CA1282565C - Process for surface modifying a microporous membrane - Google Patents

Abstract

ABSTRACT

Producing a surface modified skinless polyamide microporous filter membrane by providing a dope solution of a membrane forming polyamide polymer in a solvent system comprising a mixture of at least one solvent and one non-solvent for the polyamide polymer, and a surface modifying amount of a surface modifying agent having surface adsorption and/or sequestration effects which modifies the surfaces of the microporous filter membrane, combining the dope solution with additional non-solvent for the polyamide polymer for a time sufficient to precipitate said surface modified membrane from said dope solution, and casting the dope solution on a substrate. The filter membrane comprises a polyamide microporous membrane and a water-suspendable surface modifying agent having surface adsorption and/or sequestration effects which modifies the surfaces of the microporous membrane and is bonded to substantially all of the wetted surfaces of the membrane.

Description

,82S65 _ELATED APPLICATIONS
This application is related to U.S. Patent No. 4,473,474 issued September 25, 1984, entitled "Charge Modified Microporous Membrane, Process for Charge Modifying Said Membrane and Process for Filtration of Fluid", to Ostreicher.
This application is also related to United Scates Patent No. 4,473,475 issued September 25, 1984, enti-tled "Charge Modified Microporous Membrane, Process for Charge Modifying Said Membrane, and Process for Filtration of Fluid", to Barnes, Jr. et al.
This application is further rela-ted to U.S. Patent No. 4,604,208 issued August 5, :L986, ent:Ltlecl "Anionic Charge ModiEied Microporous Membrarle, Process Eor Char~e ModlEying Said Micro-porous Membrane and F:L:Ltratlon of Fluid", to Chu eL al.

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BACKGROUND OF T~E I~VENTION
1. Field of the Invention This invention relates to microporous membranes, and more particularly to surface modified microporous mem-branes suitable for the filtration of aqueous fluids, such as biological liquids.

2~ Prior Art Microporous membranes are well known in the art.
For example, U.S. Patent No. 3,876,738 to Marinaccio et al.
(1975) describes a process for preparing a microporous mem-brane, for e~ample, by quenching a solution of a film forming polymer in a non-solvent system for the polymer. European Patent Application 0 005 536 to Pall (1979) describes a similar process.
Commercially available microporous membranes, for example, made of nylon, are available ~rom Pall Corporation, Glen Cove, New York under the trademark "ULTIPOR N66". Such membranes are advertlsed as useful for the sterile filtration of pnarmaceuticals, e.~. removal of microorganisms.
Various studies in recent years, in particular Wall~
hausser, Journal of Parenteral Drug Association, June, 1979, Vol. 33, #~, pp. 156-170, and Howard et al, Journal of the Parenteral Dru~ Association, March-April, 1930, Volume 34, ~2, p~. 94-102, have reported the phenomena of bacterial breakthro-l~h in filtration media, in spite of the fact that the media had a low micrometer rating. For example, commer-clally available membrane filters for bacterial removal are typically rated as havin~ an effective micrometer rating for ~he microre~iculate membranes structure of 0.2 micrometers or less, yet such membranestypically have only a 0.357 effec-tlve micrometer rating for spherical contaminant particles, even ~vhen rated as absolute for Ps. diminuta~ the conven-tlonal tes~ for bacterial retention. This-problem of pas-sa~e of a few microor~anisms under certain conditions has been rendered more severe as the medical uses of filter I~ ~,v~
membranes ~ increased.

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Ona method of addressing this problem is to prepare a tlghter fllter having a sufficiently small effective pore dimension to capture microorganisms, etc., by mechanical sievin~. Such microporous membranes of 0.1 micrometer rating or less may be readily prepared but flow rates at conventional ~ressure drops are prohibitively low. Increasing the pressure drop to provide the desired flow rate is not generally feasi-ble because pressure drop is an inverse function of the fourth power of pore diameter.
It has lon~ been recognized that adsorptive effects can enhance the capture of particulate contaminants. For example, Wenk, "Electrokinetic and Chemical Aspects of Water Filtration", Filtration and Separation, May/June 1974, indi-cates that surfactants, pEI, and ionic strength may be used in various ways to improve the efficiency of a filter by mo-difying the charge characteristics of either the suspension, fllter or both.
It has also been su~ested that adsorptive seques-tration tparticlo capture within pore channels), may some-times be more important in sterile filtration than bubble poinc characterization of internal geometry (representing tne "largest pore"). See, e.g., Tanny et al, Journal OI the Parenteral Drug Assoclation, November-December 1978, Vol.
~1, #6, pp. 258-267 and January-February, 1979, Vol~ 33, #1, pp. 40-51 and Lukaszewicz et al, Id., July-August, 1979, Vol. 33, #4, Pl~- 187-194.
Pall et al, Colloids and Surfaces 1 (1980), pp.
~35-256, indicates that if the zeta potential of the pore walls of a membrane, e.g. nylon 66, and of the particles are ~oth low, or if they are oppositely charged, the particles wlll tend to adhere to the pore walls, and the result will ~e removal of particles smaller than the pores of the filter.
Pall et al suggest the use of membranes of substantially smaller pore size to increase the probability of obtaining microbial sterility in filtering fluids.

~2~3Z565 Zierdt, Applied and Environmental Microbiology, Dec~
1979, pp. 1166-1172, found a strong adherence by bacterla, yeast, erythrocytes, leukocytes, platelets, spores and polystyrene spheres to membrane materials during filtration through membranes with pore-size diameters much larger than the particles themselves.
~ierdt found that cellulose membranes adsorbed more bacteria, blood cells and other particles than did polycarbonate fil-ters. Of lesser adsorptive capacity were vinyl acetate, nylon, acrylic and TeflonTM membranes. Zierdt additionally found that solvent cast membrane filter materials, e.g. nylon, had strong surface charges, whereas ordinary fibrous cellulose materials which are not solvent cast do not.
Attempts to increase the short life of filter media due to pore blockage and enhance flow rates through Eilter media having small pores have been made by charge modifying the media by various means to enhance capture potential of the filter. For example, U.S~ Patents ~,007,113 and ~,007,11~ to Ostreicher, describe the use oE a melamine Eormaldehyde cat:ionic colloid to charge modify fibrous and particulate filter elements; U.S. Patent No. ~,305,782, to Ostreicher et al describes the use oE an inorganic cationic colloidal silica to charye modiEy ~uch elements. None oE-these reEererlces teaches or suyyests charge modiEy:irlg a synthetic organic po.lymer:ic microporous membrane, nor do any of the filtration media described thereln, e.g. Eiber and/or particulate, provide the advantayes oE such a membrane.
Similarly, U.S. Patent No. 3,2~2,073 (1966) and 3,352,42 (1967) to Guebert et al, describe removal of microorganisms from fluids by passage through a filter medium of conventional anionic type filter aid, e.g. diatomaceous earth, .

