Stephen P. Beaudoin

Sensitive and real-time fiber-optic-based surface plasmon resonance sensors for myoglobin and cardiac troponin I

A sensor to detect markers of cardiac muscle cell death at less than 3ngml(-1) and in less than 10min has been achieved. This fiber-optic-based surface plasmon resonance (SPR) sensor is being applied to detect myoglobin (MG) and cardiac troponin I (cTnI) in HEPES buffered saline solution. An in vivo sensor for the early detection of the onset of myocardial infarction (MI) will greatly enhance the patient care. MG and cTnI are two biological markers released from dying cardiac muscle cells during an MI, and their detection at biologically-relevant levels can be diagnostic of MI. Antibodies specific to an antigen of interest are attached to a carboxymethylated dextran layer on a gold SPR surface. With the method developed, the lower limit of detection (LOD) for MG is 2.9ngml(-1) at 25 degrees C. The biological level for MG reaches 15-30ngml(-1) in patient blood after myocardial damage. A Langmuir adsorption isotherm describes the binding well. For cTnI, a lower detection limit of 1.4ngml(-1) was achieved in preliminary tests. cTnI levels are in the range of 1-3ngml(-1) in patient blood after myocardial damage. The antibody reaction with the carboxymethylated dextran surface was optimized by modifying the reaction pH, the temperature, and the dextran chain length.

Describing Hydrodynamic Particle Removal from Surfaces Using the Particle Reynolds Number

The fundamental processes related to the removal of fine particles from surfaces in a hydrodynamic flow field are not adequately understood. A critical particle Reynolds number approach is proposed to assess these mechanisms for fine particles when surface roughness is small compared to particle diameter. At and above the critical particle Reynolds number, particle removal occurs, while below the critical value, particles remain attached to a surface. The system under consideration consists of glass particles adhering to a glass surface in laminar channel flow. Our results indicate rolling is the removal mechanism, which is in agreement with the literature. Theoretical results of the critical particle Reynolds number model for rolling removal are in general agreement with experimental data when particle size distribution, particle and surface roughness, and system Hamaker constant are taken into account.

Biocompatible polymers for antibody support on gold surfaces

The elimination or minimization of non-specific protein adsorption from serum is critical for the use of surface plasmon resonance (SPR) sensors for in vitro and in vivo analysis of complex biological solutions. The ultimate goals in this application are to minimize non-specific adsorption of protein and to maximize analyte signal. A reduction of the non-specific protein adsorption from serum of up to 73% compared to carboxymethylated-dextran 500kDa (CM-dextran) was achieved following a survey of eight biocompatible polymers and 10 molecular weights of CM-dextran. These coatings minimize non-specific adsorption on the sensor while also serving as immobilization matrices for antibody fixation to the probes. Polymers including polysaccharides: CM-dextrans, CM-hyaluronic acid, hyaluronic acid, and alginic acid were investigated. Humic acid, polylactic acid, polyacrylic acid, orthopyridyldisuldfide-polyethyleneglycol-N-hydroxysuccinimide (OPSS-PEG-NHS), and a synthesized polymer; polymethacrylic-acid-co-vinyl-acetate (PMAVA) were also used. The non-specific protein adsorption reduction was measured over a 14 day period at 0 degrees C for each polymer. Calibration curves using some of these polymers were constructed to show the performance and low detection limit possibilities of these new antibody supports. For many of the polymers, this is the first demonstration of employment as an antibody support for an optical or surface active sensor. CM-dextran is the polymer offering the largest signal for the antigen detection. However, the biocompatible polymers demonstrate a greater stability to non-specific binding in serum. These biocompatible polymers offer different alternatives for CM-dextran.

