Operating Handbook - Howllow Fiber Cartidges for Membrane Separations

8/12/2019 Operating Handbook - Howllow Fiber Cartidges for Membrane Separations

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READ ME FIRST

Operating Precautions

The information contained in this publication is not intended to constitute any representation of warranty by Amersham Biosciences.

Amersham Biosciences reserves the right to change specifications without notice.

Table of Contents

Key Performance ChartsMain Topics

1. Flush ultrafiltration (UF) cartridges prior touse to remove preservative solution andmeasure clean water flux. Followinstructions on pages 5 and 6.

2. Autoclavable and Steam-in-Place UFcartridges will benefit from a clean watersoak following first rinse, the longer thebetter.

3. Membrane water flux may be significantlyaffected by water quality and temperatureas well as wetting and cleaning procedures.

Review pages 5, 6, 7 and 10.

4. Do NOT allow UF cartridges to dry out.5. Do NOT shock membrane cartridges

during handling nor expose topressure surges during operation.

6. Do NOT shock membrane cartridgeswith rapid temperature changes.Increase or decrease temperaturegradually (nominally 1 C/minute).

7. Do NOT clamp cartridges too tightly.8. Loosen clamps before autoclaving.

Page

READ ME FIRST 2Cross Flow Filtration and Glossary of Terms 3Start-up Procedures 4New Cartridge Conditioning and

Water Flux Measurement5

Operating Considerations 7Diafiltration 9Flux Recovery

Cleaning, Sanitization, Storage,Depyrogenation

10

Autoclaving 14Backflushing 16Steam-in-Place 16

Data Log Sheet 17Quality Assurance 18Key Performance Charts 19

Page

Operating Parameters 19Nominal Feed Stream Flow Rates 20Nominal Feed Flow Rate vs. P 21Nominal UF Permeate Flow Rates 22Cartridge Physical Properties

Xampler CartridgesPilot/Process Scale CartridgesMaxCell & ProCell Cartridges

232425

2 & 3 mm Tubules 26Chemical Resistance 27


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UF/MF Operating Guide

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Cross Flow Filtration Apparatus and Glossary of Terms

1. A prefilter with a 200 rating may be desirableto protect rotary lobe pumps.

2. Pressure Gauges (particularly the inlet gauge)should be glycerine filled or mechanicallydampened.

3. If feed pump has variable speed control, inletvalve may be omitted.

4. Second permeate port may be used or blocked.

Pump

FeedReservoir

PressureGauge

Valve

HoseClamp(Optional)

Concentrate Return

PermeateReservoir

Peristaltic pumps are commonly used in laboratorysituations, while centrifugal pumps can be utilized inindustrial-scale systems. For sanitary operations,either peristaltic or rotary-lobe pumps are generallypreferred.

The membrane cartridge may be operated in either ahorizontal or vertical position . When the concen-trate stream is the product of interest, vertical orienta-tion will allow better drainage and higher recovery.Higher concentrations may also be reached when thevoid volume of the system is minimized by utilizingshort tubing lengths and by discharging the feedstream from a conical bottom tank.

One permeate port may be capped (blocked) tominimize system tubing. For UF cartridges in verticalorientation, either permeate port may be left open.However withdrawal of permeate from the lower port

RetentateFeed

Permeate

PermeateIndividual Membrane Lumen

For laboratory or pilot applications, a basic manualcontrol system consists of a pump, feed reservoir,permeate collection reservoir, pressure gauges,and valving (see below). Permeate connections aretypically of flexible tubing.

Amersham Biosciences ultrafiltration (UF) andmicrofiltration (MF) membrane cartridges areprovided with a wide range of hollow fiber and tubulelumen diameters, membrane pore sizes, surfaceareas and dimensions. Each cartridge contains abundle of polysulfone fibers or tubules potted inparallel within a plastic housing.

These cartridges are operated in a cross flowmode. In sharp contrast to single pass filtration,cross flow involves recirculation of the feed streampumped across the membrane surface. Thesweeping action created by fluid flow across themembrane surface promotes consistent productivityover the long term.

In operation, as the feed stream is pumped throughthe membrane cartridge, the retentate , includingspecies excluded by the membrane pores, contin-ues through the recirculation loop while the perme-ate , including solvent and solutes transportedthrough the membrane pores, is collected on theshell side of the cartridge.

Amersham Biosciences QuixStand Benchtop System for processing up to 10 liters, shown in concentration mode.

Glossary of Terms

Cross FlowSweeping action created by fluid flow across themembrane (also called tangential flow).

Feed StreamBulk solution to be processed via ultrafiltration ormicrofiltration (also called process solution).

Retentate

Solution containing species retained by the membrane(also called concentrate or reject).

PermeateSolution containing solvent and solutes passing throughthe membrane (also called filtrate or ultrafiltrate).

P

P

will permit more complete drainage of thepermeate-side. With MF cartridges, the MFpermeate should be withdrawn from the upperport to minimize transmembrane pressure.

Simplified System Schematic

A/G Membrane Cartridge

Valve

All Amersham Biosciences polysulfone membranes and cartridge materials are USP XXVII Class 6 safety tested. Amersham Biosciences provides both an Integrity Test Procedure Guide and a Validation Information Booklet to assist customers with validation and continual quality assurance of our products.


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Start-up Procedures

ULTRAFILTRATION

Ultrafiltration cartridges should be started-up withthe permeate ports closed , allowing the crossflow velocity to be established prior to permeatewithdrawal. If a positive displacement pump isused, both the feed inlet valve and the retentatevalve should be wide open. If a centrifugal pump isused, the feed inlet valve should be cracked openand the retentate valve should be open. The idealsystem includes a variable speed control on thepump motor. This allows the recirculation flow rateto be increased gradually until the specifiedpressure drop is achieved.

After turning on the pump, the inlet valve should beopened and the retentate valve slowly closed toestablish the preferred feed flow rate and/orpressure. If necessary, the inlet pressure may bereduced by adjusting the feed inlet valve or byinstalling a by-pass loop on the pump outlet. Sincefeed flow rate is proportional to the feed-to-retentate pressure drop along the length of acartridge, the tables on page 21 may be used toestimate feed flow rates.

