MXPA06007296A - Self-contained swab-based diagnostic systems - Google Patents

Abstract

A diagnostic test unit is provided. The test unit comprises a stem having a first end and a second end, the stem defining at least one flow channel extending between the first end and the second end. A swab is disposed at the first end of the stem, the swab being configured to collect a test sample derived from a biological source that is suspected of containing an analyte. The test unit also comprises a fluid chamber configured to contain a fluid, wherein the fluid chamber is in fluid communication with the swab via the flow channel. The test unit also comprises a rupturable seal that inhibits leakage of the fluid from the fluid chamber prior to use, and an assay for detecting the presence or absence of the analyte. The assay is in fluid communication with the swab, the flow channel, and the fluid chamber.

Description

DIAGNOSTIC SYSTEMS BASED ON HISOPO AUTO-CONTENT Background of the Invention Medical cotton swabs are commonly used to collect biological specimens from patients. Such medical cotton swabs usually include a fibrous tip at one end of a rod or an elongated stick. Once the sample is collected, it can be transferred from the tip to a test medium for the execution of an assay to determine the presence or absence of an analyte of interest. Some systems, known as "all-in-one" cotton swab systems, have been developed to provide both reagents for the immunoassay and the cotton swab in a simple, self-contained device. For example, US Pat. No. 6,248,294 issued to Nason describes a substantially self-contained diagnostic test unit for collecting and analyzing a biological specimen. The test unit has a tubular box that defines a specimen chamber to receive a biological specimen collected from a cotton swab. A reagent supply cap is removably mounted on the box to allow the specimen to be placed in the specimen chamber, at which time the supply cap can be manipulated to deliver one or more selected chemical reagents to the specimen chamber to contact the specimen collected. A diagnostic strip assembly is also mounted on the case and includes a diagnostic strip that extends along the case, substantially in parallel relative to the specimen chamber. Transfer means are provided to move the mixed specimen and reagent from the specimen chamber to contact one end of the diagnostic strip and for the drained flow therethrough in contact with one or more additional reagents selected to yield to a visual test result.

However, a problem with conventional all-in-one systems, as described above, is that the fluid contained within the apparatus often drips from the apparatus before use. Additionally, the method for using such devices typically involves several complicated steps that can decrease the real-time efficiency of the device in detecting the presence or absence of the analyte. As such there is currently a need for a device based on cotton swab, self-content is effective in detecting the presence of an analyte in a simple manner.

Synthesis of the Invention According to an embodiment of the present invention, a diagnostic test unit is described. The test unit comprises a rod having a first end and a second end, the rod defining at least one flow channel extending between the first end and the second end. A cotton swab is disposed at the first end of the rod, the cotton swab is configured to collect a test sample derived from a biological supply that is suspected of containing an analyte. The test unit also comprises a fluid chamber configured to contain a fluid, wherein the fluid chamber is in fluid communication with the cotton swab via a flow channel. The test unit also comprises a rupturable seal that inhibits dripping fluid from the fluid chamber prior to use, and an assay for detecting the presence or absence of the analyte in the test sample. The assay is in fluid communication with the cotton swab, the flow channel, and the fluid chamber.

According to another embodiment of the present invention, a method for detecting the presence or absence of an analyte within a test sample derived from a biological supply is disclosed. The method includes: i) provide a diagnostic test unit, the test unit comprises: a) a rod having a first end and a second end, the rod defines at least one flow channel that extends between the first end and the second end; b) a cotton swab placed on the first end of the rod; c) a flow chamber configured to contain a fluid, wherein the fluid chamber is in fluid communication with the cotton swab via the flow channel; d) a seal that inhibits dripping fluid from the fluid chamber before use; Y e) an assay for detecting the presence or absence of the analyte in the test sample, the assay is in fluid communication with the cotton swab, the flow channel, and the fluid chamber; ii) collect the test sample on the cotton swab; Y iii) break the seal to release the fluid from the fluid chamber, where the fluid is mixed with the test sample on the cotton swab and then contact the assay.

Other features and aspects of the present invention are described in more detail below.

Brief Description of the Drawings A complete and capable description of the present invention, which includes the best mode thereof, addressed to one of ordinary skill in the art, is disclosed more particularly in the remainder of the application, which refers to the figures appended hereto. which: Figure 1 illustrates an embodiment of a diagnostic test unit of the present invention, in which Figure 1A is a perspective view of the test unit and Figure IB is a cross-sectional view of the test unit; Figure 2 illustrates another embodiment of a diagnostic test unit of the present invention, in which Figure 2A is a perspective view of the diagnostic test unit with the first and second components shown separately and Figure 2B is a cross-sectional view of the test unit with the first component shown inserted into the second component; Figure 3 illustrates another embodiment of a diagnostic test unit of the present invention, in which in Figure 3A is a perspective view of the diagnostic test unit in the first and second components shown separately and the Figure 3B is a cross-sectional view of the test unit with the first component shown inserted into the second component; Figure 4 illustrates another embodiment of a diagnostic test unit of the present invention, in which Figure 4A is a perspective view of the diagnostic test unit with the first and second components shown separately and the figure 4B is a cross-sectional view of the test unit with the first and second components shown inserted in a reader; Y Figure 5 is a perspective view of an assay that can be used in an embodiment of the present invention.

The repeated use of reference characters in the present application and in the drawings is intended to represent the same or similar elements or features of the invention.

