1. A method for analysis of a plurality of biological samples to identify one or more unidentified metabolites of different intensities between samples that are associated with a human disease state, comprising the steps of:
a) introducing the plurality of biological samples from a healthy human and a diseased human, each of which contains a plurality of unidentified metabolites without any a priori selection of metabolites of interest, into a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTMS);
b) simultaneously obtaining, identifying and quantifying data for the plurality of unidentified metabolites detected in each of the biological samples introduced into the FTMS, wherein the identifying data comprise accurate mass and the quantifying data are intensity data;
c) creating a database comprising said identifying and quantifying data;
d) analyzing the database to determine metabolites of different intensities between samples from the healthy human and the diseased human, which metabolites of different intensities are associated with the human disease state;
e) identifying one or more unidentified metabolites associated with the human disease state so determined by a method selected from the group consisting of matching the identifying data of the unidentified metabolites to identifying data of known metabolites, determining the empirical formula of the one or more unidentified metabolites, and analyzing the MSMS fragment data of the one or more unidentified metabolites.
2. The method as defined in claim 1 further comprising:
correlating the one or more unidentified metabolites associated with the human disease state identified in step e) with gene expression data from the healthy human andor diseased human to determine the function of one or more genes affected by the human disease state.
3. The method as defined in claim 1, wherein each of the biological samples is a biological extract of metabolites.
4. The method as defined in claim 1, wherein the accurate mass is used to calculate the empirical formula of the one or more than one unidentified metabolites.
5. The method as defined in claim 4, wherein the database created in step c) of claim 1 is organized to permit searching for one or more known metabolites by empirical formula.
6. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit searching for one or more known metabolites by accurate mass.
7. The method as defined in claim 4, wherein the database created in step c) of claim 1 is organized to permit identification of unknown metabolites by the empirical formulae of the metabolites.
8. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit the comparison of one or more samples from diseased humans to one or more samples from healthy humans andor samples from different diseased humans such that the intensity of metabolites present in the samples from diseased humans can be determined relative to the samples from healthy humans andor samples from different diseased humans.
9. The method as defined in claim 1, wherein the FTMS is used with a chromatographic separation system.
10. The method as defined in claim 1, wherein the FTMS is equipped with a soft ionization source.
11. The method as defined in claim 1, wherein the FTMS is equipped with an additional mass selective pre-separation system.
12. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit the comparison of any two or more samples to each other, such that the presence or absence of an intensity of metabolites found in some samples but not in others is determined.
13. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit the comparison of one or more samples from diseased humans to one or more samples from healthy humans andor samples from different diseased humans such that the presence or absence of a difference in an intensity of metabolites present in the samples from diseased humans can be determined relative to the samples from healthy humans andor samples from different diseased humans.
14. A method for the analysis of a plurality of biological samples to identify one or more unidentified metabolites of different intensities between samples that are associated with a human disease state, comprising the steps of:
a) injecting a plurality of biological samples from a healthy human and a diseased human, each of which contains a plurality of unidentified metabolites without any a priori selection of metabolites of interest, into a Fourier Transform Ion Cyclotron Mass Spectrometer with or without the additional use of a chromatographic column;
b) ionizing the metabolites using a soft ionization source;
c) transferring the ionized metabolites to an ion cyclotron resonance (ICR) cell with or without additional mass selective pre-separation;
d) separating and measuring said ions in the ICR cell with or without simultaneous MSMS analysis occurring;
e) simultaneously determining accurate mass and intensity data of each of the ions detected;
f) transferring said data to a database that stores and organizes the data;
g) comparing intensity data of the biological samples from the healthy human and the diseased human contained within the database to one another to determine metabolites of different intensities as between samples, which metabolites of different intensities are associated with the human disease state; and
h) identifying one or more unidentified metabolites so determined, by a method selected from the group consisting of matching the accurate mass data of the unidentified metabolites to accurate mass data of known metabolites, calculating the empirical formula of the one or more unidentified metabolites, and analyzing the MSMS fragment data of the one or more unidentified metabolites.
15. The method as defined in claim 14 further comprising:
correlating the one or more unidentified metabolites associated with the human disease state identified in step h) with gene expression data from the healthy human andor diseased human to determine the function of one or more genes affected by the human disease state.
16. A method for analysis of a plurality of biological samples to identify one or more unidentified metabolites from said samples that are associated with a human disease state, when compared with a database of known metabolites, comprising the steps of:
a) introducing a plurality of biological samples from a healthy human and a diseased human, each of which contains a plurality of unidentified metabolites without any a priori selection of metabolites of interest, into a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTMS);
b) simultaneously obtaining, identifying and quantifying data for the plurality of unidentified metabolites detected in each of the biological samples introduced into the FTMS, wherein the identifying data comprise accurate mass data and the quantifying data are intensity data;
c) creating a database comprising said identifying and quantifying data;
d) comparing the identifying and quantifying data of the said database with a known database containing identifying and quantifying data of known metabolites; and
e) identifying one or more unidentified metabolites so compared by matching said identifying data of unidentified metabolites to said identifying data of known metabolites; and
f) comparing intensity data of the biological samples from the healthy human and the diseased human for the metabolites identified in step e) to identify metabolites that are associated with the human disease state.
17. A method for analysis of a plurality of biological samples to create and organize a database, by metabolic concentration, to indicate unidentified metabolites associated with a human disease state comprising the steps of:
a) introducing a plurality of biological samples from a healthy human and a diseased human, each of which contains a plurality of unidentified metabolites without any a priori selection of metabolites of interest, into a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTMS);
b) simultaneously obtaining, identifying and quantifying data for the plurality of unidentified metabolites detected in each of the biological samples introduced into the FTMS, wherein the identifying data comprise accurate mass data and the quantifying data are intensity data;
c) creating a database comprising said identifying and quantifying data; and
d) organizing the database by metabolic concentration whereby the organization of said identifying and quantifying data indicates which of the unidentified metabolites is associated with the human disease state.
