CA1340920C - Test device and method for colored particle immunoassay - Google Patents
Test device and method for colored particle immunoassayInfo
- Publication number
- CA1340920C CA1340920C CA000604025A CA604025A CA1340920C CA 1340920 C CA1340920 C CA 1340920C CA 000604025 A CA000604025 A CA 000604025A CA 604025 A CA604025 A CA 604025A CA 1340920 C CA1340920 C CA 1340920C
- Authority
- CA
- Canada
- Prior art keywords
- test
- ligand
- site
- cell
- protein
- 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.)
- Expired - Lifetime
Links
- 238000012360 testing method Methods 0.000 title claims abstract description 154
- 238000000034 method Methods 0.000 title claims abstract description 50
- 239000002245 particle Substances 0.000 title claims abstract description 34
- 238000003018 immunoassay Methods 0.000 title description 8
- 239000003446 ligand Substances 0.000 claims abstract description 68
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 44
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 44
- 239000007788 liquid Substances 0.000 claims abstract description 36
- 230000027455 binding Effects 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims description 22
- 239000002594 sorbent Substances 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 10
- 239000012530 fluid Substances 0.000 claims description 8
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 6
- 239000013642 negative control Substances 0.000 claims description 6
- 102000011022 Chorionic Gonadotropin Human genes 0.000 claims description 5
- 108010062540 Chorionic Gonadotropin Proteins 0.000 claims description 5
- 238000004891 communication Methods 0.000 claims description 5
- 229940084986 human chorionic gonadotropin Drugs 0.000 claims description 5
- 239000013641 positive control Substances 0.000 claims description 5
- 230000002776 aggregation Effects 0.000 claims description 4
- 238000004220 aggregation Methods 0.000 claims description 4
- 239000004816 latex Substances 0.000 claims description 4
- 229920000126 latex Polymers 0.000 claims description 4
- 239000000186 progesterone Substances 0.000 claims description 3
- 229960003387 progesterone Drugs 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000004576 sand Substances 0.000 claims 1
- 230000003381 solubilizing effect Effects 0.000 claims 1
- 239000000523 sample Substances 0.000 description 37
- 238000003556 assay Methods 0.000 description 26
- 239000008279 sol Substances 0.000 description 12
- 229910052751 metal Inorganic materials 0.000 description 10
- 239000002184 metal Substances 0.000 description 10
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000010931 gold Substances 0.000 description 8
- 229910052737 gold Inorganic materials 0.000 description 8
- 210000001124 body fluid Anatomy 0.000 description 7
- 239000010839 body fluid Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 210000002700 urine Anatomy 0.000 description 7
- 102000014914 Carrier Proteins Human genes 0.000 description 6
- 108091008324 binding proteins Proteins 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 238000011161 development Methods 0.000 description 5
- -1 e.g. Substances 0.000 description 5
- 239000003550 marker Substances 0.000 description 5
- 239000011324 bead Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000003365 glass fiber Substances 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 230000002860 competitive effect Effects 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 241000220317 Rosa Species 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004520 agglutination Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 231100000319 bleeding Toxicity 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000013011 mating Effects 0.000 description 2
- 230000006911 nucleation Effects 0.000 description 2
- 238000010899 nucleation Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 206010003445 Ascites Diseases 0.000 description 1
- 101710125089 Bindin Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010058683 Immobilized Proteins Proteins 0.000 description 1
- 101150061776 Kcnip3 gene Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000013096 assay test Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009582 blood typing Methods 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000005465 channeling Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940015047 chorionic gonadotropin Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012612 commercial material Substances 0.000 description 1
- 238000002967 competitive immunoassay Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- JCYWCSGERIELPG-UHFFFAOYSA-N imes Chemical class CC1=CC(C)=CC(C)=C1N1C=CN(C=2C(=CC(C)=CC=2C)C)[C]1 JCYWCSGERIELPG-UHFFFAOYSA-N 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003821 menstrual periods Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012205 qualitative assay Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920005992 thermoplastic resin Polymers 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- G01N33/74—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
- G01N33/76—Human chorionic gonadotropin including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5023—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures with a sample being transported to, and subsequently stored in an absorbent for analysis
-
- 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
- G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0681—Filter
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0825—Test strips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
- B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/805—Test papers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/81—Packaged device or kit
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/97—Test strip or test slide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/807—Apparatus included in process claim, e.g. physical support structures
- Y10S436/81—Tube, bottle, or dipstick
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/811—Test for named disease, body condition or organ function
- Y10S436/814—Pregnancy
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/815—Test for named compound or class of compounds
- Y10S436/817—Steroids or hormones
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/815—Test for named compound or class of compounds
- Y10S436/817—Steroids or hormones
- Y10S436/818—Human chorionic gonadotropin
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- Y10T436/255—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction
Abstract
The present invention provides a method and a test cell for detecting a ligand in a liquid sample. According to the method of the present invention a solution is transported along a flow path in the test cell. The solution is brought into contact with a test site visible through a window in a wall of the test cell. The solution includes a liquid sample suspected to contain a ligand and a conjugate. The test site has immobilized thereon a first protein having a binding site specific to a first epitope on the ligand. The conjugate comprises coloured particles coupled to a second protein selected from the group consisting of proteins having a binding site specific to a second epitope on the ligand and proteins which bind with the first protein in competition with the ligand. The solution is then transported to progressively produce at the test site a complex comprising the ligand for a time sufficient to visually determine through the window whether a colour is developed at the test site.
Description
TEST DEVICE AND METHOD
SIR COLORED PARTICLE IMMUNOASSAY
BACKGROUND OF' THE INVENTION
This. invention relates to assays for ligands, e.g., antigens, in a liquid sample such as a body fluid. More particularly, the invention relates to a method amd apparatus for the detection of a ligand in a body fluid such as urine using a conjugate comprising colored particles and a novel flow-through test cell.
Many types of ligand-receptor assays have been used to detect the presence of various substances, often generally called ligands, in body fluids such ass urine. These assays involve antigen antibody reacaions, synthetic conjugates comprising radioactive, enzymatic, fluorescent, or visually observable metal sol tags, and specially designed reactor chambers. In all these assays, there is a receptor, e.5~., an antibody, which is specific for the selected ligand or antigen. and a means for detecting the: presence, and often the amount, of the ligand-receptor reaction product. Most current tests are designed to make a quantitative determination, but in many circumstances all that is required is a positive/negative indication. Ezamples of such qualitative assays include blood typing and most types of urinalysis. For these tests, visually observable indicia such as the presence of agglutination or a color changes are preferred.
~~~Q~ Z~
Even the positive/negative assays must be very .~ensit:ive because of the often small concentration of the ligand of interest in the test fluid. False positives can also be troublesome, particularly with agglutination and other rapid detection mcahods such as dipstick and color change tests. Because of these problems, sandwich assays and other sE:nsitive detection methods which use metal sols or othE:r types Qf colored particles have been developed. These techniques have not solved all of the problems encountered in these rapid detection methodls .
It is an object of this invention to provide ' a rapid, sensitive method for detecting ligands in body fluids. Another object is to provide an assay which has high sensitivity and fewer false positives than conventional assays. A further object is to provide a tea t cell for detection of low levels of ligand.s in body fluids. Another object is to provide an assay system which involves a minimal number of procedural steps, and yields reliable results even when used by untrained persons.
Theae and other objects and features of the invention will be apparent from the following description,. drawing, and claims.
13409 ~0 $~$~ OF T;HE INVENTION
The invention features a method and test cell for the detection of a preselected ligand in a liquid sample such as a body fluid.
The test cell useful in the practice of the invention ha;s an elongate outer casing which houses an interior permeable material, e.g., glass fiber, capable: of transporting an aqueous solution by capillary action, wicking, or simple wetting. The casing defines a sample inlet, and interior regions which, for ease of description, can be designated as a test volumE: and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet, and preferably is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and eztending from the inlet and through the test volume. In the test volume is a test site cornprising a first protein having a binding site specific: to a first epitope of the ligand immobilized in fluid communication with the flow path, e:.g., bound to the permeable material or to latez particles entrapped in or bonded to the permeable material. A window such as a hole or transparent :>ection of the casing permits observations of the test site through the casing wall.
In a preferred embodiment, the flow path is restricted or narrowed in the test area, thereby channeling and concentrating fluid flow into contact - ~ ~ with th.e test: site. It is also preferred that the - - test cell include a solution filtering means disposed in the flow path between the sample inlet and the -4- 13409 ~0 teat site. The filtration means can comprise a ' separate, conventional filter element disposed within the casing of the test cell in fluid communication with the permeable material defining the flow path, but preferably is defined simply by a portion of the permeable material itself. The provision of such a filtration means in the test cell has the effect of removing by entrapment from impure samples, such as urine samplea, a portion of the particulates and nonspecific interfering factors which sometimes cause false positive readings.
The: method of the invention re3quires the use of a conjugate comprising a second protein bound to colored particles such as a metal sol or colloid, preferably gold. The conjugate can take two distinct forms, depending on whether the assay is designed to ezploit the "sandwich" or "competitive" technique.
In the case of the sandwich technique, the second protein comprises a site which binds to a second epitope on the ligand. This type of conjugate reacts with the ligand to form a complez in the liquid sample. The complez is detected by visual observation of color development at the test site in the test cell. At the test site, the ligand bound with the conjugate reacts with the immobilized first binding protein to form a "sandwich" of the first . protei;n, ligand, second protein, and colored particles. This sandwich complez is progressively produced at the test site. as sample continuously gasses by, filling the reservoir. As more and more conjua,ate is immobilized, the colored particles aggregate at the test site and become visible through the window, indicating the presence of ligand in the liquid sample.
In the case of the competitive technique, the second protein binds with the first protein in competition with the ligand. The second protein comprises, for ezample, an authentic-sample of the ligand or a fraction thereof which has comparable affinity for the first protein. As the liquid sample is transported in contact with the test site, ligand, if any, and the conjugate compete for sites of attachment to the first protein. If no--ligand is present, colored particles aggregate at the test site, and the presence of color indicates the absence of detectable levels of ligand in the sample. If ligand is present. the amount of conjugate which binds .at the test site is reduced, and no color, or a paler color, develops.
In one embodiment of the invention, the test liquid is mized with the conjugate outside the test cell. In another embodiment, the conjugate is dispos~sd in freeze-dried or other preserved form on the permeable material between the inlet and the test site. .and the sample liquid resolubilizes the conjug~~te as it passes along the flow path.
Color development at the test site may be compared with the color of one or more standards or internal controls to determine whether the develo~~ment of color is a~true indication of the presen~~e or absence of the iigand, or an artifact caused by nonspecific sorption.
In one embodiment employing the sandwich technique, the standard consists of a negative control site, preferably disposed adjacent the test site, and visible through a second window prozimate the first. The negative control site preferably is prepared identically to the test site, ezcept immobilization of the first binding protein is omitted. Therefore, although the conjugate will reach the control site, it aggregates due only to non-specific binding. If the test site is not appreciably more intense in color than the control site, the assay is considered negative...-In another embodiment. the assay and test cell may include a positive control. Thus, when ezploiting the sandwich technique, the cell may have an autlhentic sample of the ligand immobilized at a control site. If no color develops at this control site, 'the assay is considered inconclusive. When ezploi~ting the competitive technique, the development of col~~r at the positive control site means the assay results are inconclusive.
Broadly, the method of the invention involves the use of a test cell of the type described above ~to achieve an easily readable, sensitive, reproducible indication of the presence of a ligand, e.g., lnuman chorionic gonadotropin (hCG), in a test sample such as a human urine sample. The method involves the step of transporting the sample and a conjugate comprising a protein bound to a metal sol or othi~r colored particle along a flow path and in contact with a test site comprising immobilized bindin~~ protein specific to an epitope of the ligand, __ 1340 ~0 and preferably also in contact with a control site. Preferably, the colored particle comprises a gold sol; the flow path in the region of the test rite i:~ reduced in cross-section relative to other parts of the flow path; the sample is passed through a filtration means after it enters the test cell but before it contacts the test site; and the test site comprises latex particles entrapped or otherwise fixed in the flow path having the immobilized protein on their surface. In the practice of the process, either the conjugate is premixed with the sample, or the conjugate is dispo~>ed in preserved form, e.g., lyophilized, in the flow path between the inlet and the test site. In either cage, placement of the test cell in the sample, or application of the sample to the inlet, initiates flow, and the result is read by observing color development at the test site, or by comparing the color of the test site and control site.
The use oj= the colored particle detection system in combination with the filtration means, the concentrating effect of flow of the sample, and the ease of comparison between the colors of the test a.nd control sites, together enable construction of a family of extremely sensitive assay systems which minimize falser positives and can be used effectively by untrained persons.
-8- 13409 ~0 BRIEF DESCRIPTION OF THE DRAWTU~
Figure 1 is a cut-away, schematic, top view of an embodiment of a test cell useful in ezplaining the test ce711 and process of the invention;
Figure 2 is a cross-sectional side view of the to t cell of Figure 1;
FiS~ure 3 is a perspective view of a currently preferred test cell constructed in accordance with the invention;
Figure 4A is a cross-sectional, top view of the test cell of Figure 3;
Figure 4B is a cross-sectional, side view of the test cell of Figure 3 taken at line-~iB-98 of ' Figure 4A;
Figure 5 is a cross sectional view of the cell of Figure 3 taken at line 5-5 of Figure 4B; and Figure 6 is a perspective view of another embodiment o~f a test cell constructed in accordance with the invention.
Like reference characters in the respective drawn figures indicate corresponding parts.
_g_ ThE: invention provides a test cell for conducting a sandwich or competitive immunoassay, and a process which utilizes the test cell and a conjugate comprising colored particles. As disclosed below, various features of the process and test cell of the invention cooperate to enable untrained personnel reliably to assay a liquid sample for the presence of eztremely small quantities of a particular l.igand while avoiding false positives and simplifying test procedures. The invention is ideal for use in owe=-the-counter assay test kits which will enable a consumer to self diagnose, for ezample, pregnancy, venereal disease, and other disease, infection, or clinical abnormality which results in the presence of an antigenic marker substance in a body fluid. including determination of the presence of metabolites of drugs or tozins. The assay process and the cell are engineered specifically to detect the presence of a preselected individual ligand present in a body or other fluids.
Broadly, the test cell and process of the invention can be used to detect any ligand which has hereto;Eore been assayed using known immunoassay procedures. or known to be detectable by such procedures, using polyclonal or monoclonal antibodies or other proteins comprising binding sites for liganda. Various specific assay protocols, reagents, and analytes useful in the practice of the invention are known per se, see, e.g., U.S. 4,313,734, columns 4-18, ~3nd U.,S. 4,366,241, columns 5-40.
The combination of features believed to be respon:~ible for the ezcellent sensitivity and -lo- 1 3 4 0 9 2 0 reproducibility of assays constructed in accordance with the invention is the use of the novel test cell which Nerves to concentrate ligand from a test sample at a tEa t site in the cell, and the use of a metal sol or other colored particle as a marker system which permits direct visual observation of color develo~~ment. False positives are reduced while maintaining excellent sensitivity by including in the test cE:ll a negative control or control site whose color i.s compared with the test site, and by including a filtration means which limits the introduction to/the test site of contamiirants from the sample.
The assay is conducted by simply placing the inlet of the test cell in contact with a liquid test sample. One then merely waits for the test sample to pass through the cell and into reactive contact with the test site (and optionally one or more control sites) visib:Le through a window or windows in the cell's ezter:ior casing. In one embodiment. the conjugate is mined with the sample and incubated briefly before the test cell is inserted. In another embodiment. 1=he conjugate is disposed in preserved form in the l:low path within the cell. If the ligand is present in the sample, it passes through the inlet and the: interior of the cell along the flow path past the test and control sites, where, in the sandwich embodiment, it reacts with immobilized binding protein, e.g., antibody, at the test site, and perhaps. also non-specifically at the control site. A
"sandwich" forms at the test site comprising immobilized binding protein-ligand binding protein-colored particle. The presence of the sandwich com;plez and thus the ligand is indicated by the development of color caused by aggregation of the metal a~ol particles at the test site. A deeper color at the test cite than at the negative control site is a positive indication of the presence of the ligand.
Hy providing a reservoir of sorbent material disposed beyond the test and control sites, a relatively large volume of the test liquid and any ligand it contains can be drawn through the test area to aid sensiitivity. Optionally, the region of the flow path in the test cell defining the test and control. sites is restricted in cross-sectional area relative to other regions of the flow path. This feature: produces a "bottle-neck" effect wherein all ligand in the. entire volume of sorbed sample must pass through the restricted flow area immediately about t:he test site where it will be immobilized by reaction with binding protein.
Frorn the foregoing, it will be apparent that the success of the test procedure is dependent on ligand present in the sample reacting with the conjugate, or on reproducible competition between the ligand and the conjugate for sites of attachment at the test site. In accordance with the invention, as noted above, the assays can be conducted by premizing the con.jugatE~ with the liquid sample prior to introduction into~the elongate test cell.
Alternatively, the conjugate may be disposed in preserved foi:m, e~g., freeze-dried, in the flow path within the test cell upstream of the test and control sites. In this case, the cell is placed directly in the liquid sample solution without premizing.
Ligand, if any, passing up through the cell and entrained within the liquid moves into contact with the conjugate forming an immune complez or initiating competition j~ situ as flow continues. This latter technique has the advantage that it eliminates a manipulative step in the assay procedure, and accordingly a possible source of error.
