Highly selective chromatography-molecular rotational resonance spectroscopy systems and methods
The capabilities of a gas or liquid chromatography-molecular rotational resonance (GC/LC-MRR) instrument exceed those of high-resolution mass spectrometry and nuclear magnetic resonance in terms of selectivity, resolution, and compound identification. MRR detection provides high specificity for selective gas- or liquid-phase separations, including the ability to resolve co-eluting peaks and isomeric compounds without any loss of specificity or accuracy. MRR can perform both qualitative identification and absolute quantification of analyte components separated by GC or LC without a reference standard. GC-MRR is ideal for compound-specific isotope analysis (CSIA) and can identify enantiomers and enantiomeric excess. GC-MRR measurements are especially useful for studying biosynthetic/degradation and geochemical isotopic compounds.
1. A system comprising:
a chromatograph to separate an analyte into components, wherein the components include co-eluting components that cannot be separated with the chromatograph;
a molecular rotational resonance (MRR) spectrometer, in fluid communication with the chromatograph, to measure MRR spectra of the components; and
a processor, operably coupled to the MRR spectrometer, to resolve, based at least in part on at least one of the MRR spectra, at least one of an isomer, an isotopologue, or an isotopomer among the components of the analyte and to form a total molecular chromatogram of the analyte based at least in part on the MRR spectra of the components.
2. The system of claim 1 , wherein the chromatograph is a gas chromatograph.
3. The system of claim 2 , wherein the MRR spectrometer is a microwave MRR spectrometer having an expansion chamber, and further comprising:
a source of carrier gas, in fluid communication with the gas chromatograph and the expansion chamber, to push the analyte through the gas chromatograph and to push at least one of the components into the expansion chamber.
4. The system of claim 3 , wherein the expansion chamber comprises a resonant cavity.
5. The system of claim 2 , wherein the MRR spectrometer comprises a flow cell to receive the components of the analyte from the gas chromatograph.
6. The system of claim 1 , wherein the chromatograph is a liquid chromatograph.
7. The system of claim 6 , wherein the MRR spectrometer is a microwave MRR spectrometer having an expansion chamber, and further comprising:
a volatilization interface, in thermal communication with the liquid chromatograph, to volatilize the at least one of the components; and
a source of carrier gas, in fluid communication with the volatilization interface, to push the at least one of the components out of the volatilization interface and into the expansion chamber.
8. The system of claim 1 , wherein the MRR spectrometer is configured to measure an MRR spectrum having a bandwidth of at least 50 MHz of at least one eluate exiting the chromatograph.
9. The system of claim 1 , further comprising:
an auxiliary detector, operably coupled to the chromatograph, to detect a peak in an output of the chromatograph; and
wherein the processor is configured to trigger measurement of the MRR spectrum in response to the peak and/or to process the MRR spectrum based at least in part on the peak.
10. The system of claim 1 , further comprising:
a nozzle, in fluid communication with the chromatograph and the MRR spectrometer, to rotationally cool molecules of the at least one of the components before the MRR spectrometer measures the MRR spectrum.
11. A method of analyzing an analyte, the method comprising:
separating the analyte into components with a chromatograph, wherein the components include co-eluting components that cannot be separated with the chromatograph;
measuring molecular rotational resonance (MRR) spectra of the co-eluting components with an MRR spectrometer in fluid communication with the chromatograph; and
resolving, based at least in part on the MRR spectra, the co-eluting components of the analyte.
12. The method of claim 11 , wherein separating the analyte into components comprises sampling a continuous flow of the analyte with the chromatograph.
13. The method of claim 12 , further comprising:
detecting a peak in an output of the chromatograph; and
triggering measurement of at least one of the MRR spectra in response to detecting the peak.
14. The method of claim 11 , wherein measuring the MRR spectra comprises measuring a broadband spectrum of an eluate exiting the chromatograph.
15. The method of claim 11 , further comprising:
rotationally cooling molecules of at least one of the components before measuring the MRR spectra, and
wherein measuring the MRR spectra comprises exciting at least one of the components with a microwave excitation signal.
16. The method of claim 11 , further comprising:
identifying at least one unknown component of the analyte based at least in part on at least one of the MRR spectra.
17. The method of claim 11 , further comprising:
quantifying at least one of the components based at least in part on at least one of the MRR spectra.
18. The method of claim 11 , further comprising:
forming a total molecular chromatogram of the analyte based at least in part on the MRR spectra.
19. The method of claim 11 , wherein the chromatograph is a gas chromatograph, the MRR spectrometer is a microwave MRR spectrometer having an expansion chamber, and further comprising:
pushing the analyte through the gas chromatograph into the expansion chamber with a first carrier gas; and
pushing the co-eluting components into the expansion chamber with a second carrier gas different than the first carrier gas.
20. The method of claim 11 , wherein the chromatograph is a liquid chromatograph, the MRR spectrometer is a microwave MRR spectrometer having an expansion chamber, and further comprising:
volatilizing at least one of the components with a volatilization interface; and
pushing the at least one of the components out of the volatilization interface and into the expansion chamber with a carrier gas.
21. The method of claim 11 , further comprising:
attaching a chiral tag to at least one of the components before measuring the corresponding MRR spectrum; and
identifying an enantiomer among the components of the analyte based on at least one of the MRR spectra and/or determining an enantiomeric excess of the components of the analyte based on at least one of the MRR spectra.
22. A system comprising:
a gas chromatograph to separate an analyte into components;
a molecular rotational resonance (MRR) spectrometer, in fluid communication with the gas chromatograph, to interrogate a first spectral line or band of a first one of the components and to interrogate a second spectral line or band different than the first spectral line or band of a second one of the components; and
a pulsed-jet supersonic expansion source, in fluid communication with a column of the gas chromatograph and a vacuum chamber of the MRR spectrometer, to convey the components from the column into the vacuum chamber.
23. The system of claim 22 , wherein the pulsed-jet supersonic expansion source is configured to rotationally cool molecules of the analyte for MRR analysis by the MRR spectrometer.
24. The system of claim 22 , wherein the pulsed-jet supersonic expansion source is configured to rotationally cool molecules of the analyte to a temperature of under 10 K for MRR spectrum analysis by the MRR spectrometer.
25. The system of claim 22 , wherein the MRR spectrometer is configured to analyze analytes with molecular weights greater than 150 amu.