Rigid Macroporous Polymer Monoliths
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Rigid Macroporous Polymer Monoliths**
By Eric C. Peters, Frantisek Svec, and Jean M. J. Frchet*
The recent explosive growth of such fields as combinato-rial chemistry, solid phase synthesis, catalysis, and separa-tion science has rekindled the interest of both academiaand industry in the general area of crosslinked polymersupports. First introduced over 50 years ago, these materi-als are primarily produced in the shape of regular beads.[1,2]
Beads are easy to prepare and handle, they do not possesssharp edges that may break to form fines, and they mayreadily be used in packed beds for continuous flow opera-tions. Most applications reported to date involve the use ofslightly crosslinked (gel-type) copolymers that requireswelling to become porous. Although swelling in a goodsolvent opens the polymer matrix, allowing virtually allof the copolymer sites to be accessed by reagents, the issueof swelling also limits the choice of solvents that may beused with the gel beads. In addition, swollen beads maybe difficult to handle, and rapid changes in solvent strengthoften lead to the shattering of some beads.
1.1. Macroporous Polymers
A search for polymeric matrices suitable for the manu-facture of ion-exchange resins with enhanced osmoticshock resistance and faster kinetics led to the discovery ofmacroporous polymers in the 1950s. These polymers arecharacterized by fixed porous structures that persist regard-less of the solvent employed, and even in the dry state.Their internal structure consists of an interconnected arrayof polymer microglobules separated by pores, and theirstructural rigidity is secured through extensive crosslinking.In addition to the manufacture of ion-exchangers, macro-porous beads have found numerous other applications suchas adsorbents, supports for solid phase synthesis and the im-mobilization of enzymes, polymeric reagents and catalysts,chromatographic packings, and as media in diagnostics.
Just like their gel-type counterparts, macroporous beadsare produced by classical suspension polymerization. An
organic mixture containing monovinyl and divinyl mono-mers, an initiator, and a porogenic solvent is dispersed uponstirring in an aqueous medium.[1,2] Traditional porogensinclude inert diluents that may either be solvating or non-solvating solvents for the polymer being produced, solublelinear polymers, or mixtures of the above. Thermally in-duced decomposition of the initiator causes polymerizationto start within the individual droplets, ultimately leading tothe production of spherical polymer particles. After poly-merization, the inert porogen is washed away from the poly-mer beads, revealing the typical macroporous morphology:therefore, beads prepared with 50 % porogen have 50 % in-ternal pore volume. Both the mechanism of pore formationand methods for its control during this process have been in-vestigated extensively, and are described elsewhere.
1.2. Preparation of Macroporous Beads
The efficient production of polymer beads by suspensionpolymerization requires optimization of numerous parame-ters, including reactor geometry, the shape and speed of themechanical stirrer, and the nature and amount of suspen-sion stabilizing agent used among others. This technologyhas already been developed to such a degree that excellentcontrol over bead size and porosity is routinely achievedfor a number of different monomer systems during indus-trial scale production. However, polymer beads containingcertain reactive functional groups might be difficult to pre-pare directly by a classical suspension polymerization pro-cess due to the solubility or reactivity of the functionalmonomer in water. Therefore, either multistep post-poly-merization functionalizations are often performed on pre-cursor beads, or non-traditional suspending media such assaturated aqueous salt solutions, hydrophobic liquids,
or perfluorocarbons are employed, making the overallprocess far less predictable and convenient.
1.3. Diffusion Versus Convection
Porous polymer beads are typically used either in a batchoperation or as a packed bed. Despite the many advantagesthat led to their widespread use, columns and reactorspacked with typical particulate materials also have somelimitations. Chief among these are the slow diffusionalmass transfer of high molecular weight solutes into thestagnant liquid present in the pores of the beads, as well asthe large void volume between the packed particles.[15,16]
Adv. Mater. 1999, 11, No. 14 WILEY-VCH Verlag GmbH, D-69469 Weinheim, 1999 0935-9648/99/1410-1169 $ 17.50+.50/0 1169
[*] Prof. J. M. J. Frchet, Dr. E. C. Peters, Dr. F. SvecDepartment of ChemistryUniversity of CaliforniaBerkeley, CA 94720-1460 (USA)
[**] Support of this research by a grant from the National Institute of Gen-eral Medical Sciences, National Institutes of Health (GM-48364) isgratefully acknowledged. ECP would also like to thank the Rohm andHaas Company for its financial sponsorship.
