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Premature ovarian insufficiency (POI) - the loss of ovarian function before the age of 40 years, a decade before natural menopause - is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women's decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI.

Although a woman's fertility declines markedly in her late-30s and early-40s, gradually more and more women start a family at this stage of their lives, with the average age of childbirth progressively increasing. More women are storing their eggs (oocytes) to give them the potential opportunity to have a baby in the future. Nonetheless, the number of egg freezing cycles accounts for less than 2% of IVF cycles, and the number of cycles using stored eggs is even lower. The technology for freezing eggs changed dramatically about a decade ago with the development of a technique of rapid freezing called vitrification, which gives success rates almost as good as using fresh eggs. The growing use of this technique, and the publicity surrounding how this technique may have been promoted, has led to this paper. It is essential that women are very clearly informed about the likely success rates of egg freezing, particularly as it is entirely provided by the private sector, with the associated concerns of financial costs and inappropriate or inaccurate marketing. Its success is strongly dependent on the age of the woman at the time of freezing her eggs, with much higher success rates in those aged 35 years and under. Current legislation only allows women to store eggs for 10 years, which conflicts with the better success rates when women do so at a younger age. The reasons behind the increase in egg freezing are complex, but the most common reason given by women storing eggs is that they do not have a partner and are concerned that by the time they do find themselves in a relationship within which they wish to start a family, they may not be able to. We conclude that elective egg freezing provides women with an opportunity to take action about the drop in their fertility, but at present most women who are doing this are already in their later 30s when the success rates are limited. We strongly support the need for improved and continuing education of both women and men regarding the decline in female fertility with age.

Summary The Super-scan meat analyser measures protein, fat and moisture on an homogenate of the sample by infrared absorption in the transmittance rather than the reflectance mode. A preliminary evaluation of the instrument using fifty-two samples of chicken or turkey meat indicated that the instrument gave reliable results for fat but not for protein and moisture. Regression equations were obtained from the combined data and used to correct the protein and moisture results. These equations were tested on a further twenty-eight samples of turkey meat and the results obtained demonstrated that the instrument could be used for the rapid analysis of poultry meat.

Summary Near infra-red (NIR) analysis has been developed over the last 20 years into a routine method for many agricultural commodities and food constituents. The theoretical and statistical framework, which has made this possible, is reviewed and the extent of the applications presented. The development of a NIR method is demonstrated and the difficulties and limitations of the method are discussed. On-line methods of using NIR analysis are being developed and this is expected to be one of the most important applications for the future use of NIR in the food industry.

Variable cationisation of the alkylethoxylate surfactant Synperonic A7‡ has been observed during a ToF-SIMS study of its interaction with a leaf surface, either by itself or as a component in a simple herbicide formulation. Depending on the conditions, cationisation predominantly by K + , Na + and H + was found. By deliberate surfactant solution doping with alkali bromides, the cationisation channel could be manipulated. Comparison of the apparent molecular weight dependence, derived from the ToF-SIMS spectra, with that measured by HPLC-MS, showed a further dependence on the cationising species, with Na+ giving the best match. An understanding of these effects is critical to the correct interpretation of the spectra from this surfactant.

The method originally proposed in 1988 as “CARNAC” has been re-developed to incorporate the use of wavelet compression, modern programming techniques that make it potentially more transportable and some refinements of the technique. The idea is demonstrated on the small database that was used for program testing as it gives surprisingly acceptable results.

