FIELD OF THE INVENTION  
         [0001]    The present invention discloses a method, device, and kit to non-invasively sample epidermal cells, or other DNA bearing material taken from the surface of the epidermis, for example oils or sweat, of a test subject while ensuring the collection of a large enough quantity of cells or other material for subsequent biological analyses. In particular, the method obtains cells by taking a sample of the epidermis by means of an abrading and/or cutting surface that scrapes off and retains cell samples for subsequent genetic characterization. The abrading and/or cutting surface would be single use, in a sealed container, where the sample can be returned without contamination. Cellular material, such as DNA (deoxyribonucleic acid), can be released from the collected cells in a manner that enables the cellular material to be analyzed by biological methods. For example, DNA could be amplified by a method such as the polymerase chain reaction. Also provided are devices for taking and storing the epidermal sample and a kit for taking and storing the epidermis. The present invention allows an epidermal sample to be easily obtained and stably stored for a long period of time. In the present specification the term “cells” encompasses free cells and/or tissue that are collections of cells with or without intercellular bonds.  
         BACKGROUND OF THE INVENTION  
         [0002]    Genetic identification, including DNA profiling methods, can discern one individual from another. By virtue of its accuracy, genetic analysis is regarded as the best tool for identification in fields such as forensics, medical diagnostics and genealogy (paternity). In practice, in the U.K. and the U.S., DNA profile databases for prisoners have been constructed. These databases contain DNA profiles of criminals and evidence obtained at crime scenes. Using a computer, the known profiles in these databases are compared against unknown profiles from crime scene evidence.  
           [0003]    Advancement of DNA analysis techniques will lead to a large variety of tests for genetic diseases and predispositions in the near future. One of the limitations of almost all existing tests is that an invasive or offensive procedure must be employed to obtain a sample for subsequent analyses. Some examples of current sampling methods include blood withdrawal, hair pulling, or buccal swabbing. Furthermore, many of these methods can expose medical personnel to infectious agents. Though these techniques are effective, test subjects would prefer a completely non-invasive, painless, and non-offensive test.  
           [0004]    Many times a long-term storage solution is needed to maintain the integrity of the sample once the cells have been collected. Whatman and Schleicher &amp; Schuell have both been granted patents regarding long term storage of DNA bearing material. Whatman uses chemically treated paper to deactivate and destroy microorganisms while attaching the DNA permanently to the paper. See U.S. Pat. Nos. 6,322,983, 6,294,203, 5,985,327, 5,976,572, 5,972,386, 5,756,126, all of which are incorporated herein by reference, as well as www.whatman.com. Schleicher &amp; Schuell, also chemically treats paper to collect, store, and purify the DNA sample. See U.S. Pat. Nos. 6,168,922 and 5,939,259, both of which are incorporated herein by reference, as well as the homepage www.s-and-s.com. Both methods described above require that the sample be applied to the paper in a liquid form.  
           [0005]    WO 97/18009, incorporated herein by reference, discloses a system and a kit for non-invasive collection of DNA-bearing material from the inner cheeks of a living person or corpse. This includes swabs of high modulus fibers that scrape DNA material from the inner cheeks to obtain sufficient material for future identification. It specifically teaches away from sampling cells from skin. It also mentions a kit that includes the swabs and a means for obtaining and recording ink fingerprints.  
           [0006]    U.S. Pat. No. 6,355,439 Chung, et al., incorporated herein by reference, discloses a method for obtaining human DNA for genetic analysis, by taking a sample of the epidermis of test subject by means of an adhesive sheet, and by extracting DNA from the epidermis stuck on the adhesive sheet. It also discloses combined sheets for storing DNA and a kit for taking the epidermis. In addition, a figured epidermal print for fingerprint identification and the epidermal scraps for subsequent DNA analysis of a test subject can be taken at the same time.  
           [0007]    U.S. Pat. No. 5,879,326 to Godshall et al., incorporated herein in its entirety by reference, discloses a method and apparatus for mechanically disrupting a layer of skin having a known thickness without substantially disrupting underlying dermis layers below the skin to facilitate the delivery of compounds across the disrupted layer.  
           [0008]    U.S. Pat. No. 5,732,719 to Godbout, incorporated herein by reference, discloses a filing implement comprising a strip of fiberglass with embedded diamond particles having a grit ranging from 50 to 500 mesh.  
