Thomas Ballet, Laurence Boulangé, Yves Bréchet, Franz Bruckert, Paolo

Mangiagalli, Laurent Nault, Marianne Weidenhaupt; Institut National Polytechnique de Grenoble; UMR 5628, CNRS-INPG, 3 L Nel, F-38016 Grenoble 1, FRANCE

Kinetics of Insulin Amyloid Fiber Formation on Hydrophobic Surfaces

Sluzky et al .(1991) showed that insulin solutions buffered at pH 7 aggregated, when the solution was exposed to hydrophobic surfaces upon agitation. We reproduced these experiments and showed that such aggregates are similar to insulin amyloid fibers that spontaneously grow in solution at pH 2 and 60̊C. Both bind Thioflavin T, a well-known fluorescent marker of the extensive intermolecular ?-sheets that constitute the core of amyloid fibers. In both cases, aggregation kinetics proceeds in two phases: a lag time, where nucleation takes place, and a growth phase, where the protein in the bulk solution aggregates. The insulin aggregates formed on hydrophobic surfaces at pH 7 are able to induce the growth of insulin amyloid fibers in solution at pH 2 and 60̊C, suggesting that both aggregates are structurally similar.We further characterized insulin adsorbed on hydrophobic surfaces, during the lag time and the growth phase. Both phases are very sensitive to temperature and require agitation. Adsorbed insulin accumulates on hydrophobic surfaces right before the onset of the growth phase. This protein material binds Thioflavin T which, in contrast to Thioflavin T in amyloid fibers, does not fluoresce. Seeding experiments show that the preincubation of insulin on hydrophobic surfaces reduces the duration of the lag time. These results show that hydrophobic surfaces are able to catalyze a conformational change in insulin that resultsin its accumulation on the surface and into the release of amyloid fibers.

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Xiaoping Cao; Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340

Email: xiaoping.cao@pfizer.com.

Characterizing Surface Properties of Pharmaceutical Materials Using Atomic Force Microscopy

With the rapid development of atomic force microscopy (AFM), AFM has been shown to be a powerful tool for pharmaceutical research. It has been utilized to study a variety of samples such as films and single crystals through surface morphology mapping and property probing. This presentation gives an overview of AFM applications in pharmaceutical research through several detailed case studies. A wide range of pharmaceutical excipients and active pharmaceutical ingredients are covered including ethylcellulose, hydroxypropyl methylcellulose, lactose, sucrose, sulfamerazine, ascorbic acid, and ibuprofen. Different sample preparations are employed for AFM experiments. Complementary techniques such as transmission light microscopy and Raman spectroscopy are used to aid surface characterizations. Detailed surface characteristics are discussed including morphology, phase differentiation, physical and mechanical properties. Moreover, the implications of those properties to pharmaceutical research are also discussed.

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Cetin Cetinkaya, Ilgaz Akseli, Mohammad Miraskari, Huan Zhang, and Weiqiang Ding; Dept. of Mechanical and Aeronautical Engineering , Clarkson University, Potsdam, NY 13699-5725, USA

Non-Contact Rolling Bond Stiffness Characterization of Polyvinylpyrrolidone (PVP) Particles: Relevance to Pharmaceutical Tablet Compaction

Adhesion properties of powders used in tablet compaction play a critical role on the mechanical properties and, consequently, the therapeutic properties of the resulting tablet. Two experimental techniques, based on a contact pushing and a non-contact base and air-coupled acoustic excitation, were utilized to characterize the adhesion behavior of Polyvinylpyrrolidone (PVP) particles. The microspherical PVP particles deposited on silicon substrates were excited by an ultrasonic transducer and the out-of-plane transient particle response was acquired by an interferometer (vibrometer). The resonance frequencies of the particle rocking motion were extracted by comparing the vibrational spectra of the particles to those of the substrate. The obtained frequencies were then used to determine the work of adhesion the contact. Rolling resistance moment-based lateral pushing experiments were also conducted on similar PVP particles. The resulting slope of force-displacement curves were utilized to obtain the work of adhesion. In characterizing the particle/substrate adhesion bond, different contact modes the contact area were considered. For each case, the expected resonance frequencies of the rocking motion were extracted using their relation to the slope of force-displacement curves from the contact lateral pushing experiments. The existence of all the possible modes of the particle/substrate bond were verified because all the expected natural frequencies were observed in the non-contact acoustic measurements.

