This PDF file contains the front matter associated with SPIE Proceedings Volume 6416, including the Title Page, Copyright information, Table of Contents, Introduction (if any), and the Conference Committee listing.

The availability of rapid and specific biosensors is of great importance for many areas of biomedical research and modern biotechnology. This includes a need for DNA sensors where the progress of molecular biology demands routine detection of minute concentrations of specific gene fragments. A promising alternative approach to traditional DNA essays utilizes novel smart materials, including conducting polymers and nanostructured materials such as quantum dots. We have constructed a number of DNA sensors based on smart materials that allow rapid one-step detection of unlabeled DNA fragments with high specificity. These sensors are based on functionalized conducting polymers derived from polypyrrole (PPy) and poly(p-phenylenevinylene) (PPV). PPy based sensors provide intrinsic electrical readout via cyclic voltammetry and electrochemical impedance spectroscopy. The performance of these sensors is compared to a novel self-assembled monolayer-PNA construct on a gold electrode. Characterization of the novel PNA based sensor shows that it has comparable performance to the PPy based sensors and can also be read out effectively using AC cyclic voltammetry. Complementary to such solid substrate sensors we have developed a novel optical DNA essay based on a new PPV derived cationic conducting polymer. DNA detection in this essay results from sample dependent fluorescence resonance energy transfer changes between the cationic conducting polymer and Cy3 labeled probe oligonucleotides. As an alternative to such fluorochrome based sensors we discuss the use of inorganic nanocrystals ('quantum dots') and present data from water soluble CdTe quantum dots synthesized in an aqueous environment.

An effect of electron beam (EB) irradiation on wettability was studied for polypropylene for biomedical application. EB irradiation enhanced the wettability on polypropylene samples. To discuss the effect, the wettability was evaluated by using contact angle of sessile drop. EB irradiation decreased the contact angle. Based on ESR results, the effects of electron beam on the wettability were discussed. EB irradiation broke the weakly bonded pairs and formed the dangling bonds in polypropylene.

The Atomic Force Microscope (AFM) has been used for the characterization of polydimethylsiloxane (PDMS) surfaces with embedded, randomly dispersed micron-sized glass beads as a model system for a nano-topographical composite material with adjacent hydrophobic/hydrophilic areas. The use of lateral force microscopy (LFM) for the differentiation of regions within a composite material allowed for a mapping of the position of the hydrophilic glass beads, the determination of the height of the protruding beads and the surface area of the glass. Material properties of the PDMS were obtained from AFM contact-mode scans, contact angle measurements and from Fourier transform infrared spectroscopy for both, unexposed surfaces and surfaces exposed for 3 hours with a 185 nm deep UV light source. The UV exposure was found to have an effect on the lateral force signal via a change in the stiffness of the PDMS but the resulting lower contrast was still sufficient for the discrimination of the different regions.

Although CD4+ T-cells are an important target of HIV detection, there have been still major problems in making a diagnosis and monitoring in the third world and the region with few medical facilities. Then, it is necessary to use portable diagnosis devices at low cost when you put an enumeration of CD4+ T-cells. In general, the counting of CD4 below 200cells/uL makes it necessary to initiate antiretroviral treatment in adults (over 13 years old). However, lymphocyte subsets (including CD4 counts) of infants and young children are higher than those of adults. This fact shows the percentage of CD4+ T-cells of blood subsets, i.e., CD4/CD45%, CD4/CD8% or CD4/CD3% means a more reliable indicator of HIV infection than absolute counts in children. To know the percentage of CD4+ T-cell by using two fluorescent dyes of different emission wavelength, at least, one laser and two PMT detectors are in general needed. Then, it is so hard to develop a portable device like a 'toaster size' because this makes such a device more complex including many peripheral modules. In this study, we developed a novel technique to control the intensity of fluorescent dye-doped silica nanoparticles. I synthesized FITC-doped silica nanoparticles conjugated CD4 antibody 10 times brighter than FITC-conjugated CD45 antibody. With the difference of intensity of two fluorescent dyes, we measured two parameters by using only a single detector and laser. Most experiments were achieved with uFACS (microfabricated fluorescence-activated cell sorter) on an inverted microscope (IX71, Olympus). In conclusion, this method enables us to discriminate the difference between CD4 and CD45 in an intensity domain simultaneously. Furthermore, this technique would make it possible develop much cheaper and smaller devices which can count the number of CD4 T-cells.

