What is the Membrane Filter Integrity Test

Generally speaking, the integrity testing methods are divided into two categories: destructive and non-destructive, which will be explained separately below.

Destructive Testing

For sterilizing-grade membrane filters, destructive testing refers to bacterial challenge testing, which is the fundamental method to demonstrate that the filter can meet stringent sterilizing-grade filter standards. In bacterial challenge testing, a certain number of samples are randomly selected from each batch of products according to statistical principles. Following standard testing methods (e.g., ASTM F838-83), the filters undergo bacterial challenge testing using a Brevundimonas diminuta ATCC 19146 bacterial solution. The filter needs to achieve a bacterial retention of at least 10^7 CFU/cm^2 of membrane to be considered a sterilizing-grade filter.

Non-Destructive Testing

Non-destructive integrity testing methods mainly include bubble point and water intrusion testing based on capillary principles, as well as diffusion flow and hold pressure testing based on diffusion principles. Below is a brief introduction to each:

Bubble Point Testing

Bubble point testing is based on the capillary model. The filter structure is filled with micro-pore channels, which form many “capillaries.” When the filter membrane is completely wetted by a liquid, the liquid is retained inside the membrane due to surface tension. To force the liquid out of the membrane pores, an additional gas pressure is applied. The minimum pressure required to completely expel the liquid from the membrane pores, overcoming surface tension, is the membrane’s bubble point pressure, also known as the bubble point. The testing method based on this principle is called bubble point testing. This is also the most widely used non-destructive integrity testing method.

The formula for calculating the bubble point value is as follows:

  • P = Bubble point pressure
  • d = Pore size
  • k = Shape correction factor
  • θ = Liquid-solid contact angle
  • σ = Surface tension

The bubble point value is directly related to the filter’s pore size. For a filter membrane, there are many micro-pores, and the bubble point value of each pore may not be the same. Therefore, the bubble point value of the filter membrane refers to the bubble point value of the largest possible membrane pore, which is the bubble point of the largest diameter pore. When the bubble point is reached, at least one pore of the membrane will be dried, and gas will rapidly pass through this dry pore downstream, indicating that the bubble point has been reached. For large-area filters, due to significant diffusion flow, manual bubble point determination in manual integrity testing may affect the judgment of the bubble point. Therefore, diffusion flow testing is recommended for large-area filters; for small-area filters, since the bubble point is directly related to the filter’s pore size, bubble point testing is recommended.

Water Intrusion Testing

HydroCorr testing, also known as the “squeezing water method” or “water intrusion method,” is developed based on the surface tension and capillary phenomena of water on hydrophobic filter surfaces. The minimum pressure required to force water into the largest membrane pore is called water intrusion pressure. During HydroCorr testing, the pressure applied should be lower than the water intrusion pressure. For an intact filter, water will not pass through the filter membrane to the downstream. The HydroCorr testing process measures the apparent flow of water caused by the compressed folding of the filter structure.

  • d = Pore size
  • k = Shape correction factor
  • θ = Liquid-solid contact angle
  • σ = Surface tension

HydroCorr is a highly sensitive method for testing the integrity of hydrophobic filter membranes based on water flow rates, without using alcohols. Since the filter membrane is not wetted, it can be immediately put into use after integrity testing with minimal or no drying required.
Water intrusion testing is an online integrity testing method for hydrophobic filters, also known as the Water Intrusion Test (WIT). WIT measures the rate of decrease in air pressure upstream of hydrophobic filters submerged in water.

WIT is performed using water as the medium, and the applied pressure must be sufficient to overcome the capillary pressure in the membrane pores to allow water to flow freely through the hydrophobic micropores of the membrane. This initial critical pressure is called the Water Penetration Point (WPP), which is determined by the material and hydrophobicity of the filter membrane and is inversely proportional to the pore size.

During WIT, a hydrophobic filter installed in a filter housing is immersed upstream in water. Under a test pressure lower than the critical pressure WPP, water cannot pass through the membrane but only intrudes into the membrane matrix, primarily invading the largest membrane pore. The water intruding into the membrane matrix does not mix with the water passing through the membrane. This intrusion is a slow process, requiring a long period of pressure to obtain water downstream. During WIT, water is injected from upstream into the filter with a filter core, trapping a column of air inside the filter housing. During the test, the water intrusion or passage through the membrane causes a decrease in volume, increasing the volume of air, and resulting in a pressure drop. Fully automatic integrity testers measure the decrease in air pressure corresponding to the volume of water invading the membrane pores within a specified time, allowing the determination of filter integrity. WIT has a corresponding relationship with empirical values for microbial challenge tests and has been certified by international authoritative institutions.

The operating sequence of the Water Intrusion Test (WIT) for hydrophobic filter membrane integrity testing

  1. Fill the upstream of the hydrophobic filter with water
  2. Close all upstream valves
  3. Connect the integrity tester (with water intrusion test function)
  4. Start the test: set parameters, and confirm, and the tester will automatically conduct the WIT test
  5. Print the test results simultaneously after completion of the test
  6. Open the drain valve at the bottom of the filter housing to completely drain the water
  7. Open the air inlet and drain valves of the filter housing to introduce compressed air
  8. Start the filtration operation of the filtration system

Diffusion Flow Testing

Diffusion flow testing is based on the dissolution-diffusion model. When the filter membrane is completely wetted by a liquid, if there is compressed gas on the upstream side of the filter, and the pressure value of this compressed gas is lower than the bubble point pressure, the filter membrane remains completely wetted. Since the gas concentration on the compressed gas side is higher than the atmospheric pressure side, gas molecules will dissolve into the wetted liquid and diffuse to the atmospheric pressure side. If a tube is connected downstream, a slow gas flow will be observed, which is diffusion flow. The testing method for integrity based on this principle is called diffusion flow testing. Gas diffusion follows Fick’s law, and the diffusion flow rate is directly proportional to the pressure difference and membrane area. To eliminate the influence of different testing pressures, diffusion flow testing is conducted at a fixed pressure (usually 80% of the bubble point value).

The formula for calculating diffusion flow is as follows:

  • K = Diffusion/dissolution coefficient
  • P1, P2 = Pressure difference on both sides
  • P = Membrane opening pressure
  • L = Effective membrane flow path length
  • A = Membrane area
  • DF = Diffusion flow

Measuring the gas diffusion flow rate under test pressure can measure diffusion flow, but diffusion flow is unrelated to the filter pore size. For large-area filters, diffusion flow testing results are not affected, so diffusion flow testing is recommended for large-area filters. For small-area filters, since diffusion flow is small and measurement errors may be significant, bubble point testing directly related to pore size is recommended.