Apparatus and Method for Automated Process Monitoring and Control with Near Infrared Spectroscopy

• US 20150247794A1
• Filed: 02/26/2015
• Published: 09/03/2015
• Est. Priority Date: 02/28/2014
• Status: Active Grant

• Current Assignee: Nirrin Technologies, Inc.
• Original Assignee: Asl Analytical, Inc.
• Inventors: Olesberg, Jonathon Todd, Arnold, Mark Allen, Koerperick, Edwin John, Evans, Christine Esther, Small, Gary Wray
• Granted Patent: US 9,540,701 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: C12Q 3/00 Condition responsive control processes apparatus therefor C12M1/36; controlling or regulating in general G05
• CPC Class Codes: G01N 2021/399 Diode laser
• CPC Class Codes: G01N 21/314 with comparison of measurements at specific and non-specific wavelengths dual wavelength spectrometry G01J3/427
• CPC Class Codes: G01N 21/3577 for analysing liquids, e.g. polluted water
• CPC Class Codes: G01N 21/359 using near infrared light
• CPC Class Codes: G01N 21/39 using tunable lasers
• CPC Class Codes: G01N 21/51 inside a container, e.g. in an ampoule G01N21/53 takes precedence
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 2201/067 Electro-optic, magneto-optic, acousto-optic elements
• CPC Class Codes: G01N 2201/0846 Fibre interface with sample, e.g. for spatial resolution

Abstract

A system and method for continuous, real-time process monitoring and control by means of near-infrared (NIR) spectroscopy provides analysis of static or flowing fluid streams which may range from clear to highly optically dense, including fluids primarily of aqueous composition. A NIR source passes through a wavelength selector to select one or more spectral segments, which are passed through the fluid stream at a fluid sampling interface and received at a sensor. A wavelength reference material is positioned in the optical path for calibration. Quantification of a plurality of characteristics or parameters of a fluid and suspended solids or cells contained therein may be performed. An all-solid-state implementation of the optical system ensures high robustness in laboratory and industrial settings.

Claims

1. An apparatus for fluid analysis, said apparatus comprising:

a. a near infrared electromagnetic radiation source;

b. an optical wavelength selector positioned in an optical path from the near infrared electromagnetic radiation source, and configured to select one or more spectral segments of the near infrared electromagnetic radiation;

c. a wavelength reference material positioned in the optical path and comprising at least one polymer optical element, said polymer optical element being at least partially transparent in at least a portion of a near infrared spectral range and exhibiting an absorption spectrum that differs in magnitude between at least two wavelengths;

d. a fluid sampling interface positioned in the optical path;

e. a sensor positioned at a termination of the optical path; and

f. a controller configured to determine the quantity of one or more substances in a fluid sample based upon the measured spectrum of near infrared electromagnetic radiation of said fluid sample at the fluid sampling interface, wherein the controller comprises a sensor input connected to the sensor to receive a sensor signal from the sensor,

wherein the controller is configured to adjust a wavelength axis of a measurement based upon a comparison utilizing the wavelength reference material for the entire spectrum collected over a wavelength range of interest.

2. The apparatus of claim 1, wherein the wavelength axis is adjusted by the controller by applying a regression fit over the entire wavelength range of interest whereby both shift and scale operations are performed.

3. The apparatus of claim 1, further comprising a second sensor positioned in a second optical path from the near infrared electromagnetic radiation source, and wherein the controller further comprises a second sensor input connected to the second sensor to receive a second sensor signal from the second sensor.

4. The apparatus of claim 1, wherein said near infrared electromagnetic radiation source is selected from the group consisting of a tungsten-halogen bulb assembly, a near-infrared light emitting diode, a near-infrared superluminescent diode, and a near-infrared tunable laser.

5. The apparatus of claim 1, wherein said optical wavelength selector is an Acousto Optic Tunable Filter (AOTF) tuned for near-infrared operation.

