Abstract:
A system for mixing a sample with a combined buffer includes a sampler body, the sampler body including a first reservoir and a second reservoir. The system further includes a first separator forming a first enclosure with the sampler body for the first reservoir. The system further includes a second separator forming a second enclosure with the sampler body for the first reservoir. The system further includes a third separator, in conjunction with the second separator, forming a third enclosure and a fourth enclosure, respectively, both in conjunction with the sampler body, for the second reservoir.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of Provisional Application No. 62/337,557 filed on May 17, 2016, titled “Systems and Methods For A Multi-Chambered Sampler” the entire disclosure of which is hereby incorporated by reference. 
     
    
     BACKGROUND 
       [0002]    Systems that provide for point-of-care testing of analytes are important for doctors, health professionals, and consumers. Point-of-care testing may allow for rapid results that replicate or approach the accuracy and precision available for laboratory testing. One type of point-of-care testing relies on lateral flow test strips and the use of antibodies and markers in order to determine the concentration of various analytes. As part of such a lateral flow assay, a premix step with a buffer or other reagents may be useful. Instead of providing a user in a point-of-care setting with test tubes and a vial or reagent, a “sampler” may be provided that receives a sample and includes a premixed reagent (in many cases, a buffer). The sampler then may be used to readily apply the sample to a lateral flow test strip. This greatly increases the usability of the system for consumers and other health professionals, since no test tubes are required. One downside of such samplers is that they may contain only one compartment, so if multiple reagents or substances are used, they may need to be premixed and stored in the sampler together. This may decrease the effective life of such reagents. 
       SUMMARY 
       [0003]    In one embodiment, a system for mixing a sample with a combined buffer includes a sampler body, the sampler body including a first reservoir and a second reservoir. The system further includes a first separator forming a first enclosure with the sampler body for the first reservoir. The system further includes a second separator forming a second enclosure with the sampler body for the first reservoir. The system further includes a third separator, in conjunction with the second separator, forming a third enclosure and a fourth enclosure, respectively, both in conjunction with the sampler body, for the second reservoir. Optionally, the first and third separators are foil. Alternatively, the second separator is a septum. In one alternative, the first reservoir includes a first buffer and the second reservoir includes a second buffer. In another alternative, the system further includes a blood collector, the blood collector including a piercing projection, and the blood collector shaped to mate with the sampler body, such that when the blood collector is inserted into the sampler body at an aperture in the sampler body, liquid cannot escape from the combination of the sampler body and the blood collector. Alternatively, upon insertion of the blood collector into the sampler body, the piercing projection of the sampler body pierces the first and second separators. Optionally, the sampler body includes a capillary tube that holds the sample. Alternatively, upon insertion of the blood collector into the sampler body, the first and second buffers mix with the sample. Optionally, the sampler body includes a cylindrical cavity that houses the first and second reservoirs. In one configuration, the septum provides one pound of force resistance to piercing. In another configuration, the septum has four equal quadrants joined by a thin connector material. Optionally, the septum is molded plastic. Alternatively, the four equal quadrants are thicker that the thin connector material. 
         [0004]    In one embodiment, a method for mixing a sample with a combined buffer includes providing a sampler body. The sampler body includes a first reservoir and a second reservoir. The sampler body further includes a first separator forming a first enclosure with the sampler body for the first reservoir. The sampler body further includes a second separator forming a second enclosure with the sampler body for the first reservoir. The sampler body further includes a third separator, in conjunction with the second separator, forming a third enclosure and a fourth enclosure, respectively, both in conjunction with the sampler body, for the second reservoir. The method further includes providing a blood collector, the blood collector including a piercing projection, and the blood collector shaped to mate with the sampler body, such that when the blood collector is inserted into the sampler body at an aperture in the sampler body, liquid cannot escape from the combination of the sampler body and the blood collector. The method further includes inserting the blood collector into the sampler body; advancing the blood collector and breaking the first separator; and advancing the blood collector and breaking the second separator. Optionally, the first reservoir includes a first buffer and the second reservoir includes a second buffer. In one alternative, the method further includes mixing the first and second buffers; and mixing a sample held in the blood collector with the first and second buffers by agitating the combined sampler body and blood collector. Optionally, the first and third separators are foil. Alternatively, the second separator is a septum. Optionally, the sampler body includes a capillary tube that holds the sample. 
