WO2006087697A2

WO2006087697A2 - Testing device for examining fluid specimens particularly urine

Info

Publication number: WO2006087697A2
Application number: PCT/IL2006/000120
Authority: WO
Inventors: Haim Zaklad
Original assignee: Analyte Works Ltd.
Priority date: 2005-02-15
Filing date: 2006-01-31
Publication date: 2006-08-24
Also published as: EP1859267A2; WO2006087697A3

Abstract

A testing device for use in examining a fluid specimen for a preselected substance in the specimen including a housing (2) having a section (2a) for receiving and examining a sample of the specimen to produce a quantitative measurement of the preselected substance therein. The housing includes a second section (2b) formed with a cell for receiving a second sample of the specimen. The device also includes a sensor (21) for sensing and measuring a particular electrical or physical property of the second sample in the cell useful in interpreting the results of the quantitative measurement of the substance in the first-mentioned section (2a) of the housing (2). In the described preferred embodiment, the housing (2) is of a plastic material for use as a disposable point-of-care unit, the fluid specimen is urine or other body fluid, the preselected substance is a biomarker, such as a thromboxane, and the sensor (21) senses electrical conductivity to produce a concentration-normalized measurement of the biomarker.

Description

TESTING DEVICE FOR EXAMINING FLUID SPECIMENS PARTICULARLY URINE

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a testing device for use in examining a fluid specimen for a preselected substance in the specimen. The invention is particularly useful, and is therefore described below, when implemented in a disposable point-of- care unit, e.g., a unit for examining urine or other body— fluid specimens in order to detect and quantitatively measure a preselected biomarker, or analyte, indicative of a particular medical condition of the subject. The novel point-of-care unit of the present invention conveniently permits examining the same body-fluid specimen in a manner which enables the quantitative measurement of the body— fluid specimen to provide a more accurate indication of the medical condition of interest.

As described in International Patent Application PCT/IL01/00642, assigned to the same assignee as the present application, the analysis of certain body fluids of a person, such as urine, for various types of biomarkers or analytes, can provide very useful information as to the medical condition of the person. As further described therein, a more reliable indication of the person's medical condition can be provided by normalizing the measured biomarker concentration according to a particular property of the specimen. For example, a measurement of the concentration of a thromboxane in a person's urine specimen, when normalized according to the electrical conductivity of the urine specimen (which corresponds to the dilution or water content of the urine specimen), provides a much more reliable indication of an acute coronary condition in the person than a thromboxane concentration measurement when not so normalized. As further described in the above-cited patent application, time is of the essence in diagnosing, and rendering the appropriate treatment for, an acute coronary condition after occurrence of the condition.

OBJECTS AND BRIEF SUMMARY OF THE PRESENT INVENTION

An object of the present invention is to provide a testing device which may be used quickly for examining a fluid specimen for a preselected substance in a specimen, and for a particular property of the specimen useful for interpreting the results of such an examination. Another object of the invention is to provide a testing device which may be implemented in a disposable, point-of-care unit. A further object of the invention is to provide a testing device particularly useful for examining urine or other body-fluid specimens of a subject (e.g., a person or animal) in a quick and facile manner in order to provide a more accurate indication of the medical condition of the subject, particularly the occurrence of an acute coronary condition.

According to a broad aspect of the present invention, there is provided a testing device for use in examining a fluid specimen for a preselected substance in the specimen, including a housing having a section for receiving and examining a sample of the specimen to produce a quantitative measurement of the preselected substance therein, characterized in that the housing includes a second section formed with a cell for receiving a second sample of the specimen; and in that the device also includes a sensor for sensing and measuring a particular property of the second sample in the cell useful in interpreting the results of the quantitative measurement of the substance in the first-mentioned section of the housing.

In one described preferred embodiment, the sensor includes spaced electrodes in the cell located to be immersed by the second sample in the cell for sensing the electrical conductivity of the second sample. The electrical conductivity of the second sample closely correlates to the concentration, or amount of water, in the sample. Such a measurement, therefore, enables the quantitative measurement of the preselected substance to be corrected or "normalized" according to the concentration, or quantity of water, in the urine specimen, which provides a more accurate indication of the occurrence of an acute coronary condition, as described in the above-cited International Patent Application. While electrode-type sensors are particularly useful for measuring electrical conductivity, and thereby concentration, of the fluid specimen, it will be appreciated that electrode sensors could also be used for measuring other properties of the fluid specimen, e.g., electrochemical activity, pH, composition, temperature, etc.