           [0009]    U.S. Pat. No. 6,168,922 to Harvey, et al., incorporated herein by reference, discloses devices and methods for the collection, storage, and purification of nucleic acids, such as DNA or RNA, from fluid samples for subsequent genetic characterization, primarily by conventional amplification methods. It can be used to collect, store, or purify nucleic acids either from a biological source other than untreated whole blood, the biological source having naturally occurring nucleic acid amplification inhibitors present, (including either a buccal swab, cerebrospinal fluid, feces, lymphatic fluid, a plasma sample, a saliva sample, a serum sample, urine, or a suspension of cells or viruses), or from a treated whole blood source that has naturally occurring nucleic acid amplification inhibitors present, as well as added blood stabilization components that also inhibit nucleic acid amplification. In particular, an absorbent material that does not bind nucleic acids irreversibly is impregnated with a chaotropic salt. A biological source sample is contacted with the impregnated absorbent material. Any nucleic acids present in the biological source can be either eluted or resolubilized off the absorbent material.  
           [0010]    U.S. Pat. No. 2,835,246 to Boettger, incorporated herein by reference discloses a medical specimen handling device which is shaped as a spoon or has a head which is grooved for the direct taking of swabs. In this device, the sample collection segment folds back or detaches to be stored in the container which also acts as the handle for the sample collection segment. This device is designed for collection and secure handling of liquid medical specimens and is not suitable for scraping and retention of epidermal samples.  
           [0011]    U.S. Pat. No. 4,981,143 to Sakita, et al., incorporated herein by reference, discloses a cell sampler designed to obtain cells, particularly cells from the cervical canal of the uterus, for cytology, by scraping cells from a soft tissue area. The cell sampler has a stick shaped abrading segment having a number of edges adapted to scrape off cells from the cervical canal. There is a conical/pyramidal stick shaped abrading segment and a spatula shaped abrading segment. The abrading segment tapers to a reduced width to aid in insertion into the body cavity to be sampled. The thin handles and tapered design of these devices make them unsuitable for collection of skin scrapings which require the application of significant pressure. These devices do not provide for secure storage of the collected sample.  
           [0012]    U.S. Pat. No. 5,137,030 issued to Darougar, incorporated herein by reference, discloses a slotted probe for collecting mucous tissue scrapings into the slots. This device is designed for sampling soft tissue and does not provide for secure storage of the collected sample.  
           [0013]    There is a need for sampling devices and methods to painlessly sample skin cells in sufficient quantity for nucleic acid, for example DNA or RNA analysis, or other biological analyses, for example, cytological or diagnostic analysis. There is also a need for improved devices and methods for long-term storage of DNA bearing samples.  
         SUMMARY OF THE INVENTION  
         [0014]    The present invention provides a method, apparatus, and kit to painlessly sample skin cells in sufficient quantity for DNA analysis or for analyses other than DNA analysis, for example, cytological or other scientific analyses, from humans or animals or other life forms.  
           [0015]    The present invention permits sampling epidermal cells from animals, including endangered species without killing or permanently harming them. For example, cells could be sampled from the footpads of such animals.  
           [0016]    This invention provides an apparatus that loosens, scrapes, and retains epidermal cell samples from the epidermis of a test subject. Typical apparati include bladed devices wherein the blade top wall optionally has additional abrasive and/or adhesive.  
           [0017]    The “epidermis” (used herein interchangeably with the term “epidermal skin”) is defined as external (surface) skin not including interior body or body cavity tissues. The present sampling method collects epidermal cells which are relatively dry upon collection (of course the water naturally in the cells and incidental moisture which may be present on the skin at the time of collection are permitted). This contrasts with collection of blood or buccal cells which, by nature, are suspended in liquid. The lack of suspending water addresses the concern of DNA degradation by microorganisms. Reduced water content inhibits the growth of bacteria, yeasts and molds. To further ensure the integrity of the sample, the sampling device can either be covered with a cap with or without a desiccant or placed inside a vapor barrier bag, with or without desiccant. The bag can then be sealed.  
           [0018]    The present invention also provides improved devices and methods for long-term storage of DNA bearing samples.  
           [0019]    The device is envisioned as single use but it could also be designed for multiple uses. When a cell sample has been taken, the portion of the device containing the sampled tissue and cells is sealed and stored for later use as appropriate. The sample is covered with a tape or other cover to prevent contamination. For longer term storage, a desiccant can be used to maintain a controlled low humidity environment. The desiccant, which can be placed in the cover in some instances, or inside a vapor barrier bag in other instances, will reduce moisture required for viability of microorganisms. In the latter case, the entire sampling device would be placed in a vapor barrier bag containing a desiccant and the bag would be heat or otherwise sealed to maintain the integrity of the sample over a longer time period. Maintaining the sample in a controlled humidity environment provides for long-term storage of the sample.  
           [0020]    In the present specification the term “loosen” means mechanical, chemical, or other means of breaking bonds between cells so that a cell or group of cells is freed from the original structure to which the cell or group of cells was bonded. Examples of loosening means include an abrading device having an abrading surface, enzymes such as, but not restricted to, papain to break bonds between cells, or devices which generate sonic energy to break cell bonds. As used in the present specification an abrading surface (also termed in the present specification as an “abrading or cutting” surface) to abrade the surface of the skin encompasses an abrasive or cutting surface that causes mechanical disruption of the epidermis. Typical abrading surfaces include a knife-like or blade-like instrument, sandpaper, a file, or a rasp, to forcibly separate cells. In some instances the loosening device also acts as the scraping device, in other instances the loosening device is used in conjunction with a scraping device.  
