- Email: [email protected]
Analysis and monitoring: membrane flow comparison
FISE_Sept06_Column_A&M.qxd
40
22/08/2006
11:40
Page 40
Column
Filtration+Separation September 2006
Analysis and monitoring:
membrane flow comparison I
n many areas of filtration and separation, it is important to achieve a balance between retentivity and performance. In the second of a two-part column, Maik Jornitz and Theodore Meltzer delve into the subject of “flow”, when comparing different microporous membranes.
[Note: for part one of the column, see pages 38-39, Filtration + Separation, July-August 2006.]
Absence of rating standards That a membrane of greater flux is at hand for a membrane labelled 0.1µm-rated is not disputed. The question is whether its assigned pore size rating justifies it being compared with a membrane classified to a different rating standard. The various filter manufacturers do not necessarily use the same protocol for classifying the porosity ratings. The use of an identical numerical pore size designation by two different manufacturers does not necessarily mean that the membranes that are so characterised, are identically sized. The consequences of this lack of pore size standardisation can be overemphasised. The interchange of like-rated membranes of different manufacture, albeit with some adjustments, has long been successfully practiced. Nevertheless, standardisation is absent, and the opportunity for ambiguity exists. To put it broadly, one person’s 0.1 µm may be another’s 0.2/0.22 µm. Table 1: Filter type Polycarbonate Asymmetric Polysulfone Polyvinylidene Fluoride Nylon 66 Cellulose Mixesters
In water 100.0 100.0 74.8 82.1 89.4
The data in table 1 assembled by Tolliver and Schroeder (1983) demonstrates that among several 0.2/0.22µm-rated membranes thus defined by organism retentions, there is a wide divergence in results using 0.198 µm latex spheres. More to the point, Krygier (1986) reported that nylon filters rated by their manufacturer as being 0.2s would be rated as 0.46s by latex bead retention; while membranes rated as 0.1s would be rated as 0.28s. To complicate matters further, the numerical pore size ratings of most, if not all, membranes, do not describe actual pore dimensions.
Opportunities to take judgment calls Opportunities for judgment calls exist for the individual filter producer as well. The standards for any ratings produced by any manufacturer cover an acceptable, but not identical, range of measurements of a relevant parameter. As Schroeder (2001) points out, the pore size / retention correlation is not a step function. Thus, in its manufacture, a membrane lot may, and indeed will, incur some variation in its pore
In 0.05% surfactant 100.0 100.0 19.2 1.0 25.1
Table 1: Percentage retention of 0.198 µm latex particle by various 0.2 µm-rated membranes (Courtesy of Tolliver & Schroeder).
size across the substantial membrane area that is produced. The possibility exists for judgment calls to be made in assigning pore size labels. One fabricator may, on the basis of flux, consider a membrane to be an open 0.1. Another filter producer, using a somewhat different rating system might classify it as being a tight 0.2. This could give rise to a labelled 0.1, not so handicapped by reduced flows, being compared with a labelled 0.2, not so advantaged by enhanced flows. The more open 0.1 may not flow faster than an average 0.2, but may do so against a tight 0.2. There are also possibilities for comparisons to be based on misconceptions. Double membrane constructions are often classified by the rating of the down-stream membrane alone. Thus, a 0.2µm over a 0.2µm construction, may simply be labelled as being 0.2µm-rated. This so called 0.2 filter, actually a double-layered 0.2 filter – its flow disadvantaged by the extra 0.2 membrane layer – may undergo comparison with a single, more open 0.1 filter; to the advantage of the latter (see figure 1).
Variations within and between ratings Pairs of 10” cartridges of a 0.2µm-rating, and of a 0.1µm rating were obtained from each of four different filter manufacturers, and were measured for their flow rates. Figure 2 shows the difference in flow rates found among the filters of each pore size
FISE_Sept06_Column_A&M.qxd
22/08/2006
11:40
Page 41
Column
Filtration+Separation September 2006
however, require the presentation of supportive data to validate the publicised assertion. The risk of not doing so is that the numbers may ungenerously and perhaps incorrectly be attributed to a marketing department finding rather than to an R&D development.
