US20020110486A1 - Analyte test strip with two controls - Google Patents

Analyte test strip with two controls Download PDF

Info

Publication number
US20020110486A1
US20020110486A1 US10/121,636 US12163602A US2002110486A1 US 20020110486 A1 US20020110486 A1 US 20020110486A1 US 12163602 A US12163602 A US 12163602A US 2002110486 A1 US2002110486 A1 US 2002110486A1
Authority
US
United States
Prior art keywords
measurement area
sample
channel
bladder
layer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10/121,636
Inventor
Robert Shartle
Herbert Chow
Christa Hartmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LifeScan Inc
Original Assignee
LifeScan Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LifeScan Inc filed Critical LifeScan Inc
Priority to US10/121,636 priority Critical patent/US20020110486A1/en
Assigned to LIFESCAN, INC. reassignment LIFESCAN, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SHARTLE, ROBERT JUSTICE, CHOW, HERBERT, HARTMANN, CHRISTA
Publication of US20020110486A1 publication Critical patent/US20020110486A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483Physical analysis of biological material
    • G01N33/487Physical analysis of biological material of liquid biological material
    • G01N33/49Blood
    • G01N33/4905Determining clotting time of blood
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/525Multi-layer analytical elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302Apparatus specially adapted for immunological test procedures
    • G01N33/5304Reaction vessels, e.g. agglutination plates
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54386Analytical elements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366Apparatus specially adapted for solid-phase testing
    • G01N33/54386Analytical elements
    • G01N33/54387Immunochromatographic test strips
    • G01N33/54388Immunochromatographic test strips based on lateral flow
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/558Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0621Control of the sequence of chambers filled or emptied
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12Specific details about manufacturing devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0681Filter
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0822Slides
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0825Test strips
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/087Multiple sequential chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0887Laminated structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0403Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406Moving fluids with specific forces or mechanical means specific forces capillary forces
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0688Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/84Systems specially adapted for particular applications
    • G01N21/8483Investigating reagent band
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/745Assays involving non-enzymic blood coagulation factors
    • G01N2333/7454Tissue factor (tissue thromboplastin, Factor III)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90Enzymes; Proenzymes
    • G01N2333/914Hydrolases (3)
    • G01N2333/948Hydrolases (3) acting on peptide bonds (3.4)
    • G01N2333/95Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
    • G01N2333/964Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue
    • G01N2333/96425Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals
    • G01N2333/96427Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general
    • G01N2333/9643Proteinases, i.e. endopeptidases (3.4.21-3.4.99) derived from animal tissue from mammals in general with EC number
    • G01N2333/96433Serine endopeptidases (3.4.21)
    • G01N2333/96441Serine endopeptidases (3.4.21) with definite EC number
    • G01N2333/96447Factor VII (3.4.21.21)
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/11Automated chemical analysis
    • Y10T436/112499Automated chemical analysis with sample on test slide
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/25Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Definitions