paper filter pulp, fullers earth, charcoal, etc., having an adsorbed c~tionic, organic, polyelectrolyte coatin~. The coated filter aid media is said to possess numerous cationic sites which are freely available to attract an~ hold parti-cles bearing a negative surface charge.
U.S. Patent No. 4,178,438 to Hasset et al (1979) describes a process for the purification of industrial efflu-ent using cationically modified cellulose containing material, e.~., bleached or unbleached pine sulphite cellulose, kraft sulphate cellulose, paper, cardboard products, textiles fibers made of cotton, rayon staple, jute, woodfibers, etc.
The cationic substituent is bonded to the cellulose via a ~roupin~ -0-C~2~N- , where the nitrogen belongs to an alnide ~rou~ of the cationic part and the oxygen to the cellulose part.
There are numerous references which describe the treatment of porous membranes for various objects. U.S.
Patent No. 3,556,305 to Shorr tl9?1) describes a tripartite nembrane for use in reverse osmosis comprising an anisotropic porous substrate, an ultra-thin adhesive layer over the porous substrate, and a thi~ di~usive membrane ~ormed over the adhesive layer and bounct to the substrate by the adhesive layer. ~uch anisotropic porous membranes are distinguished from isotro~ic, homo~eneous membrane structures used for microfiltration whose flow and retention properties are in de~endent of flow direction and which do not function properly ~ u hs ~ Je l/
when ~i~ed in the invention o~ Shorr.
U,S. Patent No. 3,556,992 to ,Uassuco (1971) describes another anisotropic ultra-filtration membrane having thereon an adherinJ coatin~ of irreversibly compressed gel.
U.S. Patent No. 3,808,305 to Gregor (1974) describes a charged membrane of macroscopic homogeneity prepared by pro-viding a solution containing a matrix polymer, polyelectro-lytes (for char~e) and a crosslinking agent. The solvent is ~, -i5 evaporated fron~ a cast film which is then chemically cross-linked. The membranes are used for ultrafiltration.
U.S. Patent No. 3,944,485 (1976) and 4,045,352 (1977) to Rembaum et al describe ion exchange hollow fibers produced by introducin~ into the wall of the pre-formed fiber, poly-merizable liquid monomers which are then polymerized to form solid, insoluble, ion exchan~e resin particles embedded within the wall of the fiber. The treated fibers are useful as membranes in water treat~ent, dialysis and generally to separate ionic solutions. See also U.S. Patent No. 4 ,014,798 to Hembaum (1977).
U.S. Patent No. 4,005,012 to Wrasidlo (1977) describes a process for producin~ a semi-permeable anisotropic membrane useful in reverse osmosis processes. The membranes are pre-pared by formin~ a polymeric ultra-thin film, possessing semi-permeable properties by contacting an amine modified polyepi-halohydrin with a polyfunctional a~ent and depositing this film on the external surface of à microporous substrate.
Preferred semi-permeable membranes are polysulfone, polysty-rene, cellulose butyrate, ce~lulose nitrate and cellulose acetate.
U.S. Pa~ent l`lo. 4,12$,~62 to Latty (1978) describes a coated semi-permeable reverse osmosls membra!le having an external layer or ¢oatin~ o~ a cationic polyelectrolyte pre-ferably poly~vinylimidazoline) in the bi-sulfate form.
U.S. Patent .~o. 4,214,020 to Ward et al (1980) de-scribes a novel method of coatin~ the exteriors of a bundle of hollow-fiber semi-permeable membranes for use in fluid se~arations. Typical polymers coated are polysulfones, poly-styrenes, polycarbonates, cellulosic polymers, polyamides and polyimides. Numerous depositable materials are listed, see col. 10, lines 55 - col. 12, for example, poly(epichlor-hydrin) or polyamides.
U.S. Patent No. 4,239,714 to Sparks et al (1980) descri~es a method of modifyin" the pore size distribution ~l2~ S65 of a separation media to provide it with a sharp upper cut-off of a preselected molecular size. This is accomplished by effectively blocking the entrances to all of the pores larger than a pre-selected desired cut-off size, but leaving unchanged the smaller pores. The separation media may be in the form of polymeric membranes, e.g. cellulose acetate, cellulose nitrate, poly-carbonates, polyolefins, polyacrylics, and polysulfones. The pores are filled with a volatile liquid which is evaporated to form voids at the pore entrances and a concentrated solution of a cross-linkable or polymerizable pore blocking agent, such as protein, enzyme, or polymeric materials is then applied to the surface of the membrane.
U.S. Pa-tent No. 4,250,029 to Kiser et al (1981) describes coated membranes having two or more external coatings of polyelectrolytes with at least one oppositely charged ad]acent pair separated by a layer oE material which is substantially charge neutralized. Kiser et al is primarily directed to the use of charged me~branes to repel ions and thereby prevent passage through the membrane pores. The coated membranes are described as ordinary semi-permeable memhranes used for ultrafiltratlon, reverse osmosis, elec-trod:ialys:Ls or o-ther Eiltration processes~ A ~icroscopic observatlon o.E-the coated membranes shows microscopic hills and valleys oE polyelectrolyte coak.ing Eormed on the original external smooth sk:Ln of the rnembrane. rl'he tnembranes are particularly useful for deioni~iny a~leous solutions. Preferred membranes are organic polymeric membranes used for ultrafiltration and reverse osmosis processes, e.g., polyimide, polysulfone, aliphatic and aromatic nylons, polyamides, etc. PreEerred membranes are anisotropic hollow fiber membranes having an apparent pore diameter of from about 21 to about 480 angstxoms.
Charge modified microporous filter membranes are disclosed in Canadian Patent No. 1,044,537 of Ostreicher, issued ~L~82~;6~ii December 19, 1978, (correspondlng -to Japanese Patent No. 923,649).
As disclosed therein, an isotropic cellulose mixed ester membrane, was trea-ted with a cationic colloidal melamine-formaldehyde resin to provide charge functionality. The mernbrane achieved only marginal charge modification. Additionally, the membrane was discolored and embrittled by the treatment, extractables exceeded desirable limits for certain critical applications, and the membrane was not thermally sanitizable or sterilizable. Ostreicher also suggests such treatment for the nylon membranes prepared by the methods described in U.S. Patent No. 2,783,894 to Lovell (1957) and U.S. Patent No. 3,408,315 to Paine (1968). It has been demonstrated that nylon microporous membranes treated according to said Ostreicher reference would also demonstrate marginal charge rnodification, high extractables and/or inability to be thermally sanitizable or sterilizable.
The afo.resaid Ostreicher U.S. Patent No. 4,473,474 (publ:ished as European 0050804 on May 5, 1982) generally deseribes a novel cationie charge modl~led mieroporous membrane comprising a hyclroph:i:Lic orgarlie polymerlc i~icroporous membrane ancl a charge modify:incJ amotmt o:E a prlmary catlonle eharge modi~ying agent bonded to substantla:L:Ly alL o~ the lnterna:L mierostructure of the memb.rane. ~`he prlmary chc~r-~e modl~yin~ agent ls a water-soluble organle polymer havlng a molecular weight greater than about 1,000 whereln each monomer thereof has at least one epoxlde group eapable of bondlng to the sur:~aee of the membrane and at least one ter-tia-cy amine or cluaternary ammonium group. Preferably, a portion of the epoxy groups on the organie polymer are bonded to a secondary charge modifying agent selected from the group consisting of:
i) aliphatic amines having at least one primary amino or at least two secondary amino groups; and -" ~21~25~i~

ii) aliphatic amines having at least one secondary amino and a carboxyl or hydroxyl substituent.

The membrane is made by a process for ca-tionically charge modifying a hydrophilic organic polymeric microporous membrane by applying to the membrane the aforesaid charge modifying agents, preferably by contacting the men~rane with aqueous solutions of the charge modifying agents. The preferred microporous membrane is nylon, the preferred primary and secondary charge modifying agents are, respectively, polyamido-polyamine epichlorohydrin and tetraethylene pentamine. The charge modified microporous membrane may be used for the filtration of fluids, particularly parenteral of biological liquids. The membrane has low extractables and is sanitizable or sterilizable.
The aforesaid Chu et al U.S. Patent No. 4,604,208 generally describes a novel anionic charge modified microporous membrane comprising a hydrophilic organic polymeric microporous membrane and a charge moclifying amount of anionie charge modifying agent bonded to suhstantiaL:Ly aLl of ~he membrane microstructure.
'rhe cmion:ic charge modiEying agent is preferably a water-soluble polymer having anionic f~tnctional groups, e.g. ccarboxyl, phos-phonous, phosphonic and s~lLfonic groups. '~'he charged me.mbrane is made by a process Oe applying the anion.ic charge modifying agent to the membrane, preEerably by contacting the membrane with aclueous solutions of the charge modifying agent.
The just described Patents describe a comparatively complex treatment of a preformed membrane requiring treatment, rinse and drying steps which involve complicated equipment and expensive capital investment.

OBJECl'S AND SUMM~RY OF T~E INVENTION
It is an object of this invention to provide a process for surface modifying a hydrophilic organic polymeric 325~iS

microporous membrane so as to provide a novel surface modi-fied micro~orous membrane, particularly suitable for the microfiltration of biolo~ical or parenteral liquids.
It is another object of this inventon to provide an isotro~ic, surface modified microporous membrane which pre-ferably has low extractables suitable for the microfiltration of biolo~ical or parenteral liquids.
I~ is yet another object of this invention to pre-pare a sanitizable or sterilizable microporous membrane ~or the efficient removal of bacteria, viruses and pyrogen from contaminated liquids.
A still further object of this invention is to pro-vide a process for enhancing the filtration, adsorptive and/or capacity of microporous membranes without affecting the internal microreticulate structure, I~ is still a further object o~ this invention to provide a process for producin~ a microporous membrane cap-a~le o~ ca~turin~ anionic or cationic particulate contaminant of a size smaller than the e~ective pore size of the membrane.
These and other obJects of thls invention are attained by a process for surEace rnodlfying a hydrophilic organic poly-meric microporous membrane by ~orming the membrane from a com~osition containin~ surface modifying a~ents. The pre-~`erred microporous membrane is nylon, the preferred surface modi~yin~ a~ents are ~olyamido-polyamine epichlorohydrin, ethylene diamine tetraacetic acid, carbon, silica and other chromato~ra~hic additives, poly (styrene sulfonic acid) and ~oly (acrylic acid).
The surface modified microporous membrane produced by tnis invention may be used for the microfiltration of fluids, particularly parenteral or biological liquids.

BRIEF DESCRIPTION OF THE FIGURES
Fi~ure 1 is a time vs. transmittance graph of mem-~ranes described in Example V.

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DETAlT~n DESCRIPTION OF THE INVENTION
The process of this invention produces a hydrophilic surface modified organic polymeric microporous membrane.
~ the use of the term "microporous membrane" as used herein is meant a skinless ("symmetric"), isotropic or anisotropic porous membrane having a pore size of at least .05 microns or larger, or an initial bubble point (IBP), as that term is used herein, in water of less than 120 psi. A maximum pore size useful for this invention is about 1.2 micron or an IBP of greater than about 10 psi. By "isotropic" it is meant that the pore structure is substantially the same throughout the cross-sectional structure of the membrane. By "anisotropic" is meant that the pore size differs from one surface to the other. mere are a number of commerc:ially available membranes nat encompassed by the term "microporous membrane" or "microfiltration membrane" such as those having one side foxmed with a very light thin s]cin layer (skinned, i.e. asymmetrlc) which is supported by a much more porous open structure which are typically used for reverse osmosis, ultra-Eiltratlon and dialysis. Thus, by the ~erm "microporous membrane"
or "microEiltratlon membrane" are mecmt membranes suitc~ble for the removal oE suspencled soLids arld par-ticulates from Eluids and which do not funct:ion as ultraEiltration or reverse osmosis membranes but which mc~ have adsorptive and/or se~uestration capac:ity.
By "surface IwdiEied microporous membranes" are meant microporous membranes which provide surface adsorption and/or sequestration effects in addition to the microfiltration effects of the membranes per se. By adsorptive surface, it is meant a surface that has controlled molecular geometry and/or surface functionality that allows species to be attached to the surface by means of ionic, covalent, hydrogen and/or Van Der Walls bonding and/or molecular geometric effects, e.g. ionic exchange, affinity, frontal, size exclusion and the like.