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Peilin Chen; Research Center for Applied Sciences, Academia Sinica, Nankang, Taipei 115, TAIWAN

Observation of Enhanced Cell Adhesion and Transfection Efficiency on the Superhydrophobic Surfaces

Ever since the discovery of the importance of the surface roughness to the water repellent behavior of plant leaves, scientists have developed various strategies to produce the so-called “superhydrophobic surfaces”, whose water contact angles are larger than 150 degree. It is generally believed that the water repellent properties of the superhydrophobic materials could reduce the water contact area on the surfaces, therefore, minimizing the adsorption of particles or molecules. In the past few years, several potential applications of the superhydrophobic surfaces have been identified including coatings for self-cleaning, fog condensation, contamination reduction, oxidation reduction, oil water separation, and rapid water spreading. However, there are very limited research activities in exploring the possibility of using the superhydrophobic materials for biological applications. Here we report a surprising observation of enhanced cell adhesion and transfection efficiency on the patterned superhydrophobic surfaces. It was found that the cells attached preferentially on the roughened area allowing the formation of cell microarrays when the patterned superhydrophobic surfaces were used in the cell culture. It was also observed that the transfection efficiency of the CHO cells and NIH 3T3 cells was greatly improved on the superhydrophobic surfaces. Therefore, we conclude that the patterned superhydrophobic surfaces could be used as cell microarrays with the advantages of improved cell adhesion, nature separation of colonies and enhanced transfection efficiency.

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Arthur J. Coury; 154 Warren Avenue, Boston, Massachusetts 02116

Local Drug Delivery from Synthetic Hydrogel Implants

Synthetic hydrogels provide an ideal depot for the incorporation and delivery of bioactive molecules to body tissues in certain applications. Beginning in the early 1990s, groups that I have been associated with have developed a family of poly (oxyethylene)-based biocompatible, resorbable hydrogels with strong, durable tissue adherence. These hydrogels, originally developed as surgical sealants, can incorporate drugs ranging from small molecules to large biologics which can be delivered to specific tissues in sustained fashion. Each effective drug delivery system is subject to the specific application of a set of design principles. These and several examples of preclinical therapeutic drug delivery will be provided.

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Laila J. Jallo¹, Yuhua Chen¹, Xi Han¹, James Bowen², Frank Etzler³, and Rajesh Davé¹

1) New Jersey Center for Engineered Particulates, New Jersey Institute of Technology, 138 Warren Street, Newark, NJ, 07102-1982, USA

2) Department of Chemical Engineering, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

3) Boeringer-Ingleheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877

Adhesion Force Prediction for Fine Particles from Surface Energy and Surface Roughness Measurements

Fine powder flow is a topic of great interest to industry, in particular for the pharmaceutical industry; a major concern being their poor flow behavior due to high cohesion. We present results for fine aluminum as well as pharmaceutical powders, where cohesion reduction is achieved via surface modification. Results of the bulk properties for these powders are presented to illustrate the improvement in flow, fluidization, and dispersion. For Aluminum powders, the adhesion force model of Derjaguin-Muller-Toporov (DMT) is utilized to quantify the inter-particle adhesion force of both original and surface modified powders (under 10 μm in size). Inverse Gas Chromatography (IGC) is utilized for the determination of surface energy of the samples, and Atomic Force Microscopy (AFM) is utilized to evaluate surface roughness of the powders. For selected samples, the AFM is utilized for direct evaluation of the particle pull-off force. The results indicate that surface modification reduced the surface energy and altered the surface nano-roughness, resulting in drastic reduction of the inter-particle adhesion force. Surface modification resulted in two to three fold reductions in the particle Bond number. In order to examine the influence of the particle scale property such as the Bond number with the bulk-scale flow characterization, Angle of Repose (AOR) and other measurements are done showing very good qualitative agreements. The results indicate a promising method that may be used to predict flow behavior of cohesive and surface modified powders utilizing very small samples, and that the surface modification can drastically improve the powder flow for industrially relevant