  • This invention relates to a fluidic medical diagnostic device for measuring the concentration of an analyte in or a property of a biological fluid.
  • a variety of medical diagnostic procedures involve tests on biological fluids, such as blood, urine, or saliva, and are based on a change in a physical characteristic of such a fluid or an element of the fluid, such as blood serum.
  • the characteristic can be an electrical, magnetic, fluidic, or optical property.
  • optical property When as optical property is monitored, these procedures may make use of a transparent or translucent device to contain the biological fluid and a reagent.
  • a change in light absorption of the fluid can be related to an analyte concentration in, or property of, the fluid.
  • a light source is located adjacent to one surface of the device and a detector is adjacent to the opposite surface. The detector measures light transmitted through a fluid sample.
  • the light source and detector can be on the same side of the device, in which case the detector measures light scattered and/or reflected by the sample.
  • a reflector may be located at or adjacent to the opposite surface.
  • References to “light” throughout this specification and the appended claims should be understood to include the infrared and ultraviolet spectra, as well as the visible. References to “absorption” are meant to refer to the reduction in intensity as a light beam passes through a medium; thus, it encompasses both “true” absorption and scattering.
  • a transparent test device is described in Wells et al. WO94/02850, published on Feb. 3, 1994.
  • Their device comprises a sealed housing, which is transparent or translucent, impervious, and rigid or semi-rigid.
  • An assay material is contained within the housing, together with one or more assay reagents at predetermined sites.
  • the housing is opened and the sample introduced just before conducting the assay.
  • the combination of assay reagents and analyte in the sample results in a change in optical properties, such as color, of selected reagents at the end of the assay.
  • the results can be read visually or with an optical instrument.
  • the indicator includes a “half-bulb cavity”; which is compressible.
  • the bulb is compressed and released to form a suction that draws fluid from a source, through a half-tubular cavity that has an indicator imprinted on its wall.
  • the only controls on fluid flow into the indicator are how much the bulb is compressed and how long the indicator inlet is immersed in the source, while the bulb is released.
  • U.S. Pat. No. 3,640,267 issued on Feb. 8, 1972 to Hurtig et al., discloses a container for collecting Kilo samples of body fluid that includes a chamber that has resilient, collapsible walls. The walls are squeezed before the container inlet is placed into the fluid being collected. When released, the walls are restored to their uncollapsed condition, drawing fluid into and through the inlet. As with the Davis device, discussed above, control of fluid flow into the indicator is very limited.
  • U.S. Pat. No. 4,088,448, issued on May 9, 1978 to Lilja et al. discloses a cuvette, which permits optical analysis of a sample mixed with a reagent.
  • The-reagent is coated on the walls of a cavity, which is then filled with a liquid sample.
  • the sample mixes with the reagent to cause an optically-detectable change.
  • a number of patents, discussed below, disclose devices for diluting and/or analyzing biological fluid samples. These devices include valve-like designs to control the flow of the sample.
  • U.S. Pat. No. 4,426,451 issued on Jan. 17, 1984 to Columbus, discloses a multi-zone fluidic device that has pressure-actuatable means for controlling the flow of fluid between the zones. His device makes use of pressure balances on a liquid meniscus at the interface between a first zone and a second zone that has a different cross section. When both the first and second zones are at atmospheric pressure, surface tension creates a back pressure that stops the liquid meniscus from proceeding from the first zone to the second.
  • the configuration of this interface or “stop junction” is such that the liquid flows into the second zone only upon application of an externally generated pressure to the liquid in the first zone that is sufficient to push the meniscus into the second zone.
  • U.S. Pat. No. 4,868,129 issued on Sep. 19, 1989 to Gibbons et al., discloses that the back pressure in a stop junction can be overcome by hydrostatic pressure on the liquid in the first zone, for example by having a column of fluid in the first zone.
  • U.S. Pat. No. 5,230,866 issued on Jul. 27, 1993 to Shartle et al., discloses a fluidic device with multiple stop junctions in which the surface tension-induced back pressure at the stop junction is augmented; for example, by trapping and compressing gas in the second zone. The compressed gas can then be vented before applying additional hydrostatic pressure to the first zone to cause fluid to flow into the second zone.
  • rupture junctions By varying the back pressure of multiple stop junctions in parallel, “rupture junctions” can be formed, having lower maximum back pressure.
  • U.S. Pat. No. 5,472,603, issued on Dec. 5, 1995 to Schembri discloses using centrifugal force to overcome the back pressure in a stop junction.
  • the first zone is at atmospheric pressure plus a centrifugally generated pressure that is less than the pressure required to overcome the back pressure.
  • the second zone is at atmospheric pressure.
  • additional centrifugal pressure is applied to the first zone, overcoming the meniscus back pressure.
  • the second zone remains at atmospheric pressure.
  • European Patent Application EP 0,803,288, of Naka et al. published on Oct. 29, 1997, discloses a device and method for analyzing a sample that includes drawing the sample into the device by suction, then reacting the sample with a reagent in an analytical section. Analysis is done by optical or electrochemical means. In alternate embodiments, there are multiple analytical sections and/or a bypass channel. The flow among these sections is balanced without using stop junctions.
  • U.S. Pat. No. 5,700,695 issued on Dec. 23, 1997 to Yassinzadeh et al., discloses an apparatus for collecting and manipulating a biological fluid that uses a “thermal pressure chamber” to provide the driving force for moving the sample through the apparatus.
  • U.S. Pat. No. 5,736,404 issued on Apr. 7, 1998, to Yassinzadeh et al., discloses a method for determining the coagulation time of a blood sample that involves causing an end of the sample to oscillate within a passageway. The oscillating motion is caused by alternately increasing and decreasing the pressure on the sample.
  • the present invention provides a fluidic diagnostic device for measuring an analyte concentration or property of a biological fluid.
  • the device comprises a first layer and second layer at least one of which has a resilient region over at least part of its area, separated by an intermediate layer, in which cutouts in the intermediate layer form, with the first and second layers,
  • a first bladder at the second end of the first channel comprising at least a part of the resilient region in at least the first or second layer and having a volume that is at least about equal to the combined volume of the first measurement area and first channel;
  • the device comprises
  • a first layer which has a resilient region over at least a part of its area, and a second layer, separated by an intermediate layer, in which recesses in a first surface of the intermediate layer form, with the first layer,
  • a bladder at the second end of the channel, comprising at least a part of the resilient region in the first layer and having a volume that is at least about equal to the combined volume of the measurement area and channel;
  • a stop junction in the channel between the measurement area and bladder that comprises two passages substantially normal to the first surface of the intermediate layer, each passage having a first end in fluid communication with the channel and a second end in fluid communication with a recess in a second surface of the intermediate layer, which recess provides fluid communication between the second ends of the passages.
  • the device is particularly well adapted for measuring prothrombin time (PT time), with the biological fluid being whole blood and the measurement area having a composition that catalyzes the blood clotting cascade.
  • PT time prothrombin time
  • FIG. 1 is a plan view of a device of the present invention.
  • FIG. 2 is an exploded view of the device of FIG. 1.
  • FIG. 3 is a perspective view of the device of FIG. 1.
  • FIG. 4 is a schematic of a meter for use with a device of this invention.
  • FIG. 4A depicts an alternative embodiment of an element of the meter of FIG. 4.
  • FIG. 5 is a graph of data that is used to determine PT time.
  • FIG. 6 is a plan view of an alternative embodiment of a device of this invention.
  • FIGS. 6A, 6B, and 6 C depict a time sequence during which a sample is admitted to the device of FIG. 6.
  • FIG. 7 is a schematic of a device having multiple measurement areas in parallel, multiple stop junctions in parallel, and a single bladder.
  • FIG. 8 is a schematic of a device having multiple measurement areas in series, with a single stop junction, a single bladder, and a filter over the sample port.
  • FIG. 9 is a schematic of a device having multiple measurement areas and multiple stop junctions arranged in an alternating series, as well as multiple bladders.
  • FIG. 10 is a schematic of a device that includes multiple measurement areas in parallel, a single bladder, and a single bypass channel.
  • FIG. 11 is a schematic of a device having multiple measurement areas in series, multiple stop junctions in series, multiple-bladders in series, and multiple bypass channels.
  • FIG. 12 is an exploded view of an injection-molded device of this invention.
  • FIG. 13 is a perspective view of the device of FIG. 12.
  • This invention relates to a fluidic device for analyzing biological fluid.
  • the device is of the type that relates a physical parameter of the fluid, or an element of the fluid, to an analyte concentration in the fluid or to a property of the fluid.
  • physical parameters e.g., electrical, magnetic, fluidic, or optical
  • the device includes a sample application area; a bladder, to create a suction force to draw the sample into the device; a measurement area, in which the sample may undergo a change in an optical parameter, such as light scattering; and a stop junction to precisely stop flow after filling the measurement area.
  • the device is substantially transparent over the measurement area, so that the area can be illuminated by a light source on one side and the transmitted light measured on the opposite side.
  • the measurement on the sample may be of a parameter that is not changing, but typically the sample undergoes a change in the measurement area, and the change in transmitted light is a measure of the analyte or fluid property of interest.
  • light that is scattered from a fluid sample or light that passes through the sample and is reflected back through a second time (by a reflector on that opposite side) can be detected by a detector on the same side as the light source.
  • This type of device is suitable for a variety of analytical tests of biological fluids, such as determining biochemical or hematological characteristics, or measuring the concentration in such fluids of proteins, hormones, carbohydrates, lipids, drugs, toxins, gases, electrolytes, etc.
  • analytical tests of biological fluids, such as determining biochemical or hematological characteristics, or measuring the concentration in such fluids of proteins, hormones, carbohydrates, lipids, drugs, toxins, gases, electrolytes, etc.
  • the procedures for performing these tests have been described in the literature. Among the tests, and where they are described, are the following:
  • TPA Assay Mann, K. G., et al., Blood, 76, 755, (1990).; and Hartshorn, J. N. et al., Blood, 78, 833 (1991).
  • APTT Activated Partial Thromboplastin Time Assay: Proctor, R. R. and Rapaport, S. I. Amer. J. Clin. Path, 36, 212 (1961); Brandt, J. T. and Triplett, D. A. Amer. J. Clin. Path., 76, 530 (1981); and Kelsey, P. R. Thromb. Haemost. 52, 172 (1984).
  • HbAlc Assay (Glycosylated Hemoglobin Assay): Nicol, D. J. et al., Clin. Chem. 29, 1694 (1983).
  • the present device is particularly well suited for measuring blood-clotting time—“prothrombin time” or “PT time”—and details regarding such a device appear below.
  • the modifications needed to adapt the device for applications such as those listed above require no more than routine experimentation.
  • FIG. 1 is a plan view of a device 10 of the present invention.
  • FIG. 2 is an exploded view and FIG. 3 a perspective view of the device.
  • Sample is applied to sample port 12 after bladder 14 has been compressed.
  • the region of layer 26 and/or layer 28 that adjoins the cutout for bladder 14 must be resilient, to permit bladder 14 to be compressed.
  • Polyester of about 0.1 mm thickness has suitable resilience and springiness.
  • top layer 26 has a thickness of about 0.125 mm, bottom layer 28 about 0.100 mm.
  • the volume of bladder 14 is preferably at least about equal to the combined volume of channel 16 and measurement area 18 . If measurement area 18 is to be illuminated from below, layer 28 must be transparent where it adjoins measurement area 18 .
  • reagent 20 contains thromboplastin that is free of bulking reagents normally found in lyophilized reagents.
  • stop junction 22 adjoins bladder 14 and measurement area 18 ; however, a continuation of channel 16 may be on either or both sides of stop junction 22 , separating the stop junction from measurement area 18 and/or bladder 14 .
  • sample flow stops When the sample reaches stop junction 22 , sample flow stops.
  • the principle of operation of stop junctions is described in U.S. Pat. No. 5,230,866, incorporated herein by reference.
  • all the above elements are formed by cutouts in intermediate layer 24 , sandwiched between top layer 26 and bottom layer 28 .
  • layer 24 is double-sided adhesive tape.
  • Stop junction 22 is formed by an additional cutout in layer 26 and/or 28 , aligned with the cutout in layer 24 and sealed with sealing layer 30 and/or 32 .
  • the stop junction comprises cutouts in both layers 26 and 28 , with sealing layers 30 and 32 .
  • Each cutout for stop junction 22 is at as least as wide as channel 16 .
  • an optional filter 12 A to cover sample port 12 .
  • the filter may separate out red blood cells from a whole blood sample and/or may contain a reagent to interact with the blood to provide additional information.
  • a suitable filter comprises an anisotropic membrane, preferably a polysulfone membrane of the type available from Spectral Diagnostics, Inc., Toronto, Canada.
  • Optional reflector 18 A may be on, or adjacent to, a surface of layer 26 and positioned over measurement area 18 . If the reflector is present, the device becomes a transflectance device.
  • the method of using the strip of FIGS. 1, 2, and 3 can be understood with reference to a schematic of the elements of a meter shown in FIG. 4, which contemplates an automated meter. Alternatively, manual operation is also possible. (In that case, bladder 14 is manually depressed before sample is applied to sample port 12 , then released.)
  • the first step the user performs is to turn on the meter, thereby energizing strip detector 40 , sample detector 42 , measurement system 44 , and optional heater 46 .
  • the second step is to insert the strip.
  • the strip is not transparent over at least a part of its area, so that an inserted strip will block the illumination by LED 40 a of detector 40 b .
  • Detector 40 b thereby senses that a strip has been inserted and triggers bladder actuator 48 to compress bladder 14 .
  • a meter display 50 then directs the user to apply a sample to sample port 12 as the third and last step the user must perform to initiate the measurement sequence.
  • the empty sample port is reflective. When a sample is introduced into the sample port, it absorbs light from LED 42 a and thereby reduces the light that is reflected to detector 42 b . That reduction in light, in turn, signals actuator 48 to release bladder 14 .
  • the resultant suction in channel 16 draws sample through measurement area 18 to stop junction 22 .
  • Measurement system 44 includes an LED/detector pair (like 44 a and 44 b ) for each measurement area. Analysis of the transmitted light as a function of time (as described below) permits a calculation of the PT time, which is displayed on the meter display 50 .
  • sample temperature is maintained at about 37° C. by heater 46 .
  • the detector senses a sample in sample port 12 , simply by detecting a reduction in (specular) reflection of a light signal that is emitted by 42 a and detected by 42 b .
  • a simple system cannot easily distinguish between a whole blood sample and some other liquid (e.g., blood serum) placed in the sample port in-error or, even, an object (e.g., a finger) that can approach sample port 12 and cause the system to erroneously conclude that a proper sample has been applied.
  • another embodiment measures diffuse reflection from the sample port. This embodiment appears in FIG. 4A, which shows detector 42 b positioned normal to the plane of strip 10 . With the arrangement shown in FIG.
  • the signal detected by 42 b increases abruptly, because of scattering in the blood sample, then decreases, because of rouleaux formation (discussed below).
  • the detector system 42 is thus programmed to require that type of signal before causing actuator 48 to release bladder 14 .
  • the delay of several seconds in releasing bladder 14 does not substantially affect the readings described below
  • FIG. 5 depicts a typical “clot signature” curve in which the current from detector 44 b is plotted as a function of time.
  • Blood is first detected in the measurement area by 44 b at time 1 .
  • the blood fills the measurement area.
  • the reduction in current during that time interval is due to light scattered by red cells and is thus an approximate measure of the hematocrit.
  • sample has filled the measurement area and is at rest, its movement having been stopped by the stop junction.
  • the red cells begin to stack up like coins (rouleaux formation).
  • the rouleaux effect allows increasing light transmission through the sample (and less scattering) in the time interval between points 2 and 3 .
  • clot formation ends rouleaux formation and transmission through the sample reaches a maximum.
  • the PT time can be calculated from the interval B between points 1 and 3 or between 2 and 3 .
  • blood changes state from liquid to a semi-solid gel, with a corresponding reduction in light transmission.
  • the reduction in current C between the maximum 3 and endpoint 4 correlates with fibrinogen in the sample.
  • the device pictured in FIG. 2 and described above is preferably formed by laminating thermoplastic sheets 26 and 28 to a thermoplastic intermediate layer 24 that has adhesive on both of its surfaces.
  • the cutouts that form the elements shown in FIG. 1 may be formed, for example, by laser- or die-cutting of layers 24 , 26 , and 28 .
  • the device can be formed of molded plastic.
  • the surface of sheet 28 is hydrophilic. (Film 9962, available from 3M, St. Paul. Minn.) However, the surfaces do not need to be hydrophilic, because the sample fluid will fill the device without capillary forces.
  • sheets 26 and 28 may be untreated polyester or other thermoplastic sheet, well known in the art.
  • the device can be used in any orientation. Unlike capillary fill devices that have vent holes through which sample could leak, the present device vents through the sample port before sample is applied, which means that the part of the strip that is first inserted into the meter is without an opening, reducing the risk of contamination.
  • FIG. 6 is a plan view of another embodiment of the device of the present invention, in which the device to includes a bypass channel 52 that connects channel 16 with bladder 14 .
  • the function and operation of the bypass channel can be understood by referring to FIGS. 6A, 6B, and 6 C which depict a time sequence during which a sample is drawn into device 10 for the measurement.
  • FIG. 6A depicts the situation after a user has applied a sample to the strip, while bladder 14 is compressed. This can be accomplished by applying one or more drops of blood.
  • FIG. 6B depicts the situation after the bladder is decompressed.
  • the resulting reduced pressure in the inlet channel 16 draws the sample initially into the measurement area 18 .
  • stop junction 22 the sample encounters a back pressure that causes it to stop and causes additional sample to be drawn into the bypass channel.
  • FIG. 6C depicts the situation when a reading is taken. Sample is isolated and at rest in measurement area 18 . Excess sample and/or air has been drawn into bypass channel 52 .
  • the bypass channel of FIG. 6 provides an important improvement over the operation of the “basic” strip-of FIGS. 1 - 3 .
  • stop junction 22 stops the flow of sample after it fills measurement area 18 .
  • the stop junction accomplishes the flow stoppage as a result of surface tension acting on the meniscus at the leading edge of the fluid at an abrupt change in cross section of the flow channel.
  • the pressure on the bladder side of the stop junction remains below atmospheric pressure while the pressure on the sample side remains open to atmosphere.
  • there is an ambient pressure imbalance on the two sides The greater the imbalance, the greater the risk that the stop junction will leak and that sample will flow through the stop junction, interfering with rouleaux formation, and, consequently, providing inaccurate values of PT.
  • bypass channel 52 minimizes that risk.
  • the reduced pressure on the bladder side of the stop junction draws sample into the bypass channel (FIGS. 6B, 6C) until the ambient pressure is equalized at atmospheric pressure on both sides of the stop junction. Note that the (reduced) pressure on the bladder side is relatively uncontrolled.
  • the bypass channel 52 by enabling the pressures on the two sides of the stop junction to equilibrate, permits the use of larger bladders that have greater suction. Larger bladders, in turn, provide more reliable operation of the system.
  • FIG. 7 depicts an embodiment of the present invention in which there are multiple (three are shown) measurement areas “in parallel”. That is to say that the channels 116 P, 216 P, and 316 P fill substantially simultaneously (assuming they have the same dimensions).
  • the situation depicted in FIG. 7, with channels and measurement areas filled with blood, is achieved, as discussed above, by applying sample to sample pott 112 while bladder 114 is compressed, then releasing bladder 114 .
  • the first step is to apply sample to sample well 112 while bladder 114 is compressed.
  • the second step is to release the bladder. Sample flows to measurement areas 118 P, 218 P, and 318 P, and flow stops when sample reaches stop junctions, 122 P, 222 P, and 322 P, respectively.
  • the optional second and third measurement areas may contain, for example, reagents that neutralize the presence of interferents (such as heparin) in the blood, or that provide a built-in control on the PT measurement, or that measure another blood parameter (such as APPT)
  • interferents such as heparin
  • APPT another blood parameter
  • FIG. 8 is a schematic illustration of an embodiment in which multiple measurement areas are “in series”, meaning that they fill sequentially.
  • measurement areas 118 S, 218 S, and 318 S fill sequentially, through a single channel 116 S, until the sample reaches stop junction 122 S.
  • a potential drawback of this design is that sample passing from one measurement area to the next may carry over reagent.
  • FIG. 9 is a schematic of another embodiment of a device that is adapted for multiple sequential tests.
  • stop junctions 122 T, 222 T, and 322 T permit a user to control the timing of sequential filling of measurement areas 118 T, 218 T, and 318 T.
  • bladders 114 , 214 , and 314 are all compressed before a blood sample is applied to sample well 112 .
  • Bladder 114 is then released to draw blood into measurement area 118 T to stop junction 122 T.
  • bladder 214 is released to permit blood to break through stop junction 122 T and enter measurement area 218 T to stop junction 222 T.
  • bladder 314 is decompressed, permitting sample to break through stop function 222 T and flow to stop junction 322 T.
  • the device of FIG. 9 must be carefully formed, since the force drawing sample into the device—caused by decompressing a bladder—must be balanced against the opposing force—exerted by a stop junction. If the drawing force is too great, a stop junction may prematurely permit sample to pass; if it's too small, it will not draw the sample through a stop junction, when that is intended.
  • FIG. 10 depicts a preferred embodiment of the present device. It is a parallel multi-channel device that includes bypass channel 152 P. Bypass channel 152 P serves a purpose in this device that is analogous to that served by bypass channel 52 in the device of FIG. 6, which was described above.
  • Measurement area 118 P contains thromboplastin.
  • measurement areas 218 P and 318 P contain controls, more preferably, the controls described below.
  • Area 218 P contains thromboplastin, bovine eluate, and recombinant Factor VIIa.
  • the composition is selected to normalize the clotting time of a blood sample by counteracting the effect of an anticoagulant, such as warfarin.
  • Measurement area 318 P contains thromboplastin and bovine eluate alone, to partially overcome the effect of an anticoagulent. Thus, 3 measurements are made on the strip. PT time of the sample, the measurement of primary interest, is measured on area 118 P. However, that measurement is validated only when measurements on areas 218 P and 318 P yield results within a predetermined range. If either or both of these control measurements are outside the range, then a retest is indicated. Extended stop junction 422 stops flow in all three measurement areas.
  • FIG. 11 depicts a device that includes bypass channels 152 S and 252 S to permit timed filling of measurement areas 118 T and 218 T. Operation of the device of FIG. 11 is analogous to that of the device of FIG. 9, described above, with the following exception.
  • First bypass channel 152 S has a region in which a reagent that causes clotting, such as thromboplastin, is coated. As a first measurement is made in reagent area 118 T, a clot forms in blood that had been drawn into bypass channel 152 S. Thus, when the second bladder is decompressed, blood is blocked from being drawn through bypass 152 S and instead is drawn though stop junction 122 T to measurement area 218 T and bypass channel 252 S.
  • FIG. 12 is an exploded view of an injection-molded device 110 , including top layer 126 and bottom layer 128 sandwiching intermediate layer 124 .
  • the intermediate layer has depressions in its top surface that form sample port 112 , channel 116 , measurement area 118 , and optional bypass channel 152 .
  • Stop junction 122 passes through the thickness of intermediate layer 124 .
  • the principle of operation of the injection molded device is the same as described above. It provides greater flexibility in the design of the stop junction, as well as the other elements of the device, because a wide range of channel cross sections are feasible.
  • the molded structure also provides more rigidity, although it is substantially more costly.
  • a strip of this invention is made by first passing a double-sided adhesive tape (RX 675SLT, available from Scapa Tapes, Windsor, Conn.) sandwiched between two release liners into a laminating and rotary die-cutting converting system.
  • RX 675SLT double-sided adhesive tape
  • the pattern shown in FIG. 6, with the exception of the stop junction, is cut through the top release liner and tape, but not through the bottom release liner, which is then removed as waste, along with the cutouts from the tape.
  • Polyester film treated to be hydrophilic (3M9962, available from 3M, St. Paul, Minn.) is laminated to the exposed bottom side of the tape.
  • Reagent thromboplastin, available from Ortho Clinical Diagnostics, Raritan, N.J.
  • Reagent is then printed onto the reagent area ( 18 ) of the polyester film by bubble jet printing, using printing heads 51612A, from Hewlett Packard, Corvallis, Oreg.
  • a sample port is cut in untreated polyester film (AR1235, available from Adhesives Research, Glen Rock, Pa.) and then laminated, in register, to the top of the double-sided tape (after removing the release layer).
  • a die then cuts the stop junction through the three layers of the sandwich.
  • strips of single-sided adhesive tape (MSX4841, available from 3M, St. Paul, Minn.) are applied to the outside of the polyester layers to seal the stop junction.
  • Reagent that is bubble-jet printed onto areas 118 P, 218 P, and 318 P is, respectively, thromboplastin; thromboplastin, bovine eluate, and recombinant Factor VIIa; and thromboplastin and bovine eluate alone.
  • the bovine eluate (plasma barium citrate bovine eluate) is available from Haembtologic Technologies, Burlington, Vt.; and recombinant Factor VIIa from American Diagnostica, Greenwich, Conn.
  • Measurements made on a whole blood sample using the strip of this Example yield a curve of the type shown in FIG. 5 for each of the measurement areas.
  • the data from the curves for the controls are used to qualify the data from the curve for measurement area 118 P.
  • the PT time can be determined more reliably than can be done with a strip having a single measurement area.
  • the device of FIGS. 12 and 13 is formed by sandwiching middle layer 124 between top layer 126 and bottom layer 128 .
  • the middle and bottom layers are injection molded polycarbonate (Lexan*121) and have thicknesses of 6.3 mm and 1.5 mm, respectively.
  • Top layer 126 is made by die cutting 0.18 mm Lexan* 8010 sheet. The elements are ultrasonically welded after the reagent of Example 1 is applied to reagent area 118 .
  • the Lexan* material is available from General Electric, Pittsfield, Mass.

Abstract

A fluidic medical diagnostic device permits measurement of analyte concentration or a property of a biological fluid, particularly the coagulation time of blood. The device has at one-end a sample port for introducing a sample and at the other end a bladder for drawing the sample to a measurement area. A channel carries the sample from the sample port to the measurement area, and a stop junction, between the measurement area and bladder, halts the sample flow. The desired measurement can be made by placing the device into a meter which measures a physical property of the sample—typically, optical transmittance—after it has interacted with a reagent in the measurement area.