Detailed Description of Representative Incorporations Definitions As used herein, the term "analyte" generally refers to a substance to be detected. For example, the analytes may include antigenic substances, haptens, antibodies, and combinations thereof. Those of analytes include, but are not limited to toxins, organic compounds, proteins, peptides, microorganisms, amino acids, nucleic acids, hormones, steroids, vitamins, drugs (which include those administered for therapeutic purposes as well as those administered for illicit purposes), drug intermediaries or by-products, bacteria, virus particles as well as metabolites of or antibodies to any of the above instances. Specific examples of some analyte include ferritin; the creatinine kinase MB (CK-MB); digoxin; phenytoin; phenobarbital; carbamzepine; vancomycin; gentamicin; theophylline; valproic acid; quinidine; the luteinizing hormone (LH); follicle stimulating hormone (FSH); the estradiolo; progesterone; the C-reactive protein; the lipocalinas; IgE antibodies; the cytosines; vitamin B2 micro-globulin; glycated hemoglobin (Gly. Hb); cortisol; the digitoxin; N-acetylprocainamide (NAPA); procainamide; antibodies to rubella, such as rubella-IgC and rubella IgM; antibodies to toxoplasmosis; such as toxoplasmosis IgC (Toxo-IgC) and toxoplasmosis IgM (Toxo-IgM); testosterone; the salicylates; acetaminophen; the surface antigen of hepatitis B virus (HBsAg); antibodies to the hepatitis B core antigen, such as the anti-hepatitis B core antigen IgC e 'IgM (Anti-HBC); the human immunodeficiency virus 1 and 2 (HIV 1 and 2); the human T-cell 1 and 2 leukemia virus (HTLV); the hepatitis B e antigen (HBeAg); Antibodies to the hepatitis B e antigen (Anti-HBe); the influenza virus; the hormone that stimulates the thyroid (TSH); thyroxine (T4); total triiodothyronine (Total T3); free triiodothyronine (Free T3); the carcinoembryonic antigen (CEA); lipoproteins, cholesterol, and triglycerides; and alpha fetoprotein (AFP). Drugs of abuse and controlled substances include, but are not intended to be limited to, amphetamines; the methamphetamines; barbiturates, such as amobarbital, secobarbital, pentobarbital, phenobarbital, and barbital; benzodiazepines, such as librium and valium; cannabinoids, such as has is and marijuana; cocaine; fentanyl; the LSD; methaqualone; opiates, such as heroin, morphine, codeine, hydromorphone, hydrocodone, methadone, oxycodone, oxymorphone and opium; phencyclidine; and propoxyhene. Other potential analytes can be described in the patents of the United States of America Nos. 6, 436, 651 granted to Everhart and others and in 4,366,241 granted to Tom and others.

As used herein, the term "test sample" generally refers to a biological material suspected of containing the analyte. The test sample can be derived from any biological supply, such as a physiological fluid, which includes blood, intestinal fluid, saliva, eye lens fluid, spinal cord fluid, sweat, urine, milk, the ascites fluid, the mucosa, the synovial fluid, the peritoneal fluid, the vaginal fluid, the amniotic fluid, and so on. In addition to physiological fluids, other liquid samples may be used such as water, food products, and so on, for the execution of environmental or food production tests. In addition, a solid material suspected of containing the analyte can be used as the test sample. The test sample can be used directly as it is of the biological supply or following a previous treatment to modify the character of the sample. For example, such pretreatment may include preparing blood plasma, viscous fluids that are diluted, and the like. Previous treatment methods can also involve filtration, precipitation, dilution, distillation, mixing, concentration, inactivation of interfering components, addition of reagents, etc. Furthermore, it can also be beneficial to modify a solid test sample to form a liquid medium or to release the analyte.

Detailed description Reference may now be made in detail to several embodiments of the invention, one or more examples of which are disclosed below. Each example is provided by way of explanation of the invention, not limitation of the invention. In fact, it may be apparent to those skilled in the art that various modifications and variations may be made in the present invention without departing from the scope or spirit of the invention. For example, the features illustrated or described as part of an embodiment may be used in another embodiment to yield to still further incorporation. Therefore, it is the intention that the present invention cover such modifications and variations as come within the scope of the appended claims and their equivalents.

In general, the present invention is directed to a diagnostic test unit that is accurate, reliable, efficient, and easy to use. The test unit contains a cotton swab to collect a test sample suspected of containing an analyte of interest. As is well known in the art, the cotton swab can be formed from a variety of different absorbent materials, such as cotton, jersey, pulp, etc., and can possess any desired shape and / or size. The cotton swab is disposed at one end of a rod, which contains one or more flow channels. A fluid is contained within a fluid chamber that is in fluid communication with the flow channel (s). For example, the fluid may be a buffer fluid, such as a phosphate buffered saline (PBS) (e.g., pH 7.2) or 2- (N-morpholino) ethane sulfonic acid (MES) (e.g. 5.3). Other types of fluid use of additives for the fluid may include detergents, salts, lysis agents (such as for example for the detection of microbes, for example, streptococcus bacteria or yeasts), blocking agents (e.g. bovine serum albumin), other proteins, and so on. Still other potential materials that may be present within the fluid include labeled microparticles, detection probes, dyes, electrochemically active agents (e.g., redox mediators), or other reagents used to create a signal for detection. The volume of fluid contained within the fluid chamber is generally determined by the amount of reagent required for one. sample of particular test. Example fluid volumes are from about 50 to about 1000 microliters of fluid, with a typical amount that is from about 100 to about 200 microliters.

