Chemistry: analytical and immunological testing – Optical result
Reexamination Certificate
1999-05-25
2002-09-10
Alexander, Lyle A. (Department: 1743)
Chemistry: analytical and immunological testing
Optical result
C436S175000, C436S177000, C436S808000, C436S063000, C422S105000, C422S105000, C422S051000, C422S067000
Reexamination Certificate
active
06448088
ABSTRACT:
TECHNICAL FIELD
This invention relates to a method and apparatus for analyzing a urine sample. More particularly, this invention relates to a preferably disposable urine sample holder and a method and system for using the same to perform chemical, qualitative, quantitative, and semi-quantitative analyses of a subject's urine sample.
BACKGROUND ART
Urinalysis involves chemical testing of the urine for clinically important chemically detectable constituents and parameters, and examining centrifuged sediment from the urine sample under magnification so as to identify and semi-quantitate the presence of formed bodies in the urine. A general discussion of the present state of the art relating to urinalysis is presented in an article authored by Jonathan Ben-Ezra et al, in
Clinical Chemistry
, Vol 44:1, pages 92-95 (1998).
Chemical testing of a urine sample generally involves analyzing the urine for one or more of the following constituents: glucose; bilirubin; ketones; blood; albumen; nitrites; red blood cells and free hemoglobin; leukocyte esterase; pH; urobilinogin; ascorbic acid; and specific gravity. These various determinations are made through the use of a dipstick having various chemical reagent bands printed thereon. Such dipsticks are commercially available from Bayer Corporation of Elkhart, Indiana, as well as other commercial sources. The dipstick is dipped into a well mixed urine sample, and after a time period of thirty seconds to two minutes, the various reagent bands are visually or optically examined for color changes. The bands can be visually compared to a preprinted color chart in order to determine the amount of each of the constituents or parameters being measured. It is also possible to optically scan the dipstick and thereby obtain instrument readings of color intensity or wave length through the use of an instrument manufactured by Ames. Currently available instruments for optically scanning the dipstick bands do not distinguish lysed red blood cells from intact red blood cells, since lysed red blood cells create a different, color distribution on the blood band than do intact red blood cells. With lysed cells, the reaction color is relatively evenly distributed over the blood band, while with whole cells, the reaction color tends to be spotted on the blood band. Presently available instruments do not quantify the number of spots formed on the blood band from whole cells, but can merely quantify the overall color intensity sensed on the band.
In present day technology for quantitatively analyzing a urine sample for the presence of formed bodies such as both red and white blood cells; bacteria; crystals; fecal matter; parasites; spermatozoa; ova from parasites; as well as other formed bodies such as casts, the urine sample is centrifuged so as to separate the liquid phase from the formed body sediment in the urine, thereby concentrating the sediment. Ninety to ninety five percent of the liquid phase is then drawn off from the sediment and discarded, the sediment is re-suspended in the remaining liquid, and a drop of the re-suspended sediment is examined under magnification on a microscope slide at low power, i.e., about 100×, for the presence or absence of one or more of the aforesaid formed bodies which are morphologically distinguishable, one from another. This type of analysis provides a crude quantification of target formed bodies which are present in urine.
In present day technology for detecting rare events such as casts in the urine sample, the urine sample sediment is examined as above on a microscope slide. Proteinacious casts which are casts of the renal tubules, may be found in small quantities in normal urine. They may be described by the type of cells they contain such as those having included red cells, which are called red cell casts. The red cell casts are formed in the kidney and are indicative of bleeding in the kidneys prior to the renal collecting ducts and therefore can provide useful information to the clinician. White blood cell casts are indicative of infection of the kidney itself, as opposed to infection in just the urinary bladder. Types of casts include red cell casts, white cell casts, tubular epithelial cell casts, granular or waxy casts containing degenerated cellular components, and clear or hyaline casts. Other than hyaline casts, casts are rarely seen in normal healthy patients, and the range of quantity is described in the literature. Instruments have been developed which both determine the chemical constituents of the urine and also assist in the microscopic analysis. Such an instrument is the Yellow IRIS, which automatically places the sample on the urine dipstick and then reads the chemical results. For analyzing the particulate components, urine is passed through a flow cell, where a high speed camera captures the images of the particles as they pass through the flow cell and then displays the images so that the technician can classify them. This approach requires less technological time than a purely manual approach, but the instrument is very expensive, prone to malfunctions, and requires a technologist to interpret the particulates which are photographed.
It would be highly desirable to have a single system which could be used to perform a complete urine sample analysis, i.e., urine chemistry, urine blood cell counts, urine bacteria counts, rare event detection, all without significant human intervention, and in an uncomplicated and reliable instrument.
DISCLOSURE OF THE INVENTION
This invention relates to an improved method and paraphernalia for performing a complete analysis of a urine sample. A uniquely configured sample holder is employed for transporting, mixing and dispersing the urine sample, and for providing separate areas in which the various analyses are performed. The sample holder includes a urine sample source well into which the urine sample is introduced and may be transported to the analyzing instrument. The urine sample source well is connected by separate passages with disparate chambers In which the various analyses are performed. A means for re-suspending the urine sediment in the sample prior to introduction into the analytic chambers is included in the sample holder. The sediment re-suspension can be achieved by agitation of the sample holder, or by the inclusion of a mixing ball or balls in the urine sample chamber. One of chambers contains a miniaturized dipstick which is provided with the various reagent bands which allow the complete chemical analysis of the urine sample. A portion of the mixed urine in the source well is drawn off into the dipstick chamber where the urine is absorbed into the dipstick.
A second specially configured chamber which is shallow in one portion and deeper in another portion is provided in the sample holder for analyzing and enumerating the formed bodies, such as blood cells, bacteria and the like, in the urine. The variation of chamber depth is necessary so that the greatest dynamic range of enumeration may be accomplished, as described in co-pending U.S. patent application Ser. No. 09/256,486, filed Feb. 23, 1999. The range of some particulates, such as bacteria, may vary by as much as six logs. This specially configured chamber contains a dry coating of a colorant, such as acridine orange, which is dissolved in the urine and which can differentially highlight the various formed elements, such as blood cells and bacteria which may be present in the urine sample. When stained with a colorant such as acridine orange, it has been observed that the bacteria present in urine may be distinguished from crystalline particulates present in urine by virtue of the bacteria' characteristic 540 nm and 620 nm fluorescent emissions when excited by light in the 460 nm range, which is due to the ubiquitous presence of both RNA and DNA in bacteria, and the absence of the same in urate, phosphate, oxalate, and other less frequently seen crystals in urine. The bacteria may be similarly distinguished from cellular particulates, such as leukocytes, epithelial cells,
Levine Robert A.
Wardlaw Stephen C.
Alexander Lyle A.
Jones William W.
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