood sample contained therein adjacent a point-of-care testing device and dispensing a portion of a sample to the testing device in accordance with an embodiment of the present invention. 
         FIG.  7    is a perspective view of a biological fluid collection system being connected to a first blood collection device in accordance with an embodiment of the present invention. 
         FIG.  7 A  is an elevation view of a closure of a biological fluid collection system connected to a first blood collection device in accordance with an embodiment of the present invention. 
         FIG.  8    is a perspective view of a biological fluid collection system being connected to a second blood collection device in accordance with an embodiment of the present invention. 
         FIG.  9    is a perspective view of a closure in accordance with an embodiment of the present invention. 
         FIG.  10    is an elevation view of a closure in accordance with an embodiment of the present invention. 
         FIG.  11    is an exploded view of a closure in accordance with an embodiment of the present invention. 
         FIG.  12    is a cross-sectional view of a closure in accordance with an embodiment of the present invention. 
         FIG.  13    is a perspective view of a mixer in accordance with an embodiment of the present invention. 
         FIG.  14    is a perspective view of an open cell foam material in accordance with an embodiment of the present invention. 
         FIG.  15    is a microscopic view of the microstructure of an open cell foam material having a dry anticoagulant powder distributed throughout its microstructure in accordance with an embodiment of the present invention. 
     
    
    
     Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate exemplary embodiments of the disclosure, and such exemplifications are not to be construed as limiting the scope of the disclosure in any manner. 
     DETAILED DESCRIPTION 
     The following description is provided to enable those skilled in the art to make and use the described embodiments contemplated for carrying out the invention. Various modifications, equivalents, variations, and alternatives, however, will remain readily apparent to those skilled in the art. Any and all such modifications, variations, equivalents, and alternatives are intended to fall within the spirit and scope of the present invention. 
     For purposes of the description hereinafter, the terms “upper”, “lower”, “right”, “left”, “vertical”, “horizontal”, “top”, “bottom”, “lateral”, “longitudinal”, and derivatives thereof shall relate to the invention as it is oriented in the drawing figures. However, it is to be understood that the invention may assume various alternative variations, except where expressly specified to the contrary. It is also to be understood that the specific devices illustrated in the attached drawings, and described in the following specification, are simply exemplary embodiments of the invention. Hence, specific dimensions and other physical characteristics related to the embodiments disclosed herein are not to be considered as limiting. 
     The present disclosure provides a biological fluid collection system that receives a sample and provides flow-through blood stabilization technology and a precise sample dispensing function for point-of-care and near patient testing applications. A biological fluid collection system of the present disclosure is able to effectuate distributed mixing of a sample stabilizer within a blood sample and dispense the stabilized sample in a controlled manner. In this manner, a biological fluid collection system of the present disclosure enables blood micro-sample management, e.g., passive mixing with a sample stabilizer and controlled dispensing, for point-of-care and near patient testing applications. 
     Advantageously, a biological fluid collection device of the present disclosure provides a consistent blood sample management tool for point-of-care and near patient testing applications, blood draw, passive mixing technology, and controlled small sample dispensing capability to point-of-care cartridge and standard Luer interfaces with near patient testing receiving ports. 
     A biological fluid collection system  1  of the present disclosure utilizes a mixer  6  and a closure  10  with a syringe  4 . The syringe  4  and closure  10  allow a user to draw a sample  2  from multiple different blood collection devices, such as a Luer line, a tube holder, or other blood collection devices. The syringe  4  also allows for easy drawing of a sample  2  and dispensing of a stabilized sample. The use of a mixer  6  enables automatic mixing of a sample stabilizer  8 , such as an anticoagulant, and a blood sample  2  before collection within the syringe  4 . The syringe  4  also provides a vacuum to draw in a blood sample  2  and functions as a dispensing mechanism for transfer of a stabilized blood sample  2  to testing devices, cartridges, or benchtop instruments. 
     Referring to  FIGS.  1 - 6   , in one embodiment, a biological fluid collection system  1  of the present disclosure is adapted to receive a biological fluid sample, such as a blood sample  2 , and includes a syringe assembly  4 , a mixer  6 , a sample stabilizer  8 , and a closure  10 . 