Control over biomolecule interactions at interfaces is becoming an increasingly important goal for a range of scientific fields and is being intensively studied in areas of biotechnological, biomedical and materials science. Improvement in the control over materials and biomolecules is particularly important to applications such as arrays, biosensors, tissue engineering, drug delivery and 'lab on a chip' devices. Further development of these devices is expected to be achieved with thin coatings of stimuli responsive materials that can have their chemical properties 'switched' or tuned to stimulate a certain biological response such as adsorption/desorption of proteins. Switchable coatings show great potential for the realisation of spatial and temporal immobilisation of cells and biomolecules such as DNA and proteins. This study focuses on protein adsorption onto coatings of the thermosensitive polymer poly(N-isopropylacrylamide) (pNIPAM) which can exhibit low and high protein adsorption properties based on its temperature dependent conformation. At temperatures above its lower critical solution temperature (LCST) pNIPAM polymer chains are collapsed and protein adsorbing whilst below the LCST they are hydrated and protein repellent. Coatings of pNIPAM on silicon wafers were prepared by free radical polymerisation in the presence of surface bound polymerisable groups. Surface analysis and protein adsorption was carried out using X-ray photoelectron spectroscopy, time of flight secondary ion mass spectrometry and contact angle measurements. This study is expected to aid the development of stimuli-responsive coatings for biochips and biodevices.

In this paper we compare the value of different molecular modeling techniques for the prediction of vibrational modes, especially in the mid- and far-infrared region. There is a wide range of different levels of theory available for molecular modelling - the choice depending on the kind of system to be investigated. For our calculations we use different theoretical approaches such as Hartree-Fock and Density functional theory. We also compare the performances of two available electronic structure programs-Gamess-US and Gaussian03. As examples, we use two different retinoids - all-trans retinal and all-trans retinoic acid - derivatives of Vitamin A.

The fabrication of hetero-structured vertically aligned nanowire arrays and enzyme immobilization on their surface is presented for a glucose sensor with high sensitivity. Hetero-structured nanowires of gold and platinum are fabricated by hybrid polycarbonate membrane assembly and electrochemical deposition processes and glucose oxidase are attached on their surface by covalent immobilization. Platinum and gold hetero-structured nanoelectrodes with enzyme are evaluated to detect hydrogen peroxide produced in the enzyme reaction without the need for the artificial redox mediator, which is not viable on a homogenous gold electrode. Chronoamperometric current behavior is demonstrated with various concentrations from 0.5 mM to 28 mM. In this research, the combination of enzyme immobilization and sensing surfaces on nanowire arrays has shown superior performance with regards to the sensitivity and response time.

In actuator capabilities of a blood extraction, a quick response, a high output power and a highly precise deflection of the smart material actuator for the blood extraction micro pump are prerequisite for a precise control of the amount of blood extraction. In Bio-MEMS fields, the development of a micro pump driven by an electromagnetic power, a piezoelectric element, electrostatic power and a shape memory alloy (SMA) such as a smart material type and a vacuum type, are investigated. However, the piezoelectric micro pump has a slow extraction speed. On the other hand, a vacuum type micro pump can extract blood very fast, however, it cannot deliver a drug as a drug delivery system(DDS.). In this research, we focus on the development of SMA type micro pump to extract blood by negative pressure generated in extraction chamber using SMA. Because, SMA shows high work output per unit volume, high power to mass ratio and the capability of being driven without high applied electric fields. In this research, the most significant factors in the factors of a needle length, an inner and an outer diameter, numbers of cuts for the SMA disk are optimized by using the experimental design method, which can estimate priority factors from a comparatively small number of experiments are investigated. In the design of factors for the SMA type micro pump, a reduction of the inner and outer diameter of the needle, the blood extraction volume and extraction time are effective factors in order to mitigate a burden of diabetic patients. The effect of the length of the needle, and especially the inner diameter of the needle showed 50% of contributing rate contribution for blood extraction volume.

