Two step-swelling

The first study of this kind was carried out by Chinese researchers in 2003 [144]. They prepared MIP beads for the SPE of tyrosine by simple suspension in water as well as by two-step swelling and suspension polymerisation. They found no substantial difference in the rebinding capacity of the beads prepared by the two methods. A more thorough analysis of various synthetic approaches to MIP beads was conducted a year later by Perez-Moral and Mayes [145]. They took a standard monomer mixture with propranolol as the template molecule and polymerised it by bulk polymerisation, suspension polymerisation, precipitation polymerisation, two-step-swelling polymerisation and emulsion core-shell polymerisation (see also Sect. 2.2.3). Care was taken to keep the polymerisation... 

Later, Hosoya et al. 1931 prepared monodisperse polymer-based CSPs from chiral methacrylamides by co-polymerization onto the surface of polymeric particles. These are synthesized by a staged templated suspension polymerization using a two-step swelling method starting from polystyrene seed particles of 1 pm size used as shape templates, onto which methyl methacrylate and later the chiral methacrylamide is co-polymerized. 

Another possibility is represented by running suspension polymerisation in media other than water. For example, a suspension polymerisation may also involve a perfluorinated liquid alkane as the dispersing phase [33]. In other examples, a two-step swelling and polymerisation method was applied to prepare molecularly imprinted beads [34]. 

Aqueous two-step swelling method (method IV in Table 12.1)... 

Aqueous two-step swelling is a technique for producing monodisperse polymer particles over a size range much greater than that achievable by direct dispersion polymerisation. The properties of the particles, such as porosity, can also be controlled. The concept was first introduced by Ugelstadt and Mork [28] and has since been adopted by many workers. It is used to produce a number of commercial products for chromatography and bioseparations, such as Mono-beads by Pharmacia and Dynabeads by Dynal. 

Fig. 12.7. Electron micrograph showing near-monodisperse imprinted beads made using the aqueous two-step swelling procedure (K. Hosoya, unpublished).

An ideal solution to the problem of finding a universal method for making monodisperse imprinted beads would be a combination of the inertness of fluori-nated liquids with the quality of beads produced by the two-step swelling process. Unfortunately, to date it has not proved possible to make a microemulsion of the organic phase in a liquid fluorocarbon. It might be possible to get some control of particle size, however, by swelling a seed latex with the smallest droplet-size suspension which can be made. Work is in progress to evaluate this possibility. Other methods are available to achieve better particle size control in suspension polymerisation and these should also be evaluated [54]. 

Fig. 17.9. Separation of racemic mixtures of naproxen, ibuprofen, and ketoprofen on poly(4-vinylpyridine-co-EDMA) CSPs (4.6 x 100 mm columns) imprinted with (S)-naproxen. (a) The column was packed with particles prepared by grinding and sieving a bulk polymer. Iso-cratic elution at 0.1 mL/min with THF-heptane-HOAc (250 250 1) and detection at 260 nm. (Adapted from [45], with permission from Elsevier Science, UK.) (b) The column was packed with beads prepared by a two-step swelling and polymerisation method. Isocratic elution at 1.0 mL/min with CHjCN-phosphate buffer (20 mM, pH 4.0) (1 1) and detection at 254 nm. (Adapted from [28], with permission from the Chemical Society of Japan.)...

Uniformly sized beads prepared by the two-step swelling and polymerisation method have recently been modified with an external hydrophilic layer to allow direct serum injection assays of naproxen [53],... 

Fig. 17.12. Separation of 3.2 nmol of racemic lV-(3,5-dinitrobenzoyl)-a-methylbenzylamine on poly((5)-(-)-methacryloyl-l-naphtylethylamine-co-EDMA) prepared by a two-step swelling and polymerisation method using racemic A-(3,5-dinitrobenzoyl)-a-methylbenzylamine as template. Isocratic elution at 1 mL/min with hexane-ethyl acetate (1 1). (Adapted from [55], with permission from the American Chemical Society, USA.)...

In principle, the two-step swelling procedure discussed above may be applied to swell polymer particles with a quite different type of monomer to... 

Spherical beads possess better hydrodynamic and diffusion properties than irregularly shaped particles. It is, hence, desirable to apply MIPs in a spherical bead format, especially for flow-through applications. Methods to synthesize spherical polymer beads are often classified according to the initial state of the polymerization mixture (i) homogeneous (i.e. precipitation polymerization and dispersion polymerization) or (ii) heterogeneous (i.e. emulsion polymerization and suspension polymerization). In addition, several other techniques have been applied for the preparation of spherical MIP beads. The techniques of two-step swelling polymerization, core-shell polymerization, and synthesis of composite beads will be detailed here. 

Two-step swelling polymerization starts with the preparation of sub-micron sized non cross-linked seed particles by emulsion polymerization. The seed particles are then added to a pre-polymerization mixture. The particles swell in the mixture and the polymerization takes place within the volume of the swollen particles [91]. The procedure, which results in monodisperse particles, has been used for the preparation of MIPs imprinted with a range of templates [92-97]. 

To use MIPs in chromatography, other techniques have been developed. Polymers have been prepared in situ in chromatographic columns [104] and in capillary systems for electrophoresis [105]. Their performance does not, however, come up to expectations and efforts have been made to obtain more homogeneous materials. This was done in two ways i) grafting or covering preformed particles by the MIP. The particles covered can be silica or trimethylolpropane trimethacrylate [52,106-108]. Sve and Frechet used a process they call two-step swelling. The first step consists of making polystyrene support beads and the... 

A Naegeli-type amylodextrin of DP 21 and containing one branch-point in each molecule has been prepared from waxy corn starch. The adsorption of monobasic fatty acids from n-hexane on to dry amylose has been found to follow Langmuir s adsorption isotherm. Changes in the physical properties of a potato starch with a high content of phosphate in the presence of cations have been described. Alkali-metal cations produced an increase in the viscosity of solutions of this potato starch, whereas alkaline-earth-metal cations initiated a two-step swelling process and lowered the viscosity. 

Ugelstad J., Kaggemd K.H., Hansen F.K., Berg A. Absorption of low molecular weight compounds in aqueous dispersions of polymer-oligomer particles. 2. A two step swelling process of polymer particles giving an enormous increase in absorption capacity. Macromol. Chem 1979 180(3) 737-744... 

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