WO1994023299A1 - Dispositif pour dosages multiples - Google Patents

Dispositif pour dosages multiples Download PDF

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Publication number
WO1994023299A1
WO1994023299A1 PCT/US1994/003488 US9403488W WO9423299A1 WO 1994023299 A1 WO1994023299 A1 WO 1994023299A1 US 9403488 W US9403488 W US 9403488W WO 9423299 A1 WO9423299 A1 WO 9423299A1
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WO
WIPO (PCT)
Prior art keywords
zone
sample
labelling
analyte
assay
Prior art date
Application number
PCT/US1994/003488
Other languages
English (en)
Inventor
Steven Paul Miller
Nol B. Quiwa
John K. Zeis
Allan D. Pronovost
Original Assignee
Quidel Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Quidel Corporation filed Critical Quidel Corporation
Publication of WO1994023299A1 publication Critical patent/WO1994023299A1/fr

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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
    • 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
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/743—Steroid hormones

Definitions

  • the present invention relates generally to devices and methods for detection of analytes in biological samples. More specifically, the present invention provides devices and methods for efficient and relatively inexpensive simultaneous detection of several analytes in a single sample or the serial detection of one or more analytes in several samples.
  • Detection of analytes in biological samples has become a vital tool of medical diagnostics. Often it is desirable to detect many different analytes in a single biological sample. For example, screening for exposure to certain diseases that have common modes of transmission is useful in many patient populations, e.g., public health screening for sexually transmitted diseases. Prenatal screening of pregnant women for infections associated with congenital malformations is another common instance in which simultaneous detection of different analytes is desirable. Previously, it was generally necessary to send biological samples to a reference laboratory for analysis. While reference laboratories could simultaneously measure some combinations of different analytes, several useful combinations required separate assays or expensive instrumentation.
  • serial determinations of disease associated analytes can provide an indication of the efficacy of treatment.
  • serial determinations of glucose provide a guide for insulin therapy of diabetes.
  • serial determinations of certain hormones can identify periods of fertility or infertility during a woman's menstrual cycle and provide guidance for facilitating or avoiding conception. Performance of these hormonal assays in a laboratory is impractical because submitting daily samples is expensive, inconvenient, and intrusive for patients.
  • Immunoassays have been developed for home use.
  • the OvuQuick Self-Test for ovulation prediction produced by Monoclonal Antibodies, Inc. is a home test kit for measurement of luteinizing hormone.
  • the kit contains a multi- step assay requiring mixing of reagents and multiple sample treatment steps.
  • the kit contains several different assay test devices which only provide one assay and requires refrigeration between uses.
  • Other multi-step immunoassays have also been described, e.g., U.S. Patent No. 4,632,901 of Valkirs et al.
  • U.S. Patent No. 4,943,522 describes lateral flow assays for the detection of a variety of analytes. Devices are described that provide a one step means of detecting the presence or concentration of a single analyte in a single sample.
  • U.S. Patent Nos. 4,938,927 and 5,141,875 describe devices and methods for rotary fluid assays. Fluid samples are applied to bodies that have wicking characteristics and react with reagents present on the bodies. The bodies are described for use with laboratory centrifuges. The devices include means for occluding fluid flow between different segments of the devices so that different assays may be performed.
  • Devices and methods are needed in the art which will provide simple and convenient simultaneous detection of multiple analytes in biological samples. Desirably, the devices and methods are completely self contained and do not require additional instrumentation. The devices should be economical to produce and simply assembled. Also desirable are devices and methods for serial determinations of one or more analytes in biological samples which are simple and accurate and can be performed in the physician's office or even by patients in the privacy of their home. Quite surprisingly, the present invention fulfills these and other needs.
  • the present invention provides devices for simultaneous detection of a plurality of target analytes in a sample, having a first matrix defining a flow path; a first sample receiving zone on the first matrix; and a plurality of assay strips located downstream from the first sample receiving zone, wherein each assay strip detects a different target analyte, which assay strips each comprise a labelling zone having a means for specifically labelling the target analyte detected by the assay strip and a capture zone located downstream from the labelling zone; whereby application of the sample to the first sample receiving zone results in specific binding of the target analytes in the sample to labelling means on the assay strips and accumulation of labelled target analytes in the capture zones.
  • the devices of the present invention may further include positive and negative test strips.
  • the test strips serve as internal positive and negative controls for the assay devices. Additionally, the assay strips may contain positive procedural control lines that provide protection against false negative results due to device malfunctions.
  • devices for a plurality of determinations of the presence or amount of an analyte in a sample.
