US4075475A
Expired / Lapsed
US
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Programmed thermal degradation-mass spectrometry analysis method facilitating identification of a biological specimen
Assignee: Allied Healthcare Products Inc
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Filing: 1976-05-03
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Granted: 1978-02-21
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Expires: 1996-05-03
Abstract
Abstract A method facilitating the rapid and objective classification and/or identification of an unknown biological specimen is disclosed. A physical sample of the specimen is controllably heated in accordance with a predetermined nonisothermal time dependent function causing the sample to undergo controlled thermal degradation and give off a characteristic time dependent sequence or evolution pattern of gaseous degradation components (molecular fragments). This sequence of gaseous degradation components is then directly passed into an ionization source and ionized to provide a respectively corresponding time dependent sequence of characteristic ions. These ions are then analyzed in a mass spectrometer and measured data is recorded representing the respective quantities of ions having particular masses being produced as a function of time or temperature. This recorded data for an unknown biological specimen is then correlated with analogous time or temperature dependent data earlier recorded for known biological specimen thereby facilitating the classification and/or identification of the unknown biological specimen. The method may be used to facilitate the classification and identification of many different types of biological specimen such as, for example, biological organisms (e.g., bacteria, yeast, molds, fungi, viruses and unicellular animals) and/or biological tissues (e.g., lymphocytes, leukocytes, phagocytes, erythrocytes and platelets).
Inventors
- 👤 Terence H. Risby
- 👤 Alfred L. Yergey, III
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 21:16
CPC Classifications
H; H01; H01J; H01J49/00; H01J49/02; H01J49/04; H01J49/0468; H01J49/0472; G; G01; G01N; G01N31/00; G01N31/12
Claims Analysis
Total Claims: 59
Claim 1
Independent Claim
279 words
A method facilitating the classification and identification of an unknown biological specimen, said method comprising the following steps: (a) providing a physical sample of at least one biological specimen; (b) controllably heating said sample in accordance with a predetermined non-isothermal time dependent function so as to cause the sample temperature to increase from a first predetermined temperature to a second higher predetermined temperature during a correspondingly predetermined time span thereby causing the sample to undergo controlled thermal degradation and to give off a characteristic time dependent sequence of gaseous degradation components; (c) providing a mass spectrometer having an ionization source therein; (d) directly passing said gaseous degradation components within said ionization source from said heating step and ionizing said components in the same characteristic time dependent sequence involved in the formation of said components during said heating step to provide a respectively corresponding time dependent sequence of ions of said components; and (e) analyzing and detecting the mass of at least some of said ions of the components within said mass spectrometer during said predetermined time span and recording a set of measured data representing the respective quantities of ions having particular masses being produced as a function of time or temperature during said predetermined time span; (f) said steps a-e above being carried out at least once for a sample of biological specimen having known predetermined identity; (g) said steps a-e above being repeated at least once for a sample of biological specimen having unknown identity thereby facilitating the classification and identification of such unknown biological specimen through comparison of the set of measured data resulting therefrom with the set of measured data resulting from said steps a-f.
Claim 2
Independent Claim
279 words
A method facilitating the classification and identification of an unknown biological specimen, said method comprising the following steps: (a) providing a physical sample of at least one biological specimen; (b) controllably heating said sample in accordance with a predetermined non-isothermal time dependent function so as to cause the sample temperature to increase from a first predetermined temperature to a second higher predetermined temperature during a correspondingly predetermined time span thereby causing the sample to undergo controlled thermal degradation and to give off a characteristic time dependent sequence of gaseous degradation components; (c) providing a mass spectrometer having an ionization source therein; (d) directly passing said gaseous degradation components within said ionization source from said heating step and ionizing said components in the same characteristic time dependent sequence involved in the formation of said components during said heating step to provide a respectively corresponding time dependent sequence of ions of said components; and (e) analyzing and detecting the mass of at least some of said ions of the components within said mass spectrometer during said predetermined time span and recording a set of measured data representing the respective quantities of ions having particular masses being produced as a function of time or temperature during said predetermined time span; (f) said steps a-e above being carried out at least once for a sample of biological specimen having known predetermined identity; (g) said steps a-e above being repeated at least once for a sample of biological specimen having unknown identity thereby facilitating the classification and identification of such unknown biological specimen through comparison of the set of measured data resulting therefrom with the set of measured data resulting from said steps a-f.