           [0021]    The term “scrape” is defined as using mechanical means by which cells or groups of cells freed by loosening are collected in proximity to each other. Typical scraping devices include those having abrading (abrasive or cutting) surfaces, e.g., physical edges or, on a finer level, sandpaper or other such abrasive surfaces, which loosen and collect cells and cell groups. As mentioned above, some abrading surfaces can be used to both loosen and scrape cells.  
           [0022]    The term “retain” means mechanical, chemical, or other means by which a collection of loosened cells or loosened groups of cells are held in proximity to one another such that actions including shaking, dropping, or moving of the sampling device displace a minimal number of the cells from the retention area. Examples of mechanical retention include using a spoon shaped surface that can be sealed with adhesive tape or a cover or using a tube or other vessel into which samples can be placed. Chemical means of retention include the use of adhesives. Typical adhesives include acrylates or conventional pressure sensitive adhesives. However, adhesives such as a surface of imitation gecko toe hairs that works using van der Waals forces as explained in http://www.nature.com/nsu/020826/020826-2.html are also suitable.  
           [0023]    The device is useful for loosening, scraping, and retaining epidermal cell samples but not useful for loosening, scraping, and retaining body cavity tissue cell samples. In contrast to devices used for cell samples taken from a variety of body cavities, the present devices are designed to collect and store cells from the epidermis, a keratinized epithelial tissue. The body cavities typically contain softer tissue of non-keratinized epithelium. The “tougher” construction of the epidermis allows it to act as a protective barrier, and also makes it more difficult to obtain a cell or tissue sample. Thus, without the first step of aggressive action to loosen cells, it is unlikely that the existing devices would collect and securely retain enough cellular matter from the epidermis for subsequent nucleic acid, e.g., DNA, extraction and analysis. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0024]    [0024]FIG. 1 shows a side view of a first embodiment of a device of the present invention having a collection and scraping surface having one or more slanted knife edge projections.  
         [0025]    [0025]FIG. 2 shows a front cross-sectional view along view II-II of FIG. 1.  
         [0026]    [0026]FIG. 3 shows a top view of the skin cell scraping and collection device of FIG. 1.  
         [0027]    [0027]FIG. 4 shows an exploded top view of a second embodiment of the present invention having a collection and scraping surface having one or more slanted knife edge projections and a sliding cover.  
         [0028]    [0028]FIG. 5 shows a partial cross-sectional side view along view V-V along a longitudinal axis “L” of the embodiment of FIG. 4 in a closed position.  
         [0029]    [0029]FIG. 6 shows a partial cross-sectional side view of the embodiment of FIG. 4 in an open position.  
         [0030]    [0030]FIG. 7 shows a top view of a third embodiment of the present invention having a collection and scraping surface having one or more slanted knife edge projections and a hinged cover in an open position.  
         [0031]    [0031]FIG. 8 shows a partial cross-sectional side view of the embodiment of FIG. 7 along view VIII-VIII with the hinged cover in the open position.  
         [0032]    [0032]FIG. 9 shows a partial cross-sectional side view of the third embodiment of FIG. 7 with the hinged cover in a closed position.  
         [0033]    [0033]FIG. 10 shows a front view of the cover of the embodiment of FIG. 7.  
         [0034]    [0034]FIG. 11 shows a side view of a fourth embodiment of a device of the present invention having a collection and scraping surface having one row, or a series of rows, having slanted leading knife edge projections extending from the surface.  
         [0035]    [0035]FIG. 12 shows a top view of the embodiment of FIG. 11.  
         [0036]    [0036]FIG. 13 shows a partial cross-sectional side view of the embodiment of FIG. 11 modified to have a slidable cover.  
         [0037]    [0037]FIG. 14 shows a partial cross-sectional side view of the embodiment of FIG. 11 modified to have a hinged cover.  
         [0038]    [0038]FIG. 15 shows a side view of a fifth embodiment of a device of the present invention having a collection and scraping surface having a single blade extending from an angle from a plane to scrape off (loosen) and collect a surface skin cells sample.  
         [0039]    [0039]FIG. 16 shows a partial cross-sectional side view of the embodiment of FIG. 15 modified to have a slidable cover.  
         [0040]    [0040]FIG. 17 shows a partial cross-sectional side view of the embodiment of FIG. 15 modified to have a hinged cover  
         [0041]    [0041]FIG. 18 shows a top view of a sixth embodiment of a device of the present invention having a stick made of a suitable material such as polystyrene or polycarbonate and a spoon-like hollow lined with abrasive.  