  • the devices contain: a matrix defining a flow path; a plurality of sample receiving zones on the matrix; a plurality of assay strips located downstream from the sample receiving zones, wherein each assay strip is in fluid connection with only one sample receiving zone and comprises a labelling zone having a means for labelling the analyte and a capture zone located downstream from the labelling zone; whereby application of the sample to the sample receiving zone results in specific binding of the analyte in the sample to the labelling means on the assay strips and accumulation of labelled analyte in the capture zones.
  • Devices of this type may also contain test strips for internal control purposes.
  • Methods for simultaneously determining the presence or amount of a plurality of analytes in a sample comprising: applying the sample to a device of the present invention that detects multiple analytes in a sample; and observing the accumulation of visible label within the capture zone of the device as a result of analyte present in the sample specifically binding to the labelling complex in the labelling means and the resulting analyte-labelling complexes flowing into and being captured within the capture zone.
  • Methods for serially detecting the presence and/or amount of an analyte in a series of samples are also provided.
  • Fig. 1 illustrates one type of assay strip employed in devices constructed in accordance with the principles of the present invention.
  • Fig. 2 illustrates an assay strip having a positive procedural control line.
  • Fig. 3 illustrates a matrix of a device for simultaneous detection of different analytes in a sample constructed in accordance with the principles of the present invention.
  • Fig. 4 illustrates a top plate for a device for the simultaneous detection of different analytes in a biological sample.
  • Fig. 5 illustrates a matrix of a device for serial detection of an analyte in different biological samples constructed in accordance with the principles of the present invention.
  • Fig. 6 illustrates a top plate for a device for serial detection of an analyte in different biological samples.
  • Fig. 7 illustrates a matrix of a device for the simultaneous detection of different analytes in a sample having positive and negative control strips.
  • Fig. 8 illustrates a top plate for a device for the simultaneous detection of different analytes in a sample having positive and negative control strips.
  • the present invention provides devices and methods for one-step detection of analytes in biological samples.
  • the devices and methods provide a simple and rapid method of detection that may be performed by medical assistants in the office of a health care provider or even by the patient in the privacy of the home.
  • the assays of the present invention are self contained and require no special instrumentation.
  • the devices are also easy and economical to produce, providing greater availability to the public. The quickness with which assay results may be obtained also allows for prompt treatment or other actions, as appropriate.
  • analytes in a biological sample may be simultaneously detected by devices of the present invention.
  • Devices of this type are particularly useful for detection of analytes such as antibodies in biological samples.
  • Antibodies to different infectious agents which are transmitted in similar manners, e.g., sexually transmitted diseases may be quickly identified by simple screening in sexually transmitted disease clinics.
  • Antibodies to infectious agents that cause diseases in particular patient populations, e.g., the pathogens causing congenital malformations in TORCHES syndrome during pregnancy may also be simultaneously detected with the devices of the present invention.
  • IgE antibodies to different common allergens may be detected as taught by the present invention to diagnose or confirm atopic conditions.
  • devices of the present invention may detect a single analyte in different samples.
  • Devices of this type are particularly useful in serial determinations of an analyte that reflects a physiological state or disease condition. For example, daily serial determinations of urinary luteinizing hormone and progesterone metabolite levels can indicate infertile periods during a woman's menstrual cycle and provide an easy in home method of facilitating contraception by the rhythm method.
  • the devices and methods of the present invention employ lateral flow methodology for detection of analytes.
  • the samples are generally biological fluids.
  • the biological fluid sample may be whole blood, plasma, serum, nasal secretions, sputum, salvia, urine, sweat, transdermal exudates, cerebrospinal fluid, or the like.
  • Analytes in biological tissue samples may also be detected by homogenizing or otherwise liquefying the tissue sample.
  • the sample whether a fluid or liquified tissue, may be diluted with physiological buffers, such as physiological saline, to facilitate sample flow in the devices of the present invention. Persons of skill will appreciate that dilution of the sample will alter the concentration of analyte in the diluted sample and appropriate calculations will be required to normalize the assay results in some instances.
  • the present invention may also be employed for the detection of analytes in samples which are not biological. For example, water samples may be conveniently analyzed for the presence of a variety of different toxins using devices of the present invention.
  • the devices and methods of the present invention employ lateral flow assay techniques as generally described in U.S. Patent Nos. 4,943,522; 4,861,711; 4,857,453; 4,855,240; 4,775,636; 4,703,017; 4,361,537; 4,235,601; 4,168,146; 4,094,647; co-pending application U.S.S.N. 07/639,967, European Patent Application Nos. 451,800; 158,746; 276,152; 306,772 and British Patent Application No. 2,204,398; each of which is incorporated herein by reference.
