Abstract:
A micro-fluidic device is defined including a channel for conveying blood fluid. A container is defined within the channel for capturing debris generated from the puncture of skin.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a 371 national stage of PCT/US2013/070539 filed Nov. 18, 2013, which claims the benefit of U.S. Provisional Application No. 61/796,648 filed Nov. 16, 2012, the entire contents of which are hereby incorporated by reference in their entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates to method and apparatus for collecting very small biological samples for further processing. 
       BACKGROUND OF THE INVENTION 
       [0003]    Microfluidics is directed to the science of the flow of small amounts of liquid in very small liquid conduits. The liquids often flow in along flow paths that are micro-meters in size or less. In addition there are a variety of other dimensions that are of interest in modern science such as nano-fluidics and milli-fluidics. In very small areas such as the areas defined on a micro, nano, or milli scale, a liquid such as blood behaves differently than in a larger area. 
         [0004]    With the advent of micro and nano technology a number of technologies are emerging that will manage micro, nano, and milli scale fluid flows. However, there are still many challenges involved in the flow of liquids in small areas. 
         [0005]    Many microfluidic devices are defined by the fact that they include one or more flow paths or channels that are 1 mm or less in dimension. A number of different fluids are use in microfluidic devices such as protein or antibody solutions, buffers, bacterial cell suspensions, and whole blood samples. 
         [0006]    To obtain blood samples for use in a microfluidic flow devices a lancet may be used. However, the lancet device is not part of the microfluidic device. 
         [0007]    As such, a method and apparatus is presented for extracting and managing the flow of liquids in small areas for analysis. 
       SUMMARY OF THE INVENTION 
       [0008]    In view of the foregoing considerations, Point of Care (FOC) instruments are being developed, which carry out testing by the bedside or in the physician&#39;s office. 
         [0009]    In one embodiment, a method and apparatus are disclosed for managing whole blood. Specifically, particles of the blood are captured, while the remaining fluid portion of the blood is directed and collected for further processing. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0010]    The accompanying drawings, which are incorporated into and form a part of the specification, illustrate one or more embodiments of the present invention and, together with the description, serve to explain the principles of the invention. The drawings are only for the purpose of illustrating one or more embodiments of the invention and are not to be construed as limiting the invention. In the drawings: 
           [0011]      FIG. 1  displays a first perspective view of a sample collection device implemented in accordance with the teachings of the present invention. 
           [0012]      FIG. 2  displays a second perspective view of a sample collection device implemented in accordance with the teachings of the present invention. 
           [0013]      FIG. 3  displays a second embodiment of a sample collection device implemented in accordance with the teachings of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0014]    For the purposes of promoting an understanding of the principles and operation of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated device, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to those skilled in the art to which the invention pertains. 
         [0015]    Described herein are embodiments pertaining to fluid collection devices that provide for the procurement of a fluid sample, such as a biological fluid, and separating out debris from the fluid sample, without the need for increased gravity, such as through the use of a centrifuge. 
         [0016]    The term “debris” as used herein in the context of fluid that is procured for sampling and analysis typically refers to particles in the fluid sample that have a density different than the fluid being collected. The particles typically, but not necessarily, have a density that is higher than the fluid. Debris includes, but is not limited to, living or dead cells or tissues, or fragments thereof, in the procured fluid sample. Fluids sampled typically refer to whole blood, but may also include, urine, semen, sweat, saliva, tears, mucus, tissue homogenates, and the like. In the case of blood, reference to “debris” is meant to also include interstitial fluid and/or intracellular fluid, as will be explained in further detail herein. 
         [0017]    As used herein, the term “cleanse” (or other verb forms thereof), with respect to the fluid treatment refers to the separation of debris from the fluid that may be collected for further analysis. Cleansing does not necessarily involve complete separation, but rather, reduction in the amount of debris in the fluid sample. 
         [0018]    Alternatively, the particles separated out from the fluid may also be analysed. For example, if the fluid is blood, blood cells may be separated out and counted to provide for a hemocrit analysis. 
         [0019]    Certain embodiments pertain to simple to use devices that include a component that assists in accessing the fluid sample. In a specific embodiment, the component is a lancet that makes a micropuncture in the skin of a subject to allow for the flow of a small amount (e.g. less than a milliliter) of blood. Upon procurement of the blood sample, blood sample is then subjected to structural features of the device that encourage the separation of debris from the fluid to enable the collection of a cleansed fluid sample. 
