Abstract:
A diagnostic device for performing a diagnostic blood test of a subject comprising a thimble-like element adapted to be engaged with the subject&#39;s Finger, a puncturing unit for producing a blood sample from the subject&#39;s finger, and an at least one test element in flow communication with said blood sample.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    The present invention generally relates to medical diagnostics devices and more specifically to a diagnostic thimble mountable on a subject&#39;s finger for performing a rapid blood test. 
         [0003]    2. Discussion of the Related Art 
         [0004]    Diagnostics test kits for rapid detection of specific medical conditions and diseases are becoming increasingly widespread in the field of medical diagnosis. Such kits allow for immediate point-of-care diagnosis in the most basic of healthcare settings with no need for expensive instrumentation and with minimal specialized training. 
         [0005]    A well-known format for performing rapid assays is the lateral flow platform where a sample is applied to a test strip impregnated with assay specific reagents, typically a binding assay such as immunoassay. The sample is applied to one end of the test strip and is drawn through the strip by capillary action to pass through a reaction zone where the analyte, when present, reacts with the pre-impregnated reagents and further into a detection zone where the appearance of a visible or otherwise detectable signal indicates presence of the analyte in the sample. There exist many variations of this basic structure, regarding the number and nature of the immobilized, labeling and other reagents located along the strip and their interaction with the analyte as well as to the nature and formation of the signal. A great variety of analytes may be detected in this manner. In particular relevant to the present invention are rapid diagnostic blood tests where the presence of a specific substance in the blood is indicative of the presence or absence of a disease or a physiological condition, such as for example, the Determine® series from Inverness Medical for the detection of sexually transmitted diseases, including HIV, Hepatitis B and Syphilis. 
         [0006]    Although available rapid blood testing kits, such as the Determine® series, significantly shorten and simplify blood test procedures, they still require separate actions for collecting a blood sample from a tested subject and transferring the sample to the test device for analysis. Collection of blood sample visually involved withdrawing blood by means of a syringe needle or the use of a lancet to injure a body area such as a fingertip and collecting blood from the injury by means of a capillary tube. Such procedures are typically performed by a trained person and may expose the person to infectious blood samples. Moreover, blood sample collection and sample testing are not necessarily performed by the same person. Often blood specimens are collected in one location while tests are performed in another location. This requires transporting the collected specimens and a double identification recordation first for labeling the collected blood samples and then for labeling the test devices, e.g., test strips. In particular, where large groups of people are to be screened for an infectious agent, such as for example HIV, and where it is possible that tested individuals will not come for follow-up, it is particularly desirable to have means for obtaining rapid results while providing easy identification means that prevents possible mismatch between test subjects and test results. Additionally, some people and in particular children are intimidated by the sight of a needle or a lancet or by the sight of blood and consequently may not cooperate with the medical personnel who are trying to take a sample of their blood. In such cases it is desirable to conceal the sight of the lancing element from the tested subject and to perform the act of injury as fast as possible. 
         [0007]    It will be therefore desirable to have an all-in-one self-contained diagnostic device, which allows performing both collection and subsequent analysis of a blood sample in the same device with no need to transfer the collected sample to a separate test device. Such a device will simplify test procedure, will reduce the time required for the test and will minimize exposure of personnel to collected blood samples. It will be also desirable to have such an all-in-one blood test device which can be mounted on a subject finger before the test is started and which can be activated with minimum awareness of the subject to the act of injury. Such a device will further eliminates the need to manage separate identification labels for blood samples and for test devices and will prevent possible mismatch between tested subjects and test results. 
       SUMMARY OF THE PRESENT INVENTION 
       [0008]    It is a general object of the present invention to provide an all-in-one self-contained rapid diagnostic device for performing both collection and analysis of a blood sample of a test subject by a one-step operation with no need to manipulate blood samples. 
         [0009]    It is a further object of the invention to provide such a diagnostic device as defined above which is configured as a thimble to be placed over the end of the subject&#39;s finger and to optionally remain attached to the finger until the test is complete and test results are visibly displayed. 
         [0010]    Such a device has the advantages of simplifying test procedure and minimizing exposure of health care practitioners to blood samples and to lancing devices. It has the further advantage of eliminating the need to manage separate identification records of blood samples and test devices. 
         [0011]    Accordingly the present invention provides a diagnostic device engagabale with a subject&#39;s finger for a rapid detection of a pre-selected analyte in the subject&#39;s blood. The analyte may be a blood borne pathogen or any other substance the presence of which is indicative of a disease or a physiological condition. 