Claim 3
Dependent Claim
23 words
A method as in claim 1, wherein step b comprises substantially linearly raising the temperature of the sample during said predetermined time span.
Claim 4
Dependent Claim
49 words
A method as in claim 1, further comprising the step of repeating steps a-f for a plurality of different biological specimen each having known predetermined identities thereby providing a corresponding plurality of sets of said measured data for comparison with the set of measured data resulting from step g.
Claim 5
Dependent Claim
83 words
A method as in claim 3, further comprising the steps of: cross-correlating the set of measured data resulting from step g with the sets of measured data resulting from repeating steps a-f; and selecting the set of measured data resulting from repeating steps a-f which most closely correlates with the set of data resulting from step g and classifying and/or identifying the unknown biological specimen based upon the classification and/or identification of the known biological specimen corresponding to said selected set of data.
Claim 6
Dependent Claim
32 words
A method as in claim 1, wherein step d comprises ionizing said components in an ionizing process which does not diminish the mass of said components by more than one mass number.
Claim 7
Dependent Claim
16 words
A method as in claim 5, wherein said ionizing step comprises chemical ionization of said components.
Claim 8
Dependent Claim
21 words
A method as in claim 6, wherein said steps a and b are carried out in a chemical ionization ion source.
Claim 9
Dependent Claim
51 words
A method as in claim 7, wherein said step d comprises the passing of a reagent gas over said sample and into a chemical ionization zone within said chemical ionization source whereby said components of thermal degradation are swept along by said reagent gas away from the site of said sample.
Claim 10
Dependent Claim
19 words
A method as in claim 1, wherein said steps a and b are carried out within said ionization source.
Claim 11
Dependent Claim
28 words
A method as in claim 1, wherein said steps a and b comprise placement of said sample onto a heated solids probe operatively associated with said ionization source.
Claim 12
Dependent Claim
88 words
A method as in claim 10, wherein said heated solids probe includes an electrical heater therein for heating said sample and a temperature sensor providing an electrical indication of the probe temperature and including the step of: utilizing the temperature sensor electrical output to control the supply of electrical energy to said heater so as to cause the temperature of said sample to increase in accordance with said predetermined non-isothermal time dependent function from said first temperature to said second higher temperature during said corresponding predetermined time span.
Claim 13
Dependent Claim
102 words
A method as in claim 1, further comprising the step of: detecting the total ion current within said mass spectrometer resulting from the ionization of said components during said predetermined time span and recording further measured data showing the intensity of such total ion current as a function of time or temperature during said predetermined time span; said just stated step of detecting the total ion current being included in step e as carried forth in steps f and g to thereby provide said further measured data as a part of the sets of measured data resulting from steps f and g.
Claim 14
Dependent Claim
49 words
A method as in claim 12, further comprising the step of repeating steps a-f for a plurality of different biological specimen each having known predetermined identities thereby providing a corresponding plurality of sets of said measured data for comparison with the set of measured data resulting from step g.
Claim 15
Dependent Claim
84 words
A method as in claim 13, further comprising the steps of: cross-correlating the set of measured data resulting from step g with the sets of measured data resulting from repeating steps a-f; and selecting the set of measured data resulting from repeating steps a-f which most closely correlates with the set of data from step g and classifying and/or identifying the unknown bioligical specimen as being of the same classification and/or identification as the known biological specimen corresponding to said selected set of data.
Claim 16
Dependent Claim
89 words
A method as in claim 1, further comprising the step of: analyzing and detecting the mass of at least some of said ions of the components within said mass spectrometer during said predetermined time span and recording further measured data showing the spectrum and relative quantities of masses comprising said ions at different instants during said predetermined time span; and utilizing particular predetermined masses in step e selected from among at least one of the said recorded spectra of masses occurring at some instant during said predetermined time span.