In accordance with one aspect of the present invention, a user can in a controlled manner release the fluid from the fluid chamber after the test sample is collected on the cotton swab. Several mechanisms can be employed to impart such selective control over fluid release. For example, a seal may be used that is relatively flexible to the diffusion of the fluid therethrough. The seal can be formed from a variety of different materials, such as non-porous films, metal stamps (for example, aluminum foil), etc. Some appropriate materials used in the manufacture of films to form the stamp can be the thermoplastic polymers, such as polyolefins (for example, polyethylene, polypropylene, etc.), which include homopolymers, copolymers, terpolymers and mixtures thereof; ethylene vinyl acetate; the ethylene acrylate of ethylene; ethylene acrylic acid; the ethylene methyl acrylate; the normal ethylene butyl acrylate; the polyurethane; the poly (ether ester); the poly (amide-ether) block copolymers; and the similar ones. Other suitable materials may include non-thermoplastic materials, silicone-based materials, other elastomeric materials, and so forth. In some embodiments, it is desired to minimize the thickness of the seal so that a user can easily break it. In such instances, the thickness of the seal may be less than about 0.05"inches, in some embodiments between about 0.0003 inches to about 0.01 inches, and in some additions, between about 0.0007 inches to about 0.02 inches.

Therefore, before use, the seal can retain fluid within the fluid chamber and inhibit leakage. To release the fluid and "start the diagnostic test, a user can simply break the seal." In some embodiments, once released, the fluid initially contacts the cotton swab, mixes with the test sample, and then flows into the sample. (the) flow channel (s) Desirably, the flow channel (s) is (are) of sufficient length to allow an increased amount of time for the test sample for the fluid to be mixed before contacting In other embodiments, the fluid initially flows into the flow channel (s) and then contacts the cotton swab and mixes with the test sample, in any case, after contacting the cotton swab and flowing into the flow channel (s), and the resulting test / fluid mixture sample can then contact an assay to detect the presence or absence of an analyte.

One or more of the components of the diagnostic test unit may be disposable or discarded after use. This reduces the possibility of contamination after the execution of multiple tests, and therefore increases the accuracy. However, although one or more components of the diagnostic test unit may be disposable, the test unit may also include components to be reused. For example, the disposable test unit may include a reader that quantitatively or qualitatively detects the presence of an analyte. As is well known in the art, such a reader can use any of a variety of detection techniques. For example, the reader can use optical detection techniques (for example, fluorescence, reflectance, densitometry, phosphorescence, diffraction, etc.); electrochemical detection techniques, and so on. In one embodiment, the reflectance reader can be used to detect the presence of probes that exhibit a visual color (eg, dyed latex microparticles). A suitable reflectance reader is described, for example, in the published United States of America patent application No. 2003/0119202 issued to Kaylor et al., which is incorporated herein in its entirety by reference to the same for all purposes. The reader can include a variety of optional components that benefit a user. For example, the reader may include a monitor (e.g., an LED monitor (light emitting diode)) to provide digital or analogous results to a user. The reader may also include one or more input devices (eg, buttons or keys) that can be used, for example, to facilitate data storage, allow connections from a computer or the Internet, etc. If desired, The reading can also function as a retainer for other components of the test unit.

Regardless of the specific manner in which it is formed, a significant benefit of the diagnostic test unit of the present invention is that most, if not all, components of the diagnostic unit (e.g., cotton swab) , the rod, the flow channel (s), the breakable seal, the test, etc.), can be included within a single unit, for example, these are "self-contained". Moreover, the self-contained test unit is also multifunctional. For example, the test unit is capable of accomplishing multiple tasks, such as blood filtration, cell lysis, transporting labels such as conjugate particles for testing, etc. In addition, the rod itself is multifunctional in that it is a support for the cotton swab while also providing fluid / reagent transport to the cotton swab. Such a multifunctional, self-contained test unit provides a number of benefits to a user, which. they include simplicity, convenience, low costs, improved security, and so on.

Of course, the present invention provides numerous other benefits equally. For example, the assay and / or reagents for the assay can be pre-supplied with the diagnostic test unit to reduce the possibility of contamination before use, thereby improving accuracy and reliability. Another benefit of the present invention is that the cotton swab can function as a filter of contaminants from the test sample and / or the fluid before contacting the assay, thereby improving the accuracy and reliability of the diagnostic test.

Several embodiments of the diagnostic test unit of the present invention can now be described in greater detail. It should be understood, however, that the embodiments described below are merely exemplary, and that any appropriate configuration of the diagnostic test unit may also be used in the present invention. In this regard, referring to Figure 1, an incorporation of a cotton swab diagnostic test unit 10 that can be formed in accordance with the present invention can now be described in greater detail. As shown, the diagnostic test unit 10 includes a rod 22 having a first end 31 and a second end 33. A cotton swab 24 is retained at the first end 31 of the rod 22. A base portion 40 is also arranged at the second end 33 of the rod 22. The base portion 40 may be integrally formed with or separate from the rod 22. For example, in one embodiment, the rod 22 is removable from the base part 40 by a user. In this manner, a user can remove the rod 22 and the cotton swab 24 when desired to collect a test sample, and then reposition the rod 22 on the base portion 40 when desired to initiate the diagnostic test. The rod 22 and the base part 40 can be made from any of a variety of materials, such as molded or blown plastic.

The rod 22 and the base part 40 can have a shape to allow easy manual handling during use. For example, the rod 22 can be generally elongated and tubular, while the base part 40 has a substantially conical shape. As will be described in more detail below, the generally elongated shape of the rod 22 can facilitate mixing of the test sample and a fluid, and also facilitate mixing with the cotton swab 24. Additionally, the "curved" shape of the Base portion 40 may facilitate grasping of diagnostic test unit 10 by a user. It should be understood that the shapes and / or sizes described above are purely exemplary, and that virtually any shape and / or size can be used to form the rod 22 and the base part 40. For example, other examples of shapes Suitable for the rod 22 and / or the base part 40 include, but are not limited to, the square, the rectangular, the triangular, the circular, the oval, the trapezoidal,. the elliptical, the parabolic, the irregular shapes, and so on.