A second embodiment of the invention is described wherein the sensor is an optical sensor for sensing an optical property of the second sample in the cavity. Such an optical sensor may sense, for example, index of refraction, color, turbidity, fluorescence, or other optical property of the sample, to provide useful information for interpreting, correcting or normalizing the quantitative measurement made of the preselected substance.

According to further features in both described preferred embodiments, the first section of the housing includes an inlet port for introducing the first sample of the specimen; a reaction zone containing a reagent selectively reactable with the preselected substance of the first sample; and an observation window for observing the results of the reaction of the reagent with the preselected substance of the first sample. The first section of the housing preferably further includes a capillary-flow strip between the inlet port and the observation window for producing a slow, controlled lateral flow of the fluid specimen through the reaction zone and to the observation window. In the described preferred embodiments, an absorbent pad is provided in contact with the capillary-flow strip and located downstream of the observation window for producing a capillary flow of the fluid specimen through the capillary-flow strip. In one described preferred embodiment, the reagent in the reaction zone of the first housing section is selectively reactable with a preselected substance, e.g., a thromboxane, in a urine specimen; and the particular property measured in the second housing section is the electrical conductivity of the second sample in the cell of the second housing section. As indicated above, and as described more particularly below and in the above-cited International Patent Application PCT/ILO 1/00642, such a concentration-normalized measurement of thromboxane provides a more reliable indication of the occurrence an acute coronary condition than a thromboxane concentration measurement which was not so normalized.

The integrated nature of the testing device constructed in accordance with the present invention, coupled with the availability of various disposable testing devices for biomarkers, enables the invention to be implemented in disposable point-of-care devices which can be conveniently used, e.g. at the patient's bedside, and which can be immediately interpreted to provide a more accurate indication of the patient's medical condition than the disposable point-of-care devices heretofore used for this purpose.

While such a testing device is particularly useful when implemented in a disposable point-of-care unit for examining urine specimens to provide an immediate indication of a person's medical condition, it may also be implemented in devices for examining other body fluids, such as blood, perspiration, saliva, etc., as well as in devices for examining non-body fluids, such as contaminated water, liquid food products, lubricating oil to indicate the condition of an internal combustion engine, etc. In addition, the quantitative measurement in the first housing section could be effected by a microarray-based genomic chip as known in the art

Further features and advantages of the invention will be apparent from the description below.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, with reference to the accompanying drawings, wherein:

Fig. 1 is a longitudinal sectional view illustrating one form of testing device constructed in accordance with the present invention;

Fig. 2 is a top plan view of the testing device of Fig. 1; Fig. 3 is a block diagram illustrating one form of measuring system that may be included in the testing device of Figs. 1 and 2; and

Fig. 4 illustrates another testing device constructed in accordance with the present invention.

It is to be understood that the foregoing drawings, and the description below, are provided primarily for purposes of facilitating understanding the conceptual aspects of the invention and possible embodiments thereof, including what is presently considered to be a preferred embodiment. In the interest of clarity and brevity, no attempt is made to provide more details than necessary to enable one skilled in the art, using routine skill and design, to understand and practice the described invention. It is to be further understood that the embodiments described are for purposes of example only, and that the invention is capable of being embodied in other forms and applications than described herein.

DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

The testing device illustration in Figs. 1 and 2 is particularly useful as a disposable point-of-care device for examining a urine specimen of a subject (i.e., a person or animal) in order to indicate the medical condition of the subject, e.g., to indicate whether the subject has suffered an acute coronary condition, as described in the above-cited International Patent Application PCT/IL01/00642. The testing device does this by examining the subject's urine specimen for a preselected substance or biomarker in the specimen, in this case a thromboxane, and for a particular property of the specimen, in this case the electrical conductivity of the specimen, which corresponds to the concentration, or water content, of the urine. The measured urine concentration is then used to normalize the measured thromboxane concentration, to produce a concentration-normalized measurement of thromboxane which, as described in the above-cited patent application, produces a more accurate indication of whether or not an acute coronary condition has occurred in the person. Further details of the above test procedure, and how the results of the test procedure, are utilized to provide the indication of the medical condition of the person are described in International Patent Application PCT/ILO 1/00642, the contents of which are incorporated herein by reference.

