US20030119203A1 - Lateral flow assay devices and methods for conducting assays - Google Patents
Lateral flow assay devices and methods for conducting assays Download PDFInfo
- Publication number
- US20030119203A1 US20030119203A1 US10/035,014 US3501401A US2003119203A1 US 20030119203 A1 US20030119203 A1 US 20030119203A1 US 3501401 A US3501401 A US 3501401A US 2003119203 A1 US2003119203 A1 US 2003119203A1
- Authority
- US
- United States
- Prior art keywords
- probe
- analyte
- membrane
- lateral flow
- calibration
- 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
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54386—Analytical elements
- G01N33/54387—Immunochromatographic test strips
- G01N33/54388—Immunochromatographic test strips based on lateral flow
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54366—Apparatus specially adapted for solid-phase testing
- G01N33/54386—Analytical elements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
Definitions
- Membrane-based test devices particularly devices used in diagnostic medicine, employ a variety of internal and external calibrators to provide a qualitative or a quantitative result for an analyte of interest in a test solution.
- One type of membrane-based test device is a lateral flow assay.
- lateral flow assays are membrane-based test devices in which a sample that is suspected of containing the analyte of interest is placed at or near one end of a membrane strip. The sample is carried to the opposite end of the membrane strip by a liquid phase that traverses the membrane strip by capillary action. While traversing the membrane strip, the analyte in the test sample, if any, encounters one or more “capture” reagents with which it may react to produce a detectable signal.
- the dipstick is a stick having a small reagent impregnated membrane (stripped with capture reagents on different zones and wicking pads on one end and the other) end for dipping into a test solution either containing or suspected of containing the analyte of interest.
- the dipstick membrane (hereinafter “dipstick”) develops a color that is proportional to the concentration of the analyte of interest in the test sample.
- the user determines the concentration of the analyte by comparing the color on the membrane to the color on an external calibration, such as a series of colored plates that are printed on a label. This is a subjective determination.
- lateral flow assay methods are limited in their sensitivity by not using an internal calibration mechanism that takes into account widely varying differences in temperature, flow conditions, capillary action, pressure, and other factors that affect movement or deposition of analyte on a membrane or support. Any system that compares the migration characteristics of analyte on a given test strip with references taken on another separate strip at another time and place will not achieve maximum sensitivity and accuracy.
- a lateral flow assay system, apparatus, and method are provided in the invention.
- the assay provides a method to detect the quantity of analyte residing in a test solution.
- the assay further comprises a probe.
- the probe may be of various types. Probes are configured for generating a detectable signal. Probes may be covalently reacted with antibody to form probe-conjugates and this conjugate then may travel to react with analyte to form a probe-conjugate analyte complex (or “sandwich”). Once this species is immobilized upon a detection zone it is referred to as a “sandwich complex”. All these described species may be able to migrate on a membrane and may be used for analyte detection.
- a membrane may be configured to provide a sample pad, conjugate pad, detection zone, calibration zone and wicking pad.
- the probes and probe-conjugates may be dried down upon the membrane and made available for analyte as the analyte moves along the membrane from one end of the membrane to the other end.
- analyte molecules join probe conjugates, they form probe conjugate analyte complexes, which are capable of becoming mobilized, and moving to a detection zone.
- a first capture reagent may be immobilized.
- the first capture reagent may be composed of any ligand specific binder, thus, one example of such a capture reagent is an antibody.
- This first capture reagent may immobilize such probe-conjugate analyte complexes to form a “sandwich complex”, or “sandwich” upon the detection zone.
- a calibration zone also may be provided.
- the calibration zone comprises at least two control lines, however, in some applications of the invention, three, four, or more control lines may be provided.
- the control lines may have applied thereon a predetermined amount of a second capture reagent.
- the second capture reagent may be configured to immobilize probe-conjugates or probes that migrate to the control lines without analyte, thereby positioning them for generating a calibration or control signal.
- each control line may have a predetermined amount of the second capture reagent.
- the first control line nearest the detection zone may have the least amount of second capture reagent, while the last control line furthest from the detection zone may have the greatest amount of second capture reagent.
- the control lines may vary by predetermined amount from each other, so as supply a suitable calibration curve, as shown in herein and described with reference to FIG. 2.
- Some applications of the invention utilize visual comparisons.
- reading devices such as reflectometer or spectrophotometer may be employed to compare the intensity of signals generated with reference standards that are generated in the assay.
- Spectrophotometric methods may be employed to compare the intensity of signals generated with reference standards that are generated in the course of the assay.
- a calibration data curve may be generated using signal intensity data generated from the control lines.
- the curve may provide a “look-up table” that may be automatically applied in an algorithm of an analytical instrument.
- the probe in some cases may comprise a microparticle that is capable of generating a visual signal, such as a latex bead, for example, that includes red or blue or another colored dye.
- the probe may generate fluorescent signals that are detectable and are proportional to the amount of such species in a given zone.
- the invention may be directed to a method for detecting the quantity of an analyte in a test solution.
- the method may include applying a plurality of probes that are configured for migrating to preselected locations and, when they become sandwich complexes, generating a detectable signal.
- Internal calibration methods are useful because such methods may provide more accurate, more reliable and more reproducible results than external calibration methods.
- signals related to the analyte in the sample are usually measured at the same time and/or upon the same membrane device that generates the calibration signals.
- the simultaneous measurements can eliminate some potential interference to provide more consistent and sensitive detections.
- FIG. 1 is a top view of one embodiment of the invention, showing a lateral flow assay having three control lines in a calibration zone;
- FIG. 1A shows a perspective schematic view of the movement of fluids and the formation of complexes upon the surface of the membrane strip of a lateral flow assay, showing the membrane strip after a test sample containing analyte has been applied to the sample pad,
- FIG. 1B shows the same schematic view of the membrane test strip shown in FIG. 1A, but at a later time after migration of fluids have occurred and complexes have formed;
- FIG. 2 shows a calibration curve that may be used in some applications of the invention.
- the invention makes it possible to use multiple control lines to quantify analytes of interest in a lateral flow assay format.
- the method and apparatus of the invention relate to conducting internal calibrations by: (1) quantifying the analyte and (2) calibrating the assay device, at about the same time, on the same membrane device. That is, calibration and sample testing may occur on the same device, by affording a built-in calibration data curve generated using the testing device.
- a multi-point calibration technique may be employed in a lateral flow assay format.
- the method may be used for quantitative and semi-quantitative detection.
- the probes used may reveal color intensity, fluorescence intensity, as examples.
- the probes for control lines may be microparticles such as latex beads, for example, labeled with essentially any signal generating species.
- the probes may comprise labeled latex beads further conjugated with antibodies, as further described herein.
- the antibodies may be dried upon the conjugate zone of the membrane.
- Various amounts of predetermined capture reagents may be provided on solid substrates, such as porous membranes, to form multiple control lines for calibration purposes.
- the capture reagents may be antibodies.
- the capture reagents may be any molecules which are capable of forming strong interactions with probes and/or probe conjugates.
- the membrane-based device of the invention comprises several components, including a membrane, a sample pad, a conjugate pad and a wicking pad, or a combination of these items.
- the membrane typically includes at least two zones, that is, a detection zone and a control zone. A sample pad contacts one end of the conjugate pad.
- One design of the assay device includes a liquid sample flow direction through a sample pad, conjugate pad, detection zone of the membrane, control zone of the membrane, and wicking pad.
- the wicking pad assists in promoting capillary action and fluid flow one-way through the membrane of the device, and the wicking pad “pulls” the liquid containing the analyte along the membrane from one end of the membrane to another end of the membrane.
- the lateral flow assay 20 comprises a membrane 23 as a solid support, and includes a sample pad 21 .
- the sample pad 21 is configured to receive a liquid sample containing analyte 40 (seen in FIG. 1A).
- a conjugate pad 22 is provided further “downstream” of capillary movement direction 29 , as shown by the arrow on the left side of the FIG. 1.
- Conjugate pad 22 typically contains probes 41 and probe conjugates 42 (see FIG. 1A) in a form that makes the probe conjugates available for bonding with the analyte 40 as the analyte 40 passes from the sample pad 21 .
- a typical method employs microparticles as probes 41 , and their conjugate deposited on the conjugate pad 22 .
- Such particles may be comprised of latex, or other suitable material, as further described herein. Latex microparticles, when used as probes, may be colored with dyes that are visible to the eye, or to detection apparatus. Sometimes a probe 41 emits light (as in the case of fluorescence methods), or the probe 41 may be detected by other techniques once it has migrated and complexed, as further described herein.
- a detection zone 31 is shown in FIG. 1.
- the detection zone 31 may comprise an immobilized capture reagent along detection line 24 , as further described in connection with FIG. 1A.
- a calibration zone 32 is shown with three control lines 25 - 27 .
- a wicking pad 28 also is shown.
- a membrane 23 is provided in which molecules of the analyte 40 to be detected have been deposited upon the sample pad 21 .
- the analyte 40 which is fluidized, moves in the direction of the arrow shown in FIG. 1A from one end of the membrane to the other.
- FIG. 1A shows a schematic view in which the components of the assay 20 are enlarged for purposes of explanation.
- FIG. 1A shows membrane 23 at a point when the test sample or test solution has been applied to the sample pad 21 for only a short period of time.
- Probes 41 are seen upon the conjugate pad 22 .
- probes 41 are dried or immobilized upon the conjugate pad 22 .
- Probe conjugate 42 also is immobilized upon the conjugate pad 22 .
- Once molecules of analyte 40 bind with probe conjugates 41 - 42 , they become probe conjugate analyte complexes (such as probe analyte conjugate complex 49 - 50 shown in FIG. 1B) which are mobile along the membrane 23 .
- the detection zone 24 is shown in FIG. 1A having several capture reagents 43 a - c immobilized upon the detection zone 44 . These capture reagents 43 a - c serve as stationary binding sites for the probe analyte conjugate complexes 49 - 50 which migrate to them, as further shown in FIG. 1B. The chemical identity of capture reagents 43 a - c is further described herein.
- the calibration zone 32 is shown near the end of the membrane 23 .
- the calibration zone 32 provides at least two or more control lines, shown in this particular example as control lines 25 - 27 .
- the control lines are provided with a “binder” which is used to bind probe 41 molecules which pass the length of the membrane 23 .
- the “binder” may include an antibody, such as second antibody 47 a - c shown in FIG. 1B.
- the control lines 25 - 27 have a certain and specific amount of second antibody 47 a - c provided thereon, so that in a saturated environment having large amounts of probe 41 or probe conjugate 42 , they will reveal a specific, exact, and predetermined level of signal intensity. It will be recognized that thousands of molecules are provided upon the membrane 23 , but the FIGS. 1 A- 1 B show only a few molecules, for purposes of illustration.
- FIG. 1B shows the membrane 23 of FIG. 1A at a later point in time after the solution has migrated as shown in the arrow of FIG. 1B.
- a probe conjugate complex 49 and a probe conjugate complex 50 may be seen migrating from the conjugate pad 22 to the detection zone 44 .
- sandwich complexes 45 a, b and c have formed by the union of probe conjugate complexes similar to that shown as probe conjugate complex 49 with capture a - c (FIG. 1A), forming an immobilized sandwich complex 45 a - c within the detection zone.
- Probes 41 and probe conjugates 42 which are not bound to analyte also become mobile through the detection line 24 (see for example probe 52 ), and continue beyond the detection line 24 to the calibration zone 32 .
- the calibration zone 32 includes calibration lines 25 , 26 , and 27 .
- the calibration lines 25 - 27 may be pre-loaded upon the membrane 23 with a second capture reagent, such as second antibody 47 , and thus an intensity of color is generated upon the calibration lines 25 - 27 upon migration of probe 41 or probe conjugates 42 .
- a control probe complex 56 may be formed when a probe 41 attaches.
- a control probe conjugate complex 57 may be formed by attachment of a probe conjugate 42 . Both probes 41 and probe conjugates 42 are available for binding in the detection zone 32 .
- probe molecules such as dyed microparticles
- each calibration line 25 - 27 reaches its full and predetermined potential for signal intensity. That is, the amount of probe 41 molecules that are deposited upon calibration lines 25 - 27 are predetermined because the amount of capture reagent employed on the calibration lines 25 - 27 is set at a predetermined and known level.
- a comparison may be made between the intensity levels of the calibration lines 25 - 27 and the detection line 24 to calculate the amount of analyte 40 present in the sample or solution. This comparison step may occur visually, or with the aid of a reading device (not shown). Wicking pad 28 receives the fluid that has migrated through membrane 23 .
- the membrane 23 which is employed in the assay may be a cellulose ester.
- Nitrocellulose is known provides good results in some applications. It should be understood that the term “nitrocellulose” refers to nitric acid esters of cellulose, which may be nitrocellulose alone, or a mixed ester of nitric acid and other acids, in particular, aliphatic carboxylic acids having from one to seven carbon atoms.
- nitrocellulose may be a suitable material for producing the membrane, it is to be understood that other materials may also be employed for such solid supports including but not limited to nylon, rayon, and the like.
- the pore size of the solid support is such that the probe, when bound to the analyte remains on the surface of the membrane 23 .
- good results have been obtained with nitrocellulose having a pore size of from about 0.1 to 0.5 microns.
- the invention can be configured for detecting a broad range of analytes, including therapeutic drugs, drugs of abuse, hormones, vitamins, proteins (including antibodies of all classes), peptides, steroids, bacteria, viruses, parasites, components or products of bacteria, fungi, allergens of all types, antigens of all types, products or components of normal or malignant cells, and the like.
- analytes are examples of analytes that may be tested using the present invention: T.sub.4, T.sub.3, digoxin, hCG, insulin, theophylline, luteinizing hormone, organisms causing or associated with various disease states, such as streptococcus pyogenes (group A), Herpes Simplex I and II, cytomegalovirus, chlamydiae, and others known in the art.
- U.S. Pat. No. 4,366,241 (Tom et al.) lists at columns 19-26 a variety of potential analytes of interest that are members of an immunologic pair, including proteins, blood clofting factors, hormones, microorganisms, pharmaceutical agents, and vitamins. Any of these analytes are suitable for use as the analyte in present invention.
- HBAPAg human bone alkaline phosphatase antigen
- hCG human chorionic gonadotropin
- hLH human luteinizing hormone
- hFSH human follicle stimulating hormone
- CCA carcinoembryonic antigen
- PSA prostate specific antigen
- CA-549 a breast cancer antigen
- HBsAg hepatitis B surface antigen
- HBsAb hepatitis B surface antibody
- HBcAg hepatitis B core antigen
- HBcAb hepatitis A virus antibody
- an antigen of human immunodeficiency virus HIV I such as gp 120, p66, p41, p31, p24 or p17
- the p41 antigen of HIV II and the respective antiligand (preferably a mono
- probe-conjugate refers to a species that is capable of carrying an analyte in a lateral flow assay to form a probe conjugate complex, which binds with a first capture reagent in the detection zone 24 to become a “sandwich complex” in detection area or detection zone 24 .
- microparticle is a more specific reference to a particular type of probe, and may include any beads or probes to which an antibody may be bound, whether covalently, or non-covalently such as by adsorption.
- An additional requirement for some particles that are used in a quantitative assay is that the particle contributes a signal, usually light absorption, which would cause the zone in which the particles were located to have a different signal than the rest of the membrane 23 .
- the microparticle employed typically must be capable of being retained by the membrane 23 .
- the microparticle when a microparticle is subject to liquid flow, the microparticle must be capable of remaining substantially immobilized.
- the microparticles may be of any shape but are preferably spherical.
- the nature of the microparticle may vary widely. It may be naturally occurring or synthetic. It can be a single material, a few materials, or a combination of a wide variety of materials.
- Naturally occurring microparticles include nuclei, mycoplasma, plasmids, plastids, mammalian cells (e.g., erythrocyte ghosts), unicellular microorganisms (e.g., bacteria) and the like.
- Synthetic microparticles may be prepared from synthetic or naturally occurring materials, or combinations thereof.
- latex microparticles may be prepared from a synthetic material such as styrene.
- Other microparticles may be prepared from naturally occurring materials, such as polysaccharides, e.g., agarose, or the like. (See, e.g., Gould, et al., U.S. Pat. No. 4,837,168, which describes the use of a variety of particles.)
- Preferred microparticles are microspheres of latex (i.e., a natural or a synthetic polymer) or glass; more preferably microspheres of latex.
- the microspheres of glass or latex are also referred to in the art as “beads” or “microbeads.”
- a typical size for such beads is about 0.3 microns, but the invention may employ microparticles having greater or lesser size.
- the mean diameter for the microparticle component of the present invention is within the range from about 0.01 microns to about 100 microns and more typically from about 0.1 microns to about 75 microns.
- the mean diameter and type of the microparticle chosen for a particular application will depend upon the pore size of the membrane and/or its composition.
- Latex microparticles for use in the present invention are commercially available as polymeric microspheres of substantially uniform diameter (hereinafter “polymeric microspheres”), such as from Bangs Laboratories of Carmel, Ind., or Dow Chemical Co. of Midland, Mich.
- the polymeric microspheres typically are composed of one or more members of the group consisting of polystyrene, butadiene styrenes, styreneacrylic-vinyl terpolymer, polymethylmethacrylate, polyethylmethacrylate, styrene-maleic anhydride copolymer, polyvinyl acetate, polyvinylpyridine, polydivinylbenzene, polybutyleneterephthalate, acrylonitrile, vinylchloride-acrylates and the like or an aldehyde, carboxyl, amino, hydroxyl, or hydrazide derivative thereof.
- the underivatized polymeric microspheres such as polystyrene
- Techniques for adsorbing a protein or polypeptide on a hydrophobic particle are provided in the publication by Cantarero, et al. “The Absorption Characteristics of Proteins for Polystyrene and Their Significance in Solid Phase Immunoassays,” Analytical Biochemistry 105, 375-382 (1980); and Bangs, “Latex Immunoassays,” J. Clin. Immunoassay, 13 127-131 (1980) both of which are incorporated herein by reference.
- the covalent bonding of a binding partner to a microparticle may be accomplished either directly, such as by reacting an activated chemical functional group on the surface of a microparticle with an appropriate chemical functional group on the binding partner, or indirectly, such as by covalently binding the binding partner to a spacer molecule that has been covalently bound to the surface of the microparticle.
- membrane as used herein is meant a test device that employs a membrane and one or more reagents to detect the concentration of an analyte of interest in a test solution, preferably an aqueous test solution. At least one of the reagents associated with the membrane device is a binding partner of the analyte of interest.