The base part 40 defines a chamber 70 from which a fluid is supplied to be mixed with a test sample collected on the cotton swab 24. The chamber 70 is in fluid communication with the cotton swab 24 disposed on the In the illustrated embodiment, for example, the rod 22 defines a first flow channel 50 that extends between the first end 31 and the second end 33 so that the fluid is able to flow from the base portion 40 in the first channel 50, and then to the cotton swab 24, as exemplified by the directional arrows shown in. Figure IB. The size and / or surface energy of the first channel 50 can be selected to facilitate mixing between the test sample and the fluid, so that the capillary forces facilitate the flow of fluid from the base portion 40 to the cotton swab. 24. For example, the length of the first channel 50 may be greater than about 1 centimeter, in some embodiments from about 1 to about 15 centimeters, and in some embodiments, from about 5 to about 10 centimeters. The width (or diameter) of the first channel 50 may be substantially constant, or alternatively may vary as a function of length. For example, in the embodiment illustrated in Figure 1, the width of the first channel 50 gradually decreases from the first end 31 to the second end 33. In spite of everything, the width of at least a portion of the first aesthetically smaller channel 50 of around 3 millimeters, in some incorporations from around 0.01 to around 3 millimeters, and in some incorporations from around 0.05 to 1 millimeter.

After contacting the cotton swab 24, the fluid is mixed with the test sample collected by the user and then flows through a second flow channel 52, where it contacts an assay 60 (FIG. IB). The second channel 52 may have the same or different size and shape as the first channel 50. Of course, a small part of the fluid and the test sample may also flow back through the first channel 50 without contacting the test 60. Without attempting to be limited by the theory, however, it is believed that the capillary forces imparted by the dimensions of the first channel 50 may ultimately force more, if not all, of the mixture, through the second channel 52. It should be understood that the use of two channels is merely exemplary, and that any number of channels can be used in the present invention. For example, as will be described in more detail below, a single flow channel can be used in some embodiments of the present invention.

As shown, a seal 46 may also be positioned between the first channel 50 and the fluid within the chamber 70 that is relatively flexible to the diffusion of the fluid therethrough. To release fluid from the chamber 70 and the first channel 50, the user can, in one embodiment, press a button 44 or any other activation device to break the seal 46 and release the fluid. Specifically, the button 44 is connected to a movable pin 48 which is placed in contact with the seal 46 upon the pressing of the button 44. Therefore, when depressed, the bolt 48 moves in a vertical direction until it contacts the seal 46. and is inserted through it. Once seal 46 is broken, fluid is released from chamber 70.

Referring to Figure 2, another embodiment of a diagnostic test unit based on a cotton swab 100 that can be formed in accordance with the present invention is shown. In this embodiment, the diagnostic test unit 100 includes two-components, e.g., a first component 102 and a second component 104. Similar to the embodiment shown in Figure 1, the first component 102 includes a rod 122 having a first end 131 and a second end 133. A cotton swab 124 is retained at the first end "131 of the stem 122. Additionally, a base part 140 is also disposed at the second end 133 of the rod 122. The second component 104 has an outer wall 180 defining a fluid chamber 170 within which a fluid is retained. Before use, a seal 146 inhibits dripping of the fluid from the chamber 170. Once the test sample is collected, the first component 102 can be inserted into the second component 104 to initiate the diagnostic test. Specifically, a user may insert the cotton swab 124 into an opening 147 of the second component 104 until the cotton swab 124 contacts the seal 146 and causes it to break. Alternatively, the seal 146 can be broken in several other ways, such as by tightening the outer wall 180 of the second component 104 with sufficient force to cause the seal 146 to break. If desired, several seal mechanisms can be used to ensure that a substantial amount of fluid did not drip from the opening 147 after insertion of the cotton swab 124. For example, a hydraulic seal, such as o-rings, rings- t, rings ~ d, v-rings, etc., can be used. As is well known in the art, such hydraulic seals can provide a seal fit between the outer surface of the rod 122 and the interior surface of the opening 147.

After breaking the seal 146, the fluid is released from the chamber 170 and contacts the cotton swab 124. The fluid then flows through the cotton swab 124 and into a flow channel 150, where it contacts an assay 60 to detect the presence of an analyte within the test sample. The dimensions of the flow channel 150 can, as previously described, be sufficient to facilitate mixing of the test sample and the fluid, as well as to promote capillary flow. In addition to the capillary forces associated with the dimensions of the channel 150, an absorbent pad 174 contained within the base portion 140 can also assist in promoting capillary action and fluid flow a. through the channel 150. For example, the absorbent pad 170 can be formed from a cellulosic base material.

Another embodiment is shown in Figure 4 a diagnostic test unit 300 can be used in the present invention. The embodiment shown in Figure 4 operates in a manner similar to Figure 2, without the use of the base part 140 (Figure 2). Specifically, the diagnostic test unit 300 includes two components, e.g., a first component 302 and a second component 304. Similar to the embodiment shown in Figure 1, the first component 302 includes a shank 322 having a first end 331 and a second end 333. A cotton swab 324 is retained at the first end 331 of the stem 322. The second component 304 has an outer wall 380 defining a fluid chamber 370 in which a fluid is retained. Before use, a seal 346 inhibits dripping of the fluid from chamber 370, once the test sample is collected, the first component 302 can be inserted into the second component 304 to initiate the test diagnosis. Specifically, a user can insert the cotton swab 324 into the opening 347 of the second component 304 until the cotton swab 324 contacts the seal 346 and causes it to break. After breaking the seal 346, the fluid is released from the chamber 370 and contacts the cotton swab 324. The fluid then flows through the cotton swab and into a flow channel 350, where it contacts an assay 60 to detect the presence of an analyte within the test sample.

