System and method for the non-destructive assessment of the quantitative spatial distribution of components of a medical device

• US 7,478,008 B2
• Filed: 07/19/2007
• Issued: 01/13/2009
• Est. Priority Date: 03/16/2007
• Status: Active Grant

• Current Assignee: Cardinal Health Switzerland 515 GmbH (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Papandreou, George, Balss, Karin Maria, Maryanoff, Cynthia Anne, Veselov, Vladimir, Llanos, Gerard
• Primary Examiner(s): Bui; Bryan
• Application Number:
  US11/780,342
• Publication Number:
  US 20080228428A1
• Time in Patent Office: 544 Days
• Field of Search: 702/32, 702/137, 702/152, 702/180, 702/189, 702/190, 702/191, 356/326, 356/432, 356/630, 356/317, 356/318, 600/407, 600/473, 600/476, 250/339.05, 250/339.07, 250/339.11
• US Class Current: 702/137
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 21/95 characterised by the material or shape of the object to be examined G01N21/89 - G01N21/91, G01N21/94 take precedence
• CPC Class Codes: G16C 20/20 Identification of molecular entities, parts thereof or of chemical compositions
• CPC Class Codes: G16C 20/70 Machine learning, data mining or chemometrics
• CPC Class Codes: G16H 40/20 for the management or administration of healthcare resources or facilities, e.g. managing hospital staff or surgery rooms

Abstract

A method and system for the non-destructive analysis of medical devices uses a confocal Raman microscope and other non-destructive analytical tools to assess the spatial distribution of components of an object such as the distribution of an active pharmaceutical ingredient (API) within a polymer matrix. In a preferred embodiment, confocal Raman spectroscopy was used to differentiate each component found in the sirolimus-eluting coronary stent. The unique spectral features identified for each component were then used to develop three separate calibration curves to describe the solid phase distribution found on drug-polymer coated stents. The calibration curves were obtained by analyzing confocal Raman spectral depth profiles from a set of 16 unique formulations of drug-polymer coatings sprayed onto stents and planar substrates.

Claims

1. A system for a non-destructive analysis of a spatial distribution and identification of one or more components of an object without addition of an image enhancement agent comprising:

a sample and analysis tracking module for collecting and storing information about the object;

an analysis processing module to collect data regarding the distribution of components of the object and information regarding collection of the data; and

a data processing module for analytically processing the data to determine the spatial distribution and identification of the one or more components of the object.

2. The system of claim 1 wherein the sample and analysis tracking module collects and stores a description of the object, fabrication date of the object, and the analysis date.

3. The system of claim 1 wherein the analysis processing module comprises an analytical instrument for collecting information about the object.

4. The system of claim 3 wherein the analytical instrument comprises a confocal Raman microscope.

5. The system of claim 3 wherein the analysis processing module further comprises a positioning device for controlling the position of the object relative to the analytical instrument.

6. The system of claim 5 wherein the analysis processing module further comprises a bar code scanner for reading an identifying bar code on the object.

7. The system of claim 6 wherein the analysis processing module further comprises a programmable logic controller for controlling the functions of the analytical instrument, positioning device and bar code scanner.

8. The system of claim 1 wherein the output of the data processing module includes information about the composition of components and the spatial distribution of components of the object including identification of manufacturing and formulation defects of the object.

9. The system of claim 8 wherein the output is displayed as a visual representation.

10. The system of claim 8 wherein the output is displayed as a numeric representation.

11. The system of claim 1 further comprising a central database that receives and stores data from the analysis processing module and the data processing module.

12. The system of claim 3 wherein the analytical instrument is selected from the group consisting of:

a confocal Raman microscope, a confocal fluorescence microscope, a scanning polarized and phased light microscope, an x-ray photoelectron imaging system, a near IR Imaging system and a dynamic static ionization mass spectrometer (dynamic SIMS).

13. The system of claim 1 wherein the data processing module comprises a filter to filter the data received from the analysis processing module to remove noise.

14. The system of claim 13 wherein the filter removes noise from the data resulting from cosmic rays.

15. The system of claim 13 wherein the filter comprises a band-pass filter used to exclude the laser line at the detector of a confocal Raman microscope.

16. The system of claim 1 wherein the data processing module comprises a clustering algorithm.

17. The system of claim 16 wherein the clustering algorithm is the K-means clustering algorithm.

18. The system of claim 1 further comprising a set of training sets and validation sets for each type of object to be analyzed.