Claim 17
Dependent Claim
48 words
A method as in claim 15, wherein the further measured data comprising said spectra of masses is included with the sets of measured data resulting from steps f and g to thereby provide further measured data for use in comparison to classify and/or identify the unknown biological specimen.
Claim 18
Dependent Claim
49 words
A method as in claim 16, further comprising the step of repeating steps a-f for a plurality of different biological specimen each having known predetermined identities thereby providing a corresponding plurality of sets of said measured data for comparison with the set of measured data resulting from step g.
Claim 19
Dependent Claim
82 words
A method as in claim 17, further comprising the steps of: cross-correlating the set of measured data resulting from g with the sets of measured data resulting from repeating steps a-f; and selecting the set of measured data resulting from repeating steps a-f which most closely correlates with the set of data resulting from step g and classifying and/or identifying the unknown biological specimen based upon the classification and/or identification of the known biological specimen corresponding to said selected set of data.
Claim 20
Dependent Claim
84 words
A method as in claim 15, further comprising the steps of: detecting the total ion current within said mass spectrometer resulting from the ionization of said components during said predetermined time span and recording further measured data showing the intensity of such total ion current as a function of time or temperature during said predetermined time span; and determining from said total ion current data particular different instants of time during said predetermined time span for recording and utilization of said spectra of masses.
Claim 21
Dependent Claim
27 words
A method as in claim 1, wherein said biological specimen includes a biological organism selected from a group comprising bacteria, yeast, molds, fungi, viruses and unicellular animals.
Claim 22
Dependent Claim
25 words
A method as in claim 1, wherein said biological specimen includes a biological tissue selected from a group comprising lymphocytes, leucocytes, phagocytes, erythrocytes and platelets.
Claim 23
Independent Claim
337 words
A method facilitating the classification and identifcation of an unknown biological specimen, said method comprising the following steps: (a) providing a physical sample of at least one biological specimen; (b) controllably heting said sample in accordance with a predetermined non-isothermal time dependent function so as to cause the sample temperature to increase from a first predetermined temperature to a second higher predetermined temperature during a correspondingly predetermined time span thereby causing the sample to undergo controlled thermal degradation and to give off a characteristic time dependent sequence of gaseous degradation components; (c) providing a mass spectrometer having a chemical ionization source therein; (d) directly passing said gaseous degradation components within said chemical ionization source from said heating step and chemically ionizing said components in the same characteristic time dependent sequence involved in the formation of said components during said heating step to provide a respectively corresponding sequence of chemically ionized ions of said components; and (e) analyzing and detecting the intensity of ion current corresponding to different masses of said chemically ionized ions within said mass spectrometer at successive instants of time during said predetermined time span and recording measured data showing the spectrum of ions being produced and their relative intensities at each of said successive instants of time thereby effectively accumulating a three dimensional array of recorded measured data having one functional coordinate corresponding to ion intensity, another functional coordinate corresponding to ion mass and another functional coordinate corresponding to temperature or time elapsed during said predetermined time span; (f) said steps a-e above being carried out at least once for a sample of biological specimen having known predetermined identity; (g) said steps a-e above being repeated at least once for a sample of biological specimen having unknown identity thereby facilitating the classification and/or identification of such unknown biological specimen through comparison of at least a part of the three dimensional array of measured data resulting therefrom with at least a part of the three dimensional array of measured data resulting from said steps a-f.