A method for compensation of nonlinearities, mainly hysteresis, using augmented linear control for a piezoelectric stack actuator is presented in this paper, with its application in intra-cytoplasmic sperm injection (ICSI). The linear control, realized via a PID control, is enhanced by a regulated chatter signal with variation of duty cycle as well as direction (sign), with constant magnitude and period. The main idea is to augment the PID control signal, which does most of the feedback control, in a low hassle manner by increasing or decreasing the signal via the regulated chatter signal, which does most of the nonlinearities compensation. The variation of duty cycle and direction is updated via an iterative learning technique, taking into consideration the repetitive motion required in the ICSI application. This device is used for assisting oocyte (egg cell) penetration during ICSI process, where the actuator is required to drive a needle, containing a sperm cell, to penetrate an oocyte and then inject the sperm into the oocyte. This technique is able to satisfy the requirements of the process, where a highly-precise motion is mandatory.

Various speech production substitutes, which aim to reconstruct speech functions, have been developed and used practically by speech impaired individuals. However, conventional speech production substitutes have various drawbacks; therefore, perfect speech production substitutes are expected to be developed. We focused on the PZT ceramics sounder as a sound source in an electric drive artificial larynx. We first developed the artificial larynx that uses a PZT ceramic sounder and then evaluated its performance. The vocalized sound of the artificial larynx user shows good characteristics at the formant frequency, which is important for vowel discrimination. The characteristic feature of our artificial larynx is its individual structure, and this typical structure implies that the sound source and the implant are separated. This structure facilitates a high biocompatibility in our artificial larynx. In our previous work, the improvement in the acoustic characteristics of the sound source was described. The improvement is achieved by the optimization of the electric control and its structure. In this paper, we present the results of shape optimization and new shape PZT ceramics sounder evaluation. The optimized shape is decided on FEM analysis, and prototype PZT ceramics sounder based on above analysis is manufactured by way of trial. Additionally, the performance of prototype sounder is evaluated by acoustic analysis. Until now, we have researched about the immobilization of biomolecules onto the metal surface. It is believed that biomolecular immobilization on the sound source surface improves its biocompatibility. In the future, we aim to realize implantable sound sources that employ biomolecular immobilization technology.

In this study, an automatic blood vessel searching system (BVSS) is newly developed, which is built in the health monitoring system (HMS) and the drug delivery system (DDS) to extract the blood, evaluates the blood sugar level and injects the insulin for the diabetic patients. Main subjects of our BVSS development are 1) a transmittance photo imaging of the finger by using the LED light as a near-infrared light source with peak wave length of 870 nm, and 2) an image processing to detect the location of the center of the blood vessel cross section. The sharp edge focus method was applied in our BVSS to detect the depth of blood vessel. We carried out experiments by using blood vessel phantoms, which consist of an artificial cylindrical blood vessel and skin tissue, which are made of the teflon tube and the silicone rubber. The teflon tube has the size of 0.6 mm in diameter and is filled with the human blood. The experimental results demonstrated that the estimated depth, which is obtained by image analysis corresponding to given depths, shows a good agreement with the real values, and consequently the availability of our BVSS is confirmed.

Active control of microdroplets in microchannels is an important task in droplet-based microfluidics. The break- up process of droplets at an T-junction is usually controlled passively by the fluidic resistance of the branches. We used thermal control to actively manipulate aqueous droplets in microchannels. The temperature affects both viscosity and interfacial tension between the phases. The concept was first simulated with a two-dimensional model. The simulation results show that increasing temperature at a branch can change the size ratio of the two daughter droplets from 0 to 1. That means, droplet switching is possible with this concept. Control of droplet size during the formation process and splitting process was demonstrated experimentally by varying the temperature of the branches. At a critical temperature, droplet switching can be achieved. The used control temperature of less than 40°C shows that this active control concept is suitable for biochemical applications. Thermal control promises to be a simple and effective manipulation method for droplet-based lab on a chip.

