GB2335491A - Detecting microorganisms - Google Patents
Detecting microorganisms Download PDFInfo
- Publication number
- GB2335491A GB2335491A GB9814600A GB9814600A GB2335491A GB 2335491 A GB2335491 A GB 2335491A GB 9814600 A GB9814600 A GB 9814600A GB 9814600 A GB9814600 A GB 9814600A GB 2335491 A GB2335491 A GB 2335491A
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- microorganisms
- gaseous
- mass spectrometer
- gaseous atmosphere
- species
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- 244000005700 microbiome Species 0.000 title claims abstract description 72
- 241000894007 species Species 0.000 claims abstract description 33
- 239000007789 gas Substances 0.000 claims abstract description 16
- 238000001514 detection method Methods 0.000 claims abstract description 13
- 241000195493 Cryptophyta Species 0.000 claims abstract description 5
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims abstract description 5
- 241000700605 Viruses Species 0.000 claims abstract description 5
- 210000004962 mammalian cell Anatomy 0.000 claims abstract description 5
- 230000000241 respiratory effect Effects 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 33
- 238000004458 analytical method Methods 0.000 claims description 27
- 238000001819 mass spectrum Methods 0.000 claims description 16
- 238000012258 culturing Methods 0.000 claims description 14
- 241000894006 Bacteria Species 0.000 claims description 10
- 238000013375 chromatographic separation Methods 0.000 claims description 6
- 238000013528 artificial neural network Methods 0.000 claims description 5
- 238000004949 mass spectrometry Methods 0.000 claims description 5
- 210000004027 cell Anatomy 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- 241000233866 Fungi Species 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 abstract 1
- 238000005259 measurement Methods 0.000 description 4
- 238000009640 blood culture Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010633 broth Nutrition 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000642 dynamic headspace extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000002124 flame ionisation detection Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000007412 host metabolism Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000000865 membrane-inlet mass spectrometry Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 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
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/02—Devices for withdrawing samples
- G01N1/22—Devices for withdrawing samples in the gaseous state
- G01N1/2226—Sampling from a closed space, e.g. food package, head space
- G01N2001/2229—Headspace sampling, i.e. vapour over liquid
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Analytical Chemistry (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
Microoganisms are detected by; introducing a gaseous atmosphere associated with the microorganisms to a mass spectrometer; detecting gaseous species present in the gaseous atmosphere with the mass spectrometer; and correlating the detection of said gaseous species with the presence of the microorganisms. Microoganisms may be viruses, algae, yeasts, plant on mammalian cells. Atmosphere may be the headspace adjacent microoganisms or respiratory gases.
Description
Y 2335491 DETECTING MICROORGANISMS This invention relates to the detection
of microorganisms by mass spectrometry.
It is known that bacteria can be identified by gas chromatographic analysis of a gaseous headspace associated with the bacteria. Anaerobic bacteria have been detected in this way by gas chrornatogmphy (GC) using a flame ionisation detector (L. Larsson and E. Holst, Acta path. Microbiol Immunol. Scand. Sect. B, 90 (1982) 125). GC with flame ionisation detection has also been used to identify aerobic and anaerobic bacteria in blood cultures via sampling of the associated headpsace (S-W Ho, Chinese J Microbiol Immunol, (L9 (1986) 18). The bacteria are identified by reference to a spectrum of peaks which are registered at characteristic retention times and which correspond to individual gaseous species present in the headspace. However, if different gaseous species exhibit similar affinities for the GC column employed in the analysis, it becomes difficult or impossible to positively identify which of these different species are actually present, because the associated peaks in the chromatograph overlap or are completely superimposed upon each other. Almost certainly, this problem limits the number of bacterial species which may be identified by those techniques. Additionally, the identification of bacteria from very complex headspace atmospheres, which might contain "extraneous" gaseous species produced by other bacterial species or by other metabolic processes, is made extremely difficult.
The present invention provides a solution to these problems. Furthermore, the detection of other types of microorganisms is provided.
For the avoidance of doubt, the term "gaseous" is understood to encompass all spycies present in the gas phase, including volatile species.
According to a first aspect of the present invention there is provided a method for detecting microorganisms comprising the steps of:
introducing a gaseous atmosphere associated with the microorganisms to a mass spectrometer; detecting gaseous species present in the gaseous atmosphere with the mass spectrometer; and correlating the detection of said gaseous species with the presence of the microorganisms.
