Raman spectroscopy for monitoring drug-eluting medical devices

• US 20050171436A1
• Filed: 01/09/2004
• Published: 08/04/2005
• Est. Priority Date: 01/09/2004
• Status: Abandoned Application

• Current Assignee: Prescient Medical, Inc.
• Original Assignee: Prescient Medical, Inc.
• Inventors: Clarke, Richard H., Womble, M. Edward
• Application Number:
  US10/754,158
• Publication Number:
  US 20050171436A1
• Time in Patent Office: Days
• US Class Current: 600/476
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/0086 using infrared radiation
• CPC Class Codes: A61B 5/4839 combined with drug delivery

Abstract

The present invention provides low-resolution Raman spectroscopic systems and methods for in situ monitoring of drug-eluting devices in a lumen of a subject. A preferred system can employ multi-mode radiation in making in situ Raman spectroscopic measurements of the lumen and/or device. For example, a system can include a light source such as a multi-mode laser, and a light detector to measure spectral patterns and differentiates spectral features of drugs released in a target region. Drug-release curves can be extrapolated or otherwise predicted using the Raman spectrum taken during or subsequent to device insertion and/or activation.

Claims

1. A system for monitoring a drug-eluting device in using low-resolution Raman spectroscopy comprising:

a catheter having a first end and a second end with an excitation fiber extending therebetween, the excitation fiber suitable to transmit multi-mode radiation from the first end to the second end to irradiate a target region;

a multi-mode laser coupled to the first end of the excitation fiber, the laser generates multi-mode radiation for irradiating the target region to produce a Raman spectrum consisting of scattered electromagnetic radiation;

a low-resolution dispersion element positioned to receive and separate the scattered radiation into different wavelength components;

a detection array, optically aligned with the dispersion element for detecting at least some of the wavelength components of the scattered light; and

a processor for processing the data from the detector array to monitor a drug eluted from the medical device.

2. The system of claim 1, wherein the target region is any of the group consisting of a device package, a device, and a lumen in a subject.

3. The system of claim 1, wherein the catheter further comprises:

a light directing element optically coupled to the second end of the excitation fiber to direct the laser radiation from the excitation fiber to the target region.

4. The system of claim 3, wherein the light directing element directs the laser radiation out a side of the catheter.

5. The system of claim 1, wherein the system has a resolution of between approximately 1 cm⁻

1 and approximately 40 cm<sup>−

1</sup>.

6. The system of claim 5, wherein the system has a resolution of approximately 15 cm⁻

1.

7. The system of claim 1, wherein the multi-mode laser produces a laser light with a wavelength of approximately 785 nanometers.

8. The system of claim 7, wherein the laser is a GaAs laser diode.

9. The system of claim 1, wherein the multi-mode laser produces a laser light with a power of between approximately 50 milliwatts and 1,500 milliwatts measured at the target.

10. The system of claim 9, wherein the multi-mode laser produces a laser light with a power of approximately 150 milliwatts measured at the target.

11. The system of claim 1, wherein the multi-mode laser produces a laser light with a line width of between approximately 1 nm and 10 nm.

12. The system of claim 11, wherein the multi-mode laser produces a laser light with a line width of at least 2 nm.

13. The system of claim 1, wherein the detection array detects a spectral range between approximately 400 cm⁻

1 and approximately 3,000 cm<sup>−

1</sup>.

14. The system of claim 1, wherein the wavelength components are separated by a resolution ranging from about 10 cm⁻

1 to about 100 cm<sup>−

1</sup>.

15. A method for detecting a drug-release curve indicating presence of a drug released from a drug-eluting device using low-resolution Raman spectroscopy comprising:

determining a Raman spectrum for a background of the drug-eluting device;

determining a Raman spectrum for a target in proximity of the drug-eluting device;

processing the target spectrum and the background spectrum to isolate the target spectrum from the background spectrum;

predicting a drug-release curve over a time period based on the processed spectrums.

17. The system of claim 15, wherein the multi-mode laser produces a laser light with a power of between approximately 50 milliwatts and 1,500 milliwatts measured at the target.

18. The method of claim 17, wherein the multi-mode laser produces a laser light with a power of approximately 150 milliwatts measured at the target.

19. The method of claim 15, wherein the multi-mode laser produces a laser light with a line width of between approximately 1 nm and 10 nm.

20. The method of claim 19, wherein the multi-mode laser produces a laser light with a line width of at least 2 nm.

21. The method of claim 15, wherein the detection array detects a spectral range between approximately 400 cm⁻

1 and approximately 3,000 cm<sup>−

1</sup>.

