Laser Based Identification of Molecular Characteristics

• US 20090296744A1
• Filed: 11/29/2006
• Published: 12/03/2009
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: The Board of Trustees of Michigan State University (Michigan State University)
• Original Assignee: The Board of Trustees of Michigan State University (Michigan State University)
• Inventors: Dantus, Marcos, Lozovoy, Vadim V.
• Granted Patent: US 8,618,470 B2
• Time in Patent Office: Days
• US Class Current: 372/5
• CPC Class Codes: G01N 21/21 Polarisation-affecting properties G01N21/19 takes precedence
• CPC Class Codes: H01S 3/0057 Temporal shaping, e.g. pulse compression, frequency chirping soliton generation and propagation G02F1/3513, H01S3/063 and H01S3/108
• CPC Class Codes: H01S 3/10053 Phase control

Abstract

Enantiomers are characterized, identified, synthesized and/or modified with a shaped laser pulse. In another aspect of the present invention, binary shaping and circular polarization are employed with a laser pulse. A further aspect of the present invention provides a quarter-wave plate in combination with one or more pulse shapers.

Claims

1. A method of manufacturing a pharmaceutical compound, the method comprising:

(a) emitting a laser beam;

(b) shaping the laser beam;

(c) polarizing the laser beam;

(d) testing the pharmaceutical compound with the shaped and polarized laser beam;

(e) automatically determining a chiral property of the pharmaceutical compound based on the test; and

(f) creating a substantially helical and propeller-like direction and curvature of the polarized and shaped laser beam to cause enantiomeric selectivity.

3. The method of claim 1 further comprising emitting the laser beam with a pulse duration less than 100 femtoseconds.

4. The method of claim 1 further comprising polarizing the laser beam with a quarter-waveplate after a shaper.

5. The method of claim 1 further comprising electro-spraying the pharmaceutical compound.

6. The method of claim 1 further comprising detecting a characteristic of the pharmaceutical compound with an ion trap mass spectrometer while interrogating ions in the pharmaceutical compound with phase and polarization shaped laser beam pulses.

7. The method of claim 1 further comprising cleaving bonds in the pharmaceutical compound with phase and polarization shaped laser beam pulses.

8. The method of claim 1 further comprising using multiphoton intrapulse phase scan to minimize distortions in the laser beam.

9. The method of claim 1 further comprising using at least two of:

(a) zero, (b) π

, (c) right, and (d) left, circular polarization to test for effectiveness in determining chiral sensitivity to different laser beam shapes.

10. The method of claim 1 further comprising:

(a) correcting phase distortions of the laser beam with a first pulse shaper; and

(b) polarizing the laser beam with a second pulse shaper after the correcting step.

2. (canceled)

11. A method of manufacturing a pharmaceutical product, the method comprising:

(a) emitting a set of laser beam pulses on the pharmaceutical product, each of the pulses having a duration of less than 100 femtoseconds;

(b) shaping the pulses to control phase and amplitude in the pulses;

(c) automatically detecting and compensating for distortions in the pulses, without a genetic learning algorithm;

(d) polarizing the pulses after step (b) to control the electric field direction therein; and

(e) detecting or changing a characteristic of the pharmaceutical product with the shaped and polarized pulses.

12. The method of claim 11 further comprising creating a substantially helical and propeller-like direction and curvature of the polarized and shaped laser beam pulses to cause enantiomeric selectivity.

13. The method of claim 11 further comprising polarizing the laser beam pulses with a quarter-wave plate after a shaper.

14. The method of claim 11 further comprising electro-spraying the pharmaceutical product.

15. The method of claim 11 further comprising detecting a characteristic of the pharmaceutical product with an ion trap mass spectrometer while interrogating ions in the pharmaceutical product with phase and polarization shaped laser beam pulses.

16. The method of claim 11 further comprising cleaving bonds in the pharmaceutical product with phase and polarization shaped laser beam pulses.

17. The method of claim 11 further comprising using multiphoton intrapulse phase scan to minimize distortions in the laser beam pulses.

18. The method of claim 11 further comprising using at least two of:

(a) zero, (b) π

, (c) right, and (d) left, circular polarization to test for effectiveness in determining chiral sensitivity to different laser beam pulse shapes.

