Cavity-enhanced fourier transform spectroscopy for chiral analysis

Patent metadata

Field	Value
Publication number	US-11237104-B2
Application number	US-201716344688-A
Country	US
Kind code	B2
Filing date	Oct 25, 2017
Priority date	Oct 26, 2016
Publication date	Feb 1, 2022
Grant date	Feb 1, 2022

Abstract

A chiral molecule can be defined as a molecule that has a non-superimposable mirror image. These mirror images can be referred to as enantiomers. The enantiomers generally have the same set of bond lengths and bond angles in their three-dimensional geometry. Apparatus and techniques described herein can be used to perform analysis of chiral molecules using cavity-enhanced molecular rotational spectroscopy. A sample cell can define a resonant cavity, and a sample introduction port can provide pulse jet injection of an analyte molecule and a chiral tag to allow analysis of a complex comprising the analyte and chiral tag.

First claim

The claimed invention is:

1. A method of analyzing a chiral analyte having an unknown enantiopurity, comprising:
providing a chiral tag having a specified enantiopurity;
using a pulsed jet, injecting the chiral analyte and the chiral tag into a sample cell, the chiral tag bonding to the chiral analyte to form a diastereomeric complex exhibiting a molecular rotational resonance (MRR) spectrum different than an MRR spectrum of the chiral analyte;
obtaining a time-domain response from the diastereomeric complex and
determining the MRR spectrum of the diastereomeric complex based on the time-domain response.

2. The method of claim 1 , wherein the sample cell comprises a tunable resonant cavity.

3. The method of claim 1 , wherein the sample cell comprises a resonant cavity and obtaining the time-domain response comprises electrically exciting at least one mode of the resonant cavity with a sequential series of frequencies from a source.

4. The method of claim 1 , wherein the sample cell comprises a resonant cavity and obtaining the time-domain response comprises contemporaneously exciting multiple modes of the resonant cavity.

5. The method of claim 1 , wherein obtaining the time-domain response comprises exciting the diastereomeric complex with a range of frequencies falling within at least one of a microwave frequency range, a millimeter-wave range, or a terahertz frequency range.

6. The method of claim 1 , wherein the injecting is performed using a pulsed jet to provide expansion of the chiral analyte and the chiral tag into the sample cell, when the sample cell is at least partially evacuated.

7. The method of claim 1 , wherein the chiral tag comprises a racemic mixture.

8. The method of claim 1 , wherein the chiral tag comprises a racemic, isotopically-labeled composition.

9. The method of claim 1 , wherein the chiral tag is enantioenriched.

10. The method of claim 1 , wherein the chiral analyte and the chiral tag form the diastereomeric complex through non-covalent interaction.

11. The method of claim 10 , wherein the chiral analyte and the chiral tag are combined and injected using a pulsed-jet input port included as a portion of the sample cell.

12. The method of claim 11 , wherein the diastereomeric complex is a first diastereomeric complex and the sample cell comprises:
a first pulsed-jet input port to provide the first diastereomeric complex for a first measurement; and
a second pulsed-jet input port to provide a second diastereomeric complex comprising the chiral analyte and a racemic mixture of the chiral for a second measurement.

13. The method of claim 10 , wherein the chiral tag is provided using a reservoir containing a liquid-phase form of the chiral tag and an inert gas.

14. The method of claim 10 , wherein the chiral analyte is provided by ablating a liquid-phase or solid-phase form of the chiral analyte.

15. The method of claim 1 , further comprising:
distinguishing enantiomers of the chiral analyte based on the MRR spectrum of the diastereomeric complex.

16. A method, comprising:
electrically obtaining a first response elicited from a first diastereomeric complex including a chiral analyte and a racemic mixture comprising a chiral tag; and
electrically obtaining a second response elicited from a second diastereomeric complex including the chiral analyte and a specified-enantiopurity form of the chiral tag;
wherein the first and second responses are elicited by electrically exciting a range of molecular rotational resonances.

17. The method of claim 16 , comprising determining an enantiomeric excess (ee) value for the chiral analyte corresponding to diastereomers formed between the chiral analyte and the chiral tag having the specified enantiopurity at least in part by comparing spectra corresponding to the first and second responses.

18. The method of claim 16 , wherein the first sample and the second sample are in a tunable resonant cavity; and wherein the method comprises adjusting a distance between reflectors included as a portion of the tunable resonant cavity to shift the resonant frequencies of the tunable resonant cavity from a first group of frequencies to a second group of frequencies.

19. The method of claim 16 , wherein the chiral analyte and the racemic mixture comprising the chiral tag are injected using a first pulsed-jet input port included as a portion of a sample cell.

20. The method of claim 19 , wherein the chiral analyte and the chiral tag having a specified enantiopurity are injected using a second pulsed-jet input port included as a portion of the sample cell.

21. An apparatus, comprising:
a sample cell including a resonant cavity;
a source electrically coupled to the sample cell to electrically excite at least one mode of the resonant cavity;
a receiver electrically coupled to the sample cell to obtain a response elicited from a diastereomeric complex formed by a chiral analyte and a chiral tag within the sample cell, in response to excitation of the resonant cavity using the source, the receiver comprising an analog-to-digital converter to provide a digital representation of a time-domain response obtained from the sample cell; and
an isolator to isolate the source from the sample cell at least when the receiver is receiving the response elicited from the sample;
wherein the sample cell comprises at least two sample introduction ports, including at least one sample introduction port to receive the chiral analyte and the chiral tag.

22. The apparatus of claim 21 , wherein the sample cell is configured to be at least partially evacuated.

23. The apparatus of claim 21 , wherein the at least two sample introduction ports comprise pulsed jet sample introduction ports.

24. The apparatus of claim 23 , wherein the diastereomeric complex is a first diastereomeric complex and the at least two sample introduction ports include:
a first input port to provide the first diastereomeric complex for a first measurement; and
a second input port to provide a second diastereomeric complex comprising the chiral analyte and a non racemic form racemic mixture of the chiral tag for a second measurement.

25. The apparatus of claim 21 , wherein a range of frequencies corresponding to the at least one mode falls within at least one of a microwave frequency range, a millimeter-wave range, or a terahertz frequency range.

26. The apparatus of claim 21 , wherein the resonant cavity comprises a tunable resonant cavity.

27. The apparatus of claim 21 , wherein the isolator comprises a switch.

28. The apparatus of claim 21 , wherein the isolator comprises a microwave isolator coupled between the source and the sample cell and configured to attenuate or suppress signals propagating from the sample cell to the source.

29. A method of measuring enantiomeric excess of a chiral analyte of unknown enantiopurity, the method comprising:
injecting a first gas-phase sample of the chiral analyte and a racemic mixture of a chiral tag into a sample cell, the first gas-phase sample of the chiral analyte containing first enantiomers of the chiral analyte that form a first diastereomeric complex with the racemic mixture of the chiral tag and second enantiomers of the chiral analyte that form a second diastereomeric complex with the racemic mixture of the chiral tag in the sample cell, the first diastereomeric complex exhibiting a

Assignees

• Univ Virginia Patent Foundation

Inventors

• Pate Brooks Hart

Classifications

• H01J23/20

  Cavity resonators; Adjustment or tuning thereof · CPC title

• G01J3/447

  Polarisation spectrometry · CPC title

• G01J3/30

  Measuring the intensity of spectral lines directly on the spectrum itself (G01J3/42, G01J3/44 take precedence) · CPC title

• G01J1/16

  using electric radiation detectors (G01J1/20 takes precedence) · CPC title

• G01N22/00

  Investigating or analysing materials by the use of microwaves or radio waves, i.e. electromagnetic waves with a wavelength of one millimetre or more (G01N3/00 - G01N17/00, G01N24/00 take precedence) · CPC title