Patent Application
20140363353
1. Field of the Invention
The present invention relates generally to a fast flow apparatus and methods for evaluating or detecting an analyte in a sample. More specifically, the present invention provides various apparatus and methods for rapidly testing a liquid, solid or semi-solid sample for an analyte. The apparatus features two modifications from the prior art to accelerate the flow of liquid to the test strip: (1) a flexible collar that is vented to prevent a pressure differential between the run fluid container and the housing containing the test strip that tends to slow the accumulation of an adequate sample size, and (2) grooves on the sample pad backside to facilitate fast fluid flow from the point of contact with the sample toward the test strip.
2. Description of the Prior Art
Generally, “rapid testing” devices are sample testing devices that rely on the development of a visual and typically non-quantitative signal on the surface of a substrate, such as a membrane. Among rapid tests first used were simple pregnancy tests. Parenthetically, it should be noted that the term “rapid test” is a generic term of art in the industry for the class of products and methods of which the prior art is a part. The term “fast flow” is specifically directed to the two features of the present invention not found in the prior art.
The basic “lateral flow test strip” design is typical now of many tests, including veterinary tests, environmental tests, and clinical diagnostics (disease state) tests. One feature of such tests is that they often can be stored under ambient conditions, and they may not require extensive training in order to run and read them. Such features have made them quite useful for assisting in the diagnoses of diseases like HIV, which affects millions of persons in the developing countries of the world. Rapid testing devices are disclosed in, for example, U.S. Pat. Nos. 5,935,864 and 6,303,081. More relevant is U.S. Pat. No. 7,749,771 (“the '771 patent”), which is the clear predecessor of the present application. Actual field experience with the invention of the '771 patent has led to both narrowing its focus and most importantly to significant improvements that are featured in this application to achieve the fast flow characteristics described above. Thus this application is properly characterized one for an improvement patent.
Countries lacking an extensive medical infrastructure generally do not have the personnel or the facilities and equipment necessary to collect and process large numbers of clinical samples in a centralized laboratory. Hence, a disproportionate number of individuals (compared to nations with more elaborate medical infrastructures in place) may harbor infections and not know how they are infected. Simplicity, ease of sample collection and use, and protection of the user from exposure to biological fluids are high priorities when developing such a device.
A number of problems arise when clinical diagnostics are being developed. Besides stability issues relating to a product's shelf life (these can be overcome by incorporating appropriate dry chemistries, desiccation of the test, and packaging materials that allow only very low levels of moisture transmission) and especially when diagnostics are being developed for use in places like developing countries, means need to be found that (a) maintain a low overall cost for parts and manufacturing, (b) protect and maintain the integrity of the test strip itself, and (c) combine sample collection within the platform itself, in order to make a test as easy and foolproof as possible to use.
Bearing in mind the foregoing, it is a principal object of the present invention to provide devices and methods for rapid testing and analysis of a sample for the presence or absence of an analyte, but is an improvement over the prior art by reason of its fast flow attributes.
It is another principal object of the present invention to provide the ability to collect and test different bodily fluids from human or animal subjects (e.g., samples comprising oral fluid, blood-based fluids (including whole, undiluted blood), other bodily fluids such as, for example, spinal fluid or urine), as well as samples for chemical or environmental evaluations, with or without diluent or reagent.
It is related object of the present invention to provide an inexpensive, single-use lateral flow device that will, for example, aid a user (e.g., a physician or other health care provider) in the diagnosis of an infectious disease, and which will perform more quickly than prior art devices and methods by reason of its fast flow features.
It is an additional object of the present invention to provide a sample testing device that protects the test strip from contamination as well as protects the user from test samples containing infectious or toxic agents
Another object of the present invention to provide a sample testing device that allows for visual monitoring of sample volume or amount by the user.
It is a further object of the present invention that the design of it provides ease of manufactured low cost, and simplicity of use for a sample testing device.
It is an additional object of the present invention to provide flexibility in its use with lateral flow test strips, due to the ease with which the housing length is adjusted, as well as allowing for use of different absorbent collection tip shapes and sizes for specific sample quantities.
Other objects and advantages will become apparent to those skilled in the art upon reference to the following descriptions and the appended drawings.
In accordance with a principal aspect of the invention there is provided an inventive device that includes a sample pad with backside grooves for collecting the sample, a test strip coupled to the sample pad, the test strip including an indicator region configured to provide a visual indication of the presence or absence of the analyte in the sample; a housing that includes a first end and a second end, wherein the test strip is disposed within the housing, the housing allowing visualization of the test strip, and wherein at least a portion of the sample pad extends beyond the first end of the housing through a vented flexible collar; and a run fluid container configured to be positioned over the portion of the sample pad that extends beyond the first end of the housing, the run fluid container configured to form an air-tight seal around the first end of the housing.
