US4054646A
Expired / Lapsed
US
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Method and apparatus for detection of antibodies and antigens
Assignee: General Electric Co
•
Filing: 1975-08-27
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Granted: 1977-10-18
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Expires: 1995-08-27
Abstract
Abstract Method and apparatus for the detection of antibodies and antigens based upon the effect that any arbitrary antigen will adsorb onto a substrate in a monomolecular layer only, but that a corresponding specific antibody for such arbitrary antigen will bond thereto to form a bimolecular layer on the substrate. A first layer of antigen is adsorbed onto a substrate and the coated substrate is then exposed to a solution suspected of containing the specific antibody of interest. The substrate is then examined to determine whether a monomolecular or bimolecular layer is adhering thereon. Optical, including visual, electrical, and chemical means for examining the coated substrate are disclosed. The method can be reversed by replacing the antigen in each step above with its specifically reacting antibody and by replacing the antibody with its specific antigen.
Inventors
- 👤 Ivar Giaever
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 17:06
CPC Classifications
B; B82; B82Y; B82Y15/00; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; G01N33/551; G01N33/553; B82Y30/00; B82Y5/00; Y; Y10; Y10S; Y10S436/00; Y10S436/805; Y10S436/806; Y10S436/815; Y10S436/817; Y10S436/818; Y10S436/82; Y10S530/00; Y10S530/806; Y10S530/81; Y10S530/811; Y10T; Y10T428/00; Y10T428/26; Y10T428/263; Y10T428/264; Y10T428/265; Y10T428/31504; Y10T428/31725; Y10T428/31768
Claims Analysis
Total Claims: 75
Claim 1
Independent Claim
106 words
A diagnostic method for determining the presence or absence of a specific antibody or antigen in a biological sample comprising the steps of: depositing a metal onto a substrate material; contacting said substrate material with an aqueous medium containing either a corresponding specifically reacting antigen to said specific antibody or a corresponding specifically reacting antibody to said specific antigen, to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen or antibody; immersing said coated substrate material in said sample; and examining said coated substrate material to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 2
Dependent Claim
106 words
A diagnostic method for determining the presence or absence of a specific antibody or antigen in a biological sample comprising the steps of: depositing a metal onto a substrate material; contacting said substrate material with an aqueous medium containing either a corresponding specifically reacting antigen to said specific antibody or a corresponding specifically reacting antibody to said specific antigen, to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen or antibody; immersing said coated substrate material in said sample; and examining said coated substrate material to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 3
Dependent Claim
34 words
The method of claim 1 wherein said step of depositing a metal comprises evaporating a metal having high atomic mobility and poor surface wetting characteristics as metal globules onto a light transmissive substrate material.
Claim 4
Dependent Claim
29 words
The method of claim 1 to determine the absence or prsence of a specific antigen wherein the aqueous medium contains a corresponding specifically reacting antibody to said specific antigen.
Claim 5
Dependent Claim
21 words
The method of claim 1 wherein said step of depositing a metal comprises coating said substrate material with a metal film.
Claim 6
Dependent Claim
29 words
The method of claim 4 wherein the substrate material is slide like and also includes a metal oxide layer intermediate the metal of the slide and said monomolecular layer.
Claim 7
Dependent Claim
19 words
The method of claim 5 wherein said metal is titanium and said metal oxide is an oxide of titanium.
Claim 8
Dependent Claim
36 words
The method of claim 1 wherein said step of depositing a metal comprises evaporating a metal selected from the group consisting of indium, gold, silver, tin and lead, as metal globules onto a light transmissive substrate.
Claim 9
Dependent Claim
24 words
The method of claim 7 wherein said light transmissive substrate is selected from the group consisting of glass, plastic, fused silica, mica and quartz.
Claim 10
Dependent Claim
31 words
The method of claim 7 wherein said metal is indium and said examining step comprises visually examining said substrate and said determination is made by distinguishing between different shades of brown.
Claim 11
Dependent Claim
22 words
The method of claim 1 wherein said step of depositing a metal comprises coating said substrate with a thin layer of gold.
Claim 12
Dependent Claim
22 words
The method of claim 10 wherein said examining step comprises visually examining said substrate and said determination is made by reflectivity measurement.
Claim 13
Dependent Claim
17 words
The method of claim 10 wherein another metal is placed between said gold layer and said substrate.
Claim 14
Dependent Claim
11 words
The method of claim 12 wherein said another metal is indium.
Claim 15
Dependent Claim
29 words
The method of claim 1 to determine the absence or presence of a specific antibody wherein the aqueous medium contains a corresponding specifically reacting antigen to said specific antibody.