         [0005]    In another configuration, the septum has four equal quadrants joined by a thin connector material. Optionally, the septum is molded plastic. Alternatively, the four equal quadrants are thicker that the thin connector material. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0006]      FIG. 1A  shows one embodiment of a single chamber sampler body; 
           [0007]      FIG. 1B  shows an embodiment of a double chamber sampler body having a septum or other separator in the sampler body; 
           [0008]      FIGS. 2A and 2C  show a single chamber sampler body and a cross-section of sampler body  120  along cross-section line B, respectively; 
           [0009]      FIGS. 2B and 2D  show a double chamber sampler body and a cross-section of sampler body  150 , along cross-section line B, respectively; 
           [0010]      FIG. 3  shows an embodiment of a sampler body with a single buffer-filled chamber formed by foil heat staked ends; 
           [0011]      FIG. 4  shows an embodiment of a sampler body with two buffer-filled chambers formed from molded-in septum and foil heat staked ends; 
           [0012]      FIGS. 5A, 5B and 5C  show the progressive insertion of the blood collector into the septum-containing sampler body, showing the opening of the septum through the insertion force of the blood collector; 
           [0013]      FIG. 6  shows one view of an embodiment of the septum after the piercing projection has broken it; 
           [0014]      FIG. 7  shows the blood collector fully inserted into the sampler body; 
           [0015]      FIGS. 8A and 8B  show another view of the insertion of the blood collector into the sampler body; 
           [0016]      FIG. 9A  shows the sampler body oriented to mix the blood sample with the reagent mixture; 
           [0017]      FIG. 9B  shows another view of the insertion of the blood collector into the sampler body; 
           [0018]      FIGS. 10A and 10B  show views of an embodiment of a septum; 
           [0019]      FIG. 11A  shows the septum of  FIG. 10A  in a sampler body; and 
           [0020]      FIG. 11B  shows an alternative embodiment of a septum. 
       
    
    
     DETAILED DESCRIPTION 
       [0021]    Certain terminology is used herein for convenience only and is not to be taken as a limitation on the embodiments of the systems and methods for a multi-chambered sampler. In the drawings, the same reference letters are employed for designating the same elements throughout the several figures. In many embodiments, a multi-chambered sampler uses a first separator and a second separator to hold two compartments of reagents. In many embodiments, a sample collector is used to penetrate both the first and second separators. This allows for the mixing of a sample in the sample collector with both reagents. 
         [0022]    In some point-of-care tests, a required buffer is stable in the short term (hours), but unstable in the longer term (weeks to months). These point-of-care tests typically involve a sampler, including a blood collector, a sampler body, and a sampler base, and a test cartridge or test strip for receiving a sample mixed in the sampler. In order to achieve long-term stability of the buffer and hence the product, the buffer should be prepared in two stable fractions and those fractions mixed to form the active buffer just prior to use. Embodiments of the multi-chambered sampler address the issue of managing the two stable fractions of the proposed buffer while continuing to be able to offer customers an easy-to-use sampler body system. The goal is to achieve a sampler design that would keep the unstable fractions separated until needed; then the standard action of the user inserting the blood-filled blood collector into the sampler body and subsequently shaking it would automatically mix the buffer fractions together with the blood, and the combination then could be dispensed into the test cartridge in the standard fashion. 
         [0023]    Therefore, embodiments of a sampler are described herein that provide for two compartments for holding two buffers that are combined at the time of usage. This sampler is easy to use and merely requires the user to insert a mated blood collection device into the sampler. 
         [0024]      FIG. 1A  shows one embodiment of a sampler body. Sampler body  120  includes an upper end aperture  110  for the insertion of a sample collector. As shown, the central storage area  125  is a single piece. In contrast,  FIG. 1B  shows an embodiment of a sampler body having a septum  160  or other separator in sampler  150 . This effectively divides the central reagent storage area with a septum that later can be broken by the blood collection device. A molded dual chamber sampler body contains a septum  160  that is strong enough to keep the two solutions apart during storage, but weak enough that the mechanical action of inserting the blood collector into the sampler body breaks the septum and allows the solutions to mix.  FIG. 1A  shows a view of a sampler body  120  cross-section with a single central chamber  125  (after the foil staking process), and  FIG. 1B  shows a view of a sampler body  150  cross-section with a single septum  160  splitting central chamber  125  into two chambers (after the foil staking process). The foil staking process will be explained in the subsequent figures; however, the top portion of central chamber  125  is typically foil covered to seal the reagent in the central chamber  125 . In both embodiments, the sampler body  150  includes a upper foil sealing surface  105  and a lower foil sealing surface  106 . The blood collector pierces this foil. 
         [0025]      FIGS. 2A and 2C  show a sampler body  120  and a cross-section of sampler body  120 , along cross-section line B, respectively.  FIGS. 2B and 2D  show a sampler body  150  and a cross-section of sampler body  150 , along cross-section line B, respectively. Here, septum  160  is visible. Septum  160  may be formed from a variety of materials such as plastics, foils, and other materials. As shown, septum  160  includes four equal sections that are separated by a thin joint of material that may easily rip and break when the blood collector is inserted. In the embodiment shown, septum  160  may be made of plastic as well as other materials. 