Referring to the drawing, figures 1 and 2 illustrate schematically an embodiment of a test cell constructed in accordance with the invention useful in ezp:laining its principles of construction. It comprises an outer, molded casing 10 which defines a hollow, elongate enclosure filled with a permeable, sorbent material 12. Casing 10 also defines a test liquid inlet 14 and a pair of circular openings 16, 18 comprising windows through which sorbent material 12 is 'risible.
Sorbent material 12 and the interior of casing 10 together define a flow path passing generally from left to right in figures 1 and 2.
When the test cell is placed with inlet 14 disposed within or otherwise in contact with a liquid sample, the lip;uid is transported by capillary action, wicking, or simple wetting along the flow path through upstream flow section 20, test volume 22, and into rEaervoir volume 24, generally as depicted by the arrows. The flow section 20 of the flow path disposE:d inwardly of the inlet 14 serves as a filter which c:an remove from impure test samples particulate matter and interfering factors. The provisions of such a filtr;ation~means 20 downstream of the inlet 14 is bel»eved 'to contribute to the success of the system and its ability to avoid false positives.
Disposed within sozbent material 12 is a band 2Ei of dehydrated conjugate. e.g., antibody-metal sol. ~~s the liquid sample moves past band 26, the conjugate is entrained in the liquid, reconstituted, and reacts or competes with ligand, if present, dissolved in the liquid sample. Of course, conjugate band 2Ei may be eliminated, and the conjugate added to the test liquid prior to introduction of the cell 5 as previously noted.
Within the volume of sorbent material 12 disposed directly beneath circular openings 16 and 18 in casing 10 is disposed, respectively, control site 16' and test site 18'. In the drawing,'the control and test situ are illustrated as being disposed serial7:y along the flow path. Alternatively, the contro7~ and test site or sites may be disposed side by sidE: or in other spacial relationships.
Tesit site 18' comprises a preselected quantity of .antibody against an epitope of the ligand to be detected immobilized in place within the flow path. Its detailed chemical structure can vary widely,. Control site 16' is preferably identical in size and chemical makeup to test site 18', a:cepting that the immobilized antibody present at the test site lE3' is emitted at the control site 16'. Thus, any nonspeci:Eic aggregation of, e.g., ligand--conjugate or free conjugate, which occurs at test site 18' also will occur at control site 16'. A
deeper color at test site .18' as compared with contro:L site 16' is a positive indication of ligand in the sample in the sandwich assay.
The invention is not limited by the precise nature of the test site 18' and corresponding control site I~6', and in fact, control site 16' may be entirely eliminated if a reduction in sensitivity can be tolcarated. Generally, antibody or other binding protein may be immobilized at test site 18' using adsorp~~ion, absorption, or ionic or covalent coupling, in accordance with methods known per fig, A
currently preferred formulation for test site 18' is to immobilize monoclonal antibody against an epitope of the ligand on latez beads, and then to entrap or otherwise link the beads in sorbent material 12 at region 18'. Control site 16' is fabricated identically, ezcept that the latez beads._contain non specif~.c immunoglobulin, e.g., immunoglobulin from bleedings from an animal that has not been immunized.
Disposed beyond test volume 22 is a reservoir volume 24 comprising a relatively large mass o!: sorbent or supersorbent material. The purposE; of reservoir volume 24 is to assure that a reasonably large amount of test liquid is drawn through test volume 22. Increasing the volume of reservoir 24 can have the effect of increasing the sensitivity of the assay procedure, as it results in an inc:'ease :in the amount of ligand passing through the te:~t area 22. Suitable sorbents include commercial materials of the type available. foz ezample:, from The Dow Chemical Company of Midland, Michigan, anti the Chemical division of American Colloid, Arlington Heights, I11. These materials can absorb many i:imes their weight in water and are common7.y used in disposable diapers. They comprise lightly crosslirked polyacrylate salts, typically alkali metal salts.
-15- ~~ 409 20 Polyclonal antisera and indeed monoclonal antibodies or fractions thereof having specific . bindin5f properties and high affinity for virtually any antigenic: substance are known and commercially available or can be produced from stable cell lines using well known cell fusion and screening technig;ues. The literature is replete with protein immobilization protocols. See, for example, Laboratory Teachn? QlaeS ~ n BlOChem~ ctrY and Mol p~ml ar ~' o~ loa_~_v;, Ti j:csen, Vol . 15, Practice and Theory of Enzyme immunoassays, chapter 13, The Immobilization of Immunoreac:tants on Solid Phases, pp. ~5~7-328, and the reference's cited therein.
Metal sols and other types of colored particles useful as marker substances in immunoassay procedures are also known per fig. See, for example, U.S. 4,313.73'.4, February 2, 1982, to Leuvering.
F'or details and engineering principles involved in the synthesis of colored particle conjugates se:e Horisberger, Evaluation of Colloidal Gold as a Cytochromic Marker for Transmission and Scanning Electron Microscopy, Biol. Cellulaire, ~
253-258 (1979); Leuvering et al, Sol Particle Immunoassay, J. Immunoassay 1 (1), 77-91 (1980), and Frens, Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions, Nature, Physical Science, ,'~,g~, pp. 20-22 (1973).
The cell can take. various forms. It will usually comprise an elongate casing comprising interfii~ting parts made of polyvinyl chloride, polypropylene, or other thermoplastic resin. Its interior flow path will contain a relatively inert A
material or a combination of materials suitable for transporting the liquid. In some circumstances it may be preferable to use a material of higher sorptivity as the reservoir, promoting the flow of liquid, and a different material for remaining portions of the flow path.
From the foregoing it should be apparent that the advantages in reproducibility, sensitivity, and avoidance of false positives of ,essay systems constructed in accordance with the invention are traceable to a combination of features of the invention. In use, the t~=st cell of the invention and the metal sol particles used as a marker together cooperate to result in an increase in color intensity progressively as ligand complexed with conjugate is t..apped at the test site by the immobilized binding protein. This approach can be utilized to design assays and test cells for E~ssent:ially any antigenic material.
The invention will be further understood from the following non-limiting examples.
Example 1 The curre,ztly preferred test device embodying the invention is shown in Figures 3, 4A, 4B and 5. A modification of the device depicted in Figure 3 is shown in Figure 6, and includes a second control site 19 in addition to control site 16' and test site 1F3', as well as a stand 21 useful for maintaining the test: cell in an incline position with the reservoir downhill. V~hen a test sample is applied to inlet 14, gravity as well as ~corption aids in transporting the sample along with the flow path.
-1'- 13 4 0 ~ 2 0 As shown in Figures 3, 4A, 4B, and 5, the prefe:'red test cell of the invention differs from the ezemphary device discussed above and shown in Figures 1 and 2 in certain of its more specific internal features. Specifically, the casing comprises a pair of interfitt:ing polymeric parts including a U-shaped top part 10 which, when the device is assembled, interfits with lower part 10'. Top and bottom parts and 10' may be connected through a hinge region 11. The bottom section 10' defines a pair of channels 28 above which is disposed a strip of glass fiber ;paper 13 (available commercially from Eaton Dikeman, Grade 111; or Whatmaa; Grade GFA). Test liquid applied through inlet 14 soaks along the paper strip :13 which def fines the f low path and a f i ltering means ~cegion 20, as well as a positive control site 16' and test site 18' visible through windows 16 and 18 consisting of openings through upper mating member 10. The paper strip 13 overlaps into reservoir volume 24, which is defined by a cavity between the interfitting top and bottom mating members 10 and 10'. The cavity in this case is filled with sorbent blotting papE:r 12 comprising the sorbent reservoir.
A suitable p<~per is sold as Grade 12A absorbent paper, a cel7lulose product available from Schleicher and Sch,uell. In one preferred embodiment, the dimensions ot: the glass fiber paper 13 were approzimately one quarter inch by three inches, and those of the absorbent material 12 approzimately two inches by five thirty seconds of an inch on each side. A number of these devices were produced and further treated to adapt them to detect pregnancy by assay of urine.
*trade-m~~rk A
Test site 18' i.n each device was fabricated as a spot within fiber paper 13 using the following technique. Latex beads available commercially and comprising polystyrene particles 0.3 micron in diameter were passively coated with purified rabbit anti-human chorionic gonadotropin. The polyclonal antibody was purified using conventional techniques from bleedings of a rabbit previously immunized with human chorionic gonadotro~?in in a manner know er se. Equal parts of a latex (0.6o by weight) having a continuous phase of glycine buffer, pH = 8.3, and a 1 mg/ml antibody solution in the same buffer were mixed acid incubated at 37°C. 15 microliters of this solution, comprising approximately 0.6o solids, were added, one drop at a time, to t=he glass fiber paper 13 to produce spot 18' after the devices had been assembled. The spots were then allowed to dry at 3'~°C. The control site 16' was produced identically to the test site disclosed immediately above, excepting that rabbit pol5rclonal non-immune gamma globulin was used in place of the anti--hCD gamma globulin.
Metal sol particles were prepared in accordance with the method of Frens, Controlled Nucleation for the Regulation of the Particle Size in Mono Dispersed Gold Solutions (1973), supra. Briefly, the gold sol was prepared by reducing a 40 solution of gold chloride with 1~ sodium citrate to produce gold particles of approximately l8nm in diameter. The particles were made immunochemicall.y reactive by admixture with a monoclonal antibody specific for human chorionic gonadotropin with no x detectable cross-reactivity with human leutinizing hormone. The antibody was purchased from Charles River Labs. and is produced using standard techniques including purification from ascites using HPLC ion ezchang~e chromatography. It was added to the gold sol as a 10 ug/ml solution in borate buffer, pH-6.
The bound antibody fraction is separated from the free fraction by either density centrifugation or gel filtration chromatography. Additional details of the currently preferred procedure for making the antibody sol conjugate are disclosed by Leuvering et al, J.
Immunoassay (198'0) supra. Individual ba~Ghes of the latez and the conjugate are titrated to optimize activit;~ so that a suitable amount of latez is applied to the test site and a suitable amount of conjugate is used in conducting the test.
Test Pr~~toco 1 To a 10 X 50 mm test tube of lyophilized , gold so;l antibody conjugate is added 0.5 ml urine sample containing a known quantities of hCG. The samples comprised hCG standards purchased from Sigma Chemical Company diluted in processed, hCG negative urine. The contents of the tube are mized by shaking in a hooizontal motion until the lyophilized antibody is dissolved. The device depicted in Figures 3-5 is then in:~erted into the tube, and the results are read after the entire fluid volume has been absorbed.
_~~,. 1409 ~Q
The results of this qualitative procedure are as follows:
Color of Color of mIU hCG Control S~~ot Reagent Shot 0 grey grey 25 grey pink hue 50 grey pink 100 grey rose 150 grey rose >150 grey dark rose The pink ~~olor ~~learly visible at 50mIU of human chorionic gonadotropin means that the test can detect pregnancy one day after a mis:>ed menstrual period. In initial stages of testing, approximately 50 negative samples from various sources have been run with no fal:~e positives or even border-line cases.
It is anticipated treat the commercial device will have less than 1o false positives.
Non-limiting ex<~mples of materials which may be assayed in accordance with the invention in addition to the human chorionic gona.dotropin noted above include human leutinizing hormone, progesterone, estrogen, and streptococcus.
Other embodiments are within the following claims.
Tnlhat is c7_aimed is:
SIR COLORED PARTICLE IMMUNOASSAY
BACKGROUND OF' THE INVENTION
This. invention relates to assays for ligands, e.g., antigens, in a liquid sample such as a body fluid. More particularly, the invention relates to a method amd apparatus for the detection of a ligand in a body fluid such as urine using a conjugate comprising colored particles and a novel flow-through test cell.
Many types of ligand-receptor assays have been used to detect the presence of various substances, often generally called ligands, in body fluids such ass urine. These assays involve antigen antibody reacaions, synthetic conjugates comprising radioactive, enzymatic, fluorescent, or visually observable metal sol tags, and specially designed reactor chambers. In all these assays, there is a receptor, e.5~., an antibody, which is specific for the selected ligand or antigen. and a means for detecting the: presence, and often the amount, of the ligand-receptor reaction product. Most current tests are designed to make a quantitative determination, but in many circumstances all that is required is a positive/negative indication. Ezamples of such qualitative assays include blood typing and most types of urinalysis. For these tests, visually observable indicia such as the presence of agglutination or a color changes are preferred.
~~~Q~ Z~
Even the positive/negative assays must be very .~ensit:ive because of the often small concentration of the ligand of interest in the test fluid. False positives can also be troublesome, particularly with agglutination and other rapid detection mcahods such as dipstick and color change tests. Because of these problems, sandwich assays and other sE:nsitive detection methods which use metal sols or othE:r types Qf colored particles have been developed. These techniques have not solved all of the problems encountered in these rapid detection methodls .
It is an object of this invention to provide ' a rapid, sensitive method for detecting ligands in body fluids. Another object is to provide an assay which has high sensitivity and fewer false positives than conventional assays. A further object is to provide a tea t cell for detection of low levels of ligand.s in body fluids. Another object is to provide an assay system which involves a minimal number of procedural steps, and yields reliable results even when used by untrained persons.
Theae and other objects and features of the invention will be apparent from the following description,. drawing, and claims.
13409 ~0 $~$~ OF T;HE INVENTION
The invention features a method and test cell for the detection of a preselected ligand in a liquid sample such as a body fluid.
The test cell useful in the practice of the invention ha;s an elongate outer casing which houses an interior permeable material, e.g., glass fiber, capable: of transporting an aqueous solution by capillary action, wicking, or simple wetting. The casing defines a sample inlet, and interior regions which, for ease of description, can be designated as a test volumE: and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet, and preferably is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and eztending from the inlet and through the test volume. In the test volume is a test site cornprising a first protein having a binding site specific: to a first epitope of the ligand immobilized in fluid communication with the flow path, e:.g., bound to the permeable material or to latez particles entrapped in or bonded to the permeable material. A window such as a hole or transparent :>ection of the casing permits observations of the test site through the casing wall.
In a preferred embodiment, the flow path is restricted or narrowed in the test area, thereby channeling and concentrating fluid flow into contact - ~ ~ with th.e test: site. It is also preferred that the - - test cell include a solution filtering means disposed in the flow path between the sample inlet and the -4- 13409 ~0 teat site. The filtration means can comprise a ' separate, conventional filter element disposed within the casing of the test cell in fluid communication with the permeable material defining the flow path, but preferably is defined simply by a portion of the permeable material itself. The provision of such a filtration means in the test cell has the effect of removing by entrapment from impure samples, such as urine samplea, a portion of the particulates and nonspecific interfering factors which sometimes cause false positive readings.
The: method of the invention re3quires the use of a conjugate comprising a second protein bound to colored particles such as a metal sol or colloid, preferably gold. The conjugate can take two distinct forms, depending on whether the assay is designed to ezploit the "sandwich" or "competitive" technique.
In the case of the sandwich technique, the second protein comprises a site which binds to a second epitope on the ligand. This type of conjugate reacts with the ligand to form a complez in the liquid sample. The complez is detected by visual observation of color development at the test site in the test cell. At the test site, the ligand bound with the conjugate reacts with the immobilized first binding protein to form a "sandwich" of the first . protei;n, ligand, second protein, and colored particles. This sandwich complez is progressively produced at the test site. as sample continuously gasses by, filling the reservoir. As more and more conjua,ate is immobilized, the colored particles aggregate at the test site and become visible through the window, indicating the presence of ligand in the liquid sample.
In the case of the competitive technique, the second protein binds with the first protein in competition with the ligand. The second protein comprises, for ezample, an authentic-sample of the ligand or a fraction thereof which has comparable affinity for the first protein. As the liquid sample is transported in contact with the test site, ligand, if any, and the conjugate compete for sites of attachment to the first protein. If no--ligand is present, colored particles aggregate at the test site, and the presence of color indicates the absence of detectable levels of ligand in the sample. If ligand is present. the amount of conjugate which binds .at the test site is reduced, and no color, or a paler color, develops.
In one embodiment of the invention, the test liquid is mized with the conjugate outside the test cell. In another embodiment, the conjugate is dispos~sd in freeze-dried or other preserved form on the permeable material between the inlet and the test site. .and the sample liquid resolubilizes the conjug~~te as it passes along the flow path.
Color development at the test site may be compared with the color of one or more standards or internal controls to determine whether the develo~~ment of color is a~true indication of the presen~~e or absence of the iigand, or an artifact caused by nonspecific sorption.
In one embodiment employing the sandwich technique, the standard consists of a negative control site, preferably disposed adjacent the test site, and visible through a second window prozimate the first. The negative control site preferably is prepared identically to the test site, ezcept immobilization of the first binding protein is omitted. Therefore, although the conjugate will reach the control site, it aggregates due only to non-specific binding. If the test site is not appreciably more intense in color than the control site, the assay is considered negative...-In another embodiment. the assay and test cell may include a positive control. Thus, when ezploiting the sandwich technique, the cell may have an autlhentic sample of the ligand immobilized at a control site. If no color develops at this control site, 'the assay is considered inconclusive. When ezploi~ting the competitive technique, the development of col~~r at the positive control site means the assay results are inconclusive.