Claim 16
Dependent Claim
25 words
The method of claim 14 wherein said specific antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 17
Dependent Claim
23 words
The method of claim 14 wherein said antigen is derived from a bacteria, a virus, a fungus, mammalian tissue or mammalian body fluids.
Claim 18
Dependent Claim
11 words
The method of claim 16 wherein the antibody is an immunoglobulin.
Claim 19
Dependent Claim
14 words
The method of claim 17 wherein the antibody is of the immunoglobulin IgG class.
Claim 20
Dependent Claim
101 words
A dignostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: coating a metal film onto a substrate material; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; placing a mercury drop on the upper surface of said layer on said substrate material; and measuring the electrical capacitance between said mercury drop and said metal coating.
Claim 21
Dependent Claim
101 words
A dignostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: coating a metal film onto a substrate material; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; placing a mercury drop on the upper surface of said layer on said substrate material; and measuring the electrical capacitance between said mercury drop and said metal coating.
Claim 22
Dependent Claim
24 words
The method of claim 19 wherein the antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 23
Dependent Claim
118 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: coating a metal film onto a substrate material, said metal being capable of forming a visible amalgam with mercury; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; placing a mercury drop on the upper surface of said layer on said substrate material; and measuring the time elapsing between said placing of a mercury drop and the appearance of a visible amalgam.
Claim 24
Dependent Claim
118 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: coating a metal film onto a substrate material, said metal being capable of forming a visible amalgam with mercury; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; placing a mercury drop on the upper surface of said layer on said substrate material; and measuring the time elapsing between said placing of a mercury drop and the appearance of a visible amalgam.
Claim 25
Dependent Claim
24 words
The method of claim 21 wherein the antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 26
Dependent Claim
96 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: coating a metal film onto a substrate material; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; coating a second metal layer onto the upper surface of said layer on said substrate material; and viewing said substrate by reflected light.
Claim 27
Dependent Claim
96 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: coating a metal film onto a substrate material; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; coating a second metal layer onto the upper surface of said layer on said substrate material; and viewing said substrate by reflected light.
Claim 28
Dependent Claim
23 words
The method of claim 23 wherein said coating of a second metal layer comprises electroplating said second metal layer onto said antigen layer.
Claim 29
Dependent Claim
24 words
The method of claim 23 wherein the antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 30
Dependent Claim
113 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: depositing indium as metal globules onto a light transmissive substrate material by evaporation from a tantalum boat at a vacuum of approximately 5 × 10 -5 mm of mercury; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; and examining said coated substrate material to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 31
Dependent Claim
113 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: depositing indium as metal globules onto a light transmissive substrate material by evaporation from a tantalum boat at a vacuum of approximately 5 × 10 -5 mm of mercury; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; and examining said coated substrate material to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 32
Dependent Claim
24 words
The method of claim 26 wherein said antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 33
Dependent Claim
123 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: evaporating a metal having high atomic mobility and poor surface wetting characteristics as metal globules onto a light transmissive substrate material; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; placing said substrate material, oriented with said metal and said layer downwards, onto a surface of a light reflecting liquid; and examining said substrate to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 34
Dependent Claim
123 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: evaporating a metal having high atomic mobility and poor surface wetting characteristics as metal globules onto a light transmissive substrate material; contacting said substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; placing said substrate material, oriented with said metal and said layer downwards, onto a surface of a light reflecting liquid; and examining said substrate to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 35
Dependent Claim
24 words
The method of claim 28 wherein said antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 36
Dependent Claim
82 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; and immersing said substrate material in an immunological bond-cleaving reagent while observing said substrate in an ellipsometer.
Claim 37
Dependent Claim
82 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate material with a monomolecular layer of said specifically reacting antigen; immersing said coated substrate material in said sample; and immersing said substrate material in an immunological bond-cleaving reagent while observing said substrate in an ellipsometer.
Claim 38
Dependent Claim
45 words
The method of claim 30 wherein said antigen is a protein, contacting is by immersing in said medium, said medium is a solution and said substrate has a surface of a material having a refractive index substantially different from the refractive index of said antibody.
Claim 39
Dependent Claim
73 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material having a metallic surface with an aqueous medium containing a corresponding specifically reacting antigen to said specific protein; immersing the resulting substrate material in said sample; and examining said substrate with electrical capacitance sensing means to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 40
Dependent Claim
73 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material having a metallic surface with an aqueous medium containing a corresponding specifically reacting antigen to said specific protein; immersing the resulting substrate material in said sample; and examining said substrate with electrical capacitance sensing means to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 41
Dependent Claim
24 words
The method of claim 32 wherein said antigen is a protein, contacting is by immersing in said medium and said medium is a solution.