By the use of the term "hydrophilic" in describing the microporous membrane, it is meant a membrane which ad-sorbs or absorbs water. Generally, such hydrophilicity is produced by a sufficient amount of hydroxyl (OH-), carboxyl (-CO~H), amino (-NH2)~ (-C-NH-), and/or similar functional O
~rou~s on the surface of the membrane. Such groups assist in the adsor~tion and/or absorption of the water onto the membrane. Such hydrophilicity of the membrane and internal microstructure of the surface modified membrane of this invention is preferred in order to render the membrane more useful for the treatment of aqueous fluids.
Preferred microporous membranes are produced from nylon. The term "nylon" is intended to embrace film forming polyamide resins includin~ copolymers and terpolymers which include the recurring amido groupin~.
While, ~ellerally, the various nylon or polyamide resins are all copolymers o~ a diamine and a dicarbo~ylic aaid, or homopolymers of a lactam o~ an amino acid, they vary widely in crystalllnity or solid structure, melting ~oint, and other physical properties. Pre~erred nylons for use in this invention are copolymers of hexamethylene dia-mine and adipic acid (nylon 66), copolymers of hexamethylene diamine a,nd sebacic acid (nylon 610) and homopolymers of poly-o-caprolactam (nylon 6).
~ lternatively, these preferred polyamide resins have a ratio of methylen~ (CH2) to amide (NHCO) groups within the ran~e about 5:1 to about 8:1, most preferably a~out 5:1 to about 7:1. Nylon 6 and nylon 66 each have a ratio of 6:l, whereas nylon 610 has a ratio of 8:1.
The nylon polymers are available in a wide variety of ~rades, which vary appreciably with respect to molecular wel~ht, within the ran~e from about 15,000 to about 42,000 and in otner characteristics.

8.~S~;5 The highly preferred species of the unites composing the polymer chain is polyhexamethylene adipamide, i.e. nylon 66, and molecular weights in the range above about 30,000 are preferred.
To the extent that commercially available polymers contain additives such as antioxidants and the like, such additives are included within the term "polymer" as used herein.
The membrane substrates can be produced by modifying the method disclosed in U.S. Pa-tent No. 3,876,738 to Marinaccio et al or described in European Patent Application No. 0 005 536 to Pall.
The Marinaccio et al process for producing membrane develops a unique fine internal microstructure through the quench technique described therein, offering a superior substrate for filtration. Broadly, Marinaccio et al produces microporous films by casting or extruding a solution of a film-forming polymer in a solvent system into a quenching bath comprised of a non-solvent system for the polymer. Although the non-solvent system may eomprise only a non-solvent, the solvent system may eonsist of any combination of materials provided the resultant non-solvent system ls eapable o:E setting a film and is not cleleterious to the fo.rmed Eilm. For exc~mple, the non~solvent system may consist of materials sueh as water/salt, aleohol/salt or other solvent-chemical mixtures. 'I'he Marinaceio et al proeess is espee:ially effeetive for produeing nylon films. More speeifieally, the general steps of the proeess involve first forming a solution of the :Eilm-forming polymer, easting the solution to form a film and q~lenehing the film in a bath whieh ineludes a non-solvent for the polymer.
The nylon solutions which can be used in the MaLinaccio et al process include solutions of certain nylons in various solvents, such as lower alkanols, e.g., methanol, ~ "," ,~
:

e~hanol and butanol, including mixtures thereof. It is known that other nylons will dissolve in solutions of acids in which f~SC)~ be)~
it behavco as a polyelectrolyte and such solutions are useful.
Representative acids include, for example, formic acid, citric acid, acetic acid, maleic acid and similar acids which react with nylons through protonation of nitrogen in the amide group characteristic of nylon.
The nylon solutions after formation are diluted with non-solvent for nylon and the non-solvent employed is miscible with the nylon solution. Dilution with non-solvent may, according to Marinaccio et al, be effected up to the point of incipient precipitation of the nylon. The non-solvents are selected on the basis of the nylon solvent utilized.
For example, when water-miscible nylon solvents are employed, water can be employed. Generally, the non-solvent can be Methyl formatel aqueous lower alcohols, such as methanol and ethanol, polyols such as glycerol, glycols, polyglycols and ethers and esters thereof, water and mixtures of such com-pouncls. Moreover, salts can also be used to control solu-tion ~ro~erties.
The ~luenchin~ bath Inay or may not be comprised of the sa~e non-solvent selected for ~reparation of the nylon solution and may also contain small amounts of the solvent em~loyed in the nylon solution. However, the ratio of sol-vent to non-solven~ is lower in the quenchin~ bath than in the polymer solution in order thQt the desired result be obtained. The quenchinO bath may also include other non-solvents, e.g. water, The formation of the polymer film can be accomplished ~y any of the reco~nized methods familiar to the art. The ~referred method is castin~ usin~ a knife`edge which controls the thickness of the cast film. The thickness of the film will be dictated by the intended use of the microporous ~roduct. In genera1, the films will be cast at thicknesses in the range of from about 1 mil to about 20 mils, prefer-a~ly froln about 1 to about 10 mils.

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Preferably, the polymer solution is cast and simul-taneously quenched, although it may be desirable to pass the cast film through a short air evaporation zone prior to the quench bath. This latter technique is, however, not pre-ferred.
- After the polymer solution is cast and quenched, it is removed from the quench bath and preferably washed free of solvent and/or non-solvent. Subsequently the film can be at least partially dried.
Pall's aforementioned European Patent Application No. 0 005 536 describes another similar method for the con-version of polymer into microporous membrane which may be used. Broadly, Pall provides a process for preparing skin-less hydrophilic alcohol-insoluble polyamide membranes by ~reparing a solution of an alcohol-insoluble polyamide resin in a polyamide solvent. Nucleation of the solution is in-duced by the controlled a~dition to the solution of a non-solvent for the polyamide resin, under controlled conditions of concentration, temperature, addition rate, and degree of fl~itation to obtain a visible precipitate of polyamide resin particles (which may or rnay not partially or completely re-dissolve) thereby forming a castln~ solution.
The castin~ solution is then spread on a substrate to form a thin film. The film is then contacted and diluted with a mixtur~ of solvent and nonsolvent liquids corltaining a substantial proportion of the solvent liquid, but less than the proportion in the casting solution, thereby preci-~ltating polyamide resin from the casting solution in the form of a thin skinless hydrophilic membrane. The resulting mem~rane is then washed and dried.
In Pall's preferred embodiment of the process, the solvent for the polyamide resin solution is formic acid and the noasolvent is water. The polyamide resin solution film is contacted with the nonsolvent by immersing the film, car-ried on the substrate, in a bath of nonsolvent comprising water containing a substantial proportion of formic acid.

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rrhe nylon membranes described in Marinaccio et al and Pall are characterized ~y hydrophilic isotropic structure, having a high effective surface area and a fine internal microstructure of controlled pore dimensions ~ith narrow pore size distribution and adequate poxe volume~ For example, a representative 0.22 micrometer rated nylon 66 membrane (polyhexamethylene adipamide) exhibits an initial bubble point (IBP) of about 45 to 50 psid, a foam all over point (F~OP) of about 50 to 55 psid, provides a flow of from 70 to 80 ml/min of water at 5 psid (47 mm. diameter discs), has a surface area (BET, nitrogen adsorption) of about 13 m2/g and a thickness of about 4.5 to 4.75 mils.
As will be apparent from the foregoing description, both the Marinaccio and Pall processes involve the formation of a nylon polymer solution or dope which is then diluted with a non-solvent, cas-t on a suitable substrate surface and contacted with additional non-solvent to cause precipitation of the polyamide resin from the dope solution in the form of a thin skinless hydrophilic membrane.
In the afo:rement:Loned Patents to Ostreicher et al, Barnes et al and Chu et al, the resulting membrane is charge modified by contacting the formed mel~brane with a charge modifying amount of a charge mod:ifying agent. ~n the present invention, the surface modifying agent (which can be a cationi.c or anionic charge modifying agent) is incorpo.rated .into the polymer solution or dope before the membrane is precipitated~ rrhe membrane can thereafter be fo.rmed by the casting technique described in Marinaccio et al and Pall or alternatively, the dope can be introduced into the quenching bath of the non-solvent under shear to produce fibers of the surface modified membrane which can be formed into a sheet material similarly to the formation of paper from fibers, e.g. as described in U.S. Patent 4,309,247 to Hou et al (1982) or made into hollow fibers to produce surface m~dified hollow fibers.