Background: Approximately one in seven of the British population has some degree of hearing loss. Studies have found that the deaf or hard of hearing often find communication in a health setting unsatisfactory. The aim of this study was to investigate the experiences of deaf people in the diagnostic imaging department. Methods: A semi-structured interview technique was used with small numbers of radiographers and deaf patients. Transcripts were analysed using thematic content analysis. Results: Deaf patients experienced difficulties at reception and with the system for calling patients. Examinations that required the patient to follow verbal instructions caused communication problems for both patients and radiographers. A high proportion of the deaf subjects had had an MRI scan, and nearly all of them found this a distressing experience. Radiographers had some awareness of communicating with the deaf, although nearly all significantly overestimated the percentage of words understood by patients who lip-read. Conclusion: Patients experienced problems with communication. In some cases these were such that informed consent may not have been given. Recommendations made for future practice include deaf awareness training for all staff, the installation of equipment that gives visual signals for breath holding, and extra time allowed for explanation to deaf patients before imaging procedures. © Greenwich Medical Media Ltd. 2004.

After a brief review of local calibration methods, a new and relatively simple method is proposed. Given a database of calibration samples, a global calibration based on all these samples and an unknown for which we wish to make a prediction, the method selects a subset of the calibration samples judged to be spectrally similar to the unknown and uses these to determine either a skew and bias or a simple bias correction to the global calibration. Spectral similarity is defined in a two-dimensional space, with one axis focussing on similarity with respect to the analyte value to be predicted, and the other on more general spectral similarity. The computations required to make a prediction are simple by the standards of local methods.

The advent of spectral imaging and recent trends towards the compilation of large spectral databases have caused renewed interest in the compression of near infrared spectra for purposes of storage. A comparison of approaches using Fourier and wavelet transforms shows that wavelets are generally, though not always, more efficient than Fourier at compressing near infrared spectra. The Daubechies extremal phase wavelet of order 4 is a good choice for this purpose.

Near infrared (NIR) spectra were measured, at five temperatures, for 48 samples of honey, from a variety of geographical and botanical sources, and the data was used to explore the possibility of using NIR spectroscopy for testing label claims concerning the geographical and botanical source of honey being offered for sale to the public. Three spectra were obtained at each temperature and a blank spectrum was also recorded to check on the state of the system. Thus a total of 16 spectra were collected for each sample, and the complete experiment amounted to 768 spectra each containing 700 data points. These data were compressed by selection and principal component analysis so that they could be used in a canonical variates analysis (CVA) program. There were sufficient numbers of honeys from four botanical sources, acacia, chestnut, heather and rapeseed, to make use of CVA. Acacia and rapeseed formed clusters that were well separated from chestnut and heather clusters, which were partially overlapped. Mahalanobis distance ( MD) calculations were used to test group membership in a cross-validation experiment in which each of the 28 members of groups was left out of the calibration calculations, one at a time. When using 10 principal components (PCs) as the input variables, 19 of the honeys were assigned to the correct group while two honeys were incorrectly assigned to another group. When using 15 PCs, the number of correct assignments reduced to 13 but there were no incorrect assignments. There were 20 honeys which did not belong to the four test groups. When these were tested for group membership at 10 PCs, 10 were incorrectly assigned to a group. This reduced to two errors at 15 PCs. Tests on the country of origin were inconclusive. These results demonstrate that the successful characterisation of the botanical source of a honey may be obtained by NIR spectroscopy. Further work with larger numbers of samples and groups will be required to realise this potential.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for the analysis of multilayer drug beads that serve as controlled-release drug delivery systems. TOF-SIMS analysis of a cross section of each bead system allowed molecular chemical information to be gained from all of the layers simultaneously, in situ. The integrity of each of the layers was evaluated through imaging of specific ion species for the drug, excipient, and coating materials. The three beads in this study each showed a unique distribution of ingredients. Images of the parent molecular ion for each drug (theophylline, paracetamol, prednisolone) showed their distribution ranged from micrometer-sized particles in one bead cross section to almost homogeneous in another bead cross section. The chemical composition of each of the layers in the beads was evaluated through mass spectrometry; the ingredients did not always match the manufacturer's specification. In addition, many common drug bead ingredients were analyzed as pure substances, providing TOF-SIMS reference spectra of these materials for the first time.