22. The method of claim 15, wherein the wavelength components are separated by a resolution ranging from about 10 cm⁻

1 to about 100 cm<sup>−

1</sup>.

23. The method of claim 15, further comprising:

providing a catheter comprising an excitation fiber through which multi-mode radiation can propagate, the excitation fiber having a first end optically coupled to a multi-mode laser, and a second end positioned in optical alignment with a light directing element to direct radiation to a target within the lumen;

inserting the catheter in proximity to the target;

activating the multi-mode laser to irradiate the target to produce the target spectrum consisting of scattered electromagnetic radiation;

collecting a portion of the scattered radiation;

separating the collected radiation into different wavelength components using a low-resolution dispersion element;

detecting at least some of the wavelength components of the scattered light using a detection array; and

processing the data from the detection array to detect the presence of the drug released by the drug-eluting device.

24. The method of claim 15, further comprising identifying the components of the target from the data.

25. The method of claim 15, wherein the step determining a Raman spectrum for a target comprises inserting a catheter into a lumen of a subject.

26. The method of claim 25, wherein the lumen is a blood vessel.

27. The method of claim 15, wherein the step of determining a Raman spectrum for drug-absorbing tissue comprises detection of a drug released by the drug-eluting medical device.

28. The method of claim 27, wherein the drug is a scar tissue inhibitor.

29. The method of claim 15, wherein the step of predicting drug-release over a time period further comprises applying a partial least squares analysis to extract chemometric information from the data.

16. The method of claim 16, wherein the step of determining a Raman spectrum for a target in proximity of the drug-eluting device comprises determining a Raman spectrum for any of the group consisting of device package, a device, and a lumen in a subject.

30. A method for determining the presence or absence of a drug using Raman scattered radiation comprising:

irradiating a target region with radiation suitable for inducing Raman scattering;

collecting Raman scattered radiation from the target region;

determining a Raman spectrum from the collected radiation; and

analyzing the Raman spectrum to determine the presence or absence of at least one drug in the target region.

31. The method of claim 30, wherein the step of irradiating a target region comprises irradiating any of the group consisting of a drug-eluting device, a drug-eluting device package, and a lumen of a subject.

32. The method of claim 30, wherein the step of irradiating a device further comprises providing multi-mode laser radiation.

33. The method of claim 32, wherein the laser radiation has a wavelength of between approximately 300 nm and approximately 1,500 nm.

34. The method of claim 32, wherein the laser radiation has a power of between approximately 50 mw and approximately 1,500 mw measured at the target.

35. The method of claim 32, wherein the laser radiation has a line width of between approximately 1 nm and approximately 10 nm.

36. The method of claim 30, wherein the step of determining a Raman spectrum further comprises separating the collected radiation into one or more wavelength components.

38. The method of claim 30, wherein the step of determining a Raman spectrum further comprises determining a spectral range of between about 400 cm⁻

1 and about 3,000 cm<sup>−

1</sup>.

39. The method of claim 30, further comprising:

providing a catheter comprising an excitation fiber through which multi-mode radiation can propagate, the excitation fiber having a first end optically coupled to a multi-mode laser, and a second end positioned in optical alignment with a light directing element to direct radiation to a target;

positioning the second end of the catheter in proximity to the target;

activating the multi-mode laser to irradiate the target;

collecting a portion of the scattered radiation;

separating the collected radiation into different wavelength components using a low-resolution dispersion element;

detecting at least some of the wavelength components of the scattered light using a detection array; and

processing the data from the detection array to detect the presence of the drug released by the drug-eluting device.

40. The method of claim 39, wherein the step of positioning the second end of the catheter further comprises inserting the second end of the catheter into a lumen of a subject.

41. The method of claim 40, wherein the lumen is a blood vessel.

42. The method of claim 30, wherein the step of analyzing the Raman spectrum further comprises differentiating background noise from the Raman spectrum.

43. The method of claim 42, wherein the background noise comprises a Raman scattering of the drug-eluting device.

44. The method of claim 30, further comprising predicting a drug-release curve based on the analyzed Raman spectrum.

45. The method of claim 44, wherein the drug-release curve is over a time period greater than the time period of the collected Raman scattered radiation.

37. The method of claim 37, wherein the wavelength components are separated by a resolution ranging from about 10 cm⁻

1 and about 100 cm<sup>−

1</sup>.