         [0012]    The diagnostic device of the invention comprises a thimble-like element adapted to be engaged with the subject&#39;s finger, a puncturing unit for producing a blood sample from the subject&#39;s finger, and an at least one test element accommodated inside the thimble-like element in a flow communication with the blood sample. The diagnostic device further comprises a display window through which test results can be visibly read. The puncturing unit may comprise a lancing element mounted within a flexible housing or any other lancet unit with an automatic retraction mechanism. The thimble-like element comprises a hollow cylindrical member including a transparent window for viewing the test results. 
         [0013]    The test element is preferably a diagnostic strip adapted for a lateral flow assay of a whole blood sample wherein the assay may be an immunoassay an enzymatic assay, a biochemical assay or a chemical assay. Preferably said assay is a positive/negative assay for detecting the presence of an analyte in the blood sample. Yet, according to other embodiments, the assay may be a quantitative or a semi-quantitative assay for detecting the concentration of the analyte. In accordance with a certain embodiment of the invention the analyte is a blood born pathogen. Preferably the diagnostic strip comprises a sample receiving zone, a whole blood separation zone for entrapping and retaining red blood cells, a reaction zone and a detection zone. 
         [0014]    Optionally the device further includes a reservoir of a releasable reagent solution adapted to release the reagent solution to facilitate running the diagnostic test. The reservoir may comprise a blister made of liquid impermeable film for encapsulating the reagent solution. Optionally the device may further comprise a safety means for preventing premature activation of the puncturing units. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0015]    The present invention will be understood and appreciated more fully from the following detailed description taken in conjunction with the drawings in which: 
           [0016]      FIG. 1  illustrates a diagnostic thimble of the present invention placed over a finger of a test subject; 
           [0017]      FIG. 2  is an isometric view of the diagnostic thimble of the invention; 
           [0018]      FIG. 3  is a cross sectional side view of the thimble placed over a subject&#39;s finger; 
           [0019]      FIG. 4  is an exploded partial longitudinal cross sectional view of the diagnostic thimble in the area designated by the broken lines of  FIG. 3 ; 
           [0020]      FIGS. 5A and 5B  illustrate two embodiments of a puncturing unit with a safety means for preventing premature puncturing; 
           [0021]      FIGS. 6A and 6B  are partial cross sections of two configurations of the diagnostic thimble of the invention incorporating a reagent reservoir; 
           [0022]      FIG. 7  illustrates a typical test strip suitable for use in the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0023]    The present invention provides a thimble-like all-in-one self-contained blood-test diagnostic device for a rapid detection of a pre-selected analyte in a blood sample. The device allows for performing a blood test by one operation step with no need to handle or manipulate blood samples, thus preventing exposure of health care providers to blood samples. The device has the further advantage of reducing to zero the time lag between initial sample collection and test performing. 
         [0024]    The device of the invention is configured as a thimble that is easily placed over the end of a finger. The term thimble refers to a device which at least partially covers a finger, having a general geometry of a hollow cylinder such as a sleeve, with one open for receiving a finger. The device includes a puncturing unit with a self retracting mechanism for producing a blood sample, at least one test element in flow communication with the sample blood so produced and a display window for viewing the test results. The test element may be any test element known in the art for rapid detection of an analyte in a whole blood sample. Preferably the test element is a lateral flow diagnostic strip configured for displaying test results within less than 30 minutes, more preferably within 5 to 15 minutes, by a clearly interpreted visible signal with no need for further equipment for interpretation. By selecting a suitable test element, the diagnostic thimble of the invention may be used to detect various diseases and medical conditions. For example, the device may be used for a rapid detection of infectious diseases such as HIV and hepatitis or for diagnosing myocardial infarction by monitoring cardiac markers. The device is especially useful for testing individuals for example young children, who fail to cooperate during blood tests. The device also allows for screening a large number of subjects in a simple straightforward manner with no need to manage separate labeling for samples and for test devices. The device may be used in developing areas where it is necessary to screen population for infectious diseases or for screening admitted patients in emergency rooms. The device may also be used at blood donation sites for screening potential donors. 
         [0025]    Turning now to the drawings, where like numerals refer to like elements, there is shown a diagnostic thimble, generally designated  10 , in accordance with a preferred embodiment of the present invention. Device  10  comprises a thimble body  12  of a cylindrical shape, a self return puncturing unit  30  and a diagnostic strip  50  mounted within thimble body  12 . Thimble body  12  is open at one end  14  for receiving a finger  5  and is preferably closed at the opposite end  16 . Thimble body  12  can be fabricated from any rigid material. Preferably body  12  is fabricated from low-cost sterilizable plastic material such as PET (polyethylene), polystyrene and the like by a mold injection process. Body  12  is provided with a clear transparent window  26  through which test results are visibly displayed. The rest of body  12  may be made transparent, translucent or opaque. In accordance with one embodiment body  12  is made opaque to obscure the sight of the lancing element and of the blood when the test is carried on. Puncturing unit  30 , comprising a lancing element  35 , is accessible from the external surface of body  12  and is provided with a self return mechanism. Device  10  may be fabricated in a variety of sizes to fit persons of various sizes. As best seen in  FIG. 3 , when in use, thimble body  12  is placed over the end of finger  5  such that piercing unit  30  is located opposite the soft tissue of finger pillow  4  where there is a high density of small blood vessels. A stopper wall  20  located at a predetermined distance from opening  14  adjusts the position of finger  5  in relation to puncturing unit  30  by preventing the finger from penetrating further into the body cavity. An elastic annular rubber flange  18  may also be provided near opening  14  to enhance the gripping of device  10  on the finger and to keep it in place. It will be realized that flange  18  is not necessarily located at opening  14  but may be located further inside cylindrical body  12  between opening  14  and puncturing unit  30 . To further enhance gripping of the thimble and to prevent its movement or removal during the test, an adhesive medical tape (not shown) may be wrapped around end  14  and the finger. 