The sample pad includes at least one longitudinal groove, and preferably three longitudinal grooves, embossed on the backside to facilitate fluid flow from the point of contact with the sample toward the test strip. The run fluid container contains a suitable diluent or reagent for running the test reaction. Further, in all embodiments the device includes a vented flexible collar at the first end of the housing, wherein the vented flexible collar allows insertion of the sample pad and the test strip into the housing and is configured to maintain coupling of the test strip to the sample pad. The flexible collar is vented using a longitudinal semicircular canal adjacent to and contiguous with the opening in the flexible collar through which the sample pad is inserted into the device housing. The venting is to maintain equal pressure between the run fluid container and the interior of the housing where the test strip is disposed. The vented flexible collar, run fluid container, and/or test strip include a color coding that provides a visual indication of the test reaction to be performed. The device also include at least one marking on the sample pad providing a visual indication of the amount of sample collected. The device can be configured for collection and testing of a fluid sample, a dry sample or a semi-solid sample such as feces.
The inventive device is configured as a dual test strip apparatus in an alternative embodiment. In this configuration, the sample testing device includes a second sample pad for collecting a second sample, a second test strip coupled to the second sample pad, the second test strip including a second indicator region configured to provide a visual indication of the presence or absence of a second analyte in the second sample; wherein the second test strip is disposed within the housing, the housing allowing visualization of the second test strip, and wherein at least a portion of the second sample pad extends beyond the second end of the housing through the second vented flexible collar. The dual test strip device can also include a second run fluid container configured to be positioned over the portion of the second sample pad that extends beyond the second end of the housing, the second run fluid container configured to form an air-tight seal around the second end of the housing. Typically, the dual test strip device further includes a fluid-impermeable element that separates the first and second sample pad. Instead of the test strips being coplanar near each other, an alternative configuration for the first and second test strips in the housing is a back-to-hack configuration. In some circumstances, the first analyte to be detected is different in type from the second analyte. One or both of the sample pad/test strip combinations can be configured for collection and testing of a fluid sample. In certain circumstances, one or both of the sample pad/test strip combinations can also be configured for collection and testing of a dry or solid sample or a semisolid sample.
The sample pad includes at least one marking providing a visual indication of the amount of sample collected. Alternatively and preferably, the sample pad includes at least two markings providing a visual indication of the amount of sample collected. Particularly suitable are a first marking indicating a minimum amount of sample sufficient for performing the test reaction, and a second marking indicating a maximum amount of sample for performing the test reaction. The device can further include a run fluid container configured to be positioned over the portion of the sample pad that extends beyond the first end of the housing through the vented flexible collar. The run fluid container can contain a suitable diluent or reagent for running the test reaction. The vented flexible collar, run fluid container, and/or test strip can comprise a color code providing a visual indication of the test reaction to be performed. The device can be configured for collection and testing of a fluid sample, a dry or solid sample and/or a semi-solid sample.
In another embodiment, the present invention provides a dual test strip device for performing first and second test reactions to detect, respectively, first and second analytes in first and second samples, the dual test strip device including a first sample pad for collecting the first sample; a first test strip coupled to the first sample pad, the first test strip including a first indicator region configured to provide a visual indication of the presence or absence of the first analyte in the first sample; a second sample pad for collecting the second sample; a second test strip coupled to the second sample pad, the second test strip including a second indicator region configured to provide a visual indication of the presence or absence of the second analyte in the second sample; and a housing comprising a first end and a second end, wherein the first and second test strips are disposed within the housing, the housing allowing visualization of the first and second test strips, and wherein at least a portion of the first sample pad extends beyond the first end of the housing and at least a portion of the second sample pad extends beyond the second end of the housing. Typically, the dual test strip device further includes a fluid-impermeable element that separates the first and second sample pad.
In another aspect, the present invention provides a method for detecting an analyte in a sample. In one embodiment, the method includes the following steps: contacting a substance to be tested with a sample pad, wherein the sample pad is coupled to a test strip having an indicator region configured to provide a visual indication of the presence or absence of the analyte; retaining contact of the substance with the sample pad until a sample of the substance is collected; positioning a run fluid container over the sample pad so that the run fluid container forms an airtight seal around a first end of a housing that contains the test strip; allowing the sample to progress through a vented flexible collar on the sample pad and onto the test strip; and reading the presence or absence of the analyte from the indicator region on the test strip.