When the correct inlet pressure and feed flow areestablished, the permeate lines should be opened.

Concentrate return to the feed reservoir should bebelow the liquid level to avoid splashing, foamingand excess air generation which could cavitate thepump.

MICROFILTRATION

Special consideration should be given to start-up ofhigh flux microfiltration membranes to avoid rapidgel layer formation and its associated flux decline.In almost all cases, the permeate ports should beblocked during startup , so that the cross flowvelocity can be fully established. If possible, eitherwater or buffer solution should be circulated initiallywithin the system followed by feed stream introduc-tion.

The inlet pressure should be as low as possible(


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New Cartridge Conditioning andWater Flux Measurement

ULTRAFILTRATION

Removal of Glycerol Preservative

Ultrafiltration (UF) membrane cartridges are pre-treated with an alcohol/glycerol solution within thepore structure to prevent drying of the membrane.This mixture enhances wetting but may cause the fibers to appear wavy. Trace amounts of alcohol(IPA) may remain when the cartridges are shipped.The glycerol must be thoroughly rinsed from thecartridge prior to use. In addition to preventingdrying, the glycerol minimizes entrained air within thepore structure of the membrane wall which maybecome locked-in reducing permeability until the airhas been displaced by liquid. Glycerol removal andwetting out will occur simultaneously when perform-ing the New Cartridge Rinsing Procedure. Mostclients elect to sanitize both UF and MF membranesprior to use. Refer to page 13 for complete details.

New Cartridge Rinsing Procedure[Recommended for all UF membranes]

The New Cartridge Rinsing Procedure should beperformed on all ultrafiltration cartridges.

Alcohol Pre-Treatment Procedure

Alcohol pre-treatment may be used to enhance

water flux of tight (30,000 NMWC and lower) UF membranes. For best results, follow procedure below before water contact, extending time of soak to overnight. If cartridge has already been exposed to water, shake out excess and then extend soak time to overnight. Either isopropyl alcohol (IPA) or ethanol may be used.

1. Fill cartridge with 100% alcohol for one hour.For best results, soak cartridge overnight.Take appropriate precautions with use ofalcohol. Be certain that both the lumen sideand the shell side of the cartridge are filledand that air has been displaced.

2. If facilities are in place, this procedure will bemore effective if the alcohol is pumpedthrough the cartridge for at least 10 minutesprior to soaking.

3. To remove alcohol, rinse with clean wateraccording to the New Cartridge RinsingProcedure.

4. The alcohol solution may be saved andreused several times before discarding.

1. Use clean water (WFI or 10,000 NMWC UFpermeate).

2. Adjust average transmembrane pressure ofcartridge to 15 psig for 1,000 NMWC and3,000 NMWC pore sizes; 10 psig for5,000 NMWC through 30,000 NMWC poresizes; and 5 psig for larger pore sizes.

3. Be certain retentate flow rate is at least 1/ 10th of the permeate flow.

4. Discharge both retentate and permeate todrain.

5. Use room temperature or warm (up to 50 C)water for rinsing. Cold water will be lesseffective. Addition of 100 ppm NaOCl toflush water will enhance glycerol

removal.6. Continue rinsing for 90 minutes. Make sure

NaOCl has been thoroughly rinsed outbefore introducing process solution.

Autoclavable/Steam-in-Place Cartridges[Extended Pre-Soak]

Before sterilizing UF cartridges in an autoclave or inan SIP sterilization procedure, the cartridge must befully rinsed of glycerol. If UF cartridges are to beautoclaved or steam sterilized, a pre-soak is recom-mended as an adjunct to the flushing procedure.

1. Rinse cartridge per New Cartridge Rinsing Proce-dure, above, for 30 minutes.

2. Soak cartridge in clean water, the longer thebetter. Be certain that both the lumen side andshell side of the cartridge are filled and that air hasbeen displaced.

3. Rinse cartridge per New Cartridge Rinsing Proce-dure, above, for 30 minutes.

MICROFILTRATION

Although microfiltration (MF) membrane cartridgesare shipped dry, without preservative solutions, it isprudent to rinse cartridges before first process expos-ure or heat sterilization. Follow New Cartridge RinseProcedure for at least 5 minutes at 5 psig (0.3 barg)inlet pressure.


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New Cartridge Conditioning andWater Flux Measurement

Clean Water Flux Evaluation

After rinsing, the next step with a new cartridge is to

obtain baseline data on clean water flux. Thesedata should be taken under easily repeatable conditions so that comparisons with water flux dataafter cleaning cycles can be made directly. Theparameters to monitor are:

Water Temperature Cartridge Inlet Pressure Cartridge Outlet Pressure Permeate Pressure

"Clean" water, which is defined as 10,000 NMWC(or tighter) ultrafiltration permeate, or WFI, is

required to assure contaminants are not presentwhich could negatively impact membrane perfor-mance.

Water flux is most reliably measured at low inletpressure. When using UF permeate or WFI,minimal cross flow is required, and the retentatevalve need only be cracked open to ensure elimina-tion of air trapped on the lumen-side.

With high flux Amersham Biosciences MF and500,000 NMWC UF membranes, parasitic pres-sure drop will occur on the permeate side of the

cartridge during clean water flux determinationsunless the inlet pressure is very low (typically


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Flux

Temperature

Flux

Pressure

Water

Process

Process Operating Considerations

Transmembrane Pressure Water flux will in-crease linearly with increasing transmembranepressure. Process flux will typically increase as afunction of transmembrane pressure. However,depending on the recirculation rate, the improve-ment in flux may become asymptotic since gel

= [(P inlet + P outlet )/2] P permeateTransmembranePressure

layer resistance to flux will increase from compac-tion. Control of permeate backpressure (restrictingpermeate flow rate) may reduce the tendency forfouling in the initial stages of a concentration,providing an overall higher average flux rate (seepage 9 for details).