         [0026]    A small opening  25  in wall  12  allows lancet  35  when fired to penetrate through wall  12  into finger tip  4 . Opening  25  is covered on the inner side of wall  12  by an elastomeric self-sealing liquid-impermeable membrane so that the hole formed by lancet  35  will immediately close on itself after the lancet is withdrawn, preventing blood from escaping through opening  25 . Test strip  50  is located downstream of opening  25  in direct contact with wall  12 . The detection zone  55  of strip  50  is placed over transparent window  26 . The sample receiving zone  52  of strip  50  extends through a hermetically sealed slit in wall  20  to the other side of the wall toward the puncturing site. When finger  5  is pressed against wall  20 , a cavity  16  is formed between the finger and walls  12  and  20  where blood is produced by lancet  35 . A second flange  18   a  (only the bottom part of which is shown in  FIG. 4 ) may optionally be provided near opening  25  to ensure that the blood would not flow toward opening  14 . Alternatively, flanges  18  and  18   a  may be the same flange located close to the upstream side of opening  25 . Thus, blood produced inside the cavity is drawn into the receiving zone of strip  50  and further downstream by capillary action into the detection zone of the strip. A wick member  19 , having one end in contact with the inner surface of membrane  17  and a second end in contact with the sample receiving zone of strip  50  may optionally be added to serve as a bridging element between the two. Wick member  19  may be made of glass fiber, polyester or other filter material known in the art. Alternatively, sample receiving end  52  may be in direct contact with membrane  17  or may be positioned on top of membrane  17  directly below lancet  35  such that blood is directly applied on the sample receiving zone. For some applications, wick  52  as well as zone  52  may be impregnated with medically approved anticoagulants or bleeding enhancers, such as for example citrate and EDTA. A liquid impermeable film  21  laid over strip  50  and partially over wick  19  envelopes strip  50  between body  12  and film  52 . 
         [0027]    Puncturing unit  30 , comprising a sterile lancing element  35 , is configured for penetrating the skin of finger tip  4  for drawing blood. Lancing element  35  may be a hollow or a solid needle or any other sharp sterile element suitable for lancing dermal tissue for producing at least one drop of blood. The size and shape of lancing element  35  as well as the depth to which it penetrates the skin tissue may vary and designed in accordance with the amount of blood required for performing the test. In its default position, the tip of lancet  35  is pointing at opening  25  from outside body  12 . Upon firing, lancing element  35  penetrates through opening  25  and membrane  17  into finger tip  4 . Puncturing unit  30  is provided with automatic return/retract mechanism for withdrawing lancet  35  back to its default retracted position immediately after firing. Various mechanisms may be employed for the firing of unit  30 .  FIG. 6  depict an embodiment according to which lancing element  35  is fixedly mounted within an elastic or spring-loaded capsule-like housing  32 . Puncturing unit  30  is fired by pressing housing  32  toward body  12  thereby lancet  35  penetrates through opening  25  into the finger. Upon release, housing  32  as well as the lancet bounce back to their default position. Alternatively, lancet  35  may be movably mounted within a rigid housing and provided with a spring mechanism that biases the lancet into its retracted position. Yet in accordance with other embodiments, the puncturing unit may be an available single-use skin pricking unit, such as For example a Unistik® unit available from Owen Mumford, mounted on body  12  and if necessary adjusted or modified to operate in association therewith. Preferably, unit  30  is further provided with a safely locking means for preventing unintentional premature actuation of the unit.  FIGS. 6A and 6B  depict two possible configurations of such a safety means. In accordance with the configuration shown in  FIG. 6A , such a safety means is formed by a movable rigid plastic slip  33  that extends across opening  23  of unit  30  and is having an outward extension  36  extending out of housing  32  through opening  34 . In its locking position slip  33  is placed beneath lancet  35  to block the lancet movement. Upon pulling slip  33 , the lancer is ready for activation. A second safety mechanism is depicted in  FIG. 6B  according to which a removable rigid cap  40 , attached to body  12  by means of adhesive rim  41 , is placed on top of unit  30  protecting unit  30  from being activated. A pulling tab  42  provided extending from rim  41  allows the removal of protective cap  40  immediately before the test is to be performed. 