Alternatively, the method uses a dual test strip device for performing first and second test reactions to detect first and second analytes in first and second samples, the method including the following steps: contacting a first substance to be tested with a first sample pad, wherein the first sample pad is coupled to a first test strip having a first indicator region configured to provide a visual indication of the presence or absence of the first analyte; retaining contact of the first substance with the first sample pad until a first sample is collected; contacting a second substance to be tested with a second sample pad, wherein the second sample pad is coupled to a second test strip having a second indicator region configured to provide a visual indication of the presence or absence of the second analyte, and wherein the second test strip is coupled to the first test strip in a back-to-back configuration; retaining contact of the second substance with the second sample pad until a second sample is collected; allowing the first sample to progress through a first vented flexible collar on the first sample pad and onto the first test strip; allowing the second sample to progress through a second vented flexible collar on the second sample pad and onto the second test strip; reading the presence or absence of the first analyte from the first indicator region on the first test strip; and reading the presence or absence of the second analyte from the second indicator region on the second test strip.
In certain embodiments of the method for detecting an analyte, the substance to be tested (or, if performing the dual test strip method, at least one of the first and second substances to be tested) is a fluid such as, for example, a biological fluid (e.g., an oral fluid, blood, spinal fluid, or urine). In other embodiments, the substance to be tested (or, if performing the dual test strip method, at least one of the first and second substances to be tested) is for a chemical or environmental evaluation of the substance.
Various other features of the invention will become apparent to those skilled in the art from the following discussion taken in conjunction with the appended drawings, in which:
As required, detailed embodiments of the present invention are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the invention which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present invention in virtually any appropriately detailed structure.
Reference is now made to the drawings, wherein like characteristics and features of the present invention shown in the various FIGURES are designated by the same reference numerals.
In one aspect, the present invention provides a device for testing a sample of a substance to be tested. The device of the present invention addresses (a) attaching the sample collection portion of the device to the test strip (e.g., the base of the test strip); (b) encasing the test strip within a housing (this protects the portion of the strip that provides the stage for the visible result, namely the membrane), with the sample collection portion at least partially protruding from the end of the housing; (c) providing a housing that allows visualization of the test strip (e.g., an essentially clear housing), so the test result can easily and readily be seen through it; (d) providing an appropriate sample collection material (e.g., for human biological fluids (including, but not limited to, oral fluids and blood or blood components)); (e) providing a means whereby the amount of sample collected may be monitored in a semi-quantitative fashion (typically visually); (f) providing a suitable container that matches the sample collection end of the device, in terms of dimensional fit of the collector to the interior of the container, and its ability when used with the device, to isolate the sample from the user; and (g) closing the housing at the distal end in order to further isolate the test strip from the environment and to further help prevent exposure to the sample, thereby preventing exposure to potentially hazardous substances such as, for example, biological samples containing an infectious agent. It should be noted that in the '771 patent, there is a recitation about leaving a small hole to equalize air pressure between the ambient pressure and the housing containing the test strip. This is no longer done, but this recitation should not be confused with the venting of the flexible collar in the present application because the venting is to equalize pressure between the run fluid container and the housing in which the test strip is disposed.
Referring to
Housing 8 is of sufficient rigidity to maintain device integrity. Housing 8 includes at least a region having sufficient clarity to allow visual inspection and interpretation of enclosed test strip 2. For example, housing 8 may be made of a clear material (such as, e.g., polyethylene or mylar) or may include a visually clear window or cutout that allows for visual inspection of test strip 2. End 12 (distal to the end 10 at which the grooved sample pad 6 is positioned) is typically sealed (e.g., using a plug). In certain variations, housing 8 includes one or more icons or lettering on its surface, and/or coloring or labeling, providing an indication to the user of any of various parameters for use of the device, including, for example, the type of test reaction corresponding to test strip 2. The distal orientation of end 12 with respect to the grooved sample pad 6 extending from end 10 of the housing facilitates easy handling of sample collection assembly 11.
