Optical Coherence Tomography (OCT) Freeze Drying Microscopy

• US 20120294328A1
• Filed: 04/24/2012
• Published: 11/22/2012
• Est. Priority Date: 05/17/2011
• Status: Active Grant

• Current Assignee: Physical Sciences Incorporated
• Original Assignee: Physical Sciences Incorporated
• Inventors: Mujat, Mircea, Kessler, William J.
• Granted Patent: US 8,911,144 B2
• Time in Patent Office: Days
• US Class Current: 374/17
• CPC Class Codes: G01B 11/24 for measuring contours or curvatures
• CPC Class Codes: G01B 9/02091 Tomographic interferometers, e.g. based on optical coherence
• CPC Class Codes: G01N 21/4795 spatially resolved investigating of object in scattering medium in vivo A61B
• CPC Class Codes: G01N 25/12 of critical point; of other phase change

Abstract

A product critical temperature during freeze drying is determined. The product is imaged using optical coherence tomography (“OCT”). The product is freeze dried while the temperature of the product is measured. The product critical temperature is the temperature at which a product structure event occurs during freeze drying.

Claims

1. A method of determining a product critical temperature during freeze drying, the method comprising:

imaging a product using optical coherence tomography (OCT);

freeze drying the product;

measuring temperature of the product during freeze drying; and

determining the product critical temperature by determining the temperature at which a product structure event occurs during freeze drying.

2. The method of claim 1 wherein the product structure event during drying is a loss of product structure if the product is amorphous and the product critical temperature is a product collapse temperature.

3. The method of claim 1 wherein the product structure event is a loss of product structure if the product is crystalline and the product critical temperature is a product eutectic temperature.

4. The method of claim 1 further comprising freeze drying the product in a standard product vial.

5. The method of claim 1 further comprising freeze drying the product in a thin film within a vial or between glass or plastic slides.

6. The method of claim 1 further comprising freeze drying the product in a vial having a diameter of about 5 mm to about 50 mm.

7. The method of claim 1 further comprising using a thermocouple to measure the product temperature.

8. The method of claim 1 further comprising using a resistance temperature detector to measure the product temperature.

9. The method of claim 1 further comprising using infrared thermometry to measure the product temperature.

15. The method of claim 8 wherein the three-dimensional structural information includes information about one or more elements forming the product solidifying and forming the product structure, while at least one or more elements forming the product remains liquid.

10. A method of providing three-dimensional structural information about a sample during freeze drying, the method comprising:

freeze drying the sample;

acquiring a three-dimensional image of the sample; and

determining the three-dimensional structural information about the sample from the three-dimensional image.

11. The method of claim 10 further comprising acquiring the three-dimensional image of the sample using optical coherence tomography (OCT).

12. The method of claim 10 wherein the three-dimensional structural information includes information about ice nucleation during freeze drying.

13. The method of claim 10 wherein the three-dimensional structural information includes information about sublimation of solvent from the sample during freeze drying.

14. The method of claim 10 wherein the three-dimensional structural information includes information about a loss of sample structure formed during a freezing phase of freeze drying.

16. The method of claim 10 further comprising acquiring images of the sample at multiple depths.

17. A system for determining a product critical temperature during freeze drying, the system comprising:

a freeze dryer including a holder for a product;

a temperature sensor coupled to the product;

a three-dimensional imager including a source of radiation and a detector positioned proximate to the holder; and

a processor coupled to the detector of the three-dimensional imager, the processor configured to receive images from the three dimensional imager, receive information about product temperature from the temperature sensor during freeze drying, and determine the product critical temperature by determining a temperature at which a product structure event occurs during freeze drying.

18. The system of claim 17 wherein the three-dimensional imager comprises an optical coherence tomography (OCT) system.

19. The system of claim 17 wherein the temperature sensor comprises one or more thermocouples configured to contact the product.

20. The system of claim 17 wherein the temperature sensor comprises one or more resistance temperature detectors configured to monitor product temperature.

21. The system of claim 17 wherein the temperature sensor comprises an infrared detector configured to monitor product temperature.

22. The system of claim 17 wherein the holder is configured to hold one or more vials capable of containing the product.

23. A system for measuring three-dimensional structural information of a sample during freeze drying, the system comprising:

a freeze dryer including a holder for the product;

a three-dimensional imager including a source of radiation and a detector positioned proximate to the holder; and

a processor coupled to the detector of the three-dimensional imager, the processor configured to receive images from the three dimensional imager and determine the three-dimensional structural information about the sample from the images.