The testing device illustrated in Figs. 1 and 2 includes a housing, generally designated 2, divided into two section 2a, 2b. As will be described below, housing section 2a is used for examining a first sample of the fluid specimen to produce a quantitative measurement of the preselected substance in the specimen; whereas housing section 2b is used for measuring a predetermined property of the specimen useful in interpreting the results of the quantitative measurement, e.g., by normalizing the substance measurement, in order to produce a more accurate indication of the person's medical condition.

In the example to be described below with respect to Figs. 1 and 2, the fluid specimen is a urine specimen of a person; the preselected substance is a biomarker, e.g., a thromboxane, of a person's urine indicating a particular medical condition; and the predetermine property of the person's specimen to be used for normalizing the measured concentration of the biomarker is the electrical conductivity of the urine specimen, which is directly related to the dilution or water content of the urine specimen.

As shown particularly in Fig. 1, housing 2 is constituted of a plastic base plate 3 joined to a plastic cover plate 4 to define a compartment 5 between them. Compartment 5 receives a capillary— flow member, generally designated 6, defining an array of capillary elements for producing a lateral flow of the fluid substance including the substance or biomarker to be detected and measured in housing section 2a. Base plate 3 is extended past cover plate 4 and is formed at one end with a cavity or cell 7 to be used in measuring, in housing section 2b, the predetermined property of the urine specimen for normalizing the biomarker measurement in housing section 2a. As indicated above, this predetermined property in the described embodiment is the electrical conductivity of the fluid specimen (urine), which provides a measurement of the dilution, or water content, of the fluid specimen. Accordingly, cell 7 includes a pair of spaced electrodes, shown at 8 in Fig. 1 and at 8a and 8b in Fig. 2, to measure the electrical conductivity of the specimen within the cell. Cover plate 4 of housing 2 is formed with an inlet port 10 at one end of housing section 2a, proximate to cell 7 in housing section 2b, for introducing a sample of the fluid specimen to be examined in housing section 2a. Cover plate 4 is further formed with an observation window 11 downstream of the inlet port 10 for observing the results of the examination. As known in the art, the detection and measurement of the biomarker or target substance in the urine specimen is effected by applying a preselected reagent to the capillary-flow member underneath, or just upstream of, the observation window 11 so as to enable the chemical reaction produced by the reagent with the preselected biomarker substance in the urine specimen to be observed via the observation window 11.

As also known in the prior art, the capillary— flow member 6 includes a capillary-flow strip 6a extending in compartment 5 from the inlet port 10 to the observation window 11, and an absorbent pad 6b pressed against the downstream end of the capillary-flow strip 6a to draw the fluid from the inlet port 10 through the length of the capillary strip 6a to the absorbent pad 6b. The reagent producing the chemical reaction indicating the quantity of the biomarker substance in the examined specimen is applied across the capillary-flow strip 6a in the form of one or more lines (two lines 11a, l ib being shown) under the observation window 11.

As further shown in Fig. 1, base plate 3 of housing 2 is formed with an elevated section 3 a to underlie the upper cover plate 4 at its inlet port 10. Elevated section 3 a extends to the beginning of observation window 11 so as to firmly engage the capillary— flow strip 6a from the inlet port to the observation window. The remaining section 3 b of base plate 3 is thereby spaced further from cover plate 4 so as to enlarge compartment 5 sufficiently to accommodate also the absorbent pad 6b of the capillary-flow member 6. The underface of the upper cover plate 4 is formed with a depending flange 4a around its inlet port 10 to firmly engage the capillary-flow strip 6a thereunder, and with a plurality of depending ribs 4b to firmly engage the absorbent pad 6b thereunder. Fig. 3 diagrammatically illustrates one form of electrical system that may be used in the testing device illustrated in Figs. 1 and 2 for testing a urine specimen of a person in order to detect or measure one or more substances or biomarkers therein to indicate the medical condition of the person. The illustrated device includes a first housing section 2a for examining the specimen to produce a quantitative measurement of the biomarker in the urine specimen, and a second housing section 2b for producing an independent measurement of a predetermined property of the specimen to be used for correcting or normalizing the biomarker measurement as described above, in order to provide a more reliable indication of the person's medical condition of interest. In this case, the biomarker is a thromboxane in the urine specimen, and the predetermined property is the electrical conductivity of the specimen, which correlates to the concentration or water content of the specimen. The biomarker examination is made in section 2a by applying two reagents in linear form across spaced portions of the capillary-flow strip 6a in alignment with the observation window 11, to produce two lines 11a, l ib observable via window 11 for producing a data line and a calibration line, respectively, indicating the quantity of the biomarker in the urine specimen.