18. A method for analysis of a plurality of biological samples, comprising the steps of:
a) introducing a plurality of biological samples from a healthy human and a diseased human, each of which contains a plurality of unidentified metabolites without any a priori selection of metabolites of interest, into a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer (FTMS);
b) simultaneously obtaining, identifying and quantifying data for the plurality of unidentified metabolites detected in each of the biological samples introduced into the FTMS, wherein the identifying data comprise accurate mass data and the quantifying data are intensity data;
c) creating a database of unidentified metabolites comprising said identifying and quantifying data; and
d) analyzing the database of unidentified metabolites, wherein the analyzing step is selected from the group consisting of:
(i) analyzing the database of unidentified metabolites to determine metabolites of different intensities between samples from the healthy human and the diseased human, which metabolites of different intensities are associated with a human disease state, and identifying one or more metabolites so determined using the identifying data by matching to a known database of known metabolites, or by the empirical formula of the one or more than one unidentified metabolites, or by the MSMS fragment data of the one or more than one unidentified metabolites;
(ii) comparing the database of the unidentified metabolites with a known database of known metabolites and identifying one or more metabolites associated with the human disease state so compared using the identifying data and matching said identifying data to said known database of known metabolites;
(iii) organizing the database of the unidentified metabolites by metabolite concentration; and
(iv) correlating the unidentified metabolites in (iii) with gene expression data from the healthy and diseased humans to determine the function of one or more genes affected by the human disease state.
19. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit the comparison of one or more samples from diseased humans to one or more samples from healthy humans such that the intensity of metabolites present in the samples from diseased humans can be determined relative to the samples from healthy humans.
20. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit the comparison of one or more samples from diseased humans to one or more samples from healthy humans such that the presence or absence of a difference in an intensity of metabolites present in the samples from diseased humans can be determined relative to the samples from healthy humans.
21. The method as defined in claim 1, wherein the database created in step c) of claim 1 is organized to permit the comparison of two or more samples such that the metabolites having different intensities in the two or more samples can be displayed.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and
a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator;
wherein the light source is a discharge lamp formed from a glass tube having an anti-reflection coating formed on at least a part of the surface thereof.
2. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and
a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator;
wherein the illuminator includes an illumination optical system to guide the light beams emitted from the light source to the optical modulator; the first reflecting element is positioned in a plane including a point generally conjugate with a point of light emission of the light source with the illumination optical system being laid between them not to shade the illumination light traveling from the light-emission point to the optical modulator; the illumination optical system includes an integrator to create a more uniform light intensity distribution within the light beam and a relay-condenser optical system laid between the integrator and light source; and the second reflecting element is positioned near the relay-condenser optical system not to shade the illumination light traveling from the light source to the optical modulator.
3. The apparatus as set forth in claim 2, wherein the first reflecting element is positioned obliquely in relation to the optic axis of the illumination optical system.
4. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator;
wherein the illuminator includes an illumination optical system to guide the light beam emitted from the light source to the optical modulator;
the illumination optical system includes an integrator to uniform the light intensity distribution within the light beam; and
the optic axis of the optical system laid downstream of the integrator is shifted in parallel to that of the optical system ranging from the light source to the integrator.
5. The apparatus as set forth in claim 4, wherein the first reflecting element is positioned between the light source and integrator not to shade the illumination light traveling from the light source to the optical modulator.
6. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator;
wherein the illuminator includes an illumination optical system to guide the light beam emitted from the light source to the optical modulator;
the illumination optical system includes a rod integrator as the integrator to uniform the light intensity distribution within the light beam; and
the second reflecting element is positioned near the light-incident end face of the rod integrator not to shade the illumination light traveling from the light source to the optical modulator.
7. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and
a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator;
wherein the illuminator includes an illumination optical system to guide the light beam emitted from the light source to the optical modulator;
the illumination optical system includes a rod integrator as the integrator to uniform the light intensity distribution within the light beam, and a condenser lens to form an image of the rod integrator; and
the optic axis of the optical system ranging from the light source to the rod integrator is shifted in parallel to that of the optical system laid downstream of the condenser lens.
8. The apparatus set forth in claim 7, wherein the first reflecting element is positioned between the rod integrator and condenser lens not to shade the illumination light traveling from the light source to the optical modulator.
9. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and
a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator; and
a sequential color shutter;
wherein the first reflecting element also serves as an analyzer of the sequential color shutter.
10. A projection-type image display apparatus including an illuminator with a light source, optical modulator illuminated by light from the illuminator and which makes spatial modulation of the illumination light according to a to-be-displayed image for either transmission or reflection, and a projection lens to form an image of the optical modulator, the apparatus comprising:
a first reflecting element to reflect, towards the light source, an unwanted one of a light beam emitted from the illuminator and that will not illuminate the optical modulator; and
a second reflecting element to guide, by reflecting, the unwanted light once reflected by the first reflecting element to the optical modulator;
wherein the illuminator includes a discharge lamp as a light source and a reflector having the sectional form of a paraboloid of revolution, and a phase-difference plate and a reflecting polarizer are provided in the optical path between the discharge lamp and optical modulator, wherein the phase-difference plate is divided along radial boundary lines concentric to the center axis of the reflector into plural zones whose retardation axes extend in different directions.
11. The apparatus as set forth in claim 10, wherein retardation axes of those zones of the phase-difference plate which are phase-retardation axis with respect to the center axis of the reflector, extend perpendicular to each other.