     The biological fluid collection system  1  of the present disclosure includes a closure  10 .  FIGS.  1 - 3  and  7 - 12    illustrate an exemplary embodiment of a closure  10  of the present disclosure. In one embodiment, a closure  10  of the present disclosure includes a cap  12  and an adapter or connector  14 . In another embodiment, the closure  10  may comprise an integral cap and adapter configuration. The closure  10  of the present disclosure allows for connection to multiple different blood collection devices. Referring to  FIG.  7   , in a first configuration, with the cap  12  connected to the adapter  14 , the closure  10  may be connected to a first blood collection device  110  via the cap  12 . In some embodiments, the cap  12  can be directly connected to a first blood collection device  110  without the adapter  14 . In one embodiment, the first blood collection device  110  includes a tube holder  112 . In a second configuration, with the cap  12  disconnected from the adapter  14 , the closure  10  may be connected to a second blood collection device  120  via the adapter  14 . Referring to  FIG.  8   , in some embodiments, the closure  10  can be removed and the first mixer end  210  of the mixer  6  can be connected to a second blood collection device  120 . In one embodiment, the second blood collection device  120  includes a line  122  ending in a Luer connector  124 . 
     In one embodiment, referring to  FIGS.  1 - 3  and  9 - 12   , the closure  10  includes a cap  12  and an adapter  14 . In another embodiment, the closure  10  may comprise an integral cap and adapter configuration. The cap  12  includes a first cap end  20 , a second cap end  22 , and defines a cap channel  24  therein. The cap  12  has a pierceable self-sealing stopper  26  within a portion of the cap channel  24  and a cap connection portion  28  at the second cap end  22 . In one embodiment, the cap connection portion  28  comprises a first Luer connection portion. 
     Referring to  FIG.  12   , in one embodiment, the cap  12  defines a first cap channel portion  30  therein, a second cap channel portion  32  therein, a third cap channel portion  34  therein, and a fourth cap channel portion  36  therein. Referring to  FIG.  12   , the first cap channel portion  30  has a first diameter D 1 , the second cap channel portion  32  has a second diameter D 2 , the third cap channel portion  34  has a third diameter D 3 , and the fourth cap channel portion  36  has a fourth diameter D 4 . In one embodiment, the first diameter D 1  is greater than the second diameter D 2 , the second diameter D 2  is greater than the third diameter D 3 , and the third diameter D 3  is greater than the fourth diameter D 4 . The first cap channel portion  30 , the second cap channel portion  32 , and the third cap channel portion  34  are configured to securely receive a stopper  26  within the cap  12 . The fourth cap channel portion  36  is configured to securely receive a portion of the adapter  14 . 
     In one embodiment, the cap  12  defines a first ledge portion  38  that is located between the first cap channel portion  30  and the second cap channel portion  32 . Also, in one embodiment, the cap  12  defines a second ledge portion  39  that is located between the second cap channel portion  32  and the third cap channel portion  34 . 
     Referring to  FIG.  12   , in one embodiment, the stopper  26  has a top portion  40 , a bottom portion  42 , and defines a shoulder portion  44  between the top portion  40  and the bottom portion  42 . 
     The first cap channel portion  30 , the second cap channel portion  32 , and the third cap channel portion  34  are configured to securely receive a stopper  26  within the cap  12 . For example, in one embodiment, the stopper  26  is contained within the cap channel  24  such that the top portion  40  of the stopper  26  is within the first cap channel portion  30  and the bottom portion  42  of the stopper  26  is within the second cap channel portion  32 . In this manner, the stopper  26  is securely contained within the cap channel  24  such that the shoulder portion  44  of the stopper  26  contacts the first ledge portion  38  of the cap  12  and the bottom portion  42  of the stopper  26  contacts the second ledge portion  39  of the cap  12  to restrain the stopper  26  within the cap channel  24 . Such engagement secures and restrains the stopper  26  within the cap channel  24  when the stopper  26  is punctured. For example, in one embodiment, when a non-patient needle  114  of a tube holder  112  contacts and pierces the stopper  26 , the stopper  26  is prevented from significant relative movement relative to the cap  12 . 
     In one embodiment, the cap  12  also includes a first wall shield portion  50 , a second wall shield portion  52 , radial ribs  54 , longitudinal ribs  56 , and outer surface  58 . Referring to  FIG.  12   , the second cap end  22  includes a second wall shield portion  52 . 
     Referring to  FIG.  12   , the first cap end  20  includes a first wall shield portion  50  that protectively shields the stopper  26 . For example, the first wall shield portion  50  provides a physical barrier that extends beyond the top portion  40  of the stopper  26  as shown in  FIG.  12   . In this manner, the stopper  26  is safely contained within the cap  12  and the first wall shield portion  50  provides protection from a portion of a blood sample on the stopper  26  splashing externally from the cap  12 . 
