GB1604884A - Assay utilizing bacteria-antibody reaction - Google Patents
Assay utilizing bacteria-antibody reaction Download PDFInfo
- Publication number
- GB1604884A GB1604884A GB18018/78A GB1801878A GB1604884A GB 1604884 A GB1604884 A GB 1604884A GB 18018/78 A GB18018/78 A GB 18018/78A GB 1801878 A GB1801878 A GB 1801878A GB 1604884 A GB1604884 A GB 1604884A
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- Prior art keywords
- gram
- bacteria
- serum sample
- incubating
- complement
- 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
Links
- 238000003556 assay Methods 0.000 title claims description 15
- 241000894006 Bacteria Species 0.000 claims description 50
- 210000002966 serum Anatomy 0.000 claims description 30
- 230000001580 bacterial effect Effects 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 25
- 230000000295 complement effect Effects 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- 239000007788 liquid Substances 0.000 claims description 18
- 241000588724 Escherichia coli Species 0.000 claims description 14
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 claims description 13
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 12
- 239000001963 growth medium Substances 0.000 claims description 12
- 239000002609 medium Substances 0.000 claims description 12
- 241000588652 Neisseria gonorrhoeae Species 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 241000588650 Neisseria meningitidis Species 0.000 claims description 9
- 241000606768 Haemophilus influenzae Species 0.000 claims description 8
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 8
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 6
- 230000000415 inactivating effect Effects 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 239000003855 balanced salt solution Substances 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 238000011534 incubation Methods 0.000 claims description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 4
- 229940098773 bovine serum albumin Drugs 0.000 claims description 4
- 238000007865 diluting Methods 0.000 claims description 4
- 239000012895 dilution Substances 0.000 claims description 4
- 238000010790 dilution Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 230000003467 diminishing effect Effects 0.000 claims description 3
- 206010022000 influenza Diseases 0.000 claims description 3
- 239000001569 carbon dioxide Substances 0.000 claims description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/04—Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
-
- 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
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
-
- 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
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/571—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses for venereal disease, e.g. syphilis, gonorrhoea
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Toxicology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
(54) ASSAY UTILIZING BACTERIA-ANTIBODY REACTION
(71) We, MERCK & CO. INC., a corporation duly organized and existing under the laws of the State of New Jersey, United States of America, of Rahway, New Jersey, United
States of America, do hereby declare the invention for which we pray that a patent may be granted to us and the method by which it is to be performed to be particularly described in and by the following statement:
The present invention is concerned with (1) an automated test to determine the antibody titer of a sample by incubating in a microtiter plate a mixture containing a test example, the bacteria whose antibody is being evaluated in the sample, growth medium and complement, and measuring bacterial growth in the incubated mixture, and (2) an automated test for determining the identity and initial concentration of bacteria in a sample by incubating in a microtiter plate a mixture containing a test example, bacterial antiserum, complement, and growth medium and measuring inhibition of bacterial growth.
The present invention provides a method of determining the antibody level to a gram negative bacterium in a serum sample comprising a) inactivating the serum sample;
(b) diluting the sample serially to obtain aliquot portions of diminishing concentrations;
(c) incubating simultaneously each of the portions, together with the culture of a gram-negative bacterium of known concentration and complement, at a physiologically acceptable temperature;
(d) adding a liquid growth medium to each of the portions from step (c):
(e) incubating each of the mixtures resulting from step (d) at a physiologically acceptable temperature;
and
(f) measuring and scoring the inhibition of bacterial growth in the liquid medium.
In a practical method of carrying out this method, the serum sample is usually mixed with rabbit complement, preferably complement from baby rabbits up to about 4 weeks old, and with the bacteria whose antibody level in the sample is being measured. After incubating the mixture for a brief period of time, e.g. for from 30 to 50 minutes, broth is added and the mixture incubated for from 15 to 30 hours, preferably for from 20 to 24 hours, at about 37"C.
The present invention also provides a method for determining the identity of an antibody to a gram-negative bacterium present in a serum sample comprising
a) inactivating the serum sample;
b) incubating the inactivated serum sample together with complement and culture of a gram negative bacterium of known concentration at a physiologically acceptable temperature;
(c) adding a liquid growth medium to the mixture resulting from step (b);
(d) incubating the mixture resulting from step (c) at a physiologically acceptable temperature;
and
(e) measuring and scoring the inhibition of the bacterial growth in the liquid medium.
