This PDF file contains the front matter associated with SPIE Proceedings Volume 6799, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.

Many bacterial species are able to colonize the surfaces of biomedical tools or devices and form biofilms creating a source of infection and other deleterious effects. Biofilms constitute environments in which bacteria grow and are protected from the host's immune system and antimicrobial medications. The bacterial adhesion, which is an important and first step in biofilm formation, is influenced by several physico-chemical and topographical factors at the interfaces between the bacterial cell and the surface. Therefore, the mechanism of initial adhesion needs to be investigated to better understand the events of anchorage and film formation as bacteria colonise surfaces. In this work, atomic force microscopy (AFM) in the tapping mode of imaging has been employed to investigate the attachment of bacteria onto a structured surface patterned with different hydrophilic and hydrophobic areas. The interactions of Escherichia coli and Staphylococcus aureus with these structures were also monitored by fluorescence microscopy. AFM was successfully employed for the study of the cell responses to both nanotopography and the surface chemistry via observation of various cell functions; including extracellular polymeric substance (EPS) mediated cellular adhesion.

Hemodialysis for chronic renal failure is the most popular treatment method with artificial organs. However, hemodialysis patients must continue the treatment throughout their life, the results of long term extracorporeal dialysis, those patients develop the various complications and diseases, for example, dialysis amyloidosis etc. Dialysis amyloidosis is one of the refractory complications, and endotoxin is thought to be the most likely cause of it, recently. Endotoxin is one of the major cell wall components of gram-negative bacteria, and it has various biological activities. In addition, it is known that a mount of endotoxin exists in living environment, and medicine is often contaminated with endotoxin. When contaminated dialyzing fluids are used to hemodialysis, above-mentioned dialysis amyloidosis is developed. Therefore, it is important that the detection and removal of endotoxin from dialyzing fluids. Until now, the measurement methods using Limulus Amebosyte Lysate (LAL) reagent were carried out as the tests for the presence of endtoxin. However, these methods include several different varieties of measurement techniques. The following are examples of them, gelatinization method, turbidimetric assay method, colorimetric assay method and fluoroscopic method. However, these techniques needed 30-60 minutes for the measurement. From these facts, they are not able to use as a "real-time endotoxin detector". The detection of endotoxin has needed to carry out immediately, for that reason, a new detection method is desired. In this research, we focused attention to adsorption reaction between ε-polylysine and endotoxin. ε-polylysine has the structure of straight chain molecule composed by 25-30 residues made by lysine, and it is used as an antimicrobial agent, moreover, cellulose beads with immobilized ε-polylysine is used as the barrier filter for endotoxin removal. The endotoxin is adsorbed to immobilized ε-polylysine, as the result of this reaction, the mass incrementation is occurred, and the existence of endtoxin can be detected immediately, by using of Quartz Crystal Microbalance (QCM). In this report, the immobilization of ε-polylysine onto the Au and Si substrate and its adsorptive activity are described. We use X-ray Photoelectron Spectroscopy (XPS) to confirm the ε-polylysine immobilization, and the adsorptive activity of immobilized ε-polylysine is measured by AFM and QCM. This molecular adsorption type endotoxin sensor aims to the realization of "real-time endotoxin detection system".

A new generation of inertial measurement technology is being developed enabling a 10-micron particle to be "aware" of its geospatial location and respond to this information. The proposed approach combines an inertially-sensitive nanostructure or nano fluid/structure system with a nano-sized chemical reactor that functions as an analog computer. Originally, a cantilever-controlled valve used to control a first order chemical reaction was proposed. The feasibility of this concept was evaluated, resulting in a device with significant size reductions, comparable gain, and lower bandwidth than current accelerometers. New concepts with additional refinements have been investigated. Buoyancy-driven convection coupled with a chemical recording technique is explored as a possible alternative. Using a micro-track containing regions of different temperatures and thermosensitive liposomes (TSL), a range of accelerations can be recorded and the position determined. Through careful design, TSL can be developed that have unique transition temperatures and each class of TSL will contain a unique DNA sequence that serves as an identifier. Acceleration can be detected through buoyancy-driven convection. As the liposomes travel to regions of warmer temperature, they will release their contents at the recording site, thus documenting the acceleration. This paper will outline the concept and present the feasibility.

Metal (especially gold) nanoparticles exhibit unique electronic, optical, and catalytic properties. In order to utilize these properties, an integration of the particles into technical setups such as a chip surface is helpful. We develop techniques to use (bio) molecular tools in order to address and control the positioning of particles on microstructured chips. These techniques are utilized for novel DNA detection schemes using optical or electrical principles. Plasmonic properties of the particles and the combination of nano-apertures with particles are promising fields for further bioanalytical developments. On the other hand, methods for defined positioning of single molecules or molecular constructs in parallel approaches are under development, in order to provide needed defined nanostructures for applications in nanoelectronics. Connecting DNA with nanoparticles, metallization of DNA or positioning of individual DNA-structures over microstructured electrode gap including subsequent metal particle binding are important steps in this direction. The utilization of (bio) molecular tools and principles based on highly specific binding and self-assembly represent a promising development in order to realize novel nanoparticle-based devices for bioanalytics, nano-optics and - electronics.