The paper presents a novel microfluidic device for identification and characterization of cells in suspensions using impedance spectroscopy. The device consists of two glass wafers: a bottom wafer comprising a microfluidic channel with two electrodes added for impedance measurement, and a top glass wafer in which inlets and outlets are realized. The fact that the device is glass-based provides a few key advantages: reduced influence from parasitic components during measurements (due to the good isolation properties of the substrate), optical transparency and hydrophilic surface of the microfluidic channel. The latter feature is especially important as it enables sample suction due to capillarity forces only. Thus, no external pumping is required and only a small volume sample suffices for the measurement. The fabrication process of this device consists of three major steps. First, via-holes and inlet/outlet holes are executed in the top glass wafer by wet etching in a 49% HF solution using a low stress amorphous silicon/silicon carbide/photoresist mask. Second, the microfluidic channel is etched into the bottom wafer and Ti/Pt electrodes are then patterned on top of it using a spray coating-based lithography. The last processing step is bonding together the top and bottom glass wafers by employing a very thin adhesive intermediate layer (SU8). This adhesive layer was applied selectively only on the bottom die, from a Teflon cylinder, using a contact imprinting method. Finally, fabricated devices were successfully tested using DI water, phosphate buffer saline (PBS), and various types of both dead cells and living cells resuspended in PBS. Clear differences between dead and live cells have been observed. The impedance measurements were carried out in the frequency range 5 kHz to 10 MHz. The measured magnitude and phase were studied using different types of cells in Dulbecco's Minimal Essential medium (DMEM). The obtained impedance spectra revealed the characteristic spectra signature for each type of cell.

This work presents the microfabrication procedures and filtering application of a novel 3-D dielectrophoretic chip that possesses a structure similar to a classical capacitor. It is made up by bonding two stainless steel meshes on the opposite sides of a glass frame which is filled with round silica beads. Double filtration actions that are derived from both mechanical and dielectrophoretic means have been tested with yeast cells and a maximum trapping efficiency of approximately 75% has been achieved with initial concentration of 5×10⁶ cells/ml. This was done at an applied voltage of 200 V and a flow rate of 0.1ml/min.

Microchip-based electrophoretic separation systems are essential components in the development of fully integrated micro total analysis systems. In this paper, a miniaturized analytical system for separating and detecting inorganic ions is described. The system was based on a polycarbonate (PC) capillary electrophoresis (CE) chip and a contactless conductivity detector, both being developed at CSIRO Microfluidics and Microfabrication Laboratories, Melbourne, Australia. The PC chip was fabricated using the soft lithography technique in conjunction with nickel plating and hot embossing. The detector electrodes were fabricated from a PCB board and attached on the separation chip bottom surface. The thin capping layer (20 micron) of the chip allowed for sensitive detection of conductivity change. The system was demonstrated to separate reliably the potassium, sodium and lithium ions in a 20mM MES/His buffer within a minute at an electrical field of 28.5kV/m. The detection limit for the current design is around 100μM. Such a system offers great promise to be integrated into robust hand-held devices for in-situ monitoring of chemical and biological samples with high speed, reliability and low costs.

Disposable polymer microfluidic chips have been used more and more in miniaturized analytical devices. The surface of the polymers often needs to be treated to acquire specific properties. This study investigates the characteristics of capillary flow in three microfluidic chips under different surface conditions and the aim is to understand how the surface property could affect the capillary flow over the shelf life of the chips. The channel surfaces of polymer chips were treated using air plasma. The interface pattern and velocity were measured by a photographic technique and a micron Particle Imaging Velocimetry (MicroPIV) method. The glass chip could maintain a capillary flow velocity of around 3.0 mm/s and showed little reduction with time. The velocity agreed well with theory by Washburn. The PDMS chip surfaces could be easily modified and the capillary flow rate could reach 4 mm/s. However, the hydrophilicity decreased rapidly over time and was lost completely within a few hours. The polycarbonate chips need more powerful surface treatment. Once modified, the surface could sustain for much longer time. It took one month for the capillary flow velocity to decrease by 50%.