6. The apparatus of claim 1, wherein said optical wavelength selector is selected from the group consisting of a planar reflection diffraction grating, a non-planar reflection diffraction grating, and a transmission diffraction grating.

7. The apparatus of claim 1, wherein said wavelength reference material comprises a polymer selected from the group consisting of polycarbonate, Kapton®

, polymethylpentene, polyether ether ketone (PEEK), and nylon.

8. The apparatus of claim 7, wherein said wavelength reference material consists essentially of a single polymer.

9. The apparatus of claim 1, wherein said fluid sampling interface comprises a cartridge, said cartridge comprising a housing, a fluid flow cell attached to the housing and positioned in the optical path, and a receiver assembly comprising at least two optical elements.

10. The apparatus of claim 9, wherein said fluid sampling interface further comprising surfaces to compress said fluid flow cell to form a defined optical path length through the fluid flow cell along the optical path.

11. The apparatus of claim 1, wherein said fluid sampling interface comprises a fiber optically coupled interface and one or more optical fibers optically connecting the optical interface to the near infrared electromagnetic radiation source and the sensor.

12. The apparatus of claim 1, wherein said fluid sampling interface comprises two or more fiber optically coupled interfaces, one or more optical fibers each connected to one of the two or more optical interfaces, and a fiber optic switch connected to each of the one or more optical fibers to selectively connect one of the two or more fiber optically coupled interfaces with the near infrared electromagnetic radiation source or the sensor.

13. The apparatus of claim 1, wherein the controller is connected to a fluid process controller to control a parameter of a fluid process based upon input to the controller from the sensor.

14. The apparatus of claim 13, wherein said parameter of a fluid process is selected from the group consisting of agitation rate, dissolved oxygen, pH, temperature, and foaming within a vessel.

15. The apparatus of claim 1, wherein the controller is connected to a pump and is configured to compare a measured quantity to a target quantity and generate a pump control output to the pump to minimize a difference between said measured quantity and said target quantity by pumping a controlled quantity of a substance into a vessel connected to the pump.

16. The apparatus of claim 1, wherein said controller is further configured to measure one or more quantities and supply at least one external output based upon said quantities to an external instrument.

17. The apparatus of claim 1, further comprising a second fluid interface positioned in a second optical path.

18. The apparatus of claim 1, wherein said sensor comprises a plurality of light sensing elements.

19. A method of determining the quantity of one or more substances in a fluid sample, said method comprising the steps of:

a. generating a beam of near-infrared electromagnetic radiation;

b. transmitting at least a portion of said near-infrared electromagnetic radiation through a polymer optical element for wavelength reference, said polymer optical element being at least partially transparent in at least a portion of the near-infrared spectral range, said polymer further comprising an absorption characteristic that differs in magnitude between at least two wavelengths, and adjusting a wavelength axis of a measurement based upon a fit of a transmission spectrum of the wavelength reference material over an entire wavelength range of interest;

c. irradiating a fluid sample within a sampling interface with said near-infrared electromagnetic radiation;

d. sensing near-infrared electromagnetic radiation having interacted with said fluid sample with a sensor; and

e. determining a quantity of a substance within said fluid sample.

20. The method of claim 19, wherein said electromagnetic radiation is transmitted through said fluid sample and the measured intensity as a function of wavelength forms a transmission optical spectrum.

21. The method of claim 19, wherein said near-infrared electromagnetic radiation transmitted through said fluid sample comprises wavenumbers between 3300 cm⁻

1 and 5600 cm<sup>−

1</sup>.

22. The method of claim 19, further comprising the step of sensing a portion of said near infrared electromagnetic radiation not having interacted with said fluid sample with a second sensor as a reference.

23. The method of claim 19, further comprising the steps of detecting air bubbles entrapped in the fluid sample and rejecting measurements contaminated by said air bubbles.

24. The method of claim 19, wherein said beam of near-infrared electromagnetic radiation is generated by a broadband optical emitter.