2~3ZSÇ;~

The surface modifying agent is bound to the internal microstructure, preferably substantially all of the internal microstructure, of the microporous membrane. sy the use of the term "hound" is meant that the surface modifying agent is sufficiently attached to or incorporated into the membrane so that it will not be significantly extracted under the intended conditions of use. By the use of the term "substantially all of the internal microstructure" as used herein, is meant substantially all of the external surface and internal pore surfaces. Typically by this is meant the surfaces which are wetted by a fluid, e.g., water, passing through the membrane or in which the membrane is immersed.
The term "surface modifying agent" means a compound, material or composition which when bound to the membrane, alters its capacity to remove a desired entity from a fluid being filtered and which is compatible with the dope. By the use of the term "charge modifying agent", is meant a compound or composition that when hound to the microporous Eilter membrane alters the "zeta potential" of the membrane (see Knight et al, "Measuring the Electro]cinetic Properties of Charged Filter Media," Filtration and Sepc~ration, pp. 30-3~, ;lc~n./Feb. 19~1).
l'he cati.onlc charge ~lodi;Eier is a compound or composition which is capable of being bound to the membrane microstructure and provides a more posit:lve zeta potential to the membrane micro-structure. PreEerably, such cationic charge modifier is a water-soluble compound having substituents capable of binding to the membrane and substituen-ts which are capable of producing a more positive "zeta potential" in the use enviromnent (e.g. aqueous) or cationic functional groups. Most preferably, the agent may be a water-soluble organic polymer capable of becoming a non-extractable constituent of the membrane.

2~6~

The cationic charge modifying agent can also be cross-linked to itself or to the membrane polymer through a cross-linking agent, for example, an aliphatic polyepoxide having a molecular weight of less than about 500.
The cationic charye modifying agent may have either a high or low charge density, or anything between these extremes, however, high charge density is preferred.
The preferred cationic charge modifier is selected from the class of polyamido-polyamine epichlorohydrin cationic resins, in particular, those described in the following U.S. patents:
2,926,116 to Keim;
2,926,154 to Keim;

3,224,986 to Butler et al;
3,311,594 to Earle, Jr.;
3,332,901 to Keim;
3,382,096 to Boardman; and 3,761,350 to Munjat et al.
Broadly, these preerred charge modifiers (hereinafter "polyatnido-polyatnine epichlorohydrin") are produced by reacting a loncJ chain polyamide w:Lth epichlorohydrin, i.e. 1 - chloro-2,3 epoxypropane having the Eormula:
,0_ CII2 CH CH2Cl.

The polyamide may be derived frorn the reaction of a polyalkylene polyamine and a saturated aliphatic dibasic carboxylic acid containing from about 3 to 10 carbon atoms. The polyamide produced is watex-soluble and contains the recurring groups:

-N~I(CnH2n~)X-CORCO-56~

where n and x are each 2 or more and R is the divalent hydro-carbon radical of the dicarboxylic acid. This polyamide is then reacted with epichlorohydrin to form the preferred water-soluble charge modifiers used in its invention.
The dicarboxylic acids which may be used in preparing the polyaMides are the saturated aliphatic dicarboxylic acids containing from 3 to 10 carbon atoms each as malonic, succinic, glutaric, adipic, azelaic and the like. Blends of two or more of the saturated carboxylic acids may also be used.
A variety of polyalkylene polyamines including poly-ethylene polyamines, polypropylene polyamines, polybutylene polyamides and so on may be employed. More specifically, the polyalkylene polyamines are polyamines containing two primary amine ~roups and at least one secondary amine group in which the nitro~en atoms are linked together by groups of the formula - C~H2n-l where n is a small integer greater than unity and the number of such ~roups in the molecule ranges from two up to about eight. The nitrogen atoms may be attached to adjacent carbon atoms in the group -CnH2n_ or to carbon ato~s further apart, hut not to the same carbon atom. Polyamines suoh as diethylenetriamine, triethylene-tetrarnine, tetraethylene-pentamine, dipropylenetriamine, and the like, and mixtures thereo~ may be used. Generally, these polyalkylene polyamines have the general formula:
H2[(CnH2n)NH]yCn~l2nN~2 wherein n is an integer of at least 2 and y is an integer of 1 to 7.
In carryin~ out the reaction of the polyalkylene polyamine with the acid, it is preferred to use an amount of dicarboxylic acid sufficient to react substantially completely witn the primary amine groups of the polyalkylene polyamine but insufficient to react with the secondary amine groups to any subst~ntial extent. The polyamide produced is then re-acted with the epichlorohydrin to form the preferred poly-amido-polyamine epichlorohydrin charge modifying agent.

~282~;65 rrypically, in the polyamide-epichlorohydrin reaction it is preferred to use sufficient epichlorohydrin to convert all of the secondary amine groups to tertiary amine groups, and/or quaternary ammonium groups (including cyclic structures). Generally, however, from about 0.5 mol to about 1.8 moles of epichlorohydrin for each secondary amine group of the polyamide may be used.
The epichlorohydrin may also be reacted with a polyamino-ureylene containing tertiary amine ni-trogens to produce the primary charge modifying agents which may be utilized in this invention (see for example the aforementioned Earle, Jr.).
Other suitable charge modifying agents of the foregoing type may be produced by reacting a heterocyclic dicarboxylic acid with a diamine or polyalkylene polyamine and reacting the resultant product wlth epichlorohydrin (see for example the aforementioned Munjat et al.) The polyami.do-polyamine epichlorohydrin cationic resins are available commercially as Polycup 172, 1884, 2002 or S2064 (Hercules; Cascamide Resln p~-420 ~Borden); or Nopcobond 35 (Nopco). Most preferably, the poly~mido-polyamine epichlorhydrin resin is Polycup 1~84 or Hercules ~4308, whe.rein the charged nitrogen atom orms part o~ a heterocyclic group:ing and is bonded through methylene to a dependlny, reactive epoxide yroup. The terms Polycup, Cascamide, Nopcobond and Hercules are all trade-marks.

~ 25~5 Each monomer group in R 4308 has the general formula:

-_ CH _ --~ 2- CH CH

~,+ .

. ~ Cl-_ ~ CH3CH2-CH-CH2 O __ Polycup 172, 2002 and 1884, orl the other hand, have ~onomer groups of the general formula:
r- R Cl- - !
. ~ !
- -- Ctc~2)4 --- CNHCH2 CH2 --~ NCH2 - CH2NH -O O ' CH2 wherein R is methyl or hydrogen (Polycup 172 and 2002, R=H;
~nd Polycup 1884, R-CH3).
A secondary charge modifying agent may be used to enhance the cationic char~e of the primary charge modifying agent and/or enhance the bonding of the primary charge modi-fying a~ent. The secondary charge modifying agent may be selected from the group consistin~ of:
(i) aliphatic amines having at least one p.ri-mary amino or at least two secondary amino groups;
and , 56~

(ii) aliphatic amines having at least one secoadary amine and a carboxyl or hydroxyl sub-stituent.
Preferably, the secondary char~e modifyin~ agent is a polyamide having the formula:
H

H2N-(Rl-N~ R2--NH2 wherein R1 and R2 are alkyl of 1 to 4 carbon atoms and x is ar, inte~er from O to 4. Preferably, R1 and R2 are both ethyl.
Preferred polyamines are:
Ethylene diamine H2N-(cH2)2-NH2-NH2 ~iethylenetriamine H2N-(cH2)2-NH-(cH2)2-NH2 Triethylenetetramine H2N-(cH2-cH2-NH)2-cH2-cH2-NH2 Tetraethylenepentamine ~2N-(cH2-cH2-NH)3-cH2-cH2-NH2 The highly ~referred polyamine is tetraethylene pentamine.
Alternatively, aliphatic amines used in this inven-tion may have at least one secondary amine and a carboxyl or hydroxyl substituent. Exemplary of such aliphatic amines are ~amlna-amino-butyric acid (H2NCH2CH2CH2COOH) and 2-amino ethan~ 2Nc~2c~l2o~)-The secondary charge modifyinK agent is bonded tothe micro~orous membrane by bondin~ to a portion of the epoxide subs~ituents of the polymeric primary charge modifying agent.
The amount of primary and secondary cationic charge , , ~ modifying a~entsutilized is an amount sufficient to enhance the electropositive capture potential of the microporous membrane. Such an amount is hi~hly dependent on the speci-fic char~e modifyin~ents utilized. For general guidance, nowever, it has been iound that a wei~ht ratio of primary to secondary charge modifyin~ a~ent of from about 2:1 to about 5~U:1, preferably from about 25:1 to about 75:1 is generally sufficient.
In another embodiment of the present invention~ the foregoin~ "secondary" char~e modifyin~ agent can be used as ' , tne char~e modifying agent by the cojoint employment of an ali~hatic polyepoxide crosslinking agent having a molecular weight of less than about 500. Preferably, the polyepoxide is a di- or tri- epoxide having a molecular weight of from about 1~6 to about 300. Such polyepoxides have viscosities (undiluted) of less than about 200 centipoises at 25C. Due to the necessity of the epoxide to act as a crosslinking a~ent, monoepoxides, e.g. glycidyl ethers, are unsuitable.
Similarly, it is theorized that a polyepoxide offering greater than three epoxy groups offers no benefit and in fact may limit the coupling reactions of the polyepoxide by steric hindrance. Additionally, the presence of unreacted epoxide groups in the cationically charge modified micropor-ous membrane may be undesirable in the finished product.
Highly preferred polyepoxides have the formula:
R(O-C~2-CH~,CH2)n wherein R is an alkyl of l to 6 carbon atoms and n is ~'rom 2 to 3. The limitation that the number of carbon atoms in the non-epoxide portion --(R)-- be less than 6 is so that the polyepoxide will be soluble in water or ethanol-water mix-tur~s, e.~, u~ to 20% ethanol. While higher carbon content materials are l'unctionally suitable, their application would involve the use of polar organic solvents with resulting problems in toxicity, flammability and vapor emissions.
The anionic charge modifying agent is a compound or cornposition which is capable of bonding to the membrane microstructure without substantial pore size reduction or pore blockage and provides an anionic charge or neKative zeta potential to the membrane microstructure. Preferably, such anionic char~e modifier is a water-soluble compound havin~ substituents capable of binding to the membrane and substituents which are capable of producin~ a more negative "zeta potential" in the use environment (e.g. aqueous) or anionic functional grou~s.