We report on the study of the hydration of a series of poly(ether urethanes) of varying poly(ethylene oxide) content within their soft segments using surface plasmon resonance (SPR). The study of the extent and dynamics of polymer film swelling upon hydration by SPR reveals that the technique is sensitive to the influence of polymer composition (soft segment and chain extender) of the polyurethane which are known to control polymer hydration. SPR analysis has been able to monitor the kinetics of these structural changes in situ, showing rapid initial hydration which appears to slow in an exponential fashion with time. The observed changes in surface elasticity of the polyurethane films on hydration were also confirmed by force−distance atomic force microscopy data. These data revealed a change in surface compliance which mirrored the measured modification in the surface refractive index as measured by SPR. These findings are discussed in the context of the polyurethane surface structure and the potential ...

Pluronic surfactants, PEO–PPO–PEO triblock copolymers, have been investigated widely due to their protein-resistant properties in applications as coatings for implants and in controlled drug release systems. We have studied a wide range of these copolymers, varying in both PEO and PPO block size, by adsorbing them to a polystyrene surface and investigating their subsequent resistance to human serum albumin adsorption. This investigation has been carried out in real time, using surface plasmon resonance, with the surfaces subsequently visualized by atomic force microscopy. This approach has allowed determination of the effect of the lengths of the PEO and PPO polymer chains on protein resistivity. For low-molecular-weight Pluronics a significant, yet not complete, reduction in albumin adsorption has been observed whereas higher molecular weight Pluronics appear to completely inhibit adsorption within the time frame of this experiment. An increase in the PPO block size of the copolymer also appears to increase its protein resistance. This work further confirms that the binding strength of the anchoring block to the hydrophobic surface, rather than the length of the protruding hydrophillic PEO chains, determines a copolymer's protein resistance capability. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 42, 165–171, 1998.

High resolution imaging of the surfaces of starch granules from two different botanical sources has been performed using two complementary techniques: low voltage scanning electron microscopy (LVSEM) and atomic force microscopy (AFM). LVSEM provided superior images of uncoated granules than possible by conventional scanning electron microscopy, and these images were used to validate the features revealed at higher resolution by AFM. The AFM images demonstrated that, although intra-sample variation exists, the surfaces of wheat and potato starch granules possess substantially different topographies. Potato starch had many protrusions (50–300 nm in diameter), above a flatter surface, which contained structures in the order of 10–50 nm. Wheat starch had far fewer protrusions and generally had a smoother surface made up of 10–50 nm structures. The 10 to 300 nm structures are believed to be carbohydrate in nature and correspond to ‘blocklet’ structures, comprising groups of amylopectin side-chain clusters presenting at the granule surface. We conclude therefore that near-molecular resolution topography of the starch granule surface has been revealed, which has allowed further insight into starch granule structure and molecular organisation.

Scanning probe microscopy offers the possibility of investigating biomolecular structure and function. How- ever, successful imaging is technically limited by interac- tions between the probe and the sample. A strong attach- ment of the biomolecule to the substrate is often required. Here, we investigate the binding of the protein catalase to gold surfaces modified by self-assembled monolayers (SAMs). The chemical and physical adsorption of the pro- tein molecules onto SAMs of 3-mercaptopropanoic acid (3-MPA), 11-mercaptoundecanoic acid (11-MUA) and a mix- ture of the two acid thiols (Mixed) was investigated utilizing tapping mode atomic force microscopy (AFM), scanning tun- neling microscopy (STM) and surface plasmon resonance (SPR). The surface concentration of catalase adsorbed on the SAMs decreased in the order: Mixed> 11-MUA> 3-MPA. Utilizing the terminal carboxylic acid functionalities, cata- lase was immobilized with a water soluble carbodiimide and N-hydroxysuccinimide (NHS). Immobilization resulted in increased coverage of the protein. SPR studies on sil- ver surfaces modified by these SAMs indicate immobi- lization of carbodiimide and NHS decreased in the order: Mixed> 11-MUA> 3-MPA.

