Buffer flow

pH and Conductivity Dynamic Measurement

In addition to essential requirements such as GMP compliance, biocompatibility, and robustness against cleaning and sterilization processes, the important specifications for any process sensor include measurement range and accuracy tolerance. Response time is another significant specification; however, it largely depends on the entire measuring loop, which encompasses the cables and transmitter/integration system selected to convey the signal to the skid PLC.

In dynamic conditions such as in-line buffer dilution, chromatography, and filtration, the specific requirements for these specifications depend on the particular biopharmaceutical downstream process being carried out. In the table below, the typical requirements for dynamic measurement of pH and conductivity are described.

CPP Measuring range (depending on application) Most common accuracy tolerance Response time (t90 between two certified calibration standards)
pH 3.5 to 8.5 ± 0.15 5-10 s (depending on application)
Conductivity 1.3 μS/cm to 200 mS/cm ± 5%

Typical requirements for pH and conductivity in downstream applications. The tolerances assume a constant process temperature (e.g., ambient temperature ±1°C/°F) and a constant flow rate. Specific applications may necessitate tighter tolerances in lower ranges. Source: Cytiva Allegro - Application Note "Production of In-Specification Buffer on Demand for Batch Processes".

Flow direction

Process sensors in flow-cell – assuming both pH and conductivity are needed. Examples of Hamilton process sensors include OneFerm (Single-Use pH) and Conducell 4USF (reusable 4-pole conductivity).

Tips to keep the highest accuracy in flow cell applications

Tips for both pH and Conductivity

  • Adhere to the maintenance recommendations provided in the sensor manuals by the manufacturer.
  • Use certified buffers/standards for a 2-point calibration with reusable (RU) sensors.
  • Regularly check sensor performance and perform an in-line calibration when necessary, especially for pre-calibrated Single-Use sensors.
  • For sensor calibration or in-line product calibration (in-line process calibration), choose standards according to the application-specific measuring range:
  • - For pH working range 3.5 to 8, use buffers pH 3.06 and 9.21 respectively
  • - For conductivity, working range up to 100 mS/cm, use the corresponding standard e.g., Hamilton Conductivity Standard 100 mS/cm
  • Calibration should be performed under the same conditions as routine application such as temperature.
Ph sensor diaphragm

If both pH and conductivity are required, their positions in the flow-cell do not influence each other's measurements. The order of pH and conductivity placement does not affect accuracy, considering the specified accuracy and buffer flow direction.

Tips for Conductivity

  • Calibration must be performed in-line and in the same flow-cell as routine use to maintain the same cell constant and achieve the expected accuracy.
  • Flow-rate/pressure does not significantly influence accuracy, considering the specified tolerances.
  • Temperature has a direct impact on conductivity. Increasing temperature increases the mobility of ions within a solution and results in higher conductivity measurements. Temperature compensation can be performed using empirically derived temperature coefficients, which may be different for various solutions. Hamilton provides a graph and a temperature lookup table from 5 to 50°C for every conductivity standard to determine the raw conductivity value of the liquid standard.


Tips for pH

  • When using a Single-Use (SU) or reusable (RU) electrochemical sensor, position the sensor so that the diaphragm faces the opposite direction of the flow.
  • The importance of conductivity: with proper sensor maintenance and calibration, the expected accuracy is possible up to 1 mS/cm.
  • Changes in flow rate/pressure can influence accuracy (e.g., going up to 4 bar or more).
Ph buffer and conductivity standards

Why is the cell constant crucial for conductivity measurement accuracy?

The cell constant is a crucial parameter for conductivity sensors, as it is used to relate the measured resistance of a solution to its actual conductivity. The cell constant (K) is defined as the ratio of the distance between the electrodes to the effective cross-sectional area of the electrodes within the conductivity sensor. It has units of cm-1 and is typically represented as K = L/A, where L is the distance between the electrodes and A is the effective electrode area.

The cell constant is important for sensor accuracy because it helps to normalize the measured resistance for variations in electrode geometry and arrangement. A conductivity sensor is calibrated by using reference solutions with known conductivity values. This calibration process allows the sensor to accurately measure the conductivity of unknown samples by accounting for the unique cell constant of the sensor.

If the cell constant is incorrect or changes over time (due to fouling or damage to the electrodes), the sensor's accuracy will be compromised [33]. Therefore, it is essential to maintain the sensor properly and calibrate it regularly to ensure that the cell constant remains accurate for reliable conductivity measurements.


A = Area of Electrode Surface (cm2),

L = Distance Between Electrodes (cm),

V = Voltage, K = L/A = Cell Constant (cm-1)

Measurement accuracy diagram

Hamilton Products Used

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