Offline and inline determination of concentration of metabolites in cell culture fluid
US-2023002801-A1 · Jan 5, 2023 · US
US12422356B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-12422356-B2 |
| Application number | US-202318198701-A |
| Country | US |
| Kind code | B2 |
| Filing date | May 17, 2023 |
| Priority date | May 18, 2022 |
| Publication date | Sep 23, 2025 |
| Grant date | Sep 23, 2025 |
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A system may include a light source, to generate a probe signal, comprising incident radiation; an optical probe, to direct the incident radiation through a fluid sample; a motor, to move the optical probe along a probe axis, to change a path length of the incident radiation through the fluid sample; and a detector, to receive the incident radiation as attenuated radiation after passing through the fluid sample. The system may include a control system, arranged to: initiate an absorbance measurement by directing movement of the optical probe along the probe axis; direct the light source to emit the incident radiation; and automatically adjust at least one measurement parameter of a set of measurement parameters for the sample measurement, based upon a slope parameter m, wherein m is derived from a rate of change in an intensity of the attenuated radiation with a change in the path length.
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The invention claimed is: 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
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