In certain embodiments, housing 8 is a made of a material that can easily be cut. This feature facilitates adaptability of the device, allowing, e.g., accommodation of test strips of different lengths. For example, in one preferred embodiment, housing 8 is made of blown plastic tubing (e.g., blow molded polyethylene). Sample pad 6 can be any member configured to collect a dry or fluid sample and that will facilitate progression of the sample distally from the point of uptake to the test strip 2. In the case of a fluid sample, sample pad 6 can be configured to collect the sample by adsorption and allow the fluid sample to progress distally from the point of uptake by, e.g., capillary action. Typically, sample pad 6 is an absorbent member made of fibrous or solid type material which is embossed with grooves on its backside to facilitate fast flow. In certain variations, sample pad 6 is a substantially flat porous plastic pad (see, e.g.,
Sample pad 6 is configured so that the shape of its base conforms to the interior shape of the base of the run fluid container 14. Sample pad 6 can be pre-treated chemically (e.g., with a compatible detergent or surfactant), or with a plasma, to render the sample pad 6, or a part or parts of it, hydrophilic. In some variations, sample pad 6 is configured for use with either oral fluid or blood. Sample pad 6 can also be configured to allow for variation in sample size.
In certain embodiments, sample pad 6 includes one or more markings providing an indication of the appropriate amount of sample to be collected (e.g., fluid to be absorbed) onto the sample pad 6 for the test reaction. For example, in certain embodiments, sample pad 6 has minimum/maximum sample size indicators. (See, e.g.,
Run fluid container 14 can be any container that will fit over the flexible collar 20. In typical embodiments, run fluid container 14 is a polyethylene or polypropylene container with a snap-cap top or some alternative (e.g., a 2 mL microfuge tube) and having a relatively shallow-angled “V” shaped or “U” shaped base. The run fluid container 14 may also include a liquid diluent or reagent suitable for running the corresponding test reaction. In such variations, the run fluid container 14 will typically include a cover 24, such as, e.g., a peel away foil cover or a snap-cap top. The run fluid container 14 is typically configured to fit in a test tube rack or other suitable device that will maintain the container 14 in a substantially upright position and thereby hold the sample testing device in a substantially upright, inverted position when sample pad 6 is placed into the run fluid container 14.
In some embodiments, the sample testing device of the present invention includes two sample pad/test strip combinations for collecting two separate samples and running two corresponding test reactions (a “dual test strip” device). Such a device can include two of the sample testing devices as described above coupled in an inverted configuration (with each sample pad 6 at opposite ends) and such that each test strip 2 can be visualized and interpreted through the housing(s). Such a dual test strip device can be achieved, for example, by coupling two housings 8 of two separate devices as described above (e.g., snap-fitted or glued). In other variations, the device comprises two sample pad/test strip combinations assembled into one housing, with the test strips disposed within the housing such that each can be visualized and interpreted.
The present invention also provides methods for detecting the presence or absence of an analyte in a substance, including biological fluids or other substances, such as for chemical or environmental evaluations, including, for example, dry substances (e.g., anthrax, carbon) or non-biological fluids. Generally, the method includes collecting the substance with sample pad 6, coupled to test strip 2 enclosed within housing 8; retaining contact of the sample pad 6 with the substance until a sample sufficient for running the test reaction has been collected; allowing the sample to progress through the sample pad 6 and onto the test strip 2; and reading the presence or absence of the analyte from the indicator region on the test strip 2. In certain embodiments, run fluid container 14 (either without diluent or with an appropriate diluent or reagent, if required) is placed over the sample pad 6 to form an air-tight seal around end 10 of housing 8 containing the test strip 2. Alternatively, if a diluent is not used, the cover 32 may be placed over the sample pad 6. In some variations, the method further includes determining whether the amount of sample collected is sufficient for, or exceeds a maximum amount for, performing the test reaction.
In some variations of the method, the sample testing device used is provided with cover 32 protecting sample pad 6 from contamination, which is removed to expose sample pad 6 just prior to collection of the sample.
In certain embodiments in which the substance to be tested is a fluid, the fluid sample is collected by contacting the fluid with sample pad 6; retaining contact of the sample pad 6 with the fluid to allow saturation of the sample pad with the fluid, thereby collecting a fluid sample; and allowing the fluid sample to flow through sample pad 6 and onto test strip 2. The fluid sample can be an oral fluid sample (such as saliva) blood, plasma, serum, spinal fluid, urine, or any other fluid sample appropriate for the test reaction to be run. The fluid sample can be collected, for example, by placing the sample pad 6 inside the mouth (typically for collecting saliva) and passing it over the gums; by contacting a drop of the fluid with the tip of sample pad 6 (e.g., as for a drop of blood); or by inserting sample pad 6 into a container holding the fluid to be tested. In some variations, the sample pad 6 is saturated until a guide is triggered indicating sufficient sample quantity for the test reaction (e.g., a marking 26 on the sample pad indicating a minimum amount of fluid for the test reaction), and sample pad 6 is withdrawn from contact with the fluid prior to a maximum amount of fluid appropriate for the test reaction is collected (which can be indicated, for example, by marking 28 on the sample pad 6 indicating such a maximum).