Broadly, the method of the invention involves the use of a test cell of the type described above ~to achieve an easily readable, sensitive, reproducible indication of the presence of a ligand, e.g., lnuman chorionic gonadotropin (hCG), in a test sample such as a human urine sample. The method involves the step of transporting the sample and a conjugate comprising a protein bound to a metal sol or othi~r colored particle along a flow path and in contact with a test site comprising immobilized bindin~~ protein specific to an epitope of the ligand, __ 1340 ~0 and preferably also in contact with a control site. Preferably, the colored particle comprises a gold sol; the flow path in the region of the test rite i:~ reduced in cross-section relative to other parts of the flow path; the sample is passed through a filtration means after it enters the test cell but before it contacts the test site; and the test site comprises latex particles entrapped or otherwise fixed in the flow path having the immobilized protein on their surface. In the practice of the process, either the conjugate is premixed with the sample, or the conjugate is dispo~>ed in preserved form, e.g., lyophilized, in the flow path between the inlet and the test site. In either cage, placement of the test cell in the sample, or application of the sample to the inlet, initiates flow, and the result is read by observing color development at the test site, or by comparing the color of the test site and control site.
The use oj= the colored particle detection system in combination with the filtration means, the concentrating effect of flow of the sample, and the ease of comparison between the colors of the test a.nd control sites, together enable construction of a family of extremely sensitive assay systems which minimize falser positives and can be used effectively by untrained persons.
-8- 13409 ~0 BRIEF DESCRIPTION OF THE DRAWTU~
Figure 1 is a cut-away, schematic, top view of an embodiment of a test cell useful in ezplaining the test ce711 and process of the invention;
Figure 2 is a cross-sectional side view of the to t cell of Figure 1;
FiS~ure 3 is a perspective view of a currently preferred test cell constructed in accordance with the invention;
Figure 4A is a cross-sectional, top view of the test cell of Figure 3;
Figure 4B is a cross-sectional, side view of the test cell of Figure 3 taken at line-~iB-98 of ' Figure 4A;
Figure 5 is a cross sectional view of the cell of Figure 3 taken at line 5-5 of Figure 4B; and Figure 6 is a perspective view of another embodiment o~f a test cell constructed in accordance with the invention.
Like reference characters in the respective drawn figures indicate corresponding parts.
_g_ ThE: invention provides a test cell for conducting a sandwich or competitive immunoassay, and a process which utilizes the test cell and a conjugate comprising colored particles. As disclosed below, various features of the process and test cell of the invention cooperate to enable untrained personnel reliably to assay a liquid sample for the presence of eztremely small quantities of a particular l.igand while avoiding false positives and simplifying test procedures. The invention is ideal for use in owe=-the-counter assay test kits which will enable a consumer to self diagnose, for ezample, pregnancy, venereal disease, and other disease, infection, or clinical abnormality which results in the presence of an antigenic marker substance in a body fluid. including determination of the presence of metabolites of drugs or tozins. The assay process and the cell are engineered specifically to detect the presence of a preselected individual ligand present in a body or other fluids.
Broadly, the test cell and process of the invention can be used to detect any ligand which has hereto;Eore been assayed using known immunoassay procedures. or known to be detectable by such procedures, using polyclonal or monoclonal antibodies or other proteins comprising binding sites for liganda. Various specific assay protocols, reagents, and analytes useful in the practice of the invention are known per se, see, e.g., U.S. 4,313,734, columns 4-18, ~3nd U.,S. 4,366,241, columns 5-40.
The combination of features believed to be respon:~ible for the ezcellent sensitivity and -lo- 1 3 4 0 9 2 0 reproducibility of assays constructed in accordance with the invention is the use of the novel test cell which Nerves to concentrate ligand from a test sample at a tEa t site in the cell, and the use of a metal sol or other colored particle as a marker system which permits direct visual observation of color develo~~ment. False positives are reduced while maintaining excellent sensitivity by including in the test cE:ll a negative control or control site whose color i.s compared with the test site, and by including a filtration means which limits the introduction to/the test site of contamiirants from the sample.
The assay is conducted by simply placing the inlet of the test cell in contact with a liquid test sample. One then merely waits for the test sample to pass through the cell and into reactive contact with the test site (and optionally one or more control sites) visib:Le through a window or windows in the cell's ezter:ior casing. In one embodiment. the conjugate is mined with the sample and incubated briefly before the test cell is inserted. In another embodiment. 1=he conjugate is disposed in preserved form in the l:low path within the cell. If the ligand is present in the sample, it passes through the inlet and the: interior of the cell along the flow path past the test and control sites, where, in the sandwich embodiment, it reacts with immobilized binding protein, e.g., antibody, at the test site, and perhaps. also non-specifically at the control site. A
"sandwich" forms at the test site comprising immobilized binding protein-ligand binding protein-colored particle. The presence of the sandwich com;plez and thus the ligand is indicated by the development of color caused by aggregation of the metal a~ol particles at the test site. A deeper color at the test cite than at the negative control site is a positive indication of the presence of the ligand.
Hy providing a reservoir of sorbent material disposed beyond the test and control sites, a relatively large volume of the test liquid and any ligand it contains can be drawn through the test area to aid sensiitivity. Optionally, the region of the flow path in the test cell defining the test and control. sites is restricted in cross-sectional area relative to other regions of the flow path. This feature: produces a "bottle-neck" effect wherein all ligand in the. entire volume of sorbed sample must pass through the restricted flow area immediately about t:he test site where it will be immobilized by reaction with binding protein.
Frorn the foregoing, it will be apparent that the success of the test procedure is dependent on ligand present in the sample reacting with the conjugate, or on reproducible competition between the ligand and the conjugate for sites of attachment at the test site. In accordance with the invention, as noted above, the assays can be conducted by premizing the con.jugatE~ with the liquid sample prior to introduction into~the elongate test cell.
Alternatively, the conjugate may be disposed in preserved foi:m, e~g., freeze-dried, in the flow path within the test cell upstream of the test and control sites. In this case, the cell is placed directly in the liquid sample solution without premizing.
Ligand, if any, passing up through the cell and entrained within the liquid moves into contact with the conjugate forming an immune complez or initiating competition j~ situ as flow continues. This latter technique has the advantage that it eliminates a manipulative step in the assay procedure, and accordingly a possible source of error.
Referring to the drawing, figures 1 and 2 illustrate schematically an embodiment of a test cell constructed in accordance with the invention useful in ezp:laining its principles of construction. It comprises an outer, molded casing 10 which defines a hollow, elongate enclosure filled with a permeable, sorbent material 12. Casing 10 also defines a test liquid inlet 14 and a pair of circular openings 16, 18 comprising windows through which sorbent material 12 is 'risible.
Sorbent material 12 and the interior of casing 10 together define a flow path passing generally from left to right in figures 1 and 2.
When the test cell is placed with inlet 14 disposed within or otherwise in contact with a liquid sample, the lip;uid is transported by capillary action, wicking, or simple wetting along the flow path through upstream flow section 20, test volume 22, and into rEaervoir volume 24, generally as depicted by the arrows. The flow section 20 of the flow path disposE:d inwardly of the inlet 14 serves as a filter which c:an remove from impure test samples particulate matter and interfering factors. The provisions of such a filtr;ation~means 20 downstream of the inlet 14 is bel»eved 'to contribute to the success of the system and its ability to avoid false positives.
Disposed within sozbent material 12 is a band 2Ei of dehydrated conjugate. e.g., antibody-metal sol. ~~s the liquid sample moves past band 26, the conjugate is entrained in the liquid, reconstituted, and reacts or competes with ligand, if present, dissolved in the liquid sample. Of course, conjugate band 2Ei may be eliminated, and the conjugate added to the test liquid prior to introduction of the cell 5 as previously noted.
Within the volume of sorbent material 12 disposed directly beneath circular openings 16 and 18 in casing 10 is disposed, respectively, control site 16' and test site 18'. In the drawing,'the control and test situ are illustrated as being disposed serial7:y along the flow path. Alternatively, the contro7~ and test site or sites may be disposed side by sidE: or in other spacial relationships.
Tesit site 18' comprises a preselected quantity of .antibody against an epitope of the ligand to be detected immobilized in place within the flow path. Its detailed chemical structure can vary widely,. Control site 16' is preferably identical in size and chemical makeup to test site 18', a:cepting that the immobilized antibody present at the test site lE3' is emitted at the control site 16'. Thus, any nonspeci:Eic aggregation of, e.g., ligand--conjugate or free conjugate, which occurs at test site 18' also will occur at control site 16'. A
deeper color at test site .18' as compared with contro:L site 16' is a positive indication of ligand in the sample in the sandwich assay.
The invention is not limited by the precise nature of the test site 18' and corresponding control site I~6', and in fact, control site 16' may be entirely eliminated if a reduction in sensitivity can be tolcarated. Generally, antibody or other binding protein may be immobilized at test site 18' using adsorp~~ion, absorption, or ionic or covalent coupling, in accordance with methods known per fig, A
currently preferred formulation for test site 18' is to immobilize monoclonal antibody against an epitope of the ligand on latez beads, and then to entrap or otherwise link the beads in sorbent material 12 at region 18'. Control site 16' is fabricated identically, ezcept that the latez beads._contain non specif~.c immunoglobulin, e.g., immunoglobulin from bleedings from an animal that has not been immunized.
Disposed beyond test volume 22 is a reservoir volume 24 comprising a relatively large mass o!: sorbent or supersorbent material. The purposE; of reservoir volume 24 is to assure that a reasonably large amount of test liquid is drawn through test volume 22. Increasing the volume of reservoir 24 can have the effect of increasing the sensitivity of the assay procedure, as it results in an inc:'ease :in the amount of ligand passing through the te:~t area 22. Suitable sorbents include commercial materials of the type available. foz ezample:, from The Dow Chemical Company of Midland, Michigan, anti the Chemical division of American Colloid, Arlington Heights, I11. These materials can absorb many i:imes their weight in water and are common7.y used in disposable diapers. They comprise lightly crosslirked polyacrylate salts, typically alkali metal salts.
-15- ~~ 409 20 Polyclonal antisera and indeed monoclonal antibodies or fractions thereof having specific . bindin5f properties and high affinity for virtually any antigenic: substance are known and commercially available or can be produced from stable cell lines using well known cell fusion and screening technig;ues. The literature is replete with protein immobilization protocols. See, for example, Laboratory Teachn? QlaeS ~ n BlOChem~ ctrY and Mol p~ml ar ~' o~ loa_~_v;, Ti j:csen, Vol . 15, Practice and Theory of Enzyme immunoassays, chapter 13, The Immobilization of Immunoreac:tants on Solid Phases, pp. ~5~7-328, and the reference's cited therein.
Metal sols and other types of colored particles useful as marker substances in immunoassay procedures are also known per fig. See, for example, U.S. 4,313.73'.4, February 2, 1982, to Leuvering.
F'or details and engineering principles involved in the synthesis of colored particle conjugates se:e Horisberger, Evaluation of Colloidal Gold as a Cytochromic Marker for Transmission and Scanning Electron Microscopy, Biol. Cellulaire, ~
253-258 (1979); Leuvering et al, Sol Particle Immunoassay, J. Immunoassay 1 (1), 77-91 (1980), and Frens, Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions, Nature, Physical Science, ,'~,g~, pp. 20-22 (1973).
The cell can take. various forms. It will usually comprise an elongate casing comprising interfii~ting parts made of polyvinyl chloride, polypropylene, or other thermoplastic resin. Its interior flow path will contain a relatively inert A
material or a combination of materials suitable for transporting the liquid. In some circumstances it may be preferable to use a material of higher sorptivity as the reservoir, promoting the flow of liquid, and a different material for remaining portions of the flow path.
From the foregoing it should be apparent that the advantages in reproducibility, sensitivity, and avoidance of false positives of ,essay systems constructed in accordance with the invention are traceable to a combination of features of the invention. In use, the t~=st cell of the invention and the metal sol particles used as a marker together cooperate to result in an increase in color intensity progressively as ligand complexed with conjugate is t..apped at the test site by the immobilized binding protein. This approach can be utilized to design assays and test cells for E~ssent:ially any antigenic material.
The invention will be further understood from the following non-limiting examples.
Example 1 The curre,ztly preferred test device embodying the invention is shown in Figures 3, 4A, 4B and 5. A modification of the device depicted in Figure 3 is shown in Figure 6, and includes a second control site 19 in addition to control site 16' and test site 1F3', as well as a stand 21 useful for maintaining the test: cell in an incline position with the reservoir downhill. V~hen a test sample is applied to inlet 14, gravity as well as ~corption aids in transporting the sample along with the flow path.
-1'- 13 4 0 ~ 2 0 As shown in Figures 3, 4A, 4B, and 5, the prefe:'red test cell of the invention differs from the ezemphary device discussed above and shown in Figures 1 and 2 in certain of its more specific internal features. Specifically, the casing comprises a pair of interfitt:ing polymeric parts including a U-shaped top part 10 which, when the device is assembled, interfits with lower part 10'. Top and bottom parts and 10' may be connected through a hinge region 11. The bottom section 10' defines a pair of channels 28 above which is disposed a strip of glass fiber ;paper 13 (available commercially from Eaton Dikeman, Grade 111; or Whatmaa; Grade GFA). Test liquid applied through inlet 14 soaks along the paper strip :13 which def fines the f low path and a f i ltering means ~cegion 20, as well as a positive control site 16' and test site 18' visible through windows 16 and 18 consisting of openings through upper mating member 10. The paper strip 13 overlaps into reservoir volume 24, which is defined by a cavity between the interfitting top and bottom mating members 10 and 10'. The cavity in this case is filled with sorbent blotting papE:r 12 comprising the sorbent reservoir.
A suitable p<~per is sold as Grade 12A absorbent paper, a cel7lulose product available from Schleicher and Sch,uell. In one preferred embodiment, the dimensions ot: the glass fiber paper 13 were approzimately one quarter inch by three inches, and those of the absorbent material 12 approzimately two inches by five thirty seconds of an inch on each side. A number of these devices were produced and further treated to adapt them to detect pregnancy by assay of urine.
*trade-m~~rk A
Test site 18' i.n each device was fabricated as a spot within fiber paper 13 using the following technique. Latex beads available commercially and comprising polystyrene particles 0.3 micron in diameter were passively coated with purified rabbit anti-human chorionic gonadotropin. The polyclonal antibody was purified using conventional techniques from bleedings of a rabbit previously immunized with human chorionic gonadotro~?in in a manner know er se. Equal parts of a latex (0.6o by weight) having a continuous phase of glycine buffer, pH = 8.3, and a 1 mg/ml antibody solution in the same buffer were mixed acid incubated at 37°C. 15 microliters of this solution, comprising approximately 0.6o solids, were added, one drop at a time, to t=he glass fiber paper 13 to produce spot 18' after the devices had been assembled. The spots were then allowed to dry at 3'~°C. The control site 16' was produced identically to the test site disclosed immediately above, excepting that rabbit pol5rclonal non-immune gamma globulin was used in place of the anti--hCD gamma globulin.
Metal sol particles were prepared in accordance with the method of Frens, Controlled Nucleation for the Regulation of the Particle Size in Mono Dispersed Gold Solutions (1973), supra. Briefly, the gold sol was prepared by reducing a 40 solution of gold chloride with 1~ sodium citrate to produce gold particles of approximately l8nm in diameter. The particles were made immunochemicall.y reactive by admixture with a monoclonal antibody specific for human chorionic gonadotropin with no x detectable cross-reactivity with human leutinizing hormone. The antibody was purchased from Charles River Labs. and is produced using standard techniques including purification from ascites using HPLC ion ezchang~e chromatography. It was added to the gold sol as a 10 ug/ml solution in borate buffer, pH-6.
The bound antibody fraction is separated from the free fraction by either density centrifugation or gel filtration chromatography. Additional details of the currently preferred procedure for making the antibody sol conjugate are disclosed by Leuvering et al, J.
Immunoassay (198'0) supra. Individual ba~Ghes of the latez and the conjugate are titrated to optimize activit;~ so that a suitable amount of latez is applied to the test site and a suitable amount of conjugate is used in conducting the test.
Test Pr~~toco 1 To a 10 X 50 mm test tube of lyophilized , gold so;l antibody conjugate is added 0.5 ml urine sample containing a known quantities of hCG. The samples comprised hCG standards purchased from Sigma Chemical Company diluted in processed, hCG negative urine. The contents of the tube are mized by shaking in a hooizontal motion until the lyophilized antibody is dissolved. The device depicted in Figures 3-5 is then in:~erted into the tube, and the results are read after the entire fluid volume has been absorbed.
_~~,. 1409 ~Q
The results of this qualitative procedure are as follows:
Color of Color of mIU hCG Control S~~ot Reagent Shot 0 grey grey 25 grey pink hue 50 grey pink 100 grey rose 150 grey rose >150 grey dark rose The pink ~~olor ~~learly visible at 50mIU of human chorionic gonadotropin means that the test can detect pregnancy one day after a mis:>ed menstrual period. In initial stages of testing, approximately 50 negative samples from various sources have been run with no fal:~e positives or even border-line cases.
It is anticipated treat the commercial device will have less than 1o false positives.
Non-limiting ex<~mples of materials which may be assayed in accordance with the invention in addition to the human chorionic gona.dotropin noted above include human leutinizing hormone, progesterone, estrogen, and streptococcus.
Other embodiments are within the following claims.
Tnlhat is c7_aimed is:
Claims (26)
1. A method of detecting a ligand in a liquid sample, the method comprising the steps of:
A. transporting along a flow path in a test cell a solution, including a liquid sample suspected to contain a ligand and a conjugate into contact with a test site visible through a window in a wall of said test cell, said test site having immobilized thereon a first protein having a binding sites specific to a first epitope on the ligand, said conjugate comprising colored particles coupled to a second protein selected from the group consisting of proteins having a binding site specific to a second epitope on the ligand and proteins which bind with said first protein in competition with the ligand, and B. continuing transport of said solution to progressively produce at said test site a complex comprising said ligand for a time sufficient to visually determine through said window whether a color is developed at said test site.