  • One embodiment of the present invention is a device for simultaneous detection of a plurality of target analytes in a sample.
  • analytes in a single sample may be detected by a single application of the sample to the device.
  • the time required for detection of the different analytes will generally be approximately equal, although the times may vary significantly. So long as the detection of the different analytes is accomplished by a single application of sample to the device, the detection is considered simultaneous.
  • This embodiment of the present invention includes a first matrix defining a flow path; a sample receiving zone on the first matrix; and a plurality of assay strips located downstream from the sample receiving zone, wherein each assay strip detects a different target analyte, which assay strips each comprise a labelling zone having a means for specifically labelling the target analyte detected by the assay strip and a capture zone located downstream from the labelling zone.
  • Application of the sample to the sample receiving zone results in specific binding of the target analytes in the sample to labelling means on the assay strips and accumulation of labelled target analytes in the capture zones as the sample flows from sample receiving zone.
  • a variety of target analytes may be detected by the present invention.
  • Antibodies to infectious agents may be detected.
  • Antibodies to allergens may also be detected.
  • IgE antibodies to specific allergens may be detected to diagnose or confirm allergic conditions.
  • IgG antibodies to allergens may also be detected to assess the efficacy of desensitization treatments.
  • Hormones such as luteinizing hormone, progesterones, and progesterone metabolites may be measured to predict fertile periods in the menstrual cycle to assist either conception or contraception.
  • Tumor related antigens such as carcinoembryonic antigen, prostate specific antigen, and the like, may be detected by devices of the present invention as a screening tool for high risk populations. Persons of skill will appreciate other analytes which may be conveniently detected by the present invention.
  • non-bibulous lateral flow liquid flow in which all of the dissolved or dispersed components of the liquid are carried at substantially equal rates and with relatively unimpaired flow laterally through or across the matrix, as opposed to preferential retention of one or more components as would occur, e.g. , in materials capable of adsorbing or imbibing one or more components.
  • a representative non-bibulous matrix material is high density polyethylene sheet material.
  • Polyethylene sheets of this type are available from commercial sources,such as by Porex Technologies Corp. of Fairburn, Georgia, USA.
  • the membrane has an open pore structure with a typical density, at 40% void volume, of 0.57 gm/cc and an average pore diameter of 1 to 250 micrometers, the average generally being from 3 to 100 micrometers.
  • the membrane pore diameter is about 10 to about 50 ⁇ m, although other pore diameters may be employed for different purposes.
  • a membrane having large pores may filter particulates from a sample and selectively allow the fluid and dissolved compounds in the sample to flow downstream.
  • the membranes are from a few mils (.001 in) to several mils in thickness, typically in the range of 5 mils to 200 mils.
  • the membrane may be backed by a generally water impervious layer, or may be totally free standing. Free standing matrixes will generally be thicker since structural support for the device will be provided by the matrix.
  • Other non-bibulous membranes such as polyvinyl chloride, polyvinyl acetate, copolymers of vinyl acetate and vinyl chloride, polyamide, polycarbonate, nylon, glass fiber, orlon, polyester polystyrene, and the like, or blends can also be used.
  • Bibulous materials such as untreated paper, nitrocellulose, derivatized nylon, cellulose and the like may also be used following processing to provide non-bibulous flow. Bibulous materials may also act as filtering mechanisms as described above. Alternatively, blocking agents may block the forces which account for the bibulous nature of bibulous membranes. Suitable blocking agents include whole or derivatized bovine serum albumin or albumin from other animals, whole animal serum, casein, and non-fat dry milk.
  • the matrix defines a flow path for fluids applied to the matrix.
  • the flow path is the natural movement of fluids placed on the matrix.
  • the matrix has a sample receiving zone.
  • the sample receiving zone is the portion of the matrix to which the samples are applied. Generally, the sample receiving zone will have a low analyte retention rate. Treatment of the sample receiving zone to immobilize a protein-blocking reagent on the surface, if necessary, will typically provide low retenti' properties. This treatment also provides increased wetability and wicking action to speed the downstream flow of the sample.
  • the sample receiving zone may also serve as a means for filtering particulates from the sample as described above.
  • the sample receiving zone is in fluid contact with at least two assay strips. All assay strips are located downstream of the sample receiving zone so that fluid from sample applied to the sample receiving zone will flow into each assay strip.