     Referring to  FIGS.  9 - 12   , an outer surface  58  of the cap  12  includes radial ribs  54  and longitudinal ribs  56 . The ribs  54 ,  56  provide gripping surfaces that make it easy for a user&#39;s fingers to grip the cap  12  of the closure  10 . For example, the ribs  54 ,  56  provide ergonomically shaped surfaces that aid the user in manipulating the closure  10  and using the closure  10  in a blood collection procedure, and may provide multiple finger grip positions for the user. 
     Referring to  FIG.  7 A , the ribs  54 ,  56  also provide touch point portions  59  that ensure that the closure  10  is properly aligned and positioned within a tube holder  112 . For example, the touch point portions  59  extend outward so that the width of the cap  12  is slightly smaller than the inner diameter of the tube holder  112  and touch a portion of an interior surface  116  of the tube holder  112 . This provides a centering and alignment mechanism when the closure  10  is inserted within a tube holder  112 . In this manner, the cap  12  of the closure  10  is received within the tube holder  112  in a proper orientation, e.g., the cap  12  is properly centered within the tube holder  112  such that a non-patient needle  114  of the tube holder  112  is properly aligned with a stopper  26  of the closure  10 . 
     In one embodiment, the adapter or connector  14  includes a first adapter end  60 , a second adapter end  62 , and defines an adapter channel  64  therein. The adapter  14  has an adapter connection portion  66  at the first adapter end  60 . Referring to  FIG.  11   , in one embodiment, the adapter  14  includes a first portion  68 , a second portion  70 , and a flange portion  72  between the first portion  68  and the second portion  70 . In one embodiment, the adapter connection portion  66  comprises a second Luer connection portion for mating connection with the first Luer connection portion of the cap connection portion  28 . In one embodiment, the closure  10  is removably connectable with the first mixer end  210  of the mixer  6 . For example, the second adapter end  62  includes a connector  76  that is removably connectable with the first mixer connector  212  of the mixer  6 . 
     Referring to  FIGS.  9 - 12   , in one embodiment, the adapter  14  is removably connectable to the cap  12 . For example, the adapter connection portion  66  is removably connectable with the cap connection portion  28  of the cap  12 . In one embodiment, the cap connection portion  28  comprises a first Luer connection portion and the adapter connection portion  66  comprises a second Luer connection portion for mating connection with the first Luer connection portion. In one embodiment, the connection portions  28 ,  66  form an ISO standard Luer interface. In one embodiment, the connection portions  28 ,  66  form a spin lock Luer interface. For example, the adapter connection portion  66  may include a Luer lock thread portion  74 . In another embodiment, the connection portions  28 ,  66  form a slip lock Luer interface. The cap connection portion  28  and the adapter connection portion  66  may be threaded or snap-fit together to form a secure connection. 
     With the adapter  14  connected to the cap  12 , the adapter  14  is locked to the cap  12 , i.e., the adapter  14  and the cap  12  are protectively sealed theretogether. Referring to  FIG.  12   , with the adapter  14  connected to the cap  12 , the cap channel  24  is in fluid communication with the adapter channel  64 . 
     Referring to  FIG.  12   , with the cap  12  connected to the adapter  14 , the second wall shield portion  52  of the cap  12  protectively shields the first adapter end  60  and the first portion  68  of the adapter  14 . For example, the second wall shield portion  52  provides a physical barrier that extends beyond the flange portion  72  of the adapter  14  as shown in  FIG.  12   . In this manner, the second wall shield portion  52  and the flange portion  72  form a protective physical barrier that protectively shields the first adapter end  60  and the first portion  68  of the adapter  14 . 
     Referring to  FIGS.  1 - 3   , a closure  10  of the present disclosure is able to protectively seal a biological fluid collection system  1 , e.g., a mixer  6  and a syringe assembly  4 . For example, in one embodiment, the closure  10  is removably connectable to a first mixer end  210  of mixer  6 . With the closure  10  connected to the mixer  6 , the closure  10  seals the biological fluid collection system  1 . 
     Referring to  FIG.  2   , the closure  10  can be engaged with and protectively seal biological fluid collection system  1  to seal the mixer  6 . The closure  10  allows for the safe introduction of a blood sample into the mixer  6  and the syringe assembly  4 . 