A. transporting along a flow path in a test cell a solution, including a liquid sample suspected to contain a ligand and a conjugate into contact with a test site visible through a window in a wall of said test cell, said test site having immobilized thereon a first protein having a binding sites specific to a first epitope on the ligand, said conjugate comprising colored particles coupled to a second protein selected from the group consisting of proteins having a binding site specific to a second epitope on the ligand and proteins which bind with said first protein in competition with the ligand, and B. continuing transport of said solution to progressively produce at said test site a complex comprising said ligand for a time sufficient to visually determine through said window whether a color is developed at said test site.
2. The method of claim 1 wherein said test cell comprises a filtration means for filtering said liquid sample, said method comprising the additional step of transporting the sample through said filtration means before said sample contacts said test site.
3. The method of claim 1 wherein the cross-sectional area of said flow path is restricted about said test site whereby ligand is localized at said test sate during flow of solution thereby.
4. The method of claim 1 comprising the additional steps of transporting said solution into contact with a control site visible through a window in a wall of said test cell and comparing the color of said test site and control site.
5. The method of claim 4 wherein said control site comprises a negative control site free of said first protein.
6. The method of claim 9 wherein said control site comprises a positive control site having immobilized thereon an authentic sample of said ligand.
7. The method of claim 1 comprising the step of mixing said conjugate with said liquid sample prior to step A.
8. The method of claim 1 wherein said conjugate is disposed in said flow path, said method comprising the additional step of transporting said liquid into solubilizing contact with said conjugate prior to contact with said test site.
9. The method of claim 1 wherein said first and second proteins comprise antibodies and at least one of said proteins is a monoclonal antibody.
10. The method of claim 1 wherein said first protein has a binding site specific to an epitope of human chorionic gonadotropin.
11. The method of claim 1 wherein said first protein has a binding site specific to an epitope of human progesterone.
12. The method of claim 1 wherein said second protein has a binding site specific to a second epitope on the ligand, and when said sample contains said ligand, the complex produced in step H comprises said ligand bound to both said first and second proteins, and color is produced by aggregation of said colored particles at said test site.
13. The method of claim 1 wherein said second protein binds with said first protein in competition with the ligand, and when said sample contains said ligand, the complex produced in Step H comprises said ligand bound to sand first protein, and when said sample is free of said ligand, the complex produced in step B comprises said conjugate bound to said first protein, and color is produced by aggregation of said colored particles at said test site.
14. A test cell for detecting a ligand in a liquid sample, the test cell comprising an elongate casing for housing a permeable material and defining a liquid sample inlet, a reservoir volume, a test volume interposed between said inlet and reservoir volume, and a window through said casing at said test volume, permeable material capable of transporting an aqueous solution disposed within said casing and defining a flow path extending from said sample inlet through said test volume and into communication with said reservoir volume, a first protein having a binding site specific to a first epitope on said ligand, said first protein being immobilized at a test site, disposed within said test volume in fluid communication with said flow path and visible through said window, and a sorbent material in said reservoir volume for drawing liquid sample along said flow path and into contact with said test site.
15. The cell of claim 14 further comprising a liquid samples filtering means disposed in said flow path between said inlet and said test site.
16. The cell of claim 15 wherein said filtering means is defined by a portion of said permeable material.
17. The cell of claim 14 wherein the cross sectional area of said flow path is restricted about said test site so that ligand in liquid passing therealong is localized at said test site.
18. The cell of claim 14 wherein said casing defines, a second window through said casing and said cell further comprises a control site in fluid communication with said flow path visible through said second window.
19. The cell of claim 18 wherein said control site comprises a negative control site free of said first protein.
20. The cell of claim 19 wherein said control site comprises latex particles disposed in contact with said permeable material.
21. The cell of claim 18 wherein said control site comprises a positive control site having immobilized thereon an authentic sample of said ligand.
22. The cell of claim 14 further comprising a conjugate disposed in said flow path between said test site and said inlet, said conjugate comprising colored particles coupled to a second protein selected from the group consisting of proteins having a binding site specific to a second epitope on the ligand, and proteins which bind with said first protein in competition with the ligand.
23. The cell of claim 14 wherein said test site comprises an antibody fined to later particles disposed in contact with said permeable material.
24. The cell of claim 14 wherein said first protein binds with an epitope of human chorionic gonadotropin.
25. The cell of claim 14 wherein said first protein binds with an epitope of human progesterone.
26. The cell of claim 22 wherein at least one of said first and second proteins is a monoclonal antibody.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US211,582 | 1980-12-01 | ||
| US21158288A | 1988-06-27 | 1988-06-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1340920C true CA1340920C (en) | 2000-03-07 |
Family
ID=22787518
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000604025A Expired - Lifetime CA1340920C (en) | 1988-06-27 | 1989-06-27 | Test device and method for colored particle immunoassay |
Country Status (10)
| Country | Link |
|---|---|
| US (4) | US5714389A (en) |
| EP (1) | EP0349215B1 (en) |
| JP (1) | JP3125788B2 (en) |
| AT (1) | ATE121196T1 (en) |
| AU (3) | AU2684488A (en) |
| CA (1) | CA1340920C (en) |
| DE (1) | DE68922148T2 (en) |
| ES (1) | ES2073439T3 (en) |
| GR (1) | GR3015771T3 (en) |
| MX (1) | MX170320B (en) |
Families Citing this family (369)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3887771C5 (en) * | 1987-04-27 | 2009-06-04 | Inverness Medical Switzerland Gmbh | Immunoassays and devices therefor. |
| AU2684488A (en) | 1988-06-27 | 1990-01-04 | Carter-Wallace, Inc. | Test device and method for colored particle immunoassay |
| JPH0238972A (en) * | 1988-07-29 | 1990-02-08 | Nitto Denko Corp | Instrument and method for immunoassay |
| US6352862B1 (en) * | 1989-02-17 | 2002-03-05 | Unilever Patent Holdings B.V. | Analytical test device for imuno assays and methods of using same |
| US5252496A (en) | 1989-12-18 | 1993-10-12 | Princeton Biomeditech Corporation | Carbon black immunochemical label |
| IE75720B1 (en) * | 1990-10-08 | 1997-09-24 | Akzo Nv | Device for performing a rapid single manual assay |
| US6197556B1 (en) | 1991-12-20 | 2001-03-06 | The University Of Chicago | Nucleic acid amplification using modular branched primers |
| US6767510B1 (en) * | 1992-05-21 | 2004-07-27 | Biosite, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
| US6399397B1 (en) * | 1992-09-14 | 2002-06-04 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
| US5736410A (en) * | 1992-09-14 | 1998-04-07 | Sri International | Up-converting reporters for biological and other assays using laser excitation techniques |
| FR2720508B1 (en) * | 1994-05-25 | 1996-08-09 | Rech Developp Activ Commun | Method for detecting an analyte in a sample and device for implementing the method. |
| EP0724909A1 (en) | 1994-11-28 | 1996-08-07 | Akzo Nobel N.V. | Sample collection device |
| IT1273506B (en) * | 1995-04-06 | 1997-07-08 | Scient Marketing Service S R L | DIAGNOSTIC TEST FOR THE QUICK AND SAFE DETECTION OF A CLINICAL MARKER FOR MENOPAUSE DIAGNOSIS IN WOMEN |
| US20010051350A1 (en) * | 1995-05-02 | 2001-12-13 | Albert Nazareth | Diagnostic detection device and method |
| US6391265B1 (en) * | 1996-08-26 | 2002-05-21 | Biosite Diagnostics, Inc. | Devices incorporating filters for filtering fluid samples |
| 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 |
| US6979576B1 (en) * | 1997-07-25 | 2005-12-27 | Shu-Ching Cheng | Methods of use of one step immunochromatographic device for Streptococcus A antigen |
| GB2322192B (en) * | 1997-02-14 | 2001-01-31 | Unilever Plc | Assay devices |
| US6103536A (en) * | 1997-05-02 | 2000-08-15 | Silver Lake Research Corporation | Internally referenced competitive assays |
| US5985675A (en) | 1997-12-31 | 1999-11-16 | Charm Sciences, Inc. | Test device for detection of an analyte |
| DE69841864D1 (en) | 1997-07-16 | 2010-10-07 | Charm Sciences Inc | Test device and method for detecting residual analytes in samples |
| US6437563B1 (en) | 1997-11-21 | 2002-08-20 | Quantum Design, Inc. | Method and apparatus for making measurements of accumulations of magnetically susceptible particles combined with analytes |
| US6306642B1 (en) * | 1997-11-24 | 2001-10-23 | Quidel Corporation | Enzyme substrate delivery and product registration in one step enzyme immunoassays |
| SE9704935D0 (en) * | 1997-12-30 | 1997-12-30 | Pharmacia & Upjohn Diag Ab | Method of analysis with particles |
| US6548309B1 (en) | 1998-03-19 | 2003-04-15 | Binax, Inc. | Procedure for assay of liquids containing undissolved solids, semisolids or colloids |
| US8062908B2 (en) | 1999-03-29 | 2011-11-22 | Orasure Technologies, Inc. | Device for collection and assay of oral fluids |
| EP1696236B1 (en) * | 1998-03-30 | 2014-07-16 | OraSure Technologies, Inc. | Collection device for assay of oral fluids |
| US6303081B1 (en) * | 1998-03-30 | 2001-10-16 | Orasure Technologies, Inc. | Device for collection and assay of oral fluids |
| BR9906351A (en) * | 1998-04-14 | 2000-09-19 | Otsuka Pharma Co Ltd | Antibody assay method and antibody assay device |
| AU8662598A (en) | 1998-07-22 | 2000-02-14 | Syntron Bioresearch, Inc. | Multiple analyte assay device |
| US6372514B1 (en) | 1998-09-18 | 2002-04-16 | Syntron Bioresearch, Inc. | Even fluid front for liquid sample on test strip device |
| US6140136A (en) * | 1998-09-18 | 2000-10-31 | Syntron Bioresearch, Inc. | Analytical test device and method of use |
| US6379620B1 (en) | 1998-11-16 | 2002-04-30 | Barry M. Tydings | Assaying device and method for in field urinalysis |
| US7297554B2 (en) * | 1998-11-18 | 2007-11-20 | Microdiagnostics, Inc. | Immunoassay system |
| EP1163513A1 (en) * | 1999-02-26 | 2001-12-19 | Fertility Acoustics Inc. | Analyzing strip having a fluid cell and a method of analyzing a sample |
| US6514769B2 (en) | 1999-07-29 | 2003-02-04 | Jin Po Lee | Multiple analyte assay device with sample integrity monitoring system |
| US6699507B1 (en) | 1999-08-05 | 2004-03-02 | Wisconsin Alulmni Research Foundation | Colloidal particles of different element composition for specific labeling purposes |
| US6727073B1 (en) | 1999-11-19 | 2004-04-27 | Binax, Inc. | Method for detecting enteric disease |
| DE10003734A1 (en) * | 2000-01-28 | 2001-08-02 | Bosch Gmbh Robert | Detection method and device |
| 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 |
| CA2437298A1 (en) * | 2000-02-23 | 2001-08-30 | Besst-Test Aps | Method for correlating blood coagulation activity with markers in body fluids, e.g. urine |
| CA2399202A1 (en) * | 2000-03-09 | 2001-09-13 | Heska Corporation | Use of recombinant antigens to determine the immune status of an animal |
| US6607922B2 (en) | 2000-03-17 | 2003-08-19 | Quantum Design, Inc. | Immunochromatographic assay method and apparatus |
| US6627459B1 (en) | 2000-04-19 | 2003-09-30 | Applied Biotech, Inc. | Immunoassay controls |
| US6706474B1 (en) | 2000-06-27 | 2004-03-16 | Board Of Trustees Of The University Of Illinois | Nucleic acid enzyme biosensors for ions |
| US6417082B1 (en) | 2000-08-30 | 2002-07-09 | Advanced Micro Devices, Inc. | Semiconductor structure |
| US6764825B1 (en) * | 2000-10-13 | 2004-07-20 | Tang J. Wang | Methods and device for detecting prostate specific antigen (PSA) |
| US7041787B2 (en) * | 2000-12-29 | 2006-05-09 | Kimberly-Clark Worldwide, Inc. | Design and use of advanced zinc chelating peptides to regulate matrix metalloproteinases |
| US6600057B2 (en) | 2000-12-29 | 2003-07-29 | Kimberly-Clark Worldwide, Inc. | Matrix metalloproteinase inhibitors |
| EP2214015B2 (en) | 2001-04-19 | 2023-12-27 | Adhesives Research, Inc. | Hydrophilic diagnostic devices for use in the assaying of biological fluids |
| US20050266499A1 (en) * | 2001-04-25 | 2005-12-01 | Rockeby Biomed Corporation, Ltd. | Method and apparatus for testing for presence or absence of select biological substances |
| US7300633B2 (en) * | 2001-07-25 | 2007-11-27 | Oakville Hong Kong Company Limited | Specimen collection container |
| EP1416276B1 (en) * | 2001-08-09 | 2007-03-07 | Matsushita Electric Industrial Co., Ltd. | Biosensors and measurement method |
| SE0103072D0 (en) * | 2001-09-17 | 2001-09-17 | Pharmacia Diagnostics Ab | Multi-analyte assay device with multi-spot detection zone |
| US7879293B2 (en) * | 2001-09-28 | 2011-02-01 | Orasure Technologies, Inc. | Sample collector and test device |
| US8481334B1 (en) | 2001-11-06 | 2013-07-09 | Charm Sciences, Inc. | Method of attaching a ligand to a solid support |
| US20030166301A1 (en) * | 2001-12-10 | 2003-09-04 | Wainer Irving W. | Multiple binding moiety chromatography device, methods of using and methods of making same |
| WO2003052379A2 (en) * | 2001-12-14 | 2003-06-26 | Integrated Biotechnology Corporation | Rapid immunoassay for rsv |
| US20030119073A1 (en) * | 2001-12-21 | 2003-06-26 | Stephen Quirk | Sensors and methods of detection for proteinase enzymes |
| US6837171B1 (en) | 2002-04-29 | 2005-01-04 | Palmer/Snyder Furniture Company | Lightweight table with unitized table top |
| US20030119203A1 (en) * | 2001-12-24 | 2003-06-26 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay devices and methods for conducting assays |
| US20050109951A1 (en) * | 2001-12-27 | 2005-05-26 | Falk Fish | Novel device, system and method for fluorescence detection |
| US20030162178A1 (en) * | 2002-02-25 | 2003-08-28 | O'hagan David | Variable microarray and methods of detecting one or more anlaytes in a sample |