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Mitsuhiro Ebara¹, Takao Aoyagi¹, Masayuki Yamato², Teruo Okano²

1) Smart Biomaterials Group, Biomaterials Center, National Institute for Materials Science, JAPAN

2) Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, JAPAN

Email: EBARA.Mitsuhiro@nims.go.jp

Switchable Surface Capture/Release Systems For Cells, Biomolecules, And Analytical Beads

We report a novel approach to manipulate cell sheets using temperature-responsive cell culture dishes with nanometer-sized surface-grafted poly(N-isopropylacrylamide) (PIPAAm) which allows the cultivation of anchor-dependent mammalian cells at 37̊C (above the lower critical solution temperature; LCST), and intact cell sheets can be collected after reducing temperature below the LCST. We have further developed a non-invasive approach to observe dynamic affinity changes in cell-substrate interactions by the direct immobilization of cell adhesive peptides onto PIPAAm-grafted surfaces [1]. The time required for cell detachment below the LCST was strongly related to the cell adhesion strength according to the trend: RGD < RGDS < GRGD < GRGDS < RGDS-PHSRN. The proposed surface capture/release system can be also created inside microfluidic channels for bioanalytical beads [2]. Thus, switchable surface traps offer the potential to develop new technologies in many fields such as regenerative medicine, biological assay, and diagnosis.

[1] M. Ebara, M. Yamato, T. Aoyagi, A., K. Sakai, T. Okano, Adv Mater, 20, 3034 (2008).

[2] M. Ebara, J. M. Hoffman, A. S. Hoffman, P. S. Stayton, Lab Chip, 6, 843 (2006).

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F.J. Chen, Tommasina Bramante, Richard Deanne, George Gereg, Svetlana Sienkiewicz, Luying Wang and Frank M. Etzler; Pharmaceutical R&D, Boehringer-Ingelheim Pharmaceuticals, Inc. POB 368, 900 Ridgebury Road, Ridgefield, CT 06877

Effect of Sodium Dodecyl Sulfate on the Tabletability, Compressibility and Compactibility of Common Pharmaceutical Excipients.

Purpose. Tablet formulations sometimes contain sodium dodecyl sulfate (SDS). Tablets containing high levels of SDS do not always have acceptable tableting properties particularly at high press speeds. In this work the tensile strength of tablets containing binary mixtures of SDS and other common tablet excipients is explored.

Methods. Binary mixtures of mannitol, pre-gelatinized starch, lactose and dicalcium phosphate with SDS were prepared. The weight percent of SDS in the mixtures ranged from 0 to 45%. 9 mm round flat faced tablets were prepared at different compression forces and dwell times using an Instron UTM and a Presster. Tensile strength of the resulting tablets was determined using a USP hardness tester. Plots of tensile strength versus tablet porosity were then prepared.

Results. The plots of tensile strength versus tablet porosity, as expected from the literature, show that tablet strength decreases with increasing porosity. The plots also differ from each other depending on composition. Increased amounts of SDS generally weaken the tablets. No significant changes in tablet strength were observed upon the addition of small amounts of Mg Stearate or upon granulation of mixtures containing lactose.

Conclusions. The data are compared to Ryshkewitch- Duckworth Equation which describes the relation between tablet tensile strength and porosity. Decreased porosity increases the contact between particles and hence tensile strength. As previously discussed by Wu et al. [Pharm. Res. 23(8), 1898 (2006)], the Ryshkewitch-Duckworth Equation parameters determined for individual components can be used to predict the behavior of binary mixtures. The data collected in this study are compared to the predictions calculated using a model similar to that suggested by Wu et al. and based on adhesion science principles.

