US 4,008,388 A · Mass spectrometric system for rapid, automatic and specific identification and quantitation of compounds

Abstract

An automated mass spectrometric system which is capable of analyzing and identifying a wide variety of chemical compounds. A sample of an unknown compound, in liquid, solid or gaseous state, is introduced into the invented system. It may be a pure sample or a mixture of compounds. In either case, its mass spectrum is searched for selected peaks and an attempt is made to match such peaks to previously stored, characteristic spectra of one or more compounds in a predetermined family of compounds. Matching is on a probabilistic basis, reflecting the occurrence probabilities or uniqueness of the mass peaks found, and the accuracy with which the relative peak intensity pattern matches that of any of the compounds in the family of compounds sought. If one or more of the compounds in the family of compounds is identified as being present in the sample, its quantity is also determined automatically by the invention. Moreover a confidence index is generated as a measure of the likelihood that the compound identified as being present is in fact present. The present invention comprises a sample inlet device, preferably a flash evaporator and separator, a mass spectrometer, electronic means for controlling the operation of the mass spectrometer and electronic means for analyzing the mass peaks for identification. Based upon the results of data analysis, i.e., matching of spectra, the analysis means provides signals to the control means to alter the data acquisition, in closed loop fashion. System sensitivity and other operating parameters are automatically varied as required to obtain accurate mass peak measurements.

Claims46

Dependent claims

In a mass spectrometric system comprised of (i) means for measuring the mass spectra of sample compounds;

(ii) means for introducing a sample of a pure compound or a mixture of compounds into said measuring means;
(iii) means for controlling the operation of said measuring means so as to measure the intensities of one or more mass peaks of said sample;
and (iv) means for data input and output electrically coupled to said control means and to means for analyzing said mass peaks, said analysis means comprising:
a. first means for storing the mass spectrum of at least one target compound or a contracted mass spectrum thereof;
b. second means for storing at least one spectral matching criterion;
c. means for matching said measured mass peaks to corresponding mass peaks of said stored spectrum of said target compound on a probabilistic basis, the degree of said matching being determined with respect to said spectral matching criterion, said matching means being electrically coupled to said first and second storage means and to said measuring means,
whereby, said target compound is identified as being present in said sample or as not being present therein in accordance with said spectral matching criterion.

4 more elements

In a mass spectrometric system comprised of (i) means for measuring the mass spectra of sample compounds;

(ii) means for introducing a sample of a pure compound or a mixture of compounds into said measuring means;
(iii) means for controlling the operation of said measuring means so as to measure the intensities of one or more mass peaks of said sample;
and (iv) means for data input and output electrically coupled to said control means and to means for analyzing said mass peaks, said analysis means comprising:
a. first means for storing the mass spectrum of at least one target compound or a contracted mass spectrum thereof;
b. second means for storing at least one spectral matching criterion;
c. third means for storing a predetermined sensitivity factor with respect to each mass peak of said target compound's sepctrum, said sensitivity factor relating the measured intensity of each mass peak to a quantity of said target compound;
d. means for determining a measure of quantity of said target compound in said sample based upon the intensities of said measured mass peaks and said corresponding sensitivity factors, the mass peak at which the least quantity of said target compound is determined being stored in said second storage means as a reference peak, said quantity determination means being electrically coupled to said second and third storage means and to said measuring means;
e. means for predicting the intensity of a mass peak of said sample at least one other mass position of said target compound's mass spectrum said prediction being based upon the intensity of said reference peak and said mass spectral data for said target compound, said prediction means being electrically coupled to said first and second storage means;
and
f. means for comprising the intensity of each measured mass peak to the intensity predicted therefor with respect to a predetermined tolerance, said comparison means being electrically coupled to said prediction means and to said measuring means,
whereby, a mass peak is considered contaminated if its measured intensity exceeds said predicted intensity by more than said tolerance and said mass peak is considered uncontaminated if its measured intensity agress with said predicted intensity. within said tolerance, and said target compound is identified as being present in said sample or as not being present therein as a function of the number of uncontaminated mass peaks measured at mass positions of its spectrum and their uniqueness.

8 more elements

In a mass spectrometric system comprised of (i) means for measuring the mass spectra of sample compounds;

(ii) means for introducing a sample of a pure compound or a mixture of compounds into said measuring means;
and (iii) means for controlling the operation of said measuring means so as to measure the intensities of one or more mass peaks of said sample;
and (iv) means for the data input and output electrically coupled to said control means and to means for anaylzing said mass peaks, said anaylsis means comprising:
a. first means for storing the mass spectrum of at least one target compound or a contracted mass spectrum thereof;
b. second means for storing at least one spectral matching criterion;
c. third means for storing a predetermined sensitivity factor with respect to each mass peak of said target compound's spectrum, said sensitivity factor relating the measured intensity of each mass peak to a quantity of said target compound;
d. means for determining a measure of quantity of said target compund in said sample based upon the intensities of said measured mass peaks and said corresponding sensitivity factors, the mass peak at which the least quantity of said target compound is determined being stored in said second storage means as a reference peak, said quantity determination means being electrically coupled to said second and third storage means and to said measuring means;
e. means for predicting the intensity of a mass peak of said sample at at least one other mass position of said target compound's mass spectrum, said prediction being based upon the intensity of said reference peak and said mass spectral data for said target compound, said prediction means being electrically coupled to said first and second storage means;
f. first means for comparing the intensity of each measured mass peak to the intensity predicted therefor with respect to a predetermined tolerance, said comparison means being electrically coupled to said prediction means and to said measuring means, a mass peak being considered contaminated if its measured intensity exceeds said predicted intensity by more than said tolerance and uncontaminated if its measured intensity agrees with said predicted intensity within said tolerance;
g. means for determining a probabilistic measure of the likelihood of the presence of said target compound based upon said uncontaminated mass peaks measured, said means for determining a probabilistic measure being electrically coupled to said first comparison means;
and
h. second means for comparing said probabilistic measure to said spectral matching criteria, said second comparison means being electrically coupled to said means for determining a probabilistic measure and to said second storage means,
whereby, said target compound is identified as being present in said sample or as not being present therein in accordance with said spectral matching criterion.

