Flow cell device and bioreactor product monitoring system and method
A flowcell device, including a flow pathway and an optical subassembly, has a flowcell body that is continuous with a sample being analyzed and a temperature controlled surface. The flowcell body can be disposed between a thermalplate, actively regulated by a thermoelectric cooler, and an insulating member. The flowcell device can be employed in a bioreactor monitoring system.
1 . A method of optical interrogation, the method comprising:
regulating a temperature of a flowcell device;
flowing a sample to the flowcell device;
obtaining sequential scans that converge to a stable scan as a temperature of the sample in the flowcell device equilibrates with the flowcell temperature; and
saving the stable scan,
wherein,
the flowcell device comprises:
a flowcell body defining a flow pathway that includes a central cell, wherein the flow cell body is thermally continuous with a temperature-controlled surface; and
an optical subassembly, comprising the central cell and adjacent first and second optical windows.
2 . The method of claim 1 , further comprising occluding the sample flow to the flowcell device so that the sample is at rest in the in the flow cell.
3 . The method of claim 2 , further comprising resuming flow of a sample through the flowcell device.
4 . The method of claim 1 , wherein a standard deviation between the stable scan and the scan immediately preceding it is no greater than a threshold value.
5 . The method of claim 1 , wherein the scans are near infrared absorption spectra of at least one analyte in the sample.
6 . The method of claim 1 , wherein the sample temperature is controlled within a range of from about 15 to about 40 degrees centigrade.
7 . The method of claim 1 , wherein the sample temperature is brought to room temperature.
8 . A method for non-destructive, real-time monitoring of a bioreactor process, comprising:
continuously extracting fluid samples from a bioreactor and directing them to a flowcell;
actively regulating the flowcell temperature to maintain the fluid sample at a desired setpoint;
interrogating the fluid sample with near-infrared (NIR) spectroscopy to obtain sequential spectral measurements;
comparing the spectral measurements to detect changes; and
recording a final spectrum when a deviation of sequential measurements falls below a predefined threshold.
9 . The method of claim 8 , wherein the flowcell temperature is actively regulated using a thermoelectric cooler (TEC) thermally bonded to a thermal plate, the passive side of the TEC being in thermal contact with a heatsink to maintain efficient heat exchange.
10 . The method of claim 8 , wherein the predefined threshold for the deviation of sequential measurements is a standard deviation of less than 0.0005 in the recorded spectra.
11 . The method of claim 8 , wherein the NIR spectroscopy interrogates the fluid sample over a wavelength range from 780 nanometers to 2500 nanometers.
12 . The method of claim 8 , further comprising returning the analyzed fluid sample to the bioreactor after the final spectrum has been recorded.
13 . The method of claim 8 , wherein the sequential spectral measurements are taken at predetermined time intervals, each interval being at least 10 seconds to allow temperature equilibration of the fluid sample.
14 . The method of claim 8 , further comprising detecting and quantifying specific analytes within the fluid sample, including glucose and lactic acid, using differential absorbance at selected wavelengths.
15 . A method for optimizing spectral accuracy during optical analysis of fluid samples, comprising:
introducing a fluid sample into a flowcell featuring a thermally conductive body and optical windows;
equilibrating the temperature of the fluid sample to a predetermined setpoint using active thermal regulation;
transmitting light through the fluid sample in the flowcell's central cell using a tunable laser;
measuring the transmitted light using a photosensor;
repeating measurements over time and discarding spectra where temperature fluctuations are above a predefined threshold;
outputting a stabilized spectrum for processing.
16 . The method of claim 15 , wherein the tunable laser is configured to operate over a wavelength range of 780 nanometers to 2500 nanometers to enable near-infrared (NIR) spectroscopy.
17 . The method of claim 15 , wherein the tunable laser is configured to generate a collimated light beam, and the beam alignment is achieved using precision alignment features integrated into an optical subassembly.
18 . The method of claim 15 , wherein the tunable laser is controlled by a digital controller to selectively emit light at predetermined wavelengths optimized for detecting specific analytes in the fluid sample.
19 . The method of claim 15 , wherein the tunable laser is housed within a thermally stable enclosure to prevent wavelength drift due to ambient temperature fluctuations during operation.
20 . The method of claim 15 , wherein the tunable laser is capable of scanning multiple wavelengths sequentially within the near-infrared (NIR) spectrum, enabling simultaneous detection of multiple analytes in the fluid sample.