1. An assay device for testing the presence of an analyte in a given sample comprising: a multilayer support whereon a first analyte-binding compound or analyte-binding complex, able to bind said analyte present in said sample, is immobilized, whereby said analyte is able to bind a second enzyme labeled analyte-binding compound or enzyme labeled analyte-binding complex forming a sandwich complex, whereby said sandwich complex is able to generate upon contact with a suitable precipitating substrate for said enzyme-label a colored deposit in a one step procedure.
2. An assay device according to claim 1, wherein said multilayer support comprises:
a) an upper cover layer of a water-impermeable material having at least one hole, whereby said hole at least partly exposing a test zone,
b) an intermediate porous layer comprising at least one insoluble porous material whereon the first analyte binding compound is able to bind in said test zone, and
c) a lower absorbent layer comprising at least one layer of a hydrophilic material.
3. An assay device according to claim 2 wherein the water-impermeable material is made out of a plastic material adapted to the sample to be tested.
4. An assay device according to claims 2 or 3 wherein said test zone has a diameter of at least 1 mm.
5. An assay device according to claim 4 wherein said test zone is preferentially 3 to 4 mm.
6. An assay device according to claim 2 wherein the intermediate insoluble porous material is made from a material chosen from the group comprising nylon, nitrocellulose, cellulose, fiberglass, polysulfofone, polyvinylidene difluoride, polyester or any other polymeric material whereon a biological substance may bind.
7. An assay device according to claim 6 wherein the intermediate insoluble porous material is nitrocellulose.
8. An assay device according to either of claims 6 or 7 wherein the intermediate insoluble porous material has pores with a diameter between 0.1 and 12 m, and a thickness up to 2500 m.
9. An assay device according to claim 8 wherein the intermediate insoluble porous material has pores with a diameter preferably of 0.45 m and a thickness of 500 m.
10. An assay device according to claim 2, wherein the hydrophilic material of the device allows communication between the porous material and the absorbent layer and is AP120 or any equivalent absorbent pad.
11. An assay device according to claim 1, wherein said first analyte-binding compound and said second analyte-binding compound are substances which specifically bind the analyte and are chosen from the group comprising peptides, proteins, lipids, nucleic acids and organic molecules.
12. An assay device according to claim 11 wherein said first analyte-binding compound andor said second analyte-binding compound is preferentially an antibody which specifically binds the analyte.
13. An assay device according to claim 12 wherein said antibody is a monoclonal or polyclonal or an antibody preparation thereof.
14. An assay device according to claim 1, wherein said first analyte-binding compound is directly coupled to the porous layer of said device.
15. An assay device according to claim 1, wherein said first analyte-binding compound is indirectly coupled to the porous layer of said device.
16. An assay device according to claim 15 wherein the porous layer of said device is first coated with a capturing molecule which specifically binds said first analyte-binding compound followed by the coating of said analyte-binding compound.
17. An assay device according to claim 1 wherein said analyte is detected indirectly by the use of a detection molecule.
18. An assay device according to claim 1 wherein said second analyte-binding compound or analyte-binding complex is able to bind with a detection molecule labeled with a different enzyme (E2) than the enzyme present on said second analyte-binding compound E1), whereby said E2 enzyme upon interaction with a precipitating substrate using a one step procedure results in a colored deposit.
19. An assay device according to claim 1, wherein said second analyte-binding compound is not enzyme-labeled and is further bound by a detection molecule labeled with an enzyme which upon interaction with a precipitating substrate using a one step procedure results in a colored deposit.
20. An assay device according to any of claims 15-19, whereby said indirect coupling is realized via an avidinbiotin, biotinstreptavidin, antibodyantigen, antibodyhapten, receptorligand, sugarlectin, complementary nucleic acid, enzymesubstrate, enzymecofactor, enzymeinhibitor or immunoglobulinStaphylococcal protein A interaction.
21. An assay device according to claim 1 wherein said sample can be chosen from a group comprising cell fractions, serum, whole blood, urine, plasma for human or animal diagnostic testing; soil, mud, minerals, water, air for environmental testing; any food materials for food testing; or any other mediumsuspensionhard material which can be used for one of these purposes.
22. An assay device according to claim 1 wherein said test sample can be applied undiluted or in a diluted form using a diluent buffer and for which the dilution factor is adapted to the analyte to be detected.
23. An assay device according to claim 22 wherein said dilution is chosen between up to {fraction (1100.000)}.
24. An assay device according to claims 22 or 23 wherein said diluent buffer has a composition adapted to the analyte to be detected.
25. An assay device according to claim 1 wherein said analyte is a compound abnormally or normally-present or absent in the sample.
26. An assay device according to claim 25 wherein said compound is selected from the group comprising antigens, antibodies whereby said antigen is chosen from the group comprising any biological agent such as bacteria, viruses, molds, mycobacteria, parasites, pathogens; or any molecule such as peptides, proteins, lipids, organic molecules and nucleic acid oligomers.
27. An assay device according to claim 26 wherein said antigen is chosen from the group comprising proteins for which the level abnormally increases in certain diseased states or abnormally increases in food material.