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These limitations are particularly detrimental to processeswhere the speed of mass transfer limits the overall rate, asis the case in chromatography and catalysis.
In contrast to diffusion, which relies on concentrationgradients as its driving force, convection uses flow togreatly accelerate the rate of mass transfer. The beneficialeffects of this increase in mass transfer on the efficiency ofheterogeneous catalysts has already been demonstrated intheory for inorganic supports with large flow-throughpores. In view of their permanent pore structure thatpersists regardless of the solvent employed, macroporouspolymer beads appear well-suited for applications requir-ing high rates of mass transfer. Unfortunately, the relativelysmall pore size (mostly less than 100 nm) typical of tradi-tional macroporous polymer beads is far too small to sup-port convective flow.
In the early 1990s, Regnier et al. demonstrated thatconvective flow through the pores of modified macropor-ous beads could be achieved if they possessed pores greaterthan 600 nm in diameter. Despite the fact that convectiveflow through these beads accounted for only 2 % of totalcolumn flow, these stationary phases enabled the chro-matographic separation of biopolymers at substantially in-creased speeds compared to columns packed with classi-cal smaller pore stationary phases. Although furtherincreases in the percentage of overall convective flowshould yield further improvements in performance,[22,23] therequired changes in flow pattern would be difficult to effectin a traditional packed bed, since a column packed withspheres always has a large interparticular void volume of atleast 26 % through which preferential flow will always oc-cur. Clearly, a system containing little, or ideally, no inter-
E. C. Peters et al./Rigid Macroporous Polymer Monoliths
Eric Peters was born in Philadelphia in 1967. After obtaining his B.S. in chemistry fromGeorgetown University (1989), he worked at the Rohm and Haas Company for five years onthe development of new polymers for the biopharmaceutical industry. He received his M.S.from Cornell University (1996) and his Ph.D. from the University of California, Berkeley(1999) for his work on macroporous polymer monoliths under the supervision of Jean M. J.Frchet. Eric Peters is currently a staff scientist at the Novartis Institute for Functional Geno-mics. His research interests include the development of novel polymer solid supports and ar-chitectures, as well as their utilization in a variety of fields.
Frantisek Svec was born in Prague, Czechoslovakia. He obtained his Ph.D. in polymer chem-istry from the Institute of Chemical Technology, Prague in 1969 for his work on reactive poly-mers. After his graduation, he was appointed assistant professor at this Institute. From 1976 to1992 he worked at the Institute of Macromolecular Chemistry of the Czechoslovak Academyof Sciences in Prague. In 1992, he joined the faculty at Cornell University in Ithaca, NY, andhas been at the University of California, Berkeley since 1997. His current research interestsembrace the preparation of well-defined porous beads and monoliths, the use of these materi-als for various applications such as HPLC separations, electrochromatography, the labora-tory-on-a-chip, and molecular recognition, and the exploration of new supports and auxiliariesfor combinatorial chemistry.
Jean Frchet, born in France, studied in Lyon prior to pursuing his Ph.D. degree at SUNYSyracuse University (USA) and joining the chemistry faculty at the University of Ottawa(Canada) in 1973. In 1987 he joined Cornell University as the IBM Professor of PolymerChemistry and subsequently the Peter J. Debye Chair of Chemistry. Since 1997 he has beenProfessor of Chemistry at the University of California Berkeley and Faculty Senior Scientist atthe Lawrence Berkeley National Laboratory. His interests are at the interface of organic andpolymer chemistry.
particular void volume is required to fully realize the po-tential advantages of convective flow.
