BACKGROUND OF THE INVENTION
1. Field of the Invention.
The present invention relates generally to medical diagnostic methods and systems. More particularly, the present invention relates to methods and systems for detecting occult blood or other analytes in the water of the bowl of a flush toilet.
Colon and rectal cancers are a leading cause of death and disability throughout the world. Early detection and treatment of both diseases can significantly increase the chances of a patient's survival. A common diagnostic test for both diseases relies on the detection of occult blood in patient feces. Occult blood detection is most commonly performed by the patient obtaining small samples of fecal matter from stool following a bowel movement, spreading those samples thinly over a specially treated substrate, allowing the substrates to dry, and sending the dried substrates to a central laboratory or a doctor's office for testing. Usually, repeat samples will be taken over several days and collected prior to sending them for laboratory evaluation.
While quite useful if performed correctly, such home diagnostic stool testing suffers from both poor compliance and incompetent performance. Most patients are quite reluctant to process stool samples, even their own. Because of this reluctance, and undoubtedly for other reasons as well, many patients are unable to properly collect the samples, apply them to the substrates, and maintain the samples in proper condition before they are sent to the testing laboratory. Because of these problems, many patients who had been advised to sample their stools never complete the home testing program, and many of those tests which are completed are compromised so that the test reliability is reduced.
To promote compliance and reduce complexity, performance of occult blood assays directly in the water bowl of a toilet has been proposed. A variety of tablets, solid phase substrates, and other diagnostic agents have been formulated, where the user can simply drop these agents into the toilet bowl after use. While theoretically increasing patient compliance, the patient can still make mistakes in adding the reagents. The addition of dried reagents and related carriers can present mixing problems which limit the accuracy of the test. Moreover, the completion of such testing requires patient compliance, which is frequently absent due to a variety of factors.
For these reasons, it would be desirable to provide improved methods, systems, and reagents for performing occult blood testing in situ in the water bowl of a flush toilet. It would be further desirable to provide such methods and systems which are also useful for detecting other analytes in an analogous manner. The methods and systems should further reduce or eliminate the level of skill required by the patient to perform the assay. It would be particularly desirable if such methods and systems were to proceed automatically each time a toilet is used for defecation or urination, either by responding to the flushing of the toilet or to the use of the toilet in other ways. Such methods and systems would desirably further provide for unambiguous results and permit easy reading of those results by the patient. At least some of these objectives will be met by the inventions described hereinbelow.
2. Description of the Background Art.
The preparation of dried reagents which may be added to stool in a toilet to perform occult blood assays is described in U.S. Pat. No. 4,956,300. Other patents of interest include U.S. Pat. Nos. 6,271,046 B1; 6,221,678 B1; 6,186,946 B1; 5,196,167; 5,192,501; 5,081,040; 4,725,553; 4,625,160; 4,672,654; 4,541,987; 4,511,533; 4,175,923; and 2,828,377. Toilets which are capable of performing many functions, including measuring blood in urine, are predicted in “Japanese Masters Get Closer to the Toilet Nirvana,” New York Times, Oct. 8, 2002.
BRIEF SUMMARY OF THE INVENTION
According to the present invention, occult blood and other analytes symptomatic of gastrointestinal disease are detected by the addition of a dye reagent directly into the water of the bowl of a flush toilet. The dye reagent reacts with the analyte, if present, to produce an observable signal, usually a color change in the water.
In a first aspect of the present invention, the dye reagent is dispersed into the water, typically being in a liquid, gel, powder, or solid form which rapidly dissolves in the water and mixes stool sample to promote accurate and immediate results. In a second aspect of the present invention, the dye reagent is dispensed into the toilet bowl water in response to use of the toilet, such as flushing, sitting, or by the selective manual activation of a dosing unit. In the third aspect of the present invention, systems are provided for automatically dispensing the dye reagents into the toilet bowl water in response to use.
Dispersing or otherwise adding an amount of a dye reagent in the toilet bowl water according to the first aspect of the present invention requires that the reagent be in a dispersible and/or soluble form, usually being solution (liquid), gel, powder, or solid form which rapidly dissolves and/or dispenses in the toilet bowl water. Such dispersible forms generally exclude tablets, solid phase substrates, and other forms which will not rapidly mix or dissolve with the toilet bowl water and with the stool sample therein. Usually, although not necessarily, such dispersible dye reagents will be dispensed automatically in response to a use of the toilet, as will be described in more detail hereinbelow. Less preferably, however, the dispersible forms of the dye reagent may also be selectively or manually released into the toilet bowl water, where they will quickly mix and react with the stool, producing an observable signal when the analyte is present.