Requirements for proper comparisons
Figure 1: Flow rate comparison of a double layer 0.2 micron membrane versus 0.1 micron.
classification, and between the two pore size groups:
be a factor in causing the differences in the flow rates within each pore sized group.
• Supplier B 0.2 flowed at 6,000 l/h/10”; its 0.1 flowed at 750 l/h/10”;
Whatever the cause, it cannot be concluded that comparative flow rate measurements are reflections of the membrane flux.
• Supplier C flowed at 2500 l/h/10” for the 0.2, and 2100 l/h/10” for the 0.1 rating. The differences among the like-rated cartridges, as well as between the rated groups were far from uniform. Also evident is that the flow rate levels differentiating between the 0.1 and 0.2 rated cartridge groups varied significantly. In some instances the differences were substantial. Different cartridge construction features, such as pleat heights and densities, may well have contributed to the variations (Priebe et al 2003, Meltzer and Lindenblatt 2002, Soelkner and Rupp 1998). Nevertheless, it is not unreasonable to believe that different rating standards could also
The flow rates of the 0.2 and 0.1 micron cartridges of supplier B were 6000 l/h/10” and 750 l/h/10” respectively; a difference of about 83%. A relatively small difference in flow rates – some 17% – exists between the supplier C 0.2 µm-rated cartridge’s 2500 l/h/10”, and that of its 0.1µm-rated counterpart’s 2100 l/h/10”. One need not invoke “innovative filter manufacturing technology” – whereby a 0.1µmrated membrane flows like one that is 0.2/0.22µm-rated – to explain the relatively small difference in flows between the supplier C 0.2 and 0.1 cartridges. The documented flow rate numbers speak for themselves. Making such a claim does,
Figure 2: Flow rate comparison of multiple different 0.2 and 0.1 micron membrane filter configurations
The prevailing situation is that several filter makers do use different standards. It is conceivable that the two membranes being compared are essentially of the same rating. The different pore size ratings assigned them may be the product of different rating standards. Therefore, the claim that a particular 0.1 µm-rated filter of one manufacture has a higher flux than some 0.2/0.22 µm-rated filters of another fabrication, is of a logic commonly found in comparing apples with pears.
Nevertheless, standardisation is absent, and the opportunity for ambiguity exists. To put it broadly,, one person’s 0.1 µm may be another’s 0.2/0.22 µm The only valid comparison can be that of 0.1 and 0.2µm-rated filters of the same filter manufacturer: i.e. the same branded type, the same polymer, same manufacturer, same design, etc. and especially the same standard for pore size rating. Interestingly, relevant data exist that enable such a comparison to be made.
Flux vs. pore size rating Brock (1983) lists the flux of a series of membranes of different pore size ratings prepared by one filter manufacturer, and pore-size rated by the fabricator’s single standard. The several pore-sized membranes exhibited substantial differences in flux; especially between those of the 0.2/0.22µm-rated and 0.1µm-rated membranes. The flux of a cellulose ester membrane of 0.45µm-rating is 22 ml per second per unit area; for a 0.22µm-rated filter of identical type it is 8 ml; for a 0.1µm-rating it is 2 ml. The differences in flows among the various pore sizes are hardly subtle; only 1/3 of the flow through a 0.45 pore diameter (22 ml/min/cm2) was given by the 0.2 pore diameter (8 ml/min/cm2); and of that flow only 1/8 was exhibited by the 0.1 pore diameter (1 ml/min/cm2). Roughly 65% of the 0.45’s flux is lost in changing to the 0.2. The shift to the 0.1 pore diameter from the 0.2 lost about 87% of that flow (Brock 1983).
41
FISE_Sept06_Column_A&M.qxd
42
22/08/2006
11:40
Page 42
Column
On the basis of these data it seems to the authors improbable, if not impossible, for the 0.1s to achieve rates of flow (flux) approaching those of the 0.2/0.22s on the basis of increased porosity. The microporous membranes are already in the range of 80% porosity. How much more empty space (porosity) can be blended with proportionately less solid matrix to constitute still a membrane structure having enough mechanical strength to maintain a dependable integrity during its processing application?