The development of the scanning probe microscopes over the past decade has provided a number of exciting new surface analytical techniques making a significant progress in the characterisation of biomedical interfaces. In this review, several examples are presented to illustrate that SPM is a powerful and promising tool for surface investigations including biomolecules, cell membranes, polymers and even living cells. The ability of the SPM instrument to monitor adhesion phenomena and provide quantitative information about intermolecular interactions is also described. Moreover, the huge potential of the scanning probe microscopes to study dynamic processes at interfaces under nearly physiological conditions is highlighted. Novel applications in the field of biochemistry, microbiology, biomaterial engineering, drug delivery and even medicine are discussed.

The crystal structure of [bis(2-diphenylphosphinoethyl)phenylphosphine-P,P',P][bis(diphenylphosphino)-methane-P,P'] carbonylmolybdenum(0), [Mo(dpepp)-(dppm)(CO)] [where dppm = Ph 2 PCH 2 PPh 2 and dpepp = Ph 2 PCH 2 CH 2 P(Ph)CH 2 CH 2 PPh 2 ], is reported. In the distorted octahedral complex, the tridentate ligand adopts a facial arrangement with the monodentate ligand trans to the central P atom. All Mo-P distances are statistically dissimilar.

Poly(ethylene glycol)-dextran (PEG-DEX) conjugates have been used as a combined stabilizer and surface modifier to produce resorbable poly( DL -lactide-co-glycolide) (PLG) microparticles by, an emulsification/solvent evaporation technique. The use of PEG or dextran polymers alone was incapable of producing microparticles. Particle size measurements revealed smaller mean particle sizes (480 nm) and improved polydispersity when using a 1.2% PEG substituted conjugate relative to a 9% substituted material (680 nm). PLG microparticles modified by post-adsorbed PEG-DEX conjugates flocculated in 0.01 M salt solutions, whereas PLG microparticles prepared using PEG-DEX as a surfactant were stable in at least 0.5 M NaCl solutions. Surface modification of PLG microparticles was confirmed by zeta potential measurements and surface analysis using X-ray photoelectron spectroscopy. The presence of surface exposed dextran was confirmed by an immunological detection method using a dextran-specific antiserum in an enzyme-linked immunosorbent assay. The findings support a model in which the PEG component of the PEG-DEX conjugate provides an anchor to the microparticle surface while the dextran component extends from the particle surface to contribute a steric stabilization function. This approach offers opportunities for attaching hydrophilic species such as targeting moieties to biodegradable microparticles to improve the interaction of drug carriers and vaccines with specific tissue sites.

A new method has been developed for quantifying drug release processes within controlled release dosage forms using the confocal laser scanning microscope (CLSM). The changing internal distribution of a fluorescent marker drug (minocycline HC1) within a spherical controlled release pellet undergoing drug release was followed using CLSM, which allowed internal mapping of the drug non-invasively and without prior sample preparation. Image analysis routines were developed to quantify the changing drug concentration profile with time across the radius of the pellet, and the results were fitted to a theoretically derived mathematical model which predicted a biphasic depletion mechanism. The experimental results closely fitted the predicted profile, and enabled calculation of the drug dissolution rate constant, the diffusion coefficient of drug within the matrix, and the time drug dissolution within the matrix ended.

Poly(ethylene glycols) (PEGs) of a variety of molecular weights ranging from a few hundred Da to 900 kDa, terminated with a range of functional groups, were cast as thin films and examined by static secondary ion mass spectrometry (SSIMS). The intensities of ions in the SSIMS spectra are examined and it is demonstrated that the m/z 45 ion relative intensity (compared to the m/z 43 intensity) for hydroxy-terminated PEGs increases from 68% at very high molecular weight to 84% at 2 kDa and below. Those PEGs terminated with deuteroxy groups demonstrate a strong ion at m/z 46 at low molecular weight, which indicates that the m/z 45 intensity in hydroxy-PEG is strongly influenced by the presence of terminal groups in the PEG film. It is shown that amino- and methoxy-terminated PEGs have a similar m/z 45 relative intensity to high-molecular-weight PEG, suggesting that hydrogen abstraction in these systems does not occur to any great extent and the excess intensity at m/z 45 for hydroxy-PEG derives from fragment ions formed by the direct cleavage of polymer end groups.