| ATE309544T1 (en) * | 2002-04-09 | 2005-11-15 | Cholestech Corp | METHOD AND DEVICE FOR QUANTIFYING HIGH DENSITY LIPOPROTEIN-CHOLESTEROL |
| AU2003301457A1 (en) * | 2002-05-09 | 2004-05-04 | Keith Baumann | Bioweapon-detecting fibrous-network products and methods for making same |
| US7534560B2 (en) | 2002-05-10 | 2009-05-19 | The Board Of Trustees Of The University Of Illinois | Simple catalytic DNA biosensors for ions based on color changes |
| US6890719B2 (en) * | 2002-05-10 | 2005-05-10 | The Board Of Trustess Of The University Of Illinois | Fluorescence based biosensor |
| KR20050042264A (en) * | 2002-05-20 | 2005-05-06 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Methods and compositions for regulation and manipulation of steroidogenesis |
| ES2321696T3 (en) * | 2002-06-07 | 2009-06-10 | Cholestech Corporation | AUTOMATED CASTLE MODULE FOR AN APPLIANCE TO CARRY OUT IMMUNE TESTING AND USE OF IT. |
| US7238519B2 (en) * | 2002-06-07 | 2007-07-03 | Cholestech Corporation | Automated immunoassay cassette, apparatus and method |
| US20040018576A1 (en) * | 2002-07-24 | 2004-01-29 | Dematteo Todd M. | Bence Jones protein testing cassette |
| DE60332248D1 (en) | 2002-08-13 | 2010-06-02 | N Dia Inc | DEVICES AND METHOD FOR DETECTING FRUIT WATER IN VAGINAL SECRETS |
| US7285424B2 (en) | 2002-08-27 | 2007-10-23 | Kimberly-Clark Worldwide, Inc. | Membrane-based assay devices |
| US7432105B2 (en) * | 2002-08-27 | 2008-10-07 | Kimberly-Clark Worldwide, Inc. | Self-calibration system for a magnetic binding assay |
| US20040092036A1 (en) * | 2002-09-11 | 2004-05-13 | Lattec I/S | Device for analysing analyte compounds and use hereof |
| AU2003274629B2 (en) * | 2002-10-11 | 2009-03-12 | Zbx Corporation | Diagnostic devices |
| AU2003304256A1 (en) * | 2002-11-20 | 2005-01-13 | Laser Light Technologies, Inc. | An online flow through microchip for detecting hazardous chemical and biological agents in drinking water |
| US7781172B2 (en) | 2003-11-21 | 2010-08-24 | Kimberly-Clark Worldwide, Inc. | Method for extending the dynamic detection range of assay devices |
| US20040121334A1 (en) * | 2002-12-19 | 2004-06-24 | Kimberly-Clark Worldwide, Inc. | Self-calibrated flow-through assay devices |
| US7560272B2 (en) * | 2003-01-04 | 2009-07-14 | Inverness Medical Switzerland Gmbh | Specimen collection and assay container |
| US20040220498A1 (en) * | 2003-01-24 | 2004-11-04 | Guann-Pyng Li | Micro medical-lab-on-a-chip in a lollipop as a drug delivery device and/or a health monitoring device |
| US7459314B2 (en) * | 2003-02-13 | 2008-12-02 | Inverness Medical Switzerland Gmbh | Lateral flow immunoassay controls |
| WO2004073492A2 (en) * | 2003-02-14 | 2004-09-02 | Massachusetts Eye And Ear Infirmary | Chlamydia pneumoniae associated chronic intraocular disorders and treatment thereof |
| US7612185B2 (en) * | 2003-03-07 | 2009-11-03 | The Board Of Trustees Of The University Of Illinois | Nucleic acid biosensors |
| WO2004081529A2 (en) * | 2003-03-10 | 2004-09-23 | Robinson Joseph R | Assay device and method |
| MXPA05011159A (en) * | 2003-04-14 | 2006-05-25 | Pathogen Removal And Diagnosti | Method for identifying ligands specific for structural isoforms of proteins. |
| US20040241879A1 (en) * | 2003-06-02 | 2004-12-02 | Robinson Joseph R. | Assay device and method |
| US7393697B2 (en) * | 2003-06-06 | 2008-07-01 | Advantage Diagnostics Corporation | Diagnostic test for analytes in a sample |
| US7517495B2 (en) * | 2003-08-25 | 2009-04-14 | Inverness Medical Switzerland Gmbh | Biological specimen collection and analysis system |
| WO2005021780A1 (en) * | 2003-09-02 | 2005-03-10 | Expressive Constructs, Inc. | Signal amplification using a synthetic zymogen |
| US7378285B2 (en) * | 2003-09-22 | 2008-05-27 | Paul Lambotte | Devices for the detection of multiple analytes in a sample |
| EP1522857A1 (en) * | 2003-10-09 | 2005-04-13 | Universiteit Maastricht | Method for identifying a subject at risk of developing heart failure by determining the level of galectin-3 or thrombospondin-2 |
| EP1692501B1 (en) | 2003-11-14 | 2016-01-06 | Alere Switzerland GmbH | Rapid sample analysis and storage devices and methods of use |
| US7713748B2 (en) | 2003-11-21 | 2010-05-11 | Kimberly-Clark Worldwide, Inc. | Method of reducing the sensitivity of assay devices |
| US7943395B2 (en) | 2003-11-21 | 2011-05-17 | Kimberly-Clark Worldwide, Inc. | Extension of the dynamic detection range of assay devices |
| US7410808B1 (en) | 2003-12-08 | 2008-08-12 | Charm Sciences, Inc. | Method and assay for detection of residues |
| US7485419B2 (en) * | 2004-01-13 | 2009-02-03 | The Board Of Trustees Of The University Of Illinois | Biosensors based on directed assembly of particles |
| DE602005016527D1 (en) * | 2004-02-09 | 2009-10-22 | Rapid Pathogen Screening Inc | METHOD FOR FAST DIAGNOSIS OF TARGETS IN HUMAN BODY FLUIDS |
| US20050191704A1 (en) * | 2004-03-01 | 2005-09-01 | Kimberly-Clark Worldwide, Inc. | Assay devices utilizing chemichromic dyes |
| JP2007530946A (en) * | 2004-03-23 | 2007-11-01 | クイデル コーポレイション | Hybrid phase lateral flow assay |
| CN100357738C (en) * | 2004-03-26 | 2007-12-26 | 博奥生物有限公司 | Method of detecting small molecule compound and its special biochip |
| CA2563347C (en) | 2004-04-20 | 2014-01-14 | Genzyme Corporation | Surgical mesh-like implant |
| US7241417B2 (en) * | 2004-07-29 | 2007-07-10 | Savyon Diagnostics Ltd. | Assay device |
| US20060040258A1 (en) * | 2004-08-23 | 2006-02-23 | Huiyan Guo | Water-soluble conjugates and methods of preparation |
| US20060046310A1 (en) * | 2004-08-25 | 2006-03-02 | Zong-Li Xia | Amplification method for solid phase immunoassays |
| US20060094026A1 (en) * | 2004-11-03 | 2006-05-04 | Yi Lu | Nucleic acid enzyme light-up sensor utilizing invasive DNA |
| US7465587B2 (en) * | 2004-12-03 | 2008-12-16 | Genzyme Corporation | Diagnostic assay device |
| US7925445B2 (en) * | 2004-12-03 | 2011-04-12 | Alverix, Inc. | Read-write assay system |
| US7387890B2 (en) * | 2004-12-16 | 2008-06-17 | Chembio Diagnostic Systems, Inc. | Immunoassay devices and use thereof |
| US8118740B2 (en) * | 2004-12-20 | 2012-02-21 | Ipventure, Inc. | Moisture sensor for skin |
| US8734341B2 (en) * | 2004-12-20 | 2014-05-27 | Ipventure, Inc. | Method and apparatus to sense hydration level of a person |
| US8202217B2 (en) | 2004-12-20 | 2012-06-19 | Ip Venture, Inc. | Healthcare base |
| US10258278B2 (en) | 2004-12-20 | 2019-04-16 | Ipventure, Inc. | Method and apparatus to sense hydration level of a person |
| US11013461B2 (en) | 2004-12-20 | 2021-05-25 | Ipventure, Inc. | Method and apparatus for hydration level of a person |
| US20060154260A1 (en) * | 2005-01-07 | 2006-07-13 | Barbour William M | Sample preparation methods for diagnostic analyses |
| US7629127B2 (en) * | 2005-01-21 | 2009-12-08 | Dexall Biomedical Labs, Inc. | Method for the visual detection of specific antibodies by the use of lateral flow assays |
| US20060166222A1 (en) * | 2005-01-21 | 2006-07-27 | Yi Lu | Nucleic acid enzyme ligation sensor |
| US9101927B2 (en) * | 2005-01-31 | 2015-08-11 | Realbio Technologies Ltd. | Multistep reaction lateral flow capillary device |
| US8445293B2 (en) | 2005-02-09 | 2013-05-21 | Rapid Pathogen Screening, Inc. | Method to increase specificity and/or accuracy of lateral flow immunoassays |
| WO2006088904A2 (en) * | 2005-02-16 | 2006-08-24 | Ping Gao | Fecal sample test device and methods of use |
| WO2006098804A2 (en) | 2005-03-11 | 2006-09-21 | Chembio Diagnostic Systems, Inc. | Dual path immunoassay device |
| US7189522B2 (en) | 2005-03-11 | 2007-03-13 | Chembio Diagnostic Systems, Inc. | Dual path immunoassay device |
| US20060205090A1 (en) * | 2005-03-14 | 2006-09-14 | Newton Michael W | Water-soluble conjugates for electrochemical detection |
| CN101151532B (en) * | 2005-03-29 | 2012-12-12 | 美艾利尔瑞士公司 | Colloidal metal conjugates |
| US7939342B2 (en) | 2005-03-30 | 2011-05-10 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits employing an internal calibration system |
| EP1872136B9 (en) | 2005-04-04 | 2023-02-08 | Biogen MA Inc. | Methods and products for evaluating an immune response to a therapeutic protein |
| US20060246599A1 (en) * | 2005-04-29 | 2006-11-02 | Sarah Rosenstein | Lateral flow device |
| US7439079B2 (en) | 2005-04-29 | 2008-10-21 | Kimberly-Clark Worldwide, Inc. | Assay devices having detection capabilities within the hook effect region |
| US7803319B2 (en) * | 2005-04-29 | 2010-09-28 | Kimberly-Clark Worldwide, Inc. | Metering technique for lateral flow assay devices |
| WO2006119203A2 (en) * | 2005-04-29 | 2006-11-09 | Beckman Coulter | Fluorescence lateral flow immunoassay |
| US20060246574A1 (en) * | 2005-04-29 | 2006-11-02 | Sarah Rosenstein | Dispenser for making a lateral flow device |
| US7858384B2 (en) * | 2005-04-29 | 2010-12-28 | Kimberly-Clark Worldwide, Inc. | Flow control technique for assay devices |
| US7648844B2 (en) | 2005-05-02 | 2010-01-19 | Bioscale, Inc. | Method and apparatus for detection of analyte using an acoustic device |
| US7749445B2 (en) | 2005-05-02 | 2010-07-06 | Bioscale, Inc. | Method and apparatus for analyzing bioprocess fluids |
| EP1891447B1 (en) * | 2005-05-23 | 2011-07-06 | Phadia AB | Two step lateral flow assay methods and devices |
| US20070020699A1 (en) * | 2005-07-19 | 2007-01-25 | Idexx Laboratories, Inc. | Lateral flow assay and device using magnetic particles |
| US7892734B2 (en) * | 2005-08-11 | 2011-02-22 | The Board Of Trustees Of The University Of Illinois | Aptamer based colorimetric sensor systems |
| US20080280290A1 (en) * | 2005-08-19 | 2008-11-13 | Dawson Elliott P | Method and Device for the Collection and Isolation of Nucleic Acid |
| US20070042504A1 (en) * | 2005-08-22 | 2007-02-22 | Yimin Yu | Method for determining substance or substances in liquid sample |
| US8003399B2 (en) * | 2005-08-31 | 2011-08-23 | Kimberly-Clark Worldwide, Inc. | Nitrite detection technique |
| US7504235B2 (en) * | 2005-08-31 | 2009-03-17 | Kimberly-Clark Worldwide, Inc. | Enzyme detection technique |
| US7829347B2 (en) * | 2005-08-31 | 2010-11-09 | Kimberly-Clark Worldwide, Inc. | Diagnostic test kits with improved detection accuracy |
| US7344893B2 (en) * | 2005-10-13 | 2008-03-18 | Auric Enterprises, Llc | Immuno-gold lateral flow assay |
| US20070092978A1 (en) * | 2005-10-20 | 2007-04-26 | Ronald Mink | Target ligand detection |
| JP2009524799A (en) | 2005-11-30 | 2009-07-02 | インバーネス・メデイカル・スウイツツアーランド・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング | Apparatus and method for detecting the presence or amount of an analyte in a fluid sample |
| 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 |
| US7871568B2 (en) * | 2006-01-23 | 2011-01-18 | Quidel Corporation | Rapid test apparatus |
| US7794656B2 (en) * | 2006-01-23 | 2010-09-14 | Quidel Corporation | Device for handling and analysis of a biological sample |
| WO2007090058A2 (en) * | 2006-01-27 | 2007-08-09 | Oxonica, Inc. | Lateral flow immunoassay with encapsulated detection modality |
| US20070202561A1 (en) * | 2006-02-10 | 2007-08-30 | Becton Dickinson And Company | Electronic Detection Immunoassays that Utilize a Binder Support Medium |
| AU2007217765A1 (en) * | 2006-02-21 | 2007-08-30 | Nanogen, Inc. | Methods and compositions for analyte detection |
| PL2676967T3 (en) | 2006-02-28 | 2019-12-31 | Biogen Ma Inc. | Methods of treating inflammatory and autoimmune diseases with natalizumab |
| KR20080104343A (en) | 2006-03-03 | 2008-12-02 | 엘란 파마슈티칼스, 인크. | Methods of treating inflammatory and autoimmune diseases with natalizumab |
| US7799554B2 (en) * | 2006-03-16 | 2010-09-21 | The Board Of Trustees Of The University Of Illinois | Lateral flow devices |
| DE112006003813T5 (en) | 2006-03-20 | 2009-01-22 | Inverness Medical Switzerland Gmbh | Water-soluble conjugates for electrochemical detection |
| US7473563B2 (en) * | 2006-04-03 | 2009-01-06 | The Clorox Company | Environmental sampling and testing device |
| US7498177B2 (en) * | 2006-04-24 | 2009-03-03 | Jesus Martinez De La Fuente | Quantum dots and their uses |
| US7547557B2 (en) * | 2006-06-13 | 2009-06-16 | Quantum Design, Inc. | Directed-flow assay device |
| US20080014657A1 (en) * | 2006-07-12 | 2008-01-17 | Beckton Dickinson And Company | Use of Albumin, Bovine, P-Aminophenyl N-Acetyl B-D Glucosaminide as a Control Line for an Immunoassay Device |
| CA2658795A1 (en) | 2006-07-26 | 2008-02-07 | Abon Biopharm (Hangzhou) Co., Ltd. | A test device for detecting an analyte in a liquid sample |
| EP2049261B1 (en) | 2006-07-28 | 2018-07-04 | Diagnostics for the Real World, Ltd | Device, system and method for processing a sample |
| WO2008021954A2 (en) * | 2006-08-09 | 2008-02-21 | Biogen Idec Ma Inc. | Method for distribution of a drug |
| AU2007302626B2 (en) | 2006-09-28 | 2013-09-26 | The Macfarlane Burnet Institute For Medical Research And Public Health Limited | A method of diagnosis and kit therefor |
| US7749775B2 (en) * | 2006-10-03 | 2010-07-06 | Jonathan Scott Maher | Immunoassay test device and method of use |
| US8044257B2 (en) * | 2006-10-30 | 2011-10-25 | Kimberly-Clark Worldwide, Inc. | Absorbent article containing lateral flow assay device |
| WO2008061130A2 (en) * | 2006-11-15 | 2008-05-22 | Ucp Biosciences, Inc. | An improved collecting and testing device and method of use |
| US20080138842A1 (en) * | 2006-12-11 | 2008-06-12 | Hans Boehringer | Indirect lateral flow sandwich assay |
| US8012761B2 (en) * | 2006-12-14 | 2011-09-06 | Kimberly-Clark Worldwide, Inc. | Detection of formaldehyde in urine samples |
| US7846383B2 (en) * | 2006-12-15 | 2010-12-07 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay device and absorbent article containing same |
| US7935538B2 (en) * | 2006-12-15 | 2011-05-03 | Kimberly-Clark Worldwide, Inc. | Indicator immobilization on assay devices |
| US8377379B2 (en) * | 2006-12-15 | 2013-02-19 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay device |
| US7824879B2 (en) * | 2007-01-09 | 2010-11-02 | Cholestech Corporation | Device and method for measuring LDL-associated cholesterol |
| WO2008089248A2 (en) * | 2007-01-19 | 2008-07-24 | The Board Of Trustees Of The University Of Illinois | Amphiphilic substances and triggered liberation from lipid vesicles |
| GB0701253D0 (en) | 2007-01-23 | 2007-02-28 | Diagnostics For The Real World | Nucleic acid amplification and testing |
| US7776618B2 (en) * | 2007-03-01 | 2010-08-17 | Church & Dwight Co., Inc. | Diagnostic detection device |
| US8058415B2 (en) | 2007-04-24 | 2011-11-15 | The Board Of Trustees Of The University Of Illinois | Aptamer- and nucleic acid enzyme-based systems for simultaneous detection of multiple analytes |
| JP5214723B2 (en) | 2007-04-30 | 2013-06-19 | ナノゲン・インコーポレイテッド | Multi-analyte assay |
| ES2609818T3 (en) | 2007-06-15 | 2017-04-24 | Xiamen University | Monoclonal antibodies that bind to H5 subtype avian influenza virus hemagglutinin and uses thereof |
| GB2450351B (en) | 2007-06-20 | 2012-01-18 | Cozart Bioscience Ltd | Monitoring an Immunoassay |
| US8399261B2 (en) * | 2007-06-27 | 2013-03-19 | Inbios International, Inc. | Lateral flow assay system and methods for its use |
| WO2009012309A2 (en) * | 2007-07-16 | 2009-01-22 | The Board Of Trustees Of The University Of Illinois | Nucleic acid based fluorescent sensor for divalent copper ion detection |
| CA2694045C (en) * | 2007-07-26 | 2016-06-21 | Agamatrix, Inc. | Electrochemical analyte detection apparatus and method |
| US8568690B2 (en) * | 2007-07-31 | 2013-10-29 | The Board Of Trustees Of The University Of Illinois | MRI contrast agents and high-throughput screening by MRI |
| WO2009045632A2 (en) | 2007-08-10 | 2009-04-09 | The Board Of Trustees Of The University Of Illinois | Nucleic acid based fluorescent sensor for mercury detection |
| US9707556B2 (en) | 2007-08-17 | 2017-07-18 | Diagnostics For The Real World, Ltd. | Device, system and method for processing a sample |
| EP2255195A2 (en) | 2007-09-03 | 2010-12-01 | Protagen AG | Marker sequences for rheumatoid arthritis and use thereof |
| DE102007041657A1 (en) | 2007-09-03 | 2009-03-05 | Protagen Ag | Marker sequences for multiple sclerosis and their use |
| US8354280B2 (en) | 2007-09-06 | 2013-01-15 | Bioscale, Inc. | Reusable detection surfaces and methods of using same |
| WO2009034563A2 (en) * | 2007-09-14 | 2009-03-19 | Nanocomms Patents Limited | An analysis system |
| AU2008302367B2 (en) * | 2007-09-17 | 2013-10-03 | Red Ivory Llc | Self-actuating signal producing detection devices and methods |
| CN101836114B (en) * | 2007-10-23 | 2013-09-11 | 斯坎内克斯公司 | Immunoassay analysis method |
| US8053203B2 (en) * | 2007-10-30 | 2011-11-08 | John Wan | Methods and device for the detection of occult blood |
| EP2212698B1 (en) * | 2007-11-14 | 2014-01-08 | Nigel Robert Caterer | Methods of quantification for lateral flow devices |
| US9274056B2 (en) | 2007-12-03 | 2016-03-01 | Robert Hudak | Use of non-chelated fluorochromes in rapid test systems |
| US20090208975A1 (en) * | 2007-12-13 | 2009-08-20 | Beckman Coulter, Inc. | Device and methods for detecting a target cell |
| BRPI0906060A2 (en) | 2008-02-28 | 2015-12-01 | 3M Innovative Properties Co | isolated antibodies, methods of preparing an anti-clostridium difficile antibody, composition and method for detecting the presence of a clostridium difficile spore in a sample |
| WO2009126735A1 (en) | 2008-04-09 | 2009-10-15 | Becton Dickinson And Company | Sensitive immunoassays using coated nanoparticles |
| US20100105039A1 (en) * | 2008-06-03 | 2010-04-29 | Yi Lu | Label-free colorimetric detection |
| EP2326419B1 (en) | 2008-06-29 | 2021-04-07 | Realbio Technologies Ltd. | Liquid transfer device particularly useful as a capturing device in a biological assay process |
| GB2463549B (en) | 2008-07-15 | 2011-11-23 | L3 Technology Ltd | Assay device containing amphipathic polymers |
| US20100022916A1 (en) * | 2008-07-24 | 2010-01-28 | Javanbakhsh Esfandiari | Method and Apparatus for Collecting and Preparing Biological Samples for Testing |
| US20100024530A1 (en) * | 2008-07-29 | 2010-02-04 | Hopkins Ii Robert E | Lateral Flow Devices |
| GB0814570D0 (en) | 2008-08-08 | 2008-09-17 | Diagnostics For The Real World | Isolation of nucleic acid |
| US8062893B2 (en) | 2008-10-10 | 2011-11-22 | The Board Of Trustees Of The University Of Illinois | Fluorescent sensor for mercury |
| WO2010096126A1 (en) * | 2008-10-29 | 2010-08-26 | Bg Medicine, Inc. | Galectin-3 immunoassay |
| US9234889B1 (en) | 2008-12-18 | 2016-01-12 | Charm Sciences, Inc. | Method and test strip for detecting residues |
| CA2751161C (en) | 2008-12-30 | 2018-10-02 | Children's Medical Center Corporation | Method of predicting acute appendicitis |
| WO2010090810A2 (en) * | 2009-02-05 | 2010-08-12 | Hydradx, Inc. | Diagnostic device and method |
| DE102009010563A1 (en) | 2009-02-16 | 2010-08-26 | Matthias W. Engel | Device for the detection of analytes in body fluids |
| CN102414561A (en) * | 2009-04-28 | 2012-04-11 | 创新实验室技术公司 | Lateral-flow immuno-chromatographic assay devices |
| US9085798B2 (en) | 2009-04-30 | 2015-07-21 | Prognosys Biosciences, Inc. | Nucleic acid constructs and methods of use |
| US20100290948A1 (en) * | 2009-05-15 | 2010-11-18 | Xuedong Song | Absorbent articles capable of indicating the presence of urinary tract infections |
| US8802427B2 (en) * | 2009-06-09 | 2014-08-12 | Church & Dwight Co., Inc. | Female fertility test |
| EP2470911B1 (en) | 2009-08-25 | 2016-04-20 | BG Medicine, Inc. | Galectin-3 and cardiac resynchronization therapy |
| EP2485762B1 (en) | 2009-10-11 | 2017-12-13 | Biogen MA Inc. | Anti-vla-4 related assays |
| CN102782495B (en) | 2009-11-04 | 2014-12-31 | 托马斯·M·布坎南 | Methods and devices to enhance sensitivity and evaluate sample adequacy and reagent reactivity in rapid lateral flow immunoassays |
| US11287423B2 (en) | 2010-01-11 | 2022-03-29 | Biogen Ma Inc. | Assay for JC virus antibodies |
| ES2930469T3 (en) | 2010-01-11 | 2022-12-14 | Biogen Ma Inc | Assay for jc virus antibodies |
| CN105044320B (en) | 2010-03-25 | 2017-02-22 | 艾博生物医药(杭州)有限公司 | Detection apparatus for testing to-be-analyzed substance in liquid sample |
| US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
| ES2555106T3 (en) | 2010-04-05 | 2015-12-29 | Prognosys Biosciences, Inc. | Spatially coded biological assays |
| US20190300945A1 (en) | 2010-04-05 | 2019-10-03 | Prognosys Biosciences, Inc. | Spatially Encoded Biological Assays |
| AU2011236503B2 (en) | 2010-04-07 | 2014-10-30 | Biosensia Patents Limited | Flow control device for assays |
| ES2945032T3 (en) | 2010-05-06 | 2023-06-28 | Charm Sciences Inc | Incubator device with reader |
| WO2012003475A1 (en) | 2010-07-02 | 2012-01-05 | Bg Medicine, Inc. | Statin therapy monitored by galectin- 3 measurement |
| US8815156B2 (en) | 2010-07-19 | 2014-08-26 | Andalyze, Inc. | Sensor housing and reagent chemistry |
| US8956859B1 (en) | 2010-08-13 | 2015-02-17 | Aviex Technologies Llc | Compositions and methods for determining successful immunization by one or more vaccines |
| US9110053B2 (en) * | 2010-08-20 | 2015-08-18 | Agilent Technologies, Inc. | Dried blood spotting paper device and method |
| EP2619316B1 (en) | 2010-09-23 | 2016-12-07 | Woundchek Laboratories B.V. | Ultrasensitive detection of beta hemolytic streptococcus |
| CA2813417A1 (en) | 2010-09-30 | 2012-04-05 | Hydradx, Inc. | Diagnostic device and method for sensing hydration state of a mammalian subject |
| US8828329B2 (en) | 2010-10-01 | 2014-09-09 | Church & Dwight, Co., Inc. | Electronic analyte assaying device |
| DE102011086568A1 (en) | 2010-11-17 | 2012-05-24 | fzmb GmbH, Forschungszentrum für Medizintechnik und Biotechnologie | Amplifying signals in heterogeneous binding assays based on donor or receptor complex, comprises adding particle of first particle class and particle of second particle class to donor or receptor complex and optionally repeating steps |
| US8486717B2 (en) | 2011-01-18 | 2013-07-16 | Symbolics, Llc | Lateral flow assays using two dimensional features |
| JP2014505256A (en) | 2011-01-31 | 2014-02-27 | ビージー メディシン， インコーポレイテッド | Use of galectin-3 to detect heart failure after acute coronary syndrome and determine prognosis |
| WO2012109258A2 (en) * | 2011-02-07 | 2012-08-16 | University Of Florida Research Foundation, Inc. | Compositions adn methods for monitoring oxalate |
| US20120202297A1 (en) * | 2011-02-08 | 2012-08-09 | Hello Baby F.S.T. Llc | Gender determination method |
| US8603835B2 (en) | 2011-02-10 | 2013-12-10 | Chembio Diagnostic Systems, Inc. | Reduced step dual path immunoassay device and method |
| EP2487490A1 (en) | 2011-02-11 | 2012-08-15 | FZMB GmbH Forschungszentrum für Medizintechnik und Biotechnologie | Heterogeneous binding assays with improved optical ability to be evaluated or porous fixed phase for same |
| EP2677315A1 (en) * | 2011-02-15 | 2013-12-25 | Takahito Matumura | Urine test sheet |
| EP2694967A4 (en) | 2011-04-06 | 2014-10-29 | Ortho Clinical Diagnostics Inc | Assay device having rhombus-shaped projections |
| WO2012139110A2 (en) | 2011-04-08 | 2012-10-11 | Prognosys Biosciences, Inc. | Peptide constructs and assay systems |
| GB201106254D0 (en) | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
| WO2012151465A1 (en) | 2011-05-04 | 2012-11-08 | Pop Test, Llc | Diagnostic device |
| AR086543A1 (en) | 2011-05-25 | 2014-01-08 | Bg Medicine Inc | GALECTIN-3 INHIBITORS AND METHODS OF USE OF THE SAME, PHARMACEUTICAL COMPOSITION |
| US20130089858A1 (en) | 2011-09-16 | 2013-04-11 | Winston Wong, JR. | Molecular diagnostic assay device and method of use |
| US8987174B2 (en) | 2011-10-28 | 2015-03-24 | Prognosys Biosciences, Inc. | Methods for manufacturing molecular arrays |
| US8999728B2 (en) | 2011-12-21 | 2015-04-07 | Church & Dwight Co., Inc. | Diagnostic detection device |
| CN105833925B (en) | 2011-12-22 | 2018-11-13 | 瑞尔比奥技术有限公司 | sequential lateral flow capillary device for analyte determination |
| US20130171619A1 (en) | 2011-12-30 | 2013-07-04 | General Electric Company | Porous membranes having a hydrophilic coating and methods for their preparation and use |
| CA2862830A1 (en) | 2012-01-06 | 2013-07-11 | Bg Medicine, Inc. | Use of galectin-3 for risk assessment and detection of preeclampsia and related conditions |
| CA2802645C (en) | 2012-01-20 | 2020-08-11 | Ortho-Clinical Diagnostics, Inc. | Assay device having controllable sample size |
| US20130210036A1 (en) | 2012-01-20 | 2013-08-15 | Ortho-Clinical Diagnostics, Inc. | Controlling Fluid Flow Through An Assay Device |
| WO2013109821A1 (en) | 2012-01-20 | 2013-07-25 | Ortho-Clinical Diagnostics, Inc. | Assay device having multiplexing |
| EP2618150B1 (en) | 2012-01-20 | 2016-07-27 | Ortho-Clinical Diagnostics, Inc. | Assay device having multiple reagent cells |
| KR20130085991A (en) | 2012-01-20 | 2013-07-30 | 오르토-클리니칼 다이아그노스틱스, 인코포레이티드 | Assay device having uniform flow around corners |
| US9651508B2 (en) | 2012-01-31 | 2017-05-16 | Regents Of The University Of Minnesota | Thermal contrast assay and reader |
| US10725033B2 (en) | 2012-01-31 | 2020-07-28 | Regents Of The University Of Minnesota | Lateral flow assays with thermal contrast readers |
| US10816492B2 (en) | 2012-01-31 | 2020-10-27 | Regents Of The University Of Minnesota | Lateral flow assays with thermal contrast readers |
| WO2013134503A2 (en) | 2012-03-09 | 2013-09-12 | Invisible Sentinel, Inc. | Methods And Compositions For Detecting Multiple Analytes With A Single Signal |
| KR101360829B1 (en) * | 2012-03-15 | 2014-02-11 | (주)나비바이오텍 | Colored Particle Immunoassay Test Device |
| EP2831275A1 (en) | 2012-03-27 | 2015-02-04 | Protagen AG | Marker sequences for rheumatoid arthritis |
| EP2644704A1 (en) | 2012-03-27 | 2013-10-02 | Protagen AG | Marker sequences for rheumatoid arthritis |
| US10119968B2 (en) | 2012-06-02 | 2018-11-06 | Test Anywhere Technology | Self-contained diagnostic test with advanceable test strip |
| US9651549B2 (en) | 2012-07-13 | 2017-05-16 | Genisphere, Llc | Lateral flow assays using DNA dendrimers |
| US9874556B2 (en) | 2012-07-18 | 2018-01-23 | Symbolics, Llc | Lateral flow assays using two dimensional features |
| EP2689729A1 (en) | 2012-07-23 | 2014-01-29 | DML - ABLogics Limited | Disposable test device |
| US9611332B2 (en) | 2012-08-21 | 2017-04-04 | Janssen Pharmaceutica Nv | Antibodies to aripiprazole haptens and use thereof |
| US9751953B2 (en) | 2012-08-21 | 2017-09-05 | Janssen Pharmaceutica Nv | Antibodies to risperidone haptens and use thereof |
| AU2013305965B2 (en) | 2012-08-21 | 2017-08-24 | Saladax Biomedical Inc. | Antibodies to paliperidone and use thereof |
| AU2013305895B2 (en) | 2012-08-21 | 2017-10-19 | Saladax Biomedical Inc. | Antibodies to olanzapine haptens and use thereof |
| PT2888286T (en) | 2012-08-21 | 2018-05-09 | Janssen Pharmaceutica Nv | Antibodies to quetiapine haptens and use thereof |
| CN109970637B (en) | 2012-08-21 | 2022-04-19 | 詹森药业有限公司 | Aripiprazole hapten and application thereof in immunoassay |
| JP2015529199A (en) | 2012-08-21 | 2015-10-05 | オルソ−クリニカル ダイアグノスティクス，インコーポレイティド | Antibodies against paliperidone hapten and use thereof |
| ES2762105T3 (en) | 2012-08-21 | 2020-05-22 | Janssen Pharmaceutica Nv | Antibodies to aripiprazole and use thereof |
| CN104755929B (en) | 2012-08-21 | 2016-11-09 | 奥索临床诊断有限公司 | Antibody of quetiapine and application thereof |
| JP6339569B2 (en) | 2012-08-21 | 2018-06-06 | ヤンセン ファーマシューティカ エヌ．ベー． | Antibody to risperidone and use thereof |
| PL2888590T3 (en) | 2012-08-21 | 2020-11-30 | Janssen Pharmaceutica Nv | Antibodies to olanzapine and use thereof |
| US20140072959A1 (en) | 2012-09-12 | 2014-03-13 | Force Diagnostics, Inc. | Rapid tests for insurance underwriting |
| EP2920591A4 (en) | 2012-11-15 | 2016-10-19 | Ortho Clinical Diagnostics Inc | Calibrating assays using reaction time |
| RU2013150854A (en) * | 2012-11-15 | 2015-05-20 | Орто-Клиникал Дайэгностикс, Инк. | QUALITY CONTROL / OPERATION OF THE DEVICE FOR LATERAL FLOW-THROUGH ANALYSIS BASED ON THE FLOW MONITORING |
| EP3637105A3 (en) | 2013-01-02 | 2020-07-29 | Qiagen Sciences, LLC | Methods for predicting time-to-delivery in pregnant women |
| US8968677B2 (en) | 2013-01-22 | 2015-03-03 | Quantum Design International, Inc. | Frazil ice conjugate assay device and method |
| CA2841692C (en) | 2013-02-12 | 2023-08-22 | Zhong Ding | Reagent zone deposition pattern |
| WO2014134033A1 (en) | 2013-02-26 | 2014-09-04 | Astute Medical, Inc. | Lateral flow assay with test strip retainer |
| JP2016510991A (en) | 2013-03-11 | 2016-04-14 | エリテックグループ・ベスローテン・フェンノートシャップＥｌｉｔｅｃｈｇｒｏｕｐ Ｂ．Ｖ． | Method for accurate strand displacement isothermal amplification |
| AU2014241791B2 (en) | 2013-03-13 | 2018-04-12 | Church & Dwight Co., Inc. | Diagnostic test device with audible feedback |
| EP2778679B1 (en) | 2013-03-15 | 2017-09-27 | Ortho-Clinical Diagnostics, Inc. | Rotable disk-shaped fluid sample collection device |
| EP2777499B1 (en) | 2013-03-15 | 2015-09-16 | Ortho-Clinical Diagnostics Inc | Rotatable fluid sample collection device |
| CN105358984B (en) | 2013-03-15 | 2020-02-18 | 普罗格诺西斯生物科学公司 | Methods for detecting peptide/MHC/TCR binding |
| US9151754B2 (en) | 2013-03-15 | 2015-10-06 | Church & Dwight Co., Inc. | Diagnostic test device with improved structure |
| KR101562946B1 (en) | 2013-04-23 | 2015-10-26 | 주식회사 수젠텍 | Devices and Methods for Detecting Analytes in Samples |
| EP3004334A4 (en) | 2013-05-28 | 2016-12-21 | Biogen Ma Inc | Method of assessing risk of pml |
| US20160113911A1 (en) | 2013-06-06 | 2016-04-28 | The General Hospital Corporation | Methods and compositions for the treatment of cancer |
| WO2014210225A1 (en) | 2013-06-25 | 2014-12-31 | Prognosys Biosciences, Inc. | Methods and systems for determining spatial patterns of biological targets in a sample |
| EP2837939A1 (en) | 2013-08-13 | 2015-02-18 | Technische Universität München | Method for the detection of H.pylori infection |
| CN108051590B (en) | 2013-09-13 | 2020-12-11 | Symbolics有限责任公司 | Lateral flow assay using two-dimensional test and control signal readout modes |
| CA2928779A1 (en) | 2013-10-21 | 2015-04-30 | The General Hospital Corporation | Methods relating to circulating tumor cell clusters and the treatment of cancer |
| FR3012982B1 (en) * | 2013-11-08 | 2015-12-25 | Espci Innov | METHOD FOR STORING AND CONCENTRATING A VOLATILE COMPOUND |
| US10288608B2 (en) | 2013-11-08 | 2019-05-14 | Prognosys Biosciences, Inc. | Polynucleotide conjugates and methods for analyte detection |
| JP6651448B2 (en) | 2013-12-06 | 2020-02-19 | オーソ−クリニカル・ダイアグノスティックス・インコーポレイテッドＯｒｔｈｏ−Ｃｌｉｎｉｃａｌ Ｄｉａｇｎｏｓｔｉｃｓ， Ｉｎｃ． | Assay device with wash port |
| WO2015095527A1 (en) | 2013-12-20 | 2015-06-25 | The General Hosptial Corporation | Methods and assays relating to circulating tumor cells |
| US10416158B2 (en) | 2014-03-11 | 2019-09-17 | Wisconsin Alumni Research Foundation | Peptide MHCII tetramers to detect endogenous calnexin specific CD4 T cells |
| CA2944488C (en) | 2014-04-02 | 2023-03-21 | Chembio Diagnostic Systems, Inc. | Immunoassay utilizing trapping conjugate |
| US9606116B2 (en) | 2014-05-11 | 2017-03-28 | Lia Diagnostics, Inc. | Flexible, integrated urine-based diagnostic service |
| US9987633B2 (en) | 2014-06-09 | 2018-06-05 | 3M Innovative Properties Company | Assay devices and method of detecting a target analyte |
| US9903858B2 (en) | 2014-07-23 | 2018-02-27 | Ortho-Clinical Diagnostics, Inc. | Multiplexing with single sample metering event to increase throughput |
| US10071373B2 (en) | 2014-08-08 | 2018-09-11 | Ortho-Clinical Diagnostics, Inc. | Lateral-flow assay device having flow constrictions |
| US11033896B2 (en) | 2014-08-08 | 2021-06-15 | Ortho-Clinical Diagnostics, Inc. | Lateral-flow assay device with filtration flow control |
| US10073091B2 (en) | 2014-08-08 | 2018-09-11 | Ortho-Clinical Diagnostics, Inc. | Lateral flow assay device |
| KR20170072188A (en) | 2014-09-23 | 2017-06-26 | 티어랩 리서치, 인코포레이티드 | Systems and methods for integration of microfluidic tear collection and lateral flow analysis of analytes of interest |
| US20160116466A1 (en) | 2014-10-27 | 2016-04-28 | Chembio Diagnostic Systems, Inc. | Rapid Screening Assay for Qualitative Detection of Multiple Febrile Illnesses |
| WO2016094722A1 (en) | 2014-12-10 | 2016-06-16 | Xpecting Diagnostics, Inc. | Detection of analytes in bodily fluid to determine the initiation of parturition |
| US9476875B2 (en) | 2015-03-02 | 2016-10-25 | Chembio Diagnostic Systems, Inc. | Integrated buffer dual-path immunoassay device |
| US10557857B1 (en) | 2015-03-23 | 2020-02-11 | Intelligent Optical Systems, Inc. | System and method for bone loss assay |
| CN115728482A (en) | 2015-04-06 | 2023-03-03 | Blu诊断有限公司 | Detection device for detecting analyte in saliva sample and method of use |
| US9927443B2 (en) | 2015-04-10 | 2018-03-27 | Conquerab Inc. | Risk assessment for therapeutic drugs |
| EP3901281B1 (en) | 2015-04-10 | 2022-11-23 | Spatial Transcriptomics AB | Spatially distinguished, multiplex nucleic acid analysis of biological specimens |
| JP6728237B2 (en) | 2015-05-19 | 2020-07-22 | オーソ−クリニカル・ダイアグノスティックス・インコーポレイテッドＯｒｔｈｏ−Ｃｌｉｎｉｃａｌ Ｄｉａｇｎｏｓｔｉｃｓ， Ｉｎｃ． | Method for improving the flow of a liquid sample in an assay device |
| WO2017011727A1 (en) | 2015-07-15 | 2017-01-19 | GestVision, Inc. | Device for detecting misfolded proteins and methods of use therof |
| DK3785799T3 (en) | 2015-08-06 | 2023-03-06 | Lia Diagnostics Inc | METHODS OF MANUFACTURE FOR WATER DISPERSIBLE ASSAYS |
| JP6994461B2 (en) | 2015-12-17 | 2022-02-04 | ヤンセン ファーマシューティカ エヌ．ベー． | Antibodies to quetiapine and their use |
| EP3390449A1 (en) | 2015-12-17 | 2018-10-24 | Janssen Pharmaceutica N.V. | Antibodies to risperidone and use thereof |
| US11119102B1 (en) | 2016-02-16 | 2021-09-14 | Charm Sciences, Inc. | Test device, method, and assembly |
| EP3433377A4 (en) | 2016-03-23 | 2019-08-28 | The General Hospital Corporation | Assays and methods for detecting udp-glucose |
| EP3436828A1 (en) | 2016-04-02 | 2019-02-06 | Protagen AG | Marker sequences for rheumatoid arthritis |
| US9903866B2 (en) | 2016-04-05 | 2018-02-27 | Conquerab Inc. | Portable devices for detection of antibodies against therapeutic drugs |
| EP3258268A1 (en) | 2016-06-15 | 2017-12-20 | Protagen AG | Marker sequences for managing treatment of patients suffering from rheumatoid arthritis |
| EP3504551A1 (en) | 2016-08-23 | 2019-07-03 | Qoolabs, Inc. | Lateral flow assay for assessing recombinant protein expression or reporter gene expression |
| JP1577266S (en) * | 2016-09-16 | 2017-05-29 | ||
| US10935555B2 (en) | 2016-12-22 | 2021-03-02 | Qiagen Sciences, Llc | Determining candidate for induction of labor |
| US10656164B2 (en) | 2016-12-22 | 2020-05-19 | Qiagen Sciences, Llc | Screening asymptomatic pregnant woman for preterm birth |
| WO2018129261A1 (en) | 2017-01-05 | 2018-07-12 | Brown University | Methods and compositions relating to anti-chi3l1 antibody reagents |
| WO2018152496A1 (en) | 2017-02-17 | 2018-08-23 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Compositions and methods for the diagnosis and treatment of zika virus infection |
| EP4230649A3 (en) | 2017-04-25 | 2023-10-25 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of epstein barr virus infection |
| JP7257967B2 (en) | 2017-05-01 | 2023-04-14 | ザ チルドレンズ メディカル センター コーポレーション | Methods and compositions relating to anti-PD1 antibody reagents |
| WO2018222831A1 (en) | 2017-05-31 | 2018-12-06 | The Children's Medical Center Corporation | TARGETING LYSINE DEMETHYLASES (KDMs) AS A THERAPEUTIC STRATEGY FOR DIFFUSE LARGE B-CELL LYMPHOMA |
| WO2019018629A1 (en) | 2017-07-19 | 2019-01-24 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of hepatitis b virus infection |
| EP3732486A1 (en) | 2017-12-29 | 2020-11-04 | Proteostasis Therapeutics, Inc. | Methods of quantifying cftr protein expression |
| US20210171610A1 (en) | 2018-05-02 | 2021-06-10 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Antibodies and methods for the diagnosis, prevention, and treatment of epstein barr virus infection |
| US11293839B2 (en) | 2018-08-16 | 2022-04-05 | Epitope Biotechnology Co., Ltd. | Device for fecal sample collection and extraction |
| US11280788B2 (en) | 2019-01-31 | 2022-03-22 | Fresenius Medical Care Holdings, Inc. | Rapid diagnosis of peritonitis in peritoneal dialysis patients |
| CA3145278A1 (en) | 2019-07-26 | 2021-02-04 | Vanderbilt University | Human monoclonal antibodies to enterovirus d68 |
| EP3771908A1 (en) | 2019-07-29 | 2021-02-03 | Fundació Institut Català de Nanociència i Nanotecnologia (ICN2) | Lateral-electrophoretic bioassay |
| WO2021080629A1 (en) | 2019-10-23 | 2021-04-29 | Elitechgroup, Inc. | Methods for true isothermal strand displacement amplification |
| WO2021083983A1 (en) | 2019-10-29 | 2021-05-06 | Lifesure Limited | A lateral flow immunoassay, and uses thereof |
| AU2021220847A1 (en) | 2020-02-11 | 2022-09-01 | Vanderbilt University | Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) |
| US20230176054A1 (en) | 2020-03-20 | 2023-06-08 | Lumiradx Uk Ltd. | Coronavirus assay |
| WO2021195385A1 (en) | 2020-03-26 | 2021-09-30 | Vanderbilt University | HUMAN MONOCLONAL ANTIBODIES TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-GoV-2) |
| UY39135A (en) | 2020-03-26 | 2021-10-29 | Univ Vanderbilt | HUMAN MONOCLONAL ANTIBODIES TARGETED AGAINST SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-CoV-2) |
| US20210311043A1 (en) * | 2020-04-06 | 2021-10-07 | Medicortex Finland Oy | Method for determining a lectin-binding glycan indicative to traumatic brain injury |
| WO2021205228A1 (en) | 2020-04-07 | 2021-10-14 | Abbott Rapid Diagnostics International Unlimited Company | Assay device |
| EP4136459A1 (en) | 2020-04-13 | 2023-02-22 | Abbott Laboratories | Methods, complexes and kits for detecting or determining an amount of a ss-coronavirus antibody in a sample |
| AU2021261343A1 (en) | 2020-04-22 | 2022-11-03 | President And Fellows Of Harvard College | Isothermal methods, compositions, kits, and systems for detecting nucleic acids |
| EP3904879A1 (en) | 2020-04-27 | 2021-11-03 | Abacuslabs Ltd. | A method for distinguishing healthy individuals from individuals having infectious or inflammatory conditions |
| EP4153775A1 (en) | 2020-05-22 | 2023-03-29 | 10X Genomics, Inc. | Simultaneous spatio-temporal measurement of gene expression and cellular activity |
| US20230295274A1 (en) | 2020-07-27 | 2023-09-21 | Single Cell Technology, Inc. | Anti-sars coronavirus-2 spike protein antibodies |
| JP2023536737A (en) | 2020-08-04 | 2023-08-29 | アボット・ラピッド・ダイアグノスティクス・インターナショナル・アンリミテッド・カンパニー | Assays for detecting SARS-COV-2 |
| WO2022031804A1 (en) | 2020-08-04 | 2022-02-10 | Abbott Laboratories | Improved methods and kits for detecting sars-cov-2 protein in a sample |
| WO2022106537A1 (en) | 2020-11-20 | 2022-05-27 | Ams-Osram Ag | Test strip cassette, monitoring device and method for fabricating a test strip cassette |
| GB202105804D0 (en) | 2020-11-20 | 2021-06-09 | Univ Cape Town | Use of microvirin in the identification of mycobacterium tuberculosis mannose-capped lipoarabinomannan |
| EP4271998A1 (en) | 2020-12-30 | 2023-11-08 | Abbott Laboratories | Methods for determining sars-cov-2 antigen and anti-sars-cov-2 antibody in a sample |
| WO2022155410A1 (en) | 2021-01-15 | 2022-07-21 | President And Fellows Of Harvard College | Methods and compositions relating to anti-mfsd2a antibodies |
| AU2021359041A1 (en) | 2021-04-08 | 2022-10-27 | Abbott Rapid Diagnostics International Unlimited Company | Assay Device |
| SE2150815A1 (en) | 2021-06-23 | 2022-12-24 | SGPTH Life Science AB | Biglycan peptide and antibodies |
| WO2023028186A1 (en) | 2021-08-27 | 2023-03-02 | Abbott Laboratories | Methods for detecting immunoglobulin g, subclass 4 (igg4) in a biological sample |
| WO2023150652A1 (en) | 2022-02-04 | 2023-08-10 | Abbott Laboratories | Lateral flow methods, assays, and devices for detecting the presence or measuring the amount of ubiquitin carboxy-terminal hydrolase l1 and/or glial fibrillary acidic protein in a sample |
| EP4253567A1 (en) | 2022-03-31 | 2023-10-04 | OncoAssure Limited | A method of predicting risk of an aggressive or recurrent cancer |
| GB202204813D0 (en) | 2022-04-01 | 2022-05-18 | Bradcode Ltd | Human monoclonal antibodies and methods of use thereof |
Family Cites Families (135)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US30267A (en) * | 1860-10-02 | Bed-bottom | ||
| US5622871A (en) * | 1987-04-27 | 1997-04-22 | Unilever Patent Holdings B.V. | Capillary immunoassay and device therefor comprising mobilizable particulate labelled reagents |
| NL286850A (en) * | 1961-12-18 | 1900-01-01 | ||
| US3811840A (en) * | 1969-04-01 | 1974-05-21 | Miles Lab | Test device for detecting low concentrations of substances in fluids |
| IT1006557B (en) * | 1971-09-08 | 1976-10-20 | Bagshawe Kenneth Dawson | REACTION CELL PARTICULARLY USEFUL IN RADIOIMMUNITY TESTS |
| US4604364A (en) * | 1974-01-04 | 1986-08-05 | Kosak Kenneth M | Bioluminescent tracer composition and method of use in immunoassays |
| US4169138A (en) * | 1974-05-29 | 1979-09-25 | Pharmacia Diagnostics Ab | Method for the detection of antibodies |
| 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 |
| US4042335A (en) * | 1975-07-23 | 1977-08-16 | Eastman Kodak Company | Integral element for analysis of liquids |
| IL49685A (en) * | 1976-05-31 | 1978-10-31 | Technion Res & Dev Foundation | Specific binding assay method for determining the concentration of materials and reagent means therefor |
| US4094647A (en) | 1976-07-02 | 1978-06-13 | Thyroid Diagnostics, Inc. | Test device |
| US4045384A (en) * | 1976-07-23 | 1977-08-30 | The Dow Chemical Company | Method for forming an amide bond between a latex and protein |
| US4411518A (en) * | 1977-09-23 | 1983-10-25 | Gamma Biologicals, Inc. | Apparatus for use in qualitative determination of immunological reactions |
| US4219335A (en) * | 1978-09-18 | 1980-08-26 | E. I. Du Pont De Nemours And Company | Immunochemical testing using tagged reagents |
| AU527489B2 (en) | 1978-03-20 | 1983-03-10 | Abbott Laboratories | Sugar coated reagents for solid phase immunoassay |
| NL7807532A (en) * | 1978-07-13 | 1980-01-15 | Akzo Nv | METAL IMMUNO TEST. |
| US4258001A (en) * | 1978-12-27 | 1981-03-24 | Eastman Kodak Company | Element, structure and method for the analysis or transport of liquids |
| US4235601A (en) * | 1979-01-12 | 1980-11-25 | Thyroid Diagnostics, Inc. | Test device and method for its use |
| US4361537A (en) * | 1979-01-12 | 1982-11-30 | Thyroid Diagnostics, Inc. | Test device and method for its use |
| US4256834A (en) * | 1979-04-09 | 1981-03-17 | Syva Company | Fluorescent scavenger particle immunoassay |
| DE2916711A1 (en) * | 1979-04-25 | 1980-11-06 | Behringwerke Ag | Blood coagulation factors and process for their manufacture |
| US4294818A (en) * | 1979-07-30 | 1981-10-13 | University Patents, Inc. | Methods and materials for detection of multiple sclerosis |
| NL8000173A (en) * | 1980-01-11 | 1981-08-03 | Akzo Nv | USE OF WATER-DISPERSIBLE HYDROPHOBIC DYES AS LABELS IN IMMUNOCHEMICAL TESTS. |
| US4357142A (en) * | 1980-07-18 | 1982-11-02 | Akzona Incorporated | Glass support coated with synthetic polymer for bioprocess |
| US4376110A (en) * | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
| US4486530A (en) * | 1980-08-04 | 1984-12-04 | Hybritech Incorporated | Immunometric assays using monoclonal antibodies |
| DE3029579C2 (en) * | 1980-08-05 | 1985-12-12 | Boehringer Mannheim Gmbh, 6800 Mannheim | Method and means for separating plasma or serum from whole blood |
| US4366241A (en) * | 1980-08-07 | 1982-12-28 | Syva Company | Concentrating zone method in heterogeneous immunoassays |
| DE3044385A1 (en) | 1980-11-25 | 1982-06-24 | Boehringer Mannheim Gmbh, 6800 Mannheim | METHOD FOR CARRYING OUT ANALYTICAL PROVISIONS AND ROTOR INSERT ELEMENT SUITABLE FOR THIS |
| US4654309A (en) * | 1980-12-19 | 1987-03-31 | Minnesota Mining And Manufacturing Co. | Test method and article for estimating the concentration of free acid in liquid |
| US4348207A (en) * | 1981-01-29 | 1982-09-07 | Cooper Laboratories, Inc. | Method and means for determination of pregnancy |
| EP0063810B1 (en) | 1981-04-29 | 1986-03-05 | Ciba-Geigy Ag | New devices and kits for immunological analysis |
| IL63855A (en) * | 1981-09-16 | 1984-10-31 | Teva Pharma | Method and kit for detecting pregnancy |
| US4419453A (en) * | 1981-09-28 | 1983-12-06 | The Dow Chemical Company | Immunological agglutination assays with dyed or colored latex and kits |
| US4446232A (en) * | 1981-10-13 | 1984-05-01 | Liotta Lance A | Enzyme immunoassay with two-zoned device having bound antigens |
| US4434150A (en) * | 1981-10-19 | 1984-02-28 | Ortho Diagnostic Systems, Inc. | Immunological reagents employing polymeric backbone possessing reactive functional groups |
| US4639419A (en) * | 1981-10-22 | 1987-01-27 | Meloy Laboratories, Inc. | Immunological color change test involving two differently colored reagent spots |
| US5141875A (en) * | 1982-01-08 | 1992-08-25 | Environmental Diagnostics, Inc. | Rotary fluid manipulator |
| US5073484A (en) | 1982-03-09 | 1991-12-17 | Bio-Metric Systems, Inc. | Quantitative analysis apparatus and method |