The present invention also provides a method for determining the identity of a gram-negative bacterium selected from a pre-determined group of bacteria present in a serum sample comprising:
(a) incubating the serum sample together with a reference antiserum to a known gram-negative bacterium and complement at a physiologically acceptable temperature;
(b) adding a liquid growth medium to the mixture resulting from step (a);
(c) incubating the mixture resulting from step (b) at a physiologically acceptable temperature and
(d) measuring and scoring the inhibition of bacterial growth in the liquid medium.
This automated method can determine the identity and initial concentration of bacteria in a serum sample such as mentioned previously. The sample is mixed with antisera for the bacteria whose identity is being determined, growth medium and complement. After incubating the mixture for a short period of time, e.g. for from about 30 to 50 minutes, broth is added and the mixture is incubated for from about 15 to about 30 hours, preferably for from about 20 to about 24 hours, at about 37"C.
The automated assay methods of the present invention are applicable to antibody or bacterial determinations for all gram negative bacteria. It has particular utility in determining antibody to such pathogenic organisms as N. men in gitidis, Salmonella,
Neisseria gonorrhea, Hemophilus influenza and E. coli, or such pathogenic organisms themselves.
The assay is preferably carried out using standard 96-well assay plates, automatic pipetting equipment and automatic diluting equipment. In this way the assay is automated, uses lesser amounts of ingredients than conventional methods, and is faster and more accurate. The cost of the assay is reduced considerably compared to the manual method used heretofore while the precision of the assay is improved.
The method of the present invention may conveniently be carried out in a diagnostic test kit which includes, for bacterial determination, lyophilized samples of antibody to gram-negative bacteria such as, for example, antibody to E. coli, S. typhi, N. meningitidis strains A and C, H. influenza and N. gonorrhea. Complement may be supplied either as part of the kit or may be provided by the user of the kit. Such a kit, which constitutes another embodiment of the present invention, is used to determine the identity of any of the foregoing bacteria in clinical samples. This test has the advantage of excluding non-specific effects.
The method of the resent invention may conveniently be carried out in a diagnostic test kit which includes, for antibody determination, lyophilized samples of gram-negative bacteria such as, for example, E. coli, S. typhi, N. meningitidis strains A and C, H.
influenza and N. gonorrhea. Complement may be supplied either as part of the kit or may be provided by the user of the kit. This test also has the advantage of excluding nonspecific effects.
The following examples illustrate but do not limit the present invention.
EXAMPLE I
Frozen sera samples are thawed rapidly in cold tap water. Sera are heat inactivated at 56"C for 30 minutes and kept in ice water until removed for assay. 25 microliters of the heat inactivated sera being tested are added with sterile pipette tips to each of the 12 wells in row 1 of MICROTITER R plates (Cooke Laboratory Products). These are disposable, rigid polystyrene plates, sterile and with U wells. From 8 to 96 wells/samples are used depending upon the desired accuracy. Each plate is positioned in the automatic pipette (Cooke
Laboratory Products) and 0.025 ml of sterile balanced salt solution (Grand Island
Biological Co.) and 0.1% bovine serum albumin are added to each of the 96 wells. The plate is then positioned in the automatic diluter (Cooke Laboratory Products) which is operated according to the manufacturer's instructions. This performs two-fold dilutions if 0.025 ml diluters are being used. Using a fresh disposable tray, 0.025 ml of a fresh bacterial culture of Neisseria meningitidis is added to each well. This preparation must contain from 15 to 30 fresh viable organisms/0.025 ml. Each late is shaken for 20 to 30 seconds after addition of bacteria. Next, 0.025 ml of baby rabbit complement (PelFreeze) is added to each well with an automatic pipetter. The plates are shaken again for 20-30 seconds, and then incubated for 40 minutes in a water saturated 37"C incubator. At the end of this incubation period, 0.125 ml of Mueller Hinton broth is added to each well with the automatic pipetter. This step must be carried with a new sterile head and a new disposable plastic reservoir. The plates are incubated for 20 to 24 hours in a 37"C humidified 5 CO2 incubator. Wells with no bacterial growth are scored as negative. Wells with bacterial growth are scored as positive. The use of a test reading mirror (Cooke) makes the plate reading easier. With each test the following controls are included: number of bacteria in 0.025 ml challenge; serum control; baby rabbit complement control; inactivated baby rabbit complement control; organism control and reference sera.