Claim 42
Dependent Claim
97 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material having a metallic surface with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate with a monomolecular layer of said specifically reacting antigen, said metallic surface comprising a first electrode; immersing the resulting substrate material in said sample; placing a second electrode on the upper surface of said layer; and measuring the electrical capacitance between said first and second electrodes.
Claim 43
Dependent Claim
97 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material having a metallic surface with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate with a monomolecular layer of said specifically reacting antigen, said metallic surface comprising a first electrode; immersing the resulting substrate material in said sample; placing a second electrode on the upper surface of said layer; and measuring the electrical capacitance between said first and second electrodes.
Claim 44
Dependent Claim
40 words
The method of claim 34 wherein said antigen is a protein, contacting is by immersing in said medium, said medium is a solution and placing a second electrode comprises placing a mercury drop on the upper surface of said layer.
Claim 45
Dependent Claim
90 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material having a metallic surface with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate with a monomolecular layer of said specifically reacting antigen; immersing the resulting substrate material in said sample; and examining said substrate employing a chemical sensing means to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 46
Dependent Claim
90 words
A diagnostic method for determining the presence or absence of a specific antibody in a biological sample comprising the steps of: contacting a substrate material having a metallic surface with an aqueous medium containing a corresponding specifically reacting antigen to said specific antibody to coat all or part of said substrate with a monomolecular layer of said specifically reacting antigen; immersing the resulting substrate material in said sample; and examining said substrate employing a chemical sensing means to determine whether said substrate has a bimolecular or monomolecular layer adhering thereto.
Claim 47
Dependent Claim
75 words
The method of claim 36 wherein said antigen is a protein, contacting is by immersing in said medium, said medium is a solution, said metallic surface comprises a metal which forms a visible amalgam with mercury and said examining step further comprises the steps of: placing a mercury drop on the upper surface of said layer; and measuring the time elapsing between the placing of a mercury drop and the appearance of a visible amalgam.
Claim 48
Dependent Claim
33 words
The method of claim 36 wherein said examining step comprises immersing said substrate material in a weak acid solution to sever immunological bonds in said layer while observing said substrate in an ellipsometer.
Claim 49
Dependent Claim
64 words
A surface immunological test method for antibodies to hepatitis comprising exposing a slide like, metallized substrate having a monomolecular surface layer comprising hepatitis-associated antigen over all or part thereof to a solution of an antibody specific to the hepatitis-associated antigen and producing an immunological reaction therewith to form a bimolecular layer on the substrate which can be seen when the substrate is visually examined.
Claim 50
Dependent Claim
64 words
A surface immunological test method for antibodies to hepatitis comprising exposing a slide like, metallized substrate having a monomolecular surface layer comprising hepatitis-associated antigen over all or part thereof to a solution of an antibody specific to the hepatitis-associated antigen and producing an immunological reaction therewith to form a bimolecular layer on the substrate which can be seen when the substrate is visually examined.
Claim 51
Dependent Claim
61 words
A surface immunological test method for antigens to hepatitis comprising exposing a slide like, metallized substrate having a monomolecular surface layer comprising antibody to hepatitis-associated antigens over all or part thereof to a solution of hepatitis-associated antigen and producing an immunological reaction therewith to form a bimolecular layer on the substrate which can be seen when the substrate is visually examined.
Claim 52
Dependent Claim
61 words
A surface immunological test method for antigens to hepatitis comprising exposing a slide like, metallized substrate having a monomolecular surface layer comprising antibody to hepatitis-associated antigens over all or part thereof to a solution of hepatitis-associated antigen and producing an immunological reaction therewith to form a bimolecular layer on the substrate which can be seen when the substrate is visually examined.
Claim 53
Dependent Claim
59 words
A surface immunological test method for gonorrhea comprising exposing a slide like, metallized substrate having a monomolecular surface layer comprising Neisseria gonorrhea antigen to a solution of an antibody specific to the Neisseria gonorrhea antigen and producing an immunological reaction therewith to form a bimolecular layer on the substrate which can be seen when the substrate is visually examined.
Claim 54
Dependent Claim
59 words
A surface immunological test method for gonorrhea comprising exposing a slide like, metallized substrate having a monomolecular surface layer comprising Neisseria gonorrhea antigen to a solution of an antibody specific to the Neisseria gonorrhea antigen and producing an immunological reaction therewith to form a bimolecular layer on the substrate which can be seen when the substrate is visually examined.