The method may identify the genus of the microorganisms. Additionally, the species of the microorganisms may be identified.
In a preferred embodiment, the gaseous atmosphere is introduced to the mass spectrometer without using a gas chromatographic separation stage. This embodiment has several advantages: it enables faster analysis of samples since components in gaseous atmosphere are analysed simultaneously; it does not involve the additional expense of providing chromatography columns and it does not entail down time for replacing dirty columns. It is surprising that such measurements of the complex gaseous atmospheres associated with microorganisms can be made by mass spectrometry without a gas chromatographic pre-separation stage.
A chemometric technique may be used to analyse mass spectra produced by the mass spectrometer. Alternatively, or additionally, a neural network may be used for this analysis.
The microorganisms may comprise bacteria, viruses, microfungi, algae, yeasts, mammalian cells and/or plant cells.
The gaseous atmosphere may comprise a gaseous headspace present adjacent to the microorganisms. The microorganisms may be cultured within a culturing enclosure comprising a culturing medium, which may be a blood culture or other suitable culturing media, such as broths or gels. Usually the purpose of such culturing is to ensure that microorganisms of only a single species are present, at least pre-dominantly, in the culture.
Alternatively, the microorganisms may be detected in vivo, e.g. in or on the body of a patient. In this instance, the gaseous atmosphere may comprise emitted respiratory gases. It is surprising that microorganisms may be detected in this way, since the gaseous atmosphere is typically very complex, comprising gaseous species emanating from a large number of metabolic processes.
According to a second aspect of the invention there is provided apparatus for detecting microorganisms comprising:
a mass spectrometer; introduction means for introducing a gaseous atmosphere associated with the microorganisms to the mass spectrometer, thereby to enable detection of gaseous species present in the gaseous atmosphere; and analysis means adapted to correlate the detection of said gaseous species with the presence of microorganisms.
The analysis means may be adapted to identify the genus of the microorganisms, and, additionally, may be adapted to identify the species of the microorganisms.
In a preferred embodiment, the means for introducing a gaseous atmosphere associated with the microorganisms to the mass spectrometer does not comprise a gas chromatographic separation step.
The analysis means may perform a chemometric technique. Alternatively, or additionally, the analysis means may comprise a neural network.
The apparatus may be adapted to detect bacteria, viruses, microfungi, algae, yeast, mammalian cells and/or plant cells.
Methods and apparatus in accordance with the invention will now be described with reference to the accompanying Figure, which shows schematically an apparatus for detecting microorganisms.
The Figure shows apparatus for detecting microorganisms comprising:
a mass spectrometer 10; introduction means 12, 14 for introducing a gaseous atmosphere associated with the microorganisms to the mass spectrometer 10, thereby to enable detection of gaseous species present in the gaseous atmosphere; and analysis means 16 adapted to correlate the detection of the gaseous species with the present of microorganisms.
In this way, microorganisms can be detected by reference to mass spectra obtained by mass spectrometric analysis of certain gaseous atmospheres which are affected by the microorganisms in some way.
It is possible to utilise a gas chromatographic separation stage before the mass spectrometer 10 - in other words, to use a GC-MS approach. However, in preferred embodiments, such as that shown in the Figure, the gaseous atmosphere is introduced to the mass spectrometer 10 without using a gas chromatographic separation stage. The principal advantage of this approach is that fast analysis is possible since components in the gaseous atmosphere are analysed simultaneously, rather than being retained, often for many minutes, on a GC column. Other advantages are that the additional costs and down time associated with GC columns are avoided. It is possible to provide other forms of separation or filtration, but it is highly desirable that any method employed does not significantly affect the ability to flow the gaseous atmosphere into the mass spectrometer so that the subsequent analysis can be performed on a single mass spectrum. For example, it may prove desirable to remove water present in the gaseous atmosphere, or to reduce or standardise the water content, since differences in water content can affect the ionisation potential of gaseous species which can in turn affect mass fragmentation patterns. This might be achieved by flowing the gaseous atmosphere through a drying unit employing Naflon C tubing. It is possible to remove other solvents, and also to concentrate gaseous species by using, for example, purge and trap techniques or Tertax (RTM) tubing.