The automatic dispensing of a dye reagent, according to the second aspect of the present invention, will include the release of both dispersible and non-dispersible forms of the dye reagent. That is, in addition to the liquid, gel, and powder forms of the dried reagent, the present invention further comprises automatically dispensing even non-dispersible forms, such as tablets, substrates, solid phases, and the like. Such automatic release may be in response to any use of the toilet, including flushing, sitting on the seat of the toilet, electronic proximity sensing of a patient using the toilet, detection of fecal matter entering the toilet bowl water, detecting a change in water level or turbulence in the water of the toilet bowl alter any use, including vomiting, and the like. The latter relative use detection is particularly advantageous since it avoids the dispensing of reagent when the toilet is used without fecal matter entering the toilet bowl.
In all aspects of the methods of the present invention, the dye reagent may be dispensed into the water in the toilet tank, directly into the water in the toilet bowl, or as some combination of both. For example, when the dye reagent comprises both a dye and a separate oxidizer, as described in more detail below, the dye and the oxidizer may be dispersed together or separately into the water, with either or both going into the water in the toilet tank or into the water in the toilet bowl.
The methods of the present invention preferably provide for dispensing or releasing measured amounts of the dye reagent into the tank, typically in response to flushing. Usually, such dispensing comprises dropping a measured amount of a liquid, gel, or powder. In other instances, however, dispensing may comprise dissolving an amount of a solid dye reagent (or reagent component) into the tank or the bowl of the toilet.
In all instances, the presence of the dye reagent in the toilet bowl water will produce an observable signal in the presence of blood or other analyte, typically producing a color change in the presence of blood in the water of the toilet bowl. Preferably, the dye reagent will be selected and provided in an amount which produces an observable color change at a local blood concentration in the water of 0.2 ppm and above, preferably 0.1 ppm and above. Exemplary reagents comprise an oxidizer and a dye, where the oxidizer oxidizes the dye to produce a color change in the presence of a catalyst-peroxidase from blood hemoglobin. Exemplary dyes include 3,3′ 5,5′-tetramethylbenzidine, gum guaiac, potassium guaicosulfonate; phenolphthalin, 3,3′-dimethylbenzidine, o-toluidine, 4,4′-diaminobiphenyl, and the like. Exemplary oxidizers include alkali metal perborates, OXONE, hydrogen peroxide, and the like. Immunochromatographic detection employing a monoelonaldehyde conjugal with polyclonal antibodies might also be possible.
Optionally, the methods of the present invention may further comprise selectively adding a control reagent to the toilet bowl water to confirm that the system is working and optionally calibrate the system. Suitable control substances include ______.
Systems according to the third aspect of the present invention provide for automatically dispensing a dye reagent into water in a bowl of a flush toilet. The systems include a reservoir holding a dye reagent which is capable of producing an observable signal in the presence of analyte in the toilet bowl water, and a mechanism for dispensing an amount, preferably a measured amount, of the dye reagent into the water in the toilet bowl in response to a use of the toilet. The dispensing mechanism may be configured to release the dye reagent in the water in the toilet bowl, or the water in the water tank, or some combination thereof, so that the water and dye reagent are mixed in the toilet bowl. The dispensing mechanism may comprise a mechanical device which detects flushing of the toilet and/or rise of water in the toilet bowl or toilet tank and which releases a pre-measured amount of the dye reagent in response to such detection. The pre-measured amount may be in the form of a liquid, gel, powder, or optionally be in a solid form, such as a tablet, solid phase substrate, or the like. Alternatively, the dispensing mechanism may dispense dye and oxidizer separately into the water, where the dye and/or oxidizer may be in any of the forms just mentioned. The dye reagent will be selected to provide an observable signal, the presence of the analyte typically producing a color change in the water in the presence of the analyte, such as blood. In the case of blood detection, the preferred detection ranges, reagent dye systems and the like, have been set forth above. The systems of the present invention may further comprise a control substance which may be added to the toilet bowl water to produce the observable signal when added to the water in the absence of the analyte.