         [0042]    [0042]FIG. 19 shows a side view the sixth embodiment of a device of the present invention having a stick made of a suitable material such as polystyrene or polycarbonate and a spoon-like hollow lined with abrasive.  
         [0043]    [0043]FIG. 20 shows a top view of a modified version of the embodiment of FIG. 18 which includes a cover made of a pliable plastic that can be sealed with adhesive strips on its edges.  
         [0044]    [0044]FIG. 21 shows a top view of the seventh embodiment of the present invention which is the embodiment of FIG. 18 modified to include a cap and a rim.  
         [0045]    [0045]FIG. 22 shows a side view of the seventh embodiment of FIG. 21.  
         [0046]    [0046]FIG. 23 shows a perspective view of an eighth embodiment of a device of the present invention in which the blade-like device is placed inside a removable cap.  
         [0047]    [0047]FIG. 24 shows a bottom view of the embodiment of FIG. 23.  
         [0048]    [0048]FIG. 25 shows an embodiment of a kit of the present invention. 
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0049]    The present invention provides methods, devices and kits capable of the three steps of loosening, scraping, and retaining the sample of epidermal (surface skin) cells in some form or fashion. The three steps (loosening, scraping, and retaining) can be applied simultaneously or they can be applied sequentially.  
         [0050]    Loosening a surface skin cell sample is performed by rubbing a device having an abrasive or cutting surface, for example sandpaper, to abrade the surface of the skin or a knife-like or blade-like or rasp-like instrument to forcibly loosen cells, applying enzymes such as, but not restricted to, papain to break bonds between cells, or treating the epidermis with sonic energy to break cell bonds, or a combination of these techniques. The rubbing may be in a single direction or by a back and forth motion. The abrasive or cutting device would probably be a single use item. Thus, before use it would be in a sealed container (for example, the test tube) or individual foil or plastic sealed package (like an individual WET ONES moist towelette package). Examples of the abrasive or cutting device include sandpaper, a cheese grater-like surface having hollow open faced projections, or a surface having one or more rows having slanted leading projections with sharp edges extending from the surface.  
         [0051]    The abrasive or cutting device can simply have an abrasive or cutting surface or it may have an abrasive or cutting surface with adhesive material on the surface to further hold the scraped off sample. For example, the present invention encompasses use of sandpaper or other substrate, provided with a layer of uniform abrasive, e.g., sand or diamond particles wherein the grit has a particle size in the range of 50 to 500 mesh, optionally further provided with adhesive to retain the cell sample. The abrasive or cutting surface can be made by any conventional means. If desired, the abrasive or cutting surface can be made by nanotechnology/micromachining. In some instances, the abrasive or cutting projections comprise microtines or microblades that extend 10 to 100 μm from a surface of the abrasive or cutting device.  
         [0052]    Scraping and collecting the loosened sample is performed by rubbing the device having the abrasive or cutting surface on skin. Thus, in some instances the apparatus having the abrasive or cutting surface performs the steps of loosening, scraping and collecting the surface skin cell sample. Moreover, enzymes or sonic energy can be applied to the external skin surface prior to using the apparatus having the abrasive or cutting surface to enhance the loosening performed by the apparatus having the abrasive or cutting surface.  
         [0053]    Retaining the sample is performed by sealing the device, that now includes the scraped off skin cell sample, with a cover. This cover may contain a desiccant. The device could be placed into a container for safekeeping. A typical container is a vapor barrier pouch with desiccant to store the cell sample for a long period of time. This overcomes drawbacks of refrigerated storage. Typical freezer temperatures, e.g. minus 5 degrees F., are insufficient to protect cells from fungus and other micro-organisms. Suitable vapor barrier pouches with desiccant are available from the manufacturers listed in TABLE 1.  
                       TABLE 1                       Manufacturer of               Component   Component   Web Site                   LPS Industries   Vapor barrier bag   www.lpsind.com           and desiccant       Sorbent Systems   Vapor barrier bag   www.sorbentsystems.com           and desiccant       PolyLam   Vapor barrier and   www.polylam.com           desiccant                  
 
         [0054]    Typically, the present invention advantageously collects and stores the sample dry. In contrast, Whatman and Schleicher &amp; Schuell have both been granted patents (described above) for long term storage of DNA bearing material but require that the sample be applied to the paper in a liquid form. However, if desired, the epidermal cells may be collected, suspended in liquid, and then transferred to a sheet of Whatman, Schleicher &amp; Schuell or other filter paper.  
         [0055]    The scraped off skin cells sample would then be processed for conventional DNA analysis and/or for biological analyses other than DNA analysis, for example, cytological, diagnostic or other scientific biochemical analyses.  