Description

    CROSS-REFERENCE TO PRIOR PROVISIONAL APPLICATION
  • This application claims the benefit of U.S. Provisional Application No. 60/093,421, filed Jul. 20, 1998[0001]
  • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention [0002]
  • This invention relates to a fluidic medical diagnostic device for measuring the concentration of an analyte in or a property of a biological fluid. [0003]
  • 2. Description of the Related Art [0004]
  • A variety of medical diagnostic procedures involve tests on biological fluids, such as blood, urine, or saliva, and are based on a change in a physical characteristic of such a fluid or an element of the fluid, such as blood serum. The characteristic can be an electrical, magnetic, fluidic, or optical property. When as optical property is monitored, these procedures may make use of a transparent or translucent device to contain the biological fluid and a reagent. A change in light absorption of the fluid can be related to an analyte concentration in, or property of, the fluid. Typically, a light source is located adjacent to one surface of the device and a detector is adjacent to the opposite surface. The detector measures light transmitted through a fluid sample. Alternatively, the light source and detector can be on the same side of the device, in which case the detector measures light scattered and/or reflected by the sample. Finally, a reflector may be located at or adjacent to the opposite surface. A device of this latter type, in which light is first transmitted through the sample area, then reflected through a second time, is called a “transflectance” device. References to “light” throughout this specification and the appended claims should be understood to include the infrared and ultraviolet spectra, as well as the visible. References to “absorption” are meant to refer to the reduction in intensity as a light beam passes through a medium; thus, it encompasses both “true” absorption and scattering. [0005]
  • An example of a transparent test device is described in Wells et al. WO94/02850, published on Feb. 3, 1994. Their device comprises a sealed housing, which is transparent or translucent, impervious, and rigid or semi-rigid. An assay material is contained within the housing, together with one or more assay reagents at predetermined sites. The housing is opened and the sample introduced just before conducting the assay. The combination of assay reagents and analyte in the sample results in a change in optical properties, such as color, of selected reagents at the end of the assay. The results can be read visually or with an optical instrument. [0006]
  • U.S. Pat. No. 3,620,676, issued on Nov. 16, 1971 to Davis, discloses a calorimetric indicator for liquids. The indicator includes a “half-bulb cavity”; which is compressible. The bulb is compressed and released to form a suction that draws fluid from a source, through a half-tubular cavity that has an indicator imprinted on its wall. The only controls on fluid flow into the indicator are how much the bulb is compressed and how long the indicator inlet is immersed in the source, while the bulb is released. [0007]
  • U.S. Pat. No. 3,640,267, issued on Feb. 8, 1972 to Hurtig et al., discloses a container for collecting Kilo samples of body fluid that includes a chamber that has resilient, collapsible walls. The walls are squeezed before the container inlet is placed into the fluid being collected. When released, the walls are restored to their uncollapsed condition, drawing fluid into and through the inlet. As with the Davis device, discussed above, control of fluid flow into the indicator is very limited. [0008]
  • U.S. Pat. No. 4,088,448, issued on May 9, 1978 to Lilja et al., discloses a cuvette, which permits optical analysis of a sample mixed with a reagent. The-reagent is coated on the walls of a cavity, which is then filled with a liquid sample. The sample mixes with the reagent to cause an optically-detectable change. [0009]
  • A number of patents, discussed below, disclose devices for diluting and/or analyzing biological fluid samples. These devices include valve-like designs to control the flow of the sample. [0010]
  • U.S. Pat. No. 4,426,451, issued on Jan. 17, 1984 to Columbus, discloses a multi-zone fluidic device that has pressure-actuatable means for controlling the flow of fluid between the zones. His device makes use of pressure balances on a liquid meniscus at the interface between a first zone and a second zone that has a different cross section. When both the first and second zones are at atmospheric pressure, surface tension creates a back pressure that stops the liquid meniscus from proceeding from the first zone to the second. The configuration of this interface or “stop junction” is such that the liquid flows into the second zone only upon application of an externally generated pressure to the liquid in the first zone that is sufficient to push the meniscus into the second zone. [0011]
  • U.S. Pat. No. 4,868,129, issued on Sep. 19, 1989 to Gibbons et al., discloses that the back pressure in a stop junction can be overcome by hydrostatic pressure on the liquid in the first zone, for example by having a column of fluid in the first zone. [0012]
  • U.S. Pat. No. 5,230,866, issued on Jul. 27, 1993 to Shartle et al., discloses a fluidic device with multiple stop junctions in which the surface tension-induced back pressure at the stop junction is augmented; for example, by trapping and compressing gas in the second zone. The compressed gas can then be vented before applying additional hydrostatic pressure to the first zone to cause fluid to flow into the second zone. By varying the back pressure of multiple stop junctions in parallel, “rupture junctions” can be formed, having lower maximum back pressure. [0013]
  • U.S. Pat. No. 5,472,603, issued on Dec. 5, 1995 to Schembri (see also U.S. Pat. No. 5,627,041), discloses using centrifugal force to overcome the back pressure in a stop junction. When flow stops, the first zone is at atmospheric pressure plus a centrifugally generated pressure that is less than the pressure required to overcome the back pressure. The second zone is at atmospheric pressure. To resume flow, additional centrifugal pressure is applied to the first zone, overcoming the meniscus back pressure. The second zone remains at atmospheric pressure. [0014]
  • European Patent Application EP 0,803,288, of Naka et al., published on Oct. 29, 1997, discloses a device and method for analyzing a sample that includes drawing the sample into the device by suction, then reacting the sample with a reagent in an analytical section. Analysis is done by optical or electrochemical means. In alternate embodiments, there are multiple analytical sections and/or a bypass channel. The flow among these sections is balanced without using stop junctions. [0015]
  • U.S. Pat. No. 5,700,695, issued on Dec. 23, 1997 to Yassinzadeh et al., discloses an apparatus for collecting and manipulating a biological fluid that uses a “thermal pressure chamber” to provide the driving force for moving the sample through the apparatus. [0016]
  • U.S. Pat. No. 5,736,404, issued on Apr. 7, 1998, to Yassinzadeh et al., discloses a method for determining the coagulation time of a blood sample that involves causing an end of the sample to oscillate within a passageway. The oscillating motion is caused by alternately increasing and decreasing the pressure on the sample. [0017]
  • SUMMARY OF THE INVENTION
  • The present invention provides a fluidic diagnostic device for measuring an analyte concentration or property of a biological fluid. The device comprises a first layer and second layer at least one of which has a resilient region over at least part of its area, separated by an intermediate layer, in which cutouts in the intermediate layer form, with the first and second layers, [0018]
  • a) a sample port for introducing a sample of the biological fluid into the device; [0019]
  • b) a first measurement area, in which a physical parameter of the sample is measured and related to the analyte concentration or property of the fluid; [0020]
  • c) a first channel, having a first end and a second end, to provide a fluidic path from the sample port at the first end through the first measurement area; [0021]
  • d) a first bladder at the second end of the first channel, comprising at least a part of the resilient region in at least the first or second layer and having a volume that is at least about equal to the combined volume of the first measurement area and first channel; and [0022]
  • e) a first stop junction in the first channel between the first measurement area and first bladder that comprises a co-aligned through hole in at least the first or second layer, the through hole being overlaid with a third layer. [0023]
  • In another embodiment, the device comprises [0024]
  • a first layer, which has a resilient region over at least a part of its area, and a second layer, separated by an intermediate layer, in which recesses in a first surface of the intermediate layer form, with the first layer, [0025]
  • a) a sample port for introducing a sample of the biological fluid into the device; [0026]
  • b) a measurement area, in which the sample undergoes a change in a physical parameter that is measured and related to the analyte concentration or property of the fluid; [0027]
  • c) a channel, having a first end and a second end, to provide a fluidic path from the sample port at the first end through the measurement area; and [0028]
  • d) a bladder, at the second end of the channel, comprising at least a part of the resilient region in the first layer and having a volume that is at least about equal to the combined volume of the measurement area and channel; and [0029]
  • a stop junction in the channel between the measurement area and bladder that comprises two passages substantially normal to the first surface of the intermediate layer, each passage having a first end in fluid communication with the channel and a second end in fluid communication with a recess in a second surface of the intermediate layer, which recess provides fluid communication between the second ends of the passages. [0030]
  • The device is particularly well adapted for measuring prothrombin time (PT time), with the biological fluid being whole blood and the measurement area having a composition that catalyzes the blood clotting cascade.[0031]
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a plan view of a device of the present invention. [0032]
  • FIG. 2 is an exploded view of the device of FIG. 1. [0033]
  • FIG. 3 is a perspective view of the device of FIG. 1. [0034]
  • FIG. 4 is a schematic of a meter for use with a device of this invention. [0035]
  • FIG. 4A depicts an alternative embodiment of an element of the meter of FIG. 4. [0036]
  • FIG. 5 is a graph of data that is used to determine PT time. [0037]
  • FIG. 6 is a plan view of an alternative embodiment of a device of this invention. [0038]
  • FIGS. 6A, 6B, and [0039] 6C depict a time sequence during which a sample is admitted to the device of FIG. 6.
  • FIG. 7 is a schematic of a device having multiple measurement areas in parallel, multiple stop junctions in parallel, and a single bladder. [0040]
  • FIG. 8 is a schematic of a device having multiple measurement areas in series, with a single stop junction, a single bladder, and a filter over the sample port. [0041]
  • FIG. 9 is a schematic of a device having multiple measurement areas and multiple stop junctions arranged in an alternating series, as well as multiple bladders. [0042]
  • FIG. 10 is a schematic of a device that includes multiple measurement areas in parallel, a single bladder, and a single bypass channel. [0043]
  • FIG. 11 is a schematic of a device having multiple measurement areas in series, multiple stop junctions in series, multiple-bladders in series, and multiple bypass channels. [0044]
  • FIG. 12 is an exploded view of an injection-molded device of this invention. [0045]
  • FIG. 13 is a perspective view of the device of FIG. 12.[0046]
  • DETAILED DESCRIPTION OF THE INVENTION
  • This invention relates to a fluidic device for analyzing biological fluid. The device is of the type that relates a physical parameter of the fluid, or an element of the fluid, to an analyte concentration in the fluid or to a property of the fluid. Although a variety of physical parameters—e.g., electrical, magnetic, fluidic, or optical—can form the basis for the measurement, a change in optical parameters is a preferred basis, and the details that follow refer to an optical device. The device includes a sample application area; a bladder, to create a suction force to draw the sample into the device; a measurement area, in which the sample may undergo a change in an optical parameter, such as light scattering; and a stop junction to precisely stop flow after filling the measurement area. [0047]
  • Preferably, the device is substantially transparent over the measurement area, so that the area can be illuminated by a light source on one side and the transmitted light measured on the opposite side. The measurement on the sample may be of a parameter that is not changing, but typically the sample undergoes a change in the measurement area, and the change in transmitted light is a measure of the analyte or fluid property of interest. Alternatively, light that is scattered from a fluid sample or light that passes through the sample and is reflected back through a second time (by a reflector on that opposite side) can be detected by a detector on the same side as the light source. [0048]
  • This type of device is suitable for a variety of analytical tests of biological fluids, such as determining biochemical or hematological characteristics, or measuring the concentration in such fluids of proteins, hormones, carbohydrates, lipids, drugs, toxins, gases, electrolytes, etc. The procedures for performing these tests have been described in the literature. Among the tests, and where they are described, are the following: [0049]
  • (1) Chromogenic Factor XIIa Assay (and other clotting factors as well): Rand, M. D. et al., Blood, [0050] 88, 3432 (1996).
  • (2) Factor X Assay: Bick, R. L. Disorders of Thrombosis and Hemostasis: Clinical and Laboratory Practice. Chicago, ASCP Press, 1992. [0051]
  • (3) DRVVT (Dilute Russells Viper Venom Test): Exner, T. et al., Blood Coag. Fibrinol., 1, 259 (1990). [0052]
  • (4) Immunonephelometric and Immunoturbidimetric Assays for Proteins: Whicher, J. T., CRC Crit. Rev. Clin Lab Sci. 18:213 (1983). [0053]
  • (5) TPA Assay: Mann, K. G., et al., Blood, 76, 755, (1990).; and Hartshorn, J. N. et al., Blood, 78, 833 (1991). [0054]
  • (6) APTT (Activated Partial Thromboplastin Time Assay): Proctor, R. R. and Rapaport, S. I. Amer. J. Clin. Path, 36, 212 (1961); Brandt, J. T. and Triplett, D. A. Amer. J. Clin. Path., 76, 530 (1981); and Kelsey, P. R. Thromb. Haemost. 52, 172 (1984). [0055]
  • (7) HbAlc Assay (Glycosylated Hemoglobin Assay): Nicol, D. J. et al., Clin. Chem. 29, 1694 (1983). [0056]
  • (8) Total Hemoglobin: Schneck et al., Clinical Chem., 32/33, 526 (1986); and U.S. Pat. No. 4,088,448. [0057]
  • (9) Factor Xa: Vinazzer, H., Proc. Symp. Dtsch. Ges. Klin. Chem., 203 (1977), ed. By Witt, I [0058]
  • (10) Colorimetric Assay for Nitric Oxide: Schmidt, H. H., et al., Biochemica, 2, 22,(1995). [0059]
  • The present device is particularly well suited for measuring blood-clotting time—“prothrombin time” or “PT time”—and details regarding such a device appear below. The modifications needed to adapt the device for applications such as those listed above require no more than routine experimentation. [0060]
  • FIG. 1 is a plan view of a [0061] device 10 of the present invention. FIG. 2 is an exploded view and FIG. 3 a perspective view of the device. Sample is applied to sample port 12 after bladder 14 has been compressed. Clearly, the region of layer 26 and/or layer 28 that adjoins the cutout for bladder 14 must be resilient, to permit bladder 14 to be compressed. Polyester of about 0.1 mm thickness has suitable resilience and springiness. Preferably, top layer 26 has a thickness of about 0.125 mm, bottom layer 28 about 0.100 mm. When the bladder is released, suction draws sample through channel 16 to measurement area 18, which preferably contains a reagent 20. In order to ensure that measurement area 18 can be filled with sample, the volume of bladder 14 is preferably at least about equal to the combined volume of channel 16 and measurement area 18. If measurement area 18 is to be illuminated from below, layer 28 must be transparent where it adjoins measurement area 18. For a PT test, reagent 20 contains thromboplastin that is free of bulking reagents normally found in lyophilized reagents.
  • As shown in FIGS. 1, 2, and [0062] 3, stop junction 22 adjoins bladder 14 and measurement area 18; however, a continuation of channel 16 may be on either or both sides of stop junction 22, separating the stop junction from measurement area 18 and/or bladder 14. When the sample reaches stop junction 22, sample flow stops. For PT measurements, it is important to stop the flow of sample as it reaches that point to permit reproducible “rouleaux formation”—the stacking of red blood cells—which is an important step in monitoring blood clotting using the present invention. The principle of operation of stop junctions is described in U.S. Pat. No. 5,230,866, incorporated herein by reference.