Manual Petri-Dish
Automated Titer Titer
Sample Pre Post Pre Post
1 8 64 16 128
2 64 2048 64 1024
3 32 2048 32 512
4 2 256 2 256
5 128 4096 32 512
6 8 256 8 256
7 4 128 2 256
8 32 512 16 256
EXAMPLE 2
The following table summarizes the assay variability as a function of the number of assays per sample.
95% Confidence limits for
Number of Samples average log potency
1 + 0.692
2 + 0.489
3 + 0.399
4 + 0.346
5 + 0.309
6 + 0.282
7 + 0.262
8 + 0.245
9 + 0.231
10 + 0.219
EXAMPLE 3
TEST KIT FOR ANTIBODIES
A clinical serum sample to be tested for the presence of antibodies to E. coli, S. typhi, N.
meningitidis strains A and C, H. influenza and N. gonorrhea is heat inactivated at 560C for 30 minutes. 25 microliters of the inactivated serum being tested is added with sterile pipette tips to each second well of row A of MICROTITERR plates (Cooke Laboratory Products).
The rest of the wells of row A receive 25 microliters of sterile balanced salt solution (Grand
Island Biologicals). Each plate is positioned in the automatic pipetter and 25 microliters of sterile balanced salt solution with 0.1% bovine serum albumin is added to each of the 96 wells. The plate is then positioned in the automatic diluter which is operated according to the manufacturer's instructions. Two-fold dilutions are used. 25 microliters of a reconstituted lyophilized bacterial culture of E. coli are added with sterile pipette tips to all wells of row 1 and 2. Row 1 contains the serum and row 2 is a bacterial growth control.
Rows 3 and 4 receive S. typhi, and rows 5 and 6 receive N. meningitidis A. The bacterial preparations contain from 15-30 fresh viable organisms/25 microliters. They are supplied in the lyophilized state as part of the test kit and contain after reconstitution the required amount of bacteria. Next 25 microliters of baby rabbit complement are added to each well with an automatic pipetter. Plates are then shaken for 20-30 seconds and incubated for 40 minutes in a water saturated 37"C incubator. Then 125 microliters of Mueller-Hinton broth are added to each well with the automatic pipetter. This step must be carried out with a new sterile head and a new disposable plastic reservoir. The plates are incubated overnight (20-24 hours in a 37"C humidified 5% CO2 incubator). If a sample of serum inhibits bacterial growth, the identity as well as the titer is determined.
EXAMPLE 4
TEST K1T FOR BACTERIA
25 microliters of a clinical serum sample to be tested for the presence of the following bacteria: E. coli, S. typhi, N. meningitidis A and C, H. influenza and N. gonorrhea is added with sterile pipette tips to each well of row A of MICROTITTER " plates. Then 25 microliters of reference antisera for the tested bacteria are added to each second well of row
A. Well A2 receives antiserum to E. coli, well A4 to S. typhi, etc. These antisera are part of the kit and are supplied in the lyophilized state. Each plate is positioned in the automatic pipetter and receives 25 microliters/well of sterile balanced salt solution with 0.1% bovine serum albumin. The plate is then positioned in the automatic diluter and two-fold dilutions are performed. Next 25 microliters of baby rabbit complement are added to each well with an automatic pipetter. The plates are then shaken for 20-30 seconds and incubated for 40 minutes in a water saturated 37"C incubator. Then 125 microliters of Mueller-Hinton broth are added to each well with the automatic pipetter. The plates are incubated overnight (20-24 hours in a 37"C humidified 5% CO2 incubator). If samples of reference sera inhibit bacterial growth this serves to establish the identity and initial concentration of the bacteria in the tested sera.
WHAT WE CLAIM IS:
1. A method for determining the identity of a gram-negative bacterium selected from a pre-determined group of bacteria present in a serum sample comprising:
(a) incubating the serum sample together with a reference antiserum to a known gram negative bactenum and complement at a physiologically acceptable temperature;
(b) adding a liquid growth medium to the mixture resulting from step (a);
(c) incubating the mixture resulting from step (b) at a physiologically acceptable temperature;
and
(d) measuring and scoring the inhibition of bacterial growth in the liquid medium.
2. A method for determining the identity of an antibody to a gram negative bacterium present in a serum sample that comprises
(a) inactivating the serum sample;
(b) incubating the inactivated serum sample together with complement and culture of a gram-negative bacterium of known concentration at a physiologically acceptable temperature;
(c) adding a liquid growth medium to the mixture resulting from step (b);
(d) incubating the mixture resulting from step (c) at a physiologically acceptable temperature;
and
(e) measuring and scoring the inhibition of the bacterial growth in the liquid medium.