         [0056]    For example, the DNA from the scraped off skin cells sample would be removed and analyzed by any conventional method. Removing could be done by, e.g., washing, the cells from the abrasive or cutting surface followed by collecting the DNA from these removed cells for analysis. In the alternative, the DNA could be removed from the cells while they still adhere to the abrasive or cutting surface or while they remain in the collection well. For example, the cells may be ruptured to remove their DNA followed by a typical DNA analysis. Typical DNA analyses include, but are not limited to, hybridization behavior, electrophoretic mobility, and nucleotide sequence determination, amplification of one or more DNA sequences by polymerase chain reaction (PCR), determination of the length and/or DNA sequence of the PCR amplified DNA. In one example, the DNA sequences amplified by PCR comprise one or more short tandem repeat (STR) loci. Examples of other scientific analyses include characterization of RNA, protein, lipids and other components of the epidermis.  
         [0057]    The present invention also relates to a kit comprising the device for loosening, scraping and retaining surface skin cells as well as the vapor barrier pouch with desiccant, where the sample can be maintained without contamination.  
         [0058]    A number of embodiments of devices suitable for being employed in the method of the present invention and/or being included in the kit of the present invention, are presented below.  
         [0059]    [0059]FIG. 1 shows a side view of a skin cell scraping and collection device  10  made of a suitable material such as polymer (e.g., polystyrene), metal, glass or ceramics. The device  10  has a collection and scraping surface  12  made of a polymer and having one or more slanted knife edge projections  14  having a height “B” and an end wall  16  having a height “A” and an appropriate degree of sharpness. The dimensions are selected such that they work to abrade and/or scrape off cells but not draw blood. For example, if the knife-edge projections are sufficiently sharp to cut through (slice) skin, then the height “B” is selected such that the device cannot penetrate the epidermis so far that it draws blood, e.g. about 10 to 100 μm. For example, the height “B” could be sufficient such that the blade could penetrate the stratum corneum without substantially damaging underlying layers. If the edge sharpness is sufficient to abrade the epidermis but not cut through the epidermis then the height “B” can be in the range from about 10 μm to about 1 centimeter, or typically about 100 μm to about 5 millimeters. End wall height “A” would be any practical dimension. Typical heights “B” range from about 10 μm to 5 mm.  
         [0060]    If desired, the knife-edge projections  14  can be hollow and have an open portion  17  in the slanted wall under the edge  16  like a cheese grater as shown in FIG. 2. FIG. 2 is an end on view when viewing from near the end wall  16 . If desired, the portions of the surface  12  in the valleys between the knife edges projections  14  may be coated with adhesive to assist in retaining the skin cell sample.  
         [0061]    [0061]FIG. 3 shows a top view of the skin cell scraping and collection device  10 . The knife-edge projections are arranged transverse to a longitudinal axis “L” of the device  10 .  
         [0062]    [0062]FIG. 4 shows an exploded top view a second embodiment of a device  20  of the present invention having a collection and scraping surface  22  having one or more slanted knife edge projections  24 , an end wall  26  and a sliding cover  28 .  
         [0063]    [0063]FIG. 5 shows a partial cross-sectional side view of the embodiment of FIG. 4 with the sliding cover  28  in a closed position. FIG. 6 shows the embodiment of FIG. 4 with the sliding cover  28  in an open position.  
         [0064]    The cover  28  slides longitudinally between the closed position (FIG. 5) and the open position (FIG. 6). The device  20  may be kept in the closed position before use to prevent contamination of the collected sample. However, the device  20  may be kept in the open position before use if it is stored in a sealed package before use to prevent contamination. The device  20  is kept in the closed position after use to prevent contamination of the collected sample. The side  21  of the device  20  opposed to the collection and scraping surface  22  has a first transverse groove  25  relatively distal to the end wall  26  and a second transverse groove  27  relatively proximal to the end wall  26 . A projection, namely a transverse ridge  29 , extends from an inside wall of the cover  28  into the cover  28  to engage the first transverse groove  25  to assist in maintaining the cover  28  in the closed position as shown in FIG. 5. The ridge  29  engages the second transverse groove  27  to assist in maintaining the cover  28  in the open position as shown in FIG. 6. Although the grooves  25 ,  27  are shown in FIGS. 5 and 6 to transverse the entire surface  21  of the device  20 , grooves that do not transverse the entire surface  21  would also suffice. Likewise the ridge  29  may transverse across the entire side of the inner surface of the cover  28  from which the ridge  29  extends, or transverse across a portion of this side.  
         [0065]    [0065]FIG. 7 shows a top view of a third embodiment of the device  30  of the present invention having a collection and scraping surface  32  having one or more slanted knife edge projections  34  and cover  38  held to the device  30  by a pair of flexible hinges  36 .  
         [0066]    [0066]FIG. 8 shows a partial cross-sectional side view of the third embodiment of FIG. 7 along view VIII-VIII wherein the hinged cover  38  is in an open position.  