- the calibration device and method of the present invention is useful with essentially any membrane-based devices.
- a particularly preferred use for the calibrator of the present invention is as an internal calibrator.
- the choice and size of a microparticle for the stabilized internal calibrator of a membrane-based device is influenced by the choice of material for the membrane.
- the internal calibrator of the present invention may be affixed to the membrane by covalent or non-covalent bonding.
- calibration and sample testing may be conducted under essentially exactly the same conditions at the same time, thus providing reliable quantitative results, with increased sensitivity.
- the invention also may be employed for semi-quantitative detection.
- the multiple control lines provide a range of signal intensities
- the signal intensity of a given detection line can be compared (i.e. such as for example, visually) with the intensity of the control lines. Based upon the intensity range wherein the detection line falls, the possible concentration range for the analyte may be determined.
- the probes may be latex beads labeled with any signal generating species or the labeled latex beads further conjugated with antibodies.
- the signal ratio between the detection lines and the control lines may be plotted against the analyte concentrations for a range of analyte concentrations to generate a calibration curve, such as shown in FIG. 2 herein.
- the signal ratio may be converted to analyte concentration according to the calibration curve.
- Polyethyleneimine was used to demonstrate the invention.
- a 7.4% polyethyleneimine aqueous solution (stock solution)(1 ⁇ ), a 10 ⁇ dilution and a 100 ⁇ dilution were stripped onto Millipore SX membrane to form three control lines.
- the membrane was dried for about 1 hour at about 37 degrees Centigrade.
- a wicking pad was attached upon one end of the membrane.
- the other end of the membrane was inserted into a suspension of blue latex beads or red fluorescent latex beads containing 1.6% Tween 20 (a surfactant) or antibody-conjugated latex beads with 1.6% Tween 20. Five minutes later, the beads were captured on the lines where the polyethyleneimine solution was stripped.
- the membrane was stripped with three different polyethyleneimine solutions (1 ⁇ , 10 ⁇ , 100 ⁇ dilution) on the lines of the calibration zone 32 and anti C-reactive protein (CRP) monoclonal antibody (Mab A5804) was immobilized on the detection zone.
- CRP C-reactive protein
- the membrane was dried for about one hour at about 37 degrees Centigrade, and the wicking pad was attached to the end of the membrane to form a half dipstick.
- the other end of the half dipstick was inserted into a solution with CRP antigen and anti CRP monoclonal antibody (Mab A5801 1) conjugated to latex particles (blue).
- the solution flowed through the detection and control zones, and then to the wicking pad. One blue line on the detection zone and three blue lines on the control zone were observed.
- the membrane HF 09002 was stripped with 0.14% (calibration #1), 0.64% (calibration #2) and 1.4% (calibration #3) of polyethyleneimine solution on the calibration or calibration zone 32 .
- anti CRP monoclonal antibody at 1 mg/ml (Mab A5804) was immobilized.
- the membrane was dried at 37° C. for one hour and the wicking pad 28 was attached to the end of the membrane to form the half stick.
- the half sticks were inserted into the solutions containing the following nano-grams of CRP antigen (0. 0.54, 5.4 and 54) with excess amount of blue latex beads which are conjugated with anti CRP monoclonal antibody (Mab58011).
- the concentration of the analyte was determined to be less than about 0.54 ng.
- the analyte concentration was found to be between 0.54 and 5.4 ng.
- the analyte concentration was determined to be higher than 54 ng.
- Example 3 The same procedure as Example 3 was conducted, with the exception that the concentration of the analyte was quantified by a electronic reading device.
- electronic reading devices electronic routines make it possible to read automatically the intensities of calibration and detection lines and provide a readout or display for the analyte concentration.
- the latex beads generate a detectable colored light signal, from both the detection zone 31 and the control lines of the calibration zone 32 .
- the reading device provides a comparison means for comparing the intensity of colored light signals generated by latex beads positioned upon the control lines 25 - 27 with the intensity of signals generated by microparticle-analyte conjugates positioned upon the detection zone 31 .
- fluorescence it is possible to use fluorescence to determine the amount of analyte in a test sample.
- a probe or a microparticle which itself is capable of exhibiting the property of fluorescence, in which signals are generated from the probe or microparticle once it has been deposited in either the calibration zone 32 or the detection zone 31 .
- a receiver or a receiving device is capable of measuring the amount of signal generated in the detection zone 31 and the calibration zone 32 , and making the appropriate comparisons to determine the quantity of analyte in a given test sample.
Abstract
Disclosed is a method and apparatus for employing, in a lateral flow assay, multiple control lines to assist in improving the sensitivity of such an assay. Analytes of interest may be quantified in a lateral flow assay by conducting internally derived calibrations by quantifying the analyte and calibrating the assay device, at essentially the same time, on the same device. That is, calibration and sample testing may occur simultaneously, improving sensitivity, and reducing errors that otherwise may be introduced by comparing data produced in one assay with data or reference data produced in a different assay. A multi-point calibration technique may be employed. Visual spectrophotographic reading devices may be employed to compare intensity of signals generated by probes attached to the analyte with probes associated with control lines upon a calibration zone.
Description
- Membrane-based test devices, particularly devices used in diagnostic medicine, employ a variety of internal and external calibrators to provide a qualitative or a quantitative result for an analyte of interest in a test solution. One type of membrane-based test device is a lateral flow assay.
- In general, lateral flow assays are membrane-based test devices in which a sample that is suspected of containing the analyte of interest is placed at or near one end of a membrane strip. The sample is carried to the opposite end of the membrane strip by a liquid phase that traverses the membrane strip by capillary action. While traversing the membrane strip, the analyte in the test sample, if any, encounters one or more “capture” reagents with which it may react to produce a detectable signal.
- The early types of immunochromatography devices, such as those taught in U.S. Pat. No. 4,366,241 (Tom et al.), lacked an internal reference. Later devices, such as taught in U.S. Pat. No. 4,374,925 (Litman) do indeed employ an internal reference. In some instances, the internal references used have required fairly laborious cross-referencing to achieve results.
- One known membrane-based test device is the dipstick. The dipstick is a stick having a small reagent impregnated membrane (stripped with capture reagents on different zones and wicking pads on one end and the other) end for dipping into a test solution either containing or suspected of containing the analyte of interest. The dipstick membrane (hereinafter “dipstick”) develops a color that is proportional to the concentration of the analyte of interest in the test sample. Typically, the user determines the concentration of the analyte by comparing the color on the membrane to the color on an external calibration, such as a series of colored plates that are printed on a label. This is a subjective determination.
- External calibration of a dipstick, via colored plates, provides several problems. First, it is difficult to accurately match the color of the plates with the color on the dipstick. Secondly, the color on the plates would not fade in proportion to the adverse conditions affecting the color on the dipstick. Further, the color on the plates would at best only be accurate for a particular set of reaction conditions.
- Many of such devices and methods rely upon calibration to provide valid and meaningful results for semi-quantitative and quantitative detections. Calibration methods are often critical to provide accurate, reliable and reproducible results, especially when the environments and conditions under which the measurements are commenced are not carefully controlled. Two calibration methods, external and internal calibrations, are commonly employed. In the external calibration method, a standard curve is usually obtained from standard samples containing a series of a known amount of analyte, and the results obtained from the samples are then compared with the standard curve to extract the information regarding the presence and/or amount of the analyte in the sample. External calibration methods are often subject to interference from environmental and batch-to-batch variations, and sometimes are not reliable. When an instrument or measuring device is used, it is also subject to interference from the instability of the instrument or device.
- In general, lateral flow assay methods are limited in their sensitivity by not using an internal calibration mechanism that takes into account widely varying differences in temperature, flow conditions, capillary action, pressure, and other factors that affect movement or deposition of analyte on a membrane or support. Any system that compares the migration characteristics of analyte on a given test strip with references taken on another separate strip at another time and place will not achieve maximum sensitivity and accuracy.
- What is needed in the industry is a lateral flow assay system and method having improved sensitivity in relation to existing methods and devices. The invention of this application is directed to such an application.
- A lateral flow assay system, apparatus, and method are provided in the invention. The assay provides a method to detect the quantity of analyte residing in a test solution. The assay further comprises a probe. The probe may be of various types. Probes are configured for generating a detectable signal. Probes may be covalently reacted with antibody to form probe-conjugates and this conjugate then may travel to react with analyte to form a probe-conjugate analyte complex (or “sandwich”). Once this species is immobilized upon a detection zone it is referred to as a “sandwich complex”. All these described species may be able to migrate on a membrane and may be used for analyte detection.
- A membrane may be configured to provide a sample pad, conjugate pad, detection zone, calibration zone and wicking pad. On the conjugate pad the probes and probe-conjugates may be dried down upon the membrane and made available for analyte as the analyte moves along the membrane from one end of the membrane to the other end. When analyte molecules join probe conjugates, they form probe conjugate analyte complexes, which are capable of becoming mobilized, and moving to a detection zone.
- Upon the detection zone, a first capture reagent may be immobilized. The first capture reagent may be composed of any ligand specific binder, thus, one example of such a capture reagent is an antibody. This first capture reagent may immobilize such probe-conjugate analyte complexes to form a “sandwich complex”, or “sandwich” upon the detection zone.
- A calibration zone also may be provided. The calibration zone comprises at least two control lines, however, in some applications of the invention, three, four, or more control lines may be provided. The control lines may have applied thereon a predetermined amount of a second capture reagent. The second capture reagent may be configured to immobilize probe-conjugates or probes that migrate to the control lines without analyte, thereby positioning them for generating a calibration or control signal.
- In general, each control line may have a predetermined amount of the second capture reagent. Thus, commonly, the first control line nearest the detection zone may have the least amount of second capture reagent, while the last control line furthest from the detection zone may have the greatest amount of second capture reagent. In some applications, the control lines may vary by predetermined amount from each other, so as supply a suitable calibration curve, as shown in herein and described with reference to FIG. 2.
- Some applications of the invention utilize visual comparisons. In other applications, reading devices such as reflectometer or spectrophotometer may be employed to compare the intensity of signals generated with reference standards that are generated in the assay. Spectrophotometric methods may be employed to compare the intensity of signals generated with reference standards that are generated in the course of the assay.
- In some applications, a calibration data curve may be generated using signal intensity data generated from the control lines. The curve may provide a “look-up table” that may be automatically applied in an algorithm of an analytical instrument.
- The probe in some cases may comprise a microparticle that is capable of generating a visual signal, such as a latex bead, for example, that includes red or blue or another colored dye. In other applications, the probe may generate fluorescent signals that are detectable and are proportional to the amount of such species in a given zone.
- The invention may be directed to a method for detecting the quantity of an analyte in a test solution. The method may include applying a plurality of probes that are configured for migrating to preselected locations and, when they become sandwich complexes, generating a detectable signal.
- Internal calibration methods are useful because such methods may provide more accurate, more reliable and more reproducible results than external calibration methods. Using internal calibration methods, signals related to the analyte in the sample are usually measured at the same time and/or upon the same membrane device that generates the calibration signals. The simultaneous measurements can eliminate some potential interference to provide more consistent and sensitive detections.
- A full and enabling disclosure of this invention, including the best mode shown to one of ordinary skill in the art, is set forth in this specification. The following Figures illustrate the invention:
- FIG. 1 is a top view of one embodiment of the invention, showing a lateral flow assay having three control lines in a calibration zone;
- FIG. 1A shows a perspective schematic view of the movement of fluids and the formation of complexes upon the surface of the membrane strip of a lateral flow assay, showing the membrane strip after a test sample containing analyte has been applied to the sample pad,
- FIG. 1B shows the same schematic view of the membrane test strip shown in FIG. 1A, but at a later time after migration of fluids have occurred and complexes have formed; and
- FIG. 2 shows a calibration curve that may be used in some applications of the invention.
- Reference now will be made to the embodiments of the invention, one or more examples of which are set forth below. Each example is provided by way of explanation of the invention, not as a limitation of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in this invention without departing from the scope or spirit of the invention.
- The invention makes it possible to use multiple control lines to quantify analytes of interest in a lateral flow assay format. In particular, the method and apparatus of the invention relate to conducting internal calibrations by: (1) quantifying the analyte and (2) calibrating the assay device, at about the same time, on the same membrane device. That is, calibration and sample testing may occur on the same device, by affording a built-in calibration data curve generated using the testing device. A multi-point calibration technique may be employed in a lateral flow assay format.
- The method may be used for quantitative and semi-quantitative detection. The probes used may reveal color intensity, fluorescence intensity, as examples. The probes for control lines may be microparticles such as latex beads, for example, labeled with essentially any signal generating species. Alternately, the probes may comprise labeled latex beads further conjugated with antibodies, as further described herein. The antibodies may be dried upon the conjugate zone of the membrane.
- Various amounts of predetermined capture reagents may be provided on solid substrates, such as porous membranes, to form multiple control lines for calibration purposes. In yet another embodiment, the capture reagents may be antibodies. In yet another embodiment, the capture reagents may be any molecules which are capable of forming strong interactions with probes and/or probe conjugates.
- The membrane-based device of the invention comprises several components, including a membrane, a sample pad, a conjugate pad and a wicking pad, or a combination of these items. The membrane typically includes at least two zones, that is, a detection zone and a control zone. A sample pad contacts one end of the conjugate pad.
- One design of the assay device includes a liquid sample flow direction through a sample pad, conjugate pad, detection zone of the membrane, control zone of the membrane, and wicking pad. In general, the wicking pad assists in promoting capillary action and fluid flow one-way through the membrane of the device, and the wicking pad “pulls” the liquid containing the analyte along the membrane from one end of the membrane to another end of the membrane.
- Turning now to FIG. 1, a
lateral flow assay 20 is provided in top view. Thelateral flow assay 20 comprises amembrane 23 as a solid support, and includes asample pad 21. Thesample pad 21 is configured to receive a liquid sample containing analyte 40 (seen in FIG. 1A). Aconjugate pad 22 is provided further “downstream” ofcapillary movement direction 29, as shown by the arrow on the left side of the FIG. 1. -
Conjugate pad 22 typically containsprobes 41 and probe conjugates 42 (see FIG. 1A) in a form that makes the probe conjugates available for bonding with theanalyte 40 as theanalyte 40 passes from thesample pad 21. A typical method employs microparticles asprobes 41, and their conjugate deposited on theconjugate pad 22. Such particles may be comprised of latex, or other suitable material, as further described herein. Latex microparticles, when used as probes, may be colored with dyes that are visible to the eye, or to detection apparatus. Sometimes aprobe 41 emits light (as in the case of fluorescence methods), or theprobe 41 may be detected by other techniques once it has migrated and complexed, as further described herein. - A
detection zone 31 is shown in FIG. 1. Thedetection zone 31 may comprise an immobilized capture reagent alongdetection line 24, as further described in connection with FIG. 1A. Acalibration zone 32 is shown with three control lines 25-27. Awicking pad 28 also is shown. - Referring to FIG. 1A, a
membrane 23 is provided in which molecules of theanalyte 40 to be detected have been deposited upon thesample pad 21. Theanalyte 40, which is fluidized, moves in the direction of the arrow shown in FIG. 1A from one end of the membrane to the other. - FIG. 1A shows a schematic view in which the components of the
assay 20 are enlarged for purposes of explanation. FIG. 1A showsmembrane 23 at a point when the test sample or test solution has been applied to thesample pad 21 for only a short period of time.Probes 41 are seen upon theconjugate pad 22. Typically, probes 41 are dried or immobilized upon theconjugate pad 22. Probe conjugate 42 also is immobilized upon theconjugate pad 22. Once molecules ofanalyte 40 bind with probe conjugates 41-42, they become probe conjugate analyte complexes (such as probe analyte conjugate complex 49-50 shown in FIG. 1B) which are mobile along themembrane 23. - The
detection zone 24 is shown in FIG. 1A having several capture reagents 43 a-c immobilized upon the detection zone 44. These capture reagents 43 a-c serve as stationary binding sites for the probe analyte conjugate complexes 49-50 which migrate to them, as further shown in FIG. 1B. The chemical identity of capture reagents 43 a-c is further described herein. - The
calibration zone 32 is shown near the end of themembrane 23. Thecalibration zone 32 provides at least two or more control lines, shown in this particular example as control lines 25-27. In many cases, the control lines are provided with a “binder” which is used to bindprobe 41 molecules which pass the length of themembrane 23. The “binder” may include an antibody, such as second antibody 47 a-c shown in FIG. 1B. The control lines 25-27 have a certain and specific amount of second antibody 47 a-c provided thereon, so that in a saturated environment having large amounts ofprobe 41 orprobe conjugate 42, they will reveal a specific, exact, and predetermined level of signal intensity. It will be recognized that thousands of molecules are provided upon themembrane 23, but the FIGS. 1A-1B show only a few molecules, for purposes of illustration. - FIG. 1B shows the
membrane 23 of FIG. 1A at a later point in time after the solution has migrated as shown in the arrow of FIG. 1B. Aprobe conjugate complex 49 and aprobe conjugate complex 50 may be seen migrating from theconjugate pad 22 to the detection zone 44. Several sandwich complexes 45 a, b and c have formed by the union of probe conjugate complexes similar to that shown as probe conjugate complex 49 with capture reagent 43 a-c (FIG. 1A), forming an immobilized sandwich complex 45 a-c within the detection zone. - Probes41 and probe conjugates 42 which are not bound to analyte, also become mobile through the detection line 24 (see for example probe 52), and continue beyond the
detection line 24 to thecalibration zone 32. Thecalibration zone 32 includescalibration lines membrane 23 with a second capture reagent, such as second antibody 47, and thus an intensity of color is generated upon the calibration lines 25-27 upon migration ofprobe 41 or probe conjugates 42. Acontrol probe complex 56 may be formed when aprobe 41 attaches. Likewise, a control probe conjugate complex 57 may be formed by attachment of aprobe conjugate 42. Both probes 41 and probe conjugates 42 are available for binding in thedetection zone 32. - An excess of probe molecules, such as dyed microparticles, can be employed in the
assay 20, so that each calibration line 25-27 reaches its full and predetermined potential for signal intensity. That is, the amount ofprobe 41 molecules that are deposited upon calibration lines 25-27 are predetermined because the amount of capture reagent employed on the calibration lines 25-27 is set at a predetermined and known level. A comparison may be made between the intensity levels of the calibration lines 25-27 and thedetection line 24 to calculate the amount ofanalyte 40 present in the sample or solution. This comparison step may occur visually, or with the aid of a reading device (not shown). Wickingpad 28 receives the fluid that has migrated throughmembrane 23. - The
membrane 23, or solid support, which is employed in the assay may be a cellulose ester. Nitrocellulose is known provides good results in some applications. It should be understood that the term “nitrocellulose” refers to nitric acid esters of cellulose, which may be nitrocellulose alone, or a mixed ester of nitric acid and other acids, in particular, aliphatic carboxylic acids having from one to seven carbon atoms. - Although nitrocellulose may be a suitable material for producing the membrane, it is to be understood that other materials may also be employed for such solid supports including but not limited to nylon, rayon, and the like.