Claim 24
Independent Claim
337 words
A method facilitating the classification and identifcation of an unknown biological specimen, said method comprising the following steps: (a) providing a physical sample of at least one biological specimen; (b) controllably heting said sample in accordance with a predetermined non-isothermal time dependent function so as to cause the sample temperature to increase from a first predetermined temperature to a second higher predetermined temperature during a correspondingly predetermined time span thereby causing the sample to undergo controlled thermal degradation and to give off a characteristic time dependent sequence of gaseous degradation components; (c) providing a mass spectrometer having a chemical ionization source therein; (d) directly passing said gaseous degradation components within said chemical ionization source from said heating step and chemically ionizing said components in the same characteristic time dependent sequence involved in the formation of said components during said heating step to provide a respectively corresponding sequence of chemically ionized ions of said components; and (e) analyzing and detecting the intensity of ion current corresponding to different masses of said chemically ionized ions within said mass spectrometer at successive instants of time during said predetermined time span and recording measured data showing the spectrum of ions being produced and their relative intensities at each of said successive instants of time thereby effectively accumulating a three dimensional array of recorded measured data having one functional coordinate corresponding to ion intensity, another functional coordinate corresponding to ion mass and another functional coordinate corresponding to temperature or time elapsed during said predetermined time span; (f) said steps a-e above being carried out at least once for a sample of biological specimen having known predetermined identity; (g) said steps a-e above being repeated at least once for a sample of biological specimen having unknown identity thereby facilitating the classification and/or identification of such unknown biological specimen through comparison of at least a part of the three dimensional array of measured data resulting therefrom with at least a part of the three dimensional array of measured data resulting from said steps a-f.
Claim 25
Dependent Claim
23 words
A method as in claim 22, wherein step b comprises substantially linearly raising the temperature of the sample during said predetermined time span.
Claim 26
Dependent Claim
49 words
A method as in claim 22, further comprising the step of repeating steps a-f for a plurality of different biological specimen each having known predetermined identities thereby providing a corresponding plurality of arrays of said measured data for comparison with the array of measured data resulting from step g.
Claim 27
Dependent Claim
83 words
A method as in claim 24, further comprising the steps of: cross-correlating the array of measured data resulting from step g with the arrays of measured data resulting from repeating steps a-f; and selecting the array of measured data resulting from repeating steps a-f which most closely correlates with the array of data resulting from step g and classifying and identifying the unknown biological specimen based upon the classification and identification of the known biological specimen corresponding to said selected array of data.
Claim 28
Dependent Claim
32 words
A method as in claim 22, wherein step d comprises ionizing said components in an ionizing process which does not diminish the mass of said components by more than one mass chamber.
Claim 29
Dependent Claim
16 words
A method as in claim 26, wherein said ionizing step comprises chemical ionization of said components.
Claim 30
Dependent Claim
21 words
A method as in claim 27, wherein said steps a and b are carried out in a chemical ionization ion source.
Claim 31
Dependent Claim
51 words
A method as in claim 28, wherein said step d comprises the passing of a reagent gas over said sample and into a chemical ionization zone within said chemical ionization source whereby said components of thermal degradation are swept along by said reagent gas away from the site of said sample.
Claim 32
Dependent Claim
19 words
A method as in claim 22, wherein said steps a and b are carried out within said ionization source.
Claim 33
Dependent Claim
28 words
A method as in claim 22, wherein said steps a and b comprise placement of said sample onto a heated solids probe operatively associated with said ionization source.
Claim 34
Dependent Claim
88 words
A method as in claim 31, wherein said heated solids probe includes an electrical heater therein for heating said sample and a temperature sensor providing an electrical indication of the probe temperature and including the step of: utilizing the temperature sensor electrical output to control the supply of electrical energy to said heater so as to cause the temperature of said sample to increase in accordance with said predetermined non-isothermal time dependent function from said first temperature to said second higher temperature during said corresponding predetermined time span.
Claim 35
Dependent Claim
102 words
A method as in claim 22, further comprising the step of: detecting the total ion current within said mass spectrometer resulting from the ionization of said components during said predetermined time span and recording further measured data showing the intensity of such total ion current as a function of time or temperature during said predetermined time span; said just stated step of detecting the total ion current being included in step e as carried forth in steps f and g to thereby provide said further measured data as a part of the arrays of measured data resulting from steps f and g.
Claim 36
Dependent Claim
49 words
A method as in claim 33, further comprising the step of repeatng steps a-f for a plurality of different biological specimen each having known predetermined identities thereby providing a corresponding plurality of arrays of said measured data for comparison with the array of measured data resulting from step g.