3. A method of determining the antibody level to a gram negative bacterium in a serum sample comprising a inactivating the serum sample; b) diluting the sample serially to obtain aliquot portions of diminishing concentrations;
(c) incubating simultaneously each of the portions, together with the culture of a gram-negative bacterium of known concentration and complement, at a physiologically acce table temperature; d adding a liquid growth medium to each of the portions from step (c); (e) incubating each of the mixtures resulting from step (d) at a physiologically acceptable temperature;
and
(f) measuring and scoring the inhibition of bacterial growth in the liquid medium.
4. A method according to Claims 1, 2 or 3, in which the first incubation is carried out under a water-saturated atmosphere at about 37"C and the second incubation is carried out under a humidified atmosphere containing about 5% carbon dioxide.
5. A method according to Claim 1, in which steps (a) to (d) are carried out in a multiwell assay plate for a series of E. coli, S. typhi, N. meningitidis, H. influenzae and/or
N. gonorrhea gram-negative bacteria.
6. A method according to Claim 2, in which steps (a) to (e) are carried out in a multiwell assay plate for a series of reference antisera to E. coli, S. typhi, N. men in gitidis, H. influenzae and/or N. gonorrhea gram-negative bacteria.
7. A test kit for carrying out the.method of Claim 1 comprising
(a) a lyophilized antiserum to a known gram-negative bacterium to be used in step (a) as the reference antiserum;
(b) a medium for the growth of the bacterium;
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (9)
- **WARNING** start of CLMS field may overlap end of DESC **.EXAMPLE 4 TEST K1T FOR BACTERIA25 microliters of a clinical serum sample to be tested for the presence of the following bacteria: E. coli, S. typhi, N. meningitidis A and C, H. influenza and N. gonorrhea is added with sterile pipette tips to each well of row A of MICROTITTER " plates. Then 25 microliters of reference antisera for the tested bacteria are added to each second well of row A. Well A2 receives antiserum to E. coli, well A4 to S. typhi, etc. These antisera are part of the kit and are supplied in the lyophilized state. Each plate is positioned in the automatic pipetter and receives 25 microliters/well of sterile balanced salt solution with 0.1% bovine serum albumin. The plate is then positioned in the automatic diluter and two-fold dilutions are performed. Next 25 microliters of baby rabbit complement are added to each well with an automatic pipetter. The plates are then shaken for 20-30 seconds and incubated for 40 minutes in a water saturated 37"C incubator. Then 125 microliters of Mueller-Hinton broth are added to each well with the automatic pipetter. The plates are incubated overnight (20-24 hours in a 37"C humidified 5% CO2 incubator). If samples of reference sera inhibit bacterial growth this serves to establish the identity and initial concentration of the bacteria in the tested sera.WHAT WE CLAIM IS: 1. A method for determining the identity of a gram-negative bacterium selected from a pre-determined group of bacteria present in a serum sample comprising: (a) incubating the serum sample together with a reference antiserum to a known gram negative bactenum and complement at a physiologically acceptable temperature; (b) adding a liquid growth medium to the mixture resulting from step (a); (c) incubating the mixture resulting from step (b) at a physiologically acceptable temperature; and (d) measuring and scoring the inhibition of bacterial growth in the liquid medium.
- 2. A method for determining the identity of an antibody to a gram negative bacterium present in a serum sample that comprises (a) inactivating the serum sample; (b) incubating the inactivated serum sample together with complement and culture of a gram-negative bacterium of known concentration at a physiologically acceptable temperature; (c) adding a liquid growth medium to the mixture resulting from step (b); (d) incubating the mixture resulting from step (c) at a physiologically acceptable temperature; and (e) measuring and scoring the inhibition of the bacterial growth in the liquid medium.
- 3. A method of determining the antibody level to a gram negative bacterium in a serum sample comprising a inactivating the serum sample; b) diluting the sample serially to obtain aliquot portions of diminishing concentrations; (c) incubating simultaneously each of the portions, together with the culture of a gram-negative bacterium of known concentration and complement, at a physiologically acce table temperature; d adding a liquid growth medium to each of the portions from step (c); (e) incubating each of the mixtures resulting from step (d) at a physiologically acceptable temperature; and (f) measuring and scoring the inhibition of bacterial growth in the liquid medium.
- 4. A method according to Claims 1, 2 or 3, in which the first incubation is carried out under a water-saturated atmosphere at about 37"C and the second incubation is carried out under a humidified atmosphere containing about 5% carbon dioxide.
- 5. A method according to Claim 1, in which steps (a) to (d) are carried out in a multiwell assay plate for a series of E. coli, S. typhi, N. meningitidis, H. influenzae and/or N. gonorrhea gram-negative bacteria.
- 6. A method according to Claim 2, in which steps (a) to (e) are carried out in a multiwell assay plate for a series of reference antisera to E. coli, S. typhi, N. men in gitidis, H. influenzae and/or N. gonorrhea gram-negative bacteria.
- 7. A test kit for carrying out the.method of Claim 1 comprising (a) a lyophilized antiserum to a known gram-negative bacterium to be used in step (a) as the reference antiserum; (b) a medium for the growth of the bacterium;and (c) complement to promote the bacterial growth.
- 8. A test kit for carrying out the method of Claim 2 or 3 comprising (a) a lyophilized gram-negative bacterium for preparing the culture required in step (b); (b) a medium for the growth of the bacterium; and (c) complement to promote the bacterial growth.
- 9. A test kit according to Claim 8, in which the lyophilized gram-negative bacterium is E. coli, S. typhi, N. meningitidis, N. influenza or N. gonorrhea.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US79477277A | 1977-05-09 | 1977-05-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1604884A true GB1604884A (en) | 1981-12-16 |
Family
ID=25163629
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB18018/78A Expired GB1604884A (en) | 1977-05-09 | 1978-05-05 | Assay utilizing bacteria-antibody reaction |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS542318A (en) |
| BE (1) | BE866664A (en) |
| BR (1) | BR7802880A (en) |
| CA (1) | CA1109790A (en) |
| DE (1) | DE2820071A1 (en) |
| ES (1) | ES469586A1 (en) |
| FR (1) | FR2390502A1 (en) |
| GB (1) | GB1604884A (en) |
| IT (1) | IT1117351B (en) |
| NL (1) | NL7804410A (en) |
| PT (1) | PT67981B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2172704A (en) * | 1985-03-18 | 1986-09-24 | Nat Res Dev | Antigenically active protein and its use in the diagnosis of gonorrhoea |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2537725B1 (en) * | 1982-12-09 | 1985-07-12 | Pasteur Institut | METHOD FOR THE IMMUNOBACTERIOLOGICAL DETECTION OF PATHOGENIC GERM IN CONTAMINATED BIOLOGICAL MEDIA |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3864624A (en) * | 1972-05-31 | 1975-02-04 | Yokogawa Electric Works Ltd | Standard voltage generating circuit |
| GB1378103A (en) * | 1972-08-31 | 1974-12-18 | Research Corp | Serological reagent and test for neisseria gonorrhoeae antibodies |
-
1978
- 1978-04-25 NL NL7804410A patent/NL7804410A/en not_active Application Discontinuation
- 1978-05-02 PT PT67981A patent/PT67981B/en unknown
- 1978-05-03 BE BE187354A patent/BE866664A/en unknown
- 1978-05-05 CA CA302,714A patent/CA1109790A/en not_active Expired
- 1978-05-05 FR FR7813376A patent/FR2390502A1/en not_active Withdrawn
- 1978-05-05 IT IT49223/78A patent/IT1117351B/en active
- 1978-05-05 GB GB18018/78A patent/GB1604884A/en not_active Expired
- 1978-05-08 DE DE19782820071 patent/DE2820071A1/en not_active Withdrawn
- 1978-05-08 ES ES469586A patent/ES469586A1/en not_active Expired
- 1978-05-08 BR BR7802880A patent/BR7802880A/en unknown
- 1978-05-09 JP JP5414378A patent/JPS542318A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2172704A (en) * | 1985-03-18 | 1986-09-24 | Nat Res Dev | Antigenically active protein and its use in the diagnosis of gonorrhoea |
Also Published As
| Publication number | Publication date |
|---|---|
| PT67981B (en) | 1980-05-05 |
| IT1117351B (en) | 1986-02-17 |
| CA1109790A (en) | 1981-09-29 |
| JPS542318A (en) | 1979-01-09 |
| NL7804410A (en) | 1978-11-13 |
| FR2390502A1 (en) | 1978-12-08 |
| IT7849223A0 (en) | 1978-05-05 |
| BR7802880A (en) | 1979-01-02 |
| DE2820071A1 (en) | 1978-11-23 |
| PT67981A (en) | 1978-06-01 |
| ES469586A1 (en) | 1979-09-16 |
| BE866664A (en) | 1978-11-03 |
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