- In accordance with a particular preferred embodiment, the pore size of the solid support is such that the probe, when bound to the analyte remains on the surface of the
membrane 23. Thus, for example, good results have been obtained with nitrocellulose having a pore size of from about 0.1 to 0.5 microns. - It is to be understood that the invention can be configured for detecting a broad range of analytes, including therapeutic drugs, drugs of abuse, hormones, vitamins, proteins (including antibodies of all classes), peptides, steroids, bacteria, viruses, parasites, components or products of bacteria, fungi, allergens of all types, antigens of all types, products or components of normal or malignant cells, and the like.
- The following analytes are examples of analytes that may be tested using the present invention: T.sub.4, T.sub.3, digoxin, hCG, insulin, theophylline, luteinizing hormone, organisms causing or associated with various disease states, such as streptococcus pyogenes (group A), Herpes Simplex I and II, cytomegalovirus, chlamydiae, and others known in the art.
- U.S. Pat. No. 4,366,241 (Tom et al.) lists at columns 19-26 a variety of potential analytes of interest that are members of an immunologic pair, including proteins, blood clofting factors, hormones, microorganisms, pharmaceutical agents, and vitamins. Any of these analytes are suitable for use as the analyte in present invention.
- Other examples of preferred ligands or analytes that may be detected include the following: human bone alkaline phosphatase antigen (HBAPAg); human chorionic gonadotropin (hCG); human luteinizing hormone (hLH); human follicle stimulating hormone (hFSH); creatine phosphokinase MB isoenzyme; ferritin; carcinoembryonic antigen (CEA); prostate specific antigen (PSA); CA-549 (a breast cancer antigen); hepatitis B surface antigen (HBsAg); hepatitis B surface antibody (HBsAb); hepatitis B core antigen (HBcAg); hepatitis B core antibody (HBcAb); hepatitis A virus antibody; an antigen of human immunodeficiency virus HIV I, such as gp 120, p66, p41, p31, p24 or p17; the p41 antigen of HIV II; and the respective antiligand (preferably a monoclonal antibody) to any one of the above ligands. The HIV antigens are described more fully in U.S. Pat. No. 5,120,662 and in Gelderblood et al., Virology 156:171-176 1987, both of which are incorporated herein by reference.
- As used herein, the term “probe-conjugate” refers to a species that is capable of carrying an analyte in a lateral flow assay to form a probe conjugate complex, which binds with a first capture reagent in the
detection zone 24 to become a “sandwich complex” in detection area ordetection zone 24. - As used herein, the term “microparticle” is a more specific reference to a particular type of probe, and may include any beads or probes to which an antibody may be bound, whether covalently, or non-covalently such as by adsorption. An additional requirement for some particles that are used in a quantitative assay is that the particle contributes a signal, usually light absorption, which would cause the zone in which the particles were located to have a different signal than the rest of the
membrane 23. - The microparticle employed typically must be capable of being retained by the
membrane 23. For example, when a microparticle is subject to liquid flow, the microparticle must be capable of remaining substantially immobilized. The microparticles may be of any shape but are preferably spherical. The nature of the microparticle may vary widely. It may be naturally occurring or synthetic. It can be a single material, a few materials, or a combination of a wide variety of materials. Naturally occurring microparticles include nuclei, mycoplasma, plasmids, plastids, mammalian cells (e.g., erythrocyte ghosts), unicellular microorganisms (e.g., bacteria) and the like. Synthetic microparticles may be prepared from synthetic or naturally occurring materials, or combinations thereof. - For example, latex microparticles may be prepared from a synthetic material such as styrene. Other microparticles may be prepared from naturally occurring materials, such as polysaccharides, e.g., agarose, or the like. (See, e.g., Gould, et al., U.S. Pat. No. 4,837,168, which describes the use of a variety of particles.) Preferred microparticles are microspheres of latex (i.e., a natural or a synthetic polymer) or glass; more preferably microspheres of latex. The microspheres of glass or latex are also referred to in the art as “beads” or “microbeads.”
- A typical size for such beads is about 0.3 microns, but the invention may employ microparticles having greater or lesser size. For example, the mean diameter for the microparticle component of the present invention is within the range from about 0.01 microns to about 100 microns and more typically from about 0.1 microns to about 75 microns. The mean diameter and type of the microparticle chosen for a particular application will depend upon the pore size of the membrane and/or its composition.
- Latex microparticles for use in the present invention are commercially available as polymeric microspheres of substantially uniform diameter (hereinafter “polymeric microspheres”), such as from Bangs Laboratories of Carmel, Ind., or Dow Chemical Co. of Midland, Mich. Although any polymeric microsphere that is capable of adsorbing or of being covalently bound to a binding partner may be used in the present invention, the polymeric microspheres typically are composed of one or more members of the group consisting of polystyrene, butadiene styrenes, styreneacrylic-vinyl terpolymer, polymethylmethacrylate, polyethylmethacrylate, styrene-maleic anhydride copolymer, polyvinyl acetate, polyvinylpyridine, polydivinylbenzene, polybutyleneterephthalate, acrylonitrile, vinylchloride-acrylates and the like or an aldehyde, carboxyl, amino, hydroxyl, or hydrazide derivative thereof.
- The underivatized polymeric microspheres, such as polystyrene, are hydrophobic and passively adsorb other hydrophobic molecules, including most proteins and antibodies. Techniques for adsorbing a protein or polypeptide on a hydrophobic particle are provided in the publication by Cantarero, et al. “The Absorption Characteristics of Proteins for Polystyrene and Their Significance in Solid Phase Immunoassays,” Analytical Biochemistry 105, 375-382 (1980); and Bangs, “Latex Immunoassays,” J. Clin. Immunoassay, 13 127-131 (1980) both of which are incorporated herein by reference.
- Various procedures for adsorbing molecules on polymeric microspheres are also described, in general terms, in Bangs, L. B., “Uniform Latex Particles,” presented at a workshop at the 41st National Meeting, Amer. Assoc. Clin. Chem., 1989, and available in printed form from Seragen Diagnostics Inc., Indianapolis, Ind.; or Galloway, R. J., “Development of Microparticle Tests and Immunoassays,” i.e., Seradyn Inc. of Indiana which is incorporated herein by reference.
- The covalent bonding of a binding partner to a microparticle may be accomplished either directly, such as by reacting an activated chemical functional group on the surface of a microparticle with an appropriate chemical functional group on the binding partner, or indirectly, such as by covalently binding the binding partner to a spacer molecule that has been covalently bound to the surface of the microparticle.
- By the phrase “membrane” as used herein is meant a test device that employs a membrane and one or more reagents to detect the concentration of an analyte of interest in a test solution, preferably an aqueous test solution. At least one of the reagents associated with the membrane device is a binding partner of the analyte of interest.
- The calibration device and method of the present invention is useful with essentially any membrane-based devices. A particularly preferred use for the calibrator of the present invention is as an internal calibrator. The choice and size of a microparticle for the stabilized internal calibrator of a membrane-based device is influenced by the choice of material for the membrane. The internal calibrator of the present invention may be affixed to the membrane by covalent or non-covalent bonding.
- In the practice of the invention, calibration and sample testing may be conducted under essentially exactly the same conditions at the same time, thus providing reliable quantitative results, with increased sensitivity.
- The invention also may be employed for semi-quantitative detection. As the multiple control lines provide a range of signal intensities, the signal intensity of a given detection line can be compared (i.e. such as for example, visually) with the intensity of the control lines. Based upon the intensity range wherein the detection line falls, the possible concentration range for the analyte may be determined. The probes may be latex beads labeled with any signal generating species or the labeled latex beads further conjugated with antibodies.
- The signal ratio between the detection lines and the control lines may be plotted against the analyte concentrations for a range of analyte concentrations to generate a calibration curve, such as shown in FIG. 2 herein. To determine the quantity of an unknown sample, the signal ratio may be converted to analyte concentration according to the calibration curve.
- Polyethyleneimine was used to demonstrate the invention. A 7.4% polyethyleneimine aqueous solution (stock solution)(1×), a 10× dilution and a 100× dilution were stripped onto Millipore SX membrane to form three control lines. The membrane was dried for about 1 hour at about 37 degrees Centigrade. A wicking pad was attached upon one end of the membrane. The other end of the membrane was inserted into a suspension of blue latex beads or red fluorescent latex beads containing 1.6% Tween 20 (a surfactant) or antibody-conjugated latex beads with 1.6
% Tween 20. Five minutes later, the beads were captured on the lines where the polyethyleneimine solution was stripped. - In another example, the membrane was stripped with three different polyethyleneimine solutions (1×, 10×, 100− dilution) on the lines of the
calibration zone 32 and anti C-reactive protein (CRP) monoclonal antibody (Mab A5804) was immobilized on the detection zone. The membrane was dried for about one hour at about 37 degrees Centigrade, and the wicking pad was attached to the end of the membrane to form a half dipstick. The other end of the half dipstick was inserted into a solution with CRP antigen and anti CRP monoclonal antibody (Mab A5801 1) conjugated to latex particles (blue). The solution flowed through the detection and control zones, and then to the wicking pad. One blue line on the detection zone and three blue lines on the control zone were observed. - In the above examples, it was observed that the signal intensities of the control lines were significantly different. The control line stripped with 7.4% polyethyleneimine stock solution exhibited the most signal intensity while the control line stripped with 100× dilution solution exhibited the least signal intensity. This observation was true for blue colored and red fluorescent latex beads alone, as well as these beads further conjugated with antibodies.
- The membrane HF 09002 was stripped with 0.14% (calibration #1), 0.64% (calibration #2) and 1.4% (calibration #3) of polyethyleneimine solution on the calibration or
calibration zone 32. On thedetection line 24, anti CRP monoclonal antibody at 1 mg/ml (Mab A5804) was immobilized. The membrane was dried at 37° C. for one hour and thewicking pad 28 was attached to the end of the membrane to form the half stick. The half sticks were inserted into the solutions containing the following nano-grams of CRP antigen (0. 0.54, 5.4 and 54) with excess amount of blue latex beads which are conjugated with anti CRP monoclonal antibody (Mab58011). It was observed that three calibration lines were formed with different intensities, where the line had 1.4% polyethyleneimine concentration exhibits the highest line intensity and the line had 0.14% polyethyleneimine concentration had the least line intensity. The same experiments were carried out with a mixture of blue latex beads and latex beads antibody conjugate and the same results were observed. (Experiments with different polyelectrolytes were also carried out, such thatline 1, 2 and 3 may be totally different polymers). - Results from Example 3 are provided below in Table 1.
TABLE 1 Signal Intensities of Calibration and Detection Lines Calibration #1 A A A A Calibration #2 B B B B Calibration #3 C C C C Detection None (0 ng) C (0.54 ng) B (5.4 ng) A (54 ng) Line - The results indicated that the intensity of calibration line #3 represents 0.54 ng of analyte,
calibration line # 2 represents 5.4 ng of analyte, and calibration line #1 represents 54 ng of analyte. When an unknown sample was tested, the analyte concentration could be visually determined by comparing the detection line intensity with the three calibration lines. - When the detection line intensity was less than calibration line #3, the concentration of the analyte was determined to be less than about 0.54 ng. When the detection line intensity was visually determined to be between calibration line #3 and #2, the analyte concentration was found to be between 0.54 and 5.4 ng. When the detection line intensity was found to be higher than calibration line #3, the analyte concentration was determined to be higher than 54 ng.
- The same procedure as Example 3 was conducted, with the exception that the concentration of the analyte was quantified by a electronic reading device. In such diagnostic reading devices, electronic routines make it possible to read automatically the intensities of calibration and detection lines and provide a readout or display for the analyte concentration.
- The latex beads generate a detectable colored light signal, from both the
detection zone 31 and the control lines of thecalibration zone 32. The reading device provides a comparison means for comparing the intensity of colored light signals generated by latex beads positioned upon the control lines 25-27 with the intensity of signals generated by microparticle-analyte conjugates positioned upon thedetection zone 31. - In yet another application of the invention, it is possible to use fluorescence to determine the amount of analyte in a test sample. In this manner, it is possible to use a probe or a microparticle which itself is capable of exhibiting the property of fluorescence, in which signals are generated from the probe or microparticle once it has been deposited in either the
calibration zone 32 or thedetection zone 31. A receiver or a receiving device is capable of measuring the amount of signal generated in thedetection zone 31 and thecalibration zone 32, and making the appropriate comparisons to determine the quantity of analyte in a given test sample. - It is understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention, which broader aspects are embodied in the exemplary constructions. The invention is shown by example in the appended claims.
Claims (22)
1. A lateral flow assay for detecting the quantity of analyte residing in a test solution, the assay comprising:
(a) a plurality of probes, the probes being configured for generating a detectable signal, wherein the probes are capable of combining with analyte to form a probe conjugate analyte complex;
(b) a membrane, the membrane being configured for mobilizing a test solution containing both probes and probe conjugate analyte complexes, the membrane comprising:
(i) a detection zone, the detection zone having deposited thereon an immobilized first capture reagent, wherein the immobilized first capture reagent is configured for bonding with probe-conjugate analyte complexes to form sandwich complexes that generate signals;
(ii) a calibration zone, the calibration zone comprising at least first and second control lines, wherein the first and second control lines each have applied thereon a predetermined amount of a second capture reagent, the second capture reagent being configured to immobilize probes upon the first and second control lines to form control probe complexes capable of generating a control signal.
2. The lateral flow assay of claim 1 , further comprising:
(c) a comparison means for comparing the intensity of signals generated by control probe complexes positioned upon said first and second control lines with the intensity of signals generated by sandwich complexes positioned upon the detection zone.
3. The lateral flow assay of claim 2 , further wherein a calibration curve is generated using signal intensity data generated by control probe complexes positioned upon the control lines.
4. The lateral flow assay of claim 1 in which the probe comprises a microparticle that is capable of generating a visual signal.
5. The lateral flow assay of claim 4 in which the microparticle is capable of generating a color intensity.
6. The lateral flow assay of claim 1 in which the probe is capable of generating a fluorescent signal.
7. The lateral flow assay of claim 1 in which the probe comprises a microparticle.
8. The lateral flow assay of claim 7 in which the microparticle exhibits a color intensity.
9. The lateral flow assay of claim 2 in which a detection device is provided for detecting signals generated by control probe complexes positioned upon respective control lines with the intensity of signals generated by sandwich complexes positioned upon the detection zone.
10. The lateral flow assay of claim 2 wherein the probe comprises a microparticle, further wherein the comparison means comprises a device adapted for comparing intensity of light signals generated from the first and second control lines with the intensity of signals generated by sandwich complexes positioned upon the detection zone.
11. The lateral flow assay of claim 10 , further wherein a calibration curve is generated using signal intensity data from the first and second control lines.
12. The lateral flow assay of claim 11 in which an automated system of generating the curve and performing the comparison is provided.
13. A method of detecting the quantity of an analyte present in a test solution, the method comprising:
(a) providing a membrane with a test solution containing analyte;
(b) providing a plurality of probes and probe conjugates upon the membrane;
(c) binding the probe conjugates with the analyte to form probe analyte conjugates;
(d) wherein the membrane comprises a first end and a second end, the membrane having a first capture reagent immobilized upon a detection zone, the membrane being configured for mobilizing a test solution containing probe-analyte conjugates from the first end to the second end of the membrane;
(e) capturing within a detection zone probe-analyte conjugates, thereby forming immobilized signal generating sandwich complexes within the detection zone;
(f) providing a calibration zone upon the membrane, the calibration zone comprising at least first and second control lines having predetermined amounts of a second capture reagent immobilized upon said control lines;
(g) capturing, with the second capture reagent, probes upon the first and second control lines by forming control probe complexes upon said control lines;
(h) generating a first set of control signals from the control probe complexes;
(i) generating a second set of measured signals from the sandwich complexes in the detection zone; and
(j) comparing the control signals to the measured signals to determine the quantity of analyte present in the test solution.
14. The method of claim 14 , wherein prior to step (j), the method further comprises the step of generating a signal intensity curve, further wherein step (j) comprises comparing control signals to the signal intensity curve to provide a determination of the quantity of analyte present in a test solution.
15. The method of claim 14 in which the probe comprises a microparticle that is capable of generating a signal.
16. The method of claim 15 in which the microparticle is capable of generating a color intensity.
17. The method of claim 16 in which the microparticle is a latex bead.
18. The method of claim 14 in which the probe is capable of generating a fluorescent signal.
19. The method of claim 13 in which a third control line is employed.
20. The method of claim 19 in which a fourth control line is employed.
21. The method of claim 19 in which the probes comprise latex beads.
22. The method of claim 21 in which latex beads further include coloring agents for providing a visually detectable signal.