  • As shown in FIG. 2, all the above elements are formed by cutouts in [0063] intermediate layer 24, sandwiched between top layer 26 and bottom layer 28. Preferably, layer 24 is double-sided adhesive tape. Stop junction 22 is formed by an additional cutout in layer 26 and/or 28, aligned with the cutout in layer 24 and sealed with sealing layer 30 and/or 32. Preferably, as shown, the stop junction comprises cutouts in both layers 26 and 28, with sealing layers 30 and 32. Each cutout for stop junction 22 is at as least as wide as channel 16. Also shown in FIG. 2 is an optional filter 12A to cover sample port 12. The filter may separate out red blood cells from a whole blood sample and/or may contain a reagent to interact with the blood to provide additional information. A suitable filter comprises an anisotropic membrane, preferably a polysulfone membrane of the type available from Spectral Diagnostics, Inc., Toronto, Canada. Optional reflector 18A may be on, or adjacent to, a surface of layer 26 and positioned over measurement area 18. If the reflector is present, the device becomes a transflectance device.
  • The method of using the strip of FIGS. 1, 2, and [0064] 3 can be understood with reference to a schematic of the elements of a meter shown in FIG. 4, which contemplates an automated meter. Alternatively, manual operation is also possible. (In that case, bladder 14 is manually depressed before sample is applied to sample port 12, then released.) The first step the user performs is to turn on the meter, thereby energizing strip detector 40, sample detector 42, measurement system 44, and optional heater 46. The second step is to insert the strip. Preferably, the strip is not transparent over at least a part of its area, so that an inserted strip will block the illumination by LED 40 a of detector 40 b. (More preferably, the intermediate layer is formed of a non-transparent material, so that background light does not enter measurement system 44.) Detector 40 b thereby senses that a strip has been inserted and triggers bladder actuator 48 to compress bladder 14. A meter display 50 then directs the user to apply a sample to sample port 12 as the third and last step the user must perform to initiate the measurement sequence. The empty sample port is reflective. When a sample is introduced into the sample port, it absorbs light from LED 42 a and thereby reduces the light that is reflected to detector 42 b. That reduction in light, in turn, signals actuator 48 to release bladder 14. The resultant suction in channel 16 draws sample through measurement area 18 to stop junction 22. Light from LED 44 a passes through measurement area 18, and detector 44 b monitors the light transmitted through the sample as it is clotting. When there are multiple measurement areas, measurement system 44 includes an LED/detector pair (like 44 a and 44 b) for each measurement area. Analysis of the transmitted light as a function of time (as described below) permits a calculation of the PT time, which is displayed on the meter display 50. Preferably, sample temperature is maintained at about 37° C. by heater 46.
  • As described above, the detector senses a sample in [0065] sample port 12, simply by detecting a reduction in (specular) reflection of a light signal that is emitted by 42 a and detected by 42 b. However, that simple system cannot easily distinguish between a whole blood sample and some other liquid (e.g., blood serum) placed in the sample port in-error or, even, an object (e.g., a finger) that can approach sample port 12 and cause the system to erroneously conclude that a proper sample has been applied. To avoid this type of error, another embodiment measures diffuse reflection from the sample port. This embodiment appears in FIG. 4A, which shows detector 42 b positioned normal to the plane of strip 10. With the arrangement shown in FIG. 4A, if a whole blood sample has been applied to sample port 12, the signal detected by 42 b increases abruptly, because of scattering in the blood sample, then decreases, because of rouleaux formation (discussed below). The detector system 42 is thus programmed to require that type of signal before causing actuator 48 to release bladder 14. The delay of several seconds in releasing bladder 14 does not substantially affect the readings described below
  • FIG. 5 depicts a typical “clot signature” curve in which the current from [0066] detector 44 b is plotted as a function of time. Blood is first detected in the measurement area by 44 b at time 1. In the time interval A, between points 1 and 2, the blood fills the measurement area. The reduction in current during that time interval is due to light scattered by red cells and is thus an approximate measure of the hematocrit. At point 2, sample has filled the measurement area and is at rest, its movement having been stopped by the stop junction. The red cells begin to stack up like coins (rouleaux formation). The rouleaux effect allows increasing light transmission through the sample (and less scattering) in the time interval between points 2 and 3. At point 3, clot formation ends rouleaux formation and transmission through the sample reaches a maximum. The PT time can be calculated from the interval B between points 1 and 3 or between 2 and 3. Thereafter, blood changes state from liquid to a semi-solid gel, with a corresponding reduction in light transmission. The reduction in current C between the maximum 3 and endpoint 4 correlates with fibrinogen in the sample.
  • The device pictured in FIG. 2 and described above is preferably formed by laminating [0067] thermoplastic sheets 26 and 28 to a thermoplastic intermediate layer 24 that has adhesive on both of its surfaces. The cutouts that form the elements shown in FIG. 1 may be formed, for example, by laser- or die-cutting of layers 24, 26, and 28. Alternatively, the device can be formed of molded plastic. Preferably, the surface of sheet 28 is hydrophilic. (Film 9962, available from 3M, St. Paul. Minn.) However, the surfaces do not need to be hydrophilic, because the sample fluid will fill the device without capillary forces. Thus, sheets 26 and 28 may be untreated polyester or other thermoplastic sheet, well known in the art. Similarly, since gravity is not involved in filling, the device can be used in any orientation. Unlike capillary fill devices that have vent holes through which sample could leak, the present device vents through the sample port before sample is applied, which means that the part of the strip that is first inserted into the meter is without an opening, reducing the risk of contamination.
  • FIG. 6 is a plan view of another embodiment of the device of the present invention, in which the device to includes a [0068] bypass channel 52 that connects channel 16 with bladder 14. The function and operation of the bypass channel can be understood by referring to FIGS. 6A, 6B, and 6C which depict a time sequence during which a sample is drawn into device 10 for the measurement.
  • FIG. 6A depicts the situation after a user has applied a sample to the strip, while [0069] bladder 14 is compressed. This can be accomplished by applying one or more drops of blood.
  • FIG. 6B depicts the situation after the bladder is decompressed. The resulting reduced pressure in the [0070] inlet channel 16 draws the sample initially into the measurement area 18. When the sample reaches stop junction 22, the sample encounters a back pressure that causes it to stop and causes additional sample to be drawn into the bypass channel.
  • FIG. 6C depicts the situation when a reading is taken. Sample is isolated and at rest in [0071] measurement area 18. Excess sample and/or air has been drawn into bypass channel 52.
  • The bypass channel of FIG. 6 provides an important improvement over the operation of the “basic” strip-of FIGS. [0072] 1-3. In the basic strip, stop junction 22 stops the flow of sample after it fills measurement area 18. As was discussed earlier, it is important to stop the flow in order to facilitate rouleaux formation. As was also discussed earlier, the stop junction accomplishes the flow stoppage as a result of surface tension acting on the meniscus at the leading edge of the fluid at an abrupt change in cross section of the flow channel. In the basic strip, the pressure on the bladder side of the stop junction remains below atmospheric pressure while the pressure on the sample side remains open to atmosphere. Thus, there is an ambient pressure imbalance on the two sides. The greater the imbalance, the greater the risk that the stop junction will leak and that sample will flow through the stop junction, interfering with rouleaux formation, and, consequently, providing inaccurate values of PT.
  • [0073] Bypass channel 52 minimizes that risk. The reduced pressure on the bladder side of the stop junction draws sample into the bypass channel (FIGS. 6B, 6C) until the ambient pressure is equalized at atmospheric pressure on both sides of the stop junction. Note that the (reduced) pressure on the bladder side is relatively uncontrolled. The bypass channel 52, by enabling the pressures on the two sides of the stop junction to equilibrate, permits the use of larger bladders that have greater suction. Larger bladders, in turn, provide more reliable operation of the system.
  • FIG. 7 depicts an embodiment of the present invention in which there are multiple (three are shown) measurement areas “in parallel”. That is to say that the [0074] channels 116P, 216P, and 316P fill substantially simultaneously (assuming they have the same dimensions). The situation depicted in FIG. 7, with channels and measurement areas filled with blood, is achieved, as discussed above, by applying sample to sample pott 112 while bladder 114 is compressed, then releasing bladder 114. As discussed above, the first step is to apply sample to sample well 112 while bladder 114 is compressed. The second step is to release the bladder. Sample flows to measurement areas 118P, 218P, and 318P, and flow stops when sample reaches stop junctions, 122P, 222P, and 322P, respectively. The optional second and third measurement areas may contain, for example, reagents that neutralize the presence of interferents (such as heparin) in the blood, or that provide a built-in control on the PT measurement, or that measure another blood parameter (such as APPT)
  • FIG. 8 is a schematic illustration of an embodiment in which multiple measurement areas are “in series”, meaning that they fill sequentially. In this embodiment, [0075] measurement areas 118S, 218S, and 318S fill sequentially, through a single channel 116S, until the sample reaches stop junction 122S. A potential drawback of this design is that sample passing from one measurement area to the next may carry over reagent.
  • FIG. 9 is a schematic of another embodiment of a device that is adapted for multiple sequential tests. In that [0076] embodiment stop junctions 122T, 222T, and 322T permit a user to control the timing of sequential filling of measurement areas 118T, 218T, and 318T. In operation, bladders 114, 214, and 314 are all compressed before a blood sample is applied to sample well 112. Bladder 114 is then released to draw blood into measurement area 118T to stop junction 122T. At a selected later time, bladder 214 is released to permit blood to break through stop junction 122T and enter measurement area 218T to stop junction 222T. Finally, when the user wishes to use measurement area 318T, bladder 314 is decompressed, permitting sample to break through stop function 222T and flow to stop junction 322T. The device of FIG. 9 must be carefully formed, since the force drawing sample into the device—caused by decompressing a bladder—must be balanced against the opposing force—exerted by a stop junction. If the drawing force is too great, a stop junction may prematurely permit sample to pass; if it's too small, it will not draw the sample through a stop junction, when that is intended.
  • FIG. 10 depicts a preferred embodiment of the present device. It is a parallel multi-channel device that includes [0077] bypass channel 152P. Bypass channel 152P serves a purpose in this device that is analogous to that served by bypass channel 52 in the device of FIG. 6, which was described above. Measurement area 118P contains thromboplastin. Preferably, measurement areas 218P and 318P contain controls, more preferably, the controls described below. Area 218P contains thromboplastin, bovine eluate, and recombinant Factor VIIa. The composition is selected to normalize the clotting time of a blood sample by counteracting the effect of an anticoagulant, such as warfarin. Measurement area 318P contains thromboplastin and bovine eluate alone, to partially overcome the effect of an anticoagulent. Thus, 3 measurements are made on the strip. PT time of the sample, the measurement of primary interest, is measured on area 118P. However, that measurement is validated only when measurements on areas 218P and 318P yield results within a predetermined range. If either or both of these control measurements are outside the range, then a retest is indicated. Extended stop junction 422 stops flow in all three measurement areas.
  • FIG. 11 depicts a device that includes [0078] bypass channels 152S and 252S to permit timed filling of measurement areas 118T and 218T. Operation of the device of FIG. 11 is analogous to that of the device of FIG. 9, described above, with the following exception. First bypass channel 152S has a region in which a reagent that causes clotting, such as thromboplastin, is coated. As a first measurement is made in reagent area 118T, a clot forms in blood that had been drawn into bypass channel 152S. Thus, when the second bladder is decompressed, blood is blocked from being drawn through bypass 152S and instead is drawn though stop junction 122T to measurement area 218T and bypass channel 252S.
  • All the previous figures depict the device of this invention as a laminated strip structure; however, the device could also be an injection-molded structure of the type shown in FIGS. 12 and 13. FIG. 12 is an exploded view of an injection-molded device [0079] 110, including top layer 126 and bottom layer 128 sandwiching intermediate layer 124. The intermediate layer has depressions in its top surface that form sample port 112, channel 116, measurement area 118, and optional bypass channel 152. Stop junction 122 passes through the thickness of intermediate layer 124. Sample flow stops at the interface between stop junction 122 and channel A, which is formed by a depression in the bottom surface. Thus, the sample flows from sample port 112 through channel 116 to measurement area 118 into stop junction 122.
  • The principle of operation of the injection molded device is the same as described above. It provides greater flexibility in the design of the stop junction, as well as the other elements of the device, because a wide range of channel cross sections are feasible. The molded structure also provides more rigidity, although it is substantially more costly. [0080]
  • The following examples demonstrate the present invention in its various embodiments, but are not intended to be in any way limiting. [0081]
  • EXAMPLE 1
  • A strip of this invention is made by first passing a double-sided adhesive tape (RX 675SLT, available from Scapa Tapes, Windsor, Conn.) sandwiched between two release liners into a laminating and rotary die-cutting converting system. The pattern shown in FIG. 6, with the exception of the stop junction, is cut through the top release liner and tape, but not through the bottom release liner, which is then removed as waste, along with the cutouts from the tape. Polyester film treated to be hydrophilic (3M9962, available from 3M, St. Paul, Minn.) is laminated to the exposed bottom side of the tape. Reagent (thromboplastin, available from Ortho Clinical Diagnostics, Raritan, N.J.) is then printed onto the reagent area ([0082] 18) of the polyester film by bubble jet printing, using printing heads 51612A, from Hewlett Packard, Corvallis, Oreg. A sample port is cut in untreated polyester film (AR1235, available from Adhesives Research, Glen Rock, Pa.) and then laminated, in register, to the top of the double-sided tape (after removing the release layer). A die then cuts the stop junction through the three layers of the sandwich. Finally, strips of single-sided adhesive tape (MSX4841, available from 3M, St. Paul, Minn.) are applied to the outside of the polyester layers to seal the stop junction.
  • EXAMPLE 2
  • A procedure that is similar to the one described in Example 1 is followed to make a strip of the type depicted in FIG. 10. Reagent that is bubble-jet printed onto [0083] areas 118P, 218P, and 318P is, respectively, thromboplastin; thromboplastin, bovine eluate, and recombinant Factor VIIa; and thromboplastin and bovine eluate alone. The bovine eluate (plasma barium citrate bovine eluate) is available from Haembtologic Technologies, Burlington, Vt.; and recombinant Factor VIIa from American Diagnostica, Greenwich, Conn.
  • Measurements made on a whole blood sample using the strip of this Example yield a curve of the type shown in FIG. 5 for each of the measurement areas. The data from the curves for the controls ([0084] measurement areas 218P and 318P) are used to qualify the data from the curve for measurement area 118P. As a result, the PT time can be determined more reliably than can be done with a strip having a single measurement area.
  • EXAMPLE 3
  • The device of FIGS. 12 and 13 is formed by sandwiching [0085] middle layer 124 between top layer 126 and bottom layer 128. The middle and bottom layers are injection molded polycarbonate (Lexan*121) and have thicknesses of 6.3 mm and 1.5 mm, respectively. Top layer 126 is made by die cutting 0.18 mm Lexan* 8010 sheet. The elements are ultrasonically welded after the reagent of Example 1 is applied to reagent area 118. The Lexan* material is available from General Electric, Pittsfield, Mass.
  • The invention having been fully described, it will be apparent to one of ordinary skill in the art that many modifications and changes may be made to it without departing from the spirit and scope of the present invention. [0086]