The use of biodegradable derivatives of poly(organo phosphazenes) for the preparation of nanoparticles and their surface modification with the novel poly(ethylene oxide) derivative of poly(organo phosphazene) has been assessed using a range of in vitro characterization methods. The nanoparticles were produced by the precipitation solvent evaporation method from the derivative cosubstituted with phenylalanine and glycine ethyl ester side groups. A reduction in particle size to less than 200 nm was achieved by an increase in pH of the preparation medium. The formation (and colloidal stability) of these nanoparticles seems to be controlled by two opposite effects : attractive hydrophobic interactions between phenylalanine ester groups and electrostatic repulsions arising from the carboxyl groups formed due to (partial) hydrolysis of the ester bond(s) at the high pH of the preparation medium. The poly[(glycine ethyl ester)phosphazene] derivative containing 5000-Da poly(ethylene oxide) as 5% of the side groups was used for the surface modification of nanoparticles. Adsorbed onto the particles, the polymer produced a thick coating layer of approximately 35 nm. The coated nanoparticles exhibited reduced surface negative potential and improved colloidal stability toward electrolyte-induced flocculation, relative to the uncoated system. However, the steric stabilization provided was less effective than that of a Poloxamine 908 coating. This difference in effectiveness of the steric stabilization might indicate that, although both the stabilizing polymers possess a 5000-Da poly(ethylene oxide) moiety, there is a difference in the arrangements of these poly(ethylene oxide) chains at the particle surface.

Critical problems associated with the analysis of biological macromolecules and polymeric biomaterials by scanning probe microscopy are identified. The problems of molecular immobilisation and distribution and data validation are discussed. A number of solutions are described, including the application of a conductive coating and the covalent attachment of biomolecules to suitable substrates. Recent work in the authors' laboratory is described. The conductive coating approach has been employed to study helical macromolecules (including polysaccharides and DNA) and protein molecules. A variety of covalent attachment procedures have been examined, including the adsorption of thiolated proteins onto gold surfaces, the coupling of proteins to self-assembled monolayers, and the attachment of biotinylated molecules to streptavidin-coated polystyrene surfaces. Studies of polymeric biomaterials are also described. Scanning tunnelling microscopy and transmission electron microscopy have been compared in studies of poly(ethylene oxide), and the interactions of ferritin with a ferritin antibody immobilised on a polystyrene surface have been examined.

An investigation was made of the correlation between quantitative surface analytical data obtained by XPS and static SIMS and the chromatographic performance of a range of n-alkyl-bonded silica (C1-C18) packing materials. A series of acidic, basic, and neutral solutes was used to study the retention behavior. For comparison, analysis of bulk total percentage carbon (%C) and alkyl surface density of the bonded silica particulates were also included. Significant correlations were observed, in the majority of cases, between the retention factor (k) and the XPS C:Si atomic ratio, which was similar to that obtained between k and the bulk %C or k and the bonded alkyl chain length. Similar significant correlations were also obtained between k and the static SIMS alkyl:Si ion peak area ratios. XPS alkyl:Si atomic ratios were calculated as an estimate of alkyl surface coverage of the silica support, and these correlated well with the surface density calculated from the bulk %C and the surface area of the packing material. The XPS alkyl:Si ratio also demonstrated a significant correlation with the peak asymmetry factor derived for basic solutes. These studies confirm that both XPS and static SIMS can generate surface chemical data from chromatography particulates, which has direct relevance to the prediction of chromatographic behavior. We believe that these techniques will prove to be effective tools to assist in the characterization of chromatographic supports and stationary phases.