This study describes an application based on the optical flow algorithm to construct a 2D velocity field plot. The estimated velocity field is used to track the movement of blood in real time. This methodology has been applied to medical images to quantify blood flow turbulence in the right atrium of the heart. Blood intensity fields that are obtained from clinical MRI scan sequences can be analyzed using this method. Septal defects and other heart diseases can be assessed for degrees of abnormality and post-surgical success can be evaluated. We have developed this technique specifically for characterizing the turbulence generated due to such heart abnormalities. The degree of turbulence and fluid shear stress can be determined from the measured flow field. The cardio dynamics information that is based on flow analysis and visualization of blood offers potential for the detection and quantification of myocardial malfunctioning.

The chemical warfare agent Sarin is an organophosphate that is highly toxic to humans as they can act as cholinesterase inhibitors, that disrupts neuromuscular transmission. As these nerve agents are colorless, odorless and highly toxic, they can be introduced into drinking water as a means of terrorist sabotage. Hence, numerous innovative devices and methods have been developed for rapid detection of these organophosphates. Microfluidic technology allows the implementation of fast and sensitive detection of Sarin. In this paper, a micro-total analysis systems (TAS), also known as Lab-on-a-chip, fitted with an optical detection system has been developed to analyze the presence of the nerve agent sarin in water samples. In the present set-up, inhibition of co-introduced cholinesterase and water samples containing trace amounts of nerve agent sarin into the microfluidic device was used as the basis for selective detection of sarin. The device was fabricated using polymeric micromachining with PMMA (poly (methymethacrylate)) as the substrate material. A chromophore was utilized to measure the activity of remnant cholinesterase activity, which is inversely related to the amount of sarin present in the water samples. Comparisons were made between two different optical detection techniques and the findings will be presented in this paper. The presented measurement method is simple, fast and as sensitive as Gas Chromatography.

The culture of human Embryonic Stem (ES) cells in microchannel bioreactors can be highly beneficial for ES cell biology studies and ES tissue engineering applications. In the present study we examine the use of Human Foreskin Fibroblasts (HFF) cells as feeder cells for human ES culture in a microchannel perfusion bioreactor. PDMS microchannels (depth:130 micron) were fabricated using conventional soft-lithography techniques. The channels were sterilized, coated with a human fibronectin solution and seeded with cells. Following a period of static incubation, culture medium was perfused through the channels at various flow rates and cell growth was monitored throughout the culture process. Mass transport and fluid mechanics models were used to evaluate the culture conditions (shear stress, oxygen levels within the micro-bioreactor as a function of the medium flow rate. The conditions for successful long-term culture (>7 days) of HFF under flow were established. Experiments with human embryonic stem cells cultured in microchannels show that the conditions essential to co-culture human ES cell on HFF cells under perfusion differ from the conditions necessary for HFF cell culture. Human ES cells were found to be highly sensitive to flow and culture conditions and did not grow under flow rates which were suitable for HFF long-term culture. Successful culture of undifferentiated human ES cell colonies in a perfusion micro-bioreactor is a basic step towards utilizing microfluidic techniques to explore stem cell biology.

The deformability of erythrocytes is of great importance for oxygen delivery in the microcirculation. Reduced RBC deformability is associated with several types of hemolytic anaemias, malaria, sepsis and diabetes. Aging of erythrocytes is also associated with loss of deformability as well as reduction in cell volume. An automated rheoscope has been developed, utilizing a microfabricated glass flow cell, high speed camera and advanced image-processing software. RBCs suspended in a high viscosity medium were filmed flowing through a microchannel. The system produces valuable data such as velocity profiles of RBCs, spatial distribution within the microchannel, cell volume and deformation index (DI) curves. The variation of DI across the channel height, due to change in shear stress, was measured for the first time. Such DI curves were obtained for normal and Thalassemia RBCs and their diagnostic potential was demonstrated. The spatial distribution and velocity of RBCs and rigid microspheres were measured. Both RBC and rigid spheres showed enhanced inward lateral migration, however the RBCs form a depletion region at the center of flow. The volume and surface area of the flowing cells have been estimated based on a fluid mechanics model and experimental results and fell within the normal range. Hence, the system developed, provides means for examining the behavior of individual RBCs in microchannels, and may serve as a microfabricated diagnostic device for deformability and volume measurements.