Claims (21)

We claim:
1. A fluidic diagnostic device for measuring an analyte concentration or property of a biological fluid, comprising
a first layer and second layer, at least one of which has a resilient region over at least a part of its area, separated by an intermediate layer, in which cutouts in the intermediate layer form, with the first and second go layers,
a) a sample port for introducing a sample of the biological fluid into the device;
b) a first measurement area, in which a physical parameter of the sample is measured and related to the analyte concentration or property of the fluid;
c) a first channel, having a first end and a second end, to provide a fluidic path from the sample port at the first end through the first measurement area;
d) a first bladder, at the second end of the first channel, comprising at least a part of the resilient region in at least the first or second layer and having a volume that is at least about equal to the combined volume of the first measurement area and first channel; and
e) a first stop junction in the first channel between the first measurement area and first bladder that comprises a co-aligned through hole in the first or second layer, the through hole overlaid with a third layer.
2. The device of claim 1 in which the sample port comprises co-aligned through holes in the first and intermediate layers.
3. The device of claim 1 in which the first stop junction further comprises a second through hole aligned with the first through hole, the second through hole being overlaid with a fourth layer.
4. The device of claim 1, further comprising a bypass channel, to provide an additional path from the first channel to the bladder, without traversing the first measurement area and first stop junction.
5. The device of claim 1 in which at least the first or second layer is substantially transparent adjoining the first measurement area, and the physical parameter that is measured is optical transmission.
6. The device of claim 5 further comprising a reflective surface adjoining the first measurement area.
7. The device of claim 1 in which the physical parameter of the sample undergoes a change in the measurement area.
8. The device of claim 7 in which the first measurement area contains a composition that facilitates blood clotting, the biological fluid is whole blood, and the property being measured is prothrombin time.
9. The device of claim 8 in which the composition comprises thromboplastin.
10. The device of claim 1 further comprising a filter adjoining the sample port for filtering the biological fluid being introduced into the sample port.
11. The device of claim 10 in which the filter comprises an anisotropic membrane.
12. The device of claim 11 in which the filter material is polysulfone.
13. The device of claim 1 further comprising at least one additional measurement area between the first measurement area and the stop junction.
14. The device of claim 1 further comprising at least one alternate fluidic path from the first channel to the bladder, each such alternate path including a corresponding measurement area and stop junction.
15. The device of claim 4 in which the first measurement area contains a composition that facilitates blood. clotting, the biological fluid is whole blood, and the property being measured is prothrombin time.
16. The device of claim 15 further comprising at least one alternate fluidic path from the first channel to the bladder, each such alternate path including a corresponding measurement area and stop junction.
17. The device of claim 16 in which a first alternate path is to a measurement area that overcomes the effect of an anticoagulant and a second alternate path is to a measurement area that partially overcomes the effect of an anticoagulant.
18. The device of claim 17 in which the measurement area in the first alternate path comprises thromboplastin, bovine eluate, and recombinant Factor VIIa and the measurement area in the second alternate path comprises thromboplastin and bovine eluate.
19. The device of claim 13 further comprising at least one set of channel, measurement area, and stop junction between the first stop junction and first bladder and, adjoining the first bladder, an additional bladder for each such set.
20. The device of claim 19 further comprising a bypass channel from the first channel to the first bladder and an additional bypass channel from the channel of each additional set to the corresponding additional bladder.
21. A fluidic diagnostic device for measuring an analyte concentration or property of a biological fluid, comprising
a first layer, which has a resilient region over at least a part of its area, and a second layer, separated by an intermediate layer, in which recesses in a first surface of the intermediate layer form, with the first layer,
a) a sample port for introducing a sample of the biological fluid into the device;
b) a measurement area, in which the sample undergoes a change in a physical property that is to measured and related to the analyte concentration or property of the fluid;
c) a channel, having a first end and a second end, to provide a fluidic path from the sample port at the first end through the measurement area; and
d) a bladder, at the second end of the channel, comprising the resilient region in the first layer and having a volume that is at least about equal to the combined volume of the measurement area and channel; and
a stop junction in the channel between the measurement area and bladder that comprises two passages substantially normal to the first surface of the intermediate layer, each passage having a first end in fluid communication with the channel and a second end in fluid communication with a recess in a second surface of the intermediate layer, which recess provides fluid communication between the second ends of the passages.
US10/121,636 1998-07-20 2002-04-11 Analyte test strip with two controls Abandoned US20020110486A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/121,636 US20020110486A1 (en) 1998-07-20 2002-04-11 Analyte test strip with two controls

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US9342198P 1998-07-20 1998-07-20
US09/333,765 US6521182B1 (en) 1998-07-20 1999-06-15 Fluidic device for medical diagnostics
US10/121,636 US20020110486A1 (en) 1998-07-20 2002-04-11 Analyte test strip with two controls

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US09/333,765 Continuation US6521182B1 (en) 1998-07-20 1999-06-15 Fluidic device for medical diagnostics

Publications (1)

Publication Number Publication Date
US20020110486A1 true US20020110486A1 (en) 2002-08-15

Family

ID=26787520

Family Applications (8)

Application Number Title Priority Date Filing Date
US09/333,765 Expired - Lifetime US6521182B1 (en) 1998-07-20 1999-06-15 Fluidic device for medical diagnostics
US10/052,447 Abandoned US20020064480A1 (en) 1998-07-20 2002-01-17 Fluidic device for medical diagnostics
US10/121,636 Abandoned US20020110486A1 (en) 1998-07-20 2002-04-11 Analyte test strip with two controls
US10/121,425 Abandoned US20020110922A1 (en) 1998-07-20 2002-04-11 Vacuum loaded test strip and method of use
US10/264,662 Abandoned US20030031594A1 (en) 1998-07-20 2002-10-03 Vacuum loaded test strip with stop junction and bypass channel
US10/330,456 Abandoned US20030156983A1 (en) 1998-07-20 2002-12-26 Fluidic device for medical diagnostics
US10/330,790 Expired - Lifetime US7022286B2 (en) 1998-07-20 2002-12-26 Fluidic device for medical diagnostics
US10/666,846 Abandoned US20040109790A1 (en) 1998-07-20 2003-09-18 Vacuum loaded test strip with stop junction and bypass channel

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US09/333,765 Expired - Lifetime US6521182B1 (en) 1998-07-20 1999-06-15 Fluidic device for medical diagnostics
US10/052,447 Abandoned US20020064480A1 (en) 1998-07-20 2002-01-17 Fluidic device for medical diagnostics

Family Applications After (5)

Application Number Title Priority Date Filing Date
US10/121,425 Abandoned US20020110922A1 (en) 1998-07-20 2002-04-11 Vacuum loaded test strip and method of use
US10/264,662 Abandoned US20030031594A1 (en) 1998-07-20 2002-10-03 Vacuum loaded test strip with stop junction and bypass channel
US10/330,456 Abandoned US20030156983A1 (en) 1998-07-20 2002-12-26 Fluidic device for medical diagnostics
US10/330,790 Expired - Lifetime US7022286B2 (en) 1998-07-20 2002-12-26 Fluidic device for medical diagnostics
US10/666,846 Abandoned US20040109790A1 (en) 1998-07-20 2003-09-18 Vacuum loaded test strip with stop junction and bypass channel

Country Status (13)

Country Link
US (8) US6521182B1 (en)
EP (1) EP0974840B1 (en)
JP (1) JP2000055911A (en)
KR (1) KR100634714B1 (en)
CN (1) CN1199038C (en)
AT (1) ATE229649T1 (en)
CA (1) CA2277639A1 (en)
DE (1) DE69904403T2 (en)
DK (1) DK0974840T3 (en)
ES (1) ES2189353T3 (en)
IL (1) IL130807A (en)
NO (1) NO993536L (en)
TW (1) TW411268B (en)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020064480A1 (en) * 1998-07-20 2002-05-30 Shartle Robert Justice Fluidic device for medical diagnostics
US20020098114A1 (en) * 1998-07-20 2002-07-25 Harding Ian A. Microdroplet dispensing for a medical diagnostic device
US6673617B2 (en) * 2002-03-14 2004-01-06 Lifescan, Inc. Test strip qualification system
US6682933B2 (en) * 2002-03-14 2004-01-27 Lifescan, Inc. Test strip qualification system
DE102004024432A1 (en) * 2004-05-14 2005-12-08 Tesa Ag Use of a hydrophilic surface film in medical diagnostic strips
US20060000709A1 (en) * 2004-06-30 2006-01-05 Sebastian Bohm Methods for modulation of flow in a flow pathway
US20060002817A1 (en) * 2004-06-30 2006-01-05 Sebastian Bohm Flow modulation devices
US20060004303A1 (en) * 2004-06-30 2006-01-05 Weidenhaupt Klaus P Fluid handling devices
US20060001551A1 (en) * 2004-06-30 2006-01-05 Ulrich Kraft Analyte monitoring system with wireless alarm
US20080014658A1 (en) * 2006-07-13 2008-01-17 Tesa Aktiengesellschaft Web material with a coating allowing very rapid spreading and/or transport of fluids
KR100834286B1 (en) 2007-01-23 2008-05-30 엘지전자 주식회사 Multi layer strip for bio material and apparatus for measuring bio material
US20080176068A1 (en) * 2007-01-19 2008-07-24 Tesa Ag Web material with an ultrathin coating varnish allowing rapid sustained spreading and/or very rapid, sustained transport of fluids
EP1983060A1 (en) 2007-04-17 2008-10-22 Tesa AG Biosensor and production of same
US20080302274A1 (en) * 2007-06-07 2008-12-11 Tesa Aktiengesellschaft Hydrophilic coating lacquer
DE102008006225A1 (en) 2008-01-25 2009-07-30 Tesa Ag Biosensor and its production
US20100092768A1 (en) * 2008-10-13 2010-04-15 Tesa Ag Pressure-sensitive adhesive tape with functionalized adhesive and use thereof
DE102008051008A1 (en) 2008-10-13 2010-04-15 Tesa Se Pressure-sensitive adhesive tape with functionalized adhesive and its use
US8956518B2 (en) 2011-04-20 2015-02-17 Lifescan, Inc. Electrochemical sensors with carrier field
WO2018155865A1 (en) * 2017-02-27 2018-08-30 (주)오상헬스케어 Blood analysis strip

