Raman chemical imaging of implantable drug delivery devices

• US 8,416,405 B2
• Filed: 08/07/2009
• Issued: 04/09/2013
• Est. Priority Date: 08/08/2008
• Status: Active Grant

• Current Assignee: Chemimage Corporation
• Original Assignee: Chemimage Corporation
• Inventors: Panza, Janice, Maier, John
• Primary Examiner(s): Toatley, Gregory J
• Assistant Examiner(s): ALLI, IYABO
• Application Number:
  US12/537,671
• Publication Number:
  US 20100033717A1
• Time in Patent Office: 1,341 Days
• Field of Search: 356/301, 356328-334, 435/4, 435/5, 435/32, 435/25, 435/39, 600/607, 600/600, 600473-478
• US Class Current: 356/301
• CPC Class Codes: G01J 3/44 Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 2201/129 Using chemometrical methods

Abstract

A system and method of determining an attribute of a biological tissue sample or a drug delivery device. A sample is illuminated with substantially monochromatic light to thereby generate Raman scattered photons. The Raman scattered photons are assessed to thereby generate a spectroscopic data set wherein said spectroscopic data set comprises at least one of: a Raman spectra and a spatially accurate wavelength resolved image. The spectroscopic data set is evaluated to determine at least one of: an attribute of a biological tissue sample and a drug delivery device. In one embodiment, the biological tissue comprises arterial tissue. In another embodiment, the drug delivery device is a drug-eluting stent. In another embodiment, Raman chemical imaging can be used to evaluate a sample and identify at least one of: the tissue, a drug, a drug delivery device, and a matrix associated with a drug delivery device.

Claims

1. A method comprising:

illuminating a biological tissue sample using wide-field illumination comprising a drug delivery device to generate interacted photons;

assessing the interacted photons to generate at least one spatially accurate wavelength resolved Raman chemical image; and

analyzing the spatially accurate wavelength resolved Raman chemical image to evaluate the drug delivery device, wherein analyzing further comprises comparing the image to at least one reference data set.

2. The method of claim 1 wherein comparing the spatially accurate wavelength resolved Raman image to at least one reference data set further comprises applying one or more chemometric techniques.

3. The method of claim 2 wherein the chemometric technique is selected from the group consisting of:

principle component analysis, minimum noise fraction, linear discriminate analysis, Mahalanobis distance, partial least squares discriminate analysis, Euclidean distance, partial least squares regression, support vector machines, maximum likelihood estimation, Bayesian classification, neutral networks, hidden markov models, and k-nearest neighbors, and combinations thereof.

4. The method of claim 1 wherein the drug delivery device further comprises at least one of:

a controlled release drug delivery device, an environmentally responsive drug delivery device, a biodegradable drug delivery device, a responsive drug delivery device, and combinations thereof.

5. The method of claim 1 wherein the drug delivery device further comprises a drug-eluting stent.

6. The method of claim 1 wherein the biological tissue sample further comprises arterial tissue sample.

7. The method of claim 1 wherein the biological tissue sample comprises arterial tissure and the drug delivery device comprises drug-eluting stent, further comprising detecting para-strut amorphous material in the arterial tissue.

8. The method of claim 7 farther comprising assessing the para-strut amorphous material to thereby identity at least one of:

fibrin, a protein, fluid, a cell, a cellular component, and combinations thereof.

9. The method of claim 1 wherein evaluating the drug delivery device further comprises distinguishing between a matrix of the drug delivery device and at least one drug associated with the drug delivery device.

10. The method of claim 1 wherein evaluating the drug delivery device further comprises distinguishing between a biological tissue in contact with the drug delivery device and a matrix of the drug delivery device.

11. The method of claim 1 wherein evaluating the drug delivery device further comprises assessing the biological tissue in contact with the drug delivery device.

12. The method of claim 11 wherein assessing the biological tissue further comprises determining the presence of a drug associated with the drug delivery device in the biological tissue.

13. The method of claim 11 wherein assessing the biological tissue further comprises determining a concentration of a drug associated with the drug delivery device in the biological tissue.

14. The method of claim 11 wherein assessing the biological tissue further comprises measuring the rate of diffusion of a drug associated with the drug delivery device into the biological tissue.

15. The method of claim 11 wherein assessing the biological tissue further comprises measuring a change in the molecular composition of the biological tissue in response to a drug associated with the drug delivery device.

16. The method of claim 1 wherein evaluating the drug delivery device further comprises measuring degradation of a matrix associated with the drug delivery device.

17. The method of claim 1 wherein evaluating the drug delivery device further comprises measuring the size of the drug delivery device.

18. The method of claim 1 further comprising:

generating a visible image representative of the biological tissue sample; and

assessing the visible image using at least one of;

histology, morphology, morphometry, and combinations thereof.