         [0028]    The size and shape of lancing element  35  as well as the depth to which it penetrates the skin tissue may be designed in accordance with the amount of blood required for the specific diagnostic test strip embedded within the thimble. Typically, the amount of blood required for lateral flow assays is in the range of 5 to 100 μL. Such amounts can be easily obtained by means of piercing the top layers of the skin. However it is sometimes necessary to add a small amount of an additional reagent, usually a diluent fluid, such as a buffer solution, in order to perform the test. The buffer could be for example a phosphate buffered saline or Tris buffered saline. For this purpose, the diagnostic thimble of the invention may further include a small reservoir of medically approved buffer or other appropriate reagent solution, adapted to release its content at the same time, or at a predetermined time before or after, puncturing unit  30  is fired.  FIGS. 6A and 6B  illustrate two embodiments of the diagnostic thimble with an additional reagent reservoir  81 . In accordance with the embodiment depicted in  FIG. 6A , a blister  81  filled with the required amount of reagent solution, is positioned above membrane  17  in the path of lancet  35  such that when puncturing unit  30  is activated blister  81  is punctured to release its content. Blister  81  may be fabricated from any thin liquid impermeable membrane such as polyethylene, nylon or the like that is easily punctured by a sharp element. The amount of reagent in blister  81  is typically in the range of 20 to 100 μL, depending on the specific diagnostic test.  FIG. 9B  depicts another configuration according to which blister  81  is located in cavity  16  downstream of the puncturing site and upstream of strip  50 . The device is provided with an additional puncturing unit  80 , similar in design to puncturing unit  30  adapted for puncturing blister  81 . In accordance with this embodiment, blister  81  is punctured either simultaneously or shortly before or after unit  30  is fired such that the reagent solution released from blister  81  is mixed with the blood as it flows into cavity  16  and further into strip  50 . 
         [0029]    Diagnostic strip  50  may be any diagnostic test strip known in the art for detecting an analyte in a whole blood sample by a lateral flow assay, including immunoassays, enzymatic assays, biochemical assays and chemical assays.  FIG. 7  illustrates a typical test strip suitable for use in the present invention, comprising a sample receiving zone  52 , a whole blood separation zone  54 , a reaction zone  56 , a detection zone  55  and an absorbent pad or wick  58  for receiving the fluid and promoting capillary flow through the strip. The different zones may be constructed from one or more bibulous or non-bibulous porous solid phase materials ordered sequentially in an abutting or partial overlapping manner to form a fluid communication therebetween. Strip  50  may be supported on a backing support and/for laminated between two impermeable non-absorbing films such as mylar films, at least one of which is transparent or translucent for allowing viewing the signal. The lateral flow assay is carried out by applying the sample at the sample receiving zone  52  and allowing it to travel along the strip by capillary action, to react with the reagents provided in zone  56  and further downstream to be captured and concentrated at the detection/capture zone  55 . Sample receiving zone  52  is the area of a test strip  50  where the sample is applied. Sample receiving zone  52  can include a bibulous or non-bibulous material, such as filter paper, nitrocellulose, glass fibers, polyester or other appropriate materials. Zone  52  can also include compounds or molecules that may be necessary or desirable for optimal performance of the test, for example, buffers, stabilizers, surfactants and the like. Separation zone  54  is constructed from a material capable of separating the fluid portion of the whole blood sample from the red blood cells by entrapping and retaining the red blood cells therein while transporting the blood plasma or blood serum downstream along the strip so as not to obscure the detection zone  55  by the red color of the red-blood cells. Separation zone  54  may be made of a porous membrane that acts as a physical barrier for the red blood cells or m ay be treated with cell agglutinating reagent to facilitate the separation of the red blood cells from the blood fluid. Reaction or reagent zone  56  is where reagents useful in the detection of the analyte, such as a labeled specific binding member of a first specific binding pair, are bound either movably or immobilized. Typically, the analyte, when present, reacts with the reagents impregnated in zone  56  to form signal generating products that are carried further to be caught at detection zone  55 . Detection zone  55  typically comprises a region T where a member of second specific binding pairs, different from the first binding specific pair, is immobilized to the strip for capturing the analyte-label pair thereby producing a signal. Detection zone  55  may further include a control zone C to indicate that the test on the test has performed correctly. It will be realized that  FIG. 7  is given by way of illustration only and that other test strips of different structures may be used without departing from the scope of the present invention. 
         [0030]    It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather the scope of the present invention is defined only by the claims which follow.