Granted Patent B2

US 12,422,356 · App. 18/198,701 · Granted Sep 23, 2025

Inventors: Matthew Muller (Cranford, NJ); Richard Hall, III (Bernardsville, NJ); Yusheng Zhang (Stewartsville, NJ); Peter Halatin (Howell, NJ)

Assignee: Repligen Corporation

G01N21/33G01N2201/062

Abstract

Claims (60)

1. An absorbance measurement system, comprising:

a light source, to generate a probe signal, comprising incident radiation;

an optical probe, arranged to direct the incident radiation through a fluid sample;

a motor, arranged to move the optical probe along a probe axis, to change a path length of the incident radiation through the fluid sample;

a detector, disposed to receive the incident radiation as attenuated radiation after passing through the fluid sample; and

a control system, arranged to:

initiate an absorbance measurement of the fluid sample by directing movement of the optical probe along the probe axis; and

direct the light source to emit the incident radiation; and

wherein the light source comprises a light emitting diode (LED), configured to receive a triggering signal from the control system and to generate the incident radiation at a characteristic wavelength upon receipt of the triggering signal,

wherein the detector is configured to detect an intensity of the attenuated radiation over a wavelength range spanning the characteristic wavelength, and over a detection interval of no more than 10 microseconds; and

wherein the control system is arranged to direct the motor to move the optical probe in a pair of opposite directions along the probe axis, wherein intensity of the attenuated radiation is recorded while the motor moves the probe along a first direction of the pair of opposite directions and while the motor moves the probe along a second direction of the pair of opposite directions.

2. The absorbance measurement system of claim 1 , wherein the control system is arranged to synchronize the triggering signal, for generation of the incident radiation by the LED, and a receipt of the intensity of the attenuated radiation to less than 10 microseconds.

3. The absorbance measurement system of claim 1 , wherein the control system is arranged to:

receive, at a plurality of instances during a measurement interval, a set of probe position information during continuous movement of the optical probe;

determine the change in the path length, over the measurement interval, based upon the set of probe position information;

receive, at the plurality of instances, a set of intensity information for the attenuated radiation; and

automatically change the at least one measurement parameter, for a subsequent measurement interval of the absorbance measurement, based upon a value of a slope parameter m, determined from the change in the path length over the measurement interval, and a change in the intensity of the attenuated radiation over the measurement interval.

4. The absorbance measurement system of claim 3 , wherein the at least one measurement parameter comprises a maximum path length of optical probe, a motion profile of the optical probe, and a data collection rate of the set of probe position information and the set of intensity information.

5. The absorbance measurement system of claim 1 , wherein the control system to determine a concentration C of a material in the fluid sample, where C=m/e, wherein e is a molar absorptivity of the material.

6. A method of determining a concentration of a material in a fluid sample, comprising:

initiating a sample measurement of the fluid sample to determine the concentration, by sending a signal to move an optical probe through a sample vessel containing the fluid sample;

triggering, at a plurality of instances during a measurement interval, a light source to emit an incident radiation through the optical probe and the fluid sample, wherein a path length L of the incident radiation through the fluid sample is varied; and

receiving, at the plurality of instances during the measurement interval, a measurement of an intensity/of attenuated radiation, derived from the incident radiation after passing through the fluid sample;

wherein the light source comprises a light emitting diode (LED), configured to receive a triggering signal from the control system and to generate the incident radiation at a characteristic wavelength upon receipt of the triggering signal,

wherein the detector is configured to detect an intensity of the attenuated radiation over a wavelength range spanning the characteristic wavelength, and over a detection interval of no more than 10 microseconds; and

wherein the control system is arranged to direct the motor to move the optical probe in a pair of opposite directions along the probe axis, wherein intensity of the attenuated radiation is recorded while the motor moves the probe along a first direction of the pair of opposite directions and while the motor moves the probe along a second direction of the pair of opposite directions.

7. The method of claim 6 , wherein m=DA/DL, wherein DA=log I 1 −log I 2 , where I 1 represents the intensity I at a first instance, I 2 represents the intensity I and a second instance, and DL represents a change in the path length L between the first instance and the second instance.