     The closure  10  of the present disclosure allows for connection to multiple different blood collection devices. For example, in one embodiment, the closure  10  allows for connection to a first blood collection device  110  ( FIG.  7   ) in a first configuration and connection to a second blood collection device  120  ( FIG.  8   ) in a second configuration. An advantage of the closure  10  of the present disclosure is that it enables a single closure device to accommodate a variety of connection options. 
     Referring to  FIGS.  7   , in a first configuration, with the cap  12  connected to the adapter  14 , the closure  10  may be connected to a first blood collection device  110  via the cap  12 . In some embodiments, the cap  12  can be directly connected to a first blood collection device  110  without the adapter  14 . In one embodiment, the first blood collection device  110  includes a tube holder  112  having a non-patient needle  114  through which biological fluid is passed, and an interior wall or surface  116  which defines a tube cavity  118 . 
     In a second configuration, with the cap  12  disconnected from the adapter  14 , the closure  10  may be connected to a second blood collection device  120  via the adapter  14 . Referring to  FIG.  8   , in some embodiments, the closure  10  can be removed and the first mixer end  210  of the mixer  6  can be connected to a second blood collection device  120 . In one embodiment, the second blood collection device  120  includes a line  122  ending in a Luer connector  124 . 
     Referring to  FIGS.  1 - 6   , the biological fluid collection system  1  includes a syringe assembly  4  for automatic drawing of a stabilized blood sample  2  within the syringe assembly  4 . In one embodiment, the syringe assembly  4  includes a collection chamber  136  and the syringe assembly  4  is able to create a vacuum that draws a sample  2  through a mixer  6  and into the collection chamber  136 . The syringe  4  allows for easy drawing of a sample and dispensing of a stabilized sample. 
     Referring to  FIGS.  1 - 6   , in one embodiment, the syringe assembly  4  includes a syringe barrel  112 , a plunger  114 , and a stopper  116 . Referring to  FIGS.  1 - 6   , the syringe barrel  112  generally includes a barrel body or sidewall  130  extending between a first or distal end  132  and a second or proximal end  134 . The sidewall  130  defines a collection chamber, elongate aperture, or interior chamber  136  of the syringe barrel  112 . In one embodiment, an interior chamber  136  may span the extent of the syringe barrel  112  so that the syringe barrel  112  is cannulated along its entire length. In one embodiment, the syringe barrel  112  may be in the general form of an elongated cylindrical barrel as is known in the art in the general shape of a hypodermic syringe. In alternative embodiments, the syringe barrel  112  may be in other forms for containing a fluid for delivery, such as in the general form of an elongated rectangular barrel, for example. The syringe barrel  112  may be formed of glass, or may be injection molded from thermoplastic material such as polypropylene and polyethylene according to techniques known to those of ordinary skill in the art, though it is to be appreciated that the syringe barrel  112  may be made from other suitable materials and according to other applicable techniques. In certain configurations, the syringe barrel  112  may include an outwardly extending flange  140  about at least a portion of the proximal end  134 . The flange  140  may be configured for easy grasping by a medical practitioner. 
     The first end  132  of the syringe barrel  112  includes an outlet opening  138  which is in fluid communication with the chamber  136 . In one embodiment, the barrel  112  of the syringe assembly  4  is removably connectable with a second mixer end  214  of the mixer  6 . For example, the first end  132  of the syringe barrel  112  includes a connector  142  that is removably connectable with the second mixer connector  216  of the mixer  6 . 
     The proximal end  134  of the syringe barrel  112  is generally open-ended, but is intended to be closed off to the external environment as discussed herein. The syringe barrel  112  may also include markings, such as graduations located on the sidewall  130 , for providing an indication as to the level or amount of fluid contained within the interior chamber  136  of the syringe barrel  112 . Such markings may be provided on an external surface of the sidewall  130 , an internal surface of the sidewall  130 , or integrally formed or otherwise within the sidewall  130  of the syringe barrel  112 . In other embodiments, alternatively, or in addition thereto, the markings may also provide a description of the contents of the syringe or other identifying information as may be known in the art, such as maximum and/or minimum fill lines. 
