Particle size determination using Raman spectroscopy

1. A method for determining the size of particles dispersed in a light-transmissive medium, comprising:

directing an excitation light into the medium, wherein the excitation light is monochromatic;

collecting from the medium a first Raman spectrum using a Raman spectrometer;

analyzing the first Raman spectrum to determine a composition of the medium;

computing a first ratio of red light in the first Raman spectrum to blue light in the first Raman spectrum;

waiting a pre-determined period of time;

after the pre-determined period, directing the excitation light into the medium and collecting from the medium a second Raman spectrum using the Raman spectrometer;

computing a second ratio of red light in the second Raman spectrum to blue light in the second Raman spectrum;

comparing the second ratio to the first ratio; and

determining the size and a count of particles dispersed in the medium based on the comparison of the second ratio to the first ratio.

2. The method of claim 1 , wherein the excitation light is a laser operating at 532 nanometers (nm), 785 nm, or 933 nm.

3. The method of claim 1 , wherein the red light in the first Raman spectrum and the red light in the second Raman spectrum have a first wavenumber range, and wherein the blue light in the first Raman spectrum and the blue light in the second Raman spectrum have a second wavenumber range,

wherein the first wavelength range has greater wavenumbers than the second wavenumber range,

wherein the first wavenumber range and the second wavenumber range are selected based on an intensity of light within each respective wavenumber range in the first Raman spectrum and on the distance of the first wavenumber range from the second wavenumber range in the first Raman spectrum.

4. The method of claim 1 , wherein the second ratio being greater than the first ratio indicates more particles sized approximately from 40 nm to 900 nm were dispersed in the medium when the second Raman spectrum was collected.

5. The method of claim 1 , wherein the second ratio being less than the first ratio indicates fewer particles sized approximately from 40 nm to 900 nm were dispersed in the medium when the second Raman spectrum was collected.

6. A method for controlling a crystal nucleation process within a light-transmissive medium, comprising:

directing an excitation light into the medium, wherein the excitation light is monochromatic;

collecting from the medium a first Raman spectrum using a Raman spectrometer;

analyzing the first Raman spectrum to determine a composition of the medium;

computing a first ratio of red light in the first Raman spectrum to blue light in the first Raman spectrum;

waiting a pre-determined period of time;

after the pre-determined period, directing the excitation light into the medium;

collecting from the medium a second Raman spectrum using the Raman spectrometer;

computing a second ratio of red light in the second Raman spectrum to blue light in the second Raman spectrum;

comparing the second ratio to the first ratio;

determining the size and a count of particles dispersed in the medium based on the comparison of the second ratio to the first ratio; and

repeating the waiting, the directing, the collecting, the computing, the comparing, and the determination of particle size and count until a pre-determined crystal nucleation state is reached.

7. The method of claim 6 , wherein the excitation light is a laser operating at 532 nm, 785 nm, or 933 nm.

8. The method of claim 6 , wherein the red light in the first Raman spectrum and the red light in the second Raman spectrum have a first wavenumber range, and wherein the blue light in the first Raman spectrum and the blue light in the second Raman spectrum have a second wavenumber range,

wherein the first wavelength range has greater wavenumbers than the second wavenumber range,

wherein the first wavenumber range and the second wavenumber range are selected based on an intensity of light within each respective wavenumber range in the first Raman spectrum and on the distance of the first wavenumber range from the second wavenumber range in the first Raman spectrum.

9. The method of claim 6 , wherein the second ratio being greater than the first ratio indicates more particles sized approximately from 40 nm to 900 nm were dispersed in the medium when the second Raman spectrum was collected.

10. The method of claim 6 , wherein the second ratio being less than the first ratio indicates fewer particles sized approximately from 40 nm to 900 nm were dispersed in the medium when the second Raman spectrum was collected.

11. The method of claim 6 , further comprising analyzing the second Raman spectrum to determine crystal polymorph species dispersed in the medium.

12. The method of claim 6 , further comprising:

after the computing of the first ratio, changing a parameter of the nucleation process.

13. A system for determining particle size in a light-transmissive medium, comprising:

at least one probe embodied to direct laser light into a sample including particles dispersed in a light-transmissive medium and to collect Raman emission spectra from the sample, wherein the Raman emission spectra illuminate the dispersed particles;

a detector configured to receive the collected Raman emission spectra from the sample; and

a processor configured to analyze the collected Raman emission spectra to determine the size of particles resulting from the illumination of the particles by the Raman emission spectra,

wherein the processor is further configured to determine particle size by:

analyzing the first Raman spectrum to determine a composition of the medium;

computing a first ratio of red light in the first Raman spectrum to blue light in the first Raman spectrum;

computing a second ratio of red light in the second Raman spectrum to blue light in the second Raman spectrum;

comparing the second ratio to the first ratio; and

determining the size and a count of particles dispersed in the medium based on the comparison of the second ratio to the first ratio.

14. The system of claim 13 , wherein the determination of particle size is based on Tyndall scattering.

15. The system of claim 13 , wherein the determination of particle size is indicative of nucleation.

16. The system of claim 13 , wherein the probe includes an extended path length to enhance sensitivity.

17. The system of claim 13 , wherein the processor is configured to control the probe and the detector.

18. The system of claim 13 , wherein the processor is configured to control a nucleation process by:

analyzing the first Raman spectrum to determine a composition of the medium;

computing a first ratio of red light in the first Raman spectrum to blue light in the first Raman spectrum;

computing a second ratio of red light in the second Raman spectrum to blue light in the second Raman spectrum;

comparing the second ratio to the first ratio;

determining the size and a count of particles dispersed in the medium based on the comparison of the second ratio to the first ratio; and

repeating the computing a second ratio, the comparing, and the determining until a predetermined crystal nucleation state is reached.

19. The system of claim 13 , further comprising a vessel embodied to hold the light-transmissive medium, wherein the vessel is configured with at least one process connection to enable a connection of the at least one probe.

20. The system of claim 13 , further comprising a second probe embodied to direct laser light into the sample and to collect a second Raman emission spectrum from the sample, wherein the second Raman emission spectrum illuminates the dispersed particles, wherein the at least one probe is used to determine particle size, and wherein the second probe is used to identify crystal polymorph species dispersed in the medium.