If desired, both the first component 302 and the second component 304 can be placed in a reader 390 to analyze the test results. As shown in Figure 4B, the end 333 of the shank 322 can be inserted through an opening 391 of the reading 390. The first component 302 can be placed on the second component 304, as previously described, which is before or after the insertion of the rod 322 in the reader 390. The reader 390 may include a variety of optional components that benefit a user. For example, the reader 390 may include a monitor 395 (e.g., LED monitor (light emitting diode) to provide digital or analogous results to a user. The reader 390 may also include one or more buttons 393 that can be used, for example. example, to facilitate the storage of data, to allow connections to a computer or the Internet, etc. In some cases, the reader 390 can be reused for other diagnostic tests, while the remaining components of the unit Moreover, in some embodiments, the test 60 can also be contained within the reader 390. This can provide a number of benefits, such as allowing the test 60 to be washed with a liquid supplied by a separate rinse reservoir (not shown) present inside the reader 390.

Referring to Figure 3, yet another incorporation of a cotton swab diagnostic test unit 200 that can be formed in accordance with the present invention is shown. Similar to the embodiment shown in figure 2, the diagnostic test unit 200 includes two components, for example, a first component 202 and a second component 204. As previously described, the first component 202 includes a rod 222 having a first end 231 and a second end 233. A cotton swab 224 is retained on the first end 231 of the rod 222. In this embodiment, a syringe 240 is also disposed at the second end 233 of the rod 222. The syringe 240 includes a box 245 defining an opening 249 through which is inserted a movable shaft 242. The box 245 also defines the fluid chamber 270 within which the fluid is retained. Prior to collection of the test sample, the fluid remains sealed within the chamber 270 between a base 244 of the shaft 242 and a seal 246. As previously described in greater detail, the seal 246 is impermeable to liquid and inhibits dripping premature of the fluid in a channel 250 of the rod 222.

As indicated by the directional arrows of Figure 3A, a user can insert the cotton swab 224 in a detection chamber 247 defined by an outer wall 290 of the second component 204 after collecting the test sample. The size and shape of the detection chamber 247 can be selected to correspond to the size and shape of the cotton swab 224 and / or of the rod 2-22. If desired, a rim 271 may be positioned within the sensing chamber 247 to prevent over-insertion of the shaft 222. Primarily, the rim 271 prevents the cotton swab 224 from being placed so far into the bottom of the test 60 of the test of diagnosis so as to be ineffective. Instead of the edge 271, several other stop mechanisms may also be used. For example, in one embodiment, the width (or the diameter) of a portion of the shaft 222 can simply be larger than the width (or diameter) of the opening 247, thereby inhibiting over-insertion. As previously mentioned, the hydraulic seal mechanisms can also be used to inhibit the dripping of fluid through the detection chamber 247 after the insertion of the cotton swab 224.

Upon insertion of the cotton swab 224 into the detection chamber 247, a user can reactivate the diagnostic test by depressing the shaft 242 as shown by the directional arrow of Figure 3B. The tightening of the shaft 242 causes the pressure of the fluid within the fluid chamber 270 to increase until the seal 246 breaks. The rupture of the seal 246 allows the fluid to flow from the chamber 270 into a flow channel 250 within the rod 222. The fluid flows through the channel 250 and mixes with the test sample present in the cotton swab 224. After , the fluid mixture and the test sample can contract a test 60 to detect the presence of an analyte within the test sample.

For illustrative purposes only, several examples of the tests 60 of FIGS. 1 to 4 can now be described in greater detail. It should be understood, however, that other tests are also contemplated by the present invention. In fact, the present invention is not limited to any particular assay configuration. In this regard, referring to Figure 5, an embodiment of an assay 60 is illustrated to be a membrane-based, lateral-flow immunoassay. Immunoassays use mechanisms of the immune systems, where the antibodies are produced in response to the presence of antigens that are pathogenic or foreign to the organisms. These antibodies and antigens, for example, immunoreactive ones, are capable of binding to each other, thus causing a highly specific reaction mechanism that can be used to determine the presence or concentration of that particular antigen in a sample of proof.

In the illustrated embodiment, the test 60 contains a porous membrane 63 that can be made from any of a variety of materials through which a fluid is capable of passing. For example, the materials used to form the porous membrane 63 can include, but are not limited to natural, synthetic, or naturally occurring materials that are synthetically modified, such as polysaccharides (e.g., cellulose materials such such as paper and cellulose derivatives, such as cellulose acetate and nitrocellulose); the polyether sulfone; the polyethylene; the nylon; polyvinylidene fluoride (PVDF); The polyester; polypropylene; the silica; inorganic materials, such as deactivated alumina, diatomaceous earth, MgSO4, and other finely divided inorganic material uniformly dispersed in a porous polymer binder, with polymers such as vinyl chloride, vinyl chloride-propylene copolymer , the vinyl chloride-vinyl acetate copolymer; the fabric, both occur naturally (for example, cotton) and synthetic (example, nylon and rayon); porous gels, such as silica gel, agarose, dextran, and gelatin; polymeric films, such as polyacrylamide; and the similar ones. In particular, the porous membrane 463 is formed from nitrocellulose and / or polyether sulfone materials It should be understood that the term "nitrocellulose" refers to the nitric acid esters of cellulose, which may be nitrocellulose. alone, or a mixed ester of nitric acid and other acids, such as aliphatic carboxylic acids having from 1 to 7 carbon atoms.

The assay 60 may also contain an absorbent pad 68. The absorbent pad 68 generally recites fluid that has migrated through the complete porous membrane 63. As is well known in the art, the absorbent pad 60 can assist in promoting capillary action and fluid flow through the membrane 63. Some suitable materials that can be used to form the sample pad include, but are not limited to to nitroselulose, cellulose, polyethylene-porous pads, and fiberglass filter paper. If desired, the sample pad may also contain one or more test pretreatment reagents, either covalently or non-covalently coupled thereto. In the illustrated embodiment, the test sample traveling from the pad demonstrates (not shown) a conjugate pad 62 that is placed in communication with one end of the sample pad. The conjugate pad 62 is formed of a material through which a fluid is capable of passing. For example, in one embodiment, the conjugate pad 62 is formed of glass fibers. Although only a conjugate pad 62 is shown, it should be understood that other conjugate pads may also be used in the present invention.