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K. Fricke, K. Schröder, T. v. Woedtke and K.-D. Weltmann; Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Strasse 2, 17489 Greifswald, GERMANY

 email: k.fricke@inp-greifswald.de

Atmospheric Pressure Plasma Sources - Modification and Decontamination of Biomedical Relevant Surfaces

Atmospheric pressure plasma sources are used in a variety of technical applications. Especially the plasma based treatment of polymers is of increasing interest due to its huge potential for different applications. Plasma in medicine is another extremely promising field using non thermal plasmas operating at atmospheric pressure. Cold plasma enables the use of this technology for heat sensitive materials like medical devices and implants but also biological tissue. In the case of antimicrobial treatment, a heavy plasma exposure is anticipated to ensure the inactivation of bacteria as well as the removal of the inorganic and organic material from the surface. This can be achieved by specific plasma treatment that combines lethal effects against microorganism cells by producing charged particles, UV/VUV radiation and reactive neutral species (excited atoms and molecules, radicals), with the ablation of organic compounds by dry etching. In the study presented here it will be characterized to which extent plasma doses effective for biological decontamination have the potential to modify polymer surfaces. Besides microbiological diagnostics, chemical and morphological surface properties before and after plasma exposure are characterized by XPS and contact angle measurements. The aim of this work is to find treatment conditions for selective plasma-based surface decontamination without damaging influences on application-relevant material characteristics.

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A.E. Jefferson, D.R. Williams and J. Y. Y. Heng; Surfaces and Particle Engineering Laboratory, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom.

Surface Energy Heterogeneity of Pharmaceutical Powders

Finite dilution Inverse Gas Chromatography (IGC) allow the surface energy of a sample to be measured at different surface coverages. An approach for interpreting data from such experiments is presented: by fitting the results of simulated experiments to measured data the surface energy distribution of a sample can be predicted. A computational model for adsorption from the gas phase to a heterogeneous surface is proposed, based on a Henry's law isotherm. Using the model the simulation-fitting approach is demonstrated for mannitol and lactose powders. The addition of fines to coarse lactose powder are shown to have a significant effect on the powder's surface energy distribution. In contrast the surface energy distributions of different particle size fractions of mannitol, obtained by sieving, do not show significant differences in their surface energy distributions.”

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T. Delmas, M. M. roberts and JYY Heng; Imperial College London, South Kensington Campus, London SW7 2AZ

Geometrical and Chemical Interactions for Controlled Nucleation and Crystallization of Lysozyme

In an effort to better understand, direct and control the crystallization of molecular and macromolecular compounds, an approach using colloidal templates as substrates for heterogeneous nucleation was investigated. These templates combine both tuneable chemical functionalities and geometrical features, altering the crystal-substrate interactions. Colloidal templates were prepared from silica nanoparticles, where the surface chemistry was modified by silanisation. Particle size varied from 30 to 700 nm, with silanols, NH2, CF3, phenyl or dodecyl as surface functional groups. Here, we report on the template assisted crystallization of chicken egg white lysozyme (CEWL). Nucleation was dramatically affected by the surface chemistry and topology of the templates. Using 220 nm particles, hydrophobic templates generally produced fewer, larger crystals, while a larger number of small crystals were obtained on hydrophilic templates. The use of different particle sizes also affected the crystal size, the optimal for nucleation being 432nm. Classical Nucleation Theory (CNT) can interpret surface chemistry effects but does not support the effect of particle size. This paper reports that the combined use of both geometrical and chemical interactions results in an increased ability to control the nucleation and growth of protein crystals.

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Matthias Lauer ^1,4 O. Grassmann¹, M. Siam¹, L. Jacob², J. Tardio², S. Page², J. Kindt³, A. Engel⁴, J. Alsenz²

1) F. Hoffmann-La Roche Ltd., Discovery Technologies, Molecular Structure Research, CH-4070 Basel, SWITZERLAND.

2) F. Hoffmann-La Roche Ltd., Preformulation R&D, CH-4050 Basel, SWITZERLAND.

3) Veeco GmbH, Dynamostrasse 19, D-68165 Mannheim, GERMANY.

4) Center for Cellular Imaging and Nano Analytics (CINA), Biozentrum, University of Basel, Mattenstrasse 26, CH-4002 Basel, SWITZERLAND.

