Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/483—Physical analysis of biological material
  • G01N33/487—Physical analysis of biological material of liquid biological material
  • G01N33/493—Physical analysis of biological material of liquid biological material urine

Definitions

• 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.
• 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.
• time is of the essence in diagnosing, and rendering the appropriate treatment for, an acute coronary condition after occurrence of the condition.
• 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.
• 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.
• the senor 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.
• 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.
• the senor is an optical sensor for sensing an optical property of the second sample in the cavity.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• the quantitative measurement in the first housing section could be effected by a microarray-based genomic chip as known in the art
• 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.
• 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.
• 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;
• 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.
• 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;
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• the biomarker is a thromboxane in the urine specimen
• 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.
• 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.
• 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.
• Electrodes 8a, 8b may sense electrochemical activity in the cell.
• 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.
• 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.
• 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.
• body fluids such as blood, saliva, perspiration, etc.
• non-body fluids such as water to indicate the degree of contamination thereof, or a liquid food product to indicate its composition.
• the invention could also be applied for examining other types of fluid, e.g., lubricating oil to indicate the wear condition of an engine.

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• 2006
  • 2006-01-31 EP EP06701716A patent/EP1859267A2/de not_active Withdrawn
  • 2006-01-31 WO PCT/IL2006/000120 patent/WO2006087697A2/en active Application Filing

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