Priority Applications (19)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/035,014 US20030119203A1 (en) | 2001-12-24 | 2001-12-24 | Lateral flow assay devices and methods for conducting assays |
US10/132,421 US7651841B2 (en) | 2001-12-24 | 2002-04-25 | Polyelectrolytic internal calibration system of a flow-through assay |
US10/132,673 US20030119204A1 (en) | 2001-12-24 | 2002-04-25 | Internal calibration system for flow-through assays |
PCT/US2002/037652 WO2003058242A2 (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays |
BRPI0215327-0A BR0215327A (en) | 2001-12-24 | 2002-11-21 | internal calibration system for flow circulation tests |
DE60237395T DE60237395D1 (en) | 2001-12-24 | 2002-11-21 | INTERNAL CALIBRATION SYSTEM FOR FLOW TESTS |
PCT/US2002/037653 WO2003058246A1 (en) | 2001-12-24 | 2002-11-21 | Flow-through assay with an internal calibration system using polyelectrolyte |
AU2002357754A AU2002357754A1 (en) | 2001-12-24 | 2002-11-21 | Flow-through assay with an internal calibration system using polyelectrolyte |
EP02806133A EP1459068B1 (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays |
AU2002365040A AU2002365040A1 (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays |
MXPA04006215A MXPA04006215A (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays. |
CNB028259505A CN100501406C (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays |
KR1020047009945A KR101043888B1 (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays |
RU2004122925/15A RU2004122925A (en) | 2001-12-24 | 2002-11-21 | INTERNAL CALIBRATION SYSTEM OF FLOW TEST SYSTEMS |
AT02806133T ATE478338T1 (en) | 2001-12-24 | 2002-11-21 | INTERNAL CALIBRATION SYSTEM FOR FLOW TESTS |
CA2471462A CA2471462C (en) | 2001-12-24 | 2002-11-21 | Internal calibration system for flow-through assays |
TW091136621A TW594010B (en) | 2001-12-24 | 2002-12-19 | Internal calibration system for flow-through assays |
TW091136622A TW587166B (en) | 2001-12-24 | 2002-12-19 | Polyelectrolytic internal calibration system of a flow-through assay |
US12/616,821 US8137985B2 (en) | 2001-12-24 | 2009-11-12 | Polyelectrolytic internal calibration system of a flow-through assay |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/035,014 US20030119203A1 (en) | 2001-12-24 | 2001-12-24 | Lateral flow assay devices and methods for conducting assays |
Related Child Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/132,673 Continuation-In-Part US20030119204A1 (en) | 2001-12-24 | 2002-04-25 | Internal calibration system for flow-through assays |
US10/132,421 Continuation-In-Part US7651841B2 (en) | 2001-12-24 | 2002-04-25 | Polyelectrolytic internal calibration system of a flow-through assay |
US10/134,421 Continuation-In-Part US6837171B1 (en) | 2001-12-24 | 2002-04-29 | Lightweight table with unitized table top |
Publications (1)
Publication Number | Publication Date |
---|---|
US20030119203A1 true US20030119203A1 (en) | 2003-06-26 |
Family
ID=21880091
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/035,014 Abandoned US20030119203A1 (en) | 2001-12-24 | 2001-12-24 | Lateral flow assay devices and methods for conducting assays |
US10/132,421 Active 2024-11-22 US7651841B2 (en) | 2001-12-24 | 2002-04-25 | Polyelectrolytic internal calibration system of a flow-through assay |
US10/132,673 Abandoned US20030119204A1 (en) | 2001-12-24 | 2002-04-25 | Internal calibration system for flow-through assays |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/132,421 Active 2024-11-22 US7651841B2 (en) | 2001-12-24 | 2002-04-25 | Polyelectrolytic internal calibration system of a flow-through assay |
US10/132,673 Abandoned US20030119204A1 (en) | 2001-12-24 | 2002-04-25 | Internal calibration system for flow-through assays |
Country Status (4)
Country | Link |
---|---|
US (3) | US20030119203A1 (en) |
KR (1) | KR101043888B1 (en) |
AT (1) | ATE478338T1 (en) |
DE (1) | DE60237395D1 (en) |
Cited By (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040092036A1 (en) * | 2002-09-11 | 2004-05-13 | Lattec I/S | Device for analysing analyte compounds and use hereof |
WO2005057216A1 (en) * | 2003-11-21 | 2005-06-23 | Kimberly-Clark Worldwide, Inc. | Method of reducing the sensitivity of assay devices |
US20050221504A1 (en) * | 2004-04-01 | 2005-10-06 | Petruno Patrick T | Optoelectronic rapid diagnostic test system |
WO2006003394A1 (en) * | 2004-07-01 | 2006-01-12 | Central Science Laboratory (Csl) Representing The Secretary Of State For Environment, Food And Rural Affairs | Analyte detection system |
US20060240541A1 (en) * | 2005-04-22 | 2006-10-26 | Petruno Patrick T | Lateral flow assay systems and methods |
US20060286616A1 (en) * | 2005-03-22 | 2006-12-21 | Miki Furukawa | Menopause stage monitor |
WO2007053487A2 (en) * | 2005-10-28 | 2007-05-10 | Binax, Inc. | Methods and devices for detection of the strain of a pathogen |
US20070116595A1 (en) * | 2005-11-22 | 2007-05-24 | Petrilla John F | Assaying test strips having different capture reagents |
US20070122914A1 (en) * | 2005-11-30 | 2007-05-31 | Curry Bo U | Obtaining measurements of light transmitted through an assay test strip |
US20070161078A1 (en) * | 2005-07-01 | 2007-07-12 | Arbor Vita Corporation | Methods and compositions for diagnosis and treatment of influenza |
US20070185679A1 (en) * | 2004-04-01 | 2007-08-09 | Petruno Patrick T | Indicating status of a diagnostic test system |
US20070188736A1 (en) * | 2006-02-16 | 2007-08-16 | Fouquet Julie E | Obtaining measurement and baseline signals for evaluating assay test strips |
US20070224594A1 (en) * | 2005-07-01 | 2007-09-27 | Arbor Vita Corporation | Detection of influenza virus |
US20070231922A1 (en) * | 2004-04-01 | 2007-10-04 | Petruno Patrick T | Assay test strips with multiple labels and reading same |
US20080028261A1 (en) * | 2005-12-19 | 2008-01-31 | Petruno Patrick T | End-of-life disabling of a diagnostic test system |
US7410808B1 (en) | 2003-12-08 | 2008-08-12 | Charm Sciences, Inc. | Method and assay for detection of residues |
US20090180928A1 (en) * | 2005-04-22 | 2009-07-16 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
EP2180319A1 (en) * | 2008-10-21 | 2010-04-28 | Kaiwood Technology Co., Ltd. | Biological test strip |
US20100167264A1 (en) * | 2008-12-30 | 2010-07-01 | Jin Po Lee | Quantitative analyte assay device and method |
US20100175455A1 (en) * | 2009-01-14 | 2010-07-15 | Alverix, Inc. | Methods and materials for calibration of a reader |
WO2011020724A1 (en) * | 2009-08-17 | 2011-02-24 | Dst Diagnostische Systeme & Technologien Gmbh | Test system for visual analysis |
CN102012423A (en) * | 2009-09-04 | 2011-04-13 | 开物科技股份有限公司 | Biological detection test base material |
US20110097820A1 (en) * | 2003-12-23 | 2011-04-28 | Kimberly-Clark Worldwide, Inc. | Swab-Based Diagnostic Systems |
EP2325640A1 (en) * | 2008-08-22 | 2011-05-25 | DENKA SEIKEN Co., Ltd. | Test apparatus for membrane assay equipped with reference display section |
US20110171754A1 (en) * | 2007-09-14 | 2011-07-14 | Gareth Redmond | Analysis system |
US20110223689A1 (en) * | 2010-03-09 | 2011-09-15 | Nokia Croporation | Apparatus and associated methods |
US20110244598A1 (en) * | 2008-12-03 | 2011-10-06 | Roche Diagnostics Operations, Inc. | Test Element Having Combined Control and Calibration Zone |
WO2011124991A3 (en) * | 2010-04-07 | 2011-12-29 | Biosensia Patents Limited | Flow control device for assays |
CN102539769A (en) * | 2011-12-22 | 2012-07-04 | 正元盛邦(天津)生物科技有限公司 | Method for semi-quantitative diagnosis of creatine kinase isoenzyme by double indicating line immuno-chromatography |
US20120171702A1 (en) * | 2009-06-30 | 2012-07-05 | Monash University | Quantitative and self-calibrating chemical analysis using paper-based microfluidic systems |
JP4988546B2 (en) * | 2005-01-28 | 2012-08-01 | 持田製薬株式会社 | Immunochromatographic test device and semi-quantitative method using the same |
US20120225422A1 (en) * | 2011-03-03 | 2012-09-06 | RoMonics, LLC | Method and device employing a non-receptor ligand interaction with nanoparticles or other solid phase followed by specific detection |
USD667228S1 (en) | 2009-09-24 | 2012-09-18 | Yuyama Manufacturing Co., Ltd. | Sheet for a drug bag |
US8900881B2 (en) | 2008-12-30 | 2014-12-02 | Jin Po Lee | Quantitative analyte assay device and method |
CN104937418A (en) * | 2012-11-15 | 2015-09-23 | 奥索临床诊断有限公司 | Calibrating assays using reaction time |
WO2017112780A1 (en) * | 2015-12-22 | 2017-06-29 | Polymer Technology Systems, Inc. | Systems and methods for quantification of creatinine using a creatinine-protein conjugate |
US10773781B2 (en) | 2018-06-05 | 2020-09-15 | Detekt Biomedical, Llc. | Universal motorized personal watercraft propulsion assistance and training device |
CN111684280A (en) * | 2017-12-05 | 2020-09-18 | 贝克顿·迪金森公司 | Lateral flow assay and method for detecting high concentrations of analytes |
WO2021041780A2 (en) | 2019-08-29 | 2021-03-04 | ARONOWITZ, Mireya, C. | Quantitative analyte detection in lateral flow immunochemistry |
EP3913368A1 (en) * | 2020-05-22 | 2021-11-24 | Thermogenesis Holdings, Inc. | Lateral flow immunoassay test reader and method of use |
US11243160B2 (en) | 2018-03-28 | 2022-02-08 | Detekt Biomedical, Llc | Custom optical reference calibrator fabrication system |
WO2022056078A1 (en) | 2020-09-11 | 2022-03-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Rnase h-assisted detection assay for rna (radar) |
WO2023201422A1 (en) * | 2022-04-19 | 2023-10-26 | Cardiai Technologies Ltd. | Lateral flow assay test strips and systems, and methods of use thereof |
Families Citing this family (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6837171B1 (en) | 2002-04-29 | 2005-01-04 | Palmer/Snyder Furniture Company | Lightweight table with unitized table top |
SE0201468D0 (en) * | 2002-05-13 | 2002-05-13 | Peter Aasberg | Method of using luminescent polymers for detection of biospecific interaction |
US7285424B2 (en) | 2002-08-27 | 2007-10-23 | Kimberly-Clark Worldwide, Inc. | Membrane-based assay devices |
US7781172B2 (en) * | 2003-11-21 | 2010-08-24 | Kimberly-Clark Worldwide, Inc. | Method for extending the dynamic detection range of assay devices |
US7247500B2 (en) | 2002-12-19 | 2007-07-24 | Kimberly-Clark Worldwide, Inc. | Reduction of the hook effect in membrane-based assay devices |
US20050112703A1 (en) | 2003-11-21 | 2005-05-26 | Kimberly-Clark Worldwide, Inc. | Membrane-based lateral flow assay devices that utilize phosphorescent detection |
US7943395B2 (en) | 2003-11-21 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Extension of the dynamic detection range of assay devices |
US7943089B2 (en) | 2003-12-19 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Laminated assay devices |
GB0403369D0 (en) * | 2004-02-16 | 2004-03-17 | Pa Consulting Services | Devices and methods for testing analytes |
US20060019265A1 (en) * | 2004-04-30 | 2006-01-26 | Kimberly-Clark Worldwide, Inc. | Transmission-based luminescent detection systems |
US7796266B2 (en) | 2004-04-30 | 2010-09-14 | Kimberly-Clark Worldwide, Inc. | Optical detection system using electromagnetic radiation to detect presence or quantity of analyte |
US20050244953A1 (en) * | 2004-04-30 | 2005-11-03 | Kimberly-Clark Worldwide, Inc. | Techniques for controlling the optical properties of assay devices |
US7815854B2 (en) * | 2004-04-30 | 2010-10-19 | Kimberly-Clark Worldwide, Inc. | Electroluminescent illumination source for optical detection systems |
DE102004023402A1 (en) | 2004-05-12 | 2005-12-08 | Roche Diagnostics Gmbh | Method for increasing the dynamic measuring range of, in particular immunological test elements based on specific binding reactions |
US7094528B2 (en) * | 2004-06-30 | 2006-08-22 | Kimberly-Clark Worldwide, Inc. | Magnetic enzyme detection techniques |
US7521226B2 (en) | 2004-06-30 | 2009-04-21 | Kimberly-Clark Worldwide, Inc. | One-step enzymatic and amine detection technique |
US7906276B2 (en) | 2004-06-30 | 2011-03-15 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
WO2006083367A2 (en) * | 2004-11-23 | 2006-08-10 | Response Biomedical Corporation | Immunoassay employing two-step internal calibration reaction |
US7682817B2 (en) * | 2004-12-23 | 2010-03-23 | Kimberly-Clark Worldwide, Inc. | Microfluidic assay devices |
US7939342B2 (en) | 2005-03-30 | 2011-05-10 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits employing an internal calibration system |
US7858384B2 (en) * | 2005-04-29 | 2010-12-28 | Kimberly-Clark Worldwide, Inc. | Flow control technique for assay devices |
US7803319B2 (en) * | 2005-04-29 | 2010-09-28 | Kimberly-Clark Worldwide, Inc. | Metering technique for lateral flow assay devices |
CA2620079A1 (en) * | 2005-08-23 | 2007-03-01 | Paul C. Harris | Multi-directional immunochromatographic assays |
US7504235B2 (en) | 2005-08-31 | 2009-03-17 | Kimberly-Clark Worldwide, Inc. | Enzyme detection technique |
US8003399B2 (en) | 2005-08-31 | 2011-08-23 | Kimberly-Clark Worldwide, Inc. | Nitrite detection technique |
US7829347B2 (en) | 2005-08-31 | 2010-11-09 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits with improved detection accuracy |
US7279136B2 (en) | 2005-12-13 | 2007-10-09 | Takeuchi James M | Metering technique for lateral flow assay devices |
US7618810B2 (en) * | 2005-12-14 | 2009-11-17 | Kimberly-Clark Worldwide, Inc. | Metering strip and method for lateral flow assay devices |
US7745158B2 (en) | 2005-12-14 | 2010-06-29 | Kimberly-Clark Worldwide, Inc. | Detection of secreted aspartyl proteases from Candida species |
US11237171B2 (en) | 2006-02-21 | 2022-02-01 | Trustees Of Tufts College | Methods and arrays for target analyte detection and determination of target analyte concentration in solution |
US8460879B2 (en) * | 2006-02-21 | 2013-06-11 | The Trustees Of Tufts College | Methods and arrays for target analyte detection and determination of target analyte concentration in solution |
US8758989B2 (en) * | 2006-04-06 | 2014-06-24 | Kimberly-Clark Worldwide, Inc. | Enzymatic detection techniques |
US20100112680A1 (en) * | 2006-07-11 | 2010-05-06 | Paul Nigel Brockwell | Indicator system for determining analyte concentration |
US20120269728A1 (en) * | 2006-08-02 | 2012-10-25 | Antara Biosciences Inc. | Methods and compositions for detecting one or more target agents using tracking components |
US8044257B2 (en) | 2006-10-30 | 2011-10-25 | Kimberly-Clark Worldwide, Inc. | Absorbent article containing lateral flow assay device |
US8012761B2 (en) * | 2006-12-14 | 2011-09-06 | Kimberly-Clark Worldwide, Inc. | Detection of formaldehyde in urine samples |
US7935538B2 (en) * | 2006-12-15 | 2011-05-03 | Kimberly-Clark Worldwide, Inc. | Indicator immobilization on assay devices |
US7897360B2 (en) | 2006-12-15 | 2011-03-01 | Kimberly-Clark Worldwide, Inc. | Enzyme detection techniques |
US7846383B2 (en) * | 2006-12-15 | 2010-12-07 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay device and absorbent article containing same |
US8043272B2 (en) | 2007-04-30 | 2011-10-25 | Kimberly-Clark Worldwide, Inc. | Collection and testing of infant urine using an absorbent article |
US20080269707A1 (en) | 2007-04-30 | 2008-10-30 | Kimberly-Clark Worldwide, Inc. | Lateral Flow Device for Attachment to an Absorbent Article |
ES2556627T3 (en) * | 2007-08-30 | 2016-01-19 | Trustees Of Tufts College | Methods to determine the concentration of an analyte in solution |
US8535617B2 (en) * | 2007-11-30 | 2013-09-17 | Kimberly-Clark Worldwide, Inc. | Blood cell barrier for a lateral flow device |
US8222047B2 (en) * | 2008-09-23 | 2012-07-17 | Quanterix Corporation | Ultra-sensitive detection of molecules on single molecule arrays |
US20100290948A1 (en) * | 2009-05-15 | 2010-11-18 | Xuedong Song | Absorbent articles capable of indicating the presence of urinary tract infections |
US8900850B2 (en) * | 2009-09-17 | 2014-12-02 | Michael J. Lane | Lateral flow based methods and assays for rapid and inexpensive diagnostic tests |
US8236574B2 (en) * | 2010-03-01 | 2012-08-07 | Quanterix Corporation | Ultra-sensitive detection of molecules or particles using beads or other capture objects |
US8415171B2 (en) | 2010-03-01 | 2013-04-09 | Quanterix Corporation | Methods and systems for extending dynamic range in assays for the detection of molecules or particles |