The testing device illustrated in Fig. 3 further includes a first output circuit 20 in the form of a reader aligned with observation window 11 for outputting a first measurement corresponding to the quantity of the biomarker or biomarkers to be detected in the specimen sample examined in housing section 2a, and a second output circuit 21 for outputting a second measurement corresponding to the particular property of the second sample examined in cell 7 of the second housing section 2b. In this case, the property of the specimen examined in cell 7 is the electrical conductivity of the sample, and therefore output circuit 21 is in the form of a conductivity meter connected to the two electrodes 8a, 8b.

The testing device illustrated in Fig. 3 further includes a processor 22 having an input from reader 20 and another input from conductivity meter 21. Processor 22 is effective to normalize or correct the output from reader 20 in accordance with the output from conductivity meter 21 in order to produce a concentration-normalized biomarker measurement at 23, which provides a more accurate indication of the particular medical condition for which the person is being examined. For example, as described in the above-cited International Patent Application, it has been found that a more accurate indication of the occurrence of an acute coronary condition can be provided when dividing the biomarker quantity of reader 20 by the output of conductivity meter 21.

Housing 2 is preferably constructed in the form of a disposable plastic unit conveniently usable at the point-of-care. After used as described above, it may then be inserted into another unit housing the electrical system illustrated in Fig. 3 for reading out the quantitative biomarker measurement made in housing section 2a, and the electrical conductivity measurement made in section 2b. These two measurements are processed by processor 22 to produce the concentration-normalized result immediately after the examination has been made so that if any treatment is required, it can be started immediately.

Fig. 4 illustrates another testing device in accordance with the present invention, in that the device includes a different type of sensor for sensing a different property of the specimen sample in cell 7. The testing device shown in Fig. 4 is provided with a photocell type sensor 15 on one side of cell 7 and a light source 16 on the opposite side of the cell, both connected to a photocell sensor circuit 17. hi the arrangement illustrated in Fig. 4, photocell 15 and light source 16 are externally of the housing 2, and therefore the housing, or at least cell 7 of the housing, would be of transparent material. The testing device illustrated in Fig. 4 is otherwise constructed as described above with respect to Figs. 1 and 2, and therefore the remaining corresponding parts are identified by the same reference numerals.

The testing device illustrated in Fig. 4 operates in the same manner as described above with respect the testing device illustration in Figs. 1—3, except that, whereas in the device of Figs. 1-3 the electrical conductivity (or water content) of the specimen is measured in cell 7 of housing section 2b, in the device of Fig. 4 an optical property of the specimen is measured in cell 7 of housing section 2b. The optical property may be the index of refraction, fluorescence, color, turbidity, or other optical property of the specimen within cell 7 which may be found useful for interpreting, normalizing or correcting the quantitative measurement of the substance or biomarker in housing section 2a of the testing device.

Still other physical or electrical properties of the examined specimen may be used for interpreting, correcting or normalizing the measurement of the biomarker or other target substance(s) in the examined specimen. For example, electrodes 8a, 8b may sense electrochemical activity in the cell. Also, cell 7 may include an acoustical transmitter at one side, and an acoustical receiver at the opposite side, for measuring an acoustical property of the sample within the cell, which may correlate to the composition of the sample, the pH of the sample, or other physical property of the sample within the cell. In addition, other types of measurement devices could be used in housing section 2a to make the quantitative measurement, e.g. a known microarray-based genomic chip.

It will also be appreciated that the invention could be used for examining other body fluids, such as blood, saliva, perspiration, etc., to indicate particular medical conditions of the person, as well as non-body fluids, such as water to indicate the degree of contamination thereof, or a liquid food product to indicate its composition. By selecting an appropriate means for making the quantitative measurement in housing section 2a, the invention could also be applied for examining other types of fluid, e.g., lubricating oil to indicate the wear condition of an engine. Many other variations, modifications and applications of the invention will be apparent.