         [0067]    [0067]FIG. 9 shows a partial cross-sectional side view of the third embodiment of FIG. 7 wherein the hinged cover  38  is in a closed position.  
         [0068]    The cover  38  may be held in the closed position by a friction fit. However, other means for holding the cover  38  in the closed position are also possible. For example, as shown in FIG. 10, each sidewall  33  of the cover  38  may have a respective ridge  35  to fit into a respective groove  37  on opposed sides of the device  30  (FIG. 8) to assist in holding the cover  38  in the closed position.  
         [0069]    [0069]FIG. 11 shows a side view of a fourth embodiment of a skin cell scraping and collection device  40  made of a suitable material as described above for the first embodiment. The device  40  has a collection and scraping surface  42  comprising a plurality of rows  44  and an end wall  49  having a height “A”. Each row  44  has a slanted leading knife-edge projection  46  (extending a height “B”), a leading wall  47 , a top wall  48  and a trailing wall  43 . Typical dimensions for “A” and “B” of the second embodiment are as for the above described first embodiment. The top walls  48  of each knife-edge projection  46  may have a smooth surface or provide additional abrasive surfaces (e.g., optional abrasive surface  45 ). The additional abrasive surfaces are achieved by molding/machining the surface of the top walls  48  to be rough or by fixing a layer of abrasive onto the top walls  48 .  
         [0070]    A suitable abrasive surface is a single layer of uniform diamond or sand particles embedded on the surface of the top wall and having a grit ranging from 50 to 500 mesh fine grit crushed diamond, or a metal file surface or a rasp surface. If desired the abrasive surface may be a plurality of microprotrusions disclosed in U.S. Pat. No. 5,879,326 to Godshall et al. having a height sufficient to disrupt a layer of epidermis without cutting beyond a predetermined distance. If desired, the knife-edge projections  46  can be hollow and open in the slanted leading wall  47  like a cheese grater as explained above for the embodiment of FIG. 2. If desired, the walls  43  and  47  as well as the surface connecting them may be coated with adhesive to assist in retaining the retained skin cell sample. Optionally adhesive may be located in the valleys between the knife-edge projections  46 . Moreover, if desired the embodiment of FIG. 11 may have a cover, for example like that of FIG. 5 or FIG. 10.  
         [0071]    [0071]FIG. 12 shows a top view of the skin cell scraping and collection device  40  shown in FIG. 11.  
         [0072]    [0072]FIG. 13 shows a device  40  of FIG. 11 modified (as in the embodiment of FIG. 5) to have a slidable cover  48 A. The cover  48 A slides longitudinally between a closed position (FIG. 13) and an open position (not shown but easily to envision from FIG. 6). The device  40  may be kept in the closed position before use to prevent contamination of the collected sample. However, the device  40  may be kept in the open position before use if it is stored in a sealed package before use to prevent contamination. The device  40  of FIG. 13 is kept in the closed position after use to prevent contamination of the collected sample. A lower side  41 A of the device  40  of FIG. 13 opposed to the collection and scraping surface  42  has a first transverse groove  45 A relatively distal to the end wall  49  and a second transverse groove  47 A relatively proximal to the end wall  49 . A projection, namely a transverse ridge  49 A, extends from an inside wall of the cover  48 A into the cover  48 A to engage the first transverse groove  45 A to assist in maintaining the cover  48 A in the closed position as shown in FIG. 13. The ridge  49 A engages the second transverse groove  47 A to assist in maintaining the cover  48 A in the open position (not shown but easy to envision from FIG. 6). In this embodiment the grooves  45 A,  47 A transverse the entire surface  41 A of the device  40 . However, grooves that do not transverse the entire surface  41 A would also suffice. Likewise the ridge  49 A may transverse across the entire side of the inner surface of the cover  48 A from which the ridge  49 A extends, or transverse across a portion of this side.  
         [0073]    [0073]FIG. 14 shows the embodiment of the device  40  of FIG. 11 modified to have a hinged cover  48 B (as does the embodiment of FIG. 8) held to the device  40  by a pair of flexible hinges  46 B (one shown by this side view) in an open position. FIG. 14 is a partial cross-sectional view as is FIG. 8. The cover  48 B may be held in the closed position (not shown but easy to envision from FIG. 9) by a friction fit. However, other means for holding the cover  48 B in the closed position are also possible. For example, as shown in FIG. 14, opposed sidewalls of the cover  48 B may have a respective ridge  45 B to fit into a respective groove  47 B on opposed sides of the device  40  to assist in holding the cover  48  in the closed position.  