The control of protein binding into nanostructured porous surfaces is highly relevant to the development of advanced biosensors and other biodevices. Here, an investigation of the covalent immobilisation of a model protein (albumin) onto porous silicon (pSi) films was conducted using a new alkene linker, the synthesis of which was developed. This alkene linker contained both hydrophobic and hydrophilic (oligoethylene glycol) sections and terminated in a protected thiol. The alkene was attached to freshly etched porous silicon via thermal hydrosilylation, where further surface reactions resulted in the attachment of a maleimido N-hydroxysuccinimidyl (NHS) heterobifunctional crosslinker. Albumin was then covalently immobilised on the porous silicon layer through reaction of the protein's amine groups and the NHS functional group of the crosslinker. Surface modification reactions were monitored by infrared spectroscopy and interferometric reflectance spectroscopy. Protein binding was monitored by infrared spectroscopy, fluorescence imaging and atomic force microscopy.

Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H₂O₂ catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.

The control over surface wettability is of concern for a number of important applications including chromatography, microfluidics, biomaterials, low-fouling coatings and sensing devices. Here, we report the ability to tailor wettability across a surface using lateral porous silicon (pSi) gradients. Lateral gradients made by anodisation of silicon using an asymmetric electrode configuration showed a lateral distribution of pore sizes, which decreased with increasing distance from the electrode. Pore sizes were characterised using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Pore diameters ranged from micrometres down to less than 10 nanometres. Chemical surface modification of the pSi gradients was employed in order to produce gradients with different wetting or non-wetting properties. Surface modifications were achieved via silanisation of oxidised pSi surfaces introducing functionalities including polyethylene glycol, terminal amine and fluorinated hydrocarbon chains. Surface modifications were characterised using infrared spectroscopy. Sessile drop water contact angle measurements were used to probe the wettability in regions of different pore size across the gradient. For the fluorinated gradients, a comparison of equilibrium and dynamic contact angle measurement was undertaken. The fluorinated surface chemistry produced gradients with wettabilities ranging from hydrophobic to near super-hydrophobic whereas pSi gradients functionalised with polyethylene glycol showed graded hydrophilicity. In all cases investigated here, changes in pore size across the gradient had a significant effect on wettability.

The spark plasma sintering behaviour of silver nanopowder prepared by the electro-explosion method was investigated. Consolidation was carried out from 50°C to 800°C for 5 mins at 34 MPa with differential scanning calorimetry indicating a sintering onset temperature as low as 160°C and an activation energy of 86±1 kJ/mol. Near full density resulted from treatment at 300°C, and at higher temperatures a normal Hall-Petch relation is obeyed. The enhancement of Vicker's hardness to 1000MPa for materials sintered at 300°C is three times greater than for silver annealed in a conventional way. While polysynthetic twinning contributes to superior hardness, the primary cause is the sub-micron grain size.

Droplet-based in vitro compartmentalization (IVC) platform is a powerful tool in protein analysis. Reliable formation of microdroplets is important for the development of the microfluidic chip. In this study, we will examine the effect of surfactants on the formation of microdroplets in the flow focusing microfluidic device which is needed for enzyme evolution. Surfactants of Span 80 and Tween 20 are used in the continuous and dispersed phases, respectively. The droplet formation was affected distinguishably with the presence of Span 80 and Tween 20. The size of droplets decreased as the concentration of Span 80 increased. And the decrease was more pronounced with the combination of Span 80 and Tween 20.

The scanning probe microscopy-based (SPM) lithography techniques have presented significant challenges in fabricating nanostructures. Using this technique with assistance of pulse current, direct deposition or oxidation can be introduced on material surfaces. In present research, we use an atomic force microscope (AFM) to write a solid (gold) feature onto a substrate (silicon) in ambient environment. During the contact-sliding, the material on the gold (Au) tip transferred onto the surface of the single crystalline silicon (Si). This transfer takes place atomically as shown on a smoothly worn Au tip. This process is almost as simple as writing a line with a pencil. Dispersion of thermal energy inducted through friction is discussed in this presentation.

The performance of dye-sensitized solar cells (DSC) based on the TiO₂ film composed of 3 nm particles and mixtures of 3 nm and 400 nm or 25 nm particles synthesized by spray pyrolysis deposition has been investigated. An energy conversion efficiency of 8.44% (under the illumination of 100 mW/cm², AM 1.5) has been achieved with the DSC based on the nanocrystalline TiO₂ film consisting of 3 nm and 25 nm particles with a ratio of 3:4 by weight. The maximum incident photo-to-current conversion efficiency (IPCE) of the cell is 0.91, which is much higher than the maximum IPCE of the photoelectrode composed of either only 3 nm or the mixture of 3 nm and 400 nm particles (with the same ratio by weight) over the visible spectrum. SEM images show the formation of clusters in the TiO₂ film containing 25 nm particles. It is proposed that the clusters are responsible for the high IPCE by increasing the light harvesting efficiency through enhanced light scattering and facilitating the electron transport of the DSC.