The gaseous atmosphere can comprise a gaseous headspace present adjacent to the microorganisms, although, as described in more detail below, it is possible with in vivo applications for the gaseous atmosphere sampled to be spatially removed from the microorganisms contributing to it. The microorganisms can be cultured within a culturing enclosure - such as the vial 12 shown in the Figure - comprising a culturing medium 18. The culturing enclosure - which might alternatively comprise for example, a lidded culturing dish or plate - enables a headpsace 20 to form, the headspace 20 containing various gaseous species characteristic of the microorganisms. These characteristic gaseous species might be products of microorganisms metabolism, or decomposition products associated with the death of the microorganism. It is also possible that the absence of certain gaseous species from the mass spectra might be indicative of the microorganism. Such species may be absent due to metabolic of same by the microorganisms. It should be noted that it is known to identify bacteria by a technique in which cellular fatty acids are extracted from bacteria and then analysed by gas chromatography. Such techniques are time consuming, and require quite complex extraction procedures which require additional chemical reagents. The analysis of fatty acids or any other products obtained by such extraction techniques do not constitute a gaseous atmosphere associated with the microorganisms within the context of the present invention. However, it is quite possible that the mass spectrometric techniques described herein might be usefully employed in the analysis of such extraction products.
The culturing medium 18 can comprise any medium suitable for the microorganism to be detected. A particularly important - but non-limiting - example is a blood culture.
In the Figure, the introduction means comprises an autosampler 14 having a syringe 14a which can be positioned so as to puncture a seal disposed in the top of the vial 12. It is possible to position a plurality of vials in the autosampler 14, enabling a batch of samples to be analysed automatically.
The analysis means 16 comprises a computer having suitably adapted software. A number of different methods are possible which enable the complex mass spectra to be correlated with the presence of certain microorganisms. Chemometric techniques, such as Principal Components Analysis (PCA), Discriminant Function Analysis (DFA) or a "maximum entropy" technique might be applied. Alternatively, or additionally, a neural network might be used. Mass spectra can be compared against a "library" of reference mass spectra associated with different microorganisms in order to provide identification. Thus the mass spectra act as characteristic microorganism "fingerprints". It will be apparent to the skilled reader that it is not necessary to positively identify the individual gaseous species present in order to identify the microorganism. It is envisaged that the detection of identification of microorganisms will rely on a complex mass spectrometric, "fmgerprint" which will comprise a number of trace species, present in relatively low concentrations, which are characteristic of the microorganisms. It is possible to obtain mass spectra of major metabolic products such as oxygen, hydrogen and carbon dioxide, and information on these major components of the gaseous atmosphere may also assist in detection and identification.
The present invention enable the identification of the species and/or the genus of the microorganisms. It may even be possible to identify the strain of the microorganism. In fact, it may be necessary to account for strain dependent variations in mass spectra in order to correlate the mass spectra to the associated microorganism. Preferably, variations in mass spectra caused by other factors such as temperature, the culturing medium employed and the growth phase of the microorganism are also taken into account.
Apart from analysis purposes, the computer 16 is used for controlling and pre-programming the overall process. A monitor screen 16a is used to display data. It is advantageous that the overall operation of the system and the data analysis can be automated so that operators do not require a high level of skill in order to use the apparatus.
Examples of mass spectrometric systems which can be adapted to perform the present invention are the "HP 4440 Chemical Sensor" (available from HewlettPackard, Palo Alto, California, USA) and the "Smart Nose" (available from Laboratoire Dr Zesigner, Neuchatel, Switzerland). Both of these instruments use a quadruple mass spectrometer. Other forms of mass spectrometry, such as magnetic sector or time of flight (TOF) mass spectrometers, are within the scope of the invention. Also, the commercially available systems described utilise an electron impact ionisation source which operates at ca. 70 eV. The present invention recognises that the magnitude of the ionisation energy will affect the data obtained using the present technique. In particular, higher ionisation energies will result in complex mass spectra which are difficult to analyse due to extensive fragmentation (although the information content of such spectra will be high). It may be preferably to utilise "softer" ionisation sources or techniques such as chemical ionisation, operating below 70 eV, so that less complex fragmentation patterns are produced. The invention is not limited in this respect: ionisation energies corresponding to vacuum ultra-violet wavelengths might be used.