     Referring to  FIGS.  1 - 6   , the syringe assembly  4  includes a stopper  116  which is moveably or slidably disposed within the interior chamber  136 , and in sealing contact with the internal surface of the sidewall  130  of the syringe barrel  112 , thereby separating the interior chamber  136  into a proximal chamber  144  adjacent a proximal end  134 , and a distal chamber  146  adjacent a distal end  132 . The stopper  116  is sized relative to the syringe barrel  112  to provide sealing engagement with the interior surface of sidewall  130  of the syringe barrel  112 . Additionally, in one embodiment, the stopper  116  may include one or more annular ribs extending around the periphery of the stopper  116  to increase the sealing engagement between the stopper  116  and the interior surface of the sidewall  130  of the syringe barrel  112 . In alternate embodiments, a singular O-ring or a plurality of O-rings may be circumferentially disposed about the stopper  116  to increase the sealing engagement with the interior surface of the sidewall  130 . 
     The stopper  116  is slidably disposed within the chamber  136  of the barrel  112 . The stopper  116  is transitionable between a first stopper position ( FIG.  2   ), in which the stopper  116  is a first distance from the first end  132  of the barrel  112 , and a second stopper position ( FIG.  3   ), in which the stopper  116  is a second distance from the first end  132  of the barrel  112 , the second distance being greater than the first distance. 
     Referring to  FIGS.  1 - 6   , the syringe assembly  4  further includes a plunger  114  which provides a mechanism for retracting and advancing a stopper  16 . The plunger  114  includes a first plunger end  160 , a second plunger end  162 , and a flange  164 . In one embodiment, a portion of the first plunger end  160  is engaged with the stopper  116 , wherein movement of the plunger  114  away from the first end  132  of the barrel  112  moves the stopper  116  to the second stopper position ( FIG.  3   ), thereby creating a vacuum that draws the sample  2  through the mixer  6  and into the collection chamber  136  of the syringe assembly  4 . 
     Referring to  FIGS.  2  and  3   , in one embodiment, the use of a syringe assembly  4  to fill a chamber  136  of a syringe barrel  112  with a stabilized blood sample  2  will now be described. With the syringe assembly  4  in a position in which a stopper  116  is located adjacent a distal end  132  of the syringe barrel  112  ( FIG.  2   ), when it is desired to aspirate or pull the blood sample  2  through the mixer  6  and into the chamber  136  of the syringe barrel  112 , a user moves a flange  164  of a plunger  114  in a direction away from the proximal end  134  of the syringe barrel  112  until the desired amount of stabilized blood sample  2  is pulled into the chamber  136  of the syringe barrel  112 . In this manner, movement of the stopper  116  and the plunger  114  in this direction creates a vacuum inside the distal chamber  146  of the syringe barrel  112 . 
     The biological fluid collection system  1  includes a mixer  6  that allows for automatic and passive mixing of a blood sample  2  with a sample stabilizer  8 , such as an anticoagulant, blood stabilizer, or another additive, as the blood sample  2  flows through the closure  10  to the collection chamber  136  of the syringe assembly  4 . In one embodiment, the mixer  6  includes a first mixer end  210  having a first mixer connector  212 , a second mixer end  214  having a second mixer connector  216 , and a mixer structure  218 . 
     In one embodiment, the first mixer end  210  is removably connectable to the closure  10  and the second mixer end  214  is removably connectable to the syringe assembly  4 . The closure  10  is removably connectable with the first mixer end  210  of the mixer  6 , e.g., the second adapter end  62  includes a connector  76  that is removably connectable with the first mixer connector  212  of the mixer  6 . The barrel  112  of the syringe assembly  4  is removably connectable with a second mixer end  214  of the mixer  6 , e.g., the first end  132  of the syringe barrel  112  includes a connector  142  that is removably connectable with the second mixer connector  216  of the mixer  6 . In some embodiments, the mixer  6  is removably connectable to the closure  10  and the syringe assembly  4  via a press fit. 
     The mixer structure  218  of the mixer  6  is able to effectuate distributed mixing of a sample stabilizer  8  within a blood sample  2 . The mixer structure  218  may have any suitable structure or form as long as it provides for the mixing of the blood sample  2  with a sample stabilizer  8 , such as an anticoagulant or other additive, as the blood sample  2  passes through the mixer  6  and into the collection chamber  136  of the syringe assembly  4 . 
     Referring to  FIG.  13   , in one embodiment, the mixer structure  218  includes a first curved wall  250  having a first inlet end  252  and a first exit end  254 , and a second curved wall  256  having a second inlet end  258  and a second exit end  260 . The first inlet end  252  is spaced a first distance D 1  from the second inlet end  258  and the first exit end  254  is spaced a second distance D 2  from the second exit end  260 . In one embodiment, the second distance D 2  is less than the first distance D 1 . 