Effect of Operating Parameters on Membrane Flux

Temperature Water flux and, most often, processflux will increase with increasing temperature.Clean water flux will vary linearly as a function ofwater viscosity, and over a narrow range (i.e.,25 C 10 C [77 F 20 F]) changes in waterviscosity may be approximated by the ratio oftemperature change in degrees Fahrenheit. Thus,water flux or process flux measurements betweenruns may be easily compared at a standard tem-perature, using the equation:

Process flux will also increase with temperature.The degree of process flux improvement is lesspredictable than with clean water since both a gellayer and a fouling layer on the membranesurface contribute to flux resistance. With somestreams, one will observe a linear flux improvementwith temperature. With others, a step-wise im-provement may occur after a critical temperatureis reached.

As a general rule, operation should be at thehighest temperature acceptable for the membrane,

given the constraints of feed stream pH and theoperating pressure.

where,

T1 = Reference temperature (e.g., 77 F)T2 = Actual temperature (F)

Temperature Corrected Flux = (Flux) xT2

T1T2

Temperature Corrected Flux =

40 lmh x = 47.8 lmh

For example,

On a new cartridge, the measured cleanwater flux is 40 lmh at 18 C (64.4 F).

77 F

64.4 F

Examples:

When processing at 15 C the clean water flux will be about 75% of the flux at 25 C.

When processing at 35 C the clean water flux will be about 125% of the flux at 25 C.

Process flux may behave differently.


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Flux

Concentration, Cv

Cv =Vo

Vo Vpy = 1

Cv

1

Volumetric ConcentrationSystem Conversion Relationship

where,

Cv = Volumetric Concentration FactorVo = Original Feed VolumeVp = Volume of Permeate Collected y = System Conversion, %

Cv y

1X (Vp = 0) 0%

2X 50%

5X 80%

10X 90%

20X 95%

50X 98%

Recirculation Rate Recirculation rate (feedvelocity) will have little, if any, effect on themembranes clean water flux since there is ideallyneither a gel layer nor a fouling layer to restrictpermeation. On the other hand, the basic premiseof cross flow filtration is that increased velocity willreduce gel layer formation, lowering the resis-tance to permeation and, hence, improve flux.

Thin feed flow channel devices (i.e., hollow fibers,spiral-wound cartridges and plate-and-framedevices) all operate in laminar flow. Increasing therecirculation rate will increase the wall shear andtypically enhance the rate of filtration. However,the pressure losses across thin channel deviceswhich become higher with increased recirculationlimit the practical degree to which feed velocity canbe raised. In general, if high velocities are to beachieved with thin channel devices, the feed flowpath should be as short as practical. For thisreason, Amersham Biosciences offers a full rangeof hollow fiber membrane cartridges with nominal 1foot (30 cm) flow path lengths (Housing Sizes 3, 4,5, 8, 35 and 45).

Fouling streams do not respond well to feeddilution and tend to reach low, steady-state fluxlevels which are less dependent on feed concen-tration. Higher feed flow rates, exhibiting a shearrate of at least 8,000 sec -1, should be utilized.

Low-fouling streams exhibit stable flux ratesover time with low recirculation rates. The flux oflow-fouling streams is basically concentrationdependent. Thus upon feed stream dilution, thepermeate rate will increase and approach thestarting performance level. A feed flow ratewhich provides an intermediate shear rate, on theorder of 4,000 to 8,000 sec -1, is a good startingpoint for processing low fouling streams.

Shear sensitive streams contain fragile compo-nents (e.g., infected cells, viruses) which may bedamaged by high recirculation rates or high

Resistance to permeation is a function of the mem-brane pore size, feed stream components, and thedegree to which gel layer formation and fouling layer

formation occur. Increasing the feed stream recircu-lation rate will, as a general rule, reduce gel layerthickness and increase flux.

Concentration Process flux is highly dependenton feed components and overall solids concentra-tion. As expected, flux declines with concentration.The rate of decline generally follows a straight linein a semi log plot of flux (linear scale) versusconcentration factor (log scale).

Time Flux declines with time, even with cleanwater. The influence of time on the rate of fluxdecline may, however, be insignificant comparedto the effect of concentration. A rapid flux decline,while processing a stream in total recycle (i.e., noconcentration) indicates either the recirculationrate is too low or bad actor foulants are present.Flux decline as a function of time may also occurwith a process stream due to gel layer compaction.

temperature. Recirculation rates which provideshear rates on the order of 2,000 to 4,000 sec -1 arerecommended for shear sensitive streams.

See page 20 for Feed Stream Flow Rate chart.


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Diafiltration is a unit operation incorporating ultrafil-tration membranes to efficiently remove salts orother microsolutes from a solution. The microsolutesare so easily washed through the membrane with thepermeated diafiltration water that for a fully permeat-ing species, about 3 volumes of diafiltration water willeliminate 95% of the microsolute. It is interesting tonote that net effective removal of the microsolute issolely dependent on the volume of ultrafiltrateproduced and not on the microsolute concentration.

A graph of microsolute removal (assuming 0%

rejection by the membrane) is provided.

6

4

2

00 20 40 60 80 90 95 98 99

Percent of Solute Removed

D i a f i l t r a

t i o n

V o

l u m e s

Microsolute Removal as a function of Diafiltration Volume

Diafiltration

Permeate Flow Control When a product is beingclarified through a microfiltration membrane, clientsoften experience enhanced product recovery andabbreviated process times by controlling the perme-ate pressure or by controlling the permeate flowrate. Pressure control requires a pressure gaugeand valving on the permeate line. Flow control,while achievable manually by constantly monitoringthe flow rate, is most easily performed by positioninga metering pump on the permeate line. With eithermethod, the initial permeate flow should be set atroughly 40% of the fully open, non-controlledpermeate rate after 5 to 10 minutes operation. If, asthe concentration proceeds, the permeate rate fallsbelow this mark, the backpressure may be reducedor the metering pump by-passed.

PermeateControlPump

RecirculationPump

For high flux membranes, permeate flow control isan effective means of improving flow stability andincreasing overall productivity.

1. Inlet pressure gauge should be glycerine filled or mechanically dampened.2. If feed pump has variable speed control, inlet valve may be omitted.3. Gauge on permeate port should read Pressure/Vacuum.

Maintain positive pressure.