There is constant interest and research being conducted in devising new means to deliver drugs to the internal organs of the human body to overcome the shortcomings of conventional systems. In this paper we propose a micro fabricated drug delivery system capable of storing drugs in the range of micro-litres (μL) in its secondary reservoir. It will deliver drugs by electrochemical disruption of thin gold membranes. This device is proposed to be integrated in an endoscopic capsule with a view to deliver drugs in areas that are difficult to access, such as the small and large intestines. The design of the device is based on two microfabricated silicon wafers having multiple cavities etched into them. The cavities on the silicon wafers are covered by thin gold membranes. These membranes act as the openings for the release of drugs stored in a secondary reservoir sandwiched between the two silicon wafers. The secondary reservoir is being named so because the cavities in the silicon wafer act as the primary reservoir. The secondary reservoir having holes made in them can be made to align with cavities on the silicon wafers and bonded. On applying suitable voltage, the gold membranes disrupt electrochemically, providing outlets from both sides. The drug diffuses out from both ends of the device.

A model of a biological sensory neuron stimulated by a noisy analog information source is considered. It is demonstrated that action-potential generation by the neuron model can be described in terms of lossy compression theory. Lossy compression is generally characterized by (i) how much distortion is introduced, on average, due to a loss of information, and (ii) the 'rate,' or the amount of compression. Conventional compression theory is used to measure the performance of the model in terms of both distortion and rate, and the tradeoff between each. The model's applicability to a number of situations relevant to biomedical engineering, including cochlear implants, and bio-sensors is discussed.

DNA microarrays are a laboratory tool for understanding biological processes at the molecular scale and future applications of this technology include healthcare, agriculture, and environment. Despite their usefulness, however, the information microarrays make available to the end-user is not used optimally, and the data is often noisy and of variable quality. This paper describes the use of hierarchical Maximum Likelihood Estimation (MLE) for generating algorithms that improve the quality of microarray data and enhance statistical inference about gene behavior. The paper describes examples of recent work that improves microarray performance, demonstrated using data from both Monte Carlo simulations and published experiments. One example looks at the variable quality of cDNA spots on a typical microarray surface. It is shown how algorithms, derived using MLE, are used to "weight" these spots according to their morphological quality, and subsequently lead to improved detection of gene activity. Another example, briefly discussed, addresses the "noisy data about too many genes" issue confronting many analysts who are also interested in the collective action of a group of genes, often organized as a pathway or complex. Preliminary work is described where MLE is used to "share" variance information across a pre-assigned group of genes of interest, leading to improved detection of gene activity.

We describe a model of computation of the parallel type, which we call 'computing with bio-agents', based on the concept that motions of biological objects such as bacteria or protein molecular motors in confined spaces can be regarded as computations. We begin with the observation that the geometric nature of the physical structures in which model biological objects move modulates the motions of the latter. Consequently, by changing the geometry, one can control the characteristic trajectories of the objects; on the basis of this, we argue that such systems are computing devices. We investigate the computing power of mobile bio-agent systems and show that they are computationally universal in the sense that they are capable of computing any Boolean function in parallel. We argue also that using appropriate conditions, bio-agent systems can solve NP-complete problems in probabilistic polynomial time.

The increasing need to manage complex environmental problems demands a new approach and new technologies to provide the information required at a spatial and temporal resolution appropriate to the scales at which the biological processes occur. In particular sensor networks, now quite popular on land, still poses many difficult problems in underwater environments. In this context, it is necessary to develop an autonomous monitoring system that can be remotely interrogated and directed to address unforeseen or expected changes in such environmental conditions. This system, at the highest level, aims to provide a framework for combining observations from a wide range of different in-situ sensors and remote sensing instruments, with a long-term plan for how the network of sensing modalities will continue to evolve in terms of sensing modality, geographic location, and spatial and temporal density. The advances in sensor technology and digital electronics have made it possible to produce large amount of small tag-like sensors which integrate sensing, processing, and communication capabilities together and form an autonomous entity. To successfully use this kind of systems in under water environments, it becomes necessary to optimize the network lifetime and face the relative hindrances that such a field imposes, especially in terms of underwater information exchange.