  • each assay strip in a device will detect a different analyte.
  • a number of analytes equal to the number of assay strips in the device will be simultaneously detected by this embodiment of the present invention.
  • the assay strips comprise a labelling zone and a capture zone.
  • a means for labelling the target analyte is present in the labelling zone.
  • the labelling means contain labelling complexes that specifically bind to target analyte in the patient sample.
  • the labelling complexes are comprised of a visible label bound to a first analyte-binding substance.
  • the first analyte-binding substance may be, e.g., an antibody or fragment thereof which specifically binds the analyte detected by the assay strip.
  • the first analyte-binding substance may be an anti-ligand of a ligand analyte, e.g., a receptor for a particular hormone if the analyte detected by the assay strip is a hormone.
  • the analyte is an immunoglobulin
  • the first analyte-binding substance may be an antigen which is specifically bound by the immunoglobulin.
  • the labelling complex is not immobilized to the labelling zone so that the sample may solubilize or otherwise remove the labelling complexes into the fluid of the sample.
  • a variety of visible labels may be bound to the first immunoglobulin-binding substance.
  • the labels may be soluble or particulate and may include dyed immunoglobulin binding substances, simple dyes or dye polymers, dyed latex beads, dye-containing liposomes (such as described in U.S. Patent No. 4,695,554, incorporated herein by reference) , dyed cells or organisms, or metallic, organic, inorganic, or dye sols.
  • the labels may be bound to the analyte-binding substance by a variety of means which are well known in the art such as described in U.S. Patent Nos. 4,863,875 and 4,373,932, each of which is incorporated herein by reference. Generally, the same label will be used on each assay strip employed in a device of the present invention.
  • the labelling complexes contain an analyte- binding substance and the labelling complexes are solubilized or dispersed into the patient sample, target analyte in the sample which reacts with the analyte-binding substance is contacted and bound by the labelling complexes prior to entering the capture zone. In this manner, the target analyte molecules are labelled. If any of the labelled target analyte molecules are retained in the capture zone of the device, the label provides a means for detection.
  • Each assay strip has a capture zone located downstream of the labelling zone. The capture zone typically contacts the labelling zone. A second analyte-binding substance is immobilized on the capture zone.
  • the second analyte-binding substance may be, e.g., an anti-immunoglobulin antibody or fragment thereof, or an antigen which is specifically bound by the immunoglobulin.
  • the second analyte-binding substance may also be an anti- ligand of the target analyte as described above. As target analytes in the sample contact the capture zone, the analytes bind to the second analyte-binding substance and are retained in the capture zone.
  • the second analyte-binding substance will be immobilized to the capture zone in a specific pattern, such as a "+" or a "/". The pattern can aid users in identifying positive results.
  • the accumulation of visible label may be assessed either visually or by optical detection devices, such as reflectance analyzers, video image analyzers and the like.
  • the accumulation of visible label can be assessed either to determine the presence or absence of label in the capture zone or the visible intensity of accumulated label which may by correlated with the concentration or titer (dilution) of target analytes in the patient sample.
  • concentration or titer (dilution) of target analytes in the patient sample may be correlated with the concentration or titer (dilution) of target analytes in the patient sample.
  • the correlation between the visible intensity of accumulated label and analyte concentration may be made by comparison of the visible intensity to a reference standard.
  • Optical detection devices may be programmed to automatically perform this comparison by means similar to that used by the Quidel Reflective Analyzer, Catalog No. QU0801 (Quidel Corp., San Diego, CA) .
  • target analyte concentration in the sample may be determined.
  • a color key such as used in the Quidel Total IgE Test Catalog No. 0701 (a multi-step ELISA assay) .
  • target analyte concentration in the sample may be determined.
  • Video analyzers may also be used to determine the concentration of target analyte in the sample from the intensity of the accumulated label.
  • the capture zone is often contacted by a bibulous absorbent zone.
  • the absorbent zone is located downstream from the capture zone.
  • the absorbent zone is a means for removing excess sample and unbound labelling complexes from the matrix of the device.
  • the absorbent zone will consist of an absorbent material such as filter paper, a glass fiber filter, cellulose, or the like.
  • the devices of the present invention may also have a positive test strip and a negative test strip.
  • the positive and negative test strips serve as internal controls to assess the functioning of the device.
  • the test strips may be located on the matrix, downstream of and in fluid contact with the sample receiving zone.
  • the positive test strip detects a non-target analyte that is typically present in all samples.
  • non-target analytes may include, e.g., albumin or non-antigen specific IgG that is normally present in serum, plasma or blood samples; urobilinogen in urine samples, and the like.