Modeling and Validation of the van der Waals Force During the Adhesion of Nanoscale Objects to Rough Surfaces: A Detailed Description

The interactions between nanoparticles and rough surfaces are of great scientific and engineering importance and have numerous applications in surface science and biotechnology. Surface geometry and roughness play crucial roles in observed particle adhesion forces. We previously developed a model and simulation approach to describe adhesion between microscale bodies. This work provides detailed descriptions of the modeling framework, with associated experimental validation, applied to nanoscale systems. The physical systems of interest include nanoscale silicon nitride adhering to different surfaces in both dry and aqueous environments. To perform the modeling work, precise descriptions of the geometry of the particle and the roughness of the particle and substrate were generated. By superimposing the roughness and geometry models for the particle and the substrate, it was possible to precisely describe the spatial configurations of the adhering surfaces. The interacting surfaces were then discretized, and the adhesion force between the two surfaces was calculated by using Hamakers additive approach, based on van der Waals interactions. In the experimental work, an atomic force microscope (AFM) was used to measure the adhesion force (pull-off force) between nanoscale silicon nitride cantilever tips and a range of substrates in different environments. The measured and predicted force distributions were compared, and good agreement was observed between theory and experiment.

A Locally Relevant Prestonian Model for Wafer Polishing

Chemical mechanical planarization (CMP) is the primary method of wafer-scale planarization used in the manufacture of advanced integrated circuits. Prestons model, which was introduced in the 1920s for glass polishing, is an important component of much of the recently published work on CMP modeling. As applied, Prestonian models are effective in describing the average behavior of a process but are ineffective in providing fundamental understanding and locally relevant information regarding a chosen process. To date, there are still very few quantitative wafer-scale CMP removal rate and uniformity models. In this work, a locally relevant expression for material removal rate based on Prestons equation is presented. It incorporates localized kinematics and stress calculations. The model predictions are compared to experimental results for silicon dioxide polishing on a dual-axis CMP platform.

Surface forces and protein adsorption on dextran- and polyethylene glycol-modified polydimethylsiloxane

Dextran and polyethylene glycol (PEG) are often covalently bound to the surface of polydimethylsiloxane (PDMS) for the purpose of modifying its hydrophilicity and biocompatibility. In this work, the effects of the dextran and PEG on the morphology, wetting, and surface charge of the resulting surfaces were quantified and correlated with changes in the amount of fibrinogen and albumin adsorbed from aqueous solution. PDMS films were functionalized in a microwave oxygen plasma to create surface hydroxyl groups that were subsequently aminated by incubation in a (3-aminopropyl)trimethoxysilane (APTES) solution. Oxidized dextran and PEG-aldehyde were linked to the surface amines via reductive amination. This process resulted in low surface coverage of immobilized PEG in the end-on conformation and a more uniform and dense distribution of side-on immobilized dextran. The immobilized dextran reduced the contact angle of the PDMS film from 109° to 80° and neutralized the zeta potential over the pH range from 3 to 11. An atomic force microscope was used to measure the interaction force between the modified PDMS and a model hydrophobic surface (polystyrene latex) and a model hydrophilic surface (silica) in aqueous solution to show that van der Waals and hydrophobic attractive forces are the dominant forces for protein adsorption in this system. The PEG- and dextran-modified PDMS were exposed to BSA and fibrinogen to test their resistance to protein adsorption. The coatings were ineffective at reducing the adsorption of either molecule, and the dextran-modification of the PDMS caused more BSA to adsorb than in the case of the unmodified PDMS.

