IP Library › Granted Patent US 12,411,043
Granted Patent B2
US 12,411,043 · App. 18/198,513 · Granted Sep 9, 2025

No-ref-signal slope spectroscopic measurement

Inventors: Matthew Muller (Cranford, NJ); Richard Hall, III (Bernardsville, NJ); Yusheng Zhang (Stewartsville, NJ); Peter Halatin (Howell, NJ)
Assignee: Repligen Corporation
G01J3/42G01J3/10G01N21/255G01N21/3103
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Quick Facts
Patent No.
US 12,411,043
App. No.
18/198,513
Granted
Sep 9, 2025
Kind
B2
Abstract

A method includes determining whether a variation in probe radiation intensity meets a stability criterion; directing the probe radiation through a probe, when the probe is disposed at a first position, defining a first path length L 1 of the probe radiation through the fluid sample; measuring a transmitted intensity I 1 of the probe radiation after passing through the fluid sample when the probe is disposed at the first position; directing the probe radiation through the probe when the probe is disposed at a second position, defining a second path length L 2 of the probe radiation through the fluid sample; measuring a transmitted intensity I 2 of the probe radiation after passing through the fluid sample when the probe is disposed at the second position; and determining a concentration C of a material in the fluid sample based upon L 1 , I 1 , L 2 , and I 2 , when the stability criterion is met.

Claims (66)

1. A method of determining a concentration of a material, comprising:

determining whether a variation in an intensity of a probe radiation emitted by a light source of an absorbance spectroscopy system meets a stability criterion;

directing the probe radiation through a probe when the probe is disposed at a first position, defining a first path length L 1 of the probe radiation through a fluid sample containing the material;

measuring a transmitted intensity I 1 of the probe radiation after passing through the fluid sample when the probe is disposed at the first position;

directing the probe radiation through the probe when the probe is disposed at a second position, defining a second path length L 2 of the probe radiation through the fluid sample;

measuring a transmitted intensity I 2 of the probe radiation after passing through the fluid sample when the probe is disposed at the second position; and

determining a concentration C of a material in the fluid sample based upon L 1 , I 1 , L 2 , and I 2 , when the stability criterion is met;

wherein the stability criterion comprises a state of the light source wherein the variation in the intensity is below a threshold value, the method further comprising, when the variation in the intensity is greater than the threshold value;

measuring an incident intensity I 01 of the probe radiation, before passing through the fluid sample when the probe is disposed at the first position;

measuring an incident intensity I 02 of the probe radiation, before passing through the fluid sample when the probe is disposed at the second position; and

determining the concentration C of material in the fluid sample, based upon L 1 , I 1 , L 2 , I 2 , I 01 and I 02 .

2. The method of claim 1 , wherein when the stability criterion is met the concentration C is determined as:

C=(ΔA/ΔL)/e, where e is molar absorptivity of the material, ΔL is an absolute value of a difference between L 1 and L 2 , and ΔA=log I 1 −log I 2 .

3. The method of claim 1 , wherein the variation in the intensity of the probe radiation is given by a, where a=(I max −I min )/I min , where I max is a maximum value of intensity of radiation recorded in a given period and I min is a minimum value of intensity recorded in the given period.

4. The method of claim 3 , wherein a duration of the given period is one second to 100 seconds.

5. The method of claim 1 , wherein an incident intensity of the probe radiation before passing through the fluid sample is not measured at the first position or at the second position when the stability criterion is met.

6. The method of claim 1 , wherein the transmitted intensity I 1 and the transmitted intensity I 2 are determined by a measurement instrument of the absorbance spectroscopy system, the measurement instrument comprising:

a sample vessel to contain the fluid sample, the sample vessel comprising a vessel wall, wherein the probe is movable along a probe direction with respect to the vessel wall, so as to change a path length of the probe signal through the fluid sample from the first path length L 1 to the second path length L 2 .

7. The method of claim 1 , wherein C=(ΔA/ΔZ)/e, where ΔL is given by |L 1 −L 2 | and ΔA is given by log I 1 −log I 2 +log (I 01 /I 02 ).

8. The method of claim 1 , wherein the probe is disposed at the first position during a first instance, and is disposed at the second position during a second instance, the method further comprising:

directing, for at least one additional instance, the probe radiation through the probe when the probe is disposed in at least one additional position, defining a at least one additional path length L n , respectively, for the probe radiation through the fluid sample;

measuring, at the at least one additional instance, a transmitted intensity I n of the probe radiation after passing through the fluid sample; and

performing a linear regression to determine a line slope m of a set of data plotting A 1 , A 2 , A n , . . . as a function of L 1 , L 2 , L n , where A is equal to log I.