The in vitro degradation of nanospheres perpared from three benzyl ester derivatives of poly (β-malic acid) containing 80, 90 and 100% of benzylated malic acid units was studied. The progressive decrease in the molecular weight of the copolymers was observed as the nanospheres degraded, demonstrating that the degradation under the experimental conditions occurred by a simple hydrolytic cleavage of the ester bond between the monomeric units. The degradation was slow, with the weight average molecular weight decreasing to about 70% of the initial value in 5 months for all the nanosphere systems. A comparison of degradation rates for benzyl ester copolymers with the degradation rate of poly (β-malic acid) homopolymer demonstrated a decreased degradation rate of benzylated copolymers which suggests that the introduction of a pendent benzyl ester function in proximity to the ester bond in the main chain, reduces the rate of the bond cleavage. No significant difference in the degradation behaviour of highly benzylated copolymers, containing 90 and 80% of benzylated malic acid units, and fully benzylated polymer could be detected to prove an autocatalytic role on degradation of the free pendent carboxyl group in the former two copolymers.

We have previously employed scanning force microscopy (SFM) to study antibody-antigen molecular interactions on microtiter wells used for enzyme linked immunosorbant assays (ELISA). Here we demonstrate the ability of SFM to image and discriminate different types of antibody and antibody fragments bound to an ELISA well surface. The samples studied include a type IgG antibody with a proportion of bound IgM and two-dimensional films of whole IgG antibody, and Fab' and F(ab)2 antibody fragments. Molecular resolution is achieved in each case despite the size of substrate features exceeding most of the molecular dimensions observed. Analysis of the data shows that the SFM overestimates molecular dimensions by an approximately constant amount, which is proposed to principally result from the effects of a finite probe size and not from deformation of the molecular species due to the imaging forces employed.

Static secondary ion mass spectrometry (SSIMS) has been used to analyze a range of poly(lactic acid)s (PLA) and copolymers of lactic and glycolic acids (PLGA). Ion assignments for the full range of radical cations observed are presented, along with the observation of chain end contribution to the SSIMS spectra in the case of low molecular weight PLA. The ion intensities within different radical cation series in PLGA have been compared with theoretical intensity distributions. In the case of random copolymers, the radical cation intensities are almost identical with the predicted binomial distribution. Dimeric character in some of the polymers is demonstrated using a statistical approach.

A method of comparing two spectra using linear and quadratic regression is described. For every wavelength, the log(1/ R) value of the first spectrum is used as x, that of the second as y. The correlation coefficient ( r) is used to compute a similarity index which can be used to test for identity. The method has the advantage of comparing whole spectra, rather than only certain peaks, while reducing the data to a single variable. For crystalline solids with different particle sizes, better results are obtained if a quadratic rather than a linear equation is used. This procedure allows the successful identification of isomers and sugars, even when there is considerable variation in particle size.

The erosion behavior of blends of biodegradable polymers is determined by the chemical composition and the molecular organization of the surface of the material. Providing a comprehensive character...

The purpose of this study was to contribute to the understanding of the effect of titanium ions released from a metallic substrate on the molecular structure of hydroxyapatite. The effects of pH, time of incubation and concentration of titanium ions were investigated. The solids were analysed by X-ray diffraction, Fourier transform infrared spectroscopy, Fourier transform Raman spectroscopy, energy dispersive X-ray analysis and thermogravimetric analysis. The results clearly indicate the presence of a titanium phosphate, Ti(HPO4)2·nH2O (n=1–3), which probably has a double layered structure. The formation of this compound is dependent on the titanium concentration and its crystallinity increases with the time of incubation.

Summary The development of a photobleaching technique, CFMM (continuous fluorescence multipoint microphotolysis), to measur e diffusion coefficients in gel systems using a confocal scanning laser microscope is described. Diffusion coefficients (D) were determined for fluorescently labelled dextrans of varying molecular weight in agarose gels, and the results compared with two other methods. CFMM enabled diffusion coefficients to be rapidly determined from the profile across an irradiated area within a defined microscopic location of the gel. The technique was experimentally simple and produced values of D that corresponded well with classical double-diffusion cell methods.

The surface chemical analyses of a series of colloids based on poly(methyl methacrylate) and poly(4-vinylpyridine) have been carried out using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS). The colloids were prepared by the vinyl polymerization of monomers bearing the reactive functional groups hydroxyl, amide, and epoxide. XPS and TOF-SIMS provided complementary information on the functional groups at the colloid particle surfaces and gave good correlation with electrophoretic mobility and particle size data. This paper demonstrates the capability of these surface analysis techniques for studying the complex surface chemistries of copolymer colloid systems.

Surface analysis of methyl methacrylate/poly(ethylene glycol) methacrylate copolymers has been carried out using X-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SSIMS). Both techniques confirm that solvent-cast films of these random copolymers present a surface that is very similar in composition to the bulk. A slight excess of methyl methacrylate units at the polymer/ vacuum interface was noted in the XPS spectra. SSIMS reveals that the top few monolayers of the copolymer films are typical of the bulk material and also confirm the presence of a methoxy end cap in the poly(ethylene glycol) methacrylate macromonomer structure.

In situ atomic force microscopy has recorded the dynamic topographic changes occurring as a biodegradable polymer film, containing the protein bovine serum albumin (BSA), is eroded. An atomic force microscope (AFM) was operated with the scanning probe immersed in an aqueous solution allowing the surface morphology of these samples to be analyzed at the polymer/water interface. Control experiments demonstrated that the granular structure of the poly(ortho ester) surface was roughened by the degradation process. The loss of protein particles embedded in a polymer film was then followed using the AFM. Analysis of the kinetics of the erosion process was undertaken using computational analysis of the three-dimensional AFM data, which enables volume changes occurring during the erosion to be quantified. These methods of volume analysis allow the comparative rates of protein and polymer loss from the eroding polymer surface to be assessed. This data has implications for the design of surface-eroding controlled drug delivery devices and suggests a role for in situ atomic force microscopy in the comprehension of the relationship between polymer biodegradation and protein release.

A range of copolymer colloids with covalently attached polyethylene oxide (PEO) (2000 Da) chains have been prepared by potassium persulfate-initiated emulsion copolymerization of styrene with a PEO acrylate macromonomer. The surface orientation of the macromonomer chains has been confirmed by the combined use of static secondary ion mass spectrometry (SSIMS) and X-ray photoelectron spectroscopy (XPS). The surface analysis data proved entirely complementary. The detection of molecular ions diagnostic of PEG within the SSIMS spectra and their increase in relative intensity with increasing macromonomer content provided clear evidence of the surface presence of PEO for the range of polystyrene (PS)-PEO colloids. Similarly, the XPS studies showed that the level of PEO, as inferred from the ether C-O carbon environment within the C1s spectra, increased with increasing levels of macromonomer in the latex. This surface analytical data on these near-monodispersed colloids was complemented by particle size, electrophoretic mobility, and colloid stability analysis, all of which showed a marked dependence on the level of surface PEO. The relevance of these findings is discussed both in terms of the particle formation mechanism and in the context of the potential of these colloids as model systems for probing the influence of PEO surface density on colloidal biodistribution in vivo.