US9678068B2 (en) * | 2010-03-01 | 2017-06-13 | Quanterix Corporation | Ultra-sensitive detection of molecules using dual detection methods |
ES2544635T3 (en) | 2010-03-01 | 2015-09-02 | Quanterix Corporation | Methods to extend the dynamic range in assays for the detection of molecules or particles |
CN101900728A (en) * | 2010-08-05 | 2010-12-01 | 中国农业科学院油料作物研究所 | Multi-test-line immunochromatographic test strip for semi-quantitatively detecting aflatoxin B1 and preparation method thereof |
US9952237B2 (en) | 2011-01-28 | 2018-04-24 | Quanterix Corporation | Systems, devices, and methods for ultra-sensitive detection of molecules or particles |
WO2012142301A2 (en) | 2011-04-12 | 2012-10-18 | Quanterix Corporation | Methods of determining a treatment protocol for and/or a prognosis of a patients recovery from a brain injury |
US9715579B2 (en) | 2011-09-09 | 2017-07-25 | Alverix, Inc. | Distributed network of in-vitro diagnostic devices |
US9524372B2 (en) * | 2011-09-09 | 2016-12-20 | Alverix, Inc. | In-vitro diagnostic device using external information in conjunction with test results |
US9932626B2 (en) | 2013-01-15 | 2018-04-03 | Quanterix Corporation | Detection of DNA or RNA using single molecule arrays and other techniques |
JP6300676B2 (en) * | 2014-07-30 | 2018-03-28 | 株式会社日立ハイテクノロジーズ | Analysis method and automatic analyzer |
JP6312555B2 (en) * | 2014-08-14 | 2018-04-18 | デンカ生研株式会社 | Method for expanding the quantitation range in immunochromatography |
JP7046845B2 (en) | 2016-06-22 | 2022-04-04 | ベクトン・ディキンソン・アンド・カンパニー | Modular assay reader device |
US20210405044A1 (en) * | 2017-06-28 | 2021-12-30 | Becton, Dickinson And Company | Sandwich-type assays using decreasing signal portions of dose response curve to measure analytes, including analytes at high concentration |
Family Cites Families (379)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US146754A (en) * | 1874-01-27 | Improvement in harness-names | ||
US450854A (en) * | 1891-04-21 | Adolf weidenbusch | ||
US164659A (en) | 1875-06-22 | Improvement in processes of preparing pickles | ||
US17615A (en) * | 1857-06-23 | Printing-press | ||
US14073A (en) * | 1856-01-08 | Improvement in seeding-machines | ||
US55776A (en) * | 1866-06-19 | Improvement in tree-protectors | ||
US5622871A (en) | 1987-04-27 | 1997-04-22 | Unilever Patent Holdings B.V. | Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents |
US3772076A (en) | 1970-01-26 | 1973-11-13 | Hercules Inc | Reaction products of epihalohydrin and polymers of diallylamine and their use in paper |
US3700623A (en) | 1970-04-22 | 1972-10-24 | Hercules Inc | Reaction products of epihalohydrin and polymers of diallylamine and their use in paper |
CS179075B1 (en) | 1974-11-26 | 1977-10-31 | Stoy Vladimir | Mode of manufacture of spherical particles from polymer |
SE388694B (en) | 1975-01-27 | 1976-10-11 | Kabi Ab | WAY TO PROVIDE AN ANTIGEN EXV IN SAMPLES OF BODY WHEATS, USING POROST BERAR MATERIAL BONDED OR ADSORBING ANTIBODIES |
USRE30267E (en) | 1975-06-20 | 1980-05-06 | Eastman Kodak Company | Multilayer analytical element |
US4094647A (en) | 1976-07-02 | 1978-06-13 | Thyroid Diagnostics, Inc. | Test device |
US4210723A (en) | 1976-07-23 | 1980-07-01 | The Dow Chemical Company | Method of coupling a protein to an epoxylated latex |
US4115535A (en) | 1977-06-22 | 1978-09-19 | General Electric Company | Diagnostic method employing a mixture of normally separable protein-coated particles |
US4275149A (en) | 1978-11-24 | 1981-06-23 | Syva Company | Macromolecular environment control in specific receptor assays |
US4374925A (en) | 1978-11-24 | 1983-02-22 | Syva Company | Macromolecular environment control in specific receptor assays |
US4361537A (en) | 1979-01-12 | 1982-11-30 | Thyroid Diagnostics, Inc. | Test device and method for its use |
US4235601A (en) | 1979-01-12 | 1980-11-25 | Thyroid Diagnostics, Inc. | Test device and method for its use |
US4441373A (en) * | 1979-02-21 | 1984-04-10 | American Hospital Supply Corporation | Collection tube for drawing samples of biological fluids |
US4312228A (en) * | 1979-07-30 | 1982-01-26 | Henry Wohltjen | Methods of detection with surface acoustic wave and apparati therefor |
US5156953A (en) | 1979-12-26 | 1992-10-20 | Syntex (U.S.A.) Inc. | Simultaneous calibration heterogeneous immunoassay |
US5432057A (en) | 1979-12-26 | 1995-07-11 | Syva Company | Simultaneous calibration heterogeneous immunoassay |
US4533629A (en) | 1981-04-17 | 1985-08-06 | Syva Company | Simultaneous calibration heterogeneous immunoassay |
US4843000A (en) * | 1979-12-26 | 1989-06-27 | Syntex (U.S.A.) Inc. | Simultaneous calibration heterogeneous immunoassay |
US4849338A (en) | 1982-07-16 | 1989-07-18 | Syntex (U.S.A.) Inc. | Simultaneous calibration heterogeneous immunoassay |
US4540659A (en) | 1981-04-17 | 1985-09-10 | Syva Company | Simultaneous calibration heterogeneous immunoassay |
US4299916A (en) | 1979-12-26 | 1981-11-10 | Syva Company | Preferential signal production on a surface in immunoassays |
CH648052A5 (en) | 1980-02-14 | 1985-02-28 | Ciba Geigy Ag | METHOD FOR PRODUCING TRIARYL METHANE COMPOUNDS. |
US4427836A (en) | 1980-06-12 | 1984-01-24 | Rohm And Haas Company | Sequential heteropolymer dispersion and a particulate material obtainable therefrom, useful in coating compositions as a thickening and/or opacifying agent |
EP0146654A3 (en) | 1980-06-20 | 1986-08-20 | Unilever Plc | Processes and apparatus for carrying out specific binding assays |
US4366241A (en) | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
US4385126A (en) * | 1980-11-19 | 1983-05-24 | International Diagnostic Technology, Inc. | Double tagged immunoassay |
US4426451A (en) | 1981-01-28 | 1984-01-17 | Eastman Kodak Company | Multi-zoned reaction vessel having pressure-actuatable control means between zones |
US4442204A (en) | 1981-04-10 | 1984-04-10 | Miles Laboratories, Inc. | Homogeneous specific binding assay device and preformed complex method |
US4444592A (en) | 1981-06-02 | 1984-04-24 | The Sherwin-Williams Company | Pigment compositions and processes therefor |
US4363874A (en) | 1981-08-07 | 1982-12-14 | Miles Laboratories, Inc. | Multilayer analytical element having an impermeable radiation nondiffusing reflecting layer |
EP0073593A1 (en) | 1981-09-01 | 1983-03-09 | E.I. Du Pont De Nemours And Company | Size-exclusion heterogeneous immunoassay |
US4480042A (en) | 1981-10-28 | 1984-10-30 | E. I. Du Pont De Nemours And Company | Covalently bonded high refractive index particle reagents and their use in light scattering immunoassays |
US4477635A (en) | 1982-01-04 | 1984-10-16 | Minnesota Mining And Manufacturing Company | Polymeric triarylmethane dyes |
US4435504A (en) * | 1982-07-15 | 1984-03-06 | Syva Company | Immunochromatographic assay with support having bound "MIP" and second enzyme |
US4534356A (en) | 1982-07-30 | 1985-08-13 | Diamond Shamrock Chemicals Company | Solid state transcutaneous blood gas sensors |
US4632559A (en) | 1982-11-29 | 1986-12-30 | Miles Laboratories, Inc. | Optical readhead |
US4537861A (en) | 1983-02-03 | 1985-08-27 | Elings Virgil B | Apparatus and method for homogeneous immunoassay |
GB8314523D0 (en) | 1983-05-25 | 1983-06-29 | Lowe C R | Diagnostic device |
EP0127797B1 (en) | 1983-06-03 | 1987-06-16 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Labelled molecules for fluorescence immunoassays and processes and intermediates for their preparation |
CH662421A5 (en) | 1983-07-13 | 1987-09-30 | Suisse Horlogerie Rech Lab | PIEZOELECTRIC CONTAMINATION DETECTOR. |
US4537657A (en) | 1983-08-26 | 1985-08-27 | Hercules Incorporated | Wet strength resins |
US4552458A (en) | 1983-10-11 | 1985-11-12 | Eastman Kodak Company | Compact reflectometer |
US4595661A (en) * | 1983-11-18 | 1986-06-17 | Beckman Instruments, Inc. | Immunoassays and kits for use therein which include low affinity antibodies for reducing the hook effect |
US4703017C1 (en) | 1984-02-14 | 2001-12-04 | Becton Dickinson Co | Solid phase assay with visual readout |
GB8406752D0 (en) | 1984-03-15 | 1984-04-18 | Unilever Plc | Chemical and clinical tests |
US4743560A (en) | 1984-03-26 | 1988-05-10 | Becton Dickinson And Company | Solid phase assay |
US4698262A (en) | 1984-04-27 | 1987-10-06 | Becton, Dickinson And Company | Fluorescently labeled microbeads |
US4632901A (en) | 1984-05-11 | 1986-12-30 | Hybritech Incorporated | Method and apparatus for immunoassays |
FI842992A0 (en) * | 1984-07-26 | 1984-07-26 | Labsystems Oy | IMMUNOLOGISKT DEFINITIONSFOERFARANDE. |
US4661235A (en) | 1984-08-03 | 1987-04-28 | Krull Ulrich J | Chemo-receptive lipid based membrane transducers |
US4596697A (en) | 1984-09-04 | 1986-06-24 | The United States Of America As Represented By The Secretary Of The Army | Chemical sensor matrix |
US5310687A (en) * | 1984-10-31 | 1994-05-10 | Igen, Inc. | Luminescent metal chelate labels and means for detection |
US4722889A (en) * | 1985-04-02 | 1988-02-02 | Leeco Diagnostics, Inc. | Immunoassays using multiple monoclonal antibodies and scavenger antibodies |
US5026653A (en) | 1985-04-02 | 1991-06-25 | Leeco Diagnostic, Inc. | Scavenger antibody mixture and its use for immunometric assay |
CA1272127A (en) | 1985-04-04 | 1990-07-31 | Hybritech Incorporated | Solid phase system for use in ligand-receptor assays |
US4743542A (en) | 1985-04-11 | 1988-05-10 | Ortho Diagnostic | Method for forestalling the hook effect in a multi-ligand immunoassay system |
GB8509492D0 (en) | 1985-04-12 | 1985-05-15 | Plessey Co Plc | Optical assay |
DE3575203D1 (en) | 1985-06-28 | 1990-02-08 | Eastman Kodak Co | COMPACT REFLECTOR. |
US4963498A (en) | 1985-08-05 | 1990-10-16 | Biotrack | Capillary flow device |
US4806312A (en) * | 1985-08-28 | 1989-02-21 | Miles Inc. | Multizone analytical element having detectable signal concentrating zone |
US5238815A (en) | 1985-08-30 | 1993-08-24 | Toyo Soda Manufacturing Co., Ltd. | Enzymatic immunoassay involving detecting fluorescence while oscillating magnetic beads |
TW203120B (en) | 1985-10-04 | 1993-04-01 | Abbott Lab | |
US5500350A (en) | 1985-10-30 | 1996-03-19 | Celltech Limited | Binding assay device |
US4917503A (en) | 1985-12-02 | 1990-04-17 | Lifelines Technology, Inc. | Photoactivatable leuco base time-temperature indicator |
CA1291031C (en) | 1985-12-23 | 1991-10-22 | Nikolaas C.J. De Jaeger | Method for the detection of specific binding agents and their correspondingbindable substances |
US5585279A (en) | 1986-01-23 | 1996-12-17 | Davidson; Robert S. | Time-resolved luminescence binding assays using a fluorescent transition metal label other than ruthenium |
US4916056A (en) * | 1986-02-18 | 1990-04-10 | Abbott Laboratories | Solid-phase analytical device and method for using same |
US5468606A (en) | 1989-09-18 | 1995-11-21 | Biostar, Inc. | Devices for detection of an analyte based upon light interference |
US5482830A (en) * | 1986-02-25 | 1996-01-09 | Biostar, Inc. | Devices and methods for detection of an analyte based upon light interference |
US4776944A (en) | 1986-03-20 | 1988-10-11 | Jiri Janata | Chemical selective sensors utilizing admittance modulated membranes |
US5591581A (en) * | 1986-04-30 | 1997-01-07 | Igen, Inc. | Electrochemiluminescent rhenium moieties and methods for their use |
EP0272320B1 (en) | 1986-06-17 | 1994-03-23 | Baxter Diagnostics Inc. | Homogeneous fluoroassay methods employing fluorescent background rejection |
GB8618133D0 (en) * | 1986-07-24 | 1986-09-03 | Pa Consulting Services | Biosensors |
JPH0692969B2 (en) | 1986-07-30 | 1994-11-16 | 株式会社シノテスト | Immunological measurement method |
US5182135A (en) | 1986-08-12 | 1993-01-26 | Bayer Aktiengesellschaft | Process for improving the adherency of metallic coatings deposited without current on plastic surfaces |
US4935346A (en) | 1986-08-13 | 1990-06-19 | Lifescan, Inc. | Minimum procedure system for the determination of analytes |
US4867908A (en) | 1986-08-29 | 1989-09-19 | Becton, Dickinson And Company | Method and materials for calibrating flow cytometers and other analysis instruments |
GB2197065A (en) | 1986-11-03 | 1988-05-11 | Stc Plc | Optical sensor device |
US4835099A (en) | 1986-11-20 | 1989-05-30 | Becton, Dickinson And Company | Signal enhancement in immunoassay by modulation of enzymatic catalysis |
DE3788356T2 (en) | 1986-12-15 | 1994-06-23 | British Tech Group Usa | MONOMER PHTHALOCYANIN REAGENTS. |
US4954435A (en) | 1987-01-12 | 1990-09-04 | Becton, Dickinson And Company | Indirect colorimetric detection of an analyte in a sample using ratio of light signals |
US4920046A (en) | 1987-02-20 | 1990-04-24 | Becton, Dickinson And Company | Process, test device, and test kit for a rapid assay having a visible readout |
USRE38430E1 (en) | 1987-03-27 | 2004-02-17 | Becton, Dickinson And Company | Solid phase chromatographic immunoassay |
CA1303983C (en) | 1987-03-27 | 1992-06-23 | Robert W. Rosenstein | Solid phase assay |
JPH0684970B2 (en) * | 1987-03-31 | 1994-10-26 | 株式会社京都医科学研究所 | Method of detecting occult blood in feces |
US4857453A (en) | 1987-04-07 | 1989-08-15 | Syntex (U.S.A.) Inc. | Immunoassay device |
DE3856542T2 (en) | 1987-04-27 | 2003-10-30 | Inverness Medical Switzerland | Test device for carrying out specific binding tests |
US4855240A (en) | 1987-05-13 | 1989-08-08 | Becton Dickinson And Company | Solid phase assay employing capillary flow |
US4904583A (en) | 1987-05-26 | 1990-02-27 | Becton, Dickinson And Company | Cascade immunoassay by multiple binding reactions |
US5120643A (en) | 1987-07-13 | 1992-06-09 | Abbott Laboratories | Process for immunochromatography with colloidal particles |
US4842783A (en) | 1987-09-03 | 1989-06-27 | Cordis Corporation | Method of producing fiber optic chemical sensors incorporating photocrosslinked polymer gels |
US4956302A (en) | 1987-09-11 | 1990-09-11 | Abbott Laboratories | Lateral flow chromatographic binding assay device |
SE8703682L (en) | 1987-09-24 | 1989-03-25 | Wallac Oy | HOMOGENIC DETERMINATION METHOD USING AFFINITY REACTIONS |
US5073340A (en) | 1987-10-08 | 1991-12-17 | Becton, Dickinson And Company | Depositing a binder on a solid support |
US4978625A (en) | 1987-10-19 | 1990-12-18 | Becton, Dickinson And Company | Fluorescence immunoassay using water insoluble dyes |
US5275785A (en) | 1987-10-30 | 1994-01-04 | Unilever Patent Holdings B.V. | Test device for detecting an analyte in a liquid sample |
US5670381A (en) | 1988-01-29 | 1997-09-23 | Abbott Laboratories | Devices for performing ion-capture binding assays |
EP0400086B1 (en) | 1988-02-08 | 1993-01-27 | University College Cardiff Consultants Ltd. | Detection of diamines in biological fluids |
US5268306A (en) | 1988-02-29 | 1993-12-07 | Boehringer Mannheim Gmbh | Preparation of a solid phase matrix containing a bound specific binding pair |
US5145784A (en) | 1988-05-04 | 1992-09-08 | Cambridge Biotech Corporation | Double capture assay method employing a capillary flow device |
EP0341927B1 (en) | 1988-05-10 | 1993-07-14 | AMERSHAM INTERNATIONAL plc | Biological sensors |
EP0341928A1 (en) | 1988-05-10 | 1989-11-15 | AMERSHAM INTERNATIONAL plc | Improvements relating to surface plasmon resonance sensors |
GB8811919D0 (en) | 1988-05-20 | 1988-06-22 | Amersham Int Plc | Biological sensors |
US5573919A (en) | 1988-06-02 | 1996-11-12 | Carter-Wallace | Assay using an absorbent material |
GB8813307D0 (en) | 1988-06-06 | 1988-07-13 | Amersham Int Plc | Biological sensors |
AU2684488A (en) | 1988-06-27 | 1990-01-04 | Carter-Wallace, Inc. | Test device and method for colored particle immunoassay |
US4877586A (en) | 1988-07-27 | 1989-10-31 | Eastman Kodak Company | Sliding test device for assays |
US5075077A (en) | 1988-08-02 | 1991-12-24 | Abbott Laboratories | Test card for performing assays |
AT390517B (en) * | 1988-08-04 | 1990-05-25 | Avl Verbrennungskraft Messtech | OPTICAL SENSOR AND METHOD FOR THE PRODUCTION THEREOF |
US4973670A (en) | 1988-08-12 | 1990-11-27 | The Dow Chemical Company | Method for preparing hollow latexes |
US5252459A (en) | 1988-09-23 | 1993-10-12 | Abbott Laboratories | Indicator reagents, diagnostic assays and test kits employing organic polymer latex particles |
EP0363504A1 (en) | 1988-10-10 | 1990-04-18 | Dräger Nederland B.V. | Method of providing a substrate with a layer comprising a polyvinylbased hydrogel and a biochemically active material |