     The mixer structure  218  receives the sample  2  and the sample stabilizer  8  therein and effectuates distributed mixing of the sample stabilizer  8  within the sample  2 . The mixer structure  218  effectuates distributed mixing of the sample stabilizer  8  within the sample  2  and prevents a very high sample stabilizer concentration in any portion of the blood sample  2 . This prevents underdosing of the sample stabilizer  8  in any portion of the blood sample  2 . The mixer structure  218  effectuates distributed mixing of the sample stabilizer  8  within the sample  2  so that an approximately equal amount and/or concentration of the sample stabilizer  8  is dissolved throughout the blood sample  2 , e.g., an approximately equal amount and/or concentration of the sample stabilizer  8  is dissolved into the blood sample  2  from a front portion of the blood sample  2  to a rear portion of the blood sample  2 . 
     The mixer  6  and the collection chamber  136  of the syringe assembly  4  are connected and provided in fluid communication via the second mixer end  214  and the outlet opening  138 . The mixer  6  and the collection chamber  136  of the syringe assembly  4  are positioned such that a biological fluid sample, such as a blood sample  2 , collected into the collection chamber  136  of the syringe assembly  4  via the closure  10  and the mixer  6 , will first pass through a sample stabilizer  8  within the mixer  6 , then the blood sample  2  and the sample stabilizer  8  pass through the mixer structure  218 , and subsequently the sample  2  with the sample stabilizer  8  properly mixed therein flows out the second mixer end  214  into the collection chamber  136  of the syringe assembly  4 . In this way, the blood sample  2  may be mixed with a sample stabilizer  8 , such as an anticoagulant or other additive, provided within the mixer  6 , before passing through the mixing structure  218  for proper mixing of the sample stabilizer  8  within the blood sample  2 , and then the stabilized sample is received and stored within the collection chamber  136  of the syringe assembly  4 . 
     In one embodiment, a sample stabilizer  8  is disposed between the first mixer end  210  and the mixing structure  218 . The mixer  6  of the present disclosure provides passive and fast mixing of a blood sample  2  with the sample stabilizer  8 . For example, the mixer  6  allows for passive mixing of the blood sample  2  with an anticoagulant or another additive, such as a blood stabilizer, as the blood sample  2  flows through the mixing structure  218 . 
     The sample stabilizer  8  can be an anticoagulant, or a substance designed to preserve a specific element within the blood such as, for example, RNA, protein analyte, or other element. In one embodiment, the sample stabilizer  8  is disposed between the first mixer end  210  and the mixing structure  218 . In other embodiments, the sample stabilizer  8  may be disposed in other areas within the mixer  6 . 
     Referring to  FIGS.  13 - 15   , in one embodiment, the mixer  6  includes a material  240  including pores  242  that is disposed between the first mixer end  210  and the mixing structure  218  and a dry anticoagulant powder  244  that is within the pores  242  of the material  240 . In this manner, the mixer  6  may include a dry anticoagulant, such as Heparin or EDTA, deposited on or within a portion of the mixer  6 . In one embodiment, the material  240  is an open cell foam that contains dry anticoagulant dispersed within the cells of the open cell foam to promote the effectiveness of the flow-through mixing and anticoagulant uptake. In one embodiment, the sample stabilizer  8  is the dry anticoagulant powder  244 . 
     In one embodiment, the open cell foam may be treated with an anticoagulant to form a dry anticoagulant powder finely distributed throughout the pores of the open cell foam. As the blood sample  2  enters the mixer  6 , the blood sample  2  passes through the open cell foam and is exposed to the anticoagulant powder available throughout the internal pore structure of the open cell foam. In this manner, the sample  2  dissolves and mixes with the dry anticoagulant powder  244  while passing through the material  240  or open cell foam. 
     The open cell foam  240  may be a soft deformable open cell foam that is inert to blood, for example, a melamine foam, such as Basotect® foam commercially available from BASF, or may consist of a formaldehyde-melamine-sodium bisulfite copolymer. The open cell foam  240  may also be a flexible, hydrophilic open cell foam that is substantially resistant to heat and organic solvents. In one embodiment, the foam  240  may include a sponge material. 