19. A method for a non-destructive analysis of a spatial distribution and identification of one or more components of a an object without the use of image enhancement agents comprising the steps of:

collecting and storing information about the object;

collecting data regarding the distribution of components of the object and information on the collection of the data; and

,

analytically processing the data in a data processing module to determine the spatial distribution and identification of the one or more components of the object.

20. The method of claim 19 wherein the step of collecting and storing information about the object includes collecting and storing a description of the object, the fabrication date of the object, and/or the analysis date of testing.

21. The method of claim 19 wherein confocal Raman microscopy is used to collect data regarding the distribution of components of the object.

22. The method of claim 19 wherein the step of collecting data uses an analytical instrument selected from the group consisting of:

a confocal Raman microscope, a confocal fluorescence microscope, a scanning polarized and phased light microscope, and x-ray photoelectron imaging system, a near IR imaging system and a dynamic static ionization mass spectrometer (dynamic SIMS).

23. The method of claim 19 wherein the output of the step of analytically processing the data includes outputting information about the composition of components of the object, the distribution of components within the object and identification of manufacturing and formulation defects of the object.

24. The method of claim 23 wherein the output is displayed as a visual representation.

25. The method of claim 23 wherein the output is displayed as a numeric representation.

26. The method of claim 19 wherein the step of analytically processing the data further includes the steps of:

filtering the data to remove noise;

standardizing the data;

performing a clustering algorithm on the data;

comparing the data to one or more training sets and validations set for a specific type of test sample;

building a model of the quantitative spatial distribution of the components in the object;

calibrating the model using PCA and linear regression techniques; and

,

generating a visualization of the quantitative spatial distribution of components of the object for output to the user.

27. The method of claim 19 further comprising the step of storing data about the object and the spatial distribution of component in the object in a central database.

28. A system for a non-destructive analysis of a spatial distribution and identification of one or more components of a coating applied to a medical device without use of an image enhancement agent comprising:

a sample and analysis tracking module for collecting and storing a description of the medical device;

an analysis processing module comprising an analytical instrument, positioning device and a programmable controller used to collect data regarding the distribution of components of the coating applied to the medical device;

a data processing module for analytically processing the data to determine the spatial distribution and identification of the one or more components of the medical device; and

,

a central database in communication with the sample analysis tracking module, and the data processing module for storing information and data regarding the medical device.

29. The system of claim 28 wherein the analytical instrument comprises a confocal Raman microscope.

30. The system of claim 28 wherein the analytical instrument is selected from the group consisting of:

a confocal Raman microscope, a confocal fluorescence microscope, a scanning polarized and phased light microscope, an x-ray photoelectron imaging system, a near IR imaging system and a dynamic static ionization mass spectrometer.

31. The system of claim 28 wherein the data processing module comprises a filter to filter the data received from the analysis processing module to remove noise.

32. The system of claim 31 wherein the filter removes noise from the data resulting from cosmic rays.

33. The system of claim 29 wherein the filter comprises a band-pass filter used to exclude the laser line at the detector of the confocal Raman microscope.

34. The system of claim 28 wherein the data processing module comprises a clustering algorithm.

35. The system of claim 34 wherein the clustering algorithm is the K-means clustering algorithm.

36. A method for a non-destructive analysis of a spatial distribution and identification of one or more components of a coating applied to a medical device without use of image enhancement agents comprising the steps of:

collecting and storing information about the medical device;

collecting data regarding the distribution of components in the coating applied to the medical device using an analytical instrument and positioning device; and

,

analytically processing the data in a data processing module to determine the spatial distribution and identification of the one or more components in the coating applied to the medical device.

37. The method of claim 36 wherein confocal Raman microscopy is used to collect data regarding the distribution of components of the coating on the medical device.

38. The method of claim 36 wherein the step of analytically processing the data further includes the steps of:

filtering the data to remove noise;

standardizing the data;

performing a clustering algorithm on the data;

comparing the data to one or more training sets and validations set for a specific type of test sample;

building a model of the quantitative spatial distribution of the components in the coating applied to the medical device;

calibrating the model using PCA and linear regression techniques; and

,

generating a visualization of the quantitative spatial distribution of components of the coating for output to the user.

39. The method of claim 36 wherein the medical device is a drug-eluting stent having an active pharmaceutical ingredient (API) in a polymer matrix.

40. The method of claim 39 wherein the output of the step of analytically processing the data includes outputting information about the API content, API distribution, polymer matrix content, polymer matrix distribution, coating thickness and identification of manufacturing and formulation defects of the coating on the stent.