  • the non-target analyte will vary according to the nature of the sample to be tested.
  • the positive test strip contains a second labelling zone having a second means for labelling the non-target analyte, and a second capture zone.
  • the second means for labelling the non-target analyte and the second capture zone are similar in character to the corresponding components of the assay strips as described above.
  • the negative test strip generally contains a labelling zone having a label used in the assay strips. The label is not conjugated to an analyte-binding substance.
  • the capture zone of the negative test strip may have a second analyte-binding substance. Alternatively, the capture zone may not have a second analyte-binding substance.
  • Application of the sample to the device results in fluid flow into the positive and negative test strips.
  • the non-target analyte present in the sample will bind the means for labelling the non-target analyte which is then retained in the capture zone.
  • a positive result is expected on the positive test strip if the device functions properly. Lack of a positive result indicates that a device malfunction has occurred and that the results on the assay strips are suspect.
  • the unbound label is mixed with the fluid and carried to the capture zone. Because the label does not bind an analyte which is captured in the capture zone, no label should be retained and a negative result is expected.
  • a positive result on the negative test strip indicates non-specific retention of the label in the capture and positive results on the assay strips are suspect.
  • the device may have a second matrix and a second sample receiving zone.
  • the positive and negative test strips are downstream of and in fluid contact with the second sample receiving zone.
  • the construction of the positive test strip is similar to the positive test strips described above except that the labelling means includes a means for labelling a non-target analyte which is present in a test fluid.
  • the negative test strip is constructed as above, but lacks a bound label in the labelling zone.
  • a test fluid containing a known amount of the non-target analyte may be applied to the second sample receiving zone.
  • the test fluid flows into the positive test strip and negative test strip. Because the positive test strip has a means for labelling the non-target analyte and may capture the labelled non-target analyte in the capture zone, a positive result is obtained if the device is functioning properly.
  • Devices of the present invention may also contain a procedural control line on each assay strip.
  • the procedural control line is in the capture zone located downstream from the second analyte-binding substance.
  • the procedural control line is a control binding substance which will specifically bind the labelling complexes of the labelling zone.
  • the labelling complexes both bound to analyte and unbound, contact the procedural control line, the labelling complexes are captured and retained by the control binding substance.
  • the device functions properly and fluid reaches the procedural control line, label accumulates on the procedural control line ensuring sample contact with the second analyte- binding substance. Lack of label accumulation indicates device malfunction and assay results are suspect.
  • control binding substances will vary with the character of the labelling complexes.
  • the control binding substance may be an anti-IgG antibody, Staphylococcal Protein A or Protein G. Persons of skill will appreciate appropriate control binding substances.
  • the geometric configuration of the devices of the present invention is not critical and may vary. Generally, the assay strips, and positive and negative control strips, if present, extend radially from the sample receiving zone at equally spaced intervals. In a particularly convenient embodiment, the device is fan shaped approximating a quarter circle. The number and dimensions of assay strips and control strips in each device may also vary depending on the use. Analytes detected by devices of the present invention may vary considerably.
  • One particularly useful embodiment for office prenatal screening by obstetricians or midwives employs assay strips which detect serum antibodies to toxoplasma gondii, rubella virus, human cytomegalovirus, herpes simplex virus, and treponema palladium organisms.
  • Allergists may also find devices of the present invention particularly useful.
  • the devices may be employed detect IgE to common antigens, such as mites, grasses, e.g. bermuda grass, timothy grass, bent grass, perennial rye grass, and the like; dander, such as dog dander, cat dander, and the like; foods, e.g., apples, shrimp, strawberries, shellfish, and the like; insect venom, such as mosquito venom, wasp venom, bee venom, and the like; trees, such as elm, oak, acacia, and the like; bacteria such as Streptococcus pneumonia, Helicobacter pylori and the like; viruses such as hepatitis virus, and the like; flowers, such as marigold, sunflower, and the like; and weeds, such as pigweed, ragweed, Russian thistle, and the like.
  • common antigens such as mites, grasses,
  • pan-hypopituitaris may be detected by simultaneously assaying serum for thyroid stimulating hormone, luteinizing hormone, follicle-stimulating hormone, adrenocorticotropic hormone, growth hormone, prolactin, or a subcombination of these hormones.
  • Other endocrine abnormalities such as the multiple endocrine neoplasias may also be easily detected by devices of the present invention. Persons of skill will appreciate many other combinations of analytes that may be simultaneously detected by devices of the present invention.