Presented is an investigation of surface morphology of arrayed MoO_x structures with increasing aspect ratios, and their resultant superhydrophillic, and their modified superhydrophobic properties. Molybdenum oxide (MoO_x) submicron structures were grown on lithium niobate (LiNbO₃) substrates via the thermal evaporation of MoO₃ nanopowder at 750°C in a horizontal tube furnace. A mixture of 90% argon and 10% oxygen was introduced into the thermal evaporation tube at flow rate of 1L/min. This resulted in the formation of a white film which consisted of submicron tabular structures. Scanning electron micrographs revealed that the tabular molybdenum oxide grew in arrays 80-100° with respect to the plane of the substrate, with tabular structures with a thickness of approx 0.5 - 1.5μm. Initial testing of MoO_x structures revealed that they were extremely super hydrophilic. Such MoO_x arrays were coated with fluoropolymer Teflon, deposited using the RF sputtering technique. The addition of a semi-conformal Teflon layer effectively converts the superhydrophilic MoO_x layer into a superhydrophobic surface. These superhydrophobic surfaces exhibit contact angles with aqueous media in excess of 150°. Such surfaces can be utilized for the selective adsorption and desorption of protein or pharmacokinetic molecules, with applications in drug delivery and biomedical systems.

There are vast advantages of using a SAW device based micro-valve in Micro Electro Mechanical Systems (MEMS) and Nano Electro Mechanical Systems (NEMS) such as secure, reliable and low power operation, small size, simplicity in construction and cost effectiveness. In this paper, a Surface Acoustic Wave (SAW) based microvalve that generates micro actuations for micro-fluidic and similar applications is presented. The microvalve is batteryless and can be actuated wirelessly. The security of the device is enhanced by using a coded SAW correlator that is integrated as part of the microvalve. A theoretical analysis of how the actuation mechanism operates is carried out and simulation results of the new micro-valve structure are discussed. ANSYS simulation tool is used to design and simulate the micro-valve structure. Characteristics of the microvalve actuator in terms of displacement for different operating conditions are also discussed.

In this work, we have investigated the effect of changes in the properties of planar surfaces on the attachment and viability of two bacterial species of medical relevance. Polydimethylsiloxane (PDMS) surfaces showed a promising repellent effect on both live and dead E. coli and S. aureus cells. When the hydrophilicity of the PDMS was increased by UV-radiation this repellent effect disappeared. On gold surfaces coated with hydrophobic and hydrophilic self assembled monolayers (SAM) very few bacterial cells were found, compared to plain gold. Moreover, the behaviour of E. coli and S. aureus was modulated differently by the surface properties. Thus, while S. aureus cells lived in slimy conglomerates and colonised the surfaces at the same high density from both diluted and concentrated solutions, in contrast, single cells of E. coli colonised the surfaces at lower densities from diluted solutions. Also, dead E. coli cells were easily washed off from most surfaces, whilst dead S. aureus cells were frequently found attached to the surfaces, which may also be explained by its occurrence in conglomerates. Strain specific bacterial physiology and reactivity to these surfaces may possibly also be a factor in influencing the interaction. These initial results contribute to the purposeful design of species-specific pro- or anti-bacterial surfaces for the use of lab-on-a-chip devices and medical devices.

Electrorotation method is a useful technique for characterizing dielectric properties of individual cells or particles. During the electrorotation process, a dielectric cell is subjected to rotating electric field of high frequency and its rotation speed is monitored. As high conductivity buffer is used in the process, heat is generated which in turn affects cell rotation performance. In this work, we present temperature analytical results of a 4-electrode electrorotation chip using finite element method. The simulation conditions include variation of applied voltage, buffer conductivity and material of the chip. We found that the applied voltage and conductivity of buffer used are two main factors affecting temperature rise in electrorotation process.

This paper describes how multiple interferometric techniques, implemented on a single system, can be combined to provide viable measurements of both biosensors and cells, enabling collection of data in environments and with timescales not previously achievable.

In this study, a vacuum driven blood extraction device for the self-monitoring of blood glucose (SMBG) was newly developed. The health monitoring system (HMS) for SMBG consists of a blood extracting system and a drug delivery system (DDS). Our HMS extracts the blood through a micro-needle and measures the blood sugar level accurately. The main purpose of this work in HMS development are, 1) minimally invasive blood extraction, 2) a handy type automatic blood extraction, and 3) a continuous measurement of the blood sugar level. We adopted a vacuum driven type blood extraction mechanism. The vacuum driven blood extraction unit consists of a) a puncture part to open the vacuum part, b) an extraction part, and c) a measurement part. The puncture and extraction parts consist of a minimally invasive micro-needle, whose inner diameter is less than 100μm and made of titanium alloy, and a vacuum chamber, which is covered by a very thin membrane. A SMA spring and two bias springs are employed to penetrate the blood vessel through the skin with the micro-needle, and to execute the punctuation to slash the membrane in order to open the vacuum chamber. The blood is extracted into the vacuum chamber, seeps into the unwoven cloth according to the capillary principle, and is finally deposited on the blood sugar level sensor. Results show, our vacuum driven blood extraction device succeeded in extracting 12.7μl of human blood within 2 seconds. The blood sugar level was measured successfully by using a glucose enzyme sensor. Finally, the availability of our HMS device was confirmed.