P

P

1. Pressure Gauges (particularly the inlet gauge)should be glycerin filled or mechanicallydampened.

2. If feed pump has variable speed control, inletvalve may be omitted.

3. Second permeate port may be used or blocked.

4. Diafiltrate is drawn into the feed reservoir atthe same rate that permeate is withdrawn.

5. Initial concentration, followed by diafiltrationwill minimize diafiltrate volume but maymaximize total filtration time. On the other hand,initial diafiltration followed by concentration willmaximize diafiltrate volume. Partialconcentration/diafiltration/final concentrationmay minimize total filtration time with amid-range volume of diafiltrate solution.Thus, optimization of the process is requiredon a case-by-case basis.

Pump

FeedReservoir

PressureGauge

Valve

HoseClamp(Optional)

Concentrate Return

PermeateReservoir

Simplified System Schematic for Continuous Diafiltration

A/G Membrane Cartridge

Valve

DiafiltrateReservoir


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Flux Recovery Cleaning, Sanitization, Storage, Depyrogenation

Introduction

In almost all tangential flow membrane separa-tions, the rate of permeate flux declines with time,even if other operating conditions and fluid proper-

ties remain constant. Flux decline which is notassociated with a concentration effect (i.e., con-centration polarization) can occur due to a foulantlayer build-up on the membrane surface whichadds resistance to permeation.

Membrane fouling is highly dependent on thenature of the feed stream and the extent of theconcentration. Fortunately, efficient and effectivemembrane cleaning and sanitization steps havebeen developed for a wide range of applications,permitting Amersham Biosciences hollow fibermicrofiltration and ultrafiltration membrane car-

tridges to be reused over numerous processcycles. Since these membranes are polysulfoneand are supplied in polysulfone housings withepoxy potting compounds, Amersham Biosciencesmembrane cartridges withstand a wide range ofcleaning and sanitizing chemicals and solution pH.

Basic flux recovery procedures are provided below,with a recommended protocol outlined on page 13.Optimization of the procedures in terms of chemi-cal concentration, recirculation time, temperatureand pH will typically be performed on a case-by-case basis. Even with stringent cleaning proce-dures and skilled operators, it may not be possibleto recover permeate flux to new cartridge levels.Rather, it is important that the trend of flux recov-ery over time be noted and that the permeatewater flux after cleaning be higher than the aver-age initial process permeate flux. Use initial cleanwater flux as a benchmark for comparison.

Flux RecoveryCleaning Procedures

Cleaning formulations and the frequency andduration of cleaning cycles are dependent upon thestream being processed, the degree of fouling, theextent of the concentration, etc. In general,cleaning should be performed at low pressure andmoderate velocity, at temperatures of 40 to 50 C.Typical cleaning formulations for processing ofbiologicals and for general process applicationsare listed in the following tables. Alternativecleaning regimes for each process are provided inthe tables on pages 11 and 12.

In performing these cleaning procedures, one shouldtake into account the following considerations:

1. Flushing/Rinsing/Draining. Before cleaning, flush

residual feed from cartridge with clean warm(50 C) water, saline or buffer solution. Usebuffer solution to prevent precipitation ofsolutes (e.g., proteins) during flushing. Aftercleaning, rinse residual cleaning agent from thecartridge. These steps are best performed in anon-recirculating mode, such that the flush/rinsewater does not re-enter the system. Rinse times/ volumes are greatly reduced by thoroughly drainingboth the cartridge (including the permeate area) andthe system.

2. Water Quality. Cleaning and flush/rinse water

should contain


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Cleaning Procedures

* NaOCl concentration varies by membrane type. Refer to Table on page 19 for allowable NaOCl concentrations.

Preferred operating conditions for Flushing (prior to cleaning), Cleaning and Final Rinse are provided on page 13.

Blood & SerumProducts,Enzymes,Vaccines,Protein Products

Proteins,Lipoproteins,Lipids

A. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.5N NaOH at 50 C, 1 hr.3. Flush with clean water. Optional: 4. Circulate NaOCl* at 50 C, pH 10-11, 1 hr.5. Flush with clean water.

B. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.1% Tween 80 at 50 C, p H 5-8, 1 hr.3. Flush with clean water.

C. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.2% Terg-A-Zy me at 50 C, p H 9-10, 1 hr.3. Flush with clean water.

Process FoulantsAlternate Cleaning Procedures

in Order of PreferenceMammalian CellCulture

Cell Debris A. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate NaOCl* at 50 C, pH 10-11, 1 hr.3. Flush w ith clean w ater.

B. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.5N NaOH at 50 C, 1 hr.3. Flush w ith clean w ater.

C. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.2% Terg-A-Zy me at 50 C, pH 9-10, 1 hr.3. Flush w ith clean w ater.

Bacterial CellWhole Broths

Proteins,Cell Debris,Polys accharides,Lipids, Antifoams

A. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.5N NaOH at 50 C, 1 hr.3. Flush w ith clean w ater. Optional: 4. Circulate NaOCl* at 50 C, pH 10-11, 1 hr.5. Flush w ith clean w ater.

B. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.2% Terg-A-Zy me at 50 C, pH 9-10, 1 hr.3. Flush w ith clean w ater.

C. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.5% Henkel P3-11 at 50 C, pH 7-8, 1 hr.3. Flush w ith clean w ater.

Bacterial CellLysates

Proteins,Cell Debris

A. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.5N NaOH at 50 C, 1 hr.3. Flush w ith clean w ater. Optional: 4. Flush w ith H 3PO 4 at 50 C, pH 4, 1 hr.5. Flush w ith clean w ater.

B. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate NaOCl* at 50 C, pH 10-11, 1 hr.3. Flush w ith clean w ater. Optional: 4. Circulate H 3PO 4 at 50 C, pH 4, 1 hr.5. Flush w ith clean w ater.

C. 1. Flush with clean water, buffer or saline at 50 C.2. Circulate 0.1% Tween 80 at 50 C, pH 5-8, 1 hr.3. Flush w ith clean w ater.


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Cleaning Procedures (continued)

* NaOCl concentration varies by membrane type. Refer to Table on page 19 for allowable NaOCl concentrations.

Preferred operating conditions for Flushing (prior to cleaning), Cleaning and Final Rinse are provided on page 13.

Other cleaners available from:H. B. Fuller CompanyMonarch DivisionMinneapolis, MN(612) 781-8071.