9. A non-transitory computer-readable storage medium storing computer-readable program code executable by a processor to:

determine whether a variation in an intensity of a probe radiation emitted by a light source of an absorbance spectroscopy system meets a stability criterion;

cause the light source to direct the probe radiation through a probe when the probe is disposed at a first position, defining a first path length L 1 of the probe radiation through a fluid sample;

receive a transmitted intensity I 1 of the probe radiation after passing through the fluid sample;

cause the light source to direct the probe radiation through the probe when the probe is disposed at a second position, defining a second path length L 2 of the probe radiation through the fluid sample;

receive a transmitted intensity I 2 of the probe radiation after passing through the fluid sample; and

determine a concentration C of a material in the fluid sample based upon L 1 , I 1 , L 2 , and I 2 , when the variation in the intensity meets the stability criterion;

wherein when the variation in the intensity does not meet the stability criterion, the computer-readable program code is executable by a processor to:

receive, when the probe is disposed at the first position, an incident intensity I 01 of the probe radiation, before passing through the fluid sample;

receive, when the probe is disposed at the second position, an incident intensity I 02 of the probe radiation, before passing through the fluid sample; and

determine the concentration C of material in the fluid sample based upon L 1 , I 1 , L 2 , I 2 , I 01 and I 02 .

10. The non-transitory computer-readable storage medium of claim 9 , wherein the concentration Cis determined as: o

C=(ΔA/ΔL)/e, where e is molar absorptivity of the material, ΔL is an absolute value of a difference between L 1 and L 2 , and ΔA=log I 01 −log I 02 .

11. The non-transitory computer-readable storage medium of claim 9 , wherein the variation the intensity of the probe radiation is given by v, where v=(I max −I min )/I min , where I max is a maximum value of intensity of radiation recorded in a given period and I min is a minimum value of intensity recorded in the given period, wherein the stability criterion is met when v is below a threshold value.

12. The non-transitory computer-readable storage medium of claim 9 , the computer-readable program code executable by the processor to determine the concentration C without receiving measurement of an incident intensity I 01 of the probe radiation at the first position, before passing through the fluid sample, and without receiving measurement of an incident intensity I 02 of the probe radiation at the second position, before passing through the fluid sample, when the variation in the intensity meets the stability criterion.

13. The non-transitory computer-readable storage medium of claim 9 , the computer-readable program code executable by the processor to determine C by calculating a change in absorbance ΔA from the first instance to the second instance, wherein C=(ΔA/ΔL)/e, where ΔL is given by |L 1 −L 2 | and ΔA is given by log I 1 −log I 2 , +log (I 01 /I 02 ).

14. The non-transitory computer-readable storage medium of claim 9 , wherein the probe is disposed at the first position during a first instance, and is disposed at the second position during a second instance, the computer-readable program code executable by the processor to:

for at least one additional instance, cause the source to direct the probe radiation through the probe when probe is disposed in at least one additional position, defining at least one additional path length L n , respectively, for the probe radiation through the fluid sample;

measure, at the at least one additional instance, a transmitted intensity I n of the probe radiation after passing through the fluid sample; and

perform a linear regression to determine a line slope m of a set of data plotting A 1 , A 2 , A n , . . . as a function of L 1 , L 2 , L n , where A is equal to log I.

15. A measurement apparatus, comprising:

a light source, to generate a probe signal; and

a measurement instrument, to receive the probe signal, the measurement instrument comprising:

a sample vessel to contain a fluid sample, the sample vessel comprising a vessel wall;

a probe, arranged to direct the probe signal through the sample vessel, wherein the probe is movable along a probe direction with respect to the vessel wall, so as to change a path length/of the probe signal through the fluid sample;

a detector, disposed to receive the probe signal after passing through the vessel wall; and

a control system, arranged to:

determine whether a variation in an intensity of a probe radiation emitted by the light source meets a stability criterion; and

calculate a concentration C of a material in the fluid sample based upon a measured change in intensity of the probe signal as a function of a change in the path length L, when the variation in the intensity meets the stability criterion;

wherein the stability criterion comprises a state of the light source wherein the variation in the intensity is below a threshold value, when the variation in the intensity is greater than the threshold value, the control system is arranged to:

measure an incident intensity I 01 of the probe radiation, before passing through the fluid sample when the probe is disposed at the first position;

measure an incident intensity I 02 of the probe radiation, before passing through the fluid sample when the probe is disposed at the second position; and

determine the concentration C of material in the fluid sample, based upon L 1 , I 1 , L 2 , I 2 , I 01 and I 02 .