         [0074]    [0074]FIG. 15 shows a side view of a fifth embodiment of a skin cell scraping and collection device  50  made of a suitable material as described above for the first embodiment. The device  50  is much the same as the device  40  of FIG. 11. The device  50  has a thickness “A”, and a top wall surface  52  having a single blade  54  extending a height “B” from a plane having back portion  55  and front portion  57  to loosen, scrape off, and collect a surface (epidermal) skin cells sample. Relative to the front portion  57 , the single blade  54  extends from the front portion  57  at an angle “C” which is typically in the range from about 30 to about 90 degrees, more typically about 45 to about 80 degrees. Optionally, a top wall  56  of the single blade  54  may have an abrasive surface and the front portion  57  may have an adhesive surface similar to the abrasive and adhesive surfaces mentioned above for device  40 . The abrasive surface may be provided by molding/machining the surface to have a rough coat or by applying an abrasive coating to the top wall  56 .  
         [0075]    Moreover, FIG. 16 shows a modified version of the device  50  of FIG. 15 provided with a slidably removable cap  58 A in a closed position. The cap  58 A comprises a sleeve having opposed open and closed ends (much like the cap of FIG. 5) and may be held onto the device  50  in the closed position by a friction fit, and/or a transverse ridge  59 A engaging with a transverse groove  55 A. In this embodiment, the cap  58 A comes completely off in the open position (not shown, but easy to envision from the exploded view of FIG. 4).  
         [0076]    [0076]FIG. 17 shows the embodiment of the device  50  of FIG. 15 modified to have a hinged cover  58 B (as does the embodiment of FIG. 8) held to the device  50  by a pair of flexible hinges  56 B (one shown by this side view) in an open position. FIG. 17 is a partial cross-sectional view as is FIG. 8. The cover  58 B may be held in the closed position by a friction fit. However, other means for holding the cover  48 B in the closed position are also possible. For example, in a similar manner as described above for the embodiment of FIG. 8, opposed sidewalls of the cover  58 B may have a respective ridge  55 B to fit into a respective groove  57 B on opposed sides of the device  40  to assist in holding the cover  58 B in the closed position. To assist in forming a seal the device  50  of FIG. 17 can be modified to have an extended end wall  59 B having the same height as height “A” shown in FIG. 15.  
         [0077]    [0077]FIGS. 18 and 19 show a sixth embodiment of a device  60  of the present invention. Device  60  includes a stick  61  having a thickness “AA” made of a suitable material as described above for the first embodiment and having a top surface  62 . A portion of the top surface  62  has an area  64  that has been hollowed out much as a spoon to a depth “BB”. Inside this hollowed out area  64  is an abrasive surface, typically made of the same surfaces and materials as described above for the top wall  48 ,  56 . The user holds this stick  61  in his hand and rubs his thumb, or other body part, with a back and forth motion in the hollowed out portion  64  for a sufficient time to remove cells so that a sample is collected. The hollowed out portion  64  may contain adhesive to assist in retaining the sample. For example, if the abrasive surface is a file surface, adhesive may be provided in valleys between ridges of the file.  
         [0078]    If desired to further secure the collected sample in the hollowed out area  64 , a cap or tape or film is placed over the spoon area as further explained below.  
         [0079]    [0079]FIG. 20 shows a top view of the device  60  of the sixth embodiment of FIG. 18 modified to include a tape or film  65  having an adhesive strip  67 . After the cell sample has been deposited in the hollowed out depression  64 , the tape or film  65  is wrapped over the hollowed out depression  64  to seal the sample. FIG. 20 shows the adhesive strip  67  as a single strip along one edge of the film  65 . If desired, in an embodiment (not shown), the adhesive strip may extend about the entire perimeter of the tape or film  65 . In FIG. 20 the tape is attached to the stick  61  before use and folded over the hollowed out depression  64  after the sample is in the depression  64 . However, in alternate embodiments (not shown) the tape or film can be provided to have the adhesive strip, two parallel adhesive strips, or the adhesive perimeter and be initally not attached to the stick  61  and placed over the depression  64  after the sample is in the depression  64 .  
         [0080]    [0080]FIGS. 21 and 22 show top and side views respectively of a seventh embodiment of a device  70  of the present invention. Device  70  is similar to device  60  of FIG. 18 but is modified to include a cap  78  attached to the device  70  by a flexible neck (hinge)  77 . This device  70  also has a hollowed out depression  74  having a depth D and a rim  76  protruding from a surface  72  of the device  70 . After the cell sample has been deposited in the hollowed out depression  74 , the cap  78  is snapped to the rim  76  of the hollowed out depression  74  to seal the sample.  
         [0081]    [0081]FIG. 23 shows a perspective view of an eighth embodiment of a device  80  of the present invention in which a metal blade-like cutting edge  82  is placed inside a removable cap  84 . This cap  84  sits securely at the top of a cylinder  81  (or pen-like apparatus). Just below this blade-containing cap  84  is a collection well  86 .  