The terahertz (or T-ray) spectra of many small molecules of biological relevance show very characteristic, specific features that are sensitive to small changes of the molecular structure and even isomerization. On the other hand, most packaging materials like plastics, paper or even clothing are transparent for T-rays. Therefore, it is possible to differentiate and identify different substances by their spectral fingerprints, even through their packaging. This supports the potential of this technique in a wide range of applications from safety and security applications, via biosensing, through to pharmaceutical quality control. However, most of the molecular vibrations that give rise to the characteristic features in the T-ray spectra are phonon-like intermolecular vibrations of weakly bound crystalline compounds. This can be easily demonstrated by comparing the spectra of different crystals of the same molecule. Whereas this sensitivity on the intermolecular structure can be used to probe the crystalline structure and detect phase transitions, it is a hurdle when it comes to identify samples that lack such a well defined intermolecular structure. Yet, we have recently shown that a comparison of the absolute absorption values can still be used to differentiate between complex biomolecules such as RNA. In this paper we will demonstrate, based on a wide range of spectra, the potential of T-ray spectroscopy for biosensing and will show examples where this technique can be used to probe the crystalline configuration and probe phase transitions and will discuss the feasibility of using this technique for biosensing.

Liquid spectroscopy allows analysis of chemical composition and provides a better understanding of the solvation dynamics of various types of liquids. Although it has been shown that liquid spectroscopy using T-rays is feasible, liquid water absorption is still considered to be one of the most challenging problems facing THz imaging and spectroscopy in biomedical applications. The absorption coefficient for liquid water shows a very high THz absorption, 200 cm^-1 at 1 THz. This paper describes a promising novel liquid double-modulated differential time-domain spectroscopy (Double-modulated DTDS) technique to extract the optical parameters with a dual-thickness measurement. The described technique improves on the previous work, by replacing the required sample dithering technique with a rotating spinning wheel resulting in an improved noise performance up to two orders of magnitude.

Terahertz transmission through freshly excised biological tissue is limited by the tissue's high water content. Tissue fixation methods that remove water, such as fixation in Formalin, destroy the structural information of proteins hence are not suitable for THz applications. Dehydration is one possible method for revealing the tissue's underlying molecular structure and components. In this study, we measured the THz responses over time of dehydrating fresh, necrotic and lyophilized rat tissue. Our results show that as expected, THz absorption increases dramatically with drying and tissue freshness can be maintained through lyophilization. Dehydrated biological tissue with retained molecular structure can be useful for future laser-based THz wave molecular analysis.

The early detection of cancers is critical with respect to treatment and patient survival. Biopsy techniques that are currently employed for such diagnoses are invasive, time consuming and costly. A Terahertz (THz) imaging system potentially provides a fast and non-invasive way to detect and diagnose cancer. While there is proof of concept that THz can distinguish cancerous and normal tissue, the mechanisms underlying this differentiation are not well understood. A better understanding of THz spectral data can be gained through computational pattern recognition and related multivariate statistical tools. These allow for the differentiation of data into discrete and disjoint groups. Such separation of THz spectral data can provide complex information about diseased tissue, which can be used as a tool for distinguishing cancerous from non-cancerous cells as well as, discriminating between cancers at various developmental stages and, between different types of cancer.

A novel broadband high-speed impedance spectrometer has been developed for the analysis of single biological particles in a high-throughput microfluidic cytometer. The technique is based on obtaining the impulse response of the system using maximum length sequences (MLS) as the excitation signal. The impulse response is converted into the frequency domain using Fast Fourier Transform (FFT). Theoretical modeling and simulation of a single cell suspended in the cytometer show that the MLS technique is capable of high precision single particle analysis.

In this paper, we propose a new method to detect gastroesophageal reflux wirelessly. Based on passive telemetry using inductive links, impedance of the refluxate can be determined. We have designed and fabricated planar coils integrated with electrodes on flexible substrates using standard photolithography processes. The device can be implanted in the esophagus using currently available clinical techniques. In vitro experiments were conducted by passing different acidic or non-acidic solutions onto the implanted electrodes and measuring the signal amplitudes with an external receiver. Air, drinking water and different concentrations of artificial stomach fluids were used to test the impedance sensor. System configuration, device designs, fabrication processes and measurement results will be presented in this paper.