16. The measurement apparatus of claim 15 , the control system being arranged to:

receive, when the probe is disposed at a first position, a transmitted intensity 17 of the probe radiation after passing through the fluid sample;

receive, when the probe is disposed at a second position, a transmitted intensity I 2 of the probe radiation after passing through the fluid sample; and

to calculate C as (ΔA/ΔL)/e, where e is molar absorptivity of the material, ΔL is an absolute value of a difference between L 1 and L 2 , and ΔA=log I 01 −log I 02 and wherein L 1 is a first path length at the first position, and L 2 is a second path length at the second position.

17. The measurement apparatus of claim 16 , the control system being arranged to: determine the concentration C without receiving measurement of an incident intensity I 01 of the probe radiation at the first position, before passing through the fluid sample, and without receiving measurement of an incident intensity I 02 of the probe radiation at the second position, before passing through the fluid sample, when the variation in the intensity meets the stability criterion.

18. The measurement apparatus of claim 15 , the light source comprising a light emitting diode (LED) to generate radiation at a targeted wavelength, in a range of ultraviolet to infrared.

19. The method of claim 1 , wherein the concentration C of material in the fluid sample is determined based on a difference between log LI 01 and log LI 02 without regard to the absolute values of absorbance of L 1 and L 2 .

20. The non-transitory computer-readable storage medium of claim 9 ,

wherein the concentration C of material in the fluid sample is determined based on a difference between log LI 01 and log LI 02 without regard to the absolute values of absorbance of L 1 and L 2 .

21. The measurement apparatus of claim 15 , wherein the concentration C of material in the fluid sample is determined based on a difference between log LI 01 and log LI 02 without regard to the absolute values of absorbance of L 1 and L 2 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2024
From: MULLER, MATTHEW; HALL, RICHARD, III; ZHANG, YUSHENG; HALATIN, PETER
To: REPLIGEN CORPORATION
Reel/Frame 066702/0348 →
Continuity (2)
Provisional Application 63343357 · May 18, 2022
Related Publication 20230375407A1 · Nov 23, 2023
References Cited (30)
US 4634277A · Stockdale · 1987 [cited by applicant]
US 6704109B2 · Wu et al. · 2004 [cited by applicant]
US 6879741B2 · Salerno · 2005 [cited by applicant]
US 7759651B2 · Knight · 2010 [cited by applicant]
US 7808641B2 · Salerno · 2010 [cited by applicant]
US 7980745B2 · Shanbaky · 2011 [cited by applicant]
US 9404851B2 · Shih · 2016 [cited by applicant]
US 9952350B1 · DiFoggio · 2018 [cited by applicant]
US 10830778B2 · Salerno · 2020 [cited by applicant]
US 11300447B2 · Shih · 2022 [cited by applicant]
US 20150098082A1 · Wang · 2015 [cited by applicant]
US 20150244145A1 · Taubman et al. · 2015 [cited by applicant]
US 20150268095A1 · Kovacich · 2015 [cited by applicant]
US 20170356848A1 · Ehring · 2017 [cited by applicant]
US 20190212258A1 · Harrison · 2019 [cited by applicant]
US 20200003940A1 · Smith et al. · 2020 [cited by applicant]
US 20210096128A1 · Peyser · 2021 [cited by applicant]
US 20220026160A1 · Perreault · 2022 [cited by applicant]
US 20220042969A1 · Harrison · 2022 [cited by applicant]
US 20220268628A1 · Gantier · 2022 [cited by applicant]
US 20220397581A1 · Ando · 2022 [cited by examiner]
US 20230002801A1 · Dutta · 2023 [cited by applicant]
US 20230111094A1 · Matsui · 2023 [cited by examiner]
AU 2011214172A1 · 2012 [cited by applicant]
AU 2013205020A1 · 2013 [cited by applicant]
International Search Report and Written Opinion for the International Application No. PCT/US2023/022571, mailed Aug. 3, 2023, 13 pages. [cited by applicant]
The International Preliminary Report on Patentability mailed Nov. 28, 2024, for corresponding PCT/ US2023/022571 (seven (7) pages. [cited by applicant]
International Search Report and Written Opinion for the International Application No. PCT/US2023/022572, mailed Aug. 3, 2023, 12 pages. [cited by applicant]
International Search Report and Written Opinion for the International Application No. PCT/US2023/022577, mailed Aug. 8, 2023, 14 pages. [cited by applicant]
Marcus et al., “Optical path length and absorption cross section optimization for high sensitivity ozone concentration measurement,” Sensors and Actuators B: Chemical, vol. 221, 2015, pp. 570-575. [cited by applicant]
Cited By (1)
US 12,723,971