         [0020]    In clinical chemistry, the identification of the composition of a person&#39;s blood is used as an important diagnostic tool. Blood is primarily plasma, but also includes three major types of cells. Plasma comprises approximately sixty percent to seventy percent of a human blood sample, while approximately thirty to forty percent of the sample is cellular. Plasma within the sample is more than ninety percent water, with the remainder consisting of proteins, lipids, salts and the like. The three major blood cell types are red blood cells (RBCs), white blood cells (WBCs) and platelets. 
         [0021]    Extracellular fluid is typically defined as body fluid outside of cells. The fluid found inside the cells is known as intracellular fluid. The cytosol or intracellular fluid is the liquid found inside of cells. In some animals, including mammals, the extracellular fluid can be divided into two major subcomponents, interstitial fluid and blood plasma. The extracellular fluid also includes the trans-cellular fluid, which is the portion of the total body water contained within epithelial lined spaces. The interstitial fluid is a solution that bathes and surrounds the cells of multicellular animals. The interstitial fluid is found in the interstitial spaces, also known as the tissue spaces. 
         [0022]      FIG. 1  displays a first perspective view of a sample collection device implemented in accordance with the teachings of the present invention. The sample collection device is shown as  100  with the debris container identified as  110 . 
         [0023]      FIG. 2  displays a second perspective view of a sample collection device implemented in accordance with the teachings of the present invention.  FIG. 2  displays a collection device including a debris container. The disposable collection device is shown as  200 . A channel  210  is defined in a housing  253  of the device  200  by sidewalls  240  and a bottom wall  241 . An inlet to the channel  220  and an outlet to the channel  230  are also shown. A liquid such as whole blood flows through the channel along a flow path  205 . A debris container  250  is shown within the channel  210 . 
         [0024]    The debris container  250  includes an entry wall  252 , opposing side walls  251   a,b , and back wall  254 . The debris container is shown adjacent to the channel  210 . Typically, the container space  295  is below the level of the channel  210 , but its walls are flush with the channel  210 . 
         [0025]    A magnified cross-section of the debris container  250  is shown. The container includes an entry angle  260  that involves an angle that is less than 90 degrees (shown in the Figure for exemplary purposes only as a 40 degree angle) to serve as an over-hang for the container and trap the interstitial and cellular debris. A first bottom angle  270  is angled at an acute angle (shown in the Figure for exemplary purposes only as 30 degrees) to also trap the interstitial and cellular debris. The second bottom angle  280  is shown as a 90 degree angle to provide a perpendicular surface to the flow path  205  when combined with the exit angle  290  Which is also defined with a 90 degree angle. Those skilled in the art in view of the teachings herein would appreciate that angles  280  and  290  might deviate from 90 degrees. What is important is that the flow of fluid over the container allows for entry of debris into the container. For example, the 90 degree or orthogonal angle has been found to allow entry of debris, but as will be discussed with respect to  FIG. 3 , the angle  290  can be less than 90 degrees (e.g. 70 degrees). Use of the term “about” in reference to an angle of the container is intended to mean the specified angled and up to a 15 degree variance greater or lower than the specified angle. The micro-triangular/pillar array identified in the channel  210  is designed for the separation of blood cells from the plasma following the cleansing that occurs in the container  250 . 
         [0026]    In an alternative embodiment, the container space is below the channel with a slanted “ramp” in which the deeper end is at the far end of the container in the direction of the flow. Naturally, to obtain this configuration the first entry angle and first bottom angle would need to be greater than 90 degrees. 
         [0027]    In one embodiment, during operations, blood is introduced into the flow path  205 . The initial drops of blood such as blood acquired from a skin puncture will include debris among other components. The debris can interfere with the analysis of components in the blood thereby providing inaccurate or false readings in later process steps. Thus, it is advantageous to capture these items and separate them from the sample. The debris container  250  captures these items in the container  295  space of the debris container  250 . 
         [0028]      FIG. 3  displays a cross-sectional view of a second embodiment of the sample collection device  300  including an overshot spring loaded lancet and debris container. The device  300  includes a housing  353  that has a distal end  321  and a proximal end  322 . Disposed within the housing is lancet  313 , which is shown as a solid micro-needle. A drive component  311  (shown as a spring) is operatively coupled with the lancet  313 . The actuator  312  is configured to release the lancet  313 , whereby the drive component  311  directs movement of the lancet  313  upon depressing the actuator  312 . Based on the teachings herein, it will be appreciated that other drive mechanisms may be implemented, including, but not limited to, gas powered devices, hydraulic device, or even micro-motors. 
         [0029]    Upon actuation of the lancet  313 , a fluid such as whole blood is accessed from the subject (such as a human or other animal subject) and fluid is directed to the flow channel  310  at the channel inlet  320 . In typical operation, a subject places their finger at the distal end  321  and the drive component  311  is actuated by the actuator  312 . 