The successful development of micro-needles can help transport drugs and vaccines both effectively and painlessly across the skin. However, not all micro-needles are strong enough to withstand the insertion forces and viscoelasticity of the skin. The work here focuses on the micro-fabrication of high aspect ratio needles with careful control of needle-profile using dry etching technologies. Silicon micro-needles, 150μm in length with base-diameters ranging from 90 to 240μm have been investigated in this study. A novel, multiple-sacrificial approach has been demonstrated as suited to the fabrication of long micro-needle bodies with positive profiles. The parameters that control the isotropic etching are adjusted to control the ratio of the needle-base diameter to needle length. By careful control of geometry, the needle profile can be engineered to give a suitable tip size for penetration, as well as a broad needle base to facilitate the creation of either single or multiple-through holes. This approach allows the mechanical properties of the otherwise brittle needles to be optimized. Finite element analysis indicates that the micro-needles will fracture prematurely due to buckling, with forces ranging from 10 to 30mN.

A palm-size interdigital impedance sensor incorporating a 10 μL sample reservoir, temperature sensor and hybrid heater was fabricated to determine the feasibility of measuring macronutrients in ultra-small volumes of human breast milk. Comparisons with previous measurements of homogenized cows milk show excellent agreement with fat measurement. Human breast milk however shows no correlation with fat but a surprising correlation with protein. Our investigations and proposed methods to improve the correlation and measurement accuracy are discussed.

The microneedle size mimicking a female mosquito's labium which almost collects blood painless is effective to mitigate the injection pain for patients. The author has produced the microneedle production technique which can produce arbitrary size. The microneedle production technique is to deposit the microneedle material on a rotating wire substrate by a sputtering deposition method and etch the wire substrate by a chemical solution after a heat treatment. In the result, a titanium microneedle was produced (outer and inner diameter : 50 μm and 25μm) in the size mimicking that of female mosquito's labium. The inner diameter for the needle is decreased when outer diameter is decreased, hence, the rigidity of the needle is decreased and the pressure drop by pipe friction is increased. Therefore, microneedles to be able to mitigate the pain for the patient and decrease the pressure drop by pipe friction should be designed. In this study, the outer and inner diameters of 50 μm and 25 μm are defined as the basic dimension of the microneedle. Those rigidity and pressure drop by pipe friction in "n" polygonal shape circumscribed and inscribed for basic dimension in the microneedle are calculated. The best shape with "n" polygonal shape to satisfy conditions that needle has rigidity enough to inject the skin without buckling and to decrease the pressure drop by pipe friction to be able to extract blood was searched. The pressure loss became small more than the negative pressure generated with SMA micro pump in n=6. Therefore, the microneedle with sexanglular shape(n=6) made by titanium(E=110.6GPa) can be injected into the skin without buckling and decreased the pressure drop by pipe friction.

Lab on chip (LOC) systems often require the controlled movement of individual biological cells. Automated operation of these systems usually requires detectors to track individual cells. Electrical methods involving measurement of the conductivity or permittivity of regions between two electrodes are capable of providing this information. However, these detection systems can interfere with other dielectrophoretic LOC cell handling systems. Conversely optical systems are immune to electrical interference. Many LOC devices are fabricated with only the top surface of the device being transparent to light, precluding the use of transmitted optical detection. This is often due to the use of silicon, a favoured substrate. Here we present a low cost optical system suitable for detecting biological cells in microfluidic channels. A flow cell with a fluid microlayer approximately 105±10μm deep was fabricated having a 100±10μm thick glass window, and a reflective base layer. The reflective base was formed by thermal evaporation of gold onto a substrate. Particles within a microfluidic layer were epi-illuminated by a standard (red) laser DVD pickup unit. The flow cell permitted the laser beam to be focussed onto the gold reflector, and back through a beamsplitter onto a photodiode. This system was tested using polystyrene beads that were representative of biological cells. The position of the focal point significantly affected the base line reflected signal, but this micron scale position sensitivity could be overcome using the magnetic focussing coil of the DVD pickup. In this system, polystyrene beads down to 3μm in diameter were successfully detected.

The mergence of partial aspects and functional components of micro actuators and micro fluidic technology allows the development of complex micro systems, which are more and more interesting for MEMS application, especially for BioMEMS. This enormous potential is shown in this article showing the realization of an electro magnetic micro pump. The basic build-up consists of a polymer magnet integrated into a pump chamber of a fluidic PDMS device, which is located above a double layer micro coil. By applying a current, the polymer magnet performs a bidirectional movement, which results in a pumping effect by the two arranged passive check valves being perpendicularly arranged to the flow channels. The valve membrane is flexible and opens the channel towards the flow direction. The advantage of this configuration is that leakage can be avoided by the special geometrical configuration of the fluid chamber and the valves. The fabrication process includes UV depth lithography using AZ9260, electroforming of copper for the double layer spiral coil and Epon SU-8 for insulation, embedding and manufacturing of the valve seat. Furthermore, the fluidic devices are realized by replica molding of PDMS using a multilayer SU-8 master. Furthermore, a new technology for realizing micro polymer magnets was optimized and deployed. Using these fabrication processes, a magnetic micro actuator has already been developed based on the movable plunger principle, which forms the basic set-up of the micro pump. This actuator is monolithically fabricated and successfully tested. In addition, the fluidic system of the micro pump was successfully fabricated and tested. In order to connect the valve seats based on SU-8 to the PDMS fluidic chamber and the valve lips, a special bonding process was developed. The combination of the fluidic system with the electromagnetic part is currently under investigation. The dimension of the micro pump is about 10 × 6 × 3 mm.