US6448091B1 (en) | 1988-11-03 | 2002-09-10 | Igen International, Inc. | Method and apparatus for improved luminescence assays using particle concentration chemiluminescence detection |
SE8804074D0 (en) | 1988-11-10 | 1988-11-10 | Pharmacia Ab | SENSOR UNIT AND ITS USE IN BIOSENSOR SYSTEM |
SE462454B (en) | 1988-11-10 | 1990-06-25 | Pharmacia Ab | METHOD FOR USE IN BIOSENSORS |
SE8902043L (en) | 1988-11-10 | 1990-05-11 | Pharmacia Ab | PROCEDURE CHARACTERIZES MACROMOLECULES |
US5063081A (en) | 1988-11-14 | 1991-11-05 | I-Stat Corporation | Method of manufacturing a plurality of uniform microfabricated sensing devices having an immobilized ligand receptor |
US5003178A (en) * | 1988-11-14 | 1991-03-26 | Electron Vision Corporation | Large-area uniform electron source |
US5208143A (en) | 1988-11-17 | 1993-05-04 | Becton, Dickinson And Company | Immunoassay on a preblocked solid surface |
US4940734A (en) | 1988-11-23 | 1990-07-10 | American Cyanamid | Process for the preparation of porous polymer beads |
ATE115982T1 (en) * | 1988-11-23 | 1995-01-15 | Cytec Tech Corp | POROUS POLYMER BEADS AND METHODS. |
US4895017A (en) | 1989-01-23 | 1990-01-23 | The Boeing Company | Apparatus and method for early detection and identification of dilute chemical vapors |
US6352862B1 (en) | 1989-02-17 | 2002-03-05 | Unilever Patent Holdings B.V. | Analytical test device for imuno assays and methods of using same |
US5096671A (en) | 1989-03-15 | 1992-03-17 | Cordis Corporation | Fiber optic chemical sensors incorporating electrostatic coupling |
US5120662A (en) | 1989-05-09 | 1992-06-09 | Abbott Laboratories | Multilayer solid phase immunoassay support and method of use |
US5234813A (en) | 1989-05-17 | 1993-08-10 | Actimed Laboratories, Inc. | Method and device for metering of fluid samples and detection of analytes therein |
US5770416A (en) | 1989-05-26 | 1998-06-23 | Upfront Chromatography A/S | Permeable hollow particles having an outer shell of mechanically rigid porous material |
US5744101A (en) | 1989-06-07 | 1998-04-28 | Affymax Technologies N.V. | Photolabile nucleoside protecting groups |
US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
GB9008261D0 (en) | 1990-04-11 | 1990-06-13 | Ares Serono Res & Dev Ltd | Method of improving assay sensitivity |
US5166079A (en) | 1989-07-19 | 1992-11-24 | Pb Diagnostic Systems, Inc. | Analytical assay method |
JPH0366384A (en) | 1989-08-04 | 1991-03-22 | Senjiyu Seiyaku Kk | System for controlling release of physiologically active material |
US5235238A (en) | 1989-08-10 | 1993-08-10 | Dainabot Company, Limited | Electrode-separated piezoelectric crystal oscillator and method for measurement using the electrode-separated piezoelectric crystal oscillator |
AU635314B2 (en) | 1989-09-08 | 1993-03-18 | Terumo Kabushiki Kaisha | Measuring apparatus |
US5185127A (en) | 1989-09-21 | 1993-02-09 | Becton, Dickinson And Company | Test device including flow control means |
CA2003942A1 (en) | 1989-09-26 | 1991-03-26 | Julie Lia Rudolph | Solid assay support systems |
JP2979414B2 (en) | 1989-09-29 | 1999-11-15 | 富士レビオ株式会社 | Magnetic particles and immunoassay using the same |
US5075078A (en) | 1989-10-05 | 1991-12-24 | Abbott Laboratories | Self-performing immunochromatographic device |
GB8923699D0 (en) | 1989-10-20 | 1989-12-06 | Univ Strathclyde | Apparatus for assessing a particular property in a medium |
US5225935A (en) | 1989-10-30 | 1993-07-06 | Sharp Kabushiki Kaisha | Optical device having a microlens and a process for making microlenses |
US5252743A (en) * | 1989-11-13 | 1993-10-12 | Affymax Technologies N.V. | Spatially-addressable immobilization of anti-ligands on surfaces |
US6274324B1 (en) | 1989-12-01 | 2001-08-14 | Unilever Patent Holdings B.V. | Specific binding reagent comprising a variable domain protein linked to a support or tracer |
GB8927503D0 (en) | 1989-12-04 | 1990-02-07 | Kronem Systems Inc | Enzyme-amplified lanthanide chelate luminescence |
US5508171A (en) * | 1989-12-15 | 1996-04-16 | Boehringer Mannheim Corporation | Assay method with enzyme electrode system |
US5252496A (en) * | 1989-12-18 | 1993-10-12 | Princeton Biomeditech Corporation | Carbon black immunochemical label |
US5326692B1 (en) | 1992-05-13 | 1996-04-30 | Molecular Probes Inc | Fluorescent microparticles with controllable enhanced stokes shift |
DE69121021T2 (en) | 1990-05-09 | 1997-02-27 | Abbott Lab | Binding verification procedure with conjugate recovery |
EP0745689A3 (en) | 1990-05-11 | 1996-12-11 | Microprobe Corporation | A dipstick for a nucleic acid hybridization assay |
DK138090D0 (en) * | 1990-06-06 | 1990-06-06 | Novo Nordisk As | DIAGNOSTIC METHOD OF ANALYSIS |
DE4024476C1 (en) | 1990-08-02 | 1992-02-27 | Boehringer Mannheim Gmbh, 6800 Mannheim, De | |
GB9019123D0 (en) | 1990-09-01 | 1990-10-17 | Fisons Plc | Analytical device |
US5200084A (en) | 1990-09-26 | 1993-04-06 | Immunicon Corporation | Apparatus and methods for magnetic separation |
US5076094A (en) | 1990-10-03 | 1991-12-31 | The United States Of America As Represented By The United States Department Of Energy | Dual output acoustic wave sensor for molecular identification |
US5700636A (en) | 1990-10-19 | 1997-12-23 | Becton Dickinson And Company | Methods for selectively detecting microorganisms associated with vaginal infections in complex biological samples |
US5726064A (en) | 1990-11-22 | 1998-03-10 | Applied Research Systems Ars Holding Nv | Method of assay having calibration within the assay |
US6027944A (en) | 1990-11-22 | 2000-02-22 | Applied Research Systems Ars Holding Nv | Capillary-fill biosensor device comprising a calibration zone |
US5510481A (en) * | 1990-11-26 | 1996-04-23 | The Regents, University Of California | Self-assembled molecular films incorporating a ligand |
US5208535A (en) * | 1990-12-28 | 1993-05-04 | Research Development Corporation Of Japan | Mr position detecting device |
US5834226A (en) | 1991-01-31 | 1998-11-10 | Xytronyx, Inc. | One-step test for aspartate aminotransferase |
GB9102646D0 (en) | 1991-02-07 | 1991-03-27 | Fisons Plc | Analytical device |
IL97318A0 (en) | 1991-02-20 | 1992-05-25 | Diagnostic Markers Inc | Method for the very rapid detection of polyamines |
US5466574A (en) | 1991-03-25 | 1995-11-14 | Immunivest Corporation | Apparatus and methods for magnetic separation featuring external magnetic means |
US5795470A (en) | 1991-03-25 | 1998-08-18 | Immunivest Corporation | Magnetic separation apparatus |
US5196350A (en) | 1991-05-29 | 1993-03-23 | Omnigene, Inc. | Ligand assay using interference modulation |
CA2112675C (en) | 1991-07-10 | 2007-03-20 | Richard J. Massey | Methods and apparatus for improved luminescence assays using particle concentration and chemiluminescence detection |
US5428690A (en) | 1991-09-23 | 1995-06-27 | Becton Dickinson And Company | Method and apparatus for automated assay of biological specimens |
US5179288A (en) | 1991-09-30 | 1993-01-12 | Ortho Pharmaceutical Corporation | Apparatus and method for measuring a bodily constituent |
US5418136A (en) * | 1991-10-01 | 1995-05-23 | Biostar, Inc. | Devices for detection of an analyte based upon light interference |
WO1993008472A1 (en) | 1991-10-15 | 1993-04-29 | Multilyte Limited | Binding assay employing labelled reagent |
EP0539034A1 (en) | 1991-10-22 | 1993-04-28 | Konica Corporation | A novel photographic cyan coupler |
US5424219A (en) | 1991-10-25 | 1995-06-13 | Cytech Biomedical, Inc. | Method of performing assays for biomolecules and solid supports for use in such methods |
WO1993015230A1 (en) | 1992-01-22 | 1993-08-05 | Abbott Laboratories | Calibration reagents for semi-quantitative binding assays and devices |
US5221454A (en) | 1992-01-31 | 1993-06-22 | Biometric Imaging Inc. | Differential separation assay |
US5137609A (en) | 1992-01-31 | 1992-08-11 | Biometric Imaging Inc. | Differential separation assay |
US5445971A (en) | 1992-03-20 | 1995-08-29 | Abbott Laboratories | Magnetically assisted binding assays using magnetically labeled binding members |
WO1993019370A1 (en) | 1992-03-20 | 1993-09-30 | Abbott Laboratories | Magnetically assisted binding assays using magnetically-labeled binding members |
US6156270A (en) | 1992-05-21 | 2000-12-05 | Biosite Diagnostics, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
US6019944A (en) | 1992-05-21 | 2000-02-01 | Biosite Diagnostics, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
DE69313611T2 (en) | 1992-07-02 | 1998-01-08 | Erkki Soini | BIOS-SPECIFIC MULTIPARAMETER ANALYSIS PROCEDURE |
US5395754A (en) | 1992-07-31 | 1995-03-07 | Hybritech Incorporated | Membrane-based immunoassay method |
ES2113547T3 (en) * | 1992-07-31 | 1998-05-01 | Behringwerke Ag | PHOTOACTIVABLE CHEMIOLUMINISCENT MATRICES. |
US5321492A (en) | 1992-08-07 | 1994-06-14 | Miles Inc. | Dual function readhead for a reflectance instrument |
GB9217864D0 (en) * | 1992-08-21 | 1992-10-07 | Unilever Plc | Monitoring method |
US5356782A (en) | 1992-09-03 | 1994-10-18 | Boehringer Mannheim Corporation | Analytical test apparatus with on board negative and positive control |
EP0588153B1 (en) | 1992-09-14 | 1996-12-27 | Siemens Aktiengesellschaft | Gas sensor |
US6399397B1 (en) | 1992-09-14 | 2002-06-04 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
GB9221329D0 (en) * | 1992-10-10 | 1992-11-25 | Delta Biotechnology Ltd | Preparation of further diagnostic agents |
GB2273772A (en) | 1992-12-16 | 1994-06-29 | Granta Lab Ltd | Detection of macromolecules utilising light diffraction |
US5358852A (en) | 1992-12-21 | 1994-10-25 | Eastman Kodak Company | Use of calcium in immunoassay for measurement of C-reactive protein |
TW239881B (en) | 1992-12-22 | 1995-02-01 | Sienna Biotech Inc | |
US6200820B1 (en) * | 1992-12-22 | 2001-03-13 | Sienna Biotech, Inc. | Light scatter-based immunoassay |
US5327225A (en) | 1993-01-28 | 1994-07-05 | The Center For Innovative Technology | Surface plasmon resonance sensor |
FI932866A0 (en) | 1993-06-21 | 1993-06-21 | Labsystems Oy | Separeringsfoerfarande |
US5422726A (en) * | 1993-02-16 | 1995-06-06 | Tyler; Jonathan M. | Solid state spectrofluorimeter and method of using the same |
US5374531A (en) | 1993-03-22 | 1994-12-20 | Zynaxis, Inc. | Immunoassay for determination of cells |
DE4309393A1 (en) | 1993-03-23 | 1994-09-29 | Boehringer Mannheim Gmbh | Reduction of the hook effect in immunoassays with particulate carrier material |
DE4310142A1 (en) | 1993-03-29 | 1994-10-06 | Boehringer Mannheim Gmbh | Immunologically active conjugates and a process for their preparation |
JP3479100B2 (en) | 1993-06-02 | 2003-12-15 | 帝国臓器製薬株式会社 | Simple semi-quantitative immunochemical method and apparatus |
US5658443A (en) | 1993-07-23 | 1997-08-19 | Matsushita Electric Industrial Co., Ltd. | Biosensor and method for producing the same |
US5484867A (en) | 1993-08-12 | 1996-01-16 | The University Of Dayton | Process for preparation of polyhedral oligomeric silsesquioxanes and systhesis of polymers containing polyhedral oligomeric silsesqioxane group segments |
US5837546A (en) | 1993-08-24 | 1998-11-17 | Metrika, Inc. | Electronic assay device and method |
US5512131A (en) * | 1993-10-04 | 1996-04-30 | President And Fellows Of Harvard College | Formation of microstamped patterns on surfaces and derivative articles |
US5464741A (en) | 1993-10-08 | 1995-11-07 | Henwell, Inc. | Palladium (II) octaethylporphine alpha-isothiocyanate as a phosphorescent label for immunoassays |
KR0177182B1 (en) | 1993-10-20 | 1999-05-15 | 최근선 | Process for the preparation of emulsion polymer |
US5352582A (en) | 1993-10-28 | 1994-10-04 | Hewlett-Packard Company | Holographic based bio-assay |
US5455475A (en) | 1993-11-01 | 1995-10-03 | Marquette University | Piezoelectric resonant sensor using the acoustoelectric effect |
DK0653625T3 (en) | 1993-11-12 | 2003-01-13 | Inverness Medical Switzerland | Test strip reading devices |
DK0653639T3 (en) | 1993-11-12 | 2000-07-24 | Unilever Nv | Analytical devices and methods for their use |
US5527711A (en) | 1993-12-13 | 1996-06-18 | Hewlett Packard Company | Method and reagents for binding chemical analytes to a substrate surface, and related analytical devices and diagnostic techniques |
EP0744966B1 (en) * | 1994-02-17 | 2002-08-07 | The Procter & Gamble Company | Porous absorbent materials having modified surface characteristics and methods for making the same |
US5663213A (en) | 1994-02-28 | 1997-09-02 | Rohm And Haas Company | Method of improving ultraviolet radiation absorption of a composition |
GB9416002D0 (en) * | 1994-08-08 | 1994-09-28 | Univ Cranfield | Fluid transport device |
US6117090A (en) | 1994-08-25 | 2000-09-12 | Caillouette; James C. | Method and apparatus for detecting amine producing organisms in the vagina |
US5599668A (en) * | 1994-09-22 | 1997-02-04 | Abbott Laboratories | Light scattering optical waveguide method for detecting specific binding events |
GB9419267D0 (en) | 1994-09-23 | 1994-11-09 | Unilever Plc | Assay devices |
ES2169107T3 (en) | 1994-09-23 | 2002-07-01 | Inverness Medical Switzerland | CONTROL PROCEDURE AND DEVICES FOR USE IN THE SAME. |
US5620850A (en) * | 1994-09-26 | 1997-04-15 | President And Fellows Of Harvard College | Molecular recognition at surfaces derivatized with self-assembled monolayers |
US5571684A (en) | 1994-11-07 | 1996-11-05 | Litmus Concepts, Inc. | Assay for proline iminopeptidase and other hydrolytic activities |
US5728352A (en) | 1994-11-14 | 1998-03-17 | Advanced Care Products | Disposable electronic diagnostic instrument |
AU4117696A (en) | 1994-11-24 | 1996-06-17 | Unipath Limited | Recovery of and uses of specific binding agents |
US5866434A (en) | 1994-12-08 | 1999-02-02 | Meso Scale Technology | Graphitic nanotubes in luminescence assays |
KR0151203B1 (en) | 1994-12-08 | 1998-12-01 | 이헌조 | Multi-electrode type biosensor |
US5489988A (en) | 1995-01-03 | 1996-02-06 | Motorola | Environmental sensor and method therefor |
AU4213396A (en) | 1995-01-26 | 1996-08-01 | Nippon Paint Co., Ltd. | Kit for immunologically assaying biological substance and assay process |
US5569608A (en) | 1995-01-30 | 1996-10-29 | Bayer Corporation | Quantitative detection of analytes on immunochromatographic strips |
JP3962789B2 (en) * | 1995-02-21 | 2007-08-22 | ダブリュー. シディキー,イクバール | Mixing / separating apparatus and method using magnetic particles |
GB9505425D0 (en) | 1995-03-17 | 1995-05-03 | Unilever Plc | Assay devices |
US5534132A (en) | 1995-05-04 | 1996-07-09 | Vreeke; Mark | Electrode and method for the detection of an affinity reaction |
KR0156176B1 (en) | 1995-06-01 | 1998-12-01 | 구자홍 | Electrochemical immune biosensor |
SK160497A3 (en) | 1995-06-05 | 1998-06-03 | Kimberly Clark Co | Novel pre-dyes |
US6413410B1 (en) | 1996-06-19 | 2002-07-02 | Lifescan, Inc. | Electrochemical cell |
US5518689A (en) | 1995-09-05 | 1996-05-21 | Bayer Corporation | Diffused light reflectance readhead |
AUPN527995A0 (en) | 1995-09-07 | 1995-09-28 | Agen Biomedical Limited | Method and apparatus for semiquantification of an analyte |
US5788863A (en) | 1995-12-13 | 1998-08-04 | Becton Dickinson And Company | Apparatus and method for conducting an assay using reverse flow through a membrane |
US5837547A (en) | 1995-12-27 | 1998-11-17 | Caribbean Microparticles Corporation | Flow cytometer calibration method |
US5945281A (en) | 1996-02-02 | 1999-08-31 | Becton, Dickinson And Company | Method and apparatus for determining an analyte from a sample fluid |
EP0890093A4 (en) | 1996-03-19 | 2000-03-15 | Univ Utah Res Found | System for determining analyte concentration |
EP0890104B1 (en) | 1996-03-29 | 2001-08-01 | University Of British Columbia | Platelet count assay using platelet granule proteins |
US5753517A (en) | 1996-03-29 | 1998-05-19 | University Of British Columbia | Quantitative immunochromatographic assays |
US6387707B1 (en) * | 1996-04-25 | 2002-05-14 | Bioarray Solutions | Array Cytometry |
US5968839A (en) | 1996-05-13 | 1999-10-19 | Metrika, Inc. | Method and device producing a predetermined distribution of detectable change in assays |
EP0906062B1 (en) | 1996-05-17 | 2007-12-26 | Roche Diagnostics Operations, Inc. | Body fluid sampling device |
US5951492A (en) | 1996-05-17 | 1999-09-14 | Mercury Diagnostics, Inc. | Methods and apparatus for sampling and analyzing body fluid |
EP0901630B1 (en) | 1996-05-23 | 2003-08-20 | Inverness Medical Switzerland GmbH | Improvements in or relating to specific binding assays |