The colloidal properties of surfactant-free nanospheres prepared from biodegradable polyesters, i.e. a range of benzyl esters of poly(β-malic acid) (PMLABeH) and poly(lactic acid-co-glycolide) (PLGA) have been investigated. The results reveal a significant difference in the colloidal behaviour of the nanosphere systems, depending on the composition of the copolymer used in their preparation. The nanospheres from the PLGA and fully benzylated PMLABe 100 polymer were relatively less stable to addition of electrolyte and coagulated around the pH which coincided with the dissociation constant of the carboxyl group. The coagulation was associated with a decrease in the zeta potential below a certain critical value needed for electrostatical stabilization. In comparison, nanospheres prepared from partly benzylated PMLABe 80 H 20 and PMLABe 90 H 10 copolymers did not coagulate at relatively high electrolyte concentrations and at low pH values of the suspending buffer. This may be interpreted in terms of an involvement of a steric component to nanosphere stabilization, whereby the steric component appears to be associated with the presence of an increased level of carboxyl groups on the nanosphere surface. The results suggest a different construction of nanospheres prepared from partly benzylated copolymers from those prepared from fully benzylated PMLABe 100 and PLGA copolymers.

The surface degradation of melt-crystallized poly(sebacic anhydride) (PSA) has been visualized in situ in an aqueous environment using atomic force microscopy. The morphological changes accompanying degradation may be interpreted in terms of the preferential erosion of amorphous material revealing spherulitic crystalline features. The kinetics of polymer degradation were found to be pH dependent as anticipated and also dependent on the method of sample preparation, which influenced surface crystallinity. The future exploitation of in situ atomic force microscopy for the study of polymer degradation promises to provide a unique insight into the erosion process and enhance the current understanding of the relationship between polymer microstructure and erosion kinetics.

During our investigation of the surface morphology of various polyethylene glycol methacrylate copolymers we found that the rapid drying of a chloroform solution of a poly(methyl methacrylate- co -polyethylene glycol methacrylate) polymer resulted in the generation of a surface characterised by many sharp sided holes in a flat polymer matrix, which lead to extensive tip self imaging. By measuring the profiles of these holes (which are of variable size ranging from tens of nanometres to microns in depth), it is possible to estimate the gross tip profile over a wide vertical range in a totally non-destructive manner.

The swelling of hydrating HPMC tablets has been studied by NMR microscopy. The technique is non-invasive and has allowed both dimensional changes in the core and in the developing surface hydrated layer to be studied. Hydration at the edges of the tablet occurred to a greater extent than in the centre of the table surfaces, giving rise to a convex shaped hydrated layer. Gel layer development occurred to the same extent in both axial and radial directions, and was similar in all HPMC types. The predominantly axial swelling reported for all HPMC types, was shown to result almost equally from growth of the hydrated surface gel layer and expansion of the ungelled tablet core. The smaller axial expansion observed in E4M tablets was not a result of slower gel layer growth, but was entirely due to a smaller expansion of the core.

A series of alkyl-bonded silica HPLC stationary phases with a mean particle diameter of 5 μm has been prepared using a variety of dimethylalkylsilyl chlorides (i.e. monofunctional bonding agents) with alkyl chain lengths varying from C1 to C18, including phenyl and cyanopropyl groups. The stationary phases have been characterized using XPS and time-of-flight (ToF)-SIMS. Elemental analyses by XPS have identified trace quantities of iron, sodium and chlorine at the silica/dimethylalkylsilyl chain interface, and aluminum was detected by ToF-SIMS. A comparison of percentage carbon obtained by XPS with bulk carbon-loading analyses suggests that the alkyl chains are bonded to the surface of the porous silica particles. Molecular ions characteristic of the dimethylalkylsilyl groups were identified in the ToF-SIMS data together with ions attributable to these alkylsilyl groups attached to fragments of silica, the latter indicating covalent bonding to the silica surface. In addition, a series of low-mass signals corresponding to alkyl chain fragments and silyl/silica-based ions was observed. The value of high-resolution ToF-SIMS data for ion assignments is well demonstrated. The relative ion intensities of several of these low-mass ions were studied as a function of changing alkyl chain length. In general, as the alkyl chain length increased, the abundance of the silicon-containing fragments decreased, whilst the abundance of the alkyl-based fragments increased, within the ToF-SIMS spectra.