We have explored controlled movement of magnetic beads and a dumbbell structure composed of DNA, a magnetic and a non-magnetic bead in a micro fluidic channel. Movement of the beads and dumbbells is simulated assuming that a net force is described as a superposition between the magnetic and hydrodynamic drag forces. Trajectories of beads and dumbbells are observed with optical light microscopy. The experimentally measured data show a good agreement with the simulations. This dynamical approach offers the prospect to stretch the DNA within the dumbbell and investigate its conformational changes. Further on, we demonstrate that short sonication can reduce multiple attachments of DNA to the beads.

We are investigating the use of nanoscale imaging technologies that might help in the fundamental understanding of cell function and lead to early diagnosis of diseases at a single cell and molecular level. A new method has been developed that integrates nanoimprint lithography directly with biological materials to create replica cell impressions in robust storage medium to facilitate topographical analysis using Atomic Force Microscopy. Termed Bioimprint^TM, soft lithography techniques are used to transfer precise cell topography into polymeric composite for imaging in harsh probing or electron beam environments. By creating a permanent biological print that is captured in a specific moment of time, a recorded response of cellular events can be stored. The high resolution transfer of this process is illustrated by imaging membrane morphological structures consist with exocytosis, in pituitary cells. The integration of soft lithography and biological materials presents a novel method for the study and detection of biological systems at the nano scale. Applications of this technique to cancer cells has also been investigated.

The ability to evaluate and control the cellular response to substrate materials is the key to a wide range of biomedical applications ranging from diagnostic tools to regenerative medicine. Gradient surfaces provide a simple and fast method for investigating optimal surface conditions for cellular responses such as attachment and growth. By using two orthogonal gradients on the same substrate, a large space of possible combinations can be screened simultaneously. Here, we have investigated the combination of a porous silicon (pSi) based topography gradient with a plasma polymer based thickness gradient. pSi was laterally anodised on a 1.5 × 2.5cm² silicon surface using hydrofluoric acid to form a pore size gradient along a single direction. The resulting pSi was characterised by SEM and AFM and pore sizes ranging from macro to mesoporous were found along the surface. Plasma polymerisation was used to form a thickness gradient orthogonal to the porous silicon gradient. Here, allylamine was chosen as the monomer and a mask placed over the substrate was used to achieve the thickness gradient. The analysis of this chemistry based gradient was carried out using profilometry and XPS. It is expected that orthogonal gradient substrates will be used increasingly for the in vitro screening of materials used in biomedical applications.

Protein aggregation is arguably the most common and troubling manifestation of protein instability, encountered in almost all stages of protein drug development. The production process in the pharmaceutical industry can induce flows with shear and extensional components and high strain rates which can affect the stability of proteins. We use a microfluidic platform to produce accurately controlled strain regions in order to systematically study the main parameters of the flow involved in the protein aggregation. This work presents a characterization of the pressure driven flow encountered in arrays of micro channels. The micro channels were fabricated in polydimethyl siloxane (PDMS) using standard soft-lithography techniques with a photolithographically patterned KMPR mold. We present a relationship of the main geometrical variables of the micro channels and its impact on the extensional strain rate along the center line, for different cross sectional shapes and over a range of strain rates typically encountered in protein processing. Computational Fluid Dynamics (CFD) simulations have been carried out to gain more detailed local flow information, and the results have been validated with experiments. We show good agreement between the CFD and experiments and demonstrate the use of microfluidics in the production of a large range of controllable shear and extensional rates that can mimic large scale processing conditions.

Soft-lithography and plasma etching with reactive ions were used to fabricate a polymer microfluidic cell-culture bioreactor with integrated optical oxygen sensor. Platinum (II) octaethylporphyrin ketone (PtOEPK) suspended in a microporous polystyrene (PS) matrix was spin-coated to form sensor films of variable thickness from 1.1 μm to 400 nm on glass substrates. Sensor films were found to be smooth and well adhered. Arbitrary patterns with a minimum feature size of 25 μm could be routinely replicated in the PtOEPK/PS layer using polydimethylsiloxane (PDMS) elastomer stamps as etch masks in a reactive ion etcher. No effect of plasma patterning and sensor integration by plasma bonding on the sensor signal could be observed. Detection of different gaseous and dissolved oxygen concentrations with the patterned sensor followed linear Stern-Volmer behavior. Dynamic measurement of sensor intensity as a function of different oxygen concentration showed good reproducibility and a nearly instantaneous response to gas changes. For gaseous and dissolved oxygen measurement with a patterned 400 nm thick film I₀/I₁₀₀ ratios of 3.2 and 2.7 were found, respectively.