~Z82S6~

Preferred anionic functional groups may be carboxyl, phosphonous, phosphonic and sulfonic. Preferably, the anionic charge modifying agent may be a water-soluble organic polymer or polyelectrolyte having a molecular weight greater than about 2,000 and less than about 500,000 and capable of becoming a non-extractable constituent of the membrane~
The anionic charge modifying agent may have either a high or low charge density, or anything between these extremes, however high charge density is preferred. Specific preferred anionic charge modi~ying agents useful herein are poly (styrene sulfonic) acid, poly (toluene sulfonic) acid, poly (vinyl sulfonic) acid and poly (acrylic) acid. Other anionic charge modifying agents are poly (methacrylic acid), poly (itaconic acid), hydrolyzed poly (styrene/maleic anhydride) and poly (vinyl phosphonic acid).
Additionally, the alkali and alkaline earth metal salts of all of the foregoing may be utilized.
H:ighly preferred anionic charge modifying agents are poly (styrene sulfonic) acids having a molecular weight between 2,000 and 300,000 and poly ~acrylic acid) having a molecular weight between 2,000 and 300,000.
The anionic charge mod:ifying agent may also be cross-linked to the l~i.croporous membrane structure or itself in the same manner as the catLonic agents using the sc~le allphatic polyepoxide cross-linking agent having a molecular weight oE less than about 500. In additlon to the prefer:ced polyepoxides described above, certain diglycidyl ethers of aliphatic diols, O O

may be used. Examples are 1,2-ethanediol, 1,3-propanediol, and 1,4-butanediol. The preferred diglycidyl ether of 1,4-butanediol is commercially available from Ciba-Geigy, Inc. as RD-2 and from Celanese Corp. as Epi-Rez 5022 and Polyscience. m e terms RD-2, Epi-Rez and Polyscience are trademarks.

~325~iS

~ ther hi~her carbon diglycidyl ethers may be used as the polyepoxide cross-linking a~ent, for example 5-pen-tallediol diglycidyl ether. However, the appropriate polar or~anic solvents must be used for diluting such polyepoxides.
Tri~lycidyl ethers, i.e. tri-epoxides may also be utilized as the polyepo~ide cross-linking agent. The tri-e~oxides have the followin~ formula:
C~2~CH-C~12-0-CH2-CH-CH2-0-CH2-CH--CH2 C~2 Cll . ,~ O

The tri~lycidyl ether of glycerol is available from Shell, Inc. as Epon 812 and Celanese Corp. as Epi-Rez 5048.
Another preferred cross-linking agent is methylated urea formaldellyde resin, commercially available from American Cyan~nid; ~or example, Beetle 65, and melamine formaldehyde, e.g " Cymel 303 ~rom American Cyanamid.
Other water~soluble polymers havin~ polar groups can also be em~loy0d in this invention as the charge modi-fyin~ a~ent. Examples include sodium alginate, ethylene diamine tetraacetic acid, diethylene triamine tetraacetic acid, tetraethylene pentamine tetraacetic acid, quaternized polyethyleneimine, quaternized vinyl pyridine, quaternized dIethylaminoethylmethacrylate and the like. The molecular weight of the charge modifying agent does not appear to be sl~nificant so lon~ as the a~ent is soluble in the polymer "do~e". Thus, sodium alginate which has a molecular weight above 10,000 and ethylene diamine letra acetic acid which has a molecular wei~ht below 10,000 are equally employable.
~rne polyamido-polyamine epichlorohydrin cationic resins generally have a molecular weight above 10,000. For example, Polycup 1884 has a molecular weight of about 300,000 and ~4308 has a molecular weight of about 530,000.

`" ~2~32~i6S

Other surface rnodifying agents which are soluble or suspendable in aclueous solvents are such materials as carbon, diatomaceous earth, barium ferrite, iodine, aluminum, alumina, silica, kaolin, molecular sieves, carbohydrates, perlite, clays, vermiculite, asbestos, bentonite, casein and the like.
Broadly, the process of this inven-tion is directed to surface modifying a hydrophilic organic polymeric microporous membrane, e.g. nylon. The process comprises forming a dope solution of nylon polymer, water-soluble or water-suspendable membrane surface modifying agent and a solvent, diluting the resulting dope solution with a miscible non-solvent for -the nylon polymer and contacting the diluted dope solution with sufficient non-solven'c for the nylon polymer to precipitate said membrane therefrom. The dilution of the dope solution is preferably carried out up to the point of incipient precipitation of the nylon but should any precip:itation occur, the solids can be eliminated by filtration or can be redissolved by addin~ additional solvent to the d:iluted dope solution. When cast films a.re prepared, the dilu-ted dope solution is spread on a substrate surface p.rior to contact with the non-solvent :eor p.recipitation. When ~ibers c~re being prepared, the contact:ing step is conducted by extruding the clope :into a quench:ing bath ancl/o:r with the application of shear.
.~n orcle.r to provi.de the sur:Eace modifying amount of surface modifying agent to the membrane, it is preferred that the polymer dope solution contain at least about 0.01~ surface modifying agent, by weight of total solids. The maximum amount of surface modifying agent in the solution is limited by economic and solubility-suspenclability limitations~ For example, an excess of modifying agent which does not become bonded co the microporous membrane will not be economically utilized and will constitute an undesirable extrac'cive from the membrane. It has been found that the amount of surface modifying agent in the dope should not exceed about 75~ by weight of total solids.

~2~32~i6~

Af-ter the microporous membrane has been prepared, it is then dried and cured, preferably in a restrained condition to prevent shrinkage.
Drying of the membrane under restraint is described in the Assiynee's defensive publication T 103,602 -to Repetti, published November 1, 1~83. Generally, any suitable restra:ining technique may be used while drying/ such as winding -the membrane tightly abou-t a drying surface, e.g. a drum. Biaxial control is preferred and tensioniny the membrane on a stretching frame is considered the most preferred. Preferably, the restralning imposed effects no reduction in dimensions.
Final drying and curing tempera-tures should be to dry and cure the trea-ted membranes, preferably from about 120C -to 140C
for minimiza-tion of drying times without embrittlement or other de-trimental effects to the membrane.
The completed membrane may be rolled and stored for use under ambient condi-tions. It will be understood tha-t the treated rnembrane may be supplied in any of the usual commercial fomls, for example, as discs or plea-ted cartridges.
The presen-t invention provides an integral, coherent microporous me~brane of retained internal pore geometry. The surface modified membrane has an improved effective filtration ra-ting relative to the untreated rnicro~reticulate polymer structure.
For so-called sterile filtrations involving biological liquids, the filter is sanitized or sterilized by au-toclaving or hot water flushing. Accordingly, the surface modified membrane must be resistant to this type treatment, and must re-tain its integrity in use. Any modification to -the filter structure, especialiy brought about by chemical agents which may be unstable under conditions of treatment and use, must be scrutinized wi-th care to minimize the prospect of extractables contaminating the filtrate, interfering . ` i~2~32S6~;