To facilitate detection of the presence or absence of an analyte within the test sample, several detection probes can be applied to the conjugate pad 62. Although contained in the conjugate pad 62, these detection probes remain available for join with the analyte while passing the sample pad through the conjugate pad 62 (or optionally in the fluid). By binding with the analyte, the detection probes can later serve to identify the presence or absence of the analyte. The detection probes can be used for both the detection, and the calibration of the assay 60. In alternate embodiments, however, the separate calibration probes can be applied to the conjugate pad 62 for use in conjunction with the detection probes to facilitate detection and simultaneous calibration, so it eliminates inaccuracies often created by systems. calibration of conventional tests. It should be understood, however, that the detection probes and / or the calibration probes can be applied together or separately at any location of the tests 60, and do not need to be applied to the conjugate pad 62. In addition, it should also be it being understood that the detection probes and / or the calibration probes can be applied to them or to different conjugate pads. Alternatively, the detection probes and / or the calibration probes may be located in a separate area of the diagnostic test unit 10, 100, 200, or 300 (Figures 1 to 4), such as within the fluid, the channel of flow, or the cotton swab.

In some instances, it may be desired to modify the detection probes in the same manner so that they are more readily available to bind to the analyte. In such instances, the detection probes can be modified with certain specific binding members that are adhered thereto to form conjugate probes. The specific binding members generally refer to a member of a specific binding pair, for example, two different molecules where one of the molecules chemically and / or physically binds to the second molecule. For example, - specific immunoreactive binding members can include antigens, haptens, aptamers, antibodies (primary or secondary), and complexes, thereof, including those formed by recombinant DNA methods or peptide synthesis. An antibody can be a monoclonal or polyclonal antibody, in the recombinant protein or a mixture (s) or fragment (s) thereof, as well as a mixture of an antibody and other specific binding members. The details of the preparation of such antibodies and their adaptability for use as specific binding members are well known to those skilled in the art. Other common specific binding pairs include but are not limited to biotin and avidin (and derivatives thereof), biotin and streptavidin, carbohydrates and lectins, complementary nucleotide sequences (which include probes and sequences) of captured nucleic acid assays used in DNA hybridization assays to detect a target nucleic acid sequence), complementary peptide sequences that include those formed by recombinant methods, effector and receptor molecules, the hormone and the protein hormone binding, the cofactors of enzymes and enzymes, the inhibitors of enzymes and enzymes, and so on. Additionally, specific binding pairs can include members that are analogous to the original specific binding member. For example, a derivative or fragment of the analyte, for example, an analogous analog, can be used as long as it has at least one epitope in common with the analyte.

The specific binding members can generally be coupled to the detection probes using any of a variety of well-known techniques. For example, the covalent coupling of the specific binding members to the detection probes (eg, the particles) can be achieved by using carboxylic, amino, aldehyde, bromoacetyl, iodoacetyl, thiolo, epoxy functional groups and other reagents or bonds, as well as residual free radicals and radical cations, and through which a protein coupling reaction can be achieved. A functional surface group can also be incorporated as a functionalized comonomer because the detection surface can contain a relatively higher surface concentration of polar groups. Additionally, although detection probes are often functionalized after synthesis, in certain cases, such as poly (thiophenol), the probes are capable of direct covalent linkage with a protein without the need for further modification. In addition to covalent binding, or coupling techniques, such as physical adsorption, they can also be used.

In the embodiment, for example, the fluid containing the test sample is moved to the conjugate pad 62, where the analyte mixtures with the detection probes modified with a specific binding member to form analyte complexes. Because the conjugate pad 62 is in fluid communication with the porous membrane 63, the complexes can migrate from the conjugate pad 62 to the detection zone 65 present in the porous membrane 63. The detection zone 65 can contain an immobilized receptive material that is generally capable of forming a chemical or physical bond with the analyte and / or complexes thereof (eg, analyte complexes with detection probes). In some embodiments, the receptive material may be a biological receptive material. Such biological receptive materials are well known in the art and may include, but are not limited to antigens, haptens, antibodies, protein A or G, avidin, streptavidin, and complexes thereof. In some cases, it is desired that these biological receptive materials be able to bind to the analyte and / or analyte complexes with the detection probes.

These receptive materials serve as stationary binding sites for the detection probes / analyte complexes. In some instances, the use of analytes, such as antibodies, antigens, etc., have two binding sites. Upon reaching the detection zone 65, one of these binding sites is occupied by the specific binding member of the complex probes. However, the free binding site of the analyte can bind to the immobilized receptive material. When attached to the immobilized receptive material, the complex probes form a new ternary sandwich complex.

The detection zone 65 can generally provide any number of different detection regions so that a user can better determine the concentrations of a particular analyte within a test sample. Each region may contain the same receptor materials or may contain different receptor materials to capture the multiple analytes. For example, the detection zone 65 may include two or more different detection regions (e.g., lines, dots, etc.). The detection regions can be placed in the form of lines in a direction that is essentially perpendicular to the flow of the test sample through test 60. Similarly, in some embodiments, the detection regions can be placed in the form of lines in a direction that is essentially parallel to the flow of the test sample through the test device.