A droplet-based microfluidic device has been developed for the controlled dilution and sorting of droplets by means of electrokinetic forces. Neutral and cationic dyes have been tested in order to demonstrate the dilution efficiency. In addition, yeast cells and latex beads were successfully enclosed in droplets in a controlled manner. Experiments results demonstrate that even under rapid concentration changes, the rate of production and size of the droplets remained constant. Following the generation of the diluted droplets, the remaining net surface charge allows them to be sorted according to their dilution.

In this paper, we report on the design, fabrication, and testing of a polymer micro fluidic chip for Electrospray Ionization Mass Spectrometry (ESI-MS). A disposable plastic chip is designed to be fabricated using the hot-embossing process on polystyrene (PS) and polycarbonate (PC) substrates. The chip has an open reservoir, which is connected to an open channel that runs to the tip of the chip. A high voltage circuit is required to form the electrospray at the tip using methanol/water solution with an electrode wire in the reservoir. We have tried to minimize sources of impurities entering the microchannel, and hence, the MS, by careful selection of the fabrication process and electrode and use of open channel. The hot-embossing process is modeled using ANSYS to design the tool and predict the channel and reservoir shape and deformation. The simulation results provide an insight into the hot embossing process. Several samples are fabricated and tested, and the electrospray experimental results are reported. Laser machining and electroforming processes were investigated for fabricating the hot-embossing tool, and the results are reported.

The prediction of protein adsorption to surfaces from solution is a perennial unsolved problem in biomedicine, physical chemistry and other fields. Here we used neural networks and the previously developed Biomolecular Adsorption Database (BAD) to predict the amount of protein adsorbed by a set of five descriptors of the protein, surface and solution. We find a moderately good predictive ability if very large adsorption values are present and a good fit if these few outliers are eliminated. With a growing number of entries in the BAD, we expect the accuracy of the predicted values to increase substantially. This paper presents for the first time a universal and stand-alone quantitative predictor of protein adsorption.

The intensity of analog stimuli, such as the loudness of sounds, is converted by our biological sensory systems into short duration electrical pulses in nerve fibres. These pulses are known as action potentials. In many cases, the transduction process that converts stimulus intensity into an action-potential encoding introduces significant randomness that appears to reduce the quality of the encoding. Due to this inherent random noise, it is the average rate at which action potentials are produced, rather than the instantaneous rate, that encodes stimulus amplitude. In this paper the limits of performance of this transduction process are analyzed using an information theoretic perspective of neural rate coding.

Dielectrophoresis (DEP) is a popular, noncontact electrokinetic method for separating and transporting nanosize biomolecules and colloids in microdevices. DEP is the movement of polarizable particles arising from the action of nonuniform electric fields. The spatial-temporal distribution of nanosize particles moving under the action of a deterministic DEP force and stochastic Brownian thermal motion can be described by the Fokker Planck equation (FPE). The application of DEP electrokinetics in micro-technologies means nanoscale particle movement needs to be modeled and measured quantitatively. Quantitative FPE prediction (using numerical values for relevant dielectric and fluid parameters) of DEP-driven particle transport is usually achieved numerically by using Finite Element methods (FEMs). The drawbacks of FEMs are inaccuracy where the electric field is extremely inhomogeneous and they offer little insight into the mathematical structure of the FPE solution. The latter is important, not only for prediction of particle movement, but also the 'reverse' process where parameter values are estimated from measurements of DEP experiments. In this paper, a Fourier-Bessel series solution to the FPE is derived that describes particle movement under the action of DEP in a simple chamber. The solution assumes the DEP force exhibits a hyperbolic spatial profile and can be extended to the case that assumes an exponential decay. This applies to planar arrays, such as, interdigitated electrodes. Time-dependent DEP particle collection and release (after the DEP is switched off) from a surface is evaluated for strong and weak DEP forces. Temporal DEP responses can be classified as state-transitions and perturbations, respectively.

Numerical simulations of SAW correlators so far are limited to delta function and equivalent circuit models. These models are not accurate as they do not replicate the actual behaviour of the device. Manufacturing a correlator to specifically realise a different configuration is both expensive and time consuming. With the continuous improvement in computing capacity, switching to finite element modelling would be more appropriate. In this paper a novel way of modelling a SAW correlator using finite element analysis is presented. This modelling approach allows the consideration of different code implementation and device structures. This is demonstrated through simulation results for a 5×2-bit Barker sequence encoded SAW correlator. These results show the effect of both bulk and leaky modes on the device performance at various operating frequencies. Moreover, the ways in which the gain of the correlator can be optimised though variation of design parameters will also be outlined.