Absence of supporting data The announcement of a 0.1µm-rated membrane with a flux equal to or greater than that of 0.2/0.22µm-rated membranes would seem noteworthy enough to be accompanied by a simultaneous release of supporting data. One is reminded of Lord William Thompson Kelvin’s famous dictum, long a guiding principle of the scientific approach: “When you can measure what you are speaking about and can express it in numbers, you know something about it.” This condition – necessary to discussion – remains unfulfilled.
Filtration+Separation September 2006
has a greater flux than 0.2/0.22µm-rated membranes manufactured and rated by other filter fabricators is not disputed. Furthermore, the authors do not believe it to be incumbent upon the one making the claim to explain what some may consider an unlikely event. All that is required is that the data – and in particular, pertinent measurements leading to a conclusion – be made public to the industry. Its causality can be allowed to remain one of the many as yet unsolved mysteries. To claim knowledge of its etiology as stemming from greater porosities does, however, carry the implication that the matter was experimentally investigated, and that the evidence acquired serves to validate the thesis. This public statement, we believe, obligates its advocates to make available to the technical community the data validating that assertion. Validation for this purpose can be described as documented supportive data experimentally acquired.
Summary
The required data
• Flux comparisons may legitimately be made only between or among membranes classified by the same pore size rating system;
The claim that a 0.1µm-rated membrane – manufactured and rated by one producer –
• Only by assuming a common rating system can one attribute dissimilarities in flows, to
structural differences, e.g. porosities or thickness etc; • When knowledge of cause and effect are alleged, substantiating experimental data, made public, is required to confirm the claim; • The term “data” when used in technical contexts requires being expressed in terms of measurable parameters. Only when these attributes are met, will the pharmaceutical industry filter user have a clear specification and choice of which filter rating or filter performance would be optimal for her/his process. More often the case right now, the filter user has to rely on claims that might not be scientifically substantiated and required to perform tests using her/his own resources. It certainly would be helpful, if standards were established, or at least data were founded on defined methodologies and test criteria.
•
For references, please contact the editor or the authors. Authors Maik W. Jornitz – Sartorius North America Theodore H. Meltzer – Capitola Consulting Co. www.sartorius.com
40
22/08/2006
11:40
Page 40
Column
Filtration+Separation September 2006
Analysis and monitoring:
membrane flow comparison I
n many areas of filtration and separation, it is important to achieve a balance between retentivity and performance. In the second of a two-part column, Maik Jornitz and Theodore Meltzer delve into the subject of “flow”, when comparing different microporous membranes.
[Note: for part one of the column, see pages 38-39, Filtration + Separation, July-August 2006.]
Absence of rating standards That a membrane of greater flux is at hand for a membrane labelled 0.1µm-rated is not disputed. The question is whether its assigned pore size rating justifies it being compared with a membrane classified to a different rating standard. The various filter manufacturers do not necessarily use the same protocol for classifying the porosity ratings. The use of an identical numerical pore size designation by two different manufacturers does not necessarily mean that the membranes that are so characterised, are identically sized. The consequences of this lack of pore size standardisation can be overemphasised. The interchange of like-rated membranes of different manufacture, albeit with some adjustments, has long been successfully practiced. Nevertheless, standardisation is absent, and the opportunity for ambiguity exists. To put it broadly, one person’s 0.1 µm may be another’s 0.2/0.22 µm. Table 1: Filter type Polycarbonate Asymmetric Polysulfone Polyvinylidene Fluoride Nylon 66 Cellulose Mixesters
In water 100.0 100.0 74.8 82.1 89.4
The data in table 1 assembled by Tolliver and Schroeder (1983) demonstrates that among several 0.2/0.22µm-rated membranes thus defined by organism retentions, there is a wide divergence in results using 0.198 µm latex spheres. More to the point, Krygier (1986) reported that nylon filters rated by their manufacturer as being 0.2s would be rated as 0.46s by latex bead retention; while membranes rated as 0.1s would be rated as 0.28s. To complicate matters further, the numerical pore size ratings of most, if not all, membranes, do not describe actual pore dimensions.