Sodium Hydroxide,Phosphoric Acid,Nitric Acid,Citric AcidandTween-80 [Polyoxyethylene (20)sorbitan monooleate] areavailable from Lab and ChemicalSupply Houses.

Micro is available fromInternational Products Corp.PO Box 70, Burlington, NJ(609) 386-8770.

Terg-A-Zyme manufactured byAlconox, Inc., NY, NY(212) 532-4040,is available from Lab Supply Houses.

Sodium Hypochlorite(5% = 50,000 ppm NaOCl) isHousehold Bleach.

Process Foulants Alternate Cleaning ProceduresJuice andBeverageClarification

Protein, Pectin,Colloids, Tannins,Poly phenolics

A. 1. Flush with clean water.2. Circulate 0.5N NaOH at 50 C for 1 hour.3. Flush with clean water. Optional:

4. C irculate NaOCl* at 50 C, p H 10-11 for 1 hour.5. Flush with clean water.

B. Substitute 0.2% Terg-A-Zyme , 50 C,pH 9-10 for NaOH.

Dairy Protein, InsolubleCalciumComplexes

A. 1. Flush with clean water.2. Circulate H 3PO 4 at 50 C, pH 3.5-4 for 20 minutes.3. Flush with clean water.4. Circulate 0.5N NaOH at 50 C for 20 minutes.5. Flush with clean water.6. C irculate NaOCl* at 50 C, p H 10-11 for 1 hour.

Monitor and maintain chlorine level.7. Flush with clean water.

Water Treatment Iron Complexes A. 1. Flush with clean water.2. Circulate Citric Acid at 50 C, pH 2-2.5 for 1 hour.3. Flush with clean water. O ptional: if low water flux,4. Circulate a low foaming alkaline cleaner for 20 min.5. Flush with clean water.

Mineral Scale A. 1. Flush with clean water.2. Circulate HNO 3 at 50 C, pH 4 for 1 hour.3. Flush with clean water. Optional: 4. Repeat Step 2 and leave soaking overnight.5. Flush with clean water.

B. Substitute H 3 PO 4 , 50 C, pH 4 for HNO 3 .

Edible Oils O il, Grease,Colloids

A. 1. Flush with clean water.2. Circulate 0.2% Micro at 50 C, p H 9-10 for 1 hour.3. Flush with clean water. Optional: 4. If iron fouling is suspected, wash with Citric Acid,

pH 2-2.5, as noted abov e.

B. Sub stitute alternate detergent cleaners for Micro .Increase detergent concentration.


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Cleaning Procedures (continued)

Storage

Ultrafiltration cartridges must be stored wet or re-glycerized. Before storage the cartridges should bethoroughly flushed, cleaned and rinsed with cleanwater. For short-term storage, up to two weeks,cartridges need only be water-wet.

For storage up to 1 month, cartridges may be filledwith a storage solution and sealed at all endfittingsand permeate ports, or submerged in a storage bath.Acceptable storage solutions are:

1. Water with 5 to 10 ppm active chlorine (10 to20 ppm sodium hypochlorite). Monitor levelsweekly.

2. 0.1 N sodium hydroxide.3. Up to 3% formalin.4. 30% ethanol in water.5. Up to 1% sodium azide.

For storage of longer than 1 month, check periodicallyto be certain that the membranes remain wetted.

Prior to reuse it is recommended that the cartridge berinsed with a 100 ppm sodium hypochlorite solution.

Thoroughly rinse all storage solution prior to reuse.

Microfiltration cartridges may be stored dry, aftercleaning. It is advisable to clean and sanitize themicrofiltration cartridges prior to reuse. If necessary,to fully wet the membranes after extended storage,expose the membranes [inside and outside] to 70%alcohol for one hour. Drain, wet with water and rinse.

* See Shear Rate Table on page 20.** Total Recycle = Return both retentate and permeate streams to the feed reservoir.

Depyrogenation

For depyrogenation, throughly clean, sanitize andrinse the membrane cartridges, then recirculate eitherof the following for 30 to 60 minutes at 30 to 50 C.Then throughly drain & flush with non-pyrogenic water.

1. 100 ppm sodium hypochlorite, pH 10 to 11.2. 0.1N to 0.5 N sodium hydroxide, pH 13.

Flushing and Rinsing Protocols are listed in Table above.

Sanitization

For sanitization, throughly clean and rinse the mem-brane cartridges, then use any of the following:

1. Up to 100 ppm* sodium hypochlorite.If properly cleaned, 10 ppm should be sufficient.Circulate 30 to 60 minutes.

2. Up to 3% formalin.Circulate 30 to 60 minutes.

3. Up to 0.5 N sodium hydroxide.Circulate 30 to 60 minutes.

4. 100 to 200 ppm peracetic acid.Circulate 30 to 60 minutes.

5. Up to 70% ethanol in water.6. Autoclave (see page 14).

*100 ppm active NaOCl = Household bleach diluted 250:1 with water.

Operation Recommended Protocol*Flush A. Recirculate clean water or buffer in "total recycle"** for 10 minutes at 8000 to

16000 sec-1 shear rate, with 5 psig (0.3 barg) outlet pressure. Typical solutionconsumption is 3 to 4 times the system hold-up volume.

B. Drain solution.

Clean C. Recirculate cleaning solution in "total recycle" at 4000 to 8000 sec-1 shear ratefor 30 to 60 minutes with 5 psig (0.3 barg) outlet pressure. Typical solutionconsumption is 3 to 4 times the system hold-up volume.

D. Drain solution.

Rinse E. Recirculate clean water or buffer in "total recycle" for 5 minutes at 8000 to16000 sec-1 shear rate, with 5 psig (0.3 barg) outlet pressure. Typical solutionconsumption is 2 times the system hold-up volume.

F. Drain solution.

G. Repeat rinse water recirculation/drain steps "E" & "F" two more times.

H. Rinse both retentate and permeate sides with clean water/buffer, controllingthe permeate rate at 0.1 liters/minute/sq. ft. of membrane area. The retentateflow rate should be nominally 5 - 10% of the permeate flow rate.