  • Devices for a plurality of determinations of the presence or amount of one or more analytes in a series of samples are also provided. These devices are particularly useful for home monitoring of physiological conditions, such as infertile periods during a female's menstrual cycle.
  • devices of this type comprise a matrix defining a flow path; a plurality of sample receiving zones on the matrix; a plurality of assay strips located downstream from the sample receiving zones, wherein each assay strip is in fluid connection with only one sample receiving zone and comprises a labelling zone having a means for labelling the analyte and a capture zone located downstream from the labelling zone.
  • Application of a sample to the sample receiving zone results in specific binding of the analyte in the sample to labelling means on the assay strips and accumulation of labelled analyte in the capture zones.
  • the assay strips of this embodiment of the present invention are constructed and function as described above. Each assay strip is in fluid contact with only one sample receiving zone. Different samples are applied to different sample receiving zones. Thus, the same analytes are measured by each assay. Samples may be serially tested in this manner to detect changes in physiological states or disease conditions.
  • the devices of the present invention may include housings that contain the matrixes.
  • the housings are typically constructed of plastic, but other materials such as vinyls, nylons, or the like may be used.
  • the housings have a top plate covering the assay surface of the matrixes.
  • the top plate has a means for transmitting the sample to the matrix.
  • the transmitting means is a sample well that is an opening in the top plate.
  • the sample well is located over the sample receiving zone.
  • the top plate also has a means for observing accumulation of label in the capture zone following application of the sample.
  • the observation means are result windows in the top plates.
  • the result windows are located over the capture zones of the assay strips on the matrix.
  • the result windows are open, but the windows may be covered by a transparent covering such as glass or plastic.
  • the housings may also contain dividers between the assay strips to inhibit flow of sample between assay strips.
  • the top plates may have a variety of configurations.
  • a single sample well and a plurality of result windows are present. If the matrix has control test strips, result windows are located over the capture zones of the control test strips.
  • a control sample well is located over the second sample receiving zone, when present.
  • Individual sample wells for each assay strip are also generally present in devices for serially detecting an analyte in samples.
  • the present invention also provides methods for simultaneously determining the presence or amount of a plurality of analytes in a sample.
  • the methods comprise applying the sample to a device as described above and observing the accumulation of visible label within the capture zone as a result of analyte present in the sample specifically binding to the labelling complex in the labelling means and the resulting analyte-labelling complexes flowing into and being retained in the capture zone.
  • Methods for serial detection of an analyte in samples are also provided. Individual samples are applied to the sample receiving zones and accumulation of label is observed through the result windows. Samples may be serially assayed to detect changes in the level of the assay and analyte.
  • This assay strip 10 has three components, a labelling zone 12, a capture zone 14, and an absorbent zone
  • the labelling means is located in the labelling zone 12.
  • the second analyte-binding substance is located in the capture zone 14. Positive and negative test strips may have similar construction differing fr: ⁇ the assay strips as described above.
  • Fig. 2 shows one embodiment of an assay strip 10 as in Fig. 1.
  • the second analyte-binding substance 18 is immobilized in the capture zone 14 as a "+", although immobilization in any shape, including a line, is appropriate.
  • a procedural control line 20 is also present in the capture zone 14.
  • the procedural control line 20 is located downstream from the second analyte-binding substance 18. Therefore, if the procedural control line 20 is exposed to and captures visible label in the sample fluid, the second analyte-binding substance 18 will have also been exposed to the sample fluid.
  • Fig. 3 illustrates one embodiment of a device 26 for the simultaneous detection of seven different analytes in a sample.
  • the device 26 has a fan shaped matrix 24.
  • Seven assay strips 10 are located on the matrix 24.
  • Each assay strip 10 has a labelling zone 12, a capture zone 14, and an absorbent zone 16.
  • the labelling means in the labelling zones 12 and the second analyte-binding substances in the capture zones 14 will be different in each assay strip 10.
  • Each assay strip 10 is in fluid communication and located downstream from a sample receiving zone 22.
  • the assay strips 10 extend radially from the sample receiving zone 22. A sample applied to the sample receiving zone 22 will flow into each assay strip 10 resulting in detection of each target analyte.
  • Fig. 4 illustrates a housing top plate 40 for a device that simultaneously detects different analytes in a sample.
  • the top plate 40 has a sample well 42 and several result windows 44.
  • the sample well 42 is located directly over the sample receiving zone on the matrix.
  • the result windows 44 are located directly over the capture zones of the assay strips on the matrix.
