Bubble-point pressure test

The integrity of the filter assembly should be checked by an appropriate method, such as bubble-point pressure test or forward flow pressure test immediately before and after use. Results of these filter-integrity checks should be recorded in the batch record. 

Bubble Point Pressure Test Membrane filters have discrete pores or capillaries penetrating from one side of the membrane to the other. When a membrane has been completely wetted, Squid is held in these capillary pores by surface tension. The Bubble Point of a membrane is defined as the minimum gas pressure required to break this surface tension and force the liquid out of the capillaries. Bubble point is a measure of relative pore size. 

The pressure at which the slope changes is the bubble-point pressure of the mixture. The volume at this point is the volume of the bubble-point liquid. Often it is given the symbol Vsat. The volume of the bubble-point liquid can be divided by the mass of reservoir fluid in the cell to obtain a value of specific volume at the bubble point. Specific volume at the bubble point also is measured during other tests and is used as a check on the quality of the data. 

At pressures above bubble-point pressure, oil formation volume factors are calculated from a combination of flash vaporization data and separator test data. 

As pressure is increased above the bubble point pressure, pores of decreasing size have the liquid forced out, and this allows additional bulk flow of the test gas. By measuring and comparing the bulk gas flow rates of both a wetted and a dry filter medium at the same pressure, the percentage of the bulk gas... 

The bubble point test is simple, quick and reliable and is by far the most widely used method of characterizing microfiltration membranes. The membrane is first wetted with a suitable liquid, usually water for hydrophilic membranes and methanol for hydrophobic membranes. The membrane is then placed in a holder with a layer of liquid on the top surface. Air is fed to the bottom of the membrane, and the pressure is slowly increased until the first continuous string of air bubbles at the membrane surface is observed. This pressure is called the bubble point pressure and is a characteristic measure of the diameter of the largest pore in the membrane. Obtaining reliable and consistent results with the bubble point test requires care. It is essential, for example, that the membrane be completely wetted with the test liquid this may be difficult to determine. Because this test is so widely used by microfiltration membrane manufacturers, a great deal of work has been devoted to developing a reliable test procedure to address this and other issues. The use of this test is reviewed in Meltzer s book [3],... 

Although bubble point measurements can be used to determine the pore diameter of membranes using Equation (7.1), the results must be treated with caution. Based on Equation (7.1), a 0.22-pm pore diameter membrane should have a bubble point of about 200 psig. In fact, based on the bacterial challenge test, a 0.22-pm pore diameter membrane has a bubble point pressure of 40-60 psig, depending on the membrane. That is, the bubble point test indicates that the membranes has a pore diameter of about 1 pm. 

Figure 7.8 shows typical results comparing microbial challenge tests using 0.22-pm P. diminuta with membrane bubble points for a series of related membranes [6], In these tests at a microbial reduction factor of 108-109, the membrane has a bubble point pressure of only 40 psig, far below the theoretical... 

When the wetting fluid is expelled from the largest pore, a bulk gas flow will be detected on the downstream side of the filter system (Fig. 7). The bubble point measurement determines the pore size of the filter membrane, i.e., the larger the pore the lower the bubble point pressure. Therefore, filter manufacturers specify the bubble point limits as the minimum allowable bubble point. During an integrity test, the bubble point test has to exceed the set minimum bubble point. 

A completely wetted filter membrane provides a liquid layer across which, when a differential pressure is applied, the diffusive airflow occurs in accordance with Fick s law of diffusion (Fig. 8). This pressure is called test pressure and commonly specified at 80% of the bubble point pressure. In an experimental elucidation of the factors involved in the process, Reti simplified the integrated form of Fick s law to read as follows ... 

It is essential that the microbiological particle passage test is performed as part of the development of new sterile formulations. Because of its very specialized nature, the test is normally performed only by the filter manufacturers, who then provide limits for secondary physical tests (e.g., bubble point, pressure decay, forward flow, etc.), which can be applied to verify the pore size rating and integrity of the membrane filters. 

The pressure hold test can be set up as a variant of the bubble point test by using a pressure slightly below the estimated bubble point. It can be set up as a variant of the diffusion test with the pressure around 80% of the bubble point pressure, or it can be set up at lower pressures around 5-10% of the bubble point pressure. The test can be done over a very short period of time or over a protracted hold time. 

When a test gas (for example ambient air) is applied over a water moistened filter, just below the pressure level of the bubble point, test gas diffusion will occur through the water in the wetted membrane filter. This diffusion happens in all water filled pores, not only in the largest. This principle is the basis for two tests, which use different approaches to measure gas diffusion the pressure hold test and the diffusive-flow (forward flow) test. Other names for the same principle tests exist. These tests are performed at a pressure of about 80 % of the theoretical bubble point pressure of the filter. It is important that the largest pores are still filled with liquid. In this phase, diffusion occurs more or less linearly with the pressure drop over the... 

To perform a bubble test, the membrane must be kept constantly wet. Gas, normally N2, is then connected to the inlet side of the filter and the outlet is connected to tubing that is placed into a vessel containing water. As gas is allowed to flow into the filter housing, the pressure is slowly increased using the gas tank regulator. The bubble point is that pressure where a stream of bubbles first appears on the outlet or filtrate side of the membrane. If the measured bubble point pressure is less than the manufacturer s specified value, the membrane has been compromised and should not be used. The bubble point should be recorded prior to start-up and at the end of botding as well as after any interruptions (i.e., upon return from worker break periods). 

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