19. A method of operating a laser system, the method comprising:

(a) emitting a laser beam pulse;

(b) minimizing phase distortions of the pulse by pulse shaping without a genetic learning algorithm; and

(c) polarization shaping of the pulse after step (b).

20. The method of claim 19 further comprising creating a substantially helical and propeller-like direction and curvature of the polarized and shaped laser beam to cause enantiomeric selectivity.

21. The method of claim 19 further comprising:

(a) emitting the pulse with a duration of less than 51 femtoseconds; and

(b) minimizing phase distortions in an iterative manner using a series of laser beam pulses.

25. The method of claim 19 further comprising detecting a characteristic of a pharmaceutical compound with an ion trap mass spectrometer while interrogating ions in the pharmaceutical compound with phase and polarization shaped laser beam pulses.

26. The method of claim 19 further comprising cleaving bonds in a pharmaceutical compound with phase and polarization shaped laser beam pulses.

27. The method of claim 19 further comprising automatically destroying undesired enantiomers with the pulse.

22-24. -24. (canceled)

28. A method of operating a laser system, the method comprising using at least two of:

(a) vertical linear, (b) horizontal linear, (c) right circular, and (d) left circular, pulse shapes to test essentially all possible pulse shapes for determining chiral sensitivity in a specimen.

32. The method of claim 28 further comprising electro-spraying the specimen which is a pharmaceutical compound.

33. The method of claim 28 further comprising cleaving bonds in the specimen which is a pharmaceutical compound with phase and polarization shaped laser beam pulses.

34. The method of claim 28 further comprising using multiphoton intrapulse phase scan to minimize distortions in the laser beam pulse.

35. The method of claim 28 further comprising:

(a) correcting phase distortions of the laser beam pulse with a first pulse shaper; and

(b) polarizing the laser beam pulse with a second pulse shaper after the correcting step.

36. The method of claim 28 further comprising using all four of the pulse shapes.

29-31. -31. (canceled)

37. A method of operating a laser system, the method comprising:

(a) emitting a laser pulse;

(b) shaping the pulse including polarization; and

(c) detecting secondary structure of a specimen in response to interaction of the shaped pulse on the specimen.

38. The method of claim 37 wherein the secondary structure includes a secondary protein structure.

39. The method of claim 37 wherein the secondary structure includes a secondary carbohydrate structure.

40-50. -50. (canceled)

51. A laser system comprising:

a laser operably emitting laser beam pulses, each being less than 1000 fs in duration and having a bandwidth greater than 10 nm;

at least one device operably linearly and circularly polarizing the pulses;

a spectrometer; and

a controller connected to the spectrometer and device;

the controller automatically causing the device to vary the polarization based at least in part on a signal from the spectrometer, and without a genetic learning algorithm.

52-57. -57. (canceled)

58. A laser system comprising:

an ultraviolet laser pulse having a center wavelength shorter than about 420 nm and a bandwidth greater than about 10 nm;

an adaptive shaper operably varying a characteristic of the pulse; and

a detector operably detecting a chiral property of a specimen.

59. The laser system of claim 58 further comprising the detector operably detecting a characteristic of the pulse and a controller automatically varying the performance of the shaper based on a signal from the detector.

60-62. -62. (canceled)

63. A laser system comprising:

laser pulses having a second or third order harmonic wavelength;

a shaper operably varying a characteristic of the pulses;

a polarizer operably polarizing the pulses; and

a detector operably detecting a chiral characteristic of a specimen acted upon by the shaped and polarized pulses.

64-67. -67. (canceled)

68. A method of manufacturing a pharmaceutical compound, the method comprising:

(a) emitting a laser beam;

(b) shaping the beam;

(c) polarizing the laser beam;

(d) using at least two of;

(i) zero, (ii) π

, (iii) right, and (iv) left, circular polarization to test for effectiveness in determining chiral sensitivity to different laser beam shapes; and

(e) detecting or changing a characteristic of the pharmaceutical compound with the shaped and polarized beam.

69. The method of claim 68 further comprising only using binary settings of right and left polarization for testing beam shape values for enantiomer sensitivity.

70. The method of claim 68 further comprising automatically detecting and compensating for distortions in the beam without a genetic learning algorithm.

71. The method of claim 68 further comprising protein sequencing with the shaped and polarized beam.