I. It is preferred that the cartridge be oriented vertically and permeate beremoved from the upper permeate port.

J. Continue to rinse for 60 minutes. [Note: 60 minutes is a nominal time frame.To conserve water/buffer, time may be reduced to 30 minutes.]

Be certain that the sanitizing solution makescontinuous contact with all surfaces of concern.


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Page 14 2004

Autoclaving

Essentially all Amersham Biosciences UF and MF cartridge models with Housing Sizes 1 through 9 areautoclavable. Larger area UF and MF cartridges may be available in an autoclavable version so pleaseconsult with a Technical Service representative. In all cases, cartridges which have the suffix "A" in theirmodel number are autoclavable (e.g., CFP-2-E-3 A, UFP-100-E-55 A) .

Autoclaving Considerations:

a. RINSE GLYCEROL PRESERVATIVESOLUTION FROM NEW UF CARTRIDGES.Detailed instructions are provided on page 5.The cartridge must be rinsed, soaked andrinsed again to fully remove the glycerol.

b. Do NOT shock cartridges while fully wet withwater or while hot.

c. NEVER expose a warm cartridge to coldprocess fluids. ALWAYS allow cartridge tocompletely cool prior to use.

It is prudent to maintain a spare cartridge on-site should cartridge life be exceeded or autoclave cycle temperature drift too high.

d. LOOSEN all clamps before autoclaving.

e. For reuse, cartridges should only be autoclavedAFTER thorough cleaning confirmed by waterflux recovery. Due to the thermal stability ofpolysulfone, water flux values before and afterautoclaving should be similar.

Recommended Autoclave Procedure Steps as Depicted in Graphs on Page 15.[Starting Pressure = 14.7 psia; Starting Temperature = Ambient Room Temperature]

Be certainthat autoclave

temperature doesnot drift above

124 C.

Step

#

CumulativeTime

(minutes)

End of StepPressure

(psia)

End of StepTemperature

(C) Comments

Slow Warm-up

1 0 0.7 20 Pull vacuum over 6 min. in ~ 5 in Hg increments.2 6 2.7 60 Inroduce steam over several minutes.3 9 1.2 40 Pull vacuum over 3 minutes.

4 14.5 4.7 70 Introduce steam over 5.5 minutes.5 15.5 2.7 60 Pull vacuum over 1 minute.6 21.5 10.5 90 Introduce steam over 6 minutes.7 22.5 4.7 70 Pull vacuum over 1 minute.

8 28.5 14.7 100 Introduce steam over 6 minutes.9 31 10.5 90 Pull vacuum over 2.5 minutes.10 37 25 115 Introduce steam over 6 minutes.11 43 14.7 100 Pull vacuum over 6 minutes.

Residual Air Reduction and Temperature Equalization 12 50 33.7 124 Introduce steam over 7 minutes.

13 58 14.7 100 Pull vacuum over 8 minutes.14 65 33.7 124 Introduce steam over 7 minutes.15 72 14.7 100 Pull vacuum over 7 minutes.

Ramp-up and Dwell at Autoclave Temperature 16 79 33.7 124 Introduce steam over 7 minutes.

17 119 33.7 124 Dwell for up to 40 minutes.

Gradual Cool-down 18 132 14.7 100 Stop steam introduction, open bleed valve.19 150 5.7 55 Slow cool down with vacuum.20 ----- Cool cartridge completely before integrity testing.

(at least 3 hours, preferably overnight).


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Page 152004

The number of autoclave cycles validated by Amersham Biosciences is guaranteed on apro-rated basis provided an autoclave cycle which meets our approved criteria is employed.If in doubt, please submit a printout of the time/temperature/profile for our review. In practice,strict attention to proper autoclave procedures may permit 10 or more cycles per cartridge.

Autoclaving

Temperature as a Function of Time for Amersham Biosciences Recommended Autoclave Cycle

Pressure as a Function of Time for Amersham Biosciences Recommended Autoclave Cycle

See step by step description in table on page 14.

Note: Cartridge life is a function of autoclave operating cycle,temperature, cycle time and number of cycles.


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Page 16 2004

BackFlushing

Hollow fiber cartridges offer the advantage ofbackflushing for cleaning and flux recovery. Mem-branes may be backflushed with permeate atpressures of up to 10 psig provided a low velocity(about 25% of the feed rate) is used and tempera-ture is ambient (i.e.,


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Page 172004

E X P E R I M E

N T A L T E S T D A T A L O G

S H E E T

L u m e n

D i a m e

t e r

( m m

) :

C a r t r i

d g e M

o d e

l # :

M e m

b r a n e

A r e a

( m 2 ) :

P o r e

S i z e :

F e e

d S t r e a m :

p H :

T e m p e r a

t u r e

( C ) :

P a g e

___

o f

___

D a

t a T a

k e n

b y

_______

Feed

Perm.

Feed

D i a f i l t r a t i o n

Feed

Pressure

Volume

Volume

Conc.

Volume

Temp

Flow

In

Out

Perm

TMP

Permeate Flow

Date

Time

(liter)

(liter)

Factor*

(liter)

(C)

(lpm

)

(psig)

(psig)

(psig)

(psig)

(cc/min)

(lmh)

Comments

Initialclean water flux.

* F e e

d C o n c e n

t r a

t i o n

F a c

t o r = T

o t a l v o

l u m e o

f f e e

d s o

l u t i o n a

d d e

d t o t h e

f e e

d t a n

k

T o

t a l v o

l u m e o

f f e e

d r e m a

i n i n g

i n t h e

f e e

d t a n

k .

D i a f i l t r a

t i o n v o

l u m e s a r e n o

t i n c

l u d e

d i n t h e

F e e

d C o n c e n

t r a

t i o n

F a c

t o r c a

l c u

l a t i o n .


18/28

Page 18 2004

Quality Assurance

Stringent air diffusion specifications assure cartridge integrity.

Amersham Biosciences offers hundreds of UF and MF cartridge options with a range of lumen diameters,pore sizes, path lengths, active areas and endfitting connections. These products serve laboratory throughprocess-scale requirements of applications as varied as cell lysate clarification and protein concentration.Hence, this Operating Guide can only provide the basic considerations for membrane cartridge operation.Optimization of both operating criteria and cleaning regimes are, by definition, case specific.