Screening Assay to Probe API/Exipient Melt Miscibility and Stabilities using Scanning Probe Microscopy

Assay to visualize API/excipient miscibility and stability of amorphous formulations using a melt-based mixing method is presented. Raman Microscopy in combination with Atomic Force Microscopy is applied to discriminate between homogenously and heterogeneously mixed API/excipient combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. The materials` potential to restructure is imaged and quantified by phase separation analyses on molecular length scales, and the corresponding short time observation windows. It is indicated that results gathered within this study are predictive for samples processed with hot melt extrusion. The assay presented here supports the rational selection of appropriate excipients and API/excipient ratios for amorphous formulations on reasonable time scales.

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Thomas Luxbacher; Anton Paar GmbH, Anton-Paar-Strasse 20, A-8054 Graz, Austria

Assessment of Biomaterial Surfaces by Streaming Potential Measurement

The knowledge of surface charge and the isoelectric point is important for many biomedical applications. The zeta potential, formally defined as the electrical potential at the electrokinetic plane of shear, is an important property of charged solid/liquid interfaces and a descriptor of the actual surface charge of a solid immersed in a dielectric. For macroscopic solid surfaces, the zeta potential is commonly determined by the measurement of streaming potential and streaming current. The versatility of the streaming potential method allows handling of planar surfaces, cylindrical capillaries, and packed beds of granular or fibrous materials. The family of biomaterials consists of all of these types of materials like biosensors with a planar surface, hollow fiber membranes for haemodialysis, chitosan nanofibers for skin replacement, or biopolymer beads for pharmaceutical application.

Besides the evaluation of the charging behavior of such biomaterial surfaces, the zeta potential is a valuable indicator for surface stability in the presence of various liquids, and for the adsorption of proteins, polypeptides, and other biopolymers on biomaterials’ surfaces.

In this paper the application of the streaming potential method in the field of biomaterials’ surface characterization is presented with different case studies.

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G. Papandreou, ¹, K. Wolf, ²,J. Meng, ³, N. Rahbar,³ C. A. Maryanoff,² and W. Soboyejo³

1) Convergent Product Development, Cordis Corporation, 7 Powder Horn Drive, Warren, NJ 07059.

2) Convergent Product Development, Cordis Corporation, Welsh and McKean Roads, Spring House, PA 19477.

3) Princeton Institute for the Science and Technology of Materials (PRISM), Princeton University, Princeton, NJ 08544

Durability Studies of Drug-Eluting Stents

Drug-eluting stents that combine a non-degradable, conformal polymeric coating of a drug and a metallic scaffold have revolutionized the treatment of coronary artery disease. This coating must expand without cracking during the deployment of the stent, and maintain its durability for the lifetime of the implant. To evaluate durability, specimens deployed into mock vessels are exposed to physiologically relevant diametric distention levels using hydrodynamic pulsatile loading. As a model system, the CYPHER® Sirolimus-eluting Coronary Stent produced very low delamination after fatigue. To explain this result, studies of adhesion and interfacial fracture were performed. To evaluate the adhesion within and between the layers of the coating, Atomic Force Microscopy (AFM) was used to obtain the pull-off forces between coated AFM tips and substrates coated with the chemistry of the layers of the CYPHER® Stent. Brazil disk specimens were also prepared mimicking the layers of this coating and stressed to fracture. The resulting initial cracks were used to measure interfacial fracture energy over several mode mixities. Using the AFM surface energy measurements, adhesion and fracture mechanics models were used to estimate the mode mixity dependency of interfacial fracture toughness. The measured interfacial fracture energies from the Brazil disk studies were shown to be in good agreement with the model predictions. These findings explain the good durability of the CYPHER® Stent coating.