Claims

WHAT IS CLAIMED IS:

1. A testing device for use in examining a fluid specimen for a preselected substance in the specimen, including a housing having a section for receiving and examining a sample of said specimen to produce a quantitative measurement of said preselected substance therein, characterized: in that said housing includes a second section formed with a cell for receiving a second sample of said specimen; and in that said device also includes a sensor for sensing and measuring a particular property of said second sample in said cell useful in interpreting the results of said quantitative measurement of the substance in said first-mentioned section of the housing.

2. The testing device according to Claim 1, wherein said sensor includes spaced electrodes in said cell located to be immersed by the second sample in said cell.

3. The testing device according to Claim 2, wherein said spaced electrodes sense the electrical conductivity of said second sample in said cell.

4. The testing device according to Claim 2, wherein said spaced electrodes sense electrochemical activity of said second sample in said cell.

5. The testing device according to Claim 1, wherein said sensor is an optical sensor for sensing an optical property of said second sample in said cell.

6. The testing device according to Claim 4, wherein said optical property is the index of refraction of said second sample in said cell.

7. The testing device according to Claim 4, wherein said optical property is the color of said second sample in said cell.

8. The testing device according to Claim 4, wherein said optical property is the turbidity of said second sample in said cell.

9. The testing device according to Claim 4, wherein said optical property is the fluorescence of said second sample in said cell.

10. The testing device according to Claim 1, wherein said first section of the housing includes an inlet port located proximately to said cell for introducing said first-mentioned sample of the specimen into said first-mentioned section of the housing.

11. The testing device according to Claim 1, wherein said first-mentioned section of the housing includes: an inlet port for introducing said first-mentioned sample of the specimen; a reaction zone containing a reagent selectively reactable with said preselected substance of said first— mentioned sample; and an observation window for observing the results of the reaction of the reagent with the preselected substance of said first-mentioned sample.

12. The testing device according to Claim 11, wherein: said first-mentioned section of the housing further includes a capillary-flow strip between said inlet port and said observation window for producing a slow, controlled flow of the fluid specimen through said reaction zone to said observation window; said reagent in said reaction zone of said first-mentioned housing section is selectively reactable with said preselected substance in a body-fluid specimen; and said particular property detected and measured in said second housing section is an electrical property of the second sample in said cell of the second housing section.

13. The testing device according to Claim 11, wherein said first-mentioned section of the housing further includes a microarray— based genomic chip, and said particular property detected and measured in said second housing section is the electrical conductivity of the second sample in said cell of the second housing section.

14. The testing device according to Claim 1, wherein said housing is of a plastic material integrally formed with said housing sections for use as a disposable point-of-care unit.

15. The testing device according to Claim 1, further including: a first output circuit for outputting a quantitative measurement corresponding to the quantity of said preselected substance in the first-mentioned sample as measured in the first-mentioned section of the housing; a second output circuit for outputting a property measurement corresponding to the particular property of said second sample as measured in said second section of the housing; and a processor for producing a normalized quantitative measurement of said preselected substance according to said property measurement of said second sample.

16. The testing device according to Claim 15, wherein said processor normalizes said quantitative measurement by dividing it by said property measurement.

17. The testing device according to Claim 15, wherein said property measurement is of an electrical or optical property of said second sample.

18. The testing device according to Claim 15: wherein said housing is of a plastic material integrally formed with said housing sections for use as a disposable point-of-care unit; and wherein said first and second output circuits and said processor are located in a second housing for receiving said point-of-care unit and for producing said normalized quantitative measurement.

19. The testing device according to Claim 18, wherein: said first and second sections of the housing are constructed and designed to receive first and second samples of a body-fluid specimen from a subject; said first section of the housing is designed to produce a quantitative measurement of a preselected substance in said body-fluid specimen; and said sensor is designed to measure a predetermined electrical or optical property of said body-fluid specimen.

20. The testing device according to Claim 19, wherein said specimen is a urine specimen, said preselected substance is a thromboxane, said predetermined property is the electrical conductivity of said second sample which thereby provides a measurement of the dilution or water content of said urine specimen; and wherein said processor divides the measured thromboxane concentration by the measured electrical conductivity to produce a conductivity— normalized measurement of thromboxane in the urine specimen.