The future trend of smart sensors in the biopharmaceutical industry
In recent years, intelligent manufacturing and future factories have become a hot topic. The author was deeply impressed by the prospect of Mr. Li Shood, vice president of Tianjing Bioengineering and Technology, in the beginning of this year in building intelligent factories and future facilities for biopharmaceuticals.He gives a highly refined summary of the current, near and medium term and final trends of biopharmaceuticals, covering five aspects: production process, reactor form adopted, process analysis method, quality control and digital factory.Among them, the process analysis method includes the development trend from off-line standard QC detection method to near-line detection, to the final on-line, real-time sensor monitoring.
Figure 1: Future facilities for biopharmaceuticals
In addition, in 2004, the FDA issued the industry guide Process Analysis Technology (PAT) - An Architecture for Innovation in Drug Development, Manufacturing and Quality Assurance. The FDA identified the term "PAT" as a multidisciplinary analytical approach that included chemistry, physics, microbiology, mathematics and risk analysis.Therefore, as one of the underlying equipment management of the digital and intelligent engineering in the future biopharmaceutical plant, intelligent sensor is worthy of attention.In this paper, pH and DO (dissolved oxygen) sensors commonly used in biopharmaceuticals are discussed as examples.
Figure 2: Bioreactor pH and DO measurement system
As shown in the figure above, pH and DO online sensors are widely used in the on-line monitoring of pH and DO in cell culture, and the measurement system generally includes sensors and transmitters.In the process of using electrodes, process developers or production personnel generally care about the following two core questions: can the electrodes be measured accurately and reliably?How long will the electrodes last?
First: Is the electrode able to measure accurately and reliably?
For sensors: pH sensitive film impedance, reference system, diaphragm performance;Internal electrode and dissolved oxygen film properties of electrochemical oxygen;The fluorescence coating of optical dissolved oxygen will determine the zero point and slope of the corresponding electrode. Generally, the zero point and slope can be used to determine whether the sensor can be accurately measured.For transmitter: it is responsible for signal modulation and transmission, measurement loop calibration and adjustment functions, but also indirectly determines whether the sensor can accurately measure pH and DO, and even the transmission cable will indirectly affect the accuracy of measurement.
Therefore, in order to determine whether the sensor can make accurate measurement, it is required that the sensor and transmitter can provide performance diagnosis. The lowest requirement is that the sensor implements ADC (Analog-to-digital Convert), namely the transformation of the sensor from traditional Analog signal to Digital signal output.Combined with the related functions of transmitter, accurate measurement can be achieved.
Figure 3: The sensor converts the measured signal into a digital signal and outputs it with higher fidelity
Second: How long will the electrodes last?
With pH sensor as an example, the same type of sensor is the sensitive membrane, reference system, the diaphragm type is the same, the service life of the theory are all the same, but different sensors experience process, thus batch cultivation or continuous flow plus, is easy to scale of measurement environment, experienced how much time the SIP, how many times the high temperature sterilization, etc., these factors finally decided it's real life.And these information, if the electrode does not implement ADC, it is difficult to realize the collection and storage of relevant information.
With 60 years of experience in the field of process analysis, Mettler Toledo innovatively put forward the concept of INTELLIGENT sensor management ISM® around these two core issues and related issues derived from it. In 2005, Mettler Toledo took the lead in realizing the digitization and intelligentization of sensors.On the electrode head through the built-in microprocessor, collecting electrode information about themselves, such as the diaphragm type, the diffusion path length, and the process conditions of measurement, such as temperature, experience extremely acid or alkali value, etc., in combination with certain algorithm, such as "RollingAlgorithm" algorithm, with the change of the measuring conditions, more accurate, intelligent generates the following user access to relevant information, and the intuitive display with the transmitter:
1) Dynamic life Indicator (DLI), indicating the remaining service life of the sensor, which can be replaced as needed instead of regularly
2) Maintain the reminder time (TTM) and recommend the next time that should be calibrated, neither too early nor too late;
3) Adaptive calibration timer (ACT), recommending when to clean and maintain the sensor again to ensure that the sensor performance is always trustworthy;
Figure 4: The M800 transmitter displays the ISM intelligent diagnostic information
In addition to these two core issues, sensors, as one of the underlying equipment of intelligent biopharmaceutical plants, naturally also involve compliance information.ISM intelligent sensor management of form a complete set of fully functional software can realize off-line calibration after the ISM sensor plug is measured, the sensors from the measurement point to convenient offline calibration laboratory, by fully electrode after calibration of the information to the chip, stay electrode connected to the transmitter of again, transmitter automatically read have calibration of relevant information, so as to realize plug namely, at the same time the software side can output the PDF version of the calibration records, can be used as an electronic archive can also print paper version of the file.
If you want to have a more intuitive feel of how intelligent sensor management ensures the reliability and consistency of measurements during process development and production, and reduces the ease of maintenance and calibration, scan the QR code below or click on the bottom of the article to read the original, and apply to try Mettler Toledo iSense software with one click.
Figure 5: iSense software enables offline calibration of sensors
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