| US4435504A (en) * | 1982-07-15 | 1984-03-06 | Syva Company | Immunochromatographic assay with support having bound "MIP" and second enzyme |
| US4503143A (en) * | 1982-08-20 | 1985-03-05 | Btc Diagnostics Limited Partnership | Enzyme immunoassay with two-part solution of tetramethylbenzidine as chromogen |
| US4459358A (en) * | 1982-12-29 | 1984-07-10 | Polaroid Corporation | Multilayer element for analysis |
| US4487839A (en) * | 1983-01-05 | 1984-12-11 | Ortho Diagnostic Systems Inc. | Immunoassay methods employing patterns for the detection of soluble and cell surface antigens |
| US4537861A (en) * | 1983-02-03 | 1985-08-27 | Elings Virgil B | Apparatus and method for homogeneous immunoassay |
| GB8305197D0 (en) | 1983-02-24 | 1983-03-30 | Amersham Int Plc | Assay methods |
| US4496654A (en) * | 1983-04-08 | 1985-01-29 | Quidel | Detection of HCG with solid phase support having avidin coating |
| USRE34405E (en) | 1983-08-01 | 1993-10-12 | Abbott Laboratories | Determination of analytes in particle-containing medium |
| US4552839A (en) * | 1983-08-01 | 1985-11-12 | Syntex (U.S.A.) Inc. | Determination of analytes in particle-containing medium |
| US4594327A (en) * | 1983-11-02 | 1986-06-10 | Syntex (U.S.A.) Inc. | Assay method for whole blood samples |
| CA1230552A (en) * | 1983-11-07 | 1987-12-22 | Howard M. Chandler | Device and method for performing qualitative enzyme immunoassays |
| US4590169A (en) * | 1983-11-18 | 1986-05-20 | Beckman Instruments, Inc. | Direct particle agglutination immunoassays avoiding false negatives at high antigen concentrations |
| GB8331514D0 (en) | 1983-11-25 | 1984-01-04 | Janssen Pharmaceutica Nv | Visualization method |
| EP0149168B1 (en) | 1983-12-19 | 1991-04-24 | Daiichi Pure Chemicals Co. Ltd. | Immunoassay |
| 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 |
| US4757004A (en) * | 1984-03-16 | 1988-07-12 | Syntex (U.S.A.) Inc. | Chromatographic devices having modified edges |
| US4883688A (en) * | 1984-03-16 | 1989-11-28 | Syntex (U.S.A) Inc. | Method for producing chromatographic devices having modified edges |
| US4756828A (en) * | 1984-04-12 | 1988-07-12 | Syntex (U.S.A.) Inc. | Chromatographic strip having non-compressed edges |
| NZ211888A (en) | 1984-05-10 | 1987-08-31 | Abbott Lab | Biotin-antibiotin immunoassay for detecting ligands |
| US4632901A (en) * | 1984-05-11 | 1986-12-30 | Hybritech Incorporated | Method and apparatus for immunoassays |
| US4647544A (en) * | 1984-06-25 | 1987-03-03 | Nicoli David F | Immunoassay using optical interference detection |
| EP0170746A1 (en) | 1984-08-07 | 1986-02-12 | Covalent Technology Corporation | Biologically active material test |
| US5043428A (en) * | 1984-08-31 | 1991-08-27 | Behringwerke Aktiengesellschaft | Pasteurized, isoagglutinin-free factor VIII preparation and a process for its production |
| DE3432083A1 (en) | 1984-08-31 | 1986-03-06 | Behringwerke Ag, 3550 Marburg | PASTEURIZED, ISOAGGLUTININ-FREE FACTOR VIII PREPARATION AND METHOD FOR THE PRODUCTION THEREOF |
| US4999285A (en) * | 1984-11-15 | 1991-03-12 | Syntex (U.S.A.) Inc. | Chromatographic cassette |
| US4624929A (en) * | 1984-12-03 | 1986-11-25 | Syntex (U.S.A.) Inc. | Sample collector and assay device and method for its use |
| DE3445816C1 (en) | 1984-12-15 | 1986-06-12 | Behringwerke Ag, 3550 Marburg | Flat diagnostic agent |
| US4639242A (en) * | 1985-02-04 | 1987-01-27 | Babson Arthur L | Vessel and procedure for automated assay |
| US4740468A (en) | 1985-02-14 | 1988-04-26 | Syntex (U.S.A.) Inc. | Concentrating immunochemical test device and method |
| US4935339A (en) | 1985-05-07 | 1990-06-19 | Nichols Institute Diagnostics | Delayed solid phase immunologic assay |
| US4803170A (en) * | 1985-05-09 | 1989-02-07 | Ultra Diagnostics Corporation | Competitive immunoassay method, device and test kit |
| US4623461A (en) * | 1985-05-31 | 1986-11-18 | Murex Corporation | Transverse flow diagnostic device |
| US4806312A (en) * | 1985-08-28 | 1989-02-21 | Miles Inc. | Multizone analytical element having detectable signal concentrating zone |
| US4806311A (en) | 1985-08-28 | 1989-02-21 | Miles Inc. | Multizone analytical element having labeled reagent concentration zone |
| US4900663A (en) * | 1985-09-13 | 1990-02-13 | Environmental Diagnostics, Inc. | Test kit for determining the presence of organic materials and method of utilizing same |
| US4761381A (en) * | 1985-09-18 | 1988-08-02 | Miles Inc. | Volume metering capillary gap device for applying a liquid sample onto a reactive surface |
| TW203120B (en) * | 1985-10-04 | 1993-04-01 | Abbott Lab | |
| GB8526741D0 (en) | 1985-10-30 | 1985-12-04 | Boots Celltech Diagnostics | Binding assay device |
| US4868108A (en) * | 1985-12-12 | 1989-09-19 | Hygeia Sciences, Incorporated | Multiple-antibody detection of antigen |
| US4772550A (en) * | 1986-02-10 | 1988-09-20 | Miles Inc. | Heterogeneous specific binding assay employing an aggregatable binding reagent |
| US4916056A (en) * | 1986-02-18 | 1990-04-10 | Abbott Laboratories | Solid-phase analytical device and method for using same |
| US5160701A (en) | 1986-02-18 | 1992-11-03 | Abbott Laboratories | Solid-phase analytical device and method for using same |
| US4778751A (en) * | 1986-05-12 | 1988-10-18 | Diagnostic Products Corporation | Method for measuring antigens or antibodies in biological fluids using ligand labeled antigens or ligand labeled antibodies |
| AU602694B2 (en) | 1986-06-09 | 1990-10-25 | Ortho Diagnostic Systems Inc. | Improved colloidal gold membrane assay |
| AU7385387A (en) * | 1986-06-09 | 1987-12-10 | Ortho Diagnostic Systems Inc. | Immunoassay using detection of colloidal gold |
| US5120504A (en) * | 1986-07-14 | 1992-06-09 | Hybritech Incorporated | Apparatus for immunoassays with vent chennels in the container side wall |
| US5085988A (en) | 1986-09-05 | 1992-02-04 | Syntex (U.S.A.) Inc. | Immunoseparating strip |
| US4963468A (en) * | 1986-09-05 | 1990-10-16 | Syntex (U.S.A.) Inc. | Immunoseparating strip |
| US4959307A (en) | 1986-09-05 | 1990-09-25 | Syntex (U.S.A.) Inc. | Immunoseparating strip |
| US5085987A (en) | 1986-09-05 | 1992-02-04 | Syntex (U.S.A.) Inc. | Immunoseparating strip |
| US5260193A (en) | 1986-09-05 | 1993-11-09 | Syntex (U.S.A.) Inc. | Immunoseparating strip |
| US5260194A (en) | 1986-09-05 | 1993-11-09 | Syntex (U.S.A.) Inc. | Immunoseparating strip |
| US4960691A (en) * | 1986-09-29 | 1990-10-02 | Abbott Laboratories | Chromatographic test strip for determining ligands or receptors |
| US5030558A (en) * | 1986-11-07 | 1991-07-09 | Syntex (U.S.A.) Inc. | Qualitative immunochromatographic method and device |
| EP0271204A3 (en) | 1986-11-07 | 1989-10-25 | Syntex (U.S.A.) Inc. | Immunochromatographic method and device |
| US5232835A (en) * | 1986-11-07 | 1993-08-03 | Syntex (U.S.A.) Inc. | Qualitative immunochromatographic method and device |
| US5156952A (en) * | 1986-11-07 | 1992-10-20 | Syntex (U.S.A.) Inc. | Qualitative immunochromatographic method and device |
| US4770853A (en) * | 1986-12-03 | 1988-09-13 | New Horizons Diagnostics Corporation | Device for self contained solid phase immunodiffusion assay |
| US4774192A (en) * | 1987-01-28 | 1988-09-27 | Technimed Corporation | A dry reagent delivery system with membrane having porosity gradient |
| 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 |
| DE3705686C2 (en) * | 1987-02-23 | 1995-11-30 | Boehringer Mannheim Gmbh | Methods for the determination of antibodies |
| DE3706718A1 (en) * | 1987-03-02 | 1988-09-15 | Boehringer Mannheim Gmbh | DEVICE FOR CARRYING OUT A HETEROGENEOUS REACTION |
| CA1303983C (en) * | 1987-03-27 | 1992-06-23 | Robert W. Rosenstein | Solid phase assay |
| US4857453A (en) * | 1987-04-07 | 1989-08-15 | Syntex (U.S.A.) Inc. | Immunoassay device |
| DE3887771C5 (en) * | 1987-04-27 | 2009-06-04 | Inverness Medical Switzerland Gmbh | Immunoassays and devices therefor. |
| US4962023A (en) * | 1987-06-22 | 1990-10-09 | Louisiana State University, Agricultural And Mechanical College | Single incubation immuno sorbent assay method using particle labels to detect test antigen specific antibodies in presence of other antibodies |
| US4954452A (en) | 1987-07-09 | 1990-09-04 | Abbott Laboratories | Non-metal colloidal particle immunoassay |
| US5120643A (en) * | 1987-07-13 | 1992-06-09 | Abbott Laboratories | Process for immunochromatography with colloidal particles |
| US4981786A (en) * | 1987-09-04 | 1991-01-01 | Syntex (U.S.A.) Inc. | Multiple port assay device |
| US4956302A (en) * | 1987-09-11 | 1990-09-11 | Abbott Laboratories | Lateral flow chromatographic binding assay device |
| US4853335A (en) * | 1987-09-28 | 1989-08-01 | Olsen Duane A | Colloidal gold particle concentration immunoassay |
| US4859612A (en) * | 1987-10-07 | 1989-08-22 | Hygeia Sciences, Inc. | Metal sol capture immunoassay procedure, kit for use therewith and captured metal containing composite |
| US5254458A (en) | 1987-10-30 | 1993-10-19 | Abbott Laboratories | Immunoassays using antigens produced in heterologous organisms |
| GB8728639D0 (en) | 1987-12-08 | 1988-01-13 | Scient Generics Ltd | Device for analytical determinations |
| US5006474A (en) * | 1987-12-16 | 1991-04-09 | Disease Detection International Inc. | Bi-directional lateral chromatographic test device |
| US4891313A (en) * | 1988-01-21 | 1990-01-02 | Boehringer Manheim Corporation | Method for determination of a component of a sample |
| US5459080A (en) | 1988-01-29 | 1995-10-17 | Abbott Laboratories | Ion-capture assays using a specific binding member conjugated to carboxymethylamylose |
| US5670381A (en) | 1988-01-29 | 1997-09-23 | Abbott Laboratories | Devices for performing ion-capture binding assays |
| US5866322A (en) | 1988-01-29 | 1999-02-02 | Abbott Laboratories | Method for performing Rubella assay |
| US5459078A (en) | 1988-01-29 | 1995-10-17 | Abbott Laboratories | Methods and reagents for performing ion-capture digoxin assays |
| CA1333883C (en) | 1988-04-07 | 1995-01-10 | Shashidhara H. M. Murthy | Immunoassay utilizing biotin bridge with universal solid phase |
| US5039607A (en) * | 1988-05-17 | 1991-08-13 | Syntex (U.S.A.) Inc. | Method for immunochromatographic analysis |
| US5164294A (en) * | 1988-05-17 | 1992-11-17 | Syntex (U.S.A.) Inc. | Method for immunochromatographic analysis |
| US4981785A (en) * | 1988-06-06 | 1991-01-01 | Ventrex Laboratories, Inc. | Apparatus and method for performing immunoassays |
| DE68924098T2 (en) | 1988-06-09 | 1996-04-18 | Abbott Lab | Process and device using covalently immobilized dyes. |
| AU2684488A (en) | 1988-06-27 | 1990-01-04 | Carter-Wallace, Inc. | Test device and method for colored particle immunoassay |
| CA2025476A1 (en) | 1989-09-27 | 1991-03-28 | Shan F. Ching | Hydrophilic laminated porous membranes and methods of preparing same |
| US5075078A (en) * | 1989-10-05 | 1991-12-24 | Abbott Laboratories | Self-performing immunochromatographic device |
| US5141850A (en) * | 1990-02-07 | 1992-08-25 | Hygeia Sciences, Inc. | Porous strip form assay device method |
| JP3108115B2 (en) | 1991-03-28 | 2000-11-13 | ロート製薬株式会社 | Substance detection method by immunochromatography |
| US5686315A (en) | 1991-06-14 | 1997-11-11 | Quidel Corporation | Assay device for one step detection of analyte |
| FI96968C (en) * | 1993-12-02 | 1996-09-25 | Outokumpu Eng Contract | Process for extracting metals from large solution streams and apparatus for carrying out the process |
| US5753517A (en) | 1996-03-29 | 1998-05-19 | University Of British Columbia | Quantitative immunochromatographic assays |
| US5710005A (en) | 1996-10-29 | 1998-01-20 | Biocode, Inc. | Analyte detection with a gradient lateral flow device |
-
1988
- 1988-12-15 AU AU26844/88A patent/AU2684488A/en not_active Abandoned
-
1989
- 1989-06-23 JP JP01159819A patent/JP3125788B2/en not_active Expired - Lifetime
- 1989-06-23 AT AT89306388T patent/ATE121196T1/en active
- 1989-06-23 EP EP89306388A patent/EP0349215B1/en not_active Revoked
- 1989-06-23 DE DE68922148T patent/DE68922148T2/en not_active Revoked
- 1989-06-23 ES ES89306388T patent/ES2073439T3/en not_active Expired - Lifetime
- 1989-06-26 MX MX016603A patent/MX170320B/en unknown
- 1989-06-27 CA CA000604025A patent/CA1340920C/en not_active Expired - Lifetime
-
1992
- 1992-09-21 AU AU25267/92A patent/AU2526792A/en not_active Abandoned
- 1992-12-23 US US07/995,331 patent/US5714389A/en not_active Expired - Lifetime
-
1995
- 1995-04-13 GR GR950400750T patent/GR3015771T3/en unknown
- 1995-06-06 US US08/465,675 patent/US6485982B1/en not_active Expired - Lifetime
- 1995-07-25 AU AU27188/95A patent/AU693236B2/en not_active Expired
-
1997
- 1997-07-02 US US08/886,088 patent/US5989921A/en not_active Expired - Lifetime
-
2005
- 2005-01-12 US US11/035,047 patent/US20060040405A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2526792A (en) | 1992-12-03 |
| JP3125788B2 (en) | 2001-01-22 |
| US20060040405A1 (en) | 2006-02-23 |
| JPH02132375A (en) | 1990-05-21 |
| MX170320B (en) | 1993-08-16 |
| EP0349215B1 (en) | 1995-04-12 |
| DE68922148T2 (en) | 1995-08-10 |
| ATE121196T1 (en) | 1995-04-15 |
| AU693236B2 (en) | 1998-06-25 |
| GR3015771T3 (en) | 1995-07-31 |
| US5989921A (en) | 1999-11-23 |
| AU2718895A (en) | 1995-10-19 |
| DE68922148D1 (en) | 1995-05-18 |
| AU2684488A (en) | 1990-01-04 |
| EP0349215A1 (en) | 1990-01-03 |
| US6485982B1 (en) | 2002-11-26 |
| ES2073439T3 (en) | 1995-08-16 |
| US5714389A (en) | 1998-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1340920C (en) | Test device and method for colored particle immunoassay | |
| CA1288337C (en) | Colloidal gold membrane assay | |
| EP0823972B1 (en) | Diagnostic detection device and method | |
| CA1312544C (en) | Chromatographic binding assay devices and methods | |
| US6087184A (en) | Opposable-element chromatographic assay device for detection of analytes | |
| JP3386122B2 (en) | Testing device | |
| US6248596B1 (en) | Liposome-enhanced immunoassay and test device | |
| AU770231B2 (en) | Analytical test device and method of use | |
| US5998221A (en) | Non-instrumented assay with quantitative and qualitative results | |
| US6194220B1 (en) | Non-instrumented assay with quantitative and qualitative results | |
| EP1003037B1 (en) | Analytical test device and method of use | |
| AU701396B2 (en) | Improved diagnostic detection device | |
| EP2126573B1 (en) | Diagnostic detection device | |
| CA2172993A1 (en) | Interrupted-flow assay device | |
| AU5295996A (en) | Liposome-enhanced immunoaggregation assay and test device | |
| AU730911B2 (en) | Immunoassay device | |
| US5334538A (en) | Gold sol immunoassay system and device | |
| AU726976B2 (en) | Formulation for reducing urea effect for immuno-chromatography assays using urine samples | |
| WO1997031268A1 (en) | Chromatographic strip having detection and control zones oriented parallel to the direction of flow | |
| EP0884594A2 (en) | Analyte-fixation immunochromatographic device | |
| MXPA97008428A (en) | Device and method for the detection of diagnost |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |
Effective date: 20170307 |