25. The method of claim 19, wherein said beam of near-infrared electromagnetic radiation is generated by a tunable optical emitter.

26. The method of claim 25, wherein said beam of near-infrared electromagnetic radiation is generated by a near-infrared tunable laser diode (TLD).

27. The method of claim 19, further comprising the step of directing said beam of broadband optical radiation into a wavelength selector.

28. The method of claim 27, wherein said wavelength selector is selected from the group consisting of an Acousto Optic Tunable Filter (AOTF), a planar reflection diffraction grating, a non-planar reflection diffraction grating, and a transmission diffraction grating.

29. The method of claim 19, wherein said fluid sample is not homogeneous.

30. The method of claim 19, wherein said fluid sample is aqueous.

31. The method of claim 19, wherein a transmission distance through the fluid sample is between 0.2 mm and 5 mm.

32. The method of claim 19, wherein the substance within the fluid and for which a quantity is detected is selected from the group consisting of alcohols, sugars, lipids, organic acids, amino acids, fatty acids, and proteins.

33. The method of claim 19, wherein the quantity measured is one or more of cell density, cell viability, or turbidity.

34. The method of claim 19, wherein the quantity of the substance is measured continuously to monitor a fluid process.

35. The method of claim 19, wherein the wavelength axis of a measurement is adjusted multiple times during a fluid process.

36. The method of claim 19, wherein said quantity of the substance is measured in real-time to monitor a fluid process.

37. The method of claim 19, wherein a frequency at which the quantity of the substance is measured is greater than 1 per minute.

38. The method of claim 19, wherein said fluid sample is circulated from the process through a fluid conduit.

39. The method of claim 19, wherein the step of determining a quantity of a substance in the fluid sample is performed by means of one or more optical fibers.

40. The method of claim 19, wherein said polymer optical element for wavelength reference is intermittently positioned at least partially within a path of said electromagnetic radiation.

41. The method of claim 19, wherein said fluid sample is from a continuous process.

42. The method of claim 19, further comprising an additional analysis selected from the list consisting of electrochemical, fluorescence, UV-Vis absorption, and Raman analysis.

43. A method of controlling a fluid process, said method comprising the steps of:

a. generating a beam of near infrared electromagnetic radiation;

b. transmitting at least a portion of said near infrared electromagnetic radiation through a polymer element for wavelength reference, said polymer optical element being at least partially transparent in at least a portion of the near infrared spectral range, said polymer further comprising an absorption characteristic that differs in magnitude between at least two wavelengths, and adjusting a wavelength axis of a measurement based upon a fit of a transmission spectrum of the wavelength reference material over an entire wavelength range of interest;

c. irradiating a fluid sample within a sampling interface with near-infrared electromagnetic radiation;

d. sensing near-infrared electromagnetic radiation having interacted with said fluid sample with a sensor;

e. determining based on an output from the sensor and the optical wavelength selector one or more quantities of components of or materials suspended within said fluid sample; and

f. using said determined one or more quantities to adjust one or more parameters or quantities of a substance in said fluid process.

44. The method of claim 43, further comprising the step of controlling the quantity of at least one substance in the fluid process.

45. The method of claim 43, further comprising the step of controlling one or more parameters in the fluid process.

46. The method of claim 43, wherein said one or more parameters are selected from the group consisting of agitation rate, dissolved oxygen, pH, and foaming within the vessel.

47. The method of claim 43, wherein said controlling step controls a target concentration or concentration profile based upon at least one quantity determined based on the output from the sensor.

48. The method of claim 43, wherein said controlling step controls a target concentration or concentration profile based upon at least one substance consumption rate determined based on the output from the sensor.

49. The method of claim 43, wherein said controlling step controls a target concentration or concentration profile based upon at least one cell growth rate determined based on the output from the sensor.

50. The method of claim 43, further comprising process adjustments based on one or more additional analyses selected from the list consisting of electrochemical, fluorescence, UV-Vis absorption, and Raman analysis.