Preparation of analyte-sensitive polymeric supports for biochemical sensors

The preparation and use of multiple polymers attached to a surface plasmon resonance (SPR) sensor for optimization of signal enhancement and minimization of fouling during sensing of biological species has been achieved. These polymers are advantageous compared to the current practice of carboxymethylated-dextran (CM-dextran). The polymers offer a wide range of functionalities and different molecular weights. Using these polymers, the SPR sensors can be fabricated as fast or faster than the CM-dextran sensor. In this study, we investigated the use of nine polymers for SPR biosensors. Polysaccharides, including CM-dextran, CM-hyaluronic acid, hyaluronic acid, and alginic acid, were investigated. Humic acid, polylactic acid, polyacrylic acid, orthopyridyldisulfide-polyethyleneglycol-N-hydroxysuccinimide (OPSS-PEG-NHS) and a synthesized polymer; polymethacrylic-acid-co-vinyl-acetate (PMAVA), were also used. The polymers were chemically attached to a thiol monolayer on the SPR biosensor using carbodiimide chemistry. The polymers were functionalized for binding of anti-myoglobin (anti-MG). The sensor performance was measured using myoglobin (MG) at 25ngml(-1), a biologically relevant level for myocardial infarction detection. Most polymers offered similar performance to CM-dextran for MG detection in HEPES buffer saline pH 7.4 (HBS). In preliminary studies in bovine serum, each of the candidate polymers demonstrated better performance than CM-dextran.

Incorporation of a decorin biomimetic enhances the mechanical properties of electrochemically aligned collagen threads.

Orientational anisotropy of collagen molecules is integral to the mechanical strength of collagen-rich tissues. We have previously reported a novel methodology to synthesize highly oriented electrochemically aligned collagen (ELAC) threads with mechanical properties approaching those of native tendon. Decorin, a small leucine-rich proteoglycan (SLRP), binds to fibrillar collagen and has been suggested to enhance the mechanical properties of tendon. Based on the structure of natural decorin, we have previously designed and synthesized a peptidoglycan (DS-SILY) that mimics decorin both structurally and functionally. In this study, we investigated the effect of the incorporation of DS-SILY on the mechanical properties and structural organization of ELAC threads. The results indicated that the addition of DS-SILY at a molar ratio of 30:1 (collagen:DS-SILY) significantly enhanced the ultimate stress and ultimate strain of the ELAC threads. Furthermore, differential scanning calorimetry revealed that the addition of DS-SILY at a molar ratio of 30:1 resulted in a more thermally stable collagen structure. However, addition of DS-SILY at a higher concentration (10:1 collagen:DS-SILY) yielded weaker threads with mechanical properties comparable to collagen control threads. Transmission electron microscopy revealed that the addition of DS-SILY at a higher concentration (10:1) resulted in pronounced aggregation of collagen fibrils. More importantly, these aggregates were not aligned along the long axis of the ELAC, thereby compromising the overall tensile properties of the material. We conclude that incorporation of an optimal amount of DS-SILY is a promising approach to synthesize mechanically competent collagen-based biomaterials for tendon tissue engineering applications.

Effects of gas pressure and substrate temperature on the etching of parylene-N using a remote microwave oxygen plasma

The effects of temperature and pressure on the rate of etching of parylene-N in a downstream oxygen plasma created with a microwave source have been determined. Etch rate increases with increasing substrate temperature, with an apparent activation energy of 6.6–8.0 kcal/mol over the 373–523 K temperature range. The etch rate goes through a maximum between 0.6 and 0.8 Torr as pressure is increased from 0.4 to 1.0 Torr. The observed maxima are more pronounced as substrate temperature increases. Analyses of x-ray photoelectron spectra for unetched and etched films reveal that exposure to the plasma afterglow decreases the relative amount of aromatic carbon and creates carboxylic acid groups in the film. Residual gas analysis of the reactor effluent during etching indicates that the only volatile etch products are H2O, CO2, and CO. Likely reactions that may lead to the formation of the observed etch products are presented and discussed.

Simulation of particle adhesion: Implications in chemical mechanical polishing and post chemical mechanical polishing cleaning

We have previously described a model and a simulation approach to describe the adhesive interaction between a particle and a substrate. In this paper, we use the validated simulation to describe the adhesive interaction for alumina particles in contact with dielectric and metal films relevant to chemical mechanical polishing (CMP) and post-CMP cleaning during integrated circuit manufacture. The descriptions take into account variations in the geometry surface morphology, and mechanical properties of the particles and substrates. The predictions demonstrate that these three parameters can cause the interaction forces between particles and substrates to vary considerably compared to those for perfect spheres and flat substrates.