All Amersham Biosciences membrane productsare subjected to stringent quality control standards

to assure the utmost product integrity and consis-tency.

Amersham Biosciences quality control tests everycartridge prior to shipment. QC tests covermembrane pore size determination and integrity ofthe membrane as well as integrity of the completecartridge assembly.

For ultrafiltration products, each membrane lot ischecked for rejection of one or more standardmarkers, and clean water flux measurements aretaken. Finished cartridges are pressure tested forintegrity. Water flux and air diffusion measure-ments are recorded on a representative lot basis.Amersham Biosciences air diffusion standards areapproximately three times as stringent as anyother manufacturer in the industry.

For microfiltration products, each membranecartridge is bubble point tested for pore sizedetermination, and clean water flux measurementsare taken on a representative sample of car-tridges.

All Amersham Biosciences cartridges are pressurestressed prior to shipment. Ultrafiltration car-tridges are stressed above their normal operatingpressure limit. Microfiltration membranes arestressed to their bubble point.

The combination of clean water flux data, chemical marker rejection data and air diffusion test data clearly define both the pore size of ultrafiltration membrane fibers and the integrity of the membrane cartridge. Clean water flux data and bubble point measurements fully define microfiltration membrane pore size.

All membrane and cartridge assembly methodsare thoroughly documented with SOPs andsubscribe to basic GMP guidelines. Each car-tridge is assigned a unique serial number topermit tracking of raw material, performance dataand customer location. Certificates of analysisare available upon request.


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Page 192004

Operating Parameters

Membrane life is dependent upon feed pressure, thermal stress, pH & feed composition.

** Household bleach (e.g., Clorox ) contains ~5% (50,000 ppm) NaOCl. Active chlorine = one-half the concentration (ppm) of NaOCl. Thus, 100 ppm = 250:1 dilution of bleach in water.

* Operation at higher temperature decreases maximum allowable pressure. Contact Amersham Biosciences for guidelines.

psig x 0.06895 = barg

Key Performance Charts


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Page 20 2004

Feed Stream Flow Rate

The feed stream flow rate has a major effect on permeate flux. Guidelines for therecirculation flow rate through the cartridges are provided in terms of cartridge size,lumen diameter and shear rate. The pressure drop across the length of a cartridgeis a function of the feed flow rate and may be used in lieu of a flowmeter to deter-mine the recirculation rate.

Shear rates and flow rates are directly proportional. Highly fouling streams may require flow ratesequivalent to a shear rate well in excess of 8,000 sec -1. Shear rates based on viscosity of 1 cp.

For laboratory-scale cartridges, measuring both the permeate and retentate flowrates with a stopwatch and graduated cylinder and simply adding them together willprovide the feed flow rate.



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Page 212004

IMPORTANT NOTES TOFEED FLOW RATE vs. P TABLES

P for cartridge only.Pressure drop through piping and valves must be added.Nominal values, water, 20 C.Temperature and viscosity of solution affect pressure drop.Figures are for LAMINAR flow.IN LAMINAR FLOW, PRESSURE DROP IS A LINEAR FUNCTION OFRECIRCULATION RATE.


Feed Stream Flow Rate vs. Cartridge Pressure Drop

)C02,retaW(P.svetaRwolFdeeF

gnisuoHeziS eziS eziS eziS eziS

lanimoNDInemuL DInemuL DInemuL DInemuL DInemuL

)mm( )mm( )mm( )mm( )mm(

lanimoNwolFdeeF wolFdeeF wolFdeeF wolFdeeF wolFdeeF

erusserPporD porD porD porD porD

)nim / sretil( )gisp(

M3

5.052.0 3.3

5.0 6.6

16.0 9.1

2.1 1.4

M2X3 .052.0 7.5

5.0 4.11

M4,4

5.02.1 2.3

3.2 6.6

1 5.2 0.25 0.4

M2X4 .02.1 7.5

3.2 4.11

5

5.03.4 7.2

6.8 4.5

18 6.1

61 4.3

6

5.03.4 3.5

6.8 7.01

57.06.5 0.4

2.11 0.8

18 1.3

61 3.6

9

5.06.01 0.5

5.12 01

57.081 7.3

53 6.7

15.42 9.2

94 0.6

)C02,retaW(P.svetaRwolFdeeF

gnisuoHeziS eziS eziS eziS eziS

lanimoNDInemuL DInemuL DInemuL DInemuL DInemuL

)mm( )mm( )mm( )mm( )mm(

lanimoNwolFdeeF wolFdeeF wolFdeeF wolFdeeF wolFdeeF

erusserPporD porD porD porD porD

)nim / sretil( )gisp(

,A53,53,MTS5373,OMS53

52.081 8.463 7.9

5.062 6.235 3.5

106 6.1021 3.3

,R55,A55,55

OMS55,MTS55

5.062 3.535 6.01

57.004 0.4

08 0.8

106 0.3

021 1.9

R57,57

5.062 1.9

35 3.81

106 2.5

021 61

54 5.055 3.3

111 6.6

MSM56,56

5.055 2.5

111 5.01

1 221 0.3542 0.9

58

5.055 01

111 02

1221 7.5

542 71

M251

5.0021 7.5

042 5.11

1082 3

065 9

M451

5.0021 11

042 22

1082 7.5

065 71


22/28

Page 22 2004

= (P inlet + P outlet )/2 P permeateTransmembranePressure

Liters/min 3.785 = US gal/min psig x 0.06895 = bargIMPORTANT NOTES:

1. Values at noted average TMP, 25 C.2. Values are nominal.3. Values to be adjusted for actual pressure.4. Values to be adjusted for actual temperature.5. Permeate flow rates only valid at low pressure.

This table of nominal water flux is only valid with clean water. Particulates, bacteria anddissolved metals in the feed water will all lower membrane cartridge productivity values.

Clean water is defined as 10,000 NMWC (or tighter) UF permeate or WFI.