     The anticoagulant or other additive may be introduced into the open cell foam  240  by soaking the foam in a liquid solution of the additive and water and subsequently evaporating the water forming a dry additive powder finely distributed throughout the internal structure of the foam  240 . 
     Referring to  FIGS.  3 - 6   , after the biological fluid collection system  1  using mixer  6  to stabilize a blood sample  2  and collect the stabilized sample  2  in the collection chamber  136  of the syringe assembly  4 , the closure  10  and the mixer  6  can be removed, and a stabilized sample  2  is left in the syringe assembly  4 . A user may then use the syringe assembly  4  to dispense or transfer a stabilized blood sample  2  to a device intended to analyze the sample  2 , e.g., such as a point-of-care testing device  320  ( FIGS.  5  and  6   ), a cartridge tester, or a near patient testing device, while minimizing the exposure of the medical practitioner to the blood sample  2 . In some embodiments, the stabilized blood sample  2  may be transferred into a point-of-care cartridge or point-of-care benchtop analyzer. A user may also send the stabilized sample  2  to the core lab for analysis. 
     Referring to  FIGS.  5  and  6   , when it is desired to expel a stabilized blood sample  2  contained within a syringe barrel  112 , a syringe assembly  4  is grasped with the user&#39;s thumb on a flange  164  of a plunger  114  and with the user&#39;s fingers grasping and extending around a flange  140  of the syringe barrel  112 . In this manner, the syringe assembly  4  is grasped by a user in a well-known and well recognized manner similar to the operation of a conventional syringe. Next, the user effects a squeezing movement between the thumb on the flange  164  of the plunger  114  and four fingers grasping the flange  140  of the syringe barrel  112 , thereby causing the flange  164  of the plunger  114  to move in a direction toward a proximal end  134  of the syringe barrel  112 . In this manner, movement of a stopper  116  in this direction forces a desired amount of the stabilized blood sample  2  contained within a distal chamber  146  of the syringe barrel  112  to be forced out an outlet opening  138 , i.e., movement of the stopper  116  towards a distal end  132  of the syringe barrel  112  reduces the volume of the distal chamber  146  and forces the stabilized blood sample  2  from the syringe barrel  112 . 
     Referring to  FIGS.  5  and  6   , in one embodiment, a testing device  320  includes a receiving port  322  that is adapted to receive a portion of the syringe assembly  4  for closed transfer of at least a portion of the sample  2  from the syringe assembly  4  to the testing device  320 . 
     The closure  10  of the present disclosure allows for connection to multiple different blood collection devices. For example, in one embodiment, the closure  10  allows for connection to a first blood collection device  110  ( FIG.  7   ) in a first configuration and connection to a second blood collection device  120  ( FIG.  8   ) in a second configuration. An advantage of the closure  10  of the present disclosure is that it enables a single closure device to accommodate a variety of connection options. 
     Referring to  FIGS.  7   , in a first configuration, with the cap  12  connected to the adapter  14 , the closure  10  may be connected to a first blood collection device  110  via the cap  12 . In some embodiments, the cap  12  can be directly connected to a first blood collection device  110  without the adapter  14 . In one embodiment, the first blood collection device  110  includes a tube holder  112  having a non-patient needle  114  through which biological fluid is passed, and an interior wall or surface  116  which defines a tube cavity  118 . 
     In a second configuration, with the cap  12  disconnected from the adapter  14 , the closure  10  may be connected to a second blood collection device  120  via the adapter  14 . Referring to  FIG.  8   , in some embodiments, the closure  10  can be removed and the first mixer end  210  of the mixer  6  can be connected to a second blood collection device  120 . In one embodiment, the second blood collection device  120  includes a line  122  ending in a Luer connector  124 . 
     The biological fluid collection system  1  of the present disclosure utilizes a mixer  6  and a closure  10  with a syringe  4 . The syringe  4  and closure  10  allow a user to draw a sample  2  from either a Luer line or through a tube holder, or other blood collection device. The syringe  4  also allows for easy draw of a sample and dispensing of a stabilized sample. The use of a mixer  6  enables automatic mixing of a sample stabilizer  8 , such as an anticoagulant, and a blood sample  2  before collection within the syringe  4 . The syringe  4  also provides a vacuum to draw in a blood sample  2  and functions as a dispensing mechanism for transfer of a stabilized blood sample to testing devices, cartridges, or benchtop instruments. 
     While this disclosure has been described as having exemplary designs, the present disclosure can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this disclosure pertains and which fall within the limits of the appended claims.