US5045479A
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US
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Continuous flow competitive assay with reference system
Assignee: Johns Hopkins University
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Filing: 1988-07-05
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Granted: 1991-09-03
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Expires: 2008-07-05
Abstract
Abstract The invention relates to a continuous flow competitive assay system for the detection and measurement of chemical and biochemical analytes. It is a time-based, continuous on-line measurement of analyte concentrations comprising three functional assemblies connected in series: a sampler, a reactor and a detector. Tagged immunochemical discharged from the reactor is detected in the detector which contains a model of system response with the tagged immunochemical and keeps track of the amount of tagged immunochemical lost during the course of the operation of the reactor.
Inventors
- 👤 Arnold L. Newman
- 👤 William D. Stanbro
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 11:46
CPC Classifications
G; G01; G01N; G01N35/00; G01N35/08; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/543; G01N33/54366; G01N21/00; G01N21/62; G01N21/63; G01N21/64; G01N21/6428; G01N2021/6439; Y; Y10; Y10S; Y10S435/00; Y10S435/808; Y10T; Y10T436/00; Y10T436/11; Y10T436/117497; Y10T436/13
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
270 words
A competitive binding reaction apparatus for the continuous detection and measurement of at least one analyte in an environment, said apparatus comprising: a sample collector assembly for capturing samples of the environment, a chemical reaction assembly, a detection asseembly, and means for continuously flowing the sample from the collector assembly to the reaction assembly and then to the detection assembly; wherein said chemical reaction assembly comprises: a first immunochemical immobilized on a surface; and a second immunochemical provided with tags and specifically bound to said first immunochemical, at least one of said first and second immunochemicals able to specifically bind to the analyte; wherein said detection assembly comprises: means for detecting said tags in an exit stream from said chemical reaction assembly and producing first signals representing the total amount of tagged immunochemical in the exit stream; a reference system comprising: a closed recirculating reference loop containing a known amount of said tagged second immunochemical, means for detecting tags in said reference loop and producing second signals; means for normalizing said first signals by comparing with said second signals; a model means of a response of said chemical reaction assembly to said tagged second immunochemical when there is no sample present as a function of time, said model means providing the amount of second tagged immunochemical in the exit stream as a function of time; means comparing said normalized first signals with said model means to adjust the total amount of tagged immunochemical by the amount of tagged second immunochemical and produce third signals representing the continuous detection and measurement of the analyte; and output means showing said third signals.
Claim 2
Dependent Claim
270 words
A competitive binding reaction apparatus for the continuous detection and measurement of at least one analyte in an environment, said apparatus comprising: a sample collector assembly for capturing samples of the environment, a chemical reaction assembly, a detection asseembly, and means for continuously flowing the sample from the collector assembly to the reaction assembly and then to the detection assembly; wherein said chemical reaction assembly comprises: a first immunochemical immobilized on a surface; and a second immunochemical provided with tags and specifically bound to said first immunochemical, at least one of said first and second immunochemicals able to specifically bind to the analyte; wherein said detection assembly comprises: means for detecting said tags in an exit stream from said chemical reaction assembly and producing first signals representing the total amount of tagged immunochemical in the exit stream; a reference system comprising: a closed recirculating reference loop containing a known amount of said tagged second immunochemical, means for detecting tags in said reference loop and producing second signals; means for normalizing said first signals by comparing with said second signals; a model means of a response of said chemical reaction assembly to said tagged second immunochemical when there is no sample present as a function of time, said model means providing the amount of second tagged immunochemical in the exit stream as a function of time; means comparing said normalized first signals with said model means to adjust the total amount of tagged immunochemical by the amount of tagged second immunochemical and produce third signals representing the continuous detection and measurement of the analyte; and output means showing said third signals.
Claim 3
Dependent Claim
41 words
An apparatus according to claim 1, wherein the sample collector assembly comprises: means for capturing the sample from an environment, means for placing the sample in an aqueous solution, and means for conducting the resulting solution to the chemical reaction assembly.
Claim 4
Dependent Claim
20 words
An apparatus according to claim 1, wherein the chemical reaction assembly further comprises an aqueous compartment for enclosing said surface.
Claim 5
Dependent Claim
33 words
An apparatus according to claim 1, wherein said first immunochemical is an antibody specific to said analyte to be detected and measured and said second immunochemical is a tagged form of said analyte.
Claim 6
Dependent Claim
33 words
An apparatus according to claim 1, wherein said first immunochemical is a form of said analyte to be detected and measured and said second immunochemical is a tagged antibody specific to said analyte.
Claim 7
Dependent Claim
13 words
An apparatus according to claim 2, wherein said means conducting includes a pump.
Claim 8
Dependent Claim
52 words
An apparatus according to claim 1, wherein the tags are fluorescent and the means detecting comprises: a light source for exciting the tags in the exit stream causing them to produce emissions; and a light sensor detecting emissions produced by the fluorescent tags in the exit stream and producing said first signals.
Claim 9
Dependent Claim
67 words
An apparatus according to claim 7, wherein the reference system further comprises: a beam splitter for splitting a beam from said light source into two parts, a first part exciting the tags in the exit stream and a second part exciting tags in the reference loop; and a second light sensor detecting emissions produced by the fluorescent tags in said reference loop; and producing said second signals.
Claim 10
Dependent Claim
30 words
An apparatus according to claim 1, wherein the tags are one of cesium, barium or lithium, and the means detecting is a mass spectrometry means or an atomic absorption means.