2. Monolithic Porous Polymer Materials
The ideal implementation of a medium possessing no in-terparticular voids would involve a single continuous pieceof porous material. Monolithic open-pore polyurethanefoams were investigated in the early 1970s as stationaryphases for both high performance liquid and gas chroma-tography, but were found to suffer from excessive swellingand softening in some solvents.[24,25] Other approaches to-wards continuous media that emerged in the late 1980s in-clude stacked membranes, rolled woven matrices,[27,28]
compressed soft poly(acrylamide) gels, and macroporousdisks.[30,31]
2.1. Ordered Structures
The preparation of materials with ordered macroporousstructures that complement the classical porous polymersdescribed above has also received a great deal of atten-tion. Such materials are predicted to exhibit a numberof useful new properties, for example, their optical behav-ior enables the realization of photonic bandgaps. In con-trast to the polymerization methods described earlier, thesematerials derive their porous structure from the use ofmacroscopic shape templates, such as stable emulsions,
polymer latex,[33,34] and the interstitial volume of other po-rous structures[35,36] during their formation. Primarily em-ployed to date for the production of inorganic materials, asimilar shape templating approach has also been describedfor the preparation of organic polymers with ordered po-rous structures. Although still in its infancy, these ap-proaches may lead to improved macroporous materials fortraditional applications such as sup-ports, adsorbents, and chromatographicmedia. For example, Antonietti et al.have used two different template sys-tems simultaneously for the prep-aration of silica with a bimodal porestructure. This affords a materialcombining the increased mass trans-port characteristic of larger pores withthe large surface area normally derivedfrom smaller pore networks.
2.2. Polymerized High Internal PhaseEmulsions
Another type of macroporous poly-mer may be obtained using the dis-persed aqueous phase of a high internal
phase emulsion (HIPE) as a template system. Such water-in-oil emulsions have monomer phase volume fractionsgreater than the value of 0.74 characteristic of perfectlypacked uniform spheres. Subsequent polymerization ofthe continuous organic phase results in the formation of atrue monolithic structure possessing an interconnected sys-tem of huge pores and low bulk density. These poly-HIPE polymers have been tested in a variety of applica-tions, including composite materials for combinatorialchemistry, catalytic supports, and metal chelatingagents. However, the multiphase nature of their prep-aration imposes many of the same limitations discussedearlier for suspension systems, and the resulting monolithicmaterials are rarely used in the flow-through mode.
2.3. Rigid Polymerized Macroporous Monoliths
In the early 1990s, our research group introduced an en-tirely new class of continuous medium based on rigidmacroporous polymer monoliths.[46,47] Produced by a verysimple molding process, these novel materials are de-signed for use in a flow-through manner. The resulting in-crease in mass transfer, in conjunction with their uniquemethod of preparation, allow these materials to be used toparticular advantage in a broad variety of applicationscompared to their particulate counterparts. Inorganic sil-ica-based analogs of these materials were later reported byseveral groups starting in 1996.[48,49]
These novel monolithic media possess all of the advan-tages of traditional macroporous polymers, such as a rigid,well-defined porous structures that persist regardless of theenvironment in which the polymer is used. However, unliketraditional beads, these monolithic media are produced bypolymerizing the organic (monomer) phase in bulk withinthe confines of an unstirred mold and without the need forany suspending phase (Fig. 1). This process produces a sin-
Adv. Mater. 1999, 11, No. 14 WILEY-VCH Verlag GmbH, D-69469 Weinheim, 1999 0935-9648/99/1410-1171 $ 17.50+.50/0 1171
E. C. Peters et al./Rigid Macroporous Polymer Monoliths
Fig. 1. Schematic for the preparation of rigid macroporous polymer monoliths.
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gle continuous macroporous object with interconnectedchannels that support flow at very modest pressures. Basedon the pore size distribution profiles typically observed formacroporous beads, it is not intuitively apparent that thepolymerization process used for the preparation of a mono-lith should afford a porous material with the required highpermeability. However, Figure 2 shows that the porousstructure of these polymer monoliths is quite different fromthat produced when the identical reaction mixture is sub-jected to a suspension polymerization process. It is char-acterized by a bimodal pore size distribution consisting ofboth large micrometer-sized channels and much smallerpores in the 10 nm size range. This unique porosity profileand the lack of any observed wall effect (open channelsalong the walls of the mold due to volume shrinkage) resultfrom the absence of both the interfacial tension betweenaqueous and organic phases, as well as the dynamic forcestypical of stirred dispersions.
Fig. 2. Differential pore size distribution curves for poly(glycidyl meth-acrylate-co-ethylene dimethacrylate) beads (n) and monolith (&) preparedusing the same organic phase composition at a polymerization temperatureof 70 C .
2.3.1. Control of Pore Size and Hydrodynamic Properties
The network of large canal-like pores that traverse thelength of the monolith allows liquids to pass through thesematerials under moder...