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Odessa Petzold, Wageesha Senaratne, Ying Wei, Lijun Zou and Lung Wu; CORNING Incorporated, Sullivan Park, Corning, NY 14831

Exploiting Liver Cell Membrane Receptors and Mechano-Sensing to Modulate Cell Attachment and Morphology

(Abstract not yet available)

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Saurabh Mittra¹ and Robert E. Baier ²

1) CPF (Pepsi) & NEHF (Lipton) Inc, 25 Copeland Drive, Ayer, MA 01432

2) Department of Mechanical and Aerospace Engineering, Industry/University Cooperative Research Center for Biosurfaces, State University of New York at Buffalo, NY 14214

Infrared Microscopic Monitoring of Microfouling on Germanium Surfaces

Microfouling appears at all solid interfaces with biological fluids, depositing biofilms on a submicrometer protein-dominated “conditioning” film with secondary particulate matter—usually bacteria— growing to micrometer and thicker layers. Disadvantageous effects of microfouling range from heat transfer retardation in pasteurization of dairy products and blocking of cooling lines in beverage manufacture to masking of optical sensors and clogging of microfluidic biosensor circuits. Since heat transfer can be monitored by infrared techniques, and infrared-transparent semiconductors—especially germanium—are widely employed platforms for emerging biosensor and microfluidic lab-on-a-chip devices, this investigation employed noninvasive monitoring of microfouling processes by infrared microscopy through germanium prisms already optimized for multiple attenuated internal reflection infrared spectroscopy of thin-film deposits. The results showed closed-cell surface planar resolution of about 50 micrometers, and depth resolution of 0.5 micrometer, allowing interior “conditioning” film formation to be noninvasively monitored and discriminated from consolidated biofilm, polymer film, and mineral deposits based on both radiance vs temperature plots and thermal images, compared with pre-deposited fibrinogen and hyaluronic acid control film baselines. Infrared microscopy will have a useful role in noninvasive monitoring of induction-period and microfouling events in semiconductor-based biosensors and microfluidic circuits of the future, as well as allow remote, non-contact recording of heat transfer efficiencies in biofilm-limited food processing and bio-pharmaceutical manufacturing operations.

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Mark Poggi; Biolin Scientific, 808 Landmark Drive Suite 124, Glen Burnie, MD 21061

Enabling in vitro Real-Time Characterization of Biointerfaces with Quartz Crystal Microbalance with Dissipation Monitoring

There is a growing need for new technologies to quantitatively measure the surface properties of biological and material interfaces. One technique in particular, the Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D), fulfills the need for monitoring real-time dynamic adsorption and desorption phenomena. Capable of operating in liquids and in real-time, QCM-D provides a powerful approach to analyze the in situ thickness, structural, and viscoelastic properties of both coating formation and subsequent interactions with adsorbates of interest. This presentation will focus on the application of QCM-D for monitoring coating formation as well as measuring the response of different coatings to biomolecules. Example interactions include protein and cell adsorption, protein-protein interactions, film hydration and swelling, film drying and collapse, crosslinking, degradation, polyelectrolyte multilayer build-up, and lipid membrane formation. The QCM-D technique has allowed scientists to achieve a more fundamental understanding of how dynamic biological materials behave on the molecular scale and current research in some of these areas will be highlighted.

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Nicholas Randall; CSM Instruments, Needham MA

State-of-the-art in Surface Mechanical Properties Characterization of Biomaterials

Understanding the mechanical behavior of biological and biomaterials is essential to the development of these materials and the devices they are used in. In recent years, investigating these systems at a degree beyond the traditionally available macroscopic methods has become a great focus. The mechanical behavior of biomaterials (both biological and synthetic) span multiple magnitude levels, from the intracellular forces operating at the molecular level to macroscopic organization of multi-layer coating systems commonly employed.

CSM Instruments has been at the forefront of such research with the application of scratch, indentation and tribological test methods to the characterization of challenging new bio- and pharma- materials. Explanation will be given of how such characterization methods need to be adapted to deal with unorthodox sample geometries, compliant substrates and very soft structures. Examples will include testing of drug-eluting stent coatings, crush-testing of pharmaceutical products, testing hydrogels and soft tissues, simulating cell contacts and testing biocompatible coatings.

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Hilton Barbosa de Aguiar, Alex de Beer, Matthew L. Strader and Sylvie Roke; Max-Planck Institute for Metals Research, Stuttgart, Germany

SDS Surfactant Has a Marginal Effect on the Interfacial Tension of Nanoscopic Oil Droplets in Water

Surfactants such as sodium dodecylsulphate (SDS) can reduce the interfacial tension between bulk water and bulk n-hexadecane by 42 mM/m. Although it is commonly expected that interfacial tension lowering should also take place on the interface of nanoscopic oil droplets in water vibrational sum frequency scattering experiments indicate otherwise. In these measurements we have directly measured the adsorption of SDS onto hexadecane oil droplets with an average radius of 83 nm. We find that the interfacial density of adsorbed SDS is at least one order of magnitude lower than that at a corresponding planar interface. The derived maximum decrease in interfacial tension is only 5 mN/m.

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Jean-Sébastien Samson, Hilton Barbosa de Aguiar, Alex de Beer and Sylvie Roke; Max-Planck Institute for Metals Research, Stuttgart, GERMANY

Structure and Functionality of a Potential Liver Cancer Medicine

Liver cancer is a frequently occurring deceases that often turns out to be incurable. The most lethal form occurs when tumors are spread across the entire liver. For this type of malignancies, polymer microspheres with a radio-active Holmium complex seem to enable a promising treatment. This is mainly due to the combination of apparent robustness and biodegradability. Both from a medical and chemical perspective it is desirable investigate the structure of the microspheres. The development of sum frequency scattering (SFS) has created the possibility to observe molecular structural properties and size of buried micro- and nanostructures.

Here, we use SFS in the fingerprint region of the IR spectral range to study the interaction of the Holmium complex with the nano-crystalline domains that we have found inside the polymer microspheres, The Holmium complex preferably resides inside the crystalline domains where it rearranges the structure into one that seems more stable. This finding may explain the apparent robustness of the microspheres which is so important for the medicinal application.

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K. Schröder¹, B. Finke¹, K. Fricke¹, U. Menyes¹, A. Ohl¹, T. Vorhaben², D. Böttcher², U. T. Bornscheuer² and K.-D. Weltmann¹

1) Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Strasse 2,         17489 Greifswald, Germany

2) University of Greifswald, Institute of Biochemistry, Dept. of Biotechnology & Enzyme Catalysis, Felix-Hausdorff-Strasse 4, 17489 Greifswald, Germany

email: schroeder@inp-greifswald.de

Plasma-assisted Immobilization of Bioactive Molecules for Biomedical and Biotechnological Applications

Biomedical and biotechnological applications of polymeric materials often require specific interactions with the biochemical or biological milieu. However, their surface properties do not meet these requirements. Therefore, new surface refinements are very important topics to meet the requirements of advanced applications. Gas-discharge plasmas offer some unique possibilities. They can lead to surface activation and functionalization, often not obtainable with conventional, solvent-based chemical methods.

Essentially, there are three basic advantages of plasma activation and functionalization:

1. The superior chemical reactivity of plasmas allows surface activation of inert materials         in the nanoscale range including creation of covalently bound functional groups.

2. Properly operated plasma activation and functionalization processes do neither affect bulk         materials characteristics nor produce toxic substances.

3. Properly operated non-thermal plasmas cause only minor thermal load to substrates.

Both, plasmas at atmospheric pressure and low pressure can be applied for surface modification. While atmospheric pressure plasmas offer advantages in terms of investment cost and process integrability, low pressure plasmas excel by their superior chemical selectivity.

Examples of plasma-assisted immobilization strategies will be given for cell-adhesion molecules for biomaterials surfaces and enzyme-carriers for white biotechnology.