Claim 11
Dependent Claim
21 words
An apparatus according to claim 1, wherein the tag is a substance not ordinarily present in the analyte or its environment.
Claim 12
Dependent Claim
24 words
An apparatus according to claim 1, wherein the surface is one of microspheres, a gel or an interior surface of the chemical reaction assembly.
Claim 13
Dependent Claim
20 words
An apparatus according to claim 7, wherein the light source is a laser and the light sensor is a photodiode.
Claim 14
Dependent Claim
265 words
A competitive binding reaction method for the continuous detection and measurement of at least one analyte in an environment, said method comprising: continuously capturing samples of the environment in a sample collector assembly; flowing said samples to a chemical reaction assembly; contacting a surface in the chemical reaction assembly with said samples, said surface being provided with: a first immunochemical immobilized thereon; and a second immunochemical provided with detectable tags and specifically bound to said first immunochemical, one of said first and second immunochemicals able to specifically bind to said analyte; flowing an exit stream from said chemical reaction assembly to a detection assembly; detecting the presence of said tags in the exit stream from said chemical reaction assembly in said detection assembly and producing first signals representing the total amount of tagged immunochemical in the exit stream; providing a closed recirculating reference system containing a known amount of said tagged second immunochemical; detecting the presence of tags in said system and producing second signals; normalizing said first signals by comparing with said second signals; providing a model of the response of said chemical reaction assemble to said tagged second immunochemical when there is no sample present, as a function of time, said model providing the amount of tagged second immunochemical in the exit stream as a function of time; comparing said normalized first signals with said model to adjust the total amount of tagged immunochemical by the amount of second tagged immunochemical and produce third signals representing the continuous detection and measurement of said analyte; and displaying said third signals on an output device.
Claim 15
Dependent Claim
265 words
A competitive binding reaction method for the continuous detection and measurement of at least one analyte in an environment, said method comprising: continuously capturing samples of the environment in a sample collector assembly; flowing said samples to a chemical reaction assembly; contacting a surface in the chemical reaction assembly with said samples, said surface being provided with: a first immunochemical immobilized thereon; and a second immunochemical provided with detectable tags and specifically bound to said first immunochemical, one of said first and second immunochemicals able to specifically bind to said analyte; flowing an exit stream from said chemical reaction assembly to a detection assembly; detecting the presence of said tags in the exit stream from said chemical reaction assembly in said detection assembly and producing first signals representing the total amount of tagged immunochemical in the exit stream; providing a closed recirculating reference system containing a known amount of said tagged second immunochemical; detecting the presence of tags in said system and producing second signals; normalizing said first signals by comparing with said second signals; providing a model of the response of said chemical reaction assemble to said tagged second immunochemical when there is no sample present, as a function of time, said model providing the amount of tagged second immunochemical in the exit stream as a function of time; comparing said normalized first signals with said model to adjust the total amount of tagged immunochemical by the amount of second tagged immunochemical and produce third signals representing the continuous detection and measurement of said analyte; and displaying said third signals on an output device.
Claim 16
Dependent Claim
28 words
A method according to claim 13, comprising: capturing the samples from the environment, placing said samples in an aqueous solution, and conducting the resulting solution to said surface.
Claim 17
Dependent Claim
15 words
A method according to claim 13, wherein the contacting step occurs within an aqueous compartment.
Claim 18
Dependent Claim
33 words
A method according to claim 13, wherein said first immunochemical is an antibody specific to said analyte to be detected and measured and said second immunochemical is a tagged form of said analyte.
Claim 19
Dependent Claim
18 words
A method according to claim 13, wherein said first immunochemical is a tagged antibody specific to said analyte.
Claim 20
Dependent Claim
15 words
A method according to claim 14, wherein the conducting step is performed with a pump.
Claim 21
Dependent Claim
65 words
A method according to claim 13, wherein the tag is fluorescent and the detecting step comprises: applying a light beam to said tagged second immunochemical in the detection assembly to excite the tags in the exit stream and cause them to produce emissions; and thereafter detecting emissions from the thus excited tags in the exit stream with a light sensor and producing said first signals.
Claim 22
Dependent Claim
62 words
A method according to claim 19, wherein the detecting step also includes: applying a portion of said light beam to the known amount of tagged second immunochemical in said closed recirculating reference system to excite the tags and produce emissions; and thereafter detecting the emissions from the thus excited tags in said reference system with a light sensor and producing third signals.
Claim 23
Dependent Claim
30 words
A method according to claim 13, wherein the tags are one of cesium, barium or lithium, and the detection assembly is a mass spectrometry means or an atomic absorption means.
Claim 24
Dependent Claim
21 words
A method according to claim 13, wherein the tag is a substance not ordinarily present in the analyte or its environment.
Claim 25
Dependent Claim
24 words
A method according to claim 13, wherein the surface is one of microspheres, a gel or an interior surface of the chemical reaction assembly.
Claim 26
Dependent Claim
22 words
A method according to claim 19, wherein the light beam is produced by a laser and the light sensor is a photodiode.
Claim 27
Dependent Claim
24 words
An apparatus according to claim 8, wherein the first, second and third signals are computer signals and wherein the means comparing is a computer.
Claim 28
Dependent Claim
26 words
A method according to claim 20, wherein the first, second and third signals are computer signals and wherein the means comparing step occurs within a computer.
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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) | 1994-09-02 | 1995-03-04 | 1995-09-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1998-09-02 | 1999-03-04 | 1999-09-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2002-09-02 | 2003-03-04 | 2003-09-03 | $7700.00 | Window Closed / Lapsed |