The hydrophobic force is one of the main driving forces in protein folding and binding. However, its nature is not yet well understood and consequently there are more than 80 different scales published trying to quantify it. Most of the hydrophobicity scales are amino acid-based, but the interaction between the molecular surface of the proteins (and DNA) and surfaces they are immobilized on, e.g., on biomedical micro/nanodevices, occurs on fractions of, rather than whole amino acids. This fragmented structure of the biomolecular surface requires the derivation of atom-level hydrophobicity. Most attempts for the evaluation of atomic hydrophobicities are derived from amino acid-based values, which ignore dynamic and steric factors. This contribution reports on the Molecular Dynamics simulations that aim to overcome this simplification. The calculations examine various tripeptides in an aqueous solution and the analysis focuses on the distance of the nearest water molecules to the individual atoms in the peptides. Different environments result in a variation of average distances for similar atoms in different tripeptides. Comparison with the atomic hydrophobicities derived from the amino acid-based hydrophobicity obtained from peptide partition in water-octanol (Dgoct) and transport through the membrane interface (Dgwif) shows a similar trend to the calculated distances. The variations are likely due to the steric differences of similar types of atoms in different geometric contexts. Therefore, Molecular Dynamics simulations proved convenient for the evaluation of atomic hydrophobicities and open new research avenues. The atomic hydrophobicities can be used to design surfaces that mimic the biomolecular surfaces and therefore elicit an expected biomolecular activity from the immobilized biomolecules.

Recent analysis of elite-level half-pipe snowboard competition has revealed a number of sport specific key performance variables (KPV's) that correlate well to score. Information on these variables is difficult to acquire and analyse, relying on collection and labour intensive manual post processing of video data. This paper presents the use of inertial sensors as a user-friendly alternative and subsequently implements signal processing routines to ultimately provide automated, sport specific feedback to coaches and athletes. The author has recently shown that the key performance variables (KPV's) of total air-time (TAT) and average degree of rotation (ADR) achieved during elite half-pipe snowboarding competition show strong correlation with an athlete's subjectively judged score. Utilising Micro-Electrochemical System (MEMS) sensors (tri-axial accelerometers) this paper demonstrates that air-time (AT) achieved during half-pipe snowboarding can be detected and calculated accurately using basic signal processing techniques. Characterisation of the variations in aerial acrobatic manoeuvres and the associated calculation of exact degree of rotation (DR) achieved is a likely extension of this research. The technique developed used a two-pass method to detect locations of half-pipe snowboard runs using power density in the frequency domain and subsequently utilises a threshold based search algorithm in the time domain to calculate air-times associated with individual aerial acrobatic manoeuvres. This technique correctly identified the air-times of 100 percent of aerial acrobatic manoeuvres within each half-pipe snowboarding run (n = 92 aerial acrobatic manoeuvres from 4 subjects) and displayed a very strong correlation with a video based reference standard for air-time calculation (r = 0.78 ± 0.08; p value < 0.0001; SEE = 0.08 ×/÷ 1.16; mean bias = -0.03 ± 0.02s) (value ± or ×/÷ 95% CL).

The surface of solid indium tin oxide (ITO) glass supports for samples in electrowetting system needs to be protein-resistant. Since Teflon is the most conventional coating material used to improve the contact angle between the glass and solvent, it still unable to prevent nonspecific proteins adsorption absolutely under the applied potential. In this paper, we described a feasible method that could minimize non-specific proteins adsorption most probably during droplet processing. A regular micro-scale structure was patterned by photolithography, and dielectric layer was covered on the electrodes. Finally a thin layer of Sigmacoat® was coated by physical vapor deposition. The surface characteristic of our chip was analyzed by atomic force microscopy and Contact Angle Analyzer. We found that the adhesion of bio-molecule was efficiently decreased by this modified processing, and could prevent electrolysis more efficiently.

Polyanisidine nanofibers gas sensor based on a ZnO/36° YX LiTaO₃ surface acoustic wave (SAW) transducer was developed and tested at different concentrations of hydrogen gas in synthetic air. Nanofibrous mats of polyanisidine were synthesized without the need for templates or functional dopants by simply introducing an initiator into the reaction mixture of a rapidly mixed reaction between the monomer (anisidine) and the oxidant. The polyanisidine nanofibers are characterized using scanning electron microscopy (SEM) and Ultraviolet-Visible Spectroscopy (UV-vis). Polyanisidine nanofibers were deposited onto the SAW transducer and exposed to different concentrations of hydrogen gas. The frequency shift due to the sensor response was 294 kHz towards 1% of H₂. All tests were conducted at room temperature and the sensor performance was assessed for a two day period with a high degree of reproducibility obtained.

This paper presents a simple and reliable multi-immunosensing lab-on-a-chip detecting antibodies as multi-disease markers using electrochemical method suitable for a portable point-of-care system. Since multi-immunosensing LOCs are to be disposable and cheap, the complications associated with the liquid control need to be removed. The main complication arises from the active microfluidic part driven by the external electric power. In this paper, a multi-stacked PDMS LOC including PDMS passive valves is proposed. The sequential liquid driving by capillary attraction and the action of check valve provide a reliable immunosensing tool simply triggered by an air bladder push without an electrical power. The immunosensing-LOC with the size of "25mm × 20mm × 6 mm" is fabricated with PDMS using the replica molding and oxygen plasma bonding. The LOC consists of a PDMS valve, channel, and a glass substrate. The fluidic tests were performed using DI water. The liquids are controlled by two kinds of passive valve, one is capillary stop valve and the other is membrane type check valve. The capillary stop valve stops liquids using pressure barrier of expanded channel. The check valve stops the liquid triggered by an air bladder from flowing backward. The assembly of these two valves assures the well controlled liquid driving for the immunosensing. The model experiments were performed with anti-DNP antibody and anti-biotin antibody as target analytes. The antibodies conjugated with GOX are used as a signaling molecule for cyclic voltammetry. The different amplified signals show different target analyte affinities and make sure the multi-immunosensing.