DE19622458C2 (en) | 1996-05-24 | 1998-03-26 | Senslab Ges Zur Entwicklung Un | Enzymatic-electrochemical one-step affinity sensor for the quantitative determination of analytes in aqueous media and affinity assay |
DE19621133A1 (en) * | 1996-05-24 | 1997-11-27 | Boehringer Mannheim Gmbh | Determination method with oligomerized receptors |
WO1997045718A1 (en) | 1996-05-28 | 1997-12-04 | Novartis Ag | Optical detection apparatus for chemical analyses of small volumes of samples |
US5852229A (en) | 1996-05-29 | 1998-12-22 | Kimberly-Clark Worldwide, Inc. | Piezoelectric resonator chemical sensing device |
US6004530A (en) | 1996-06-04 | 1999-12-21 | Roche Diagnostics Gmbh | Use of metallo-porphyrin conjugates for the detection of biological substances |
US6444423B1 (en) | 1996-06-07 | 2002-09-03 | Molecular Dynamics, Inc. | Nucleosides comprising polydentate ligands |
US5876944A (en) * | 1996-06-10 | 1999-03-02 | Bayer Corporation | Method for amplification of the response signal in a sandwich immunoassay |
US20050214827A1 (en) * | 1996-07-08 | 2005-09-29 | Burstein Technologies, Inc. | Assay device and method |
WO1998001744A1 (en) * | 1996-07-10 | 1998-01-15 | Cambridge Imaging Limited | Improved imaging system for fluorescence assays |
US5660790A (en) | 1996-08-13 | 1997-08-26 | Litmus Concepts, Inc. | PH and amine test elements |
US6020047A (en) * | 1996-09-04 | 2000-02-01 | Kimberly-Clark Worldwide, Inc. | Polymer films having a printed self-assembling monolayer |
US6001658A (en) * | 1996-09-13 | 1999-12-14 | Diagnostic Chemicals Limited | Test strip apparatus and method for determining presence of analyte in a fluid sample |
US5998221A (en) | 1996-09-25 | 1999-12-07 | Becton, Dickinson And Company | Non-instrumented assay with quantitative and qualitative results |
US6194220B1 (en) * | 1996-09-25 | 2001-02-27 | Becton, Dickinson And Company | Non-instrumented assay with quantitative and qualitative results |
US5798273A (en) | 1996-09-25 | 1998-08-25 | Becton Dickinson And Company | Direct read lateral flow assay for small analytes |
ES2187622T3 (en) | 1996-09-27 | 2003-06-16 | Inverness Medical Switzerland | REAGENTS AND TEST DEVICES. |
DE69626016T2 (en) | 1996-09-27 | 2004-01-08 | Inverness Medical Switzerland Gmbh | Test kit and devices |
ES2168444T3 (en) | 1996-09-27 | 2002-06-16 | Inverness Medical Switzerland | MANUFACTURE OF TEST STRIPS. |
US5910940A (en) | 1996-10-08 | 1999-06-08 | Polaroid Corporation | Storage medium having a layer of micro-optical lenses each lens generating an evanescent field |
US6165798A (en) | 1996-10-10 | 2000-12-26 | University Of British Columbia | Optical quantification of analytes in membranes |
US5922537A (en) | 1996-11-08 | 1999-07-13 | N.o slashed.AB Immunoassay, Inc. | Nanoparticles biosensor |
US5922550A (en) | 1996-12-18 | 1999-07-13 | Kimberly-Clark Worldwide, Inc. | Biosensing devices which produce diffraction images |
US6048623A (en) | 1996-12-18 | 2000-04-11 | Kimberly-Clark Worldwide, Inc. | Method of contact printing on gold coated films |
US5962995A (en) | 1997-01-02 | 1999-10-05 | Applied Advanced Technologies, Inc. | Electron beam accelerator |
US6407492B1 (en) | 1997-01-02 | 2002-06-18 | Advanced Electron Beams, Inc. | Electron beam accelerator |
US5827748A (en) | 1997-01-24 | 1998-10-27 | The United States Of America As Represented By The Secretary Of The Navy | Chemical sensor using two-dimensional lens array |
US6057165A (en) * | 1997-02-07 | 2000-05-02 | Becton, Dickinson And Company | Quality control procedure for membrane flow-through diagnostic assay devices |
EP0859230A1 (en) | 1997-02-10 | 1998-08-19 | Cranfield University | Detection of analytes using electrochemistry |
GB2322192B (en) | 1997-02-14 | 2001-01-31 | Unilever Plc | Assay devices |
US6391558B1 (en) * | 1997-03-18 | 2002-05-21 | Andcare, Inc. | Electrochemical detection of nucleic acid sequences |
US6180288B1 (en) | 1997-03-21 | 2001-01-30 | Kimberly-Clark Worldwide, Inc. | Gel sensors and method of use thereof |
US6235471B1 (en) * | 1997-04-04 | 2001-05-22 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
EP0872736A1 (en) | 1997-04-18 | 1998-10-21 | Byk Gulden Italia S.p.A. | Assay utilizing magnetic particles |
US6103536A (en) * | 1997-05-02 | 2000-08-15 | Silver Lake Research Corporation | Internally referenced competitive assays |
US6171780B1 (en) | 1997-06-02 | 2001-01-09 | Aurora Biosciences Corporation | Low fluorescence assay platforms and related methods for drug discovery |
US6613583B1 (en) | 1997-06-27 | 2003-09-02 | Igen International, Inc. | Electrochemiluminescent label based on multimetallic assemblies |
US6136611A (en) | 1997-07-31 | 2000-10-24 | Research International, Inc. | Assay methods and apparatus |
EP0898169B1 (en) | 1997-08-11 | 2002-02-06 | F. Hoffmann-La Roche Ag | Microparticle enhanced light scattering assay and microparticle reagents therefor |
US6080391A (en) | 1997-08-14 | 2000-06-27 | Novo Nordisk A/S | Reduction of malodour |
YU11500A (en) | 1997-08-29 | 2001-09-28 | Fertility Acoustics Inc. | Method and apparatus for rapid analysis in biological samples |
US5906921A (en) | 1997-09-29 | 1999-05-25 | Matsushita Electric Industrial Co., Ltd. | Biosensor and method for quantitative measurement of a substrate using the same |
US5989924A (en) | 1997-09-30 | 1999-11-23 | Becton, Dickinson And Company | Device for determining an analyte in a sample |
EP1029244A4 (en) | 1997-10-02 | 2003-07-23 | Aclara Biosciences Inc | Capillary assays involving separation of free and bound species |
US6617488B1 (en) | 1997-10-14 | 2003-09-09 | Indicator Technologies, Inc. | Method and apparatus for indicating the conditions in an absorbent article |
US6174646B1 (en) * | 1997-10-21 | 2001-01-16 | Konica Corporation | Image forming method |
US6077669A (en) | 1997-11-04 | 2000-06-20 | Becton Dickinson And Company | Kit and method for fluorescence based detection assay |
US6087184A (en) | 1997-11-10 | 2000-07-11 | Beckman Coulter, Inc. | Opposable-element chromatographic assay device for detection of analytes |
US6030792A (en) | 1997-11-13 | 2000-02-29 | Pfizer Inc | Assays for measurement of protein fragments in biological media |
US5997817A (en) | 1997-12-05 | 1999-12-07 | Roche Diagnostics Corporation | Electrochemical biosensor test strip |
US6074725A (en) * | 1997-12-10 | 2000-06-13 | Caliper Technologies Corp. | Fabrication of microfluidic circuits by printing techniques |
EP1046027A1 (en) | 1997-12-11 | 2000-10-25 | Quidel Corporation | One-step fluorescent immunosensor test |
US6060256A (en) | 1997-12-16 | 2000-05-09 | Kimberly-Clark Worldwide, Inc. | Optical diffraction biosensor |
SE9704933D0 (en) * | 1997-12-30 | 1997-12-30 | Pharmacia & Upjohn Diag Ab | Method utilizing a new calibrator and test kit containing the calibrator |
ATE239801T1 (en) | 1998-01-22 | 2003-05-15 | Luminex Corp | MICROPARTICLES WITH MULTIPLE FLUORESCENCE SIGNALS |
DE19811622A1 (en) | 1998-03-17 | 1999-09-23 | Lre Technology Partner Gmbh | Laboratory instrument incorporating split test card housing |
EP1064088B1 (en) | 1998-03-19 | 2002-12-04 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Fabrication of multilayer-coated particles and hollow shells via electrostatic self-assembly of nanocomposite multilayers on decomposable colloidal templates |
GB9807134D0 (en) | 1998-04-02 | 1998-06-03 | Unilever Plc | Test methods devices and test kits |
US6368873B1 (en) | 1998-04-09 | 2002-04-09 | Applied Biotech, Inc. | Identification of human urine for drug testing |
US6171616B1 (en) * | 1998-04-13 | 2001-01-09 | Shin-Etsu Chemical Co., Ltd. | Solid preparation and a method of manufacturing it |
US6241863B1 (en) | 1998-04-27 | 2001-06-05 | Harold G. Monbouquette | Amperometric biosensors based on redox enzymes |
US6451607B1 (en) | 1998-05-07 | 2002-09-17 | Litmus Concepts, Inc. | External dried-reagent control for analytical test devices |
EP0959176B1 (en) | 1998-05-18 | 2012-09-05 | Rohm And Haas Company | Hollow sphere organic pigment for paper or paper coatings |
JPH11326603A (en) | 1998-05-19 | 1999-11-26 | Seiko Epson Corp | Microlens array and its production thereof, and display |
WO1999064864A1 (en) | 1998-06-12 | 1999-12-16 | New Horizons Diagnostics Inc. | Optimizing sensitivity in colloidal colorimetric flow through and lateral flow tests |
US6030840A (en) | 1998-06-15 | 2000-02-29 | Nen Life Sciences, Inc. | Neutral enhancement of lanthanides for time resolved fluorescence |
US6183972B1 (en) | 1998-07-27 | 2001-02-06 | Bayer Corporation | Method for the determination of analyte concentration in a lateral flow sandwich immunoassay exhibiting high-dose hook effect |
US6171870B1 (en) * | 1998-08-06 | 2001-01-09 | Spectral Diagnostics, Inc. | Analytical test device and method for use in medical diagnoses |
US6281006B1 (en) | 1998-08-24 | 2001-08-28 | Therasense, Inc. | Electrochemical affinity assay |
WO2000019199A1 (en) | 1998-09-29 | 2000-04-06 | Fertility Acoustics Inc. | A method of and device for determining ovulation in mammals |
GB9821526D0 (en) | 1998-10-02 | 1998-11-25 | Genosis Inc | Capture assay |
US6284472B1 (en) | 1998-10-05 | 2001-09-04 | Dade Behring Inc. | Method for extending the range of an immunoassay |
US6338790B1 (en) | 1998-10-08 | 2002-01-15 | Therasense, Inc. | Small volume in vitro analyte sensor with diffusible or non-leachable redox mediator |
BE1012241A3 (en) | 1998-10-21 | 2000-08-01 | D Tek | Analyte screening method and kit for implementing such a method. |
FI982422A0 (en) | 1998-11-09 | 1998-11-09 | Arctic Diagnostics Oy | Porphyrin compounds, their conjugates and assay methods based on the use of said conjugate |
US6261779B1 (en) | 1998-11-10 | 2001-07-17 | Bio-Pixels Ltd. | Nanocrystals having polynucleotide strands and their use to form dendrimers in a signal amplification system |
US6455861B1 (en) | 1998-11-24 | 2002-09-24 | Cambridge Research & Instrumentation, Inc. | Fluorescence polarization assay system and method |
US6221579B1 (en) | 1998-12-11 | 2001-04-24 | Kimberly-Clark Worldwide, Inc. | Patterned binding of functionalized microspheres for optical diffraction-based biosensors |
US6579673B2 (en) | 1998-12-17 | 2003-06-17 | Kimberly-Clark Worldwide, Inc. | Patterned deposition of antibody binding protein for optical diffraction-based biosensors |
JP2002536285A (en) | 1999-02-05 | 2002-10-29 | ユニヴァーシティ オブ メリーランド,ボルティモア | Emission spectral characteristics of CdS nanoparticles |
WO2000047983A1 (en) | 1999-02-11 | 2000-08-17 | University Of Southern California | Enzyme-linked immuno-magnetic electrochemical biosensor |
EP1163513A1 (en) | 1999-02-26 | 2001-12-19 | Fertility Acoustics Inc. | Analyzing strip having a fluid cell and a method of analyzing a sample |
AU3508600A (en) | 1999-02-26 | 2000-09-14 | Orchid Biosciences, Inc. | Microstructures for use in biological assays and reactions |
AU2898500A (en) | 1999-03-02 | 2000-09-21 | Helix Biopharma Corporation | Biosensor device and method |
US6287783B1 (en) | 1999-03-18 | 2001-09-11 | Biostar, Inc. | Optical assay device and method |
US6511814B1 (en) * | 1999-03-26 | 2003-01-28 | Idexx Laboratories, Inc. | Method and device for detecting analytes in fluids |
US6815218B1 (en) | 1999-06-09 | 2004-11-09 | Massachusetts Institute Of Technology | Methods for manufacturing bioelectronic devices |
WO2000078917A1 (en) | 1999-06-18 | 2000-12-28 | Umedik, Inc. | Device and method for analyzing a biologic sample |
US6294392B1 (en) | 1999-07-21 | 2001-09-25 | The Regents Of The University Of California | Spatially-encoded analyte detection |
US6372895B1 (en) | 2000-07-07 | 2002-04-16 | 3M Innovative Properties Company | Fluorogenic compounds |
KR100542033B1 (en) | 1999-09-29 | 2006-01-10 | 재팬 사이언스 앤드 테크놀로지 에이젼시 | High sensitive immunoassay |
US6306665B1 (en) | 1999-10-13 | 2001-10-23 | A-Fem Medical Corporation | Covalent bonding of molecules to an activated solid phase material |
US6136549A (en) | 1999-10-15 | 2000-10-24 | Feistel; Christopher C. | systems and methods for performing magnetic chromatography assays |
USD450854S1 (en) | 1999-11-04 | 2001-11-20 | Therasense, Inc. | Glucose strip |
WO2001038873A2 (en) | 1999-11-24 | 2001-05-31 | Biotronic Technologies, Inc. | Devices and methods for detecting analytes using electrosensor having capture reagent |
US6331438B1 (en) | 1999-11-24 | 2001-12-18 | Iowa State University Research Foundation, Inc. | Optical sensors and multisensor arrays containing thin film electroluminescent devices |
US6171646B1 (en) | 1999-12-09 | 2001-01-09 | Engineered Glass Products, Llc | Method for making an abrasion and scratch resistant coated glass article |
US6399295B1 (en) | 1999-12-17 | 2002-06-04 | Kimberly-Clark Worldwide, Inc. | Use of wicking agent to eliminate wash steps for optical diffraction-based biosensors |
US6509196B1 (en) | 2000-01-04 | 2003-01-21 | Response Biomedical Corp. | Compensation for non-specific signals in quantitative immunoassays |
US20020004246A1 (en) * | 2000-02-07 | 2002-01-10 | Daniels Robert H. | Immunochromatographic methods for detecting an analyte in a sample which employ semiconductor nanocrystals as detectable labels |
US6255066B1 (en) | 2000-02-08 | 2001-07-03 | Allan L. Louderback | Bacterial vaginosis screening technique and a diagnostic kit for use therein |
US20010055776A1 (en) | 2000-02-11 | 2001-12-27 | Dale Greenwalt | High throughput cell-based assay kits |
US20020132370A1 (en) | 2000-02-23 | 2002-09-19 | Lassen Michael Rud | Detection of a blood coagulation activity marker in a body fluid sample |
US6607922B2 (en) | 2000-03-17 | 2003-08-19 | Quantum Design, Inc. | Immunochromatographic assay method and apparatus |
JP2001349892A (en) | 2000-04-03 | 2001-12-21 | Unilever Nv | Test method and device |
JP2001349891A (en) | 2000-04-03 | 2001-12-21 | Unilever Nv | Test method and device |
US6436722B1 (en) | 2000-04-18 | 2002-08-20 | Idexx Laboratories, Inc. | Device and method for integrated diagnostics with multiple independent flow paths |
US6627459B1 (en) | 2000-04-19 | 2003-09-30 | Applied Biotech, Inc. | Immunoassay controls |
WO2001098785A2 (en) | 2000-06-19 | 2001-12-27 | Arizona Board Of Regents | Rapid flow-based immunoassay microchip |
ES2259666T3 (en) | 2000-06-21 | 2006-10-16 | Bioarray Solutions Ltd | MOLECULAR ANALYSIS OF MULTIPLE ANALYTICS USING SERIES OF RANDOM PARTICLES WITH APPLICATION SPECIFICITY. |
WO2002009865A1 (en) * | 2000-08-02 | 2002-02-07 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Production of polyelectrolyte capsules by surface precipitation |
DE10042023C2 (en) | 2000-08-08 | 2003-04-10 | Biognostic Ag | Capsules that encapsulate solid particles of signal-generating substances and their use in bioassays for the detection of target molecules in a sample |
US6420128B1 (en) * | 2000-09-12 | 2002-07-16 | Lifescan, Inc. | Test strips for detecting the presence of a reduced cofactor in a sample and method for using the same |
US7052831B2 (en) | 2000-09-29 | 2006-05-30 | Becton Dickinson And Company | Detection of multiple analytes from a single sample using a multi-well, multi-analyte flow-through diagnostic test device |
US6653149B1 (en) | 2000-10-16 | 2003-11-25 | Applied Biotech Inc. | Specimen collection device and method |
AU2002239780A1 (en) * | 2000-10-25 | 2002-06-03 | Tufts University | Polymeric microspheres |
US20020164659A1 (en) | 2000-11-30 | 2002-11-07 | Rao Galla Chandra | Analytical methods and compositions |
DE10062062C1 (en) | 2000-12-13 | 2002-02-28 | Draegerwerk Ag | Electrochemical sensor used e.g. in control technology has a microprocessor integrated on chip of an electronic device for receiving and further processing signals from the device |
US6524864B2 (en) | 2000-12-28 | 2003-02-25 | Aurora L. Fernandez Decastro | Test strip for simultaneous detection of a plurality of analytes |
US20030162236A1 (en) | 2001-03-26 | 2003-08-28 | Response Biomedical Corporation | Compensation for variability in specific binding in quantitative assays |
JP2002303629A (en) | 2001-04-06 | 2002-10-18 | Matsushita Electric Ind Co Ltd | Immune chromatography device and method for determining substance to be tested using the same |
WO2002087429A1 (en) * | 2001-04-27 | 2002-11-07 | Novartis Ag | Apparatus for measuring blood glucose concentrations |