with analyses and potentially introducing harmful toxins to a patient. Specifically, any such filter must meet the test standards in the industry, e.g. ASTM D 3861-79, and generally prove less than 5 mg. of extractables in 250 ml solvent (water at 80& .;
35% ethanol at room te~nperature) for a 293 mm diameter disc.
Biological liquids as that term is employed in the specification and claims, is a liquid system which is derived from or amenable to use with living organisms. Such liquids are ordinarily handled and processed under sani-tary or sterile conditions and therefore require sanitized or sterilized media for filtration. Included within such term are isotonic solutions for intermuscular (im) or intravenous (iv) administration, solutions designed for administration per os, as well as solutions for topical use, biological wastes or other biological fluids which may comprise filterc~ble bodies such as impurities, e.g., bacterial, viruses or pyrogens which are desirably isolated or separated for examination or disposal by immobilization or Eixa-tion upon or entrapment within filter media.
Filter membranes in accordance with this invention may be employed alone or in combination with other filter media to treat pharmaceuticals such as antibiotics, saline solutions, dextrose solutions, vacc:ines, bloocl plasma, serums, (e.g. to remove hormones or toxins), sterile water or e~e washes; beverages, such as cordials, gin, vodka, beer, scotch, whiskey, sweet and dry wines, champagne or brandy; cosmetics such as mouthwash, perfume, sharnpoo, hair tonic, face cream or shaving lotion; food products such as vinegar, vegetable oils; chemical such as antiseptics, insecti-cides, photographic solutions, electroplating solutions, cleaning compounds, solvent purification and lubrication oils, cutting oils for removal of metallic fines (e.g. where the ferrite modifying agent has been magnetized); and the like for retention of submicronic particles, removal of bacterial contaminants and : , , ~2~325~5 resolution of colloidal hazes. Illustratively, in hospital usage, membrane filters are employed to concentrate abnormal exfoliated cells from a vaginal rinse, to isolate blood ~arasites from peripheral blood, or bacteria from serum or leucocytes and casts from urine.
In the case of ~reparation for use in sterile fil-tration, the membrane is thermally sterilized or sanitized as by treatment in an autoclave at 121C. under 15 psig. for 1 hour, or hot water flushing at 85F. for 1 hour.
The membranes and fibers, etc. of this invention can also be used to provide a bactericide (e.g. where the modifying agent is iodine) or bacteriostatic treatment to fluids, to remove contaminants such as chlorine or phenol from fluids, in molecular separation columns, in bioreactors where cells, etc. are immobilized thereon, as cigarette filters, and for many other uses.
Havin~ now generally described khis invention, the same will become better understood by reference to certain s~ecific eamples, which are lncluded herein i'or the purposes of illustration only and are not intended to be limiting oi' t~le invention.
E~AMPLES
Tbe followin~ are the measurement and test procedures utilized in all the Examples.
Thickness .
The dry membrane thickness was measured with a 1/2 inch (1.27 cm) diameter platen dial indicator thickness gauge.
Gau~e accuracy was +0.00005 inches (+.05 mils).
Initial Bubble Point (IBP) and Foam-All-Over-Point (FAOP) Tests A 47 mm diameter disc of the membrane sample is placed in a special test holder which seals the edge of the disc. Above the membrane and directly in contact with its up~er face, is a perforated stainless steel support screen which prevents the membrane from deforming or rupturing when ~28~565 air ~ressure i-s a~plied to its bottom face. Above the mem-brane and support screen, the holder provides an inch deep cavity into which distilled water is introduced.
~ re~ulated air pressure is increased until a first stream of air bubbles is emitted by the water wetted membrane into quiescent pool of water. The air pressure at which this first stream of air bubbles is emitted is called the Initial bub~le Point (IBP) of the larJest pore in that membrane sample - see AST.~ D-2499-66T.
Once the Initial Bubble Point pressure has been determined and recorded, the air pressure is further in-creased until the air flow throu~h the wetted membrane sam-ple, as measured by a flow meter in the line between the regulator and the sample holder, reaches 100 cc/min. The air pressure at this flow rate is called the Foam-All-Over-Poin~ (FAOP), and is directly proportional to the mean pore diameter of the sample membrane. In this series of tests, these two parameters (IBP and FAOP) are used to determine if any chan~e has occurred in the maximum or mean pore size of the membrane sample as a result of the charge modi~ying process utilized.
Flow Rate Test A ~7 mm diameter disc of the membrane sample is placed in A test housin~ which allows pressuriæed water to flow through the membrane. Prefiltered water is passed throu~h the membrane sample at a pressure differential of 5 psid. A graduate cylinder is used to measure the volume of water passed by the membrane sample in a one minute period.
In this series of tests this parameter is used in conjunction with the IBP and F~OP to determine if any reduction in pore size or pore blocka~e has occurred as a result of the charge modifying process utilized.
Dye Adsorution Test A 47 mm diameter disc of the membrane sample is placed in a test housin~ which allows pressurized water flow ~2S~i5 through the membrane. me challenge solution consists of distilled water at a pH of 7.0, and Metanil Yellow dye (color index CI#13065:
CAS587-98-4) for cationically charged membranes and methylene blue (color index CI#52015: CAS61-73-4) for anionically charged membranes. The dye inlet concentration is adjusted to produce a 76 percent transmittance at a wavelength of 430 nm, as measured on a Perkin-Elmer ~lodel 295 Spectrophotometer for cationic membranes or 34 percent at 660 nm as measured on a Bausch & Lomb Spectronic 710 Spectrophotometer for anionic membranes. By means of a peristaltic pump the challenge solution is flowed through the membrane sample at a flow rate of ~8 ml/min. me transmittance of the effluent is measured by passing it through a constant flow cell in the aforementioned spectrophotometer. m e effluent transmittance and pressure drop across the membrane is measured and recorded as a function of time. me test is terminated when the effluent transmittance increases to 85 percent for cationic membranes or 45 percent for anionic membranes of the inlet transmittance. In this series of tests, the length of tirne that it takes to reach the 85 or 45 percent, transmittance in the effluent is called the "brealcthrough" time. Since the Metan:Ll ~ellow and methylene blue are low molecular weight charged dyes lncapcible of be:ing mechan-ically ren~ved (~llterecl) by the membrane, this brec~lcthrough time is proporti.onal to the charge adsorptive capacity oE the membrane sample. This test is therefore used to deterrnine the effectiveness of the charge modification techn:ique.
~tr~ b:e~ n ~ 3~ 9, Extractables were detennined by ASTM D-3861-79. The quantity of water-soluble extractables present in the metnbrane filters was determined by immersing the preweighed men~rane in boiling reagent grade water for an extended time and then drying and reweighing the membrane. A control membrane was employed to eliminate weighing errors caused by balance changes or changing moisture content of the membrane in the weighing procedures.
Weight changes of -the control .
( ~Z~ $~

membrane were applied as a correction factor to the weight chan~e of the test membrane filters.
EXAI~PLE I
A. Pre~aration of Microporous Membrane A representative nylon 66 membrane of 0.22 micrometer nominal ratin~, havin~ a nominal surface area of about 13 m2 an Initial Bubble Roint of about 47 psi, a Foam-All-Over-Point of about 52 psi was prepared by the method of Marinaccio et al, U.S. Patent 3,87~,738, utilizing a dope composition of 16 per-i'~ cent by weight nylon 66 (Monsanto Vydyne 66B), 7.1~ methanol a~d 76.9~ formic acid, a quench bath composition of 25Z metha-nol, 75~ water by volume (re~enerated as required by the method of Kni~ht et al, U.S. Patent 3,928,517) a casting speed of 24 inches/minute (61 cm/min), and a quench bath temperature of 20C. The membrane was cast just under the surface of the quench bath by appllcation to a casting drum rotating in the bath (9 to 10 mils as cast wet, to obtain 4.5 to 5.5 mils dry) and allowed to separate from the drum about 90 of arc from the point of application, the self-supporting mem-brane forrnin~ a shallow catenary to takeup. A portion of the uniform opaque film was dried (in restrained condition to resist shrinka~e) in a forced air oven at 89-90C. for 30 minutes.
B. Preparation of Char~e Modified 1. Membrane samples (dried and undried) were dipped in a bath of Hercules 1884 polyamido-polyamine epichlorohydrin resin (g% solids by wei~ht), and allowed to attain adsorption e~uilibrium. The treated membrane samples were washed to re-rnove excess resin and dried in restrained condition on a drum at a tem~erature of 110C. for a period of about 3 minutes.
The treated membrane samples were compared for flow and bubble point characteristics as follows, and found to be essentially identical for treated and untreated samples, evidencinO retention of pore and surface geometry. The results are set forth in Table I.

~2~32565 TABLE I
Control (No Undried Dried Treatment) Membrane Membrane Thickness (mils) 4.25 4.58 4.83 Initial Bubble Poi~t (psi)43.7 44.7 44.7 Foam-A11-Over-Point (psi) 55.0 54.0 54.7 Thickness Normalized Flow Rate (cc. mil/min. cm2 psi) 7.1 7.2 7.0 BET, N2 adsorptiOn 13.12 - 13.58 Thus, in terms of the morphological and hydrodynamic parameters that control mechanical sieving,the filtration charac-teristics of the treated membrances were essentially identical with the untreated nylon membrane.
2. Similar characterizations were conducted on an-other membrane sam~le, similarly prepared, but treated with 2$
~ercules R4308 resin (a free radical polymerized resin based U~OII diallyl nitro~en-colltaining materials, reacted with epi-chlorohydrin) in a bath adJusted to pH 10.5, overcoated with .1% tetraethylene pentamine, dried, cured, washed and redried.
rhe results are set forth in Table II.
TABLE II
Control ~ Dried Membrane Wet 528 635 ~ry 860 960 Elon~ation (C~c) Wet 140 100 ~rr 95 40 Surface area of the treated and untreated membranes remained essentially unchan~ed; tensile stren~th increased with treatment with some loss in elon~ation. The treated ~25~;5 sneet was more flexible; creasin~ of the untreated sheet resulted in cracking and splittin~.
C. Filtration Tests The Hercules 1884 treated membrane samples (Example I.B.l.) were subjected to the filtraton tests indicated below:
P~ro~en_Removal Purified E. coli endotoxin was added to a 0.9~ NaCl solution, pH 6.7 and passed through test ~ilters mounted in a 25 mm diameter stainless steel holder. Inlet and effluent endotoxin levels were determined by standard L.A.L. analysis.
Results are set ~orth in Table III.
TABLE III
Inlet Endotoxin Effluerst Endotoxin Level (pg/ml) Filter Level (pg/ml) 10 ml. 50 ml 100 ml Dried, treated .~lembrane 15000 1000 1000 1000 Control -Untreated 15000 10000 10000 10000 (P~ is "pico~ram") Yirus ~emova1 ~ S-2 bacteriopha~e was added to Houston Texas (U.S~A.) ~a~ water to produce a concentration of 3.4 x 105 PFU/ml (PFU
is "Plaque Formin~ Unit"), and 10 ml was passed through each of the test filters mounted in a 25 mm diameter stainless steel holder. Effluents were analyzed for viral content by standard ~echni~ues. Results are set forth in Table IV:
TABLE IV
Total Viral PFU Virus Removal Filter in Filtrate Efficiency (%) ~ried, treated Membrane 100 99.997 Control - untreated 250000 26.4 Monodisperse Latex Filtration The test filters were challenged with a 10 NTU dis-~erslon (NTU is "nephlometric turbidity units") of 0.109 micrometer monodisperse latex (~DL) particles at a flow rate of 0.5 g~m/ft.2 (.002 lpm/cm2), pH 7.0, R=21000-ohm-cm.
Effluent turbidities (NTU) were monitored and filtration efficiencies were calculated from equilibrium effluent tur-bidities. Results are set forth in Table V.
TABLE V
~ilter MDL Removal Efficiency Undried, treated 97.3%
Control-u~treated 10%
Dye~Removal Efficiency The test filters were challenged with a solution of blue food coloring dye (FD & C No. 1). The solution had a li~ht transmittance of 62.5% at 628 nm. The light trans-mittance of the effluent was monitored and removal efficien-cies determined (based on distilled water light transmit-tance - 100%). Results are set forth in Table VI.
TABLE VI
Throughput (litres) to ~O,o Transmittance Undried, treated 1.99 ~ried, treated 1.76 Control-untreated o EXAMPLE I I
The cationically char~ed microporous membrane of Example I.B. 1. is prepared by repeating the procedure of ~xample I.A. and incorporating the Hercules 1884 resin into the do~e composition.
EXAMPLE III
A nylon dope solution was prepared containin~ 10%
nylon, 85.3~ ~ormic acid and 4.7~ methanol. About 28% of ~ercules 1884 resin based on the wei~ht of the nylon was introduced into the dope solution. The resulting dope solu-tion was extruded through an orifice which was in near proxi-~ ~3256~