Families Citing this family (184)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6036924A (en) 1997-12-04 2000-03-14 Hewlett-Packard Company Cassette of lancet cartridges for sampling blood
US7407811B2 (en) * 1997-12-22 2008-08-05 Roche Diagnostics Operations, Inc. System and method for analyte measurement using AC excitation
US8071384B2 (en) 1997-12-22 2011-12-06 Roche Diagnostics Operations, Inc. Control and calibration solutions and methods for their use
US7390667B2 (en) * 1997-12-22 2008-06-24 Roche Diagnostics Operations, Inc. System and method for analyte measurement using AC phase angle measurements
US6391005B1 (en) 1998-03-30 2002-05-21 Agilent Technologies, Inc. Apparatus and method for penetration with shaft having a sensor for sensing penetration depth
US6084660A (en) * 1998-07-20 2000-07-04 Lifescan, Inc. Initiation of an analytical measurement in blood
US20050103624A1 (en) * 1999-10-04 2005-05-19 Bhullar Raghbir S. Biosensor and method of making
US6458326B1 (en) 1999-11-24 2002-10-01 Home Diagnostics, Inc. Protective test strip platform
US6908593B1 (en) * 2000-03-31 2005-06-21 Lifescan, Inc. Capillary flow control in a fluidic diagnostic device
IL151914A0 (en) 2000-03-31 2003-04-10 Lifescan Inc Electrically-conductive patterns for monitoring the filling of medical devices
US6488827B1 (en) * 2000-03-31 2002-12-03 Lifescan, Inc. Capillary flow control in a medical diagnostic device
JP4606543B2 (en) * 2000-04-13 2011-01-05 パナソニック株式会社 Method for confirming amount of solution to be measured and measuring system control method in optical property measuring apparatus
US6726818B2 (en) * 2000-07-21 2004-04-27 I-Sens, Inc. Biosensors with porous chromatographic membranes
KR20030020946A (en) * 2000-07-31 2003-03-10 라이프스캔, 인코포레이티드 Method and apparatus for detecting the presence of a fluid on a test strip
JP4384344B2 (en) * 2000-08-09 2009-12-16 拓之 今野 Blood coagulation time measurement method and apparatus using granular spot pattern by laser reflected light
US8641644B2 (en) 2000-11-21 2014-02-04 Sanofi-Aventis Deutschland Gmbh Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means
US6620310B1 (en) 2000-12-13 2003-09-16 Lifescan, Inc. Electrochemical coagulation assay and device
US7144495B2 (en) * 2000-12-13 2006-12-05 Lifescan, Inc. Electrochemical test strip with an integrated micro-needle and associated methods
US20040099310A1 (en) * 2001-01-05 2004-05-27 Per Andersson Microfluidic device
US6541266B2 (en) 2001-02-28 2003-04-01 Home Diagnostics, Inc. Method for determining concentration of an analyte in a test strip
US6525330B2 (en) 2001-02-28 2003-02-25 Home Diagnostics, Inc. Method of strip insertion detection
US6562625B2 (en) 2001-02-28 2003-05-13 Home Diagnostics, Inc. Distinguishing test types through spectral analysis
US7759067B2 (en) 2001-03-19 2010-07-20 Gyros Patent Ab Method for determining the amount of an analyte with a disc-shaped microfluidic device
EP1395185B1 (en) 2001-06-12 2010-10-27 Pelikan Technologies Inc. Electric lancet actuator
US9226699B2 (en) 2002-04-19 2016-01-05 Sanofi-Aventis Deutschland Gmbh Body fluid sampling module with a continuous compression tissue interface surface
US7981056B2 (en) 2002-04-19 2011-07-19 Pelikan Technologies, Inc. Methods and apparatus for lancet actuation
WO2002100254A2 (en) 2001-06-12 2002-12-19 Pelikan Technologies, Inc. Method and apparatus for lancet launching device integrated onto a blood-sampling cartridge
US8337419B2 (en) 2002-04-19 2012-12-25 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US9795747B2 (en) 2010-06-02 2017-10-24 Sanofi-Aventis Deutschland Gmbh Methods and apparatus for lancet actuation
US9427532B2 (en) 2001-06-12 2016-08-30 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
CA2448902C (en) 2001-06-12 2010-09-07 Pelikan Technologies, Inc. Self optimizing lancing device with adaptation means to temporal variations in cutaneous properties
US7344507B2 (en) 2002-04-19 2008-03-18 Pelikan Technologies, Inc. Method and apparatus for lancet actuation
US7041068B2 (en) 2001-06-12 2006-05-09 Pelikan Technologies, Inc. Sampling module device and method
ES2357887T3 (en) 2001-06-12 2011-05-03 Pelikan Technologies Inc. APPARATUS FOR IMPROVING THE BLOOD OBTAINING SUCCESS RATE FROM A CAPILLARY PUNCTURE.
US7682318B2 (en) 2001-06-12 2010-03-23 Pelikan Technologies, Inc. Blood sampling apparatus and method
US7776608B2 (en) 2001-07-09 2010-08-17 Bayer Healthcare Llc Volume meter testing device and method of use
US20030044318A1 (en) * 2001-09-05 2003-03-06 Lorin Olson Devices for analyte concentration determination and methods of using the same
US6884592B2 (en) * 2001-09-05 2005-04-26 Lifescan, Inc. Devices for analyte concentration determination and methods of manufacturing and using the same
JP2003091787A (en) * 2001-09-17 2003-03-28 Riken Keiki Co Ltd Portable gas alarm
EP1438385A1 (en) * 2001-10-25 2004-07-21 Bar-Ilan University Interactive transparent individual cells biochip processor
US6989891B2 (en) * 2001-11-08 2006-01-24 Optiscan Biomedical Corporation Device and method for in vitro determination of analyte concentrations within body fluids
EP1448489B1 (en) * 2001-11-16 2010-08-25 Stefan Ufer Flexible sensor and method of fabrication
US6746872B2 (en) 2002-01-16 2004-06-08 Lifescan, Inc. Control compositions and methods of use for coagulation tests
US6660527B2 (en) * 2002-03-28 2003-12-09 David Karl Stroup Fluid-transfer collection assembly and method of using the same
US7547287B2 (en) 2002-04-19 2009-06-16 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7297122B2 (en) 2002-04-19 2007-11-20 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7901362B2 (en) 2002-04-19 2011-03-08 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8360992B2 (en) 2002-04-19 2013-01-29 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7371247B2 (en) 2002-04-19 2008-05-13 Pelikan Technologies, Inc Method and apparatus for penetrating tissue
US8372016B2 (en) 2002-04-19 2013-02-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling and analyte sensing
US7331931B2 (en) 2002-04-19 2008-02-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7674232B2 (en) 2002-04-19 2010-03-09 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7198606B2 (en) 2002-04-19 2007-04-03 Pelikan Technologies, Inc. Method and apparatus for a multi-use body fluid sampling device with analyte sensing
US7229458B2 (en) 2002-04-19 2007-06-12 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US9314194B2 (en) 2002-04-19 2016-04-19 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
US8267870B2 (en) 2002-04-19 2012-09-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for body fluid sampling with hybrid actuation
US9795334B2 (en) 2002-04-19 2017-10-24 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7909778B2 (en) 2002-04-19 2011-03-22 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7491178B2 (en) 2002-04-19 2009-02-17 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7232451B2 (en) 2002-04-19 2007-06-19 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US7648468B2 (en) 2002-04-19 2010-01-19 Pelikon Technologies, Inc. Method and apparatus for penetrating tissue
US9248267B2 (en) 2002-04-19 2016-02-02 Sanofi-Aventis Deustchland Gmbh Tissue penetration device
US8702624B2 (en) 2006-09-29 2014-04-22 Sanofi-Aventis Deutschland Gmbh Analyte measurement device with a single shot actuator
US7892183B2 (en) 2002-04-19 2011-02-22 Pelikan Technologies, Inc. Method and apparatus for body fluid sampling and analyte sensing
US8221334B2 (en) 2002-04-19 2012-07-17 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7717863B2 (en) 2002-04-19 2010-05-18 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8784335B2 (en) 2002-04-19 2014-07-22 Sanofi-Aventis Deutschland Gmbh Body fluid sampling device with a capacitive sensor
US7291117B2 (en) 2002-04-19 2007-11-06 Pelikan Technologies, Inc. Method and apparatus for penetrating tissue
US8579831B2 (en) 2002-04-19 2013-11-12 Sanofi-Aventis Deutschland Gmbh Method and apparatus for penetrating tissue
US7976476B2 (en) 2002-04-19 2011-07-12 Pelikan Technologies, Inc. Device and method for variable speed lancet
DE10234819A1 (en) * 2002-07-31 2004-02-19 Roche Diagnostics Gmbh Test apparatus for blood, comprising compound body with test strip levels and transport channels to give complex tests in compact structure
US7604775B2 (en) 2002-08-12 2009-10-20 Bayer Healthcare Llc Fluid collecting and monitoring device
US7010432B2 (en) 2002-08-30 2006-03-07 Lifescan, Inc. Method and system for determining the acceptability of signal data collected from a prothrombin time test strip
US7049087B2 (en) * 2002-11-05 2006-05-23 Lifescan, Inc. Method for manufacturing a tissue factor-based prothrombin time reagent
US7291310B2 (en) * 2002-12-17 2007-11-06 The Regents Of The University Of Michigan Microsystem for determining clotting time of blood and low-cost, single-use device for use therein
US8574895B2 (en) 2002-12-30 2013-11-05 Sanofi-Aventis Deutschland Gmbh Method and apparatus using optical techniques to measure analyte levels
GB0300820D0 (en) * 2003-01-14 2003-02-12 Diagnoswiss Sa Membrane-microchannel strip
DE10305050A1 (en) * 2003-02-07 2004-08-19 Roche Diagnostics Gmbh Analytical test element and method for blood tests
IL154677A0 (en) * 2003-02-27 2003-09-17 Univ Bar Ilan A method and apparatus for manipulating an individual cell
US8153081B2 (en) 2003-05-29 2012-04-10 Bayer Healthcare Llc Test sensor and method for manufacturing the same
EP1628567B1 (en) 2003-05-30 2010-08-04 Pelikan Technologies Inc. Method and apparatus for fluid injection
ES2490740T3 (en) 2003-06-06 2014-09-04 Sanofi-Aventis Deutschland Gmbh Apparatus for blood fluid sampling and analyte detection
WO2006001797A1 (en) 2004-06-14 2006-01-05 Pelikan Technologies, Inc. Low pain penetrating
ES2683013T3 (en) * 2003-06-20 2018-09-24 F. Hoffmann-La Roche Ag Reagent band for test strip
US7645373B2 (en) * 2003-06-20 2010-01-12 Roche Diagnostic Operations, Inc. System and method for coding information on a biosensor test strip
US8058077B2 (en) * 2003-06-20 2011-11-15 Roche Diagnostics Operations, Inc. Method for coding information on a biosensor test strip
US7452457B2 (en) * 2003-06-20 2008-11-18 Roche Diagnostics Operations, Inc. System and method for analyte measurement using dose sufficiency electrodes
US8148164B2 (en) 2003-06-20 2012-04-03 Roche Diagnostics Operations, Inc. System and method for determining the concentration of an analyte in a sample fluid
US7645421B2 (en) 2003-06-20 2010-01-12 Roche Diagnostics Operations, Inc. System and method for coding information on a biosensor test strip
US7597793B2 (en) * 2003-06-20 2009-10-06 Roche Operations Ltd. System and method for analyte measurement employing maximum dosing time delay
US8071030B2 (en) * 2003-06-20 2011-12-06 Roche Diagnostics Operations, Inc. Test strip with flared sample receiving chamber
US7718439B2 (en) 2003-06-20 2010-05-18 Roche Diagnostics Operations, Inc. System and method for coding information on a biosensor test strip
US8206565B2 (en) 2003-06-20 2012-06-26 Roche Diagnostics Operation, Inc. System and method for coding information on a biosensor test strip
US8679853B2 (en) * 2003-06-20 2014-03-25 Roche Diagnostics Operations, Inc. Biosensor with laser-sealed capillary space and method of making
US7488601B2 (en) 2003-06-20 2009-02-10 Roche Diagnostic Operations, Inc. System and method for determining an abused sensor during analyte measurement
US8597597B2 (en) * 2003-06-26 2013-12-03 Seng Enterprises Ltd. Picoliter well holding device and method of making the same
US20060240548A1 (en) * 2003-06-26 2006-10-26 Mordechai Deutsch Materials for constructing cell-chips, cell-chip covers, cell-chips coats, processed cell-chips and uses thereof
US9200245B2 (en) 2003-06-26 2015-12-01 Seng Enterprises Ltd. Multiwell plate
US6927745B2 (en) * 2003-08-25 2005-08-09 Harris Corporation Frequency selective surfaces and phased array antennas using fluidic dielectrics
US7582472B2 (en) * 2003-08-26 2009-09-01 Smith Kenneth E Apparatus and method for liquid sample testing
EP1671096A4 (en) 2003-09-29 2009-09-16 Pelikan Technologies Inc Method and apparatus for an improved sample capture device
EP1680014A4 (en) 2003-10-14 2009-01-21 Pelikan Technologies Inc Method and apparatus for a variable user interface
US7147362B2 (en) * 2003-10-15 2006-12-12 Agilent Technologies, Inc. Method of mixing by intermittent centrifugal force
US7822454B1 (en) 2005-01-03 2010-10-26 Pelikan Technologies, Inc. Fluid sampling device with improved analyte detecting member configuration
WO2005065414A2 (en) 2003-12-31 2005-07-21 Pelikan Technologies, Inc. Method and apparatus for improving fluidic flow and sample capture
BRPI0507376A (en) 2004-02-06 2007-07-10 Bayer Healthcare Llc oxidizable species as an internal reference for biosensors and method of use
US7588724B2 (en) 2004-03-05 2009-09-15 Bayer Healthcare Llc Mechanical device for mixing a fluid sample with a treatment solution
US7665303B2 (en) * 2004-03-31 2010-02-23 Lifescan Scotland, Ltd. Method of segregating a bolus of fluid using a pneumatic actuator in a fluid handling circuit
US7156117B2 (en) * 2004-03-31 2007-01-02 Lifescan Scotland Limited Method of controlling the movement of fluid through a microfluidic circuit using an array of triggerable passive valves
US20050220630A1 (en) * 2004-03-31 2005-10-06 Sebastian Bohm Method of using triggerable passive valves to control the flow of fluid
US7059352B2 (en) * 2004-03-31 2006-06-13 Lifescan Scotland Triggerable passive valve for use in controlling the flow of fluid
US20050220644A1 (en) * 2004-03-31 2005-10-06 Sebastian Bohm Pneumatic actuator for bolus generation in a fluid handling circuit
US20050217742A1 (en) * 2004-03-31 2005-10-06 Sebastian Bohm Microfluidic circuit including an array of triggerable passive valves
CN1957254B (en) * 2004-04-07 2012-01-25 沃德劳有限合伙公司 Disposable chamber for analyzing biologic fluids
WO2005108991A2 (en) 2004-05-04 2005-11-17 Metrika, Inc Mechanical cartridge with test strip fluid control features for use in a fluid analyte meter
US8828203B2 (en) 2004-05-20 2014-09-09 Sanofi-Aventis Deutschland Gmbh Printable hydrogels for biosensors
US9775553B2 (en) 2004-06-03 2017-10-03 Sanofi-Aventis Deutschland Gmbh Method and apparatus for a fluid sampling device
WO2005120365A1 (en) 2004-06-03 2005-12-22 Pelikan Technologies, Inc. Method and apparatus for a fluid sampling device
US7569126B2 (en) 2004-06-18 2009-08-04 Roche Diagnostics Operations, Inc. System and method for quality assurance of a biosensor test strip
US7556723B2 (en) * 2004-06-18 2009-07-07 Roche Diagnostics Operations, Inc. Electrode design for biosensor
US8652831B2 (en) 2004-12-30 2014-02-18 Sanofi-Aventis Deutschland Gmbh Method and apparatus for analyte measurement test time
US20090054811A1 (en) * 2004-12-30 2009-02-26 Dirk Boecker Method and apparatus for analyte measurement test time
US8038964B2 (en) 2005-01-25 2011-10-18 Seng Enterprises Ltd. Device for studying individual cells
US7907985B2 (en) 2005-02-14 2011-03-15 Optiscan Biomedical Corporation Fluid handling cassette with a fluid control interface and sample separator
US7364562B2 (en) * 2005-10-06 2008-04-29 Optiscan Biomedical Corp. Anti-clotting apparatus and methods for fluid handling system
CN101184983A (en) * 2005-03-16 2008-05-21 雅拓晶科生物系统(私人)有限公司 Methods and device for transmitting, enclosing and analysing fluid samples
ES2717135T3 (en) 2005-07-20 2019-06-19 Ascensia Diabetes Care Holdings Ag Method to signal the user to add an additional sample to a test strip, method to measure the temperature of a sample and methods to determine the concentration of an analyte based on controlled amperometry
US7259846B2 (en) * 2005-08-30 2007-08-21 Agilent Technologies, Inc. Lab in a cuvette
KR101577176B1 (en) 2005-09-30 2015-12-14 바이엘 헬스케어 엘엘씨 Gated voltammetry analyte determination
US9561001B2 (en) 2005-10-06 2017-02-07 Optiscan Biomedical Corporation Fluid handling cassette system for body fluid analyzer
WO2007043619A1 (en) * 2005-10-13 2007-04-19 Nissui Pharmaceutical Co., Ltd. Testing device
BRPI0617460B8 (en) * 2005-10-18 2021-07-27 Fujimori Kogyo Co device that monitors thrombus formation by flowing anticoagulated blood through a channel that simulates a blood vessel while delivering an anticoagulation treatment or that promotes blood clotting; and, in vitro method for monitoring thrombus formation
US7731901B2 (en) * 2005-10-19 2010-06-08 Abbott Laboratories Apparatus and method for performing counts within a biologic fluid sample
US7723120B2 (en) * 2005-10-26 2010-05-25 General Electric Company Optical sensor array system and method for parallel processing of chemical and biochemical information
US8133741B2 (en) 2005-10-26 2012-03-13 General Electric Company Methods and systems for delivery of fluidic samples to sensor arrays
WO2007120746A2 (en) * 2006-04-11 2007-10-25 Optiscan Biomedical Corporation Anti-clotting apparatus and methods for fluid handling system
SE530244C2 (en) * 2006-05-05 2008-04-08 Hemocue Ab Method and system for quantitative hemoglobin determination
SE531948C2 (en) 2006-06-20 2009-09-15 Aamic Ab Liquid sample analyzer including filters in direct contact with projections
US7771655B2 (en) * 2006-07-12 2010-08-10 Bayer Healthcare Llc Mechanical device for mixing a fluid sample with a treatment solution
GB0617035D0 (en) 2006-08-30 2006-10-11 Inverness Medical Switzerland Fluidic indicator device
WO2008079731A1 (en) * 2006-12-22 2008-07-03 Home Diagnostics, Inc. Gel formation to reduce hematocrit sensitivity in electrochemical test
EP2101917A1 (en) * 2007-01-10 2009-09-23 Scandinavian Micro Biodevices A/S A microfluidic device and a microfluidic system and a method of performing a test
WO2008144575A2 (en) 2007-05-18 2008-11-27 Optiscan Biomedical Corporation Fluid injection and safety system
WO2008157795A1 (en) * 2007-06-20 2008-12-24 Mec Dynamics Corporation Methods and apparatus for measuring blood coagulation
WO2009001289A1 (en) * 2007-06-28 2008-12-31 Koninklijke Philips Electronics N. V. Microelectronic sensor device for optical examinations on a wetted surface
JP5112441B2 (en) * 2007-09-04 2013-01-09 パナソニック株式会社 Blood analyzer and blood analyzer using the same
EP2055384A1 (en) * 2007-10-31 2009-05-06 Leukocare AG Device for identifying constituents in a fluid
TWI362491B (en) * 2007-11-02 2012-04-21 Ind Tech Res Inst Fluid analytical device and fluid analytical method thereof
WO2009060849A1 (en) * 2007-11-05 2009-05-14 Nippon Kayaku Kabushiki Kaisha Biosensor
WO2009081409A2 (en) * 2007-12-26 2009-07-02 Seng Enterprises Ltd. Device for the study of living cells
US9145540B1 (en) 2007-11-15 2015-09-29 Seng Enterprises Ltd. Device for the study of living cells
WO2009076302A1 (en) 2007-12-10 2009-06-18 Bayer Healthcare Llc Control markers for auto-detection of control solution and methods of use
US8475734B2 (en) 2008-03-11 2013-07-02 Koninklijke Philips Electronics N.V. Filtering apparatus for filtering a fluid
US9201059B2 (en) 2008-03-14 2015-12-01 Scandinavian Micro Biodevices Aps Microfluidic system and a method of performing a test
WO2009126900A1 (en) 2008-04-11 2009-10-15 Pelikan Technologies, Inc. Method and apparatus for analyte detecting device
US20100028207A1 (en) * 2008-07-16 2010-02-04 International Technidyne Corporation Cuvette-based apparatus for blood coagulation measurement and testing
DE102008050092A1 (en) 2008-10-06 2010-04-08 Hach Lange Gmbh Mobile water analysis arrangement
US9375169B2 (en) 2009-01-30 2016-06-28 Sanofi-Aventis Deutschland Gmbh Cam drive for managing disposable penetrating member actions with a single motor and motor and control system
JP5665864B2 (en) * 2009-07-07 2015-02-04 ベーリンガー インゲルハイム マイクロパーツ ゲゼルシャフト ミットベシュレンクテル ハフツングBoehringer Ingelheim microParts GmbH Plasma separation reservoir
US8731638B2 (en) 2009-07-20 2014-05-20 Optiscan Biomedical Corporation Adjustable connector and dead space reduction
US9554742B2 (en) 2009-07-20 2017-01-31 Optiscan Biomedical Corporation Fluid analysis system
CN102762289B (en) 2009-12-18 2016-08-03 艾博特健康公司 Biological fluid analysis cartridge
US8965476B2 (en) 2010-04-16 2015-02-24 Sanofi-Aventis Deutschland Gmbh Tissue penetration device
EP2580589B1 (en) 2010-06-09 2016-08-31 Optiscan Biomedical Corporation Measuring analytes in a fluid sample drawn from a patient
CN102985804B (en) * 2010-07-09 2016-06-01 皇家飞利浦电子股份有限公司 There is the box of extensive designing for manufacturing
DE112011102770B4 (en) 2010-10-28 2014-11-20 International Business Machines Corporation Microfluidic unit with auxiliary and side channels
US9873118B2 (en) 2010-12-30 2018-01-23 Abbott Point Of Care, Inc. Biologic fluid analysis cartridge with sample handling portion and analysis chamber portion
JP6035329B2 (en) * 2011-05-26 2016-11-30 ザ ジェネラル ホスピタル コーポレイション Optical thromboelastography system and blood coagulation criteria evaluation method
WO2013006716A1 (en) 2011-07-06 2013-01-10 Optiscan Biomedical Corporation Sample cell for fluid analysis system
US8797527B2 (en) 2011-08-24 2014-08-05 Abbott Point Of Care, Inc. Biologic fluid sample analysis cartridge
US10105478B2 (en) * 2012-01-24 2018-10-23 Koninklijke Philips N.V. Analysis cartridge with filter unit
US9128038B2 (en) 2012-06-21 2015-09-08 Lifescan Scotland Limited Analytical test strip with capillary sample-receiving chambers separated by a physical barrier island
US20130341207A1 (en) 2012-06-21 2013-12-26 Lifescan Scotland Limited Analytical test strip with capillary sample-receiving chambers separated by stop junctions
US8877023B2 (en) 2012-06-21 2014-11-04 Lifescan Scotland Limited Electrochemical-based analytical test strip with intersecting sample-receiving chambers
EP2936117B1 (en) 2012-12-19 2020-11-25 The General Hospital Corporation Optical blood-coagulation sensor
JP6273107B2 (en) * 2013-08-02 2018-01-31 デンカ生研株式会社 Method for enhancing detection light using light reflector in immunochromatography
KR20160094369A (en) * 2013-09-26 2016-08-09 퀵 엘엘씨 Sample collection device for optical analysis
CN105583014B (en) * 2015-12-18 2019-01-22 中国电子科技集团公司第五十四研究所 The photon miniflow detection chip integrated based on LTCC
WO2018025041A1 (en) * 2016-08-05 2018-02-08 Vital Signs Solutions Limited Device and method for liquid analysis to detect biomarkers
EP3619517A4 (en) * 2017-05-04 2020-11-11 University of Connecticut Assembly for measuring the viscosity of fluids using microchannels
CN108152517A (en) * 2017-12-27 2018-06-12 北京乐普医疗科技有限责任公司 A kind of device and method for testing activated partial thromboplastin time
KR102428879B1 (en) 2017-12-29 2022-08-04 주식회사 앱솔로지 Diagnostic kit and control method thereof
WO2020194179A1 (en) * 2019-03-24 2020-10-01 Baldwa Mehul Biosensor for detection of analytes in a fluid
US20220212474A1 (en) * 2019-04-25 2022-07-07 Kyocera Corporation Flow path device, cartridge, and measurement system