Should testing on a dry substance be desired, such as for environmental or chemical testing, sample pad 6 would be contacted with the dry substance to collect a dry sample, such as, for example, by swabbing. Use of the sample testing device for testing of dry samples typically requires a diluent that will work with test strip 2. In certain embodiments, the diluent is contained in run fluid container 14. In alternative variations, sample pad 6 may include the diluent (e.g., having an internal pod that is prefilled with the diluent). In those embodiments in which sample pad 6 contains the diluent, cover 32 or empty run fluid container 14 may be placed over sample pad 6 and end 10 of the housing following sample collection. In yet other embodiments, two diluents may be mixed by using a first diluent or other additive contained in sample pad 6, which is mixed with a second diluent contained in run fluid container 14 when sample pad 6 is placed into the run fluid container and immersed in the second diluent.
The device of the present invention can be used to test for analytes in semisolids such as feces. If the feces contain sufficient liquid to be adsorbed by the sample pad 6, then testing can proceed in that manner. More likely run fluid is used to entrain fecal particles for adsorption by the sample pad 6 and testing.
In certain embodiments, following collection of the sample, run fluid container 14 is pressed and secured over the sample collection end of the device, covering sample pad 6 and possibly at least part of flexible collar 20 connected to end 10 of housing 8 containing test strip 2. This protects the user and the test from possible contamination, and also helps prevent cross-contamination. In some variations, run fluid container 14 creates an air-tight seal over the end of flexible collar 20, such as by positioning the run fluid container 14 so that there is a sufficiently snug fit of the run fluid container against the flange of flexible collar 20.
With some samples or test reactions (e.g., cardiac markers in whole blood samples), diluent is not used. In this case, the empty run fluid container 14, or cover 32, may be placed over sample pad 6 once the required amount of sample is collected. In certain variations in which the sample or test reaction requires a diluent (e.g., tests for HIV or TB), the sample pad 6 is inserted into a run fluid container 14 containing an appropriate amount of corresponding diluent so that sample pad 6 is immersed in the diluent, typically with the base of sample pad 6 at the base of the run fluid container 14, and the run fluid container 14 is pressed and secured over the end of the device.
The sample is allowed to progress to the indicator region of the test strip 2, where the test automatically initiates and the results are visible on the test strip through the housing 8. If necessary or desired, a timer can be used to indicate to the user an appropriate time for reading the test strip.
In those embodiments in which a dual test strip device is used to collect a sample, if additional or different samples are needed, once one test is being processed on one side, a second test may be initiated on the opposite side. The procedure set forth above is followed with the second end of the device, using the second sample pad 6b to collect the second sample. The second sample pad 6b may also be covered with cover 32b or, alternatively, run fluid container 14b, with or without diluent, as appropriate to the particular sample or test reaction.
In another aspect, the present invention provides a kit for testing a substance for the presence or absence of an analyte, the kit including at least one sample testing device as described herein. In certain embodiments, the kit includes run fluid container 14 containing a suitable diluent for running the test reaction. The run fluid container 14 is typically segregated (e.g., in a different compartment) from the sample collection assembly 11 comprising test strip 2, sample pad 6, housing 8 and vented flexible collar 20. Typically, sample collection assembly 11 is provided with cover 32 disposed over sample pad 6 and end 10 of housing 8 to protect sample pad 6 from contamination prior to sample collection. The kit can also include instructions for using the device according to one or more of the methods as described herein.
Flexible collar 20 can be appropriately labeled or color-coded to indicate, e.g., the particular type of test to be run. Color-coding of the flexible collar 20 can, for example, correspond to the color of the run fluid container 14 or test strip 2. Flexible collar 20 can be configured to accommodate different strip/sample combinations. For example, due to variations of sample size and/or volume diluent, the width of the strip can vary as can the location of the minimum or minimum/maximum sample size fill lines. The flexible collar 20 can be molded to increase or decrease the inner dimension of the opening 22 to accommodate various widths of test strip 2.
The device can further include a cover or “sheath” (not shown in
While the invention has been described, disclosed, illustrated and shown in various terms or certain embodiments or modifications which it has assumed in practice, the scope of the invention is not intended to be, nor should it be deemed to be, limited thereby and such other modifications or embodiments as may be suggested by the teachings herein are particularly reserved especially as they fall within the breadth and scope of the claims here appended.
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US12/22781 | 1/26/2012 | WO | 00 | 7/21/2014 |