mity to a recirculatin~ quench bath stream of about 25% v/va~ueous methanol. The recirculating stream produces a mo-derate shear on the dope solution entering the bath, thereby producing fine fibrils from the dope solution. The resulting fibers were blended at a ratio of 1:1 with coho cellulose fi~er and 4.3 ~rams of the resulting mixture was felted into ~ads. The electrokinetic status of the pad was determined using streaming potential techniques (Knight and Ostreicher, Measurin~ the Electrokinetic Properties of Charged Filter .~edia, Filtration and Separation, January/February, 1981, pp. 30-34). The pad had a slope Mv/Ft H2O of -6.8, an in-tercept of -90.70 and an apparent zeta potential of +0,33.
E~AMPLE IV
A~proximately 1 litre of a mixture of methanol and formic acid in a weight ratio of 0.04 was prepared and allowed to equilibriate for 1 hour. Then to four separate flasks, 150 ml of the solution was added. Thereafter, Hercules resin 1884 (35% solids) were added in amounts oi 1, 5, 10 and 15 millilitres and allowed to equilibriate in a water bath at 40C. for one hour with agitation.
A sufficient quantity of nylon was added to bring the wei~ht percenta~e o~ the nylon to 8% based on the weight o~ the methanol and acid and the flasks were shaken in a water bath at 40C. until the nylon dissolved. The composi-tions o~ the resulting doped solutions were:
Percentage Methanol 4.1 4.1 4.0 4.0 Formic Acid 87.8 87.2 86.4 85.7 ~ylon 8 7.9 7.8 7.8 1884 0.2 0.9 1.8 2.5 Cationically modified microporous membranes are pro-duced repeating the procedure of Example I. A.
.

12~3~565 EXAMPLE V
Four dope com~ositions containin~ 39 grams of Nylon 6~ and the fol10wing other ingredients were prepared:
Dope Formic_Acid Gr~ns Water Grams 4308 Resin Grams Pentamine Grams 1 231.36 ~.6~ 0 0 2 231.36 16.916 10.263 2.46 3 231.36 4.193 20.526 4.92 4 231.36 24.719 0 4.92 Dope 2 contains one equivalent wei~ht of 4308 Resin and triethylenepentamine per weight nylon, formulation 3 contains two e~uivalent weights of both resin and pentamine per weight nylon and dope 4 contains two equivalent weights of the pentamine alone. The dopes were placed in a jar mill roller bath at 20C. until full dissolution. Following the procedure of EXAMPLE I. A., two membranes were cast from each do~e just under the surface of a quench bath ~30% meth-anol, 7~% water by volume) by application to a casting drum rotatin~ in the bath usin~ an 8 mil blade to drum depth.
The membranes made from each dope were separated from the casting drum and rinsed in two successive wash baths o~
distilled water. The membrane sheets were then doubled over on top of themselves while wet and mounted in restrained condition to resist shrinka~e and placed in a forced draft oven at 80C. for one-half hour. The membranes were then subjected to .~etanil Yellow dye absorption tests, the results of which are shown in Figure 1. Thereafter, the membranes were ~subjected to flow, IBP and FOAP tests and the following results obtained:

-~8~

SampLe Flow (Ml/Min) IBP (psi) FAOP (psi) l 1 72 53.5 85 2 78 45.5 82.5 2 1 39 59 53.8 2 59.5 41.5 53 3 l 103 25 30 4 1 6 90~ 90+
2 11 85.5 90 EXAMPLE VI
To 253.6 ~rams of a Nylon 66 membrane dope for amernbrane of a 0.45 micron nominal ratin~ containing 40.576 ~rams of Nylon 6~, methanol and formic acid (16~ solids) was aaded 1.159 ærams of Hercules 1884 resin (35% solids) to ~ive 1% resin based on the nylon and the resulting mixture was a~itated until a clear solution was obtained. Membranes were pre~ared followin~ the procedure of Example I.A., using the do~e without the 1884 resin and the dope with the resin.
The membranes were dried under restrained conditions for 30 minutes at 86C. and their pro~erties were measured using test wa~er which had been prefiltered through a 0.2 micro-meter nominal ratin~ membrane. The results ~re shown in the following table:

Flow cc/Min.-Membrane Thickness ~si=an2IBP (PSi) FAOP (PSi) Do~e without resin 4.13 2.~ 41.3 47.5 ~o~e with resin 4.4 2.44 38.4 45.3 The membrane prepared with the dope which did not contain the cationic 1884 resin had an IBP/FAOP ratio of 0.8~ while the membrane prepared with the resin had a r~tio of 0.848.

s~s EXAMPLE VII
A membrane dope was prepared by combining 1805.5 parts of Nylon 66 with 9479 parts of a mixture of methanol and formic acid to obtain a 16% solids nylon dope. The mix-ture was heated with agi~ation at 30C. for about 4 hours.
A quantity of Polycup 1884 was added to the dope in a quantity such that the concentration of the cationic charge modifyin~ resin was about l~o based on the weight of the nylon. Cast membranes were then prepared using the pro-cedure described in Example I.A. A portion of the resulting wet membrane was dried in restrained condition as a single layer in an oven at 85C. for 15 minutes. The resulting nominal 0.22 micrometer rated membrane had a thickness of .1 mils. Another portion of the wet membrane was folded back onto itself and dried under restrained conditions in the 85C. oven for 60 minutes. The resulting membrane was 7.8 mils thick. Prior to drying, the wet membrane had a thickness of about 6.1-6.~ mils. The nominal pore size of the membrane was 0.3 micron.

~82565 , EXAMPLE VIII
Followin~ the procedure of Example III, pads were ~roduced usin~ other surface modifyin~ agents. The agent, blend ratio, number of ~rams felted and electrokinetic status o~ the pads are shown in the following table:

Fiber to Grams Slope Apparent ~ H0 Ratio Felted ~v/Ft H20 Intercept Zeta Pot.