Opportunities to take judgment calls Opportunities for judgment calls exist for the individual filter producer as well. The standards for any ratings produced by any manufacturer cover an acceptable, but not identical, range of measurements of a relevant parameter. As Schroeder (2001) points out, the pore size / retention correlation is not a step function. Thus, in its manufacture, a membrane lot may, and indeed will, incur some variation in its pore
In 0.05% surfactant 100.0 100.0 19.2 1.0 25.1
Table 1: Percentage retention of 0.198 µm latex particle by various 0.2 µm-rated membranes (Courtesy of Tolliver & Schroeder).
size across the substantial membrane area that is produced. The possibility exists for judgment calls to be made in assigning pore size labels. One fabricator may, on the basis of flux, consider a membrane to be an open 0.1. Another filter producer, using a somewhat different rating system might classify it as being a tight 0.2. This could give rise to a labelled 0.1, not so handicapped by reduced flows, being compared with a labelled 0.2, not so advantaged by enhanced flows. The more open 0.1 may not flow faster than an average 0.2, but may do so against a tight 0.2. There are also possibilities for comparisons to be based on misconceptions. Double membrane constructions are often classified by the rating of the down-stream membrane alone. Thus, a 0.2µm over a 0.2µm construction, may simply be labelled as being 0.2µm-rated. This so called 0.2 filter, actually a double-layered 0.2 filter – its flow disadvantaged by the extra 0.2 membrane layer – may undergo comparison with a single, more open 0.1 filter; to the advantage of the latter (see figure 1).
Variations within and between ratings Pairs of 10” cartridges of a 0.2µm-rating, and of a 0.1µm rating were obtained from each of four different filter manufacturers, and were measured for their flow rates. Figure 2 shows the difference in flow rates found among the filters of each pore size
FISE_Sept06_Column_A&M.qxd
22/08/2006
11:40
Page 41
Column
Filtration+Separation September 2006
however, require the presentation of supportive data to validate the publicised assertion. The risk of not doing so is that the numbers may ungenerously and perhaps incorrectly be attributed to a marketing department finding rather than to an R&D development.
Requirements for proper comparisons
Figure 1: Flow rate comparison of a double layer 0.2 micron membrane versus 0.1 micron.
classification, and between the two pore size groups:
be a factor in causing the differences in the flow rates within each pore sized group.
• Supplier B 0.2 flowed at 6,000 l/h/10”; its 0.1 flowed at 750 l/h/10”;
Whatever the cause, it cannot be concluded that comparative flow rate measurements are reflections of the membrane flux.
• Supplier C flowed at 2500 l/h/10” for the 0.2, and 2100 l/h/10” for the 0.1 rating. The differences among the like-rated cartridges, as well as between the rated groups were far from uniform. Also evident is that the flow rate levels differentiating between the 0.1 and 0.2 rated cartridge groups varied significantly. In some instances the differences were substantial. Different cartridge construction features, such as pleat heights and densities, may well have contributed to the variations (Priebe et al 2003, Meltzer and Lindenblatt 2002, Soelkner and Rupp 1998). Nevertheless, it is not unreasonable to believe that different rating standards could also
The flow rates of the 0.2 and 0.1 micron cartridges of supplier B were 6000 l/h/10” and 750 l/h/10” respectively; a difference of about 83%. A relatively small difference in flow rates – some 17% – exists between the supplier C 0.2 µm-rated cartridge’s 2500 l/h/10”, and that of its 0.1µm-rated counterpart’s 2100 l/h/10”. One need not invoke “innovative filter manufacturing technology” – whereby a 0.1µmrated membrane flows like one that is 0.2/0.22µm-rated – to explain the relatively small difference in flows between the supplier C 0.2 and 0.1 cartridges. The documented flow rate numbers speak for themselves. Making such a claim does,
Figure 2: Flow rate comparison of multiple different 0.2 and 0.1 micron membrane filter configurations
The prevailing situation is that several filter makers do use different standards. It is conceivable that the two membranes being compared are essentially of the same rating. The different pore size ratings assigned them may be the product of different rating standards. Therefore, the claim that a particular 0.1 µm-rated filter of one manufacture has a higher flux than some 0.2/0.22 µm-rated filters of another fabrication, is of a logic commonly found in comparing apples with pears.
Nevertheless, standardisation is absent, and the opportunity for ambiguity exists. To put it broadly,, one person’s 0.1 µm may be another’s 0.2/0.22 µm The only valid comparison can be that of 0.1 and 0.2µm-rated filters of the same filter manufacturer: i.e. the same branded type, the same polymer, same manufacturer, same design, etc. and especially the same standard for pore size rating. Interestingly, relevant data exist that enable such a comparison to be made.
Flux vs. pore size rating Brock (1983) lists the flux of a series of membranes of different pore size ratings prepared by one filter manufacturer, and pore-size rated by the fabricator’s single standard. The several pore-sized membranes exhibited substantial differences in flux; especially between those of the 0.2/0.22µm-rated and 0.1µm-rated membranes. The flux of a cellulose ester membrane of 0.45µm-rating is 22 ml per second per unit area; for a 0.22µm-rated filter of identical type it is 8 ml; for a 0.1µm-rating it is 2 ml. The differences in flows among the various pore sizes are hardly subtle; only 1/3 of the flow through a 0.45 pore diameter (22 ml/min/cm2) was given by the 0.2 pore diameter (8 ml/min/cm2); and of that flow only 1/8 was exhibited by the 0.1 pore diameter (1 ml/min/cm2). Roughly 65% of the 0.45’s flux is lost in changing to the 0.2. The shift to the 0.1 pore diameter from the 0.2 lost about 87% of that flow (Brock 1983).
41
FISE_Sept06_Column_A&M.qxd
42
22/08/2006
11:40
Page 42
Column
On the basis of these data it seems to the authors improbable, if not impossible, for the 0.1s to achieve rates of flow (flux) approaching those of the 0.2/0.22s on the basis of increased porosity. The microporous membranes are already in the range of 80% porosity. How much more empty space (porosity) can be blended with proportionately less solid matrix to constitute still a membrane structure having enough mechanical strength to maintain a dependable integrity during its processing application?
Absence of supporting data The announcement of a 0.1µm-rated membrane with a flux equal to or greater than that of 0.2/0.22µm-rated membranes would seem noteworthy enough to be accompanied by a simultaneous release of supporting data. One is reminded of Lord William Thompson Kelvin’s famous dictum, long a guiding principle of the scientific approach: “When you can measure what you are speaking about and can express it in numbers, you know something about it.” This condition – necessary to discussion – remains unfulfilled.
Filtration+Separation September 2006
has a greater flux than 0.2/0.22µm-rated membranes manufactured and rated by other filter fabricators is not disputed. Furthermore, the authors do not believe it to be incumbent upon the one making the claim to explain what some may consider an unlikely event. All that is required is that the data – and in particular, pertinent measurements leading to a conclusion – be made public to the industry. Its causality can be allowed to remain one of the many as yet unsolved mysteries. To claim knowledge of its etiology as stemming from greater porosities does, however, carry the implication that the matter was experimentally investigated, and that the evidence acquired serves to validate the thesis. This public statement, we believe, obligates its advocates to make available to the technical community the data validating that assertion. Validation for this purpose can be described as documented supportive data experimentally acquired.
Summary
The required data
• Flux comparisons may legitimately be made only between or among membranes classified by the same pore size rating system;
The claim that a 0.1µm-rated membrane – manufactured and rated by one producer –
• Only by assuming a common rating system can one attribute dissimilarities in flows, to
structural differences, e.g. porosities or thickness etc; • When knowledge of cause and effect are alleged, substantiating experimental data, made public, is required to confirm the claim; • The term “data” when used in technical contexts requires being expressed in terms of measurable parameters. Only when these attributes are met, will the pharmaceutical industry filter user have a clear specification and choice of which filter rating or filter performance would be optimal for her/his process. More often the case right now, the filter user has to rely on claims that might not be scientifically substantiated and required to perform tests using her/his own resources. It certainly would be helpful, if standards were established, or at least data were founded on defined methodologies and test criteria.
•
For references, please contact the editor or the authors. Authors Maik W. Jornitz – Sartorius North America Theodore H. Meltzer – Capitola Consulting Co. www.sartorius.com