         [0082]    In particular, the metal blade-like cutting edge  82  sits in the removable cap  84  in the top of the cylinder  81 . This removable cap  84  sits just above the collection well  86 . Once the sample has been taken, a second cap, namely a screw cap  85 , fits securely over the first cap  84  to minimize contamination and moisture transfer. Thus, a seal between the screw cap  85  and cylinder  81  is formed to minimize introduction of moisture into the sample. In FIG. 23 the cooperating threads of an upper portion of cylinder  81  and the screw cap  85  are not shown for clarity.  
         [0083]    The second (threaded screw) cap  85 , possibly contains desiccant. FIG. 24 shows a bottom view of the interior of the screw cap  85  wherein a desiccant  87  is held against the inside roof of the screw cap  85  by a silicone “O” ring  89 . A typical material of construction for the cylinder  81  is 1.5 ml polypropylene tube having a threaded end to engage the threading of the screw cap  85 . Typically, such a threaded tube is 0.5 to 2 cm, e.g. 1 cm, in diameter; and about 2 to 6 cm, e.g. 4 cm. tall (including the removable cap  84 ). The screw cap  85  is typically about 0.25 to 1.5 cm, e.g. 0.5 cm, tall. Other dimensions may also be suitable.  
         [0084]    After a sample has been taken, the sample can be secured in a sterile bag or other container to be transported to the destination. If long-term storage will be required, bags constructed with a vapor barrier material such as a metallized film should be used. When an appropriately sized desiccant is placed in such a bag with the sample, and the bag is completely sealed by heat or another mechanism, the longevity of the sample will be substantially increased due to the reduction of water vapor in the bag. By controlling the amount of water within the sample storage environment, the microorganisms whose activity relies upon water is minimized. Thus, the effective lifetime of the sample is increased.  
         [0085]    [0085]FIG. 25 shows an embodiment of a kit of the present invention. The kit includes a sampling device, e.g., device  60 , a vapor barrier bag  90  and a desiccant packet  95 . The sizing of the desiccant packet  95  depends upon the length of time the user wishes to store the sample in a controlled environment, the size and quality of the vapor barrier bag  90  as well as the type of the contents of the bag  90 . For instance, paper would require more desiccant than plastic since paper attracts and retains water more easily. The sampling device  60  and the desiccant bag  95  are inserted into the open end  92  of the vapor barrier bag  90  and the bag  90  is then sealed. Typically the open end  92  of the vapor barrier bag  90  is sealed by heat sealing or other suitable means, e.g., chemical or adhesives.  
         [0086]    An alternative storage embodiment (not shown) collects cells using a collecting device of the present invention, then suspends the collected cells in fluid and then places the collected suspended cells onto the Whatman or Schleicher &amp; Schuell papers.  
         [0087]    Processing the Sample  
         [0088]    The sample may be used in any of a variety of biological tests for target components. Examples of such tests include, but are not limited to DNA testing, cytological tests and/or diagnostic testing. Of course a given test may simultaneously fill more than one of these categories.  
         [0089]    The epidermal sample can be processed to extract and analyze various components of the epidermis. For example, the DNA in the sample can be extracted and analyzed. For example, the cells can be resuspended in a buffer and the DNA extracted using: commercially available kits such as, but not limited to, DNA IQ and QuickAmp Extraction; proteases such as Proteinase K, detergents such as sodium dodecyl sulfate (SDS) and chaotropic agents such as urea or guanidine and diatomceous earth or silica particles; organic solvent extraction such as phenol/chloroform and DNA precipitation.  
         [0090]    Some examples of subsequent DNA analyses include, but are not limited to, Polymerase Chain Reaction followed by gel electrophoresis; PCR followed by STR fragment analysis; PCR followed by DNA sequencing; Southern Blot analysis; whole genome amplification or replication followed by DNA sequencing or Southern Blot analysis.  
         [0091]    Typical diagnostic tests include assaying steps such as immunofluorescent staining and/or staining of the sample with any of a plurality of different conjugated antibodies or anti-sera.  
         [0092]    It should be apparent that embodiments other than those described above come within the spirit and scope of the present invention. Thus, the present invention is not limited by the above-provided description but rather is defined by the following claims.
The present invention discloses a method, device, and kit to non-invasively sample epidermal cells of a test subject while ensuring the collection of a large enough quantity of cells for subsequent biological testing. In particular, the method obtains human, or other living creature's, nucleic acid or other biological component for cytological or diagnostic testing and/or genetic analysis. The method takes the sample of the epidermis by means of an abrading surface which scrapes off and retains cell samples for subsequent characterization. The abrading surface could be single use, in a sealed container, where the sample can be returned without contamination. These nucleic acids can be either eluted or resolubilized off, or otherwise released after collection or storage, in a manner that enables them to be amplified by conventional amplification methods such as polymerase chain reaction. Also provided are devices for storing DNA and a kit for easily obtaining and stably storing a sample of epidermal cells and/or other DNA bearing material.