  • the sample may be applied to the sample receiving zone through the sample well 42 and label accumulation in the capture zones may be observed through the result windows 44.
  • Another embodiment of the present invention is shown in Fig. 5.
  • This device 28 provides a means for seven serial determinations of an analyte. Seven assay strips 10 are present on a matrix 24.
  • Each assay strip 10 has an individual sample receiving zone 30 that does not fluidly communicate with any other assay strip 10.
  • the assay strips 10 contain identical labelling means and second analyte-binding substances. Seven different samples may be analyzed by the device 28.
  • a housing top plate 50 for a device for serial detection of an analyte in different samples is illustrated in Fig. 6.
  • the top plate 50 has seven sample wells 52 and seven result windows 44. Each assay strip on the underlying matrix is associated with only one sample well 52 and only one result window 44. Individual samples may be applied to the assay strips through the sample wells 52 and the results discerned through the result windows 44.
  • Fig. 7 illustrates another embodiment of the present invention having a positive control strip 32 and a negative control strip 34.
  • This embodiment has a matrix 24 containing a first sample receiving zone 38 in fluid contact with five assay strips 10.
  • the matrix 24 also contains a second sample receiving zone 36 in fluid contact with a positive assay strip 32 and a negative assay strip 34.
  • the first sample receiving zone 38 does not fluidly communicate with the positive control strip 32 or the negative control strip 34.
  • the second sample receiving zone 36 does not fluidly communicate with the assay strips 10.
  • a test fluid is applied to the second sample receiving zone 36 to assess the functioning of the device 30 through the positive control strip 32 and the negative control strip 34.
  • Fig. 8 shows a housing top plate 60 of a device for simultaneous detection of five analytes in a sample.
  • the device has positive and negative control strips that are assessed by application of a control test fluid to the control strips.
  • the sample is applied to the first sample receiving zone through a sample well 64.
  • the sample can flow onto the assay strips and accumulation of label in assay strip capture zones can be detected through result windows 44.
  • the test fluid is applied to the second sample receiving zone on the matrix through a control sample well 66. Accumulation of label on the positive and negative control strips can be assessed through control result windows 62.

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Abstract

La présente invention concerne des dispositifs et des procédés pour la détection simultanée de plusieurs substances dans un échantillon biologique. On décrit également des dispositifs et des procédés pour détecter une substance dans une série d'échantillons. L'utilisation de la présente invention permet d'effectuer facilement la détection ou le dosage de substances à bas prix, ou d'effectuer la détection ou le dosage de substances à domicile ou dans un cabinet médical.
PCT/US1994/003488 1993-03-31 1994-03-30 Dispositif pour dosages multiples WO1994023299A1 (fr)

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US4055793A 1993-03-31 1993-03-31
US08/040,557 1993-03-31

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Cited By (15)

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Publication number Priority date Publication date Assignee Title
US5851777A (en) * 1996-02-05 1998-12-22 Dade Behring Inc. Homogeneous sol-sol assay
GB2339616A (en) * 1996-03-11 2000-02-02 American Bio Medica Corp Drug testing and sample transporting device
EP1018004A1 (fr) * 1998-07-22 2000-07-12 Syntron Bioresearch, Inc. Dispositif permettant de deceler differents composants
US6204068B1 (en) * 1995-03-07 2001-03-20 Erkki Soini Biospecific assay method
WO2002004667A2 (fr) * 2000-07-07 2002-01-17 Helen Lee Signal de detection et capture ameliores dans des analyses sur bandelettes
WO2002004122A2 (fr) * 2000-07-07 2002-01-17 Helen Lee Amelioration de la stabilite d'interactions d'hybridation dans des tests par bandelettes
WO2002033414A1 (fr) * 2000-10-14 2002-04-25 Helen Lee Detection de cibles multiples