Even when the detection zone 65 can indicate the presence of an analyte, it is often difficult to determine the relative concentration of the analyte within the test sample using only a detection zone 65. Thus, the assay 60 may include a calibration zone 64. In this embodiment, the calibration zone 64 is formed on the porous membrane 63 and is positioned downstream of the detection zone 65. The calibration zone 64 is provided with a receptive material that is capable of binding to any remaining non-captured detection probe and / or calibration probes passing through the length of the membrane 63. In particular, upon contact with the test sample, any probe not captures that do not agglutinate the analyte migrate through the detection zone 65 and enter the calibration zone 64 of the porous membrane 63. In the calibration zone 64, these non-captured probes then agglutinate the receiving materials.

The receiving materials used in the calibration zone 64 can be the same or different as the receiving materials used in the detection zone 65. For example, in some embodiments, the receptive material can include a poly-electrolyte that can bind to the probes not captured. Polyelectrolytes can have a net positive or negative charge, as well as a net charge that is generally neutral. For example, some suitable examples of polyelectrolytes have a net positive charge and include, but are not limited to, polylysine (commercially available from Sigma-Aldrich Chemical Company, Inc. of Saint Louis, Missouri), polyethylene imine; epichlorohydrin-functionalized polyamines and / or polyamidoamines, such as poly (dimethylamine-co-epichlorohydrin); polydiallyldimethyl ammonium chloride; cationic cellulose derivatives, such as cellulose copolymers or cellulose derivatives grafted with a water-soluble quaternary ammonium monomer; and similar. In a particular embodiment, CelQuat® SC-230M or H-100 (available from National Starch &Chemical, Inc.) which are cellulose derivatives containing a water-soluble quaternary ammonium monomer can be used. In addition, some suitable examples of polyelectrolytes having a net negative charge include polyacrylic acids such as poly (ethylene-co-methacrylic acid, sodium salt), and the like. It should also be understood that other polyelectrolytes can also be used in the present invention, such as amphiphilic polyelectrolytes (e.g., having polar and non-polar parts). For example, some instances of suitable amphiphilic polyelectrolytes include, but are not limited to, poly (styryl-bN-methyl 2-vinyl pyridinium iodide) and poly (sterile-b-acrylic acid) both of which are available from Polymer Source, Inc. of Dorval, Canada.

Similar to the detection zone 65, the calibration zone 64 can also provide any number of different calibration regions in any direction so that a user can better determine the concentration of a particular analyte within the test sample. The calibration regions can be pre-loaded onto the porous membrane 63 with different amounts of the binder so that a different signal intensity is generated for each calibration region with the migration of the non-captured probes. The overall amount of the receptor material within each calibration region can be varied by using calibration regions of different sizes and / or by varying the volume concentration in the binder in each calibration region. If desired, an excess of probe molecules can be employed in assay 60 so that each calibration region reaches its full and predetermined potential for signal strength. That is, the amount of non-captured probes that are deposited on the calibration regions are predetermined due to the amount of binder used in the calibration regions that is established at a predetermined and known level. Once captured, the signal from the probes in the detection and calibration zones 65 and 64 can be measured visually or through other detection methods (eg, instruments). When visually determined, the diagnostic test unit 10, 100, 200 or 300 may optionally be provided with an advantage 13 (Figures 1-4) as is known in the art so that a user can easily observe the test 60.

In some cases, the membrane 63 can also define a control zone (not shown) that gives a signal to the user that the assay is being carried out properly. For example, the control zone (not shown) may contain an immobilized receptor material that is generally capable of forming a chemical and physical bond with the probes or with the immobilized receptor material on the probes. Some examples of such receiving materials include, but are not limited to antigens, haptens, antibodies, protein A or G, avidita, estraptavidin, secondary antibodies and complexes thereof. In addition, it may be desirable to use various non-biological materials for the control zone receiving material. For example, in some embodiments, the control zone receptor material may also include a polyelectrolyte, as described above, which can bind to non-captured probes. Because the receptor material in the control zone is only specific for probes, a signal is formed regardless of whether the analyte is present. The control zone can be placed anywhere along the membrane 63, but is preferably positioned upstream of the detection zone 65.

Various formats can be used for testing the presence or absence of an analyte using assay 60. For example, in the embodiment described above, a "sandwich" format is used. Other examples of such sandwich type tests are described by US Pat. Nos. 4,168,146 issued to Grubb et al. And 4,366,241 issued to Tom et al., Which are hereby incorporated in their entirety by reference thereto for reference to them. all purposes In addition, other formats, such as "competitive" formats can also be used. In a competitive assay, the labeled probe is generally conjugated to a molecule that is identical or analogous to the analyte. Therefore, the labeled probe competes with the analyte of interest with respect to the available receptor material. Competitive assays are typically used for the detection of analyte such as haptens, each hapten being monovalent and capable of agglutinating only one antibody molecule. Examples of competitive immunoassay devices are written in US Pat. Nos. 4,235,601 to Deutsch et al., 4,442,204 to Liotta and 5,208,535 to Buechler et al., Which are hereby incorporated by reference in their entirety. the same for all purposes. Various other device configurations and / or assay formats can be described in U.S. Patent Nos. 5,395,754 issued to Lambotte et al .; 5,670,381 granted to Jou and others and 6,194,220 granted to Malick and others, which are incorporated herein in their entirety by reference for all purposes.

In addition, it should be understood that any detection technique can be used in the present invention. For example, as is well known in the art, assay 60 can also be an electrochemical affinity assay, which detects an electrochemical reaction between an analyte (or a complex thereof) and a capture ligand on an electrode strip. For example, several electrochemical tests are described in U.S. Patent Nos. 5,508,171 issued to Walling and others; 5,534,132 issued to Vreeke and others; 6,241,863 granted to Monbouquette; 6,270,637 granted to Crismore and others; 6,281,006 granted to Heller and others and 6,461,496 granted to Felman and others, which are hereby incorporated in their entirety for reference for all purposes.

