Chemistry: analytical and immunological testing – Process or composition for determination of physical state... – Of crystal or crystalline material
Reexamination Certificate
1999-01-21
2002-07-02
Kim, John (Department: 1723)
Chemistry: analytical and immunological testing
Process or composition for determination of physical state...
Of crystal or crystalline material
C436S164000, C436S177000, C435S004000, C435S028000, C422S051000, C422S051000, C422S067000
Reexamination Certificate
active
06413778
ABSTRACT:
This invention relates in general to devices for separating crystals from urine or other biological fluids and ascertaining their chemical identity. Also provided are methods for detecting and identifying crystals which may be present in urine or other biological fluids, and kits containing the devices and other materials and reagents needed to conduct the methods.
BACKGROUND OF THE INVENTION
Crystalluria, the presence of crystals in the urine, is a common problem which afflicts household pets such as cats and dogs. The formation of crystals and mucus in the urinary tract is a potentially life threatening condition in these animals. It is indicative of the predilection to form uroliths or stones, and can ultimately lead to a complete obstruction of the urinary system. Some studies have recorded that almost 10% of male cats and over 3% of female cats are affected by this disease.
Urine crystals may be of several different types. Most commonly crystals are formed of struvite (magnesium-ammonium-phosphate), oxalate, urate, cystine, or silicate, but may also be composed of other materials such as bilirubin, calcium carbonate, or calcium phosphate. Struvites and calcium oxalates combined comprise over 88% of the uroliths found in cats and dogs and therefore represent the cause of the great majority of these animal medical problems. The occurrence of crystalluria within these animal populations varies according to species, breed, diet, sex, age, and genetic pre-disposition. Crystalluria also occurs in a variety of other mammals. For example, it is known that calcium carbonate crystals can form in horses, rabbits, guinea pigs, and goats.
Present methods of detecting and identifying urine crystals rely on a high level of skill of a person who examines the crystals under a microscope and makes distinctions between the different types of crystals that may be present. It is sometimes required for the sample to be sent to a commercial laboratory for the analysis.
The term “habit” is commonly used by minerologists to refer to the characteristic shape or shapes of mineral crystals. Different crystal types exhibit different habits which a skilled person is able to differentiate. The judgment is based largely on the apparent structure or habit of the crystals. These methods involve specific skills, significant handling of the specimen, and are both time consuming and expensive. Microscopic detection and identification of the crystals is further complicated by the fact that their appearance can be influenced by the variable conditions of their formation, growth, and dissolution. The sensitivity of this method is also limited as it is not uncommon for the technician to fail to detect small numbers of crystals which may be present. This method of identifying the crystals also involves significant handling of the sample since it typically requires a volume of 5-10 mls of urine, which then must be concentrated to enhance the population of crystals within the examined specimen. Concentration is normally accomplished by centrifugation at 2500 rpm for 5-10 minutes, aspiration of all but 0.5 to 1.0 ml of fluid, and resuspension of the pellet.
The microscopist bases the judgment of crystal type on the physical characteristics or habit of the crystals present. Calcium oxalate dihydrate crystals typically are colorless and have a characteristic octahedral or envelope shape, having the appearance under a light microscope of squares whose corners are connected by intersecting diagonal lines. Struvite crystals are known for their colorless, orthorhombic, “coffinlid” shape, although frequently other, irregular forms are seen. They often have three to six or more sides and often have oblique ends. Cystine crystals exhibit a colorless hexagonal shape with equal or unequal sides. They may appear singly but usually aggregate in layers. As is evident from these descriptions, the differentiation of these different crystal types is based largely on subjective criteria, and is therefore prone to human error. For example, skilled persons sometimes have difficulty distinguishing struvite crystals from cystine. Calcium carbonate crystals may form as large yellow-brown or colorless spheroids with radial striations, or smaller crystals with round, ovoid, or dumbbell shapes.
Furthermore, the outer appearance of a crystal may not always correlate with its true chemical identity. For example, kidney stones are usually comprised of calcium oxalate, struvite, or cystine. However, crystals sometimes are comprised of a calcium oxalate core covered by an outer layer of struvite. Similarly, they may be comprised of a struvite core covered by an outer layer of calcium oxalate. Therefore, such crystals can be very deceiving even to the skilled person who is trying to ascertain their identity based largely on the external appearance of the crystals. The distinction is important, since the treatment programs for struvite and calcium oxalate crystals are very different.
Furthermore, before existing chemical and enzymatic analyses can be performed on crystals from urine or other biological fluids, it is necessary to first remove certain materials which are normally present and which interfere with these reactions, such as free magnesium, oxalate, and other substances. These materials are removed because they are not indicative of the presence of crystals when they are in the dissolved state. Therefore the use of these methods involves the further inconvenience of having to remove small molecular weight interfering substances such as oxalates which are typically removed by activated charcoal prior to testing.
Because of the time and expense involved in making accurate determinations of the presence and type of crystals, many veterinarians simply measure the pH of a urine sample, and make prescriptive decisions based on this criteria alone. This often results in needless changes to the animal's diet, and unnecessary inconvenience to the owner and stress on the animal.
The present invention provides a device for the convenient, rapid, and accurate determination of crystals which may be present in urine or other biological fluids and their identity. The device is inexpensive, disposable, specific, and requires only very small sample volumes. It also eliminates the need and consequent delay and expense of transmitting samples to a commercial laboratory for analysis. This results in quicker treatment for the affected animal and avoids additional stress on the animal caused by unnecessary dietary changes and inconvenience to the animal owner. Another important advantage is that the analysis of the urine crystals is based on more objective criteria, sharply reducing human error as a source of inaccuracy. Using the present invention, one is able to determine the presence of urinary crystals and identify the crystal type with almost 100% sensitivity and accuracy.
The present invention also discloses methods for detecting and identifying crystals which may be present in biological fluids, including urine. The methods may be conveniently performed in the veterinarian's office during the time typically taken for an office visit. Unlike currently available methods, a high level of training and skill is not necessary to successfully and confidently identify the crystal types, and the method can be learned in a matter of minutes.
The present invention also discloses kits which may include the devices of the present invention and reagents necessary for conducting the methods of the present invention. The kits enable the veterinarian or other animal caretaker to have conveniently available everything needed to conduct the assay and detect and identify any crystals which may be present. The kits have a shelf life of at least six months and may last one year or more, and may be conveniently stored in a small space until needed. The kits may include reagents necessary to conduct the assay in a ready-to-use format, thereby eliminating the need for mixing or preparing reagents.
SUMMARY OF THE INVENTION
The present invention relates to devices, met
Carpenter Charles R.
Clark Genevieve
Tornberg Melanie
Idexx Laboratories
Kim John
McDonnell & Boehnen Hulbert & Berghoff
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