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Xu Li, Junfei Tian and Wei Shen; Australian Pulp and Paper Institute, Department of Chemical Engineering, Monash University, Clayton Campus, VIC 3800 AUSTRALIA

E-mail: wei.shen@eng.monash.edu.au

Thread-based Low-cost Semi-quantitative Diagnostic Sensors

Multi-filament threads such as cotton thread are attractive materials for transporting liquids; the gaps between fibres in the threads provide capillary wicking channels. This property makes threads a suitable material for fabricating low-cost and low-volume microfluidic devices which can transport liquids without external forces or pumps. When used in sewing, threads have 3D passageways in sewed materials, thus makes threads naturally suitable for the fabrication of 3D microfluidic structures for sensors. Thread-based microfluidic devices can be used to measure analytes quantitatively. Thread can also be used with other porous materials (e.g., paper) to form microfluidics with enhanced sample delivering efficiency to detect multiple analytes simultaneously. Thread and thread-paper microfluidics provide a new design concept for fabrication of healthcare products and diagnostic devices. This presentation reports the research progress of the design and fabrication of the thread-based and thread-paper-based microfluidic devices, and quantitative applications of these microfluidic devices in healthcare monitoring.

Reference

X. Li, J. Tian, W. Shen, “Thread as a versatile material for low-cost microfluidic diagnostics” ACS Applied Materials and Interfaces. 2 (2010) 1–6

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Cláudia Sousa; IBB-Institute for Biotechnology and Bioengineering

Centre of Biological Engineering, University of Minho, Campus de Gualtar

4710-057 Braga, PORTUGAL

Thermodynamic Analysis of S. Epidermidis Adhesion to Biomedical Materials

(Abstract not yet available)

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Sofia Svedhem; Rickard Frost, and Bengt Kasemo; Dept. of Applied Physics, Chalmers University of Technology, 412 96 Göteborg, SWEDEN

Supported Lipid Membranes as Model Systems for Nanodrug and Nanoparticle Interactions at Biological Barriers

The present contribution will focus on the application of surface-supported lipid membrane model systems to the mimicking of biological barriers and their interactions with nanodrugs and other nanoparticles (e.g. liposomal, polymeric, or inorganic nanoparticles). Different means for formation of supported lipid membranes and in situ membrane modifications changing e.g. the membrane composition (/functionalisation) and morphology will be described. Real-time monitoring of membrane – nanoparticle interactions were achieved at such interfaces using the quartz crystal microbalance with dissipation monitoring (QCM-D) and optical reflectometry. Complementary data were obtained by different microscopic techniques. Generally, nanoparticles interacted selectively with differently charged membranes as predicted by the nanoparticle zetapotential, and it is shown how the structure of the adsorbed material depended on the properties of the supported membrane [1]. The extension of these model systems to include also hydrogel layers (glycocalix mimics) will be discussed. We foresee that approaches similar to ours will be useful for the characterization of nanoscale materials when designing e.g. drug delivery systems, and for nanoparticle toxicology screening.

[1] Frost, R., Grandfils, C., Cerda, B., Kasemo, B., and Svedhem, S. Real-time monitoring of the interaction between polymeric insulin-loaded nanodrug particles and surface-supported lipid bilayers, Langmuir, submitted

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Ruchirej Yongsunthon,Wendy Baker, Marie Bryhan, Jin Liu, Theresa Chang and

Odessa Petzold; CORNING Incorporated, Sullivan Park, Corning, NY 14831

Force Spectroscopy to Investigate Cell Reconstruction of Culture Surfaces

It is generally accepted that cell culture substrates can influence the behavior of cells grown in vitro, but it is not clear how the cells in turn affect and modify these substrates. It is possible that cell culture outcome is determined by cell-mediated substrate reconstruction, as well as the original substrate surface properties. To optimize cell culture performance, it is thus important to understand the synergistic interaction between cells and their culture surfaces. We present force spectroscopy, used in conjunction with atomic force microscopy, as a method for investigation of cell modification of substrate surfaces. Analysis of the “footprints” of hepatocytes (HepG2/C3A liver cell line) indicated that the cells secrete large polymers (e.g., 5um contour length and estimated MW 1500kDa) onto their substrate surface. Although definitive identification of the polymers has not yet been achieved, fluorescent-labeled antibody staining has specified the presence of extracellular matrix (ECM) proteins such as collagen and laminin in the cellular footprints. The stretched polymers appear to be much larger than single molecules of known ECM components, thus suggesting that the cells create larger macromolecular structures from smaller components. Preliminary results indicate that there is inter-dependence between cell morphology, extracellular polymers and proteins, and substrate surface properties.

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