It has been found that the system of the present invention provides a compact and cost-efficient, relatively simple device for facilitated collection and testing at the essentially immediate site of the analytes. The system allows quick and easy specimen collection with a swab. Then, the test unit can be manipulated to analyze the collected specimen and provide a test result. The test result can be visible so that it is easily observed by the person carrying out the test in an adequate manner and under test conditions with leading to highly reliable and consistent test results. After the initial specimen collection, the human contact with the specimen is therefore essentially precluded through the test protocol and the complete part of the device with the collected specimen contained safely there can be discarded as a unit when the test is concluded.

Although the invention has been described in detail with respect to the specific embodiments thereof, it will be appreciated by those skilled in the art to achieve an understanding of the foregoing that alterations, variations and equivalents of these embodiments can be conceived. Therefore, the scope of the present invention should be evaluated as that of the appended claims and any equivalent thereof.

Claims (20)

R E I V I N D I C A C I O N S

1. A diagnostic test unit comprising: a rod having a first end and a second end, said rod defining at least one flow channel extending between said first end and said second end; a swab placed at the first end of said rod, said swab being configured to collect a test sample derived from a biological source suspected of containing an analyte; a fluid chamber configured to contain a fluid wherein said fluid chamber is in fluid communication with said swab through said flow channel; a seal that can be broken which inhibits fluid filtration from said fluid chamber prior to use; Y an assay for detecting the presence or absence of the analyte in the test sample, said assay being in fluid communication with the swab, said flow channel and said fluid chamber.

2. A diagnostic test unit as claimed in clause 1, characterized in that the fluid is configured to flow from said fluid chamber, into the fluid channel and then make contact with said swab.

3. A diagnostic test unit as claimed in clause 1, characterized in that the fluid is configured to flow from said fluid chamber, make contact with said swab and then flow into said flow channel.

4. A diagnostic test unit as claimed in clause 1 to 3, characterized in that it further comprises a syringe placed at said second end of said rod.

5. A diagnostic test unit as claimed in clause 4, characterized in that said syringe defines said fluid chamber.

6. A diagnostic test unit as claimed in clause 1 to 3, characterized in that said fluid chamber is defined by a component configured to selectively receive said swab.

7. A diagnostic test unit as claimed in clause 6, characterized in that said seal is configured to be broken by said swab when it is received by said component.

8. A method to detect the presence or absence of an analyte within a test sample derived from a biological source, said method comprises: i) provide a diagnostic test unit, said test unit comprises: a) a rod having a first end and a second end, said rod defining at least one flow channel extending between said first end and said second end; b) a swab placed on said first end of said rod; c) a fluid chamber configured to contain a fluid, wherein said fluid chamber is in fluid communication with said swab through said flow channel; d) a seal that inhibits fluid filtration from said fluid chamber prior to use; e) an assay for detecting the presence or absence of the analyte in the test sample, said assay being in fluid communication with said swab, said flow channel and said fluid chamber. ii) collect the test sample on said swab; Y iii) breaking said seal to release said fluid from said fluid chamber, wherein said fluid mixes with the test sample on said swab and then makes contact with the test.

9. A method as claimed in clause 8, characterized in that said rupture of the seal causes the fluid to flow from the fluid chamber, into the flow channel and then to make contact with said swab.

10. A method as claimed in clause 8, characterized in that the rupture of said seal causes the fluid to flow from the first chamber, make contact with the swab and then flow into the flow channel.

11. A method as claimed in clause 8, characterized in that said seal is broken by physically piercing said seal or by fluid pressure.

12. The diagnostic test unit or method as claimed in any one of the preceding clauses, characterized in that said flow channel has a length of more than about 1 centimeter, preferably from about 1 to about 15 centimeters, and preferably from about 5 to about 10 centimeters.

13. The diagnostic test unit or method as claimed in any one of the preceding clauses, characterized in that at least a portion of said flow channel has a width of less than about 3 millimeters, preferably from about 0.01 to about 3 millimeters, and preferably from about 0.05 to about 1 millimeter.

14. The diagnostic test unit or method as claimed in any one of the preceding clauses, characterized in that it also comprises a base part placed at said second end of said rod.

15. The diagnostic test unit or method as claimed in clause 15, characterized in that said base part defines said fluid chamber.

16. The diagnostic test unit or method as claimed in clause 15, characterized in that said base part includes an absorbent pad to facilitate the transmission.

17. The diagnostic test unit or method as claimed in any one of the preceding clauses, characterized in that said rod defines at least one additional flow channel.

18. The diagnostic test unit or method as claimed in clause 17, characterized in that the fluid is capable of flowing from said fluid chamber through one of said flow channels to make contact with the swab, and the fluid it is capable of flowing from said swab through another of said flow channels to make contact with said test.

19. The diagnostic test unit or method as claimed in any one of the preceding clauses, characterized in that said test is placed within the flow channel.

20. The diagnostic test unit or method as claimed in any one of the preceding clauses, characterized in that said seal has a thickness of less than about 0.05 inches and preferably from about 0.0007 inches to about 0.02 inches. E S U M E N A diagnostic test unit is provided. The test unit comprises a rod having a first end and a second end, the rod defining at least one flow channel extending between the first end and the second end. A rod is placed on the first end of the rod, the swab being configured to collect a test sample derived from a biological source that is suspected to contain an analyte. The test unit also comprises a fluid chamber configured to contain a fluid, wherein the fluid chamber is in fluid communication with the swab through the flow channel. The test unit also comprises a rupturable seal that inhibits fluid infiltration from the fluid chamber prior to use, and an assay for detecting the presence or absence of the analyte. The test is in fluid communication with the swab, the flow channel and the fluid chamber.