Alon 0.53 1.632~9 0.69 - 1.60 Asbestosl 0.83 2.55.1 -32.90 - 0.25 Asbestos2 l.00 4.414.2 32.30 - 0.69 Asbestos3 1.00 3.625.1 -35.00 - 1.22 Asbestos4 0.97 2.917.4 -33.50 - 0.84 Casein 1.00 3.220.1 59.00 - 0.97 Silica 1.00 3.025.0 20.66 - 1.21 Cabosil 1.00 8.032.2 53.50 - 1.56 Se~hade~ (G-75)r 1.005.5 6.3 -67.24 - 0.30 Bentonite 1.00 5.446.3 64.30 - 2.25 Diatomaceous Earth D.E. 215 1.005.0 27.9 26.66 - 1.35 Kaolin 1.00 6.062.4 -70.20 - 3.02 Na-Al~inate 1.00 5.518.5 -15.82 - 0.89 Alumin~n 1.00 7.8-181.8 - 5.49 + 8.82 Carbon 1.00 4.457.5 -10.14 - 2.78 Carbon/1884 Resin 1.005.1 0.3 32.00 - 0.01 D~-215/1884 Resin 1.005.6 7.6 -26.30 - 0.37 Alwninwn (1~) l.00 3.6- 6.2 -50.99 + 0.30 1~84/5A Molecular Sie~e 0.67 2.0-29.2 -30.70 ~ 1.42 ~arium Ferrite 1.00 8.653.2 -89.50 - 2.58 E~'rA 1.00 5.519.6 - 4.34 - 0.95 rodinQ (Tincture) l.004.3 33.1 50.03 - 1.60 5~5 1: Arizona - not acid washed 2: Canadian - not acid washed 3: ~rizona - acid washed ~: Canadian - acid washed EXAMPLE IX
Followin~ the procedure of Example III, fibers were ~re~ared from a 60 ml dope solution containin~ 4.8g nylon with and without lOg powdered activated carbon. The fibers were exposed for 16 hours to 150 ml of distilled water which had been chlorinated to 450 ppm chlorine. The chlorine con-tent o~ the water was then determined to be 360 ppm for the water treated with the non~carbon containing fibers and 0.4 ppm for the water treated with the carbon containing fibers.
EXAMPLE X
Anionically charged microporous membranes are prepared by repeating the procedure of Example I.A. and incorporating the foLlowing into the dope composition:
4% polystyrene sul~onic acid and 2.7% ethylene glycol di~lycidal ether;
1.3% polyacrylic acid;
0.88'~ polyacrylic acid and 0.12% polyoxyethylene-~olyoxypropylene ~lycol;
3.6% polyacrylic acid (mw 104,000) and 1.3% hexa-methoxy methylrnelamine resin.
E~AMPLE XI
Into a polymer dope solution containing about 8%
nylon 66, was suspended activated carbon (67w% of total solids).
Tbe sus~ension was allowed to flow by gravity into a 75%/25%
by volume water/methanol non-solvent through a small orifice.
The resultin~ ~ibrils were harvested, washed and then tested for chlorine and ~henol removal from water. In both cases, 56~ii the cayacity o~ the fibrils was about 90-95~ of the particu-late carbon per se and at equivalent mass transfer rates.
The fibrils did not manifest the same degree of problems encountered with finely powdered carbon which has very poor hydrodynamic characteristics, is difficult to retain and tends to mi~rate.
EXAMPLE XII
Followin~ the proc0dure of Example I, unmodified and post-formation modified microporous membranes were prepared.
The post-formation modified microporous membranes were made by dippin~ one of the unmodified membranes into a 2 w% solu-tion of ~ercules Polycup 172 resin (0.24~ solids). The same do~e was modified by the addition of 7 w~ of the Polycup 172 resin (0.84ao solids) and duplicate microporous membranes prepared. When removed from the quench bath, the membranes ~ere air dried and then dried in a forced air oven at 40C.
for 16 hours. The five membranes were analyzed for integrity by determinin~ bubble point~ F`OAP and then challenged with Metanil Yellow dye. The results are shown in the following table:
Bubble PSI Dye Ret. Time ~lombranePoint FOAP Initial Final (min.) __ Unmodified40 46 3.0 3.6 7 3~ 44 1.9 ~.9 7 ~lodified -Post Treatment 44 50 3.9 5.0 24 ~lodified Dope 31 52 3.9 12.0 77 31 53 4.3 14.0 73 Various changes and modifications can be made in the process of the present invention without departing from ~le s~irit and scope thereof. The various embodiments which have been described herein were for the purpose of further illustrating the invention but were not intended to limit it.

Claims (60)

1. A process for producing a surface modified skinless polyamide microporous filter membrane which comprises:
(a) providing a dope solution of a membrane form-ing polyamide polymer in a solvent system comprising a mixture of at least one solvent and one non-solvent for the polyamide polymer, and a surface modifying amount of a surface modifying agent having surface adsorption and/or sequestration effects which modifies the surfaces of the microporous filter membrane, (b) combining said dope solution with additional non-solvent for the polyamide polymer for a time sufficient to precipitate said surface modified membrane from said dope solution in a manner so as to cast the dope solution in a substrate, or (b') contacting said dope solution with additional non-solvent under shear whereby fibers are formed.

2. A process according to claim 1, wherein said membrane forming polymer is a polyhexamethylene adipamide.

3. A process according to claim 2, wherein the surface modifying agent is a charge modifying agent.

4. A process according to claim 3, wherein said dope solution is provided by forming a mixture of the polyamide polymer, solvent and water-soluble cationic surface modifying agent and combining therewith a quantity of non-solvent insufficient to precipitate all of the nylon from said solution.

5. A process according to claim 4, wherein said dope solution is contacted with additional non-solvent under shear whereby fibers are formed.

6. A process according to claim 4, wherein said dope solution is cast on a substrate before or at substantially the same time it is combined with said additional non-solvent.

7. A process according to claim 6, wherein residual solvent and non-solvent is removed from said cast membrane.

8. A process according to claim 3, wherein said surface modifying agent in said dope solution is at least 0.01% of total solids.

9. A process according to claim 8, wherein the amount of said agent is up to 75%.

10. A process according to claim 8, wherein said polyamide has a methylene to amide ratio of about 5:1 to 8:1.

11. A process according to claim 10, wherein said membrane is washed and dried.

12. A process according to claim 11, wherein said cationic charge modifying agent is a cationic water-soluble polar group containing polymer.

13. A method according to claim 12, wherein said agent is a polyamido-polyamine epichlorohydrin cationic resin.

14. A process according to claim 13, wherein said cationic resin is a reaction product of polyamide with epichlorohydrin.

15. A process according to claim 13, wherein said cationic resin is a polyamine epichlorohydrin.

16. A process according to claim 13, wherein the solvent comprises formic acid.

17. A process according to claim 16, wherein said non-solvent comprises an alcohol or water.

18. A process according to claim 17, wherein said alcohol is methanol.

19. A process according to claim 3, wherein said dope solution is provided by forming a mixture of the polyamide polymer, solvent and surface modifying agent and combining therewith a quantity of non-solvent insufficient to precipitate all of the polyamide from said solution.

20. A process according to claim 19, wherein said dope solution is contacted with additional non-solvent under shear whereby fibers are formed.

21. A process according to claim 19, wherein said dope solution is cast on a substrate before or at substantially the same time it is combined with said additional non-solvent.

22. A process according to claim 21, wherein residual solvent and non-solvent is removed from said cast membrane.

23. A process according to claim 19, wherein said surface modifying agent in said dope solution is at least 0.01% of total solids.

24. A process according to claim 23, wherein the amount of said agent is up to 75%.

25. A process according to claim 23, wherein said polyamide has a methylene to amide ratio of about 5:1 to 8:1.

26. A process according to claim 25, wherein said membrane is washed and dried.

27. A process according to claim 26, wherein the anionic charge modifying agent is a water-soluble polymer having substituents thereon capable of bonding to the membrane.

28. A process according to claim 26, wherein the anionic charge modifying agent is a water soluble polymer having substituents thereon capable of bonding to the membrane and anionic functional groups.

29. A process according to claim 28, wherein the anionic functional groups are selected from the group consisting of carboxyl, phosphonous, phosphonic and sulfonic groups or mixtures thereof.

30. A process according to claim 29, wherein the anionic functional groups are carboxyl.

31. A process according to claim 29, wherein the anionic functional groups are sulfonic.

32. A process according to claim 28, wherein the anionic charge modifying agent is a water-soluble organic polymer having a molecular weight of about 2,000 to 500,000.

33. A process according to claim 28, wherein the anionic charge modifying agent is poly (styrene sulfonic acid) having a molecular weight between 2,000 and 300,000.

34. A process according to claim 28, wherein the anionic charge modifying agent is poly (acrylic acid) having a molecular weight between 2,000 and 300,000.

35. A process according to claim 28, wherein the solvent comprises formic acid.

36. A process according to claim 35, wherein said non-solvent comprises an alcohol or water.

37. A process according to claim 36, wherein said alcohol is methanol.

38. A process according to claim 2, wherein the surface modifying agent is water-suspendable.

39. A process according to claim 38, wherein the membrane surface modifying agent is carbon.

40. A process according to claim 39, wherein said dope solution is contacted with the additional non-solvent under shear whereby fibers are formed.

41. A process according to claim 39, wherein said dope solution is cast on a substrate before or at substantially the same time it is combined with said additional non-solvent.

42. A process according to claim 41, wherein residual solvent and non-solvent is removed from said cast membrane.

43. A process according to claim 39, wherein said membrane is washed and dried.

44. A process according to claim 39, wherein the solvent comprises formic acid.

45. A process according to claim 44, wherein said non-solvent comprises an alcohol or water.

46. A process according to claim 45, wherein said alcohol is methanol.

47 47. A process according to claim 3, wherein the membrane surface modifying agent is selected from the group consisting of asbestos, silica, bentonite, kaolin, aluminum, barium ferrite and iodine.

48. A process according to claim 47, wherein said dope solution is contacted with the additional non-solvent under shear whereby fibers are formed.

49. A process according to claim 47, wherein said dope solution is cast on a substrate before or at substantially the same time it is combined with said additional non-solvent.

50. A process according to claim 49, wherein residual solvent and non-solvent are removed from said cast membrane.

51. A process according to claim 47, wherein said membrane is washed and dried.

52. A process according to claim 47, wherein the solvent comprises formic acid.

53. A process according to claim 52, wherein said non-solvent comprises an alcohol or water.

54. A process according to claim 53, wherein said alcohol is methanol.

55. A surface modified microporous filter membrane comprising a polyamide microporous membrane and a water-suspendable surface modifying agent having surface adsorption and/or sequestration effects which modifies the surfaces of the microporous membrane and is bonded to substantially all of the wetted surfaces of the membrane.

56. The membrane of claim 55, wherein said surface modifying agent is carbon.

57. The membrane of claim 55, wherein said surface modifying agent is selected from the group consisting of asbestos, casein, silica, cross-linked polysaccharide, bentonite, diatomaceous earth, kaolin, aluminum, alumina, molecular sieve, barium ferrite and iodine.

58. The membrane of claim 55, wherein said microporous membrane is in sheet form.

59. The membrane of claim 55, wherein said microporous membrane is in fibrous form.

60. The membrane of claim 55, wherein said microporous membrane is in the form of a hollow tube.