Citations (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3620676A (en) * 1969-02-20 1971-11-16 Sterilizer Control Royalties A Disposable colorimetric indicator and sampling device for liquids
US3640267A (en) * 1969-12-15 1972-02-08 Damon Corp Clinical sample container
US4088448A (en) * 1975-09-29 1978-05-09 Lilja Jan Evert Apparatus for sampling, mixing the sample with a reagent and making particularly optical analyses
US4420566A (en) * 1982-06-10 1983-12-13 Eastman Kodak Company Method and apparatus for detecting sample fluid on an analysis slide
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
US4756884A (en) * 1985-08-05 1988-07-12 Biotrack, Inc. Capillary flow device
US4761381A (en) * 1985-09-18 1988-08-02 Miles Inc. Volume metering capillary gap device for applying a liquid sample onto a reactive surface
US4822568A (en) * 1986-03-28 1989-04-18 Minoru Tomita Apparatus for measuring aggregation rate of whole blood red blood cells
US4847209A (en) * 1987-11-09 1989-07-11 Miles Inc. Latex agglutination immunoassay in the presence of hemoglobin
US4849340A (en) * 1987-04-03 1989-07-18 Cardiovascular Diagnostics, Inc. Reaction system element and method for performing prothrombin time assay
US4868129A (en) * 1987-08-27 1989-09-19 Biotrack Inc. Apparatus and method for dilution and mixing of liquid samples
US4877745A (en) * 1986-11-17 1989-10-31 Abbott Laboratories Apparatus and process for reagent fluid dispensing and printing
US4935346A (en) * 1986-08-13 1990-06-19 Lifescan, Inc. Minimum procedure system for the determination of analytes
US5049487A (en) * 1986-08-13 1991-09-17 Lifescan, Inc. Automated initiation of timing of reflectance readings
US5068181A (en) * 1989-12-01 1991-11-26 Akzo N.V. Method of monitoring reagent delivery in a scanning spectrophotometer
US5100620A (en) * 1989-05-15 1992-03-31 Miles, Inc. Capillary tube/gap reagent format
US5104813A (en) * 1989-04-13 1992-04-14 Biotrack, Inc. Dilution and mixing cartridge
US5108926A (en) * 1987-09-08 1992-04-28 Board Of Regents, The University Of Texas System Apparatus for the precise positioning of cells
US5208163A (en) * 1990-08-06 1993-05-04 Miles Inc. Self-metering fluid analysis device
US5230866A (en) * 1991-03-01 1993-07-27 Biotrack, Inc. Capillary stop-flow junction having improved stability against accidental fluid flow
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
US5338688A (en) * 1990-08-02 1994-08-16 Boehringer Mannheim Gmbh Method for the metered application of a biochemical analytical liquid to a target
US5366902A (en) * 1990-10-30 1994-11-22 Hypoguard (Uk) Limited Collection and display device
US5378638A (en) * 1990-08-02 1995-01-03 Boehringer Mannheim Gmbh Analysis element and process for its manufacture
US5472603A (en) * 1992-04-02 1995-12-05 Abaxis, Inc. Analytical rotor with dye mixing chamber
US5504011A (en) * 1994-10-21 1996-04-02 International Technidyne Corporation Portable test apparatus and associated method of performing a blood coagulation test
US5508521A (en) * 1994-12-05 1996-04-16 Cardiovascular Diagnostics Inc. Method and apparatus for detecting liquid presence on a reflecting surface using modulated light
US5610287A (en) * 1993-12-06 1997-03-11 Molecular Tool, Inc. Method for immobilizing nucleic acid molecules
US5627041A (en) * 1994-09-02 1997-05-06 Biometric Imaging, Inc. Disposable cartridge for an assay of a biological sample
US5628961A (en) * 1993-10-28 1997-05-13 I-Stat Corporation Apparatus for assaying viscosity changes in fluid samples and method of conducting same
US5674699A (en) * 1993-06-08 1997-10-07 Chronomed, Inc. Two-phase optical assay
US5677195A (en) * 1991-11-22 1997-10-14 Affymax Technologies N.V. Combinatorial strategies for polymer synthesis
US5700695A (en) * 1994-06-30 1997-12-23 Zia Yassinzadeh Sample collection and manipulation method
US5708278A (en) * 1996-05-13 1998-01-13 Johnson & Johnson Clinical Diagnostics, Inc. Reflective wetness detector
US5728352A (en) * 1994-11-14 1998-03-17 Advanced Care Products Disposable electronic diagnostic instrument
US5736404A (en) * 1995-12-27 1998-04-07 Zia Yassinzadeh Flow detection appartus and method
US5827681A (en) * 1996-12-20 1998-10-27 University Technology Corporation Rapid detection and drug sensitivity of malaria
US6001307A (en) * 1996-04-26 1999-12-14 Kyoto Daiichi Kagaku Co., Ltd. Device for analyzing a sample
US6066504A (en) * 1997-06-27 2000-05-23 Hemosense, Inc. Coagulation or lysis assays using an electroactive species
US6066448A (en) * 1995-03-10 2000-05-23 Meso Sclae Technologies, Llc. Multi-array, multi-specific electrochemiluminescence testing
US6084660A (en) * 1998-07-20 2000-07-04 Lifescan, Inc. Initiation of an analytical measurement in blood
US6261519B1 (en) * 1998-07-20 2001-07-17 Lifescan, Inc. Medical diagnostic device with enough-sample indicator
US6362890B1 (en) * 1999-06-14 2002-03-26 Roche Diagnostics Gmbh Method and device for checking the liquid take up of a test layer of an analysis element
US20020064480A1 (en) * 1998-07-20 2002-05-30 Shartle Robert Justice Fluidic device for medical diagnostics
US20020098114A1 (en) * 1998-07-20 2002-07-25 Harding Ian A. Microdroplet dispensing for a medical diagnostic device
US6640267B1 (en) * 1999-09-27 2003-10-28 Cypress Semiconductor Corp. Architecture for multi-queue storage element

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL52322A (en) 1976-06-18 1980-10-26 Alfa Laval Ab Method of making reagent test device and device made accorording to this method
DE3113953A1 (en) * 1981-04-07 1982-10-21 Basf Ag, 6700 Ludwigshafen IMPACT THERMOPLASTIC MOLDS
JPS59138432A (en) * 1983-01-27 1984-08-08 Kobe Steel Ltd Mold clamping apparatus of tire vulcanizer
US4894340A (en) * 1987-12-21 1990-01-16 Suomen Sokeri Oy Microbial sulfhydryl oxidase and method
US5039617A (en) * 1989-04-20 1991-08-13 Biotrack, Inc. Capillary flow device and method for measuring activated partial thromboplastin time
KR920010809B1 (en) * 1990-05-19 1992-12-17 주식회사 금성사 Lcd projector
FI87166C (en) * 1991-07-05 1992-12-10 Leo Longlife Ltd Oy Packaging
US5217868A (en) 1992-05-01 1993-06-08 Syncor Limited Measurement of an enzyme marker as an aid to diagnosis of liver transplant rejection
WO1994002850A1 (en) 1992-07-21 1994-02-03 Medix Biotech, Inc. Transparent assay test devices and methods
CA2156226C (en) * 1994-08-25 1999-02-23 Takayuki Taguchi Biological fluid analyzing device and method
US6207369B1 (en) * 1995-03-10 2001-03-27 Meso Scale Technologies, Llc Multi-array, multi-specific electrochemiluminescence testing
JP3213566B2 (en) * 1996-04-26 2001-10-02 アークレイ株式会社 Sample analysis tool, sample analysis method and sample analyzer using the same
US6991762B1 (en) * 1996-04-26 2006-01-31 Arkray, Inc. Device for analyzing a sample
JP3498201B2 (en) * 1997-08-27 2004-02-16 アークレイ株式会社 Vacuum generator and sample analyzer using the same
HU222809B1 (en) 1997-10-03 2003-10-28 77 Elektronika Műszeripari Kft. Method and apparatus for detecting chemical component from sample mostly for detecting glucose content of blood from blood sample
US5847209A (en) * 1997-12-03 1998-12-08 Gupta; Anurag Ateet Process for recovery of solid and reusable urea from the urea adduction process
US6033866A (en) * 1997-12-08 2000-03-07 Biomedix, Inc. Highly sensitive amperometric bi-mediator-based glucose biosensor
US6069011A (en) 1997-12-10 2000-05-30 Umm Electronics, Inc. Method for determining the application of a sample fluid on an analyte strip using first and second derivatives
US6056448A (en) * 1998-04-16 2000-05-02 Lockheed Martin Corporation Vertical cavity surface emitting laser array packaging
US6866822B1 (en) * 2000-08-11 2005-03-15 Lifescan, Inc. Gimbaled bladder actuator for use with test strips