Claim 55
Dependent Claim
29 words
The method of claim 41 wherein said substrate is a metallized slide which also includes a metal oxide layer intermediate the metal of the slide and said monomolecular layer.
Claim 56
Dependent Claim
19 words
The method of claim 42 wherein said metal is titanium and said metal oxide is an oxide of titanium.
Claim 57
Dependent Claim
41 words
Medical diagnostic apparatus comprising: a substrate member; a plurality of metal globules attached to a surface of said substrate member; and a monomolecular layer of a immunologically reactive composition overlying at least a portion of said substrate and said metal globules.
Claim 58
Dependent Claim
41 words
Medical diagnostic apparatus comprising: a substrate member; a plurality of metal globules attached to a surface of said substrate member; and a monomolecular layer of a immunologically reactive composition overlying at least a portion of said substrate and said metal globules.
Claim 59
Dependent Claim
28 words
The apparatus of claim 44 having a plurality of said monomolecular layers, each said monomolecular layer overlying a corresponding said portion of said substrate and said metal globules.
Claim 60
Dependent Claim
33 words
The apparatus of claim 44 wherein: said substrate member comprises a light transmissive wafer; and said metal globules are indium particles having major dimensions in the range of 10 A to 2000 A.
Claim 61
Dependent Claim
12 words
The apparatus of claim 44 wherein the immunologically composition is an antibody.
Claim 62
Dependent Claim
13 words
The apparatus of claim 44 wherein the immunologically reactive composition is an antigen.
Claim 63
Dependent Claim
11 words
The apparatus of claim 48 wherein said antigen is a protein.
Claim 64
Dependent Claim
43 words
Medical diagnostic apparatus for detecting the presence of an antibody of interest in a fluid consisting of: a substrate having a surface including metal; and a monomolecular layer of a corresponding specifically reacting antigen to said antibody of interest attached to said surface.
Claim 65
Dependent Claim
43 words
Medical diagnostic apparatus for detecting the presence of an antibody of interest in a fluid consisting of: a substrate having a surface including metal; and a monomolecular layer of a corresponding specifically reacting antigen to said antibody of interest attached to said surface.
Claim 66
Dependent Claim
25 words
Apparatus in accordance with claim 50 wherein said surface comprises gold, tantalum, indium, titanium or titanium overcoated with a layer of an oxide of titanium.
Claim 67
Dependent Claim
34 words
Apparatus for diagnosing pregnancy in accordance with claim 50 wherein. said antigen of interest is HCG antigen; said fluid is urine; and said specifically reacting antibody is the specifically reacting antibody for HCG protein.
Claim 68
Dependent Claim
35 words
Apparatus for diagnosing hepatitis in accordance with claim 50 wherein: said antibody of interest is hepatitis antibody; said fluid is a mixture of blood and hepatitis antibody; and said specifically reacting antigen is hepatitis-associated antigen.
Claim 69
Dependent Claim
29 words
Apparatus for diagnosing hepatitis in accordance with claim 50 wherein: said antigen of interest is hepatitis-associated antigen; said fluid is blood; and said specifically reacting antibody is hepatitis antibody.
Claim 70
Dependent Claim
29 words
Apparatus in accordance with claim 50 wherein said antigen is a protein, said surface comprises gold and another metal for improving the adhesion between said gold and said substrate.
Claim 71
Dependent Claim
25 words
Apparatus in accordance with claim 55 wherein said other metal diffuses into said gold to form an alloy thereby increasing the sensitivity of said apparatus.
Claim 72
Dependent Claim
19 words
Apparatus as claimed in claim 50 wherein said surface comprises a plurality of metal globules attached to said substrate.
Claim 73
Dependent Claim
25 words
The apparatus of claim 57 wherein said metal globules consist of a metal having high atomic mobility and poor surface wetting characteristics on said substrate.
Claim 74
Dependent Claim
36 words
Apparatus for diagnosing gonorrhea in accordance with claim 50 wherein: said antigen of interest is Neisseria gonorrhea antigen; said fluid is blood serum; and said specifically reacting antibody is the antibody to the Neisseria gonorrhea antigen.
Claim 75
Dependent Claim
20 words
Apparatus in accordance with claim 59 wherein said surface comprises titanium with an overlying layer comprising an oxide of titanium.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-10-17 | 1981-04-18 | 1981-10-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-10-17 | 1985-04-18 | 1985-10-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-10-17 | 1989-04-18 | 1989-10-18 | $7700.00 | Window Closed / Lapsed |