An alternative scheme for introducing the gaseous atmosphere into a mass spectrometer would readily occur to the skilled person, such as a culturing bottle having a one way valve which is attachable to tubing which itself is in connection with the mass spectrometer, thereby permitting pumping of the gaseous atmosphere into the mass spectrometer. It may be possible to detect microorganisms in vivo, i.e. by direct measurements on a patient. For example, healing process of a wound might be assessed by "sniffing" gases emitted from the wound in some way, perhaps via a cuff or a cup which is placed over the wound. Alternatively, microorganisms might be detected by sampled emitted respiratory gases from a subject. It will be appreciated that i) the gaseous atmosphere sampled might be spatially removed from the microorganisms which produced or affected the atmosphere in some way and ii) such measurements are more difficult than the measurements described previously on cultures of single species, since other microorganisms and sundry host metabolic processes might contribute to the mass spectra obtained. Another variation is to use membrane inlet mass spectrometry MMS), in which gases are pumped across a polymeric membrane before entering the mass spectrometer. The membrane may separate the mass spectrorneter from the headspace above the microorganisms, or from a solution containing the microorganisms.
Also it is envisaged that quick assessments might be made of a patient by directly introducing gaseous atmospheres obtained from the patient into the mass spectrometer, it is also possible to store such patient gaseous atmospheres in a suitable container, such as a bag, and to transport the containers to the mass spectrometer, which might be housed in a path lab, for subsequent analysis.
1
Claims (21)
1.
A method for detecting microorganisms comprising the steps of.. introducing a gaseous atmosphere associated with the microorganisms to a mass spectrometer; detecting gaseous species present in the gaseous atmosphere with the mass spectrometer; and correlating the detection of said gaseous species with the presence of the microorganisms.
2.
microorganisms.
3.
microorganisms.
A method according to claim 1 for identifying the genus of the A method according to claim 2 for identifying the species of the
4. A method according to any of claims 1 to 3 in which the gaseous atmosphere is introduced to the mass spectrometer without using a gas chromatographic separation stage.
5. A method according to any of claims 1 to 4 in which a chemometric technique is used to analyse mass spectra produced by the mass spectrometer.
6. A method according to any of claims 1 to 5 in which a neural network is used to analyse a mass spectrum produced by the mass spectrometer.
7. A method according to any of the previous claims in which the c microorganisms comprise bacteria.
8. A method according to any of claims 1 to 6 in which the microorganisms comprise viruses, microfungi, algae, yeasts, mammalian cells and/or plant cells.
9. A method according to any of the previous claims in which the. gaseous atmosphere comprises a gaseous headspace present adjacent to the microorganisms.
10. A method according to claim 9 in which the microorganisms are cultured within a culturing enclosure comprising a culturing medium.
11. culture.
A method according to claim 10 jn which the culturing medium is a blood
12. A method according to any of claims 1 to 9 in which the microorganisms are detected in vivo.
13. A method according to claim 12 in which the gaseous atmosphere comprises emitted respiratory gases.
14.
Apparatus for detecting microorganisms comprising a mass spectrometer; introduction means for introducing a gaseous atmosphere associated with the microorganisms to the mass spectrometry thereby to enable detection of gaseous species present in the gaseous atmosphere; and analysis means adapted to correlating the detection of said gaseous species with the presence of microorganisms.
15. Apparatus according to claim 14 in which the analysis means is adapted to identify the genus of a microorganism.
16. Apparatus according to claim 15 in which the analysis means is adapted to identify the species of a microorganism.
17. Apparatus according to any of claims 14 to 16 in which the means for introducing a gaseous atmosphere associated with the microorganisms to the mass spectrometer does not comprise a gas chromatographic separation stage.
Apparatus according to any of claims 14 to 17 in which the analysis means comprise chemometric analysis.
19. Apparatus according to any of claims 14 to 18 in which the analysis means comprises a neural network.
20.
Apparatus according to any of claims 18 to 19 adapted to detect bacteria.