WO2002050544A1 (fr) * 2000-12-21 2002-06-27 Helen Lee Test à plusieurs cibles pour examen sanguin avant prélèvement
AU2003262462B2 (en) * 1998-07-22 2006-03-09 Syntron Bioresearch, Inc. Multiple analyte assay device
WO2007024633A2 (fr) * 2005-08-23 2007-03-01 Response Biomedical Corporation Essais immunochromatogrpahiques multi-directionnels
CN101595388A (zh) * 2006-12-12 2009-12-02 反应生物医学公司 多分析物免疫分析
DE10330981B4 (de) * 2003-07-09 2010-04-01 Medion Diagnostics Ag Vorrichtung und Verfahren zur simultanen Durchführung von Blutgruppenbestimmung, Serumgegenprobe und Antikörpersuch-Test
US8053226B2 (en) 2003-07-09 2011-11-08 Medion Diagnostics Ag Device and method for simultaneously identifying blood group antigens
US8431336B2 (en) 2000-07-07 2013-04-30 Diagnostics For The Real World, Ltd. Binding interactions in dipstick assays
WO2021021790A1 (fr) * 2019-07-29 2021-02-04 Siscapa Assay Technologies, Inc. Dispositifs et procédés de collecte d'échantillon

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GB2204398A (en) * 1987-04-27 1988-11-09 Unilever Plc Assays
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Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6204068B1 (en) * 1995-03-07 2001-03-20 Erkki Soini Biospecific assay method
US5851777A (en) * 1996-02-05 1998-12-22 Dade Behring Inc. Homogeneous sol-sol assay
GB2339616A (en) * 1996-03-11 2000-02-02 American Bio Medica Corp Drug testing and sample transporting device
GB2339616B (en) * 1996-03-11 2000-08-30 American Bio Medica Corp Device for the testing of body fluid samples
EP1018004A4 (fr) * 1998-07-22 2002-04-17 Syntron Biores Inc Dispositif permettant de deceler differents composants
EP1018004A1 (fr) * 1998-07-22 2000-07-12 Syntron Bioresearch, Inc. Dispositif permettant de deceler differents composants
AU2003262462B2 (en) * 1998-07-22 2006-03-09 Syntron Bioresearch, Inc. Multiple analyte assay device
WO2002004122A3 (fr) * 2000-07-07 2002-12-27 Helen Lee Amelioration de la stabilite d'interactions d'hybridation dans des tests par bandelettes
WO2002004122A2 (fr) * 2000-07-07 2002-01-17 Helen Lee Amelioration de la stabilite d'interactions d'hybridation dans des tests par bandelettes
US8431336B2 (en) 2000-07-07 2013-04-30 Diagnostics For The Real World, Ltd. Binding interactions in dipstick assays
WO2002004667A2 (fr) * 2000-07-07 2002-01-17 Helen Lee Signal de detection et capture ameliores dans des analyses sur bandelettes
WO2002004667A3 (fr) * 2000-07-07 2002-12-27 Helen Lee Signal de detection et capture ameliores dans des analyses sur bandelettes
EP1710583A2 (fr) * 2000-10-14 2006-10-11 Diagnostics for the Real World, Ltd Système de jauge confirmatoire
US7713746B2 (en) 2000-10-14 2010-05-11 Diagnostics For The Real World, Ltd. Dipstick assay
EP1710583A3 (fr) * 2000-10-14 2006-10-18 Diagnostics for the Real World, Ltd Système de jauge confirmatoire
WO2002033414A1 (fr) * 2000-10-14 2002-04-25 Helen Lee Detection de cibles multiples
WO2002033413A1 (fr) * 2000-10-14 2002-04-25 Helen Lee Analyse sur bandelette reactive
WO2002050544A1 (fr) * 2000-12-21 2002-06-27 Helen Lee Test à plusieurs cibles pour examen sanguin avant prélèvement
AP1730A (en) * 2000-12-21 2007-03-30 Lee Helen Multiple target test useful for pre-donation screening of blood.
US8053226B2 (en) 2003-07-09 2011-11-08 Medion Diagnostics Ag Device and method for simultaneously identifying blood group antigens
US7745228B2 (en) 2003-07-09 2010-06-29 Medion Diagnostics Ag Device for simultaneously carrying out blood group determination, serum cross-check and antibody detection test
DE10330981B4 (de) * 2003-07-09 2010-04-01 Medion Diagnostics Ag Vorrichtung und Verfahren zur simultanen Durchführung von Blutgruppenbestimmung, Serumgegenprobe und Antikörpersuch-Test
WO2007024633A2 (fr) * 2005-08-23 2007-03-01 Response Biomedical Corporation Essais immunochromatogrpahiques multi-directionnels
JP2009506319A (ja) * 2005-08-23 2009-02-12 レスポンス バイオメディカル コーポレーション 多角的イムノクロマトグラフィーアッセイ
WO2007024633A3 (fr) * 2005-08-23 2007-06-07 Response Biomedical Corp Essais immunochromatogrpahiques multi-directionnels
CN101595388A (zh) * 2006-12-12 2009-12-02 反应生物医学公司 多分析物免疫分析
WO2021021790A1 (fr) * 2019-07-29 2021-02-04 Siscapa Assay Technologies, Inc. Dispositifs et procédés de collecte d'échantillon

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