The global biopharmaceutical market has grown year by year, and protein drugs and vaccines have become major segments. In the whole biopharmaceutical processing process, the bioreactor is the core equipment for upstream production. According to the statistics of cultured cell types, 75% of bioreactors are used to culture mammalian cells. The adaptive pH range of mammalian cells is generally between 6.8 and 7.3. Lower than 6.8 or higher than 7.3 may have adverse effects on cell growth and the quality and yield of target products. Therefore, online pH sensor becomes indispensable process analysis sensor in the bioreactor.

Factors determining the zero point and slope of the pH electrode

Fig. 1 Schematic diagram of typical pH composite electrode structure

According to the electrochemical principle of the pH electrode, the signal intensity generated by the measuring electrode is determined by the hydrogen ion activity of the solution, that is, the pH value. The reference electrode does not react with the hydrogen ion in the measuring solution and always generates a constant potential. Therefore, the potential difference between the measuring electrode and the reference electrode can characterize the content of free hydrogen ions in the solution and measure the pH value of the solution. Most users will use the zero shift (mV) and slope shift (mV/pH) of the electrode to evaluate the electrode performance. But the factors that determine the zero point and slope are the reference system, sensitive membrane, and liquid complex.

Reference system

The reference system shall be free from interference and fast response. Considering the balance between the response time and service life of the reference system, the reference systems suitable for the biopharmaceutical industry include liquid electrolytes and gel electrolytes. The liquid electrolyte responds quickly, and the gel electrolyte has a long life. Different culture processes can be selected specifically according to the culture cycle and production batch.

Sensitive membrane

The measuring electrode measures the potential difference inside and outside the sensitive membrane. As an important part of the measuring electrode, the composition of the glass sensing membrane determines the responsiveness of the measuring electrode to hydrogen ions in the solution to be measured and its ability to resist interference from other ions. In addition, the biopharmaceutical industry has frequent high-temperature sterilization operations. Therefore, how many sterilization cycles can the sensitive membrane withstand without affecting its performance is also an important consideration.

Fluid collaterals

Early pH measurement used two electrodes, a measuring electrode, and a reference electrode to form a galvanic cell. In 1948, Dr. Ingold innovatively made two electrodes into a composite electrode by virtue of Switzerland's unique precision processing technology to reduce the operating cost of the sensor. However, the reference electrode in the composite electrode needs a liquid complex part to connect the reference system and the measured solution. Because the cell culture system is mainly an aqueous solution environment, porous ceramic materials are used to slowly drain the electrolyte in the measuring electrode, so as to prevent the uncontrolled outflow of electrolyte. This ceramic diaphragm is very suitable for electrodes for standard measurements in aqueous solutions.

Intelligent pH sensor

It is worth noting that with the continuous optimization of the culture process, the cell concentration and the concentration of the target product are significantly increased. The blockage of the ceramic pores caused by cell fragments and high-concentration proteins in the culture system will affect the electrode measurement performance to some extent. It is also important when the electrodes need to be cleaned to maintain the diaphragm bore. This can be judged from the sensitive membrane impedance of the electrode. If the ceramic hole is blocked by protein, the electrode can usually be immersed in pepsin/HCl (0.1mol/L HCl containing 5% pepsin) solution for several hours for cleaning.

The operating principle and performance characterization factors of the pH sensor itself are easy to evaluate, but the real pH measurement is determined by a system. The whole system loop involves sensors, sheaths, transmitters, and cables. The sheath plays an auxiliary role in the physical protection and cleaning calibration of electrodes. The transmitter plays the role of signal reception and decoding.

Reasons for selecting Supmea's pH electrode

High-temperature-resistant gel and high-temperature-resistant solid dielectric double liquid connection structures can be directly used for sterilization at 130 ℃. With five layers of glass coating, it is far more resistant to temperature and voltage than ordinary electrodes, with high measurement accuracy and good repeatability. S8, VP, K8S, and other interfaces can be designed to replace imported electrodes according to the actual needs of the site. In the process of use, there will be silver salt precipitation at the reference end. In order to prevent the salt bridge from blocking and ensure the stability of the point, add Ag plugs. The output signal is accurate and the service life is longer. It is equipped with a pH electrode protective sleeve, and there are PTFE sheaths and stainless steel sheaths for selection. The shell of the glass electrode is relatively fragile, which can be used with a high-temperature sleeve to greatly extend the service life of the electrode.

summary

Sharp tools make good work. Proper sensors and optimal performance are important conditions to ensure the stable operation of the process and ensure the reliability and consistency of production. Supmea pH sensors are more accurate in measurement, plug, and test, simple in compliance, and have a predictive diagnosis. They help enterprises transform from a passive, time-consuming, and labor-intensive maintenance strategy to a more lean and efficient proactive strategy, and optimize the analysis and measurement scheme.

At the same time, for the use and maintenance of online sensors, we advocate that process and production personnel should adhere to the idea that they should have a necessary understanding of the principle, use, maintenance, and other professional knowledge of sensors, evaluate and practice from the perspective of the full life cycle of model selection, use, maintenance, and other aspects, unlock the possibility of more online pH sensors, and give full play to the process analytical technology for process control The role of improving product quality and output.