28. An assay device according to claim 26 wherein said antigen is chosen from the group comprising C-reactive protein (CRP), troponin, myoglobin, HCG (human chorionic gonadotrophin), rheumatoid factors, cardiolipin, centromere (kinetochore proteins), histones, Jo-1(eponymously named, same as histidyl tRNA transferase), RNP (ribonucleoproteins eg. U1RNP),), lupus coagulant, myeloperoxidase, nucleolair auto-antigens (e.a.:PM-Sclpolymyositis-Scleroderma) (eg. U1RNP), Scl70 (same as topoisomerase 1), Sm (eponymously named as Smith antigen, same as nuclear antigen), SSARo (Sjgren syndrome antigen), SSBLa (Sjgren syndrome antigen), thyroglobulin, cell surface lipoproteins, Thyroid auto-antigens, collagen, ANCA (anti-neutrophil cytoplasmic antibodies).
29. An assay device according to claim 26 wherein said antibody belong to any class of immunoglobulin comprising IgE, IgG, IgM, IgA, IgD.
30. An assay device according to claim 26 wherein said nucleic acid oligomer is chosen from the group comprising DNA, RNA, DNARNA hybrid or chemically analogues thereof, genetically modified or not.
31. An assay device according to claim 1 whereby said enzyme-label, which is coupled to said second analyte binding compound or said detection molecule reacts in one step with a precipitating substrate and is chosen from the group comprising horse radish peroxidase (HRP), alkaline phosphatase, and dehydrogenase.
32. An assay device according to claim 1 wherein said enzyme-label is covalently or non-covalently bound to the second analyte-binding compound.
33. An assay device according to any of the claims 31 or 32 wherein said enzyme label is HRP and said precipitating substrate is chosen from the group comprising TMB (tetratmethylbenzidine) and AEC (3-amino-9 ethylcarbazole).
34. An assay device according to any of the claims 31 or 32, wherein said enzyme label is alkaline phosphatase and said substrate is chosen from the group comprising BCIP (5-bromo-4-chloro-3-indolyl phosphate) and BCIP-NBT (5-bromo-4-chloro-3-indolyl phosphate-nitro blue tetrazolium).
35. An assay device according to any of the claims 31 or 32 wherein said enzyme label is dehydrogenase and said substrate is chosen from the group comprising NBT (nitro blue tetrazolium).
36. An assay device according to claim 33 wherein the formed TMB precipitate is able to be fixated using a reagent chosen from the group comprising polyvinylic alcohol supplemented with dioctyl sulfosuccinate and dimethyl formamide.
37. An assay device according to claim 1 whereby the analysis is performed qualitatively, semi-quantitatively or quantitatively.
38. An assay device according to claim 1 containing at least one test zone which may be used for standard(s) andor positive andor negative andor cut-off control(s).
39. An assay device according to claim 1 wherein the color deposit is observed and interpreted using a card system or using a reader.
40. A diagnostic kit for testing the presence of an analyte in a given sample comprising:
an assay device as defined in claim 1 provided with a first analyte-binding compound or analyte-binding complex,
a second solution comprising an enzyme-labeled second analyte-binding compound, an enzyme-labeled second analyte-binding complex or an enzyme-labeled detection molecule,
a third solution comprising a precipitating substrate for the enzyme linked to the second analyte-binding compound, an enzyme-labeled second analyte-binding complex or an enzyme-labeled detection molecule able to generate a colored deposit upon reaction with said enzyme,
optionally a color chart for the interpretation of the colored deposit, and
optionally an instruction leaflet.
41. A diagnostic kit according to claim 40 or an assay device according to claim 1 for use in testingcontrollingdetecting clinical (human or animal), agricultural, environmental or food samples.
42. A diagnostic kit according to claim 40 or an assay device according to claim 1 for the diagnosis andor monitoring of treatment of diseases.
43. A diagnostic kit according to claim 40 or an assay device according to claim 1 for the diagnosis andor monitoring of treatment of auto-immune diseases induced by organ or non-organ specific auto-antigens.
44. A diagnostic kit according to claim 43 wherein said non-organ specific (multisystem) auto-immune disease is chosen from the group of diseases comprising systemic lupus erythematotus (SLE) and other rheumatic diseases, scleroderma with or without Crest syndrome, drug-induced lupus erythematosus (LE), polymyositis with or without scleroderma, primary Sjgren syndrome, rheumatoid arthritis, and connective tissue diseases.
45. A diagnostic kit according to claim 43 wherein said organ specific auto-immune disease is chosen from the group of diseases comprising Addison’s disease, auto-immune haemolytic anemia, chronic active hepatitis, coeliac disease, Goodpasture’s syndrome, grave’s thyrotoxicosis, Hashimoto’s thyroiditis, idiopathic thrombocytopenic purpura, Juvenile-onset diabetes, late onset diabetes, lens induced uveitis, some male infertility, multiple sclerosis, myasthenia gravis, primary biliary cirrhosis, pernicious anemia, primary myxoedema, sympathetic ophtalmia, ulcerative colitis, vasculitides, pemphigoid and Wegener’s granulomatosis.
46. A diagnostic kit according to claim 40 or any assay device according to claim 1 for the diagnosis andor monitoring of treatment of infectious diseases included by viruses, bacteria, molds, mycobacteria or parasites.
47. A diagnostic kit according to claim 40 or an assay device according to claim 1 for the diagnosis andor monitoring of treatment of allergic diseases or intolerance manifestations induced by numerous allergens from grasses, weeds, molds, foods, trees, epidermals and dust.
48. A diagnostic kit according to claim 40 or an assay device according to claim 1 for use in the testing of cardiac andor inflammatory markers.
49. A diagnostic kit according to claim 48 wherein said cardiac markers are chosen from the group comprising of myoglobin, creatine kinase and troponin and inflammatory markers are chosen from the group comprising C-reactive protein and interleukins.
50. A diagnostic kit according to claim 40 or an assay device according to claim 1 for use in testing of bacteria andor toxins.
51. A diagnostic kit according to claim 40 or an assay device according to claim 1 for use in testing of tumor antigens.
52. A diagnostic kit according to claim 40 or an assay device according to claim 1 for use in testing of drugs of abuse molecules.
53. A method for the detection of an analyte present in a test sample comprising the use of a diagnostic assay device according to claim 1.
54. A method according to claim 53 wherein the addition of the first analyte-binding compound, sample, second analyte-binding compound, substrate solution and fixation solution are performed subsequently, one after the other.
55. A method according to claim 54 wherein the addition of the first analyte-binding compound, sample, second analyte-binding compound, substrate solution and fixation solution are not all performed subsequently, and wherein some of these may be premixed in advance before applying them onto the device.
56. Use of a fixative solution in an assay device according to claim 1 or as part of a diagnostic kit according to claim 40.
57. A method for coating a porous layer in an assay device as described in claim 1 comprising the following steps:
cutting membranes into strips,
immersing said strips into an application buffer and the capturing agent or first analyte-binding compound,
incubating the membrane,
immersing the membrane in a blocking agent containing 0.2 to 10% blocking agent, whereby the blocking agent may be BSA or any other agent known to block free sites on membranes,
incubating the membranes
drying strips, and
when storage is needed, packaging of the strips are packaged and stored;
wherein the coating buffer features preferentially very low salinity and basic pH (9.12) and the analyte-binding compound is present in excess.
58. A method for coating a porous layer in a assay device as described in claim 1 comprising following steps:
cutting membranes into strips of preferably 0.8 cm wide,
immersing said strips into a bath brought at RT containing the application buffer and the capturing molecule or the first analyte-binding compound,
incubating the membrane for 3 hours at RT under gentle agitation,
immersing the membrane in a blocking agent containing 1% BSA,
incubating during 3 hours at RT under gentle agitation,
drying strips at 37 C. in an incubator for 1 hour to overnight, and,
when storage is needed, packaging of the strips in order to protect membranes from humidity and stored at RT; wherein the coating (application) buffer features preferentially very low salinity and basic pH (9.10.1), the analyte-binding compound is present in an excess.
59. A method using a device as described in claim 1 comprising following steps:
dilute sample to 100.00 into the diluent buffer, whereby the diluent buffer is a Tris buffer or of another composition of low salinity and containing 1 to 5% BSA, or use an undiluted sample,
applying 15 l or one drop of diluted sample on the membrane,
allowing the sample to soak for 1 minute at least (range: 30 up to 130) preferentially 45,
applying 25 l or one drop of conjugate (anti-CRP coupled to HRP) and allow to soak,
applying 25 l or one drop of precipitating TMB and allow to soak,
apply 25 l or one drop of fixative solution and allow to soak,
waiting for 2 minutes before reading the result and read within 30 minutes, and
covering the colored spot with a scotch band (type 3M) when a long-term storage of the result is necessary.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A medical device delivery system, comprising:
an outer sheath;
an inner catheter disposed within the outer sheath, the inner catheter having a distal end;
a tube extension coupled to the distal end of the inner catheter and extending distally therefrom to an attached distal nose cone; and
a valve implant releasable coupled to the inner catheter;
wherein the tube extension is configured to shift between a first elongated configuration and a second shortened configuration;
wherein the outer sheath is configured to shift the nose cone and attached tube extension between the first elongated configuration and the second shortened configuration of the tube extension.
2. The system of claim 1, wherein the tube extension includes a coil.
3. The system of claim 2, wherein the coil has an open pitch when the tube extension is in the first elongated configuration and the coil has a closed pitch when the tube extension is in the second shortened configuration.
4. The system of claim 1, wherein the tube extension includes a resilient polymer.
5. The system of claim 4, wherein the resilient polymer has a first thickness when the tube extension is in the first elongated configuration and the resilient polymer has a second thickness greater than the first thickness when the tube extension is in the second shortened configuration.
6. The system of claim 1, wherein the tube extension includes a tubular member having a plurality of slots formed therein.
7. The system of claim 6, wherein at least some of the slots are open when the tube extension is in the first elongated configuration and wherein at least some of the slots are closed when the tube extension is in the second shortened configuration.
8. The system of claim 1, wherein the valve implant includes a replacement aortic valve.