         [0026]      FIG. 3  shows an embodiment of a sampler body  120  with single buffer-filled chamber formed by foil heat staked ends.  FIG. 4  shows an embodiment of a sampler body  150  with two buffer-filled chambers formed from molded-in septum and foil heat staked ends. As is shown, sampler body  120  includes a top foil closure  340  and a bottom foil closure  345 . A reagent  310  (in many cases, a buffer) is stored in the chamber between the top foil closure  340  and the bottom foil closure  345 . In sampler body  150 , a first reagent  350  is stored between a top foil closure  340  and the septum  160 . A second reagent  360  is stored between the septum  160  and the bottom foil closure  345 . Although the septum and closures are described as having specific properties, alternative materials and closures may be used in some embodiments. For instance, plastics, coated papers, and other materials that may be made thin enough to pierce may be utilized for the foil closures and, similarly, the same materials or foil may be used for the septum. 
         [0027]      FIGS. 5A-5C  show the progressive insertion of a blood collector into a septum-containing sampler body showing the opening of the septum through the insertion force of the blood collector. Current insertion force of the blood collector is about five to ten pounds. Expected yield force of molded-in septum is about one pound force, so the user will be unaware of the added complexity of this sampler design. In  FIG. 5A , a blood collector  510  is used to retrieve a sample, typically a blood sample resulting from a finger prick. Blood collector  510  includes a piecing tip  520  and a capillary tube  530  that holds a sample. As shown, blood collector  510  is aligned with the top aperture  110  of sampler body  150  that includes septum  160 .  FIG. 5B  shows the sampler body  150  advanced to the septum  160 . Because of the venting mechanism  530 , the force of air attempting escape should be at a minimum. Blood collector  510  mates precisely with sampler body  150  such that no liquid will escape during insertion as the foil and septum  160  are penetrated.  FIG. 5C  shows the piercing projection  520  advanced through the septum  160 . 
         [0028]      FIG. 6  shows one view of an embodiment of the septum  160  after the piecing projection  520  has broken it. Although some material may remain, the fluid flow past septum  160  should be largely uninhibited after piercing. 
         [0029]      FIG. 7  shows blood collector  510  fully inserted into sampler body  150 , breaking the heat staked top foil seal as well as molded-in septum  160 , allowing fluids in both chambers to mix into a combined reagent  710 . 
         [0030]      FIGS. 8A and 8B  show another view of the insertion of blood collector  510  into sampler body  150 . As shown, blood collector  510  includes a piercing projection  520  and a capillary tube  530  containing a sample. The blood collector  510  aligns with the aperture  110  in sampler body  150  and may be inserted. Upon insertion, piercing projection  520  breaks foil  340  and septum  160 , allowing the first reagent  350  and the second reagent  360  to mix into reagent mixture  710 . Bottom foil  345  holds the mixture in the central chamber until the mixed sample is to be applied to a cassette or test strip. Also visible in these figures is the sampler base  810 . The sampler base  810  includes the sampler plunger  820  and the piercing projection  830  for piercing bottom foil  345  to release the sample onto a test strip after mixing. 
         [0031]      FIGS. 9A and 9B  show the next steps in the sampling process. In  FIG. 9A , the combined sampler body  150  and blood collector  510  are sealed together by virtue of their mated fit and may be agitated in order to mix the blood sample in capillary tube  530  with the reagent mixture. In  FIG. 9B , the blood sample has been mixed and capillary tube  920  is largely empty. The combined blood sample and reagent mixture  910  then is ready to be applied to a cassette or test strip by piercing the foil  345  according to a different procedure not addressed herein. In this way, the two reagents may be kept separate and combined in a seamless fashion from the point of view of the user. This improves the shelf life of the device by preventing the reagents (buffers) from degrading due to their combination. In some alternatives, additional separation layers may be added. The addition of more separation layers may increase the number of compartments provided in the central chamber. Generally, the additional separation layers or septums should be within the range of the blood sampler body such that they may be pierced during insertion; however, they cannot be placed too high towards the aperture, since this will result in the leaking/pushing out of liquid when the blood sampler body is inserted. 
         [0032]      FIGS. 10A and 10B  show views of the septum  160 . Septum  160  includes a hinge feature  1020 , breakaway sections  1010 , and tearoff sections  1030 . In some embodiments, breakaway sections are 0.020 inches thick and tearoff sections are 0.003 inches thick. This is purely exemplary. In some embodiments, breakaway sections are tenths of an inch thick and tearoff sections are hundredths of an inch thick. As above, this is merely an example. The point of this is to provide areas where the septum may rip more easily to provide a more regular breaking pattern. 
         [0033]      FIG. 11A  shows septum  160  in the sampler body.  FIG. 11B  shows an alternative embodiment of a septum  1110 . Septum  1110  includes panel sections  1120 , center section  1140 , connection section  1150 , and tearaway sections  1130  that separate the panels, center, and connection. Numerous other geometries will occur to those of ordinary skill in the art based on the teaching of this disclosure. 
         [0034]    While specific embodiments have been described in detail in the foregoing detailed description and illustrated in the accompanying drawings, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure and the broad inventive concepts thereof. It is understood, therefore, that the scope of this disclosure is not limited to the particular examples and implementations disclosed herein but is intended to cover modifications within the spirit and scope thereof as defined by the appended claims and any and all equivalents thereof.