Claim 37
Dependent Claim
85 words
A method as in claim 34, further comprising the steps of: cross-correlating the array of measured data resulting from step g with the arrays of measured data resulting from repeating steps a-f; and selecting the array of measured data resulting from repeating steps a-f which most closely correlates with the array of data resulting from step g and classifying and/or identifying the unknown biological specimen as being of the same classification and identification as the known biological specimen corresponding to said selected array of data.
Claim 38
Dependent Claim
87 words
A method as in claim 22, further comprising the step of: analyzing and detecting the mass of at least some of said ions of the components within said mass spectrometer during said predetermined time span and recording further measured data showing the spectrum and relative quantities of masses comprising said ions at different instants during said predetermined time span; and utilizing particular predetermined masses in step e from among at least one of the said spectra of masses occurring at some instant during said predetermined time span.
Claim 39
Dependent Claim
48 words
A method as in claim 36, wherein the further measured data comprising said spectra of masses is included with the arrays of measured data resulting from steps f and g to thereby provide further measured data for use in comparison to classify and/or identify the unknown biological specimen.
Claim 40
Dependent Claim
49 words
A method as in claim 37, further comprising the step of repeating steps a-f for a plurality of different biological specimen each having known predetermined identities thereby providing a corresponding plurality of arrays of said measured data for comparison with the array of measured data resulting from step g.
Claim 41
Dependent Claim
83 words
A method as in claim 38, further comprising the steps of: cross-correlating the array of measured data resulting from step g with the arrays of measured data resulting from repeating steps a-f; and selecting the array of measured data resulting from repeating steps a-f which most closely correlates with the array of data resulting from step g and classifying and/or identifying the unknown biological specimen based upon the classification and/or identification of the known biological specimen corresponding to said selected array of data.
Claim 42
Dependent Claim
84 words
A method as in claim 36, further comprising the steps of: detecting the total ion current within said mass spectrometer resulting from the ionization of said components during said predetermined time span and recording further measured data showing the intensity of such total ion current as a function of time or temperature during said predetermined time span; and determining from said total ion current data particular different instants of time during said predetermined time span for recording and utilization of said spectra of masses.
Claim 43
Dependent Claim
27 words
A method as in claim 22, wherein said biological specimen includes a biological organism selected from a group comprising bacteria, yeast, molds, fungi, viruses and unicellular animals.
Claim 44
Dependent Claim
25 words
A method as in claim 22, wherein said biological specimen includes a biological tissue selected from a group comprising lymphocytes, leucocytes, phagocytes, erythrocytes and platelets.
Claim 45
Independent Claim
248 words
A method facilitating the classification and identification of an unknown biological specimen, said method comprising the following steps: (a) providing a physical sample of a biological specimen; (b) controllably heating said sample in accordance with a predetermined non-isothermal time dependent function so as to cause the sample temperature to increase from a first predetermined temperature to a second higher predetermined temperature during a correspondingly predetermined time span thereby causing the sample to undergo controlled thermal degradation and to give off a characteristic time dependent sequence of gaseous degradation components; (c) providing a mass spectrometer having an ionization source therein: (d) directly passing said gaseous degradation components within said ionization source from said heating step and ionizing said components in the same characteristic time dependent sequence involved in the formation of said components during said heating step to provide a respectively corresponding time dependent sequence of ions of said components; and (e) analyzing and detecting the mass of at least some of said ions of the components within said mass spectrometer during said predetermined time span and recording a set of measured data representing the respective quantities of ions having particular masses being produced as a function of time or temperature during said predetermined time span thereby facilitating the classification and identification of the specimen through comparison of the resulting set of recorded measured data with other sets of previously recorded measured data produced by carrying out the above steps a-e for biological specimen having known identification or classification.