         [0030]    Upon entry into the channel  310 , the fluid encounters the debris container  350 . Similar to that shown in  FIG. 2 , a magnified cross-section of the container  350  is shown that includes an entry angle  360  that involves an angle that is less than 90 degrees (shown in the Figure for exemplary purposes only as a 40 degree angle) to serve as an over-hang for the container and trap the debris in the fluid. A first bottom angle  370  is angled at an acute angle (shown in the Figure for exemplary purposes only as 30 degrees) to also trap the interstitial and cellular debris. The second bottom angle  380  is shown as a 90 degree angle to provide a perpendicular surface to the flow path  205  when combined with the exit angle  390  which is shown with a 70 degree angle. 
         [0031]    Further to that described above with respect to the angles of the containers  250  and  350 , the entry angle  260  or  360  is typically less than about ninety degrees. In a specific embodiment, the entry angle  260  or  360  is from about 15 degrees to 60 degrees. More specifically, entry angle  260  or  360  ranges from about  25  degrees to about 45 degrees. Further still, entry angles  260  or  360  are 40 degrees or about 40 degrees. 
         [0032]    In addition, the first bottom angle  270  or  370  is one that is less than about 90 degrees. In a specific embodiment, bottom angles  270  or  370  range from about 15 degrees to 60 degrees. In a more specific embodiment, bottom angles  270  or  370  range from about 20 degrees to 40 degrees. More specifically, the bottom angle  270  or  370  is 30 degrees or about 30 degrees. 
         [0033]    With respect to the second bottom angles  280  or  380 , these angles may range from about 80 degrees to about 110 degrees. In a specific embodiment, second bottom angles  280  or  380  are 90 degrees or about 90 degrees. 
         [0034]    With respect to exit angles  290  or  390 , these angles typically range from about 60 degrees to 105 degrees. In a specific embodiment, the exit angles  290  or  390  are 70 degrees or about 70 degrees. In another specific embodiment, the exit angles  290  or  390  are 90 degrees or about 90 degrees. 
         [0035]    The container  250  or  350  includes a predetermined, minimal volume that is intended to capture the first drop of blood which contains cell debris and interstitial fluid, or even intracellular fluid typically from rupturing of cells during lancing. The presence of these elements in the fluid flowing to the reaction area can cause interference in the reaction process, either in blocking the micro-channels (debris) or corrupting the actual chemical determination of the required analyte. A following blood volume also tops-off the container, suppressing the interstitial and cellular debris contained in the container  295  space and allowing uncontaminated blood such as the remaining drops of blood acquired from a puncture to flow along the flow path. 
         [0036]    The container volume is designed such that once filled with debris, interstitial fluid, or intracellular fluid so that the subsequent drops of blood continue towards the separation area (such as the micro-triangular/pillar array filter shown in  FIG. 2 , which is the topic of a related application) where the blood cells are separated from the plasma which is used for the actual determination. The cleansing process followed by cell separation is intended to purify the sample flowing into the reaction area to pure plasma. Extracellular fluid will only be found in the first drop of blood collected due to the puncture with the lance. All subsequent drops will not contain debris or extracellular fluid 
         [0037]    The embodiment  300  includes a connector  317  configured at the proximal end  322 . The connector is adapted to allow for fluid communication with the flow channel  310  to carry the cleansed fluid to another device for analysis. 
         [0038]    It is important to an understanding of the present invention to note that all technical and scientific terms used herein, unless defined herein, are intended to have the same meaning as commonly understood by one of ordinary skill in the art. The techniques employed herein are also those that are known to one of ordinary skill in the art, unless stated otherwise. For purposes of more clearly facilitating an understanding the invention as disclosed and claimed herein, the following definitions are provided. 
         [0039]    It should be borne in mind that all patents, patent applications, patent publications, technical publications, scientific publications, and other references referenced herein and in the accompanying appendices are hereby incorporated by reference in this application to the extent not inconsistent with the teachings herein. 
         [0040]    While a number of embodiments of the present invention have been shown and described herein in the present context, such embodiments are provided by way of example only, and not of limitation. Numerous variations, changes and substitutions will occur to those of skill in the art without materially departing from the invention herein. For example, the present invention need not be limited to best mode disclosed herein, since other applications can equally benefit from the teachings of the present invention. Also, in the claims, means-plus-function and step-plus-function clauses are intended to cover the structures and acts, respectively, described herein as performing the recited function and not only structural equivalents or act equivalents, but also equivalent structures or equivalent acts, respectively. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the following claims, in accordance with relevant law as to their interpretation.