10 more elements

In a mass spectrometric system comprised of (i) means for measuring the mass spectra of sample compounds;

(ii) means for introducing a sample of a pure compound or a mixture of compounds into said measuring means;
(iii) means for controlling the operation of said measuring means so as to measure the intensities of one or more mass peaks of said sample;
and (iv) means for data input and output electrically coupled to said control means and to means for analyzing said mass peaks, said analysis means comprising:
a. first means for storing the mass spectrum of at least one target compound or a contracted mass spectrum thereof;
b. second means for storing a uniqueness factor for each mass peak in said mass spectrum of said target compound, said uniqueness factor reflecting the number of randomly selected mass spectra from a universe of compounds of interest which would have to be examined to find one having said mass peaks;
c. means for correlating each of said measured mass peaks with a corresponding uniqueness factor, said correlation means being electrically coupled to said measuring means and to said second storage means, said correlation being displayed to an operator;
d. third means for storing at least one spectral matching criterion;
and
e. means for matching said measured mass peaks to corresponding mass peaks of said stored spectrum of said target compound in accordance with said spectral matching criterion, said matching means being electrically coupled to said first and third storage means and to said measuring means,
whereby, (i) a substantially pure sample of said target compound is introduced into said measuring means through said sample introduction means, said uniqueness factors are displayed for each measured mass peak of said target compound, and said operator selects mass peaks based upon at least one mass peak selection criterion and stores the same in said first storage means and said control means, and (ii) a subsequent sample of an unknown compound is introduced into said measuring means and said target compound is identified as being present in said unknown sample or as not being present therein in accordance with said spectral matching criterion.

7 more elements

A mass spectrometric system comprising:

a. means for measuring the mass spectrum of a sample compound, said measuring means producing an ion intensity corresponding to each mass peak of said sample;
b. means for introducing a sample compound into said measuring means, said sample introduction means being in communication with said measuring means;
c. means for controlling the operation of said measuring means so as to measure the intensities of one or more mass peaks of said sample, said control means being electrically coupled to said measuring means;
d. means for converting said ion intensity into an electrical signal which is an analog of said ion intensity, said conversion means being electrically coupled to said measuring means;
and
e. means for analyzing said electrical signals, said analysis means comprising:
i. first means for storing the mass spectrum of at least one target compound, or a contracted mass spectrum thereof, and at least one spectral matching criterion;
and
ii. means for matching the mass peaks represented by said electrical signals to corresponding mass peaks of said stored spectrum of said target compound in accordance with said spectral matching criterion, said matching means being electrically coupled to said storage means,
whereby, said target compound is identified as being present in said sample or as not being present therein in accordance with said spectral matching criterion.

7 more elements

A mass spectrometric system comprising:

a. means for measuring the mass spectrum of a sample compound, said measuring means producing an ion intensity corresponding to each mass peak of said sample;
b. means for introducing a sample compound into said measuring means, said sample introduction means being in communication with said measuring means;
c. means for controlling the operation of said measuring means so as to measure the intensities of one or more mass peaks of said sample, said control means being electrically coupled to said measuring means, said control means comprising:
i. means for generating, for each mass peak to be measured, an electrical control signal whose amplitude is related to the mass position of said mass peak to be measured by a substantially constant scale factor over the mass range, said control signal generating means being electrically coupled to said measuring means;
and
ii. means for adjusting said electrical control signal to correct for both offset and scale factor error in the relationship between said electrical control signal and said mass position, said adjusting means being electrically coupled to said control signal generating means;
d. means for converting said ion intensity into an electrical signal which is an analog of said ion intensity, said conversion means being electrically coupled to said measuring means;
and
e. means for analyzing said electrical signals, said analysis means being electrically coupled to said conversion means, said analysis means comprising:
i. first means for storing the mass spectrum of at least one target compound or a contracted mass spectrum thereof;
ii. second means for storing at least one spectral matching criterion;
and
iii. means for matching said measured mass peaks to corresponding mass peaks of said stored spectrum of said target compound in accordance with said spectral matching criterion, said matching means being electrically coupled to said first and second storage means and to said conversion means,
whereby, said target compound is identified as being present in said sample or as not being present in said sample or as not being present therein in accordance with said spectral matching criterion.

11 more elements

Dependencies are inferred from the claim text.

Mass spectrometric system for rapid, automatic and specific identification and quantitation of compounds

Life of this patent

Mass spectrometric system for rapid, automatic and specific identification and quantitation of compounds

Life of this patent

Abstract

Claims46