Claim 46
Independent Claim
248 words
A method facilitating the classification and identification of an unknown biological specimen, said method comprising the following steps: (a) providing a physical sample of a biological specimen; (b) controllably heating said sample in accordance with a predetermined non-isothermal time dependent function so as to cause the sample temperature to increase from a first predetermined temperature to a second higher predetermined temperature during a correspondingly predetermined time span thereby causing the sample to undergo controlled thermal degradation and to give off a characteristic time dependent sequence of gaseous degradation components; (c) providing a mass spectrometer having an ionization source therein: (d) directly passing said gaseous degradation components within said ionization source from said heating step and ionizing said components in the same characteristic time dependent sequence involved in the formation of said components during said heating step to provide a respectively corresponding time dependent sequence of ions of said components; and (e) analyzing and detecting the mass of at least some of said ions of the components within said mass spectrometer during said predetermined time span and recording a set of measured data representing the respective quantities of ions having particular masses being produced as a function of time or temperature during said predetermined time span thereby facilitating the classification and identification of the specimen through comparison of the resulting set of recorded measured data with other sets of previously recorded measured data produced by carrying out the above steps a-e for biological specimen having known identification or classification.
Claim 47
Dependent Claim
23 words
A method as in claim 43, wherein step b comprises substantially linearly raising the temperature of the sample during said predetermined time span.
Claim 48
Dependent Claim
32 words
A method as in claim 43, wherein step d comprises ionizing said components in an ionizing process which does not diminish the mass of said components by more than one mass number.
Claim 49
Dependent Claim
16 words
A method as in claim 45, wherein said ionizing step comprises chemical ionization of said components.
Claim 50
Dependent Claim
21 words
A method as in claim 46, wherein said steps a and b are carried out in a chemical ionization ion source.
Claim 51
Dependent Claim
51 words
A method as in claim 47, wherein said step d comprises the passing of a reagent gas over said sample and into a chemical ionization zone within said chemical ionization source whereby said components of thermal degradation are swept along by said reagent gas away from the site of said sample.
Claim 52
Dependent Claim
19 words
A method as in claim 43, wherein said steps a and b are carried out within said ionization source.
Claim 53
Dependent Claim
28 words
A method as in claim 43, wherein said steps a and b comprise placement of said sample onto a heated solids probe operatively associated with said ionization source.
Claim 54
Dependent Claim
88 words
A method as in claim 50, wherein said heated solids probe includes an electrical heater therein for heating said sample and a temperature sensor providing an electrical indication of the probe temperature and including the step of: utilizing the temperature sensor electrical output to control the supply of electrical energy to said heater so as to cause the temperature of said sample to increase in accordance with said predetermined non-isothermal time dependent function from said first temperature to said second higher temperature during said corresponding predetermined time span.
Claim 55
Dependent Claim
88 words
A method as in claim 43, further comprising the step of: detecting the total ion current within said mass spectrometer resulting from the ionization of said components during said predetermined time span and recording further measured data showing the intensity of such total ion current as a function of the time or temperature during said predetermined time span; said just stated step of detecting the total ion current being included in step e to thereby provide said further measured data as a part of the recorded measured data.
Claim 56
Dependent Claim
88 words
A method as in claim 43, further comprising the step of: analyzing and detecting the mass of at least some of said ions of the components within mass spectrometer during said predetermined time span and recording further measured data showing the spectrum and relative quantities of masses comprising said ions at different instants during said predetermined time span; and utilizing particular predetermined masses in step e selected from among at least one of the said recorded spectra of masses occurring at some instant during said predetermined time span.
Claim 57
Dependent Claim
84 words
A method as in claim 53, further comprising the steps of: detecting the total ion current within said mass spectrometer resulting from the ionization of said components during said predetermined time span and recording further measured data showing the intensity of such total ion current as a function of time or temperature during said predetermined time span; and determining from said total ion current data particular different instants of time during said predetermined time span for recording and utilization of said spectra of masses.
Claim 58
Dependent Claim
27 words
A method as in claim 43, wherein said biological specimen includes a biological organism selected from a group comprising bacterial, yeast, molds, fungi, viruses and unicellular animals.
Claim 59
Dependent Claim
24 words
A method in claim 43, wherein said biological specimen includes a biological tissue selected from a group comprising lymphocytes, leucocytes, phagocytes, erythrocytes and platelets.
References Cited (Backward Citations)
No citation records indexed.
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