The high porosity of Amersham Biosciences microfiltration mem-

branes results in exceptional water permeability values for thesehollow fibers. Accurate permeate flow rates on a cartridge basis canonly be achieved with inlet pressures of a few inches of water mea-sured on a manometer, thus eliminating pressure gauge inaccuraciesat the extremes of the scale, parasitic pressure drop and permeateback pressure from the transmembrane pressure calculation. Since itis both impractical and unnecessary to measure MF cartridge produc-tivity with such accuracy, it is suggested initial clean water flux undera set of reproducible conditions be utilized to characterize the MFcartridge performance. In addition, a bubble point test can be per-formed to verify MF membrane pore size.

tnioPelbbuBFMmuminiM ])grab(gisp[tnioPelbbuB

eroPeziS

05:05O2H:HOtE

%001API

1.0 ]4.2[53 ]6.1[42

2.0 ]2.1[81 ]8.0[21

54.0 ]8.0[21 ]5.0[8

56.0 ]4.0[6 ]72.0[4


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Page 232004

Cartridge Physical PropertiesXampler Laboratory Cartridges

Amersham Biosciences offers cartridge sizes to meet laboratory, pilot and production scales. Cartridges areeasily manifolded together to achieve any process flow requirement. Our smaller, Xampler cartridgesaccept flexible tubing for both feed and permeate connections.

1/4-inTubingNipple

3/8-inTubing Barb

3/8-inTubingNipple

4

Note: VirA/Gard Cartridges (prefix VAG) have slightly reduced cartridge membrane area from standard cartridges. Please refer to Selection Guide for currently available models and their corresponding membrane areas.

1/2-in

SanitaryConnector

4M, 4X2M

3M, 3X2M

1/2-inSanitaryConnector

Sanitary, tri-clamp fittings mate with adaptor fittingsthrough the use of gaskets and clamps. Adaptorconnection to a sanitary fitting is depicted below.

Conversion from 1/2-in or 1-1/2-in sanitary connections to tubing barb connections.

Sanitary Gasket

Adaptor fromSanitary Connection

to Tubing BarbCartridge End with

SanitaryConnection

Sanitary Clamp


24/28

Page 24 2004

Cartridge Physical PropertiesPilot/Process Scale Cartridges

Pilot and process scale cartridges are available in a full range of lumen internal diameters and membraneareas. Membranes are also offered in several housing configurations that retrofit competitive hollow fibercartridges.

1-1/2-inSanitary

Connector

55R, 75R

R EndfittingConnector

35, 55, 751/2-inTubingNipple

8, 9

1-1/2-inSanitaryConnector

1/2-inTubingNipple

5, 6


1-1/2-inSanitary

Connector



25/28


Page 252004

Cartridge Physical PropertiesMaxCell & ProCell Large Process Scale Cartridges

MaxCell and ProCell cartridges are our largest elements. With 0.5 mm ID fibers, MaxCell cartridgesprovide up to 140 sq. ft. (13 sq. m.) of membrane area in a single, lightweight housing. MaxCell cartridgeshave an integrally-bonded threaded ring at each end. A sealing gasket (o-ring) and adaptor to 2-in tri-clamp are positioned on each end and secured with a locking nut. The nut is easily tightened with aMaxCell wrench set. Permeate ports on the MaxCell cartridges are 1.5-in tri-clamp.

MaxCell Cartridge

ProCell cartridge elements require stainless steelhousings for operation. These 6-in diametermodules provide 300 sq. ft. (28 sq. m.) of mem-brane area with 0.5 mm ID lumen fibers.

MaxCell cartridges can easily retrofit competitive 5-inch diameter cartridges.

45, 65, 85


LockingNut

O-ring Adaptor

2-in SanitaryConnector

ProCell Cartridge

with SS Housing

152M, 154M

1-1/2-inSanitary

Connector

2-in SanitaryConnector

O-ring

Adaptor Clamp

MaxCellCartridge

CompetitiveCartridge


26/28

Page 26 2004

Key Performance Charts for 2 & 3 mm ID Tubules

Amersham Biosciences manufactures both 2 and 3 mm ID tubules to complement its line of hollow fibermembranes. These polysulfone tubules are available in ultrafiltration pore sizes of 30,000 NMWC,100,000 NMWC and 500,000 NMWC. A 0.1 micron microfiltration membrane is provided in the 2 mm tubule

diameter. These products are typically used in food, beverage and industrial applications; hence, their KeyPerformance Charts are segregated from the general bio/pharm information provided elsewhere in thisOperating Guide.

Pressure drop for cartridge only.Pressure drop through piping and valves must be added.Nominal values, water, 20 C.Solution temperature and viscosity affect pressure drop.T = Figures are for TURBULENT flow.


27/28


Page 272004

Chemical Resistance

In general, Amersham Biosciences polysulfone membrane cartridges are resistant to aqueous mineral acids,alkalis and salt solutions. They are also resistant to most alcohols and aliphatic hydrocarbons, as well asdetergents and hydrocarbon oils. Polar organic solvents such as ketones, chlorinated hydrocarbons and

aromatic hydrocarbons should be avoided. Conservative guidelines are presented below.These guidelines are based on normal operating conditions and ambient temperature ( 25 C)adjustmentsin pressure and/or temperature or presence of other components in the feed solution may alter these recom-mendations. When at or near the acceptable upper concentration limit for solvents, maximum pressuresshould be reduced by 25%. Questions pertaining to higher chemical concentrations or membrane resistanceto chemicals not listed should be addressed to our Customer Service personnel.

Chemicals noted as Short Term Only are typicallyacceptable for membrane cleaning.

* Higher alcohol concentrations acceptable depending on operating conditions. 100% alcohol acceptable for non-pressurized exposure.

A/G Technology Polysulfone Membrane Cartridge Chemical Compatibility Reagent Usage Reagent Usage

Acetic Acid (5%) Short Term Only Isopropyl Acetate Not RecommendedAcetic Anhydride Not Recommended Isopropyl Alcohol ( 10%)* Acceptable

Acetone Not Recommended Kerosene Not RecommendedAcetonitrile ( 10%) Short Term Only Lactic Acid ( 5%) Acceptable

Aliphatic Esters Not Recommended Mercaptoethanol ( 0.1M) AcceptableAmines Not Recommended Methyl Alcohol ( 10%)* Acceptable

Ammonium Chloride (


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Operating Handbook - Howllow Fiber Cartidges for Membrane Separations

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