This work described the development of high throughput human DNA purification process with the amino-functionalized silica coated magnetic nanoparticles. The magnetic nanoparticles were synthesized with average particle size of 9 nm and silica-coated magnetic nanoparticles were obtained by controlling the coating thicknesses on magnetic nanoparticles. The silica coating thickness could be uniform-sized in the diameter of 10-40 nm by a sol-gel approach. The surface modification was performed with amino-functionalized organic silanes on silica coated magnetic nanoparticles. The spectroscopic measurements such as a FT-IR(ATR-method) and Vibrational Sample Magnetometer (VSM) were used to characterize the chemical structures and magnetic strengths. To elucidate the relationship among the surface area, pore size distribution and reactivity of the materials, XRD, TEM, BET and Zeta potential were used. The use of functionalized self-assembled magnetic nanoparticles for human DNA separation process give a lot of advantages rather than the conventional silica based process.

This work presents the highly controlled drug delivery system free from the burst release at an initial stage and equipped with the capability of long term drug release. The nanoporous drug releasing reservoir was combined with porous body resembling cancellous bone. The materials were prepared by the integration of synthesized inorganic hydroxyapatite (HA) and the hybrid gels of bicontinuous sponge-phased L3 silicate and thermo-responsive poly(N-isopropylacrylamide) (L3-PNIPAm gels). The materials were designed to have the three dimensionally interconnected heterogeneous porosity of macro- and mesoporosity, in which the HA has the macroporosity of 150μm to be impregnated the drug into the pores and the L3-PNIPAm gels have mesoporosity of 5 nm to regulate the temperature sensitive drug-release through the pore channels and polymeric network, respectively. Consequently, this bone-mimetic system gave the highly long term drug release over the 60 days without the burst release. The release rate could be controlled with the change of the HA and PNIPAm composition ratios. The structural characterization was achieved by TEM, SEM, XRD, Micro-Raman spectroscopy, BET, and the direct contact cytotoxicity test was also described.

In this article, we report a MOSFET-type biosensor assembled in a polydimethylsiloxane (PDMS) micro-fluidic channel for the electrical detection of nano-scale biomolecules. The MOSFET-type sensor was fabricated on the basis of standard complementary metal oxide semiconductor (CMOS) technology. Au which has a chemical affinity with thiol by forming a self-assembled monolayer (SAM) was used as the gate metal. In order to apply to the hybrid micro-flow-system for a prototype lab-on-a-chip, the PDMS layer with the micro-channel was aligned along with the sensing area of the MOSFET device. Thiol which was injected into the micro-fluidic channel was detected by measuring the electrical characteristics of the MOSFET sensor in both ex-situ and in-situ due to the negative charge of thiol.

In here, we present the microfluidic approach to produce monodispersed microbeads that will contain viable cells. The utilization of microfludics is helpful to synthesize monodispersed alginate hydrogels and in situ encapsulate cell into the generating hydrogels in microfludic device. First, the condition of formation of hydrogels in multiphase flows including oil, CaCl₂, and alginate was optimized. Based on the preliminary survey, microfludic device could easily manipulate the size of alginate beads having narrow size distribution. The microfluidic method manipulates the size of hydrogel microbeads from 30 to 200um with a variation less than 2%. For the proof of concept of cell entrapment, the live yeast expressing green fluorescence protein is successfully encapsulated in microfluidic device.

The patterning of biomolecules in well-defined microstructures is critical issue for the development of biosensors and biochips. However, the fabrication of microstructures with well-ordered and spatially discrete forms to provide the patterned surface for the immobilization of biomolecules is difficult because of the lack of distinct physical and chemical barriers separating patterns. This study present rapid biomolecule patterning using micromolding in capillaries (MIMIC), soft-lithographic fabrication of PEG microstructures for prevention of nonspecific binding as a biological barrier, and self assembled polymeric thin film for efficient immobilization of proteins or cells. For the proof of concept, protein (FITC-BSA), bacteria (E.coli BL21-pET23b-GFP) were used for biomolecules patterning on polyelectrolyte coated surface within PEG microstructures. The novel approach of MIMIC combined with LbL coating provides a general platform for patterning a broad range of materials because it can be easily applied to various substrates such as glass, silicon, silicon dioxide, and polymers.