21. Apparatus according to any of claims 14 to 20 adapted to detect viruses, micro fungi, algae, yeasts, mammalian cells and/or plant cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9814600A GB2335491A (en) | 1998-07-07 | 1998-07-07 | Detecting microorganisms |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9814600A GB2335491A (en) | 1998-07-07 | 1998-07-07 | Detecting microorganisms |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB9814600D0 GB9814600D0 (en) | 1998-09-02 |
| GB2335491A true GB2335491A (en) | 1999-09-22 |
Family
ID=10835010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB9814600A Withdrawn GB2335491A (en) | 1998-07-07 | 1998-07-07 | Detecting microorganisms |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2335491A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002057989A2 (en) * | 2001-01-18 | 2002-07-25 | Basf Aktiengesellschaft | Method for metabolic profiling |
| WO2005038451A2 (en) * | 2003-10-14 | 2005-04-28 | Raytheon Company | Mass spectrometer for entrained particles, and method for measuring masses of the particles |
| WO2020232425A1 (en) * | 2019-05-16 | 2020-11-19 | General Automation Lab Technologies Inc. | Method for assaying biological sample on microfabricated chip |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1582303A (en) * | 1976-05-03 | 1981-01-07 | Chemetron Corp | Programmed thermal degradation-mass spectrometry analysis method facilitating identification of a biological specimen |
| GB2161829A (en) * | 1984-07-20 | 1986-01-22 | Prutec Ltd | Microbial growth detection using a mass spectrometer |
| US5059527A (en) * | 1989-12-08 | 1991-10-22 | White David C | Detection of endotoxins of gram negative bacteria |
| EP0662517A1 (en) * | 1994-01-05 | 1995-07-12 | Inbiomed International | Method for identifying microorganisms and its application for the early detection of bacterial growth and for optimising the composition of culture media, as well as a device for performing the method |
| WO1998009314A1 (en) * | 1996-08-27 | 1998-03-05 | The Manchester Metropolitan University | Microorganism identification |
| WO1998039470A1 (en) * | 1997-03-06 | 1998-09-11 | Osmetech Plc | Detection of conditions by analysis of gases or vapours |
-
1998
- 1998-07-07 GB GB9814600A patent/GB2335491A/en not_active Withdrawn
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1582303A (en) * | 1976-05-03 | 1981-01-07 | Chemetron Corp | Programmed thermal degradation-mass spectrometry analysis method facilitating identification of a biological specimen |
| GB2161829A (en) * | 1984-07-20 | 1986-01-22 | Prutec Ltd | Microbial growth detection using a mass spectrometer |
| US5059527A (en) * | 1989-12-08 | 1991-10-22 | White David C | Detection of endotoxins of gram negative bacteria |
| EP0662517A1 (en) * | 1994-01-05 | 1995-07-12 | Inbiomed International | Method for identifying microorganisms and its application for the early detection of bacterial growth and for optimising the composition of culture media, as well as a device for performing the method |
| WO1998009314A1 (en) * | 1996-08-27 | 1998-03-05 | The Manchester Metropolitan University | Microorganism identification |
| WO1998039470A1 (en) * | 1997-03-06 | 1998-09-11 | Osmetech Plc | Detection of conditions by analysis of gases or vapours |
Non-Patent Citations (1)
| Title |
|---|
| Analytical Chemistry Vol. 47, No. 2, Feb. 1975 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002057989A2 (en) * | 2001-01-18 | 2002-07-25 | Basf Aktiengesellschaft | Method for metabolic profiling |
| WO2002057989A3 (en) * | 2001-01-18 | 2003-12-31 | Basf Ag | Method for metabolic profiling |
| WO2005038451A2 (en) * | 2003-10-14 | 2005-04-28 | Raytheon Company | Mass spectrometer for entrained particles, and method for measuring masses of the particles |
| WO2005038451A3 (en) * | 2003-10-14 | 2005-06-30 | Raytheon Co | Mass spectrometer for entrained particles, and method for measuring masses of the particles |
| US6969849B2 (en) | 2003-10-14 | 2005-11-29 | Raytheon Company | Mass spectrometer for entrained particles, and method for measuring masses of the particles |
| WO2020232425A1 (en) * | 2019-05-16 | 2020-11-19 | General Automation Lab Technologies Inc. | Method for assaying biological sample on microfabricated chip |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9814600D0 (en) | 1998-09-02 |
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| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |