Nuclear magnetic resonance analysis of multiple samples

• US 20020130661A1
• Filed: 08/24/2001
• Published: 09/19/2002
• Est. Priority Date: 02/26/1999
• Status: Active Grant

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Fisher, George G., Petucci, Christopher J., Raftery, Daniel, McNamara, Ernesto
• Granted Patent: US 6,696,838 B2
• Time in Patent Office: Days
• US Class Current: 324/318
• CPC Class Codes: G01R 33/302 Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
• CPC Class Codes: G01R 33/307 specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer
• CPC Class Codes: G01R 33/34053 Solenoid coils; Toroidal coils
• CPC Class Codes: G01R 33/3628 Tuning/matching of the transmit/receive coil
• CPC Class Codes: G01R 33/365 Decoupling of multiple RF coils wherein the multiple RF coils have the same function in MR, e.g. decoupling of a receive coil from another receive coil in a receive coil array, decoupling of a transmission coil from another transmission coil in a transmission coil array
• CPC Class Codes: G01R 33/422 of the radio frequency field

Abstract

A Nuclear Magnetic Resonance (NMR) probe device (20) is disclosed. NMR probe device (20) includes a plurality of detection coils (30, 40) each operable to detect a signal from a corresponding one of a plurality of samples (34, 44) undergoing NMR analysis. Also included is a plurality of tuning circuits (31, 41, 38, 48) each coupled to one of detection coils (30, 40) to tune the one of the detection coils (30, 40) to a corresponding resonant frequency for the NMR analysis of the corresponding one of the samples. An electromagnetic shield (22) is positioned between a first one of the detection coils (30, 40) and a second one of the detection coils (30, 40) to isolate the first one of the detection coils (30, 40) and the second one of the detection coils (30, 40) from each other.

Claims

1. An apparatus, comprising:

an NMR transmitter to analyze a number of samples;

a number of sample holders each operable to receive a corresponding one of the samples for NMR analysis;

a plurality of detection coils each operable to detect a response of the corresponding one of the samples to one or more signals from said NMR transmitter;

an adjustable magnetic field source proximate to a sample space arranged to receive said sample holders, said magnetic field source being operable to selectively provide;

a first magnetic field to generate a first response of the samples when received in said sample space,

a second magnetic field having a gradient relative to said first magnetic field to generate a second response of the samples when received in said sample space, said second response corresponding to a number of frequency shifts relative to said first response, said frequency shifts each corresponding to a different one of the samples; and

a processor operable to determine a number of spectral characterizations as a function of said first sample response and said second response, the spectral characterizations each being representative of a different one of the samples.

2. The apparatus of claim 1, wherein said first response corresponds to an unshifted composite spectrum of the samples, said second response corresponds to a shifted composite spectrum of the samples, and said processor is operable to establish a spectral mask for each of said detection coils from said first response and said second response during determination of the spectral characterizations.

3. The apparatus of claim 1, wherein said processor is operable to perform reference deconvolution during determination of the spectral characterizations.

4. The apparatus of claim 1, wherein said processor is operable to perform multidimensional NMR analysis.

5. The apparatus of claim 1, wherein the first magnetic field is generally homogeneous in said sample space.

6. The apparatus of claim 1, wherein said detection coils number at least four.

7. The apparatus of claim 1, further comprising an NMR receiver coupled to said detection coils and a control to selectively adjust the gradient.

8. The apparatus of claim 1, wherein said sample holders are each in fluid communication with sample instrumentation to perform capillary electrophoresis.

9. The apparatus of claim 1, wherein said sample holders are each mounted in a probe device sized for insertion in said sample space, said probe device including a vessel to dispose a susceptibility fluid about said sample holders when received in said sample space.

16. The apparatus of any of claims 1-15, wherein:

said detection coils are each of a microcoil variety with a diameter of less than about 1 millimeter; and

said sample holders each include a tube disposed within a corresponding one of said detection coils.

17. The apparatus of any of claims 1-15, wherein said detection coils are of a saddle or solenoid configuration.

10. An apparatus, comprising:

an NMR transmitter;

an magnet device operable to provide a magnetic field for NMR analysis;

a number of sample holders each operable to expose a corresponding one of a number of samples to the magnetic field;

a plurality of detection coils each operable to detect a response of the corresponding one of the samples to one or more signals from said NMR transmitter;

a number of tuning circuits each coupled to a different one of said detection coils to tune said different one of said detection coils to a resonant frequency for the corresponding one of the samples; and

at least one receiver coupled to said detection coils.

11. The apparatus of claim 10, further comprising an electromagnetic shield between a first one of the coils and a second one of the coils.

12. The apparatus of claim 10, further comprising a ground plane between a first one of the coils and a second one of the coils.

13. The apparatus of claim 10, wherein said tuning circuits each include at least one operator-adjustable capacitor.

14. The apparatus of claim 10, further comprising a number of transmission lines each coupled between said different one of said detection coils and a respective one of said turning circuits.

15. The apparatus of claim 10, wherein said tuning circuits are each operable to tune the resonant frequency for each of the samples to a common nucleus type.

19. The apparatus of claim 18, further comprising a plurality of sample holders each corresponding to one of said detection coils.

31. The apparatus of any of claims 19-25, wherein said sample holders each include a tube disposed within a corresponding one of said detection coils.

32. The apparatus of claim 31, wherein said sample holders each include a tube disposed within a corresponding one of said detection coils.

18. An apparatus, comprising:

NMR probe device, said NMR probe device including;

a number of detection coils each operable to detect a signal from a corresponding one of a plurality of samples undergoing NMR analysis;

a plurality of tuning circuits each coupled to a different one of said detection coils to tune said different one of said detection coils to a corresponding resonant frequency for the NMR analysis of the corresponding one of the samples; and

an electromagnetic shield positioned between a first one of said detection coils and a second one of said detection coils to isolate said first one of said detection coils and said second one of said detection coils from each other.

26. The apparatus of any of claims 18-25, further comprising:

an NMR transmitter to provide an RF signal to excite the samples;

a magnetic field source proximate to a sample space configured to receive said probe device; and

at least one NMR receiver.

27. The apparatus of any of claims 18-25, wherein said detection coils number two or more.

28. The apparatus of any of claims 18-25, wherein one of said detection coils extends along a first longitudinal axis, another of said detection coils extends along a second axis, and said first longitudinal axis crosses said second longitudinal axis at an angle between 45 and 135 degrees.

29. The apparatus of any of claims 18-25, wherein at least one of said detection coils is carried on a circuit substrate with one or more other components.

30. The apparatus of any of claims 18-25, wherein said detection coils are each of a microcoil variety with a diameter of less than about 1 millimeter and said detection coils are each of a solenoid or saddle configuration.

20. An apparatus, comprising:

an NMR probe device, said NMR prove device including;

a plurality of sample holders each operable to expose a different one of a plurality of samples to a magnetic field for NMR analysis;

a plurality of detection coils each operable to selectively detect a response from a corresponding one of the samples; and

a ground plane positioned between a first one of said detection coils and a second one of said detection coils to decouple said first one of said coils and said second one of said coils from each other.

21. The apparatus of claim 20, further comprising a plurality of tuning circuits each coupled to a respective one of said detection coils.

22. An apparatus, comprising:

an NMR probe device to perform NMR analysis on a plurality of samples, said NMR probe device including;

a plurality of sample holders each operable to receive a different one of the samples;

a plurality of detection coils each operable to detect a signal from a corresponding one of the samples undergoing the NMR analysis;

a plurality of first tuning networks each coupled to a different one of said detection coils;

a plurality at second tuning networks each including at least one adjustable element; and

a plurality of transmission lines each electrically coupled between a respective one of said first tuning networks and said second tuning networks.

23. The apparatus of claim 22, further comprising an electromagnetic shield positioned between a first one of said detection coils and a second one of said detection coils.

24. The apparatus of claim 22, further comprising a ground plane positioned between each of said detection coils.

25. The apparatus of claim 22, wherein said first tuning networks are each operable to provide coarse resonant frequency tuning to reduce power loss through said transmission lines and said second tuning networks are each operable to provide fine resonant frequency tuning for a common nucleus.

33. A method, comprising:

operating an NMR spectroscopy system including a sample space and a plurality of detection coils each disposed about a corresponding one of a plurality of separated samples in the sample space;

generating a first magnetic field in the sample space;

detecting a first response of the samples during generation of the first magnetic field;

generating a second magnetic field in the sample space, the second magnetic field including a gradient relative to the first magnetic field;

detecting a second response from the samples during generation of the second magnetic field; and

determining a plurality of NMR spectra each corresponding to a different one of the samples in accordance with the first response and the second response.

34. The method of claim 33, further comprising performing a multidimensional NMR analysis of the samples.

35. The method of claim 33, wherein said determining includes establishing a spectral mask for each of the detection coils.

36. The method of claim 33, wherein said determining includes performing reference deconvolution.

38. The method of claim 37, further comprising determining the different excitation frequency for each of the samples as a function of a magnitude of the gradient.

39. The method of claim 37, wherein the samples are each consecutively excited with the different excitation frequency.

40. The method of any of claims 33-39, wherein the detection coils each excite the corresponding one of the samples.

41. The method of any of claims 33-39, wherein the sample responses each correspond to a spectrum for the different one of the samples.

42. The method of any of claims 33-39, wherein the detection coils number at least four.

43. The method of any of claims 33-39, wherein said detection coils number at least four and are each of a microcoil variety with a diameter of less than about 1 millimeter.

44. The method of any of claims 33-39, wherein the detection coils are each disposed about a respective one of a number of tubes, and the tubes are each arranged to receive the corresponding one of the samples.

46. The method of claim 45, wherein the detection coils each extend along a respective longitudinal axis, and the respective longitudinal axis of the first one of the detection coils crosses the respective longitudinal axis of the second one of the detection coils at an angle in a range from about 45 degrees to about 135 degrees.

47. The method of claim 45, wherein the detection coils are each of a solenoid or saddle type, being positioned about a respective centerline axis, and the respective centerline axis of the first one of the detection coils is oriented at approximately a right angle relative to the respective centerline axis of the second one of the detection coils.

48. The method of claim 47, wherein the respective centerline axis of each of the detection coils is oriented at approximately a right angle to the respective centerline axis of an adjacent one of the detection coils.

37. A method, comprising:

generating a magnetic field with a predetermined gradient in a sample space containing a plurality of detection coils each disposed about a corresponding one of a number of samples;

detecting a number of sample responses each corresponding to excitation of a respective one of the samples by a different excitation frequency during generation of the magnetic field; and

determining a number of NMR spectral characterizations from the sample responses, the NMR spectral characterizations each being representative of a different one of the samples.

45. A method, comprising:

providing an NMR spectroscopy system including a magnetic field source proximate to a sample space;

positioning a plurality of sample holders in the sample cavity, the sample holders each carrying a different one of a plurality of detection coils;

orienting a first one of the detection coils relative to a second one of the detection coils to minimize cross-talk between the first one of the detection coils and the second one of the detection coils based on geometry of the first one of the detection coils and the second one of the detection coils; and

operating the NMR spectroscopy system to analyze a plurality of different samples each disposed in a corresponding one of the sample holders.

49. The method of any of claims 45-48, further comprising positioning an electromagnetic shield between the first one of the detection coils and the second one of the detection coils.

50. The method of any of claims 45-48, further comprising positioning a ground plane between the first one of the detection coils and the second one of the detection coils.

51. The method of any of claims 45-48, further comprising providing a number of adjustable tuning circuits each coupled to a corresponding one of detection coils.

52. The method of any of claims 45-48, wherein the NMR spectroscopy system includes:

an NMR transmitter to provide an RF signal to excite the samples;

a magnetic field source proximate to a sample space configured to receive said probe device; and

at least one NMR receiver.

53. The method of any of claims 45-48, wherein the detection coils number two or more, and further comprising a plurality of circuit substrates each including a ground plane and carrying one or more of the detection coils.

54. The method of any of claims 45-48, wherein the detection coils are each of a microcoil variety with a diameter of less than about 1 millimeter.

55. An apparatus, comprising:

an NMR probe device, including;

an RF excitation source;

a first coil operable to be disposed about a first sample to detect a first sample response to an excitation signal from said RF excitation source;

a second coil operable to be disposed about a second sample to detect a second sample response to the excitation signal, said second coil being connected in series with said first coil; and

wherein said first coil and said second coil are disposed relative to said RF excitation source to provide a phase difference between the first sample response and the second sample response to at least partially cancel one or more response components corresponding to a common material in the first sample and the second sample.

56. The apparatus of claim 55, wherein said first coil and said second coil are geometrically oriented to provide said phase difference of about 180 degrees.

57. The apparatus of claim 55, further comprising a first sample holder disposed within said first coil to receive the first sample and a second sample holder disposed within said second coil to receive the second sample.

58. The apparatus of claim 55, wherein said first coil and said second coil are each of a saddle or solenoid configuration.

59. The apparatus of any of claims 55-58, further comprising an excitation coil positioned about said first coil and said second coil.

60. The apparatus of claim 59, wherein said first coil is positioned about a first axis, said second coil is positioned about a second axis, said excitation coil is positioned about a third axis, and said first and second axes are generally perpendicular to said third axis.

61. The apparatus of any of claims 55-58, wherein said RF excitation source includes and NMR transmitter coupled to said first coil and said second coil to excite the first sample and the second sample in parallel, and further comprising:

a magnetic field source proximate to a sample space configured to receive said probe device; and

at least one NMR receiver coupled to said first coil and said second coil.

62. The apparatus of any of claims 55-58, wherein said first coil and said second coil are each of a microcoil variety with a diameter of less than about 1 millimeter.

63. A method, comprising:

preparing a first sample comprised of a solvent and a second sample comprised of a mixture of the solvent and an analyte;

exciting the first sample and the second sample to perform NMR analysis of the analyte; and

detecting a first sample response with a first coil and a second sample response with a second coil, the first sample response including a phase difference relative to the second sample response to reduce solvent interference with the NMR analysis of the analyte.

64. The method of claim 63, wherein said exciting includes exposing the first sample and the second sample to an RF signal radiated by an excitation coil disposed about the first coil and the second coil.

65. The method of claim 63, wherein said exciting includes providing an RF signal to the first sample with the first coil and to the second sample the second coil.

66. The method of claim 63, wherein the phase difference is approximately 180 degrees.

67. The method of any of claims 63-66, further comprising disposing a first sample holder disposed within the first coil to receive the first sample and a second sample holder within the second coil to receive the second sample.

68. The method of any of claims 63-66, wherein the first coil and the second coil are each of a microcoil variety with a diameter of less than about 1 millimeter.

69. The method of any of claims 63-66, wherein the first coil and the second coil are each of a saddle or solenoid geometry.

70. The method of any of claims 63-66, wherein the first coil is wired in series with the second coil.