8. The method of claim 6 , further comprising:

receiving a set of probe position information corresponding to a first probe position at a first instance and a second probe position at a second instance;

determining a first path length L 1 of the incident radiation from the first probe position; and

determining a second path length L 2 of the incident radiation from the second probe position, wherein DL=L 2 −L 1 .

9. The method of claim 6 , wherein the automatically adjusting comprises:

adjusting a maximum path length of the optical probe, a motion profile of the optical probe, a data collection rate of the intensity I, or combination thereof, to form a revised set of measurement parameters.

10. The method of claim 6 , wherein the light source comprises a light emitting diode (LED), the method further comprising synchronizing the triggering the light source and the receiving the measurement to less than 10 microseconds.

11. The method of claim 6 , the sending the signal to move the optical probe comprising directing a motor to move the optical probe along a probe axis.

12. The method of claim 11 , comprising signaling the motor to move the optical probe in pair of opposite directions along the probe axis, wherein the receiving the measurement of the intensity comprises:

receiving a first set of detected intensity measurements while the optical probe is moved along a first direction of the pair of opposite directions, and

receiving a second set of detected intensity measurements while the probe is moved along a second direction of the pair of opposite directions.

13. The method of claim 6 , wherein the automatically adjusting comprises:

determining whether a slope parameter m is acceptable according to a predetermined criterion;

adjusting the at least one measurement parameter when m is not acceptable; and

and continuing the sample measurement for a second measurement interval using the set of measurement parameters, without adjustment, when m is acceptable.

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

initiate a sample measurement to determine a concentration of a substance in a fluid sample, by sending a signal to move an optical probe through a sample vessel containing the fluid sample;

trigger, at a plurality of instances during a measurement interval, a light source to emit an incident radiation through the optical probe and the fluid sample, wherein a path length L of the incident radiation through the fluid sample is varied; and

receive, at the plurality of instances during the measurement interval, a measurement of an intensity/of attenuated radiation, derived from the incident radiation after passing through the fluid sample; and

wherein the light source comprises a light emitting diode (LED), configured to receive a triggering signal from the control system and to generate the incident radiation at a characteristic wavelength upon receipt of the triggering signal,

wherein the detector is configured to detect an intensity of the attenuated radiation over a wavelength range spanning the characteristic wavelength, and over a detection interval of no more than 10 microseconds; and

wherein the control system is arranged to direct the motor to move the optical probe in a pair of opposite directions along the probe axis, wherein intensity of the attenuated radiation is recorded while the motor moves the probe along a first direction of the pair of opposite directions and while the motor moves the probe along a second direction of the pair of opposite directions.

15. The non-transitory computer-readable storage medium of claim 14 , wherein m=DA/DL, wherein DA=log I 1 −log I 2 , where/represents the intensity I at a first instance, I 2 represents the intensity I and a second instance, and DL represents a change in the path length L between the first instance and the second instance.

16. The non-transitory computer-readable storage medium of claim 14 , the computer-readable program code executable by the processor to:

receive a set of probe position information corresponding to a first probe position at a first instance and a second probe position at a second instance;

determine a first path length L 1 of the incident radiation from the first probe position; and

determine a second path length L 2 of the incident radiation from the second probe position, wherein DL=L 2 −L 1 .

17. The non-transitory computer-readable storage medium of claim 14 , the computer-readable program code executable by the processor to:

adjust a maximum path length of the optical probe, a motion profile of the optical probe, a data collection rate of the intensity I, or combination thereof, to form a revised set of measurement parameters.

18. The non-transitory computer-readable storage medium of claim 14 , the computer-readable program code executable by the processor to:

determine whether a slope parameter m is acceptable according to a predetermined criterion;

adjust the at least one measurement parameter when m is not acceptable; and

and continue the sample measurement for a second measurement interval using the set of measurement parameters, without adjustment, when m is acceptable.

Assignments (1)

Continuity (2)

References Cited (28)

Cited By (1)

US 12,723,971