Transfection cell microarrays (TCMs) are a high-throughput, miniaturised cell-culture system utilising reverse transfection, in which cells are seeded onto a DNA array resulting in localised regions of transfected cells. TCMs are useful for the analysis of gene expression, and can be used to identify genes involved in many cellular processes. This is of significant interest in fields such as tissue engineering, diagnostic screening, and drug testing^{[1, 2]}. Low transfection efficiency has so far limited the application and utility of this technique. Recently, the transfection efficiency of TCMs was improved by an application of a high voltage for a short period of time to the DNA array resulting in the electroporation of cells attached to the surface^{[3, 4]}. Furthermore, application of a low voltage for a longer period of time to the DNA array was shown to improve the transfection efficiency by stimulating the desorption of attached DNA, increasing the concentration of DNA available for cellular uptake^[5]. In the present study, the optimisation of the uptake of adsorbed DNA vectors by adherent cells, utilising a voltage bias without compromising cell viability was investigated. This was achieved by depositing negatively charged DNA plasmids onto a positively charged allylamine plasma polymer (ALAPP) layer deposited on highly doped p-type silicon wafers either using a pipettor or a microarray contact printer. Surface-dependant human embryonic kidney (HEK 293 line) cells were cultured onto the DNA vector loaded ALAPP spots and the plasmid transfection events were detected by fluorescence microscopy. Cell viability assays, including fluorescein diacetate (FDA) / Hoechst DNA labelling, were carried out to determine the number of live adherent cells before and after application of a voltage. A protocol was developed to screen for voltage biases and exposure times in order to optimise transfection efficiency and cell viability. Cross-contamination between the microarray spots carrying different DNA vectors was also investigated. By application of a voltage of 286 V/cm for 10 ms, transfection efficiency was doubled compared to using only transfection reagent, whilst maintaining a cell viability of 60-70% of the positive control.

Terahertz radiation or T-rays, show promise in quality control of food products. As T-rays are inherently sensitive to water, they are very suitable for moisture detection. This proves to be a valuable asset in detecting the moisture content of dried food, a critical area for some products. As T-rays are transparent to plastics, food additives can also be probed through the packaging, providing checks against a manufacturer's claims, such as the presence of certain substances in foods.

The selective immobilization of various biomolecules in well-defined area is important technique for the development of biosensors and biochips. Especially, the fabrication of protein micropatterns preserving their functional activity on the desired surface is critical issue for the development of medical diagnostic devices and basic protein studies. In this study, we have introduced a simple but reliable method of protein patterning on functionalized polyelectrolyte thin films (PEL) through consecutive layer-by-layer adsorption of polyelectrolytes via self-assembly technique and microcontact printing (μCP). For the selection of appropriate surface, several representative surfaces modified with various functional materials including aldehyde, epoxide, poly-L-lysine, amine, and self-assembled polyelectrolyte multilayers (PEL) were investigated. The PEL surface providing electrostatic interaction force showed most high functionality in point of homogeneous patterning of proteins with high density and preservation of inherent 3-dimensional structure of proteins. Immunoassay as a model system of protein-protein interaction showed good linearity, indicating the feasibility of a quantitative measurement of the concentration of target proteins in sample. Our proposed approach based on PEL constructed by self-assembly technique in aqueous solution is green chemistry and cost-effective method to generate stable 3-D thin film on surface. The demand for strict control over the positioning and the stable immobilization of several kinds of biomolecules in fabricated structures can result in many applications.

This paper highlights a systematic investigation (related to percentage addition of solvents) of finding the appropriate solvent to reduce the viscosity of the structural grade of resin (AV138M) within castable range to effectively disperse the nano-fillers (Carbon Nano Powder - CNP and Multi Walled Carbon Nano Tubes - MWCNT). AV138M + HY998/CNP and AV138 + HY998/MWCNT were cast within-process degassing using a vacuum pump of capacity 4 torr. High energy sonic waves (27000 kHz) were used for dispersion. Morphological studies were undertaken to analyze the uniformity in dispersion of nano-fillers. The cured specimens were subjected to: Resistivity measurements using a Resistivity Meter, Glass Transition Temperature (T_g) using a Differential Scanning Calorimetry (DSC) and Tensile properties using UTM. The properties have been determined for the nanocomposites with different wt % of the fillers. It has been found that for 0.6 wt % of filler (CNP / MWCNT), there is an increase in UTS of 10 times for MWCNT compared to CNP; for 1.0 wt % of the fillers, the T_g improved by 10 ºC for MWCNT and by 4 ºC for CNP when compared with neat resin. Both CNP and MWCNT showed drop in electrical resistivity of the neat resin; a drop to the extent of 10³ has been achieved with 1 wt % MWCNT and the same was 2 wt % in case of CNP.