US20030108949A1 (en) | 2001-07-03 | 2003-06-12 | Gang Bao | Filtration-based microarray chip |
US6818456B2 (en) | 2001-07-20 | 2004-11-16 | Varian, Inc. | Color contrast system for lateral flow immunoassay tests |
US6669908B2 (en) | 2001-07-25 | 2003-12-30 | Applied Biotech, Inc. | Urine test device |
AU2002357754A1 (en) | 2001-12-24 | 2003-07-24 | Kimberly-Clark Worldwide, Inc. | Flow-through assay with an internal calibration system using polyelectrolyte |
US7214427B2 (en) | 2002-03-21 | 2007-05-08 | Aviva Biosciences Corporation | Composite beads comprising magnetizable substance and electro-conductive substance |
AU2003277309A1 (en) | 2002-10-08 | 2004-05-04 | Tara Nylese | Portable diagnostic device and method for determining temporal variations in concentrations |
US20040121334A1 (en) * | 2002-12-19 | 2004-06-24 | Kimberly-Clark Worldwide, Inc. | Self-calibrated flow-through assay devices |
-
2001
- 2001-12-24 US US10/035,014 patent/US20030119203A1/en not_active Abandoned
-
2002
- 2002-04-25 US US10/132,421 patent/US7651841B2/en active Active
- 2002-04-25 US US10/132,673 patent/US20030119204A1/en not_active Abandoned
- 2002-11-21 AT AT02806133T patent/ATE478338T1/en not_active IP Right Cessation
- 2002-11-21 KR KR1020047009945A patent/KR101043888B1/en active IP Right Grant
- 2002-11-21 DE DE60237395T patent/DE60237395D1/en not_active Expired - Lifetime
Cited By (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040092036A1 (en) * | 2002-09-11 | 2004-05-13 | Lattec I/S | Device for analysing analyte compounds and use hereof |
WO2005057216A1 (en) * | 2003-11-21 | 2005-06-23 | Kimberly-Clark Worldwide, Inc. | Method of reducing the sensitivity of assay devices |
US9063137B2 (en) | 2003-12-08 | 2015-06-23 | Charm Sciences, Inc. | Method and assay for detection of residues |
US7863057B2 (en) | 2003-12-08 | 2011-01-04 | Charm Sciences, Inc. | Method and assay for detection of residues |
US20080274566A1 (en) * | 2003-12-08 | 2008-11-06 | Charm Sciences, Inc. | Method and assay for detection of residues |
US7410808B1 (en) | 2003-12-08 | 2008-08-12 | Charm Sciences, Inc. | Method and assay for detection of residues |
US20110070127A1 (en) * | 2003-12-08 | 2011-03-24 | Saul Steven J | Method and Assay for Detection of Residues |
US20110097820A1 (en) * | 2003-12-23 | 2011-04-28 | Kimberly-Clark Worldwide, Inc. | Swab-Based Diagnostic Systems |
US20070185679A1 (en) * | 2004-04-01 | 2007-08-09 | Petruno Patrick T | Indicating status of a diagnostic test system |
US20070231922A1 (en) * | 2004-04-01 | 2007-10-04 | Petruno Patrick T | Assay test strips with multiple labels and reading same |
US20050221504A1 (en) * | 2004-04-01 | 2005-10-06 | Petruno Patrick T | Optoelectronic rapid diagnostic test system |
US20050221505A1 (en) * | 2004-04-01 | 2005-10-06 | Petruno Patrick T | Optoelectronic rapid diagnostic test system |
US7521259B2 (en) | 2004-04-01 | 2009-04-21 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US9243997B2 (en) | 2004-04-01 | 2016-01-26 | Alverix, Inc. | Lateral flow assay systems and methods |
US9989527B2 (en) | 2004-04-01 | 2018-06-05 | Alverix, Inc. | Lateral flow assay systems and methods |
US9091631B2 (en) | 2004-04-01 | 2015-07-28 | Alverix, Inc. | Lateral flow assay systems and methods |
AU2005259012B2 (en) * | 2004-07-01 | 2011-01-20 | Forsite Diagnostics Limited | Analyte detection system |
WO2006003394A1 (en) * | 2004-07-01 | 2006-01-12 | Central Science Laboratory (Csl) Representing The Secretary Of State For Environment, Food And Rural Affairs | Analyte detection system |
US20080289068A1 (en) * | 2004-07-01 | 2008-11-20 | Forsite Diagnostics Limited | Analyte Detection System |
US7763433B2 (en) | 2004-07-01 | 2010-07-27 | Forsite Diagnostics Limited | Analyte detection system |
GB2433989B (en) * | 2004-07-01 | 2009-04-08 | Central Science Lab | Analyte detection system |
GB2433989A (en) * | 2004-07-01 | 2007-07-11 | Central Science Lab | Analyte delection system |
JP4988546B2 (en) * | 2005-01-28 | 2012-08-01 | 持田製薬株式会社 | Immunochromatographic test device and semi-quantitative method using the same |
US20060286616A1 (en) * | 2005-03-22 | 2006-12-21 | Miki Furukawa | Menopause stage monitor |
US20090180928A1 (en) * | 2005-04-22 | 2009-07-16 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US7521260B2 (en) | 2005-04-22 | 2009-04-21 | Alverix, Inc. | Assay test strips and reading same |
US20090180926A1 (en) * | 2005-04-22 | 2009-07-16 | Alverix, Inc. | Assay test strips and reading same |
US20090180925A1 (en) * | 2005-04-22 | 2009-07-16 | Alverix, Inc. | Assay test strips and reading same |
US20090180927A1 (en) * | 2005-04-22 | 2009-07-16 | Alverix, Inc. | Assay test strips and reading same |
US20090180929A1 (en) * | 2005-04-22 | 2009-07-16 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US20090214383A1 (en) * | 2005-04-22 | 2009-08-27 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US10191043B2 (en) | 2005-04-22 | 2019-01-29 | Alverix, Inc. | Methods and systems for calibrating illumination source of diagnostic test system |
US8128871B2 (en) | 2005-04-22 | 2012-03-06 | Alverix, Inc. | Lateral flow assay systems and methods |
US10041941B2 (en) | 2005-04-22 | 2018-08-07 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US20060240541A1 (en) * | 2005-04-22 | 2006-10-26 | Petruno Patrick T | Lateral flow assay systems and methods |
US8043867B2 (en) | 2005-04-22 | 2011-10-25 | Petruno Patrick T | Assay test strips and reading same |
US9891217B2 (en) | 2005-04-22 | 2018-02-13 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US11782058B2 (en) | 2005-04-22 | 2023-10-10 | Alverix, Inc. | Diagnostic test system using measurement obtained from reference feature to modify operational parameter of reader |
US10753931B2 (en) | 2005-04-22 | 2020-08-25 | Alverix, Inc. | Assay test strips with multiple labels and reading same |
US20070161078A1 (en) * | 2005-07-01 | 2007-07-12 | Arbor Vita Corporation | Methods and compositions for diagnosis and treatment of influenza |
US20100112547A1 (en) * | 2005-07-01 | 2010-05-06 | Arbor Vita Corporation | Methods and compositions for diagnosis and treatment of influenza |
US20100092944A1 (en) * | 2005-07-01 | 2010-04-15 | Arbor Vita Corporation | Detection of influenza virus |
US7595152B2 (en) | 2005-07-01 | 2009-09-29 | Arbor Vita Corporation | Detection of influenza virus |
US20070224594A1 (en) * | 2005-07-01 | 2007-09-27 | Arbor Vita Corporation | Detection of influenza virus |
WO2007053487A3 (en) * | 2005-10-28 | 2009-01-15 | Binax Inc | Methods and devices for detection of the strain of a pathogen |
US8153381B2 (en) | 2005-10-28 | 2012-04-10 | Alere Scarborough, Inc. | Methods for detection of the strain of a pathogen |
WO2007053487A2 (en) * | 2005-10-28 | 2007-05-10 | Binax, Inc. | Methods and devices for detection of the strain of a pathogen |
US20080293041A1 (en) * | 2005-10-28 | 2008-11-27 | Binax, Inc. | Methods and Devices for Detection of the Strain of a Pathogen |
US20070116595A1 (en) * | 2005-11-22 | 2007-05-24 | Petrilla John F | Assaying test strips having different capture reagents |
US8632730B2 (en) | 2005-11-22 | 2014-01-21 | Alverix, Inc. | Assaying test strips having different capture reagents |
US20070122914A1 (en) * | 2005-11-30 | 2007-05-31 | Curry Bo U | Obtaining measurements of light transmitted through an assay test strip |
US20080028261A1 (en) * | 2005-12-19 | 2008-01-31 | Petruno Patrick T | End-of-life disabling of a diagnostic test system |
US8024148B2 (en) | 2005-12-19 | 2011-09-20 | Alverix, Inc. | End-of-life disabling of a diagnostic test system |
US20070188736A1 (en) * | 2006-02-16 | 2007-08-16 | Fouquet Julie E | Obtaining measurement and baseline signals for evaluating assay test strips |
US20100143884A1 (en) * | 2007-01-26 | 2010-06-10 | Arbor Vita Corporations | Detection of influenza virus |
US20110171754A1 (en) * | 2007-09-14 | 2011-07-14 | Gareth Redmond | Analysis system |
US8835184B2 (en) | 2007-09-14 | 2014-09-16 | Biosensia Patents Limited | Analysis system |
EP2325640A4 (en) * | 2008-08-22 | 2011-11-02 | Denka Seiken Kk | Test apparatus for membrane assay equipped with reference display section |
US20110143458A1 (en) * | 2008-08-22 | 2011-06-16 | Denka Seiken Co., Ltd. | Test device for membrane assay comprising reference display section |
EP2325640A1 (en) * | 2008-08-22 | 2011-05-25 | DENKA SEIKEN Co., Ltd. | Test apparatus for membrane assay equipped with reference display section |
JP5487104B2 (en) * | 2008-08-22 | 2014-05-07 | デンカ生研株式会社 | Membrane assay test device with control display |
JP2010101886A (en) * | 2008-10-21 | 2010-05-06 | Kaiwood Technology Co Ltd | Bioassay strip |
EP2180319A1 (en) * | 2008-10-21 | 2010-04-28 | Kaiwood Technology Co., Ltd. | Biological test strip |
US20110244598A1 (en) * | 2008-12-03 | 2011-10-06 | Roche Diagnostics Operations, Inc. | Test Element Having Combined Control and Calibration Zone |
US8569073B2 (en) * | 2008-12-03 | 2013-10-29 | Roche Diagnostics Operations Inc. | Test element having combined control and calibration zone |
EP3244189A1 (en) * | 2008-12-30 | 2017-11-15 | Jin Po Lee | Quantitative analyte assay device and method |
EP2384428A4 (en) * | 2008-12-30 | 2013-03-06 | Jin Po Lee | Quantitative analyte assay device and method |
US8455263B2 (en) | 2008-12-30 | 2013-06-04 | Jin Po Lee | Quantitative analyte assay device and method |
US20100167264A1 (en) * | 2008-12-30 | 2010-07-01 | Jin Po Lee | Quantitative analyte assay device and method |
EP2384428A1 (en) * | 2008-12-30 | 2011-11-09 | Jin Po Lee | Quantitative analyte assay device and method |
US9557329B2 (en) | 2008-12-30 | 2017-01-31 | Assurance Llc | Quantitative analyte assay device and method |
US8900881B2 (en) | 2008-12-30 | 2014-12-02 | Jin Po Lee | Quantitative analyte assay device and method |
US20100175455A1 (en) * | 2009-01-14 | 2010-07-15 | Alverix, Inc. | Methods and materials for calibration of a reader |
US8643837B2 (en) * | 2009-01-14 | 2014-02-04 | Alverix, Inc. | Methods and materials for calibration of a reader |
US20120171702A1 (en) * | 2009-06-30 | 2012-07-05 | Monash University | Quantitative and self-calibrating chemical analysis using paper-based microfluidic systems |
US9116146B2 (en) * | 2009-06-30 | 2015-08-25 | Monash University | Quantitative and self-calibrating chemical analysis using paper-based microfluidic systems |
US20130022965A1 (en) * | 2009-08-17 | 2013-01-24 | Dst Diagnostische Systeme & Technologien Gmbh | Test system for visual analysis |
US9261502B2 (en) * | 2009-08-17 | 2016-02-16 | Dst Diagnostische Systeme & Technologien Gmbh | Test system for visual analysis |
WO2011020724A1 (en) * | 2009-08-17 | 2011-02-24 | Dst Diagnostische Systeme & Technologien Gmbh | Test system for visual analysis |
CN102012423A (en) * | 2009-09-04 | 2011-04-13 | 开物科技股份有限公司 | Biological detection test base material |
USD667228S1 (en) | 2009-09-24 | 2012-09-18 | Yuyama Manufacturing Co., Ltd. | Sheet for a drug bag |
US20110223689A1 (en) * | 2010-03-09 | 2011-09-15 | Nokia Croporation | Apparatus and associated methods |
US8313956B2 (en) | 2010-03-09 | 2012-11-20 | Nokia Corporation | Apparatus and associated methods |
WO2011110734A1 (en) * | 2010-03-09 | 2011-09-15 | Nokia Corporation | Apparatus for analyte sensing and associated methods |
US9199232B2 (en) | 2010-04-07 | 2015-12-01 | Biosensia Patents Limited | Flow control device for assays |
WO2011124991A3 (en) * | 2010-04-07 | 2011-12-29 | Biosensia Patents Limited | Flow control device for assays |
US20120225422A1 (en) * | 2011-03-03 | 2012-09-06 | RoMonics, LLC | Method and device employing a non-receptor ligand interaction with nanoparticles or other solid phase followed by specific detection |
CN102539769A (en) * | 2011-12-22 | 2012-07-04 | 正元盛邦(天津)生物科技有限公司 | Method for semi-quantitative diagnosis of creatine kinase isoenzyme by double indicating line immuno-chromatography |
US11287424B2 (en) | 2012-11-15 | 2022-03-29 | Ortho-Clinical Diagnostics, Inc. | Calibrating assays using reaction time |
CN110412265A (en) * | 2012-11-15 | 2019-11-05 | 奥索临床诊断有限公司 | It is analyzed using the calibration in reaction time |
US9885712B2 (en) | 2012-11-15 | 2018-02-06 | Ortho-Clinical Diagnostics, Inc. | Calibrating assays using reaction time |
CN104937418A (en) * | 2012-11-15 | 2015-09-23 | 奥索临床诊断有限公司 | Calibrating assays using reaction time |
WO2017112780A1 (en) * | 2015-12-22 | 2017-06-29 | Polymer Technology Systems, Inc. | Systems and methods for quantification of creatinine using a creatinine-protein conjugate |
CN111684280A (en) * | 2017-12-05 | 2020-09-18 | 贝克顿·迪金森公司 | Lateral flow assay and method for detecting high concentrations of analytes |
US11243160B2 (en) | 2018-03-28 | 2022-02-08 | Detekt Biomedical, Llc | Custom optical reference calibrator fabrication system |
US10773781B2 (en) | 2018-06-05 | 2020-09-15 | Detekt Biomedical, Llc. | Universal motorized personal watercraft propulsion assistance and training device |
US11524758B2 (en) | 2018-06-05 | 2022-12-13 | Defekt Biomedical, LLC | Universal motorized personal watercraft propulsion mounting system |
WO2021041780A2 (en) | 2019-08-29 | 2021-03-04 | ARONOWITZ, Mireya, C. | Quantitative analyte detection in lateral flow immunochemistry |
EP3913368A1 (en) * | 2020-05-22 | 2021-11-24 | Thermogenesis Holdings, Inc. | Lateral flow immunoassay test reader and method of use |
WO2022056078A1 (en) | 2020-09-11 | 2022-03-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Rnase h-assisted detection assay for rna (radar) |
WO2023201422A1 (en) * | 2022-04-19 | 2023-10-26 | Cardiai Technologies Ltd. | Lateral flow assay test strips and systems, and methods of use thereof |
Also Published As
Publication number | Publication date |
---|---|
US20030119204A1 (en) | 2003-06-26 |
US7651841B2 (en) | 2010-01-26 |
ATE478338T1 (en) | 2010-09-15 |
KR101043888B1 (en) | 2011-06-22 |
KR20040068976A (en) | 2004-08-02 |
DE60237395D1 (en) | 2010-09-30 |
US20030124739A1 (en) | 2003-07-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20030119203A1 (en) | Lateral flow assay devices and methods for conducting assays | |
KR101540608B1 (en) | Assay strip having variable control line, and diagnosis kit using the same | |
CA2528172C (en) | Native analyte as reference in lateral flow assays | |
US7662643B2 (en) | Reduction of the hook effect in membrane-based assay devices | |
KR101311993B1 (en) | Analyte assaying by means of immunochromatography with lateral migration | |
CA2471462C (en) | Internal calibration system for flow-through assays | |
JPH1073592A (en) | Solid-phase immunoassay method | |
JPH03502246A (en) | Coagulation methods for the analysis of substances | |
JPS62231168A (en) | Improvement method for forming internal standard for analyzing analite-receptor | |
Gribnau et al. | Particle-labelled immunoassays: a review | |
US6551788B1 (en) | Particle-based ligand assay with extended dynamic range | |
AU2007319076A1 (en) | Saturation assay | |
CA2747110A1 (en) | Quantitative analyte assay device and method | |
JPWO2003029822A1 (en) | Specific binding analyzer and specific binding analysis method | |
JP2005510706A5 (en) | ||
US20210164974A1 (en) | Chromatographic strip comprising multiple test lines, diagnostic kit comprising same, and qualitative, semi-quantitative or quantitative analysis method comprising multiple competitive reaction measurement steps | |
EP4080212A2 (en) | Immunochromatographic strip and kit, and competitive immunochromatographic analysis method using same | |
US20140011190A1 (en) | Method for performing a rapid test | |
JP4109245B2 (en) | Analysis apparatus and analysis method | |
JP3481894B2 (en) | Measurement method using immunological chromatographic method | |
KR20220047198A (en) | Strips, kits for immunochromatography and sandwich immunochromatographic assays for measuring tryptase using the same | |
JPS59197862A (en) | Reagent for immunoassay to measure simultaneously multiple terms | |
KR20150140560A (en) | Assay strip having variable control line, and diagnosis kit using the same | |
AU2014200264A1 (en) | Saturation assay |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: KIMBERLY-CLARK WORLDWIDE, INC., WISCONSIN Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WEI, NING;SONG, XUEDONG;REEL/FRAME:012861/0257 Effective date: 20020311 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |