Abstract:
The present disclosure includes but is not limited to a device for collecting samples, especially liquid samples to be tested for the presence of an analyte, especially for drugs of abuse, antibodies, antigens and biological moieties such as steroids and glucose. In particular, the disclosure describes improvements in collection device design that provide a simple, non-invasive, non-hazardous method of collecting samples from a subject or patient, especially liquid samples such as saliva, oral fluid and urine. The collected sample can be stored in the disclosed device and the device can be used to apply, in a drop-wise manner, an aliquot of the sample directly to a test device.

Description:
CROSS-REFERENCE TO A RELATED APPLICATION  
       [0001]     This application claims priority of previously filed U.S. Provisional Patent Application Ser. 60/486,373 filed Jul. 11, 2003. The disclosure of the provisional application is incorporated herein by reference.  
     
    
     BACKGROUND  
       [0002]     The disclosure relates generally to the field of collecting samples, especially liquid samples to be tested for the presence of an analyte, especially for drugs of abuse, antibodies, antigens and biological moieties such as steroids and glucose. In particular, the disclosure relates to improvements in collection device design that provide a simple, non-invasive, non-hazardous method of collecting samples from a subject or patient, especially liquid samples such as saliva, oral fluid and urine.  
       SUMMARY  
       [0003]     As a non-limiting introduction to the breath of the present disclosure, the present disclosure includes several general and useful aspects, including: 
        A device, for collecting, storing and applying a sample fluid to a test device, comprising a sample collector having an absorbent member, configured to collect a liquid sample; a sample container, wherein a portion of said container is flexible; an assembly fluidly configured to expel the expressed sample from the device; and a cap. The container of the device has flexible sides such that the sides of the container can be manually pressed inward, whereby, when the device is in the inverted position, pressure, applied manually to the container sides, causes expression of a portion of the sample from the assembly.     A method of collecting a fluid sample, using the device of the present invention, comprising providing the fluid sample; contacting the fluid sample with the sample collector; inserting the sample collector into the container; and closing the container.     A method of applying a fluid sample to a test device, using the device of the present invention, comprising uncapping the device, inverting the device over the sample application zone of a test car or cassette, squeezing the sides of the container of the device and thereby applying an aliquot of the sample to the sample application zone of the test card or cassette.     A kit, comprising at least one device of the present invention, packaged together with instructions for use of said device and optionally a test device.        
 
         [0008]     The present disclosure includes a variety of other useful aspects, which are detailed herein. These aspects of the disclosure can be achieved by using the articles of manufacture and compositions of matter described herein. To gain a full appreciation of the scope of the present disclosure, it will be further recognized that various aspects of the present devices and methods can be combined to make desirable embodiments. In addition, a variety of other aspects and embodiments of the present disclosure are described herein.  
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0009]     The foregoing summary, as well as the following detailed description may be better understood when read in conjunction with the accompanying drawings, which are incorporated in and form a part of the specification. The drawings serve to explain the principles of the invention and illustrate embodiments of the present invention that are preferred at the time the application was filed. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown.  
         [0010]     In the drawings:  
         [0011]      FIG. 1  depicts one embodiment of the present invention, in the closed position.  
         [0012]      FIG. 2  is a cross-sectional view of the device shown in  FIG. 1 , illustrating the internal structure of this embodiment of the present invention.  
         [0013]      FIG. 3  is an exploded view of this embodiment of the present invention, illustrating the various parts of this embodiment and how the parts fit together.  
         [0014]      FIG. 4  illustrates the dropper assembly  210  and absorbent member  280 , of the device shown in  FIG. 1 , in the configuration that they would be used to collect a sample.  
         [0015]      FIG. 5  illustrates the insertion of a collected sample into the bulb  120  of the device shown in  FIG. 1 .  
         [0016]      FIG. 6  is a cartoon depicting the removal of the cap  110  from the dropper assembly  210 , of the device shown in  FIG. 1 .  
         [0017]      FIG. 7  is a cartoon depicting application of an aliquot of the sample  710  to a test device  700 .  
         [0018]      FIG. 8  illustrates re-capping the device, of  FIG. 1 , and sealing the cap  110  with evidence tape  800 .  
     
    
     DETAILED DESCRIPTION  
       [0000]     Definitions  
         [0019]     Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Generally, the nomenclature used herein and the manufacture or laboratory procedures described below are well known and commonly employed in the art. Conventional methods are used for these procedures, such as those provided in the art and various general references. Terms of orientation such as “up” and “down” or “upper” or “lower” and the like refer to orientation of the parts during use of the device. Where a term is provided in the singular, the inventors also contemplate the plural of that term. The nomenclature used herein and the laboratory procedures described below are those well known and commonly employed in the art. As employed throughout the disclosure, the following terms, unless other wise indicated, shall be understood to have the following meanings:  
         [0020]     “Assaying” denotes testing for or detecting the presence of a substance or material, such as, but not limited to, a chemical, an organic compound, an inorganic compound, a metabolic product, a drug or a drug metabolite, an organism or a metabolite of such an organism, a nucleic acid, a protein, or a combination thereof. Optionally, assaying denotes measuring the amount of the substance or material. Assaying further denotes an immunological test, a chemical test, an enzymatic test, and the like.  
         [0021]     An “analysis device” or “assay device” is a device for analyzing a sample or specimen. An analysis device can be used to detect the presence and/or concentration of an analyte in a sample or specimen, or to determine the presence and/or numbers of one or more components of a sample or specimen, or to make a qualitative assessment of a sample or specimen. Analysis devices of the present disclosure include but are not limited to lateral flow detection devices such as assay strip devices, and columns.  
         [0022]     “Analyte” is the compound or composition to be measured that is capable of binding specifically to a ligand, receptor, or enzyme, usually an antibody or antigen such as a protein or drug, or a metabolite, the precise nature of antigenic and drug analytes together with numerous examples thereof are disclosed in U.S. Pat. No. 4,299,916 and U.S. Pat. No. 4,275,149. Analytes can include antibodies and receptors, including active fragments or fragments thereof. An analyte can include an analyte analogue, which is a derivative of an analyte, such as, for example, an analyte altered by chemical or biological methods, such as by the action of reactive chemicals, such as adulterants or enzymatic activity. An analyte may be a drug or drug metabolite, especially, but not limited to drugs of abuse, such as, for example amphetamines (speed), cocaine, THC (cannabis/pot), opiates (heroine), phencyclidine (PCP), methadone, benzodiazepines, methamphetamines (MDMA/ecstasy), phencyclidine (PCP/angle dust), tricyclic antidepressants and barbiturates.  
         [0023]     “Sample” or “specimen” may be used interchangeably. “Sample” or “specimen” denotes any material to be assayed for the presence and/or concentration of an analyte in a sample or specimen, or to determine the presence and/or numbers of one or more components of a sample or specimen, or to make a qualitative assessment of a sample or specimen. A sample can be the same as a specimen. Preferably, a sample is a fluid sample, preferably a liquid sample. Examples of liquid samples that may be assayed using an assay device of the present disclosure include bodily fluids including blood, serum, plasma, saliva, urine, ocular fluid, semen, and spinal fluid; water samples, such as samples of water from oceans, seas, lakes, rivers, and the like, or samples from home, municipal, or industrial water sources, runoff water or sewage samples; and food samples, such as milk or wine. Viscous liquid, semi-solid, or solid specimens may be used to create liquid solutions, eluates, suspensions, or extracts that can be samples. For example, throat or genital swabs may be suspended in a liquid solution to make a sample. Samples can include a combination of liquids, solids, gasses, or any combination thereof, as, for example a suspension of cells in a buffer or solution. Samples can comprise biological materials, such as cells, microbes, organelles, and biochemical complexes. Liquid samples can be made from solid, semisolid or highly viscous materials, such as soils, fecal matter, tissues, organs or other samples that are not fluid in nature. For example, these solid or semi-solid samples can be mixed with an appropriate solution, such as a buffer, such as a diluent or extraction buffer. The sample can be macerated, frozen and thawed, or otherwise extracted to form a fluid sample. Residual particulates can be removed or reduced using conventional methods, such as filtration or centrifugation.  
         [0024]     Other technical terms used herein have their ordinary meaning in the art that they are used, as exemplified by a variety of technical dictionaries.  
         [0000]     Sample Collection, Application and Storage Device  
         [0025]     There are many problems associated with collecting and using biological samples, especially samples from people. For example, the samples pose a biohazard, may be difficult to work with, or simply offensive. It may be difficult to collect a sample from a subject, while the act of sample collection poses another biohazard risk to the technician collecting the sample. In certain instances, samples may need to be collected from unwilling subjects who may resist the sample collection. In addition, certain settings, such as law enforcement, sample collection poses additional safety, storage and convenience problems. Because of the above problems, some industries, such as, for example, the drug of abuse testing industry, are turning away from samples, such as urine, to saliva and oral fluids. The present invention seeks to remedy the afore mentioned problems and satisfy the afore mentioned long felt needs. The present invention provides a convenient, simple and sanitary method of collecting a liquid sample, especially a viscous sample, such as saliva or oral fluid. The collected fluid can be stored for later use or used immediately for assaying for an analyte of interest. In addition, the unused portion of the sample that remains in the container may be sent to a confirmation laboratory, to confirm the results of the assay conducted by the technician.  
         [0026]     These embodiments of the invention, as well as others described herein, can be achieved by using the methods, articles of manufacture and compositions of matter described herein. To gain a full appreciation of the scope of the present invention, it will be further recognized that various embodiments of the present invention can be combined to make additional desirable embodiments of the invention.  
         [0027]     Referring now to the figures,  FIG. 1  illustrates one embodiment of the present device, a device  100  for collecting, storing and applying a liquid sample, such as, but not limited to, urine or blood.  FIG. 1  illustrates the exterior of the device in an unopened state, showing a cap  110  and a container  120 .  
         [0028]      FIG. 2  is a cross-section of the present device  100 , having a dropper assembly  210 , a cap  110  and a container  120 . The dropper assembly  210  further comprises a dropper nipple  220 , having a dropper orifice  222 , through which sample can be expelled from the present device  100 . The dropper assembly  210  further comprises a neck  240  and a skirt  250 . At least the dropper nipple  220  and a portion of the neck  240  are covered by the cap  110 . The cap  110  may have a dropper stopper  224  adapted to seal the dropper orifice  222 . Optionally, the neck  240  of the dropper assembly  210  may have threads  230 , which rotatably mate with cap threads  235  inside the cap  110  and thereby seal the dropper assembly  210 . Alternatively, the cap  110  may close the dropper assembly  210  with a snap-fit seal, or any other convenient method known in the art. Optionally, the cap  110  may be tethered to the dropper assembly  210  by a cord or hinge, or other well known means.  
         [0029]     Referring to  FIG. 2  and  FIG. 3 , the container  120  of the present device  100  further comprises as lip  260 , defining a mouth  310 , and optional shoulder  270 , a flexible side wall  272  and a bottom  276 . The lip  260  and optional shoulder  270  of the container  120  are adapted to be substantially rigid. However, the side wall  272  of the container  120  must be flexible, so as to allow the sides of the container  120  of the present device  100  to be pressed inward by the application of pressure, preferably manual pressure. The side walls  272  of the container  120  may be of any convenient shape known in the art commonly used for dropper squeeze bulbs, such as bulbous, cylindrical, lobular, spherical, pear-shaped, tear-drop or box-shaped.  
         [0030]     Applying pressure to the side wall  272  of the container  120  causes a liquid sample contained in the present device  100  to be expressed through the orifice  222  of the dropper assembly  210 . The dropper assembly  210 , especially the dropper nipple  220  and dropper orifice  222 , may be configured to expel the liquid sample as a stream, drops, droplets, a mist, or the like.  
         [0031]     Still referring to  FIGS. 2 and 3 , the dropper assembly  210  further comprises a skirt  250  that attaches to the lip  260  and seals the mouth  310  of the container  120 . The dropper assembly  210  may seal the container  120  by screwing onto or snapping onto the lip  260  of the container  120 , or by any other convenient means. In certain aspects of the present device  100 , the dropper assembly  210  may be tethered to the container  120  by a string or plastic strip or hinge member.  
         [0032]     The lip  260 , optional shoulder  270 , side wall  272  and bottom  276  of the container  120  define the lumen  274  of the container  120  of the present device  100 . The lumen  274  is adapted to receive an absorbent member  280 , for collecting the liquid sample, which will be discussed in more detail below.  
         [0033]     Optionally, the interior surfaces of the container  120  and dropper assembly  210  may be treated to reduce sample components binding or sticking to them. A variety of treatments are known and used in the art, depending upon the type of sample collected and the analytes of interest.  
         [0034]     As shown in  FIGS. 3-4 , the absorbent member  280  is attached to one end of a support member  282 , such as a wood or plastic stick and is configured to collect a liquid sample. In this regard, the absorbent member  280  can comprise any type of material that can absorb a liquid sample, such as a foam or a sponge. It should be appreciated that the size and shape of the support member  282  can vary, as long as the support member  282  is adapted to fit, along with the absorbent member  280 , into the interior of the present device  100  without blocking the expression of sample through the dropper orifice  222 . Optionally, the absorbent member  280  can be soaked in a solution designed to stimulate salivation by a subject providing a sample of saliva.  
         [0035]     At the second end of the support member  282  is one or more flanges  284 , which may be of various shapes. The flanges  284  are adapted to fit into the neck  240  of the dropper assembly  210  and to provide space, around the second end of the support member  282 , though which the sample can flow, such that the orifice  222  of the dropper assembly is fluidly connected to the lumen  274  of the container  120 . In certain aspects of the present device  100 , the flanges  284  are adapted to hold the support member  282  firmly or snuggly in the neck  240  of the dropper assembly  210 , such that the entire dropper assembly  210  can act as a handle for the absorbent member  280 . In other aspects of the present device  100 , the flanges  284  may be adapted to be easily removed from the dropper assembly  210 , such that the support member  282  can be used as a handle for manipulating the absorbent member  280 .  
         [0036]      FIG. 5  illustrates one step of the use of the present device  100 , that of inserting the absorbent member  280  into the lumen  274  of the container  120  and sealing the mouth  310  of the container  120  with the dropper assembly  210 . In this particular example, the dropper assembly  210  has a skirt  250 , which snaps snuggly into the mouth  310  of the container  120 . In certain embodiments of the present device  100 , the dropper assembly  210 , remounted on the container  120 , is adapted to seal the mouth  310  of the container  120  such that the dropper assembly  210  cannot be removed again or so that tampering with the device  100  can be detected.  
         [0037]     Alternative methods of closing the mouth  310  of the container  120  are also contemplated by the inventors. For example, the skirt  250  of the dropper assembly  210  and the lip  260  of the container  120  may have mating threads by which the present device  100  may be screwed closed. Prior to the step of returning the absorbent member  280  to the interior of the container  120 , the absorbent member  280  is used to collect a liquid sample. For example, the absorbent member  280  is placed in a subject&#39;s mouth, until saturated with saliva. In another example, the absorbent member  280  is soaked in collected urine, or even held in the urine stream of a donor or patient.  
         [0038]      FIG. 6  illustrates removing the cap  110  from the dropper assembly  210 . In this particular example, the cap  110  is removed by un-screwing. The cap  110  may be attached to the dropper assembly by other convenient methods, such as snapping onto the neck  240  of the dropper assembly  210 .  
         [0039]      FIG. 7  illustrates another embodiment of the present device  100 , showing one way that an aliquot of a collected sample can be expressed from the dropper assembly  210 . Preferably, the absorbent member  280  is left inside the lumen  274  of the container  120 . With the dropper assembly  210  in place, sealing the mouth  310  of the container  120 , the un-capped device is inverted and the side walls  272  of the container are squeezed. This causes a portion of the collected sample to be expressed from the absorbent member  280 . Subsequently, the expressed sample flows into the dropper assembly  210 , thought the dropper nipple  220  and out the dropper orifice  222  (see  710 ). In certain embodiments, the expressed sample flows out of the orifice  222  in a drop-wise manner. However, the dropper assembly  210  can be adapted for the sample to be expelled from the orifice  222  as a stream, droplets, mist or the like.  
         [0040]     As illustrated in  FIG. 7 , the present device  100  may be used to apply an aliquot of sample  710  to the application area or well  720  of a test device  700 . After incubation of the test device  700 , the test results might be observed in a results zone  730 . A variety of test devices, commonly used today, could be used in conjunction with the present device  100 . For example, rapid immunoassays or chemical assays, which test for the presence of an analyte and are increasingly used in clinics, doctor&#39;s offices, law enforcement settings and employment settings, might be used. A variety of analytes could be tested for, in the sample collected with the present device  100 . For example, a sample, collected with the present device  100 , might be tested for drugs of abuse, metabolites, etiological agents or the like.  
         [0041]      FIG. 8  illustrates the final step of using the present device  100 . After expressing an aliquot of sample  710 , the device  110  is returned to the up-right position and re-capped. The cap  110  is then sealed with evidentiary tape  800 , to prevent tampering with the sample.  
         [0000]     Specimen  
         [0042]     Any type of liquid specimen may be used with the present device, including liquid specimens of the nature and character as described above in the definition portion of this disclosure. Alternatively, the sample applied to the test strip of the present device may be derived from other types of specimens dissolved in an appropriate liquid, such as a buffer or water. For example, the specimen may be composed of fine powdery materials such as talc, carbon black, pharmaceutical preparations, or gases such as argon or methane. Additional specimens can include atmospheric specimens that can be assayed for particulates or radioactive isotopes such as radon.  
         [0043]     In an alternative embodiment of the present device the specimen to be tested is a biological specimen. Such biological specimens include but are not limited to a sample from a subject such as an animal or a human. A sample from a subject can be of any appropriate type, such as a sample of fluid, tissue, organ or a combination thereof. The biological specimen can also be a sample of other biological material, such as plants, bacteria, cell or tissue cultures, viruses and prions, or food, including food such as material derived from plants or animals or combinations thereof. The sample can be processed prior to introduction into the assay device. In the alternative, a sample and reagent can be combined within a specimen collection container. Such reagents can be used to process a sample, such as digesting solid samples with appropriate reagents such as chemicals, such as acids or bases, or with enzymes such as proteases. Other reagents can be used to extract analytes from a sample, such as extraction of antigens from biological entities, such as antigens from etiological agents such as bacteria, parasites, viruses or prions such as known in the art.  
         [0044]     The sample collected by the present device  100  is any material to be assayed for the presence and/or concentration of an analyte in a sample or specimen that can be absorbed by the absorbent member  280 . Preferably, the sample is a fluid sample, preferably a liquid sample. Examples of liquid samples that may be collected using a device of the present invention include bodily fluids including blood, serum, plasma, saliva, urine, ocular fluid, semen, and spinal fluid; water samples, such as samples of water from oceans, seas, lakes, rivers, and the like, or samples from home, municipal, or industrial water sources, runoff water or sewage samples; and food samples, such as milk or wine. Viscous liquid, semi-solid, or solid specimens may be used to create liquid solutions, eluates, suspensions, or extracts that can be samples. For example, throat or genital swabs may be suspended in a liquid solution to make a sample. Samples can include a combination of liquids, solids, gasses, or any combination thereof, as, for example a suspension of cells in a buffer or solution.  
         [0045]     Samples can comprise biological materials, such as cells, microbes, organelles, and biochemical complexes. Liquid samples can be made from solid, semisolid or highly viscous materials, such as soils, fecal matter, tissues, organs, biological fluids or other samples that are not fluid in nature. For example, these solid or semi-solid samples can be mixed with an appropriate solution, such as a buffer, such as a diluent or extraction buffer. The sample can be macerated, frozen and thawed, or otherwise extracted to form a fluid sample. Residual particulates can be removed or reduced using conventional methods, such as filtration or centrifugation.  
         [0046]     The present invention is particularly useful for the collection of viscous samples, such as oral fluids and saliva. The absorbent member  280  can be configured to fit comfortably in to the mouth of a subject, such as a human. The absorbent member  280  may additionally be constructed of a sponge or foam designed to be chewed. In one aspect of the present invention, the absorbent member  280  is soaked in a solution to stimulate salivation. When the absorbent member  280  is placed in a subject&#39;s mouth, the subject can suck and chew the absorbent member  280  until the absorbent member  280  is filled with sample.  
         [0047]     In another setting, the present invention may be used to conveniently collect urine from a subject without the use of a cup. For example, the absorbent member  280  may be held in the urine stream of a pet, such as a dog or cat, or a young child.  
         [0000]     Methods of Use  
         [0048]     The present disclosure contemplates methods of use of the present device  100  described supra. One embodiment of the present method for collecting a sample comprises the steps of opening the device  110  and placing the absorbent member  280  in a liquid sample. For example, the absorbent member  280  can be placed in a patient&#39;s mouth until the absorbent member  280  has become saturated with saliva. Next, the absorbent member  280  is inserted into the lumen  274  of the container  120  until the dropper assembly  210  is mounted on the lip  260  of the container  120 . The device and sample there in could be placed in storage or, alternatively, the sample may be tested for the presence of an analyte. To test for the presence of an analyte, an appropriate test device is obtained and placed on the bench top or table. The present device  100 , containing the sample, is un-capped and inverted over the sample application zone of the test device. Next, the sides of the container  120  and thus the absorbent member  280  contained within the container  120  is squeezed. The manual pressure on the sides of the container  120  expresses some of the collected sample from the absorbent member  280 . The expressed sample flow through the flanges  284 , the dropper neck  240  and the dropper nipple  220 , and out through the dropper orifice  222 . The sample is expelled from the dropper orifice  222  into the sample application zone of the test device. After application of the sample, the present device  100  is returned to the up-right position and re-capped. The cap  110  is preferably sealed onto the dropper assembly with evidence tape  800 . The present device  100  and the sample contained therein are now ready for storage or to be shipped to another site for additional tests.  
         [0000]     Kits  
         [0049]     Another embodiment of the present device  100  is a kit, for collecting a liquid sample, packaged together with instructions for use. In certain embodiments of the present device  100 , the device  100  may be packaged together with instructions and testing device for the presence of an analyte, such as drugs of abuse or metabolites.  
         [0000]     Examples of Use  
         [0000]     Drug Testing Prior to Employment  
         [0050]     A manufacturing company has conditionally hired a new engineer. Prior to the first day of work, the engineer goes to a drug testing laboratory, where he is tested for illegal drugs. At the drug testing laboratory, the engineer chews the absorbent member of the present invention and thus produces a saliva sample for the technician. The engineer then leaves the facility. The technician replaces the absorbent member back into the container of the device. She then obtains a drug of abuse test cassette and places it on the bench top. Next, the technician removes the cap from the device of the present invention, inverts the device and applies (by squeezing the sides of the bulb) three drops of the engineer&#39;s donated saliva into each sample application well of the test cassette. She sets a timer for five minutes and allows the test device to incubate on the bench top. At the conclusion of the incubation, the technician reads and records the test and control (positive and negative) results for each drug assayed. When she is finished, the technician seals the cap onto the device with evidence tape and sends the device, with the contained saliva, to a confirmation testing laboratory.  
         [0000]     Pet Dog Urine Analysis for Bladder Infection:  
         [0051]     A pet owner takes her dog to the vet because the house-trained dog is urinating an excessive number of times and in the house. The veterinarian suspects that the dog may have a bladder infection. To determine if this is true, the vet takes the dog outside. When the dog urinates, the vet holds the absorbent member of the present invention in the urine stream. The vet inserts the absorbent member into the bulb of the device. To test for a blabber infection, the vet expels a few drops of the urine onto pH paper, which indicates that the dog&#39;s urine is in the alkaline range found in dogs with bladder infections. To confirm his findings, the vet expresses a drop of urine onto a slide and examines the urine under a microscope. The vet observes white blood cells in the urine, confirming that the dog has a bladder infection. The vet prescribes a course of antibiotics for the dog, which subsequently recovers from the bladder infection.