Patent Citations (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3620676A (en) * 1969-02-20 1971-11-16 Sterilizer Control Royalties A Disposable colorimetric indicator and sampling device for liquids
US3640267A (en) * 1969-12-15 1972-02-08 Damon Corp Clinical sample container
US4088448A (en) * 1975-09-29 1978-05-09 Lilja Jan Evert Apparatus for sampling, mixing the sample with a reagent and making particularly optical analyses
US4426451A (en) * 1981-01-28 1984-01-17 Eastman Kodak Company Multi-zoned reaction vessel having pressure-actuatable control means between zones
US4420566A (en) * 1982-06-10 1983-12-13 Eastman Kodak Company Method and apparatus for detecting sample fluid on an analysis slide
US4756884A (en) * 1985-08-05 1988-07-12 Biotrack, Inc. Capillary flow device
US4761381A (en) * 1985-09-18 1988-08-02 Miles Inc. Volume metering capillary gap device for applying a liquid sample onto a reactive surface
US4822568A (en) * 1986-03-28 1989-04-18 Minoru Tomita Apparatus for measuring aggregation rate of whole blood red blood cells
US4935346A (en) * 1986-08-13 1990-06-19 Lifescan, Inc. Minimum procedure system for the determination of analytes
US5049487A (en) * 1986-08-13 1991-09-17 Lifescan, Inc. Automated initiation of timing of reflectance readings
US4877745A (en) * 1986-11-17 1989-10-31 Abbott Laboratories Apparatus and process for reagent fluid dispensing and printing
US4849340A (en) * 1987-04-03 1989-07-18 Cardiovascular Diagnostics, Inc. Reaction system element and method for performing prothrombin time assay
US4868129A (en) * 1987-08-27 1989-09-19 Biotrack Inc. Apparatus and method for dilution and mixing of liquid samples
US5108926A (en) * 1987-09-08 1992-04-28 Board Of Regents, The University Of Texas System Apparatus for the precise positioning of cells
US4847209A (en) * 1987-11-09 1989-07-11 Miles Inc. Latex agglutination immunoassay in the presence of hemoglobin
US5104813A (en) * 1989-04-13 1992-04-14 Biotrack, Inc. Dilution and mixing cartridge
US5100620A (en) * 1989-05-15 1992-03-31 Miles, Inc. Capillary tube/gap reagent format
US5068181A (en) * 1989-12-01 1991-11-26 Akzo N.V. Method of monitoring reagent delivery in a scanning spectrophotometer
US5242606A (en) * 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
US5338688A (en) * 1990-08-02 1994-08-16 Boehringer Mannheim Gmbh Method for the metered application of a biochemical analytical liquid to a target
US5378638A (en) * 1990-08-02 1995-01-03 Boehringer Mannheim Gmbh Analysis element and process for its manufacture
US5208163A (en) * 1990-08-06 1993-05-04 Miles Inc. Self-metering fluid analysis device
US5366902A (en) * 1990-10-30 1994-11-22 Hypoguard (Uk) Limited Collection and display device
US5230866A (en) * 1991-03-01 1993-07-27 Biotrack, Inc. Capillary stop-flow junction having improved stability against accidental fluid flow
US5677195A (en) * 1991-11-22 1997-10-14 Affymax Technologies N.V. Combinatorial strategies for polymer synthesis
US5472603A (en) * 1992-04-02 1995-12-05 Abaxis, Inc. Analytical rotor with dye mixing chamber
US5674699A (en) * 1993-06-08 1997-10-07 Chronomed, Inc. Two-phase optical assay
US5628961A (en) * 1993-10-28 1997-05-13 I-Stat Corporation Apparatus for assaying viscosity changes in fluid samples and method of conducting same
US5610287A (en) * 1993-12-06 1997-03-11 Molecular Tool, Inc. Method for immobilizing nucleic acid molecules
US5700695A (en) * 1994-06-30 1997-12-23 Zia Yassinzadeh Sample collection and manipulation method
US5627041A (en) * 1994-09-02 1997-05-06 Biometric Imaging, Inc. Disposable cartridge for an assay of a biological sample
US5591403A (en) * 1994-10-21 1997-01-07 International Technidyne Corporation Portable prothrombin time test apparatus and associated method of performing a prothrombin time test
US5504011A (en) * 1994-10-21 1996-04-02 International Technidyne Corporation Portable test apparatus and associated method of performing a blood coagulation test
US5728352A (en) * 1994-11-14 1998-03-17 Advanced Care Products Disposable electronic diagnostic instrument
US5508521A (en) * 1994-12-05 1996-04-16 Cardiovascular Diagnostics Inc. Method and apparatus for detecting liquid presence on a reflecting surface using modulated light
US6066448A (en) * 1995-03-10 2000-05-23 Meso Sclae Technologies, Llc. Multi-array, multi-specific electrochemiluminescence testing
US6103196A (en) * 1995-12-27 2000-08-15 Yassinzadeh; Zia Flow detection apparatus and method
US5736404A (en) * 1995-12-27 1998-04-07 Zia Yassinzadeh Flow detection appartus and method
US6001307A (en) * 1996-04-26 1999-12-14 Kyoto Daiichi Kagaku Co., Ltd. Device for analyzing a sample
US6180062B1 (en) * 1996-04-26 2001-01-30 Kyoto Daiichi Kagaku Co., Ltd. Device for analyzing a sample
US5708278A (en) * 1996-05-13 1998-01-13 Johnson & Johnson Clinical Diagnostics, Inc. Reflective wetness detector
US5827681A (en) * 1996-12-20 1998-10-27 University Technology Corporation Rapid detection and drug sensitivity of malaria
US6066504A (en) * 1997-06-27 2000-05-23 Hemosense, Inc. Coagulation or lysis assays using an electroactive species
US6084660A (en) * 1998-07-20 2000-07-04 Lifescan, Inc. Initiation of an analytical measurement in blood
US6261519B1 (en) * 1998-07-20 2001-07-17 Lifescan, Inc. Medical diagnostic device with enough-sample indicator
US20020064480A1 (en) * 1998-07-20 2002-05-30 Shartle Robert Justice Fluidic device for medical diagnostics
US20020098114A1 (en) * 1998-07-20 2002-07-25 Harding Ian A. Microdroplet dispensing for a medical diagnostic device
US20030031594A1 (en) * 1998-07-20 2003-02-13 Shartle Robert Justice Vacuum loaded test strip with stop junction and bypass channel
US6521182B1 (en) * 1998-07-20 2003-02-18 Lifescan, Inc. Fluidic device for medical diagnostics
US20030156984A1 (en) * 1998-07-20 2003-08-21 John Lemke Fluidic device for medical diagnostics
US20030156983A1 (en) * 1998-07-20 2003-08-21 Shartle Robert Justice Fluidic device for medical diagnostics
US20030210287A1 (en) * 1998-07-20 2003-11-13 Harding Ian A. Microdroplet dispensing methods for a medical diagnostic device
US6362890B1 (en) * 1999-06-14 2002-03-26 Roche Diagnostics Gmbh Method and device for checking the liquid take up of a test layer of an analysis element
US6640267B1 (en) * 1999-09-27 2003-10-28 Cypress Semiconductor Corp. Architecture for multi-queue storage element

Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040109790A1 (en) * 1998-07-20 2004-06-10 Shartle Robert Justice Vacuum loaded test strip with stop junction and bypass channel
US20020110922A1 (en) * 1998-07-20 2002-08-15 Shartle Robert Justice Vacuum loaded test strip and method of use
US20020064480A1 (en) * 1998-07-20 2002-05-30 Shartle Robert Justice Fluidic device for medical diagnostics
US7022286B2 (en) 1998-07-20 2006-04-04 Lifescan, Inc. Fluidic device for medical diagnostics
US20030156984A1 (en) * 1998-07-20 2003-08-21 John Lemke Fluidic device for medical diagnostics
US20030210287A1 (en) * 1998-07-20 2003-11-13 Harding Ian A. Microdroplet dispensing methods for a medical diagnostic device
US20020098114A1 (en) * 1998-07-20 2002-07-25 Harding Ian A. Microdroplet dispensing for a medical diagnostic device
US20030156983A1 (en) * 1998-07-20 2003-08-21 Shartle Robert Justice Fluidic device for medical diagnostics
US6673617B2 (en) * 2002-03-14 2004-01-06 Lifescan, Inc. Test strip qualification system
US20040106212A1 (en) * 2002-03-14 2004-06-03 Harshad Patel Test strip qualification system
US20040096980A1 (en) * 2002-03-14 2004-05-20 Harshad Patel Test strip qualification system
US6682933B2 (en) * 2002-03-14 2004-01-27 Lifescan, Inc. Test strip qualification system
US6835570B2 (en) 2002-03-14 2004-12-28 Lifescan, Inc. Test strip qualification system
US6849456B2 (en) 2002-03-14 2005-02-01 Lifescan, Inc. Test strip qualification system
DE102004024432A1 (en) * 2004-05-14 2005-12-08 Tesa Ag Use of a hydrophilic surface film in medical diagnostic strips
US20060000709A1 (en) * 2004-06-30 2006-01-05 Sebastian Bohm Methods for modulation of flow in a flow pathway
US20060002817A1 (en) * 2004-06-30 2006-01-05 Sebastian Bohm Flow modulation devices
US20060004303A1 (en) * 2004-06-30 2006-01-05 Weidenhaupt Klaus P Fluid handling devices
US20060001551A1 (en) * 2004-06-30 2006-01-05 Ulrich Kraft Analyte monitoring system with wireless alarm
US20060000710A1 (en) * 2004-06-30 2006-01-05 Klaus Peter Weidenhaupt Fluid handling methods
US8343074B2 (en) 2004-06-30 2013-01-01 Lifescan Scotland Limited Fluid handling devices
US20080014658A1 (en) * 2006-07-13 2008-01-17 Tesa Aktiengesellschaft Web material with a coating allowing very rapid spreading and/or transport of fluids
US7638190B2 (en) 2007-01-19 2009-12-29 Tesa Se Web material with an ultrathin coating varnish allowing rapid sustained spreading and/or very rapid, sustained transport of fluids
DE102007003755A1 (en) 2007-01-19 2008-07-31 Tesa Ag Web-shaped material with a coating that enables a permanent fast spreading or a permanent, very fast transport of liquids
US20080176068A1 (en) * 2007-01-19 2008-07-24 Tesa Ag Web material with an ultrathin coating varnish allowing rapid sustained spreading and/or very rapid, sustained transport of fluids
US20080202928A1 (en) * 2007-01-23 2008-08-28 Hyun Seok Jung Multi-layer strip for use in measuring biological material and system for measuring biological material
KR100834286B1 (en) 2007-01-23 2008-05-30 엘지전자 주식회사 Multi layer strip for bio material and apparatus for measuring bio material
US8043489B2 (en) * 2007-01-23 2011-10-25 Lg Electronics Inc. Multi-layer strip for use in measuring biological material and system for measuring biological material
EP1983060A1 (en) 2007-04-17 2008-10-22 Tesa AG Biosensor and production of same
DE102007018383A1 (en) 2007-04-17 2008-10-23 Tesa Ag Sheet-like material with hydrophilic and hydrophobic areas and their production
US20080314745A1 (en) * 2007-04-17 2008-12-25 Tesa Ag Biosensor and its production
EP2014727A1 (en) 2007-06-07 2009-01-14 Tesa AG Hydrophilic coating finish
DE102007026998A1 (en) 2007-06-07 2008-12-11 Tesa Ag Hydrophilic coating varnish
US20080302274A1 (en) * 2007-06-07 2008-12-11 Tesa Aktiengesellschaft Hydrophilic coating lacquer
DE102008006225A1 (en) 2008-01-25 2009-07-30 Tesa Ag Biosensor and its production
US20100092768A1 (en) * 2008-10-13 2010-04-15 Tesa Ag Pressure-sensitive adhesive tape with functionalized adhesive and use thereof
DE102008051008A1 (en) 2008-10-13 2010-04-15 Tesa Se Pressure-sensitive adhesive tape with functionalized adhesive and its use
EP2177582A2 (en) 2008-10-13 2010-04-21 tesa AG Adhesive band with functionalised adhesive mass and use of the same
US8956518B2 (en) 2011-04-20 2015-02-17 Lifescan, Inc. Electrochemical sensors with carrier field
US9869653B2 (en) 2011-04-20 2018-01-16 Lifescan, Inc. Electrochemical sensors with carrier field
WO2018155865A1 (en) * 2017-02-27 2018-08-30 (주)오상헬스케어 Blood analysis strip

Also Published As

Publication number Publication date
CN1250160A (en) 2000-04-12
NO993536L (en) 2000-01-21
CN1199038C (en) 2005-04-27
US20020110922A1 (en) 2002-08-15
DK0974840T3 (en) 2003-03-31
KR20000011826A (en) 2000-02-25
EP0974840A2 (en) 2000-01-26
ES2189353T3 (en) 2003-07-01
DE69904403D1 (en) 2003-01-23
US20020064480A1 (en) 2002-05-30
IL130807A0 (en) 2001-01-28
KR100634714B1 (en) 2006-10-17
EP0974840A3 (en) 2000-03-08
US7022286B2 (en) 2006-04-04
TW411268B (en) 2000-11-11
CA2277639A1 (en) 2000-01-20
JP2000055911A (en) 2000-02-25
DE69904403T2 (en) 2003-10-30
IL130807A (en) 2003-11-23
US6521182B1 (en) 2003-02-18
EP0974840B1 (en) 2002-12-11
US20030156984A1 (en) 2003-08-21
US20030031594A1 (en) 2003-02-13
US20030156983A1 (en) 2003-08-21
NO993536D0 (en) 1999-07-19
ATE229649T1 (en) 2002-12-15
US20040109790A1 (en) 2004-06-10

Similar Documents

Publication Publication Date Title
US6521182B1 (en) Fluidic device for medical diagnostics
AU752645B2 (en) Fluidic device for medical diagnostics
US6084660A (en) Initiation of an analytical measurement in blood
US6652814B1 (en) Strip holder for use in a test strip meter
EP1311862B1 (en) Automatic meters including a gimbaled bladder actuator for use with test strips
AU2001280844A1 (en) Strip holder for use in a test strip meter
AU2001282985A1 (en) Gimbaled bladder actuator for use with test strips

Legal Events

Date Code Title Description
AS Assignment

Owner name: LIFESCAN, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SHARTLE, ROBERT JUSTICE;CHOW, HERBERT;HARTMANN, CHRISTA;REEL/FRAME:012798/0975;SIGNING DATES FROM 20000324 TO 20000329

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION