A variety of surface coatings were evaluated for their ability to promote in vitro actomyosin motility. Rabbit skeletal muscle heavy meromyosin (HMM) was adsorbed to uncoated glass and to surfaces coated with nitrocellulose, poly(methyl methacrylate) (PMMA), poly(butyl methacrylate) (PBMA), poly(tert-butyl methacrylate (PtBMA), polystyrene (PS) and hexamethyldisilazane (HMDS), and the myosin driven movement of fluorescently labeled actin filaments was recorded using epifluorescence microscopy. HMDS and uncoated glass did not support actomyosin motility, while mean velocities on other surfaces ranged from 1.7 μm sec^-1 (PtBMA) to 3.5 μm sec^-1 (NC). Nitrocellulose supported the highest proportion of motile filaments (75%), while 47 - 61% of filaments were motile on other surfaces. Within the methacrylate polymers, average filament velocities increased with decreasing hydrophobicity of the surface. Distributions of instantaneous acceleration values and angle deviations suggested more erratic and stuttered movement on the methacrylates and polystyrene than on NC, in line with qualitative visual observations. Despite the higher velocities and high proportion of motile filaments on NC, this surface resulted in a high proportion of small filaments and high rates of filament breakage during motility. Similar effects were observed on PS and PtBMA, while PBMA and PMMA supported longer filaments with less observed breakage.

The control over protein adsorption is of major importance for a variety of biomedical applications from diagnostic assays to tissue engineered medical devices. Most research has focused on the prevention of non-specific protein adsorption on solid substrates. Examples for surface modifications that significantly reduce protein adsorption include the grafting of polyacrylamide, poly (ethylene oxide) and polysaccharides. Here, we describe a method for creating surfaces that prevent non-specific protein adsorption, which in addition can be transformed into surfaces showing high protein adsorption on demand. Doped silicon wafers were used as substrate materials. Coatings were constructed by deposition of allylamine plasma polymer. The subsequent grafting of poly (ethylene oxide) aldehyde resulted in a surface with low protein fouling character. When the conductive silicon wafer was used as an electrode, the resulting field induced the adsorption of selected proteins. Surface modifications were analysed by X-ray photoelectron spectroscopy and atomic force microscopy. The controlled adsorption of proteins was investigated using a colorimetric assay to test enzymatic activity. The method described here represents an effective tool for the control over protein adsorption and is expected to find use in a variety of biomedical applications particularly in the area of biochips.

In this paper a classical AI problem is proposed to be solved by DNA computing: theorem proving. Since the complexity grows exponentially with the size of the problem, the solving process should be done in parallel. Massive parallelism is one of the advantages of DNA computers. It will be shown that the resolution refutation proof can be readily implemented by DNA hybridisation and ligation. Microreactors lend themselves to a relatively simple implementation of DNA computing. Not only is the design of the DNA critical for the success of the system but also the architecture of the microfluidic structure. Here the DNA performs the computation, while the microfluidics aids the biochemical steps necessary to manipulate the DNA, i.e. hybridisation and ligation.

It is known that rapid mixing in biosensors is required; however, these sensors may use reagents having small diffusion coefficients and whose mixing time scale is longer than the chemical reaction or molecular event time scale. Thus, it is necessary to overcome the inherent diffusion limited mixing of laminar flow. Many techniques to enhance microfluidic mixing are under development such as slanted wells, shallow grooves, electrokinetic instability mixing and surface layers. In this work, enhanced mixing is explored using lattice Boltzmann simulation techniques of two and three dimensional microfluidic channels at low Reynolds numbers. Surface temperature variations and flow field slip and no-slip boundary conditions emulating hydrophobic and hydrophilic surfaces were applied. The combined effect of wall temperature and surface property distributions presents a new way to manipulate microchannel flow fields. The momentum and thermal lattice Boltzmann equations were coupled via a body force term in the momentum equation. Also, a two dimensional, binary fluid model was incorporated. The results show how various wall temperature distributions, subjected to various velocity wall boundary conditions, can be either beneficial or counter productive to obtain uniform flow temperature profiles in, for example, PCR applications. The addition of the binary fluid model demonstrates the effects of both wall temperature and wall velocity boundary conditions.

The understanding and control of cell growth in confined microenvironments has application to a variety of fields including cell biosensor development, medical device fabrication, and pathogen control. While the majority of work in these areas has focused on mammalian and bacterial cell growth, this study reports on the growth behavior of fungal cells in three-dimensionally PDMS microenvironments of a scale similar to that of individual hyphae. Confinement was found to affect filament branching rate and angle. Overall, fungal hyphae demonstrate much more coordinated behavior during confinement than observed during growth on simple planar unconfined substrates. The remarkable difference of fungal growth behaviour observed in the PDMS microenvironments compared to open, unrestricted environments suggests that three-dimensional microstructures could be used to control and alter fungal motility.

With the advent of Raman spectrometers based on CCD array detectors, instruments have been coupled to optical microscopes leading to all the advantages of bright field microscopy with the added advantage of a direct chemical probe. The primary biological solvent, water, is a weak Raman scatterer and so these instruments can now be used to investigate the chemistry of living systems at spatial resolutions of 1 μm and below. We have developed techniques that allow us to study functional red blood cells and monitor the exchange of ligands and the development and chemistry of disease processes. These techniques take advantage of Aggregated Enhanced Raman Spectroscopy, which enables us to use the haem group of the haemoglobins and related haem pigments, such as the malarial pigment haemozoin, as a sensitive probe for changes in oxidation state, spin state and electronic structure. We have used the Raman microprobe to investigate the effect of drugs such as quinoline on the food vacuole of the malarial parasite in vivo. Sickle cell disease affects 1 out of 600 African American births and is caused by a mutant form (β6 glu→val) of haemoglobin (HbS). HbS polymerizes and forms higher order aggregates under hypoxic conditions, leading to distortion and rigidity of the erythrocyte. These rigid cells can block the microvasculature resulting in tissue ischaemia, organ damage, and ultimately death. The sensitivity of the Raman technique to haem aggregation provides a tool with which we can analyse the changes that occur between normal and sickle cells.

This work relates to porous material made by bonding together fibres of a magnetic material. When subjected to a magnetic field, the array deforms, with individual fibres becoming magnetised along their length and then tending to line up locally with the direction of the field. An investigation is presented into the concept that this deformation could induce beneficial strains in bone tissue network in the early stages of growth as it grows into the porous fibre array. An analytical model has been developed, based on the deflection of individual fibre segments (between joints) experiencing bending moments as a result of the induced magnetic dipole. The model has been validated via measurements made on simple fibre assemblies and random fibre arrays. Work has also been done on the deformation characteristics of random fibre arrays with a matrix filling the inter-fibre space. This has the effect of reducing the fibre deflections. The extent of this reduction, and an estimate of the maximum strains induced in the space-filling material, can be obtained using a simple force balance approach. Predictions indicate that in-growing bone tissue, with a stiffness of around 0.01-0.1 GPa, could be strained to beneficial levels (~1 millistrain), using magnetic field strengths in current diagnostic use (~1 Tesla), provided the fibre segment aspect ratio is at least about 10. Such material has a low Young’s modulus, but the overall stiffness of a prosthesis could be matched to that of cortical bone by using an integrated design involving a porous magneto-active layer bonded to a dense non-magnetic core.

The laser-diffraction technique has been applied to design a microfluidic channel for measuring red blood cell deformability over a range of shear stress. A laser beam traverses a diluted blood suspension and is diffracted by RBCs in the volume. The diffraction patterns are captured by a CCD-video camera, linked to a frame grabber integrated with a computer. When deforming under decreasing shear stress in the microchannel, RBCs change gradually from the prolate ellipsoid towards a circular biconcave morphology. Both the laser-diffraction image and pressure were measured with respect to time, which enable to determine the elongation index (EI) and the shear stress. The range of shear stress is 0~20Pa and the measuring time is less than 2min. The elongation index (EI) is determined from an isointensity curve in the diffraction pattern using an ellipse-fitting program. The key advantage of this design is the incorporation of a disposable element that holds the blood sample, which enables the present system to be easily used in a clinical setting.

Synchrotron FTIR maps, focal plane array and linear array images recorded of 4 μm cervical biopsy sections from the surface epithelium and glandular endometrium are compared in terms of spatial resolution and applicability to the clinical environment. Synchrotron FTIR maps using a 10 μm aperture appear to provide a better spatial resolution capable of discerning single nuclei in the tissue matrix. Unsupervised hierarchical cluster analysis performed on the synchrotron, focal plane array and linear array data in the 1700-1400 cm^-1 region show very similar clusters and mean-extracted spectra, demonstrating the robustness of FTIR microscopy and UHCA in the analysis of tissue sections. Maps recorded with the focal plane array using a conventional globar source take one-fortieth of the time but the spatial resolution precludes true single cell analysis in the tissue matrix. The high spatial resolution achieved with the synchrotron shows potential as a gold standard for FTIR diagnosis of cervical samples.

An automated classification technique is desirable to identify the different stages of sleep. In this paper a technique for differentiating the characteristics of each sleep phase has been developed. This is an ideal pre-processor stage for classifying systems such as neural networks. A wavelet based continuous Morlet transform was developed to analyse the EEG signal in both the time and frequency domain. Test results using two 100 epoch EEG test data sets from pre-recorded EEG data are presented. Key rhythms in the EEG signal were identified and classified using the continuous wavelet transform. The wavelet results indicated each sleep phase contained different rhythms and artefacts (noise from muscle movement in the EEG); providing proof that an EEG can be classified accordingly. The coefficients founded by the wavelet transform have been emphasised by statistical techniques. Hypothesis testing was used to highlight major differences between adjacent sleep stages. Various signal processing methods such as power spectrum density and the discrete wavelet transform have been used to emphasise particular characteristics in an EEG. By implementing signal processing methods on an EEG data set specific rules for each sleep stage have been developed suitable for a neural network classification solution.

Traditional ECG viewing techniques use a flat file structure and the relationship of the leads to physical structure is not clear. State space allows a 3D representation that is more representative of anatomical structure and electrical activity. This paper demonstrates how novel visualisation techniques allow easier identification of anomalies. The methods employed use Taken’s state-space theory to plot the amplitude of user selected leads on the relative axes in the state space domain. By plotting the combined values of separate leads, the direct relationship between the different viewing angles of the electrodes can be seen. A graphical user interface (GUI) was developed to view MIT-BIH database files, and files from a cardiology clinic, in various state-space formats. This software allows the user to rotate the 3D models and provides a cross-sectional view of the plots at user selected coordinates. The usefulness of these models were determined by combining the orthogonal views of leads I, aVF, and V2. This enabled the user to collaborate the vector values of the lead locations with the conventional ECG characteristics.

For large scale analysis purposes, the conversion of genomic sequences into digital signals opens the possibility to use powerful signal processing methods for handling genomic information. The study of complex genomic signals reveals large scale features, maintained over the scale of whole chromosomes, that would be difficult to find by using only the symbolic representation. Based on genomic signal methods and on statistical techniques, the paper defines parameters of DNA sequences which are invariant to transformations induced by SNPs, splicing or crossover. Re-orienting concatenated coding regions in the same direction, regularities shared by the genomic material in all exons are revealed, pointing towards the hypothesis of a regular ancestral structure from which the current chromosome structures have evolved. This property is not found in non-nuclear genomic material, e.g., plasmids.

Gene networks are composed of many different interacting genes and gene products (RNAs and proteins). They can be thought of as switching regions in n-dimensional space or as mass-balanced signaling networks. Both approaches allow for describing gene networks with the limited quantitative or even qualitative data available. We show how these approaches can be used in modeling the apoptosis gene network that has a vital role in tumor development. The open question is whether engineering changes to this network could be used as a possible cancer treatment.

In earlier work, we proposed “computing with bio-agents”, a new model of computation, of the distributed parallel type, based on the notion that motions of biological objects such as bacteria or protein molecular motors in confined spaces can be regarded as computations. Beginning with the observation that the geometric nature of the physical structures in which model biological objects move modulates the motions of the latter, we inferred that by altering the geometry, one can control the characteristic trajectories of the objects and thus perform meaningful computations. In the present work we describe designed geometries and structures that can be used to achieve various computational tasks in this framework. Specifically, we describe methods for solving difficult combinatorial problems from graph and number theory in an efficient way using bio-agents.

The demand for polymer-based DNA microarrays will increase because of their cost-effectiveness, biocompatibility and easy processing. However not all polymers are ideal substrates because of different chemical interactions of polymeric substrates with the DNA molecules. Results from AFM analysis of DNA immobilised on polymeric surfaces are evaluated using fractality, Gaussian distribution and lateral force imaging. It has been found that the nanosize defects in the substrate, such as poly-l-lysine, plays an important role in the growth of DNA aggregates in a vertical direction, whereas the covalent binding of DNA molecules on NHS-functionalised cyclo-olefin copolymer leads to the lateral growth of DNA aggregates.

Insects have a very efficient visual system that helps them to perform extraordinarily complicated navigational acts and precisely controlled aerobatic flight. Physiological evidence suggests that flight control is guided by a small system of 'tangential' neurons tuned to very specific types of complex motion by the way that they collate information from local motion detectors. One class of tangential neurons, the 'horizontal system' (HS) neurons, respond with opponent graded responses to yaw stimuli. Using the results of physiological experiments, we have developed a model, based on an array of Reichardt correlators, for the receptive field of HS neurons that view optical flow along the equator. Our model incorporates additional non-linearities that mimic known properties of the insect motion pathway, including logarithmic encoding of luminance, saturation and motion adaptation (adaptive gain-control). In this paper, we compare the response of our elaborated model with fly HS neuron responses to naturalistic image panoramas. Such responses are dominated by noise which is largely non-random. Deviations in the correlator response are likely due to the structure of the visual scene, which we term "Pattern noise". To investigate the influence of anisotropic features in producing pattern noise, we presented a panoramic image at various initial positions, and versions of the same image modified to disrupt vertical contours. We conclude that the response of the fly neurons shows evidence of local saturation at key stages in the motion pathway. This saturation reduces the effect of pattern noise and improves the coding of velocity. Our model provides an excellent basis for the development of biomimetic yaw sensors for robotic applications.

The concept of micro wall jets has been applied to the low Reynolds number (Re≤1), two-dimensional channel flows which may be found in biosensor microfluidic systems. The current numerical investigation utilizes the lattice Boltzmann method for flow field, temperature and binary fluid transport computations. Inlet and wall temperatures were specified along with various binary fluid properties to demonstrate their effect on the main channel flow due to the addition of micro wall jets. Results indicate similar levels of mixing for single and double jet configurations. The data also indicates the potential of using opposing jets to focus the binary fluid in the center of the channel.

MEMS-based microneedles have the potential to revolutionize biomedical/biotechnology applications by providing precise transdermal drug delivery and localized blood sampling. In this paper, we propose a novel theory-based model that predicts drift velocity of blood-flow through the microchannels embedded in the microneedles. The profile of blood flow in the microneedles is determined by solving the conservation of momentum equation of the liquid phase, coupled with the force balance equations at the liquid-air interface. For the first time, this work enables accurate calculation/prediction of the velocity profile of the blood flow through a vertical in-plane microneedle, considering the effect of surface tension forces which are the most prominent forces. In order to withdraw blood samples from capillaries in the dermis layer, the length of our MEMS-based in-plane microneedle has been set at 600 μm with the micro-channel thickness chosen to be 35 μm, to avoid deformation of red blood cells. Blood flow through microneedles has been computed analytically using the proposed formulation. The results are then verified by a commercial finite element simulation tool "ANSYS".

Most clinical chemistry tests are performed on cell-free serum or plasma. Therefore micro assay devices for blood tests require integrated on-chip microfluidics for separation of plasma or serum from blood. Polymers are ideally suited for these applications due to their material properties and their applicability for high volume production. These requirements are achieved by a new on-chip blood separation technique based on microchannel bend structures and a rapid processing technology for micro assay devices using injection molding or hot embossing. Different prototype polymer chips with channel dimensions down to 20 μm and aspect ratios of 4 have been fabricated by injection molding and hot embossing. The inserts for the molding tools were fabricated by an UV-LIGA technology. The separation efficiency of these chips has been tested with human blood samples. The results show different separation efficiencies up to 100 % for blood cells and plasma depending on microchannel geometry as well as cell concentration. As compared to present microfluidic devices for the separation of blood cells like filters, membranes or filtration by diffusion the microchannel bend is an integrated on-chip blood separation method. It combines the advantages of rapid separation times and a simple geometry that leads to cost-effective high volume production using injection molding.

A novel polymer microfluidic device for self-wash using only capillary force is presented. A liquid filled in a reaction chamber is replaced by another liquid with no external actuation. All the fluidic actuations in the device is pre-programmed about time and sequence, and accomplished by capillary force naturally. Careful design is necessary for exact actions. The fluidic conduits were designed by the newly derived theoretical equations about the capillary stop pressure and flow time. Simulations using CFD-ACE+ were conducted to check the validity of theory and the performance of the chip. These analytic results were consistent with experimental ones. The chip was made of polymers for the purpose of single use and low price. It was fabricated by sealing the hot-embossed PMMA substrate with a PET film. For simpler fabrication, the chip was of a single height. The embossing master was produced from a nickel-electroplating on a SU8-patterned Ni-plate followed by CMP. The contact angles of liquids on substrates were manipulated through the mixing of surfactants, and the temporal variations were monitored for a more exact design. The real actuation steps in experiment revealed the stable performance of selfwash, and coincided well with the designed ones. The presented microfluidic method can be applicable to other LOCs of special purposes through simple modification. For example, array or serial types would be possible for multiple selfwashes.

DNA computing is an interdisciplinary field accessing the possibility for the use of biomolecules, such as DNA, RNA and proteins, as a computational or control tool. Traditionally, DNA computers were thought to compete with electronic computers to solve, for example, NP-complete problems. However recently, there has been a focus shift to biomedical applications. One form of DNA computing is performed in microfluidics. A network of microreactors decides the computational aspects and DNA is the tool for selection procedures. To control complex microflow systems like this, a series of pneumatic valves are used to control the flow direction, i.e. the information direction, and to contain DNA functionalised beads in the microreactors.

Medical images are now almost all gathered and stored in a digital representation for easy transmission and archiving. High resolution is mandatory for a detailed diagnosis, which requires accurately known location and density information regarding the important features of the image called the regions of interest (ROI). Such features may include non-displaced fractures or small tumors that can often be difficult to identify. A reduction in size by using compression is necessary for efficient transmission over a wireless link where remote diagnosis may be an only option in many cases. Despite rapid advances in lossy compression, most research in the compression of medical imagery specifies that the ROI must be conserved as much as possible or compressed with a lossless or near-lossless algorithm. To ensure diagnostic integrity of these crucial regions after transmission, a multiple watermarking technique has been developed which can be used to verify the integrity of the ROI prior to diagnosis. This has the benefit of assuring that incidental degradation has not affected any of the crucial regions. A strong focus is placed on the robustness of the watermarking technique to JPEG compression as well as the issue image file size and quality tradeoff. The most useful contribution in our work is assurance of ROI image content integrity after image files are subject to incidental degradation in these environments. This is made possible with extraction of DCT signature coefficients from the ROI and embedding multiply in the Region of Backgrounds (ROB).

A wireless network of multiple sensor nodes for monitoring large numbers of mobile agents is described and investigated. Wireless monitoring provides time critical information from a number of data sources allowing near real-time analysis of the collected data. The developed wireless network provides a moderate data rate, is able to support many wireless nodes and is a low power solution. Novel network structures have been developed to satisfy all of these requirements. This paper evaluates a number of currently available wireless communication protocols, concluding that a Bluetooth wireless network satisfies the above criteria. To support a large number of devices, topologies using inter-piconet and piconet sharing methods have been developed. These network structures are outlined in detail and have been developed with the current Bluetooth hardware limitations in mind. The proposed wireless networks have been developed to be implemented with current Bluetooth hardware. A summary of network performance is included for each developed network structure, and from these figures an appropriate network structure has been chosen that satisfies the requirements of a wireless sensor network for monitoring mobile agents.

The neurons in dissociation culture autonomously re-organized their functional neuronal networks, after the process for elongating neurites and establishing synaptic connections. The spatio-temporal patterns of activity in the networks might be a reflection of functional neuron assemblies. The functional connections were dynamically modified by synaptic potentiation and the process may be required for reorganization of the functional group of neurons. Such neuron assemblies are critical for information processing in brain. To visualize the functional connections between neurons, we have analyzed the autonomous activity of synaptically induced action potentials in the living neuronal networks on a multi-electrode array, using "connection map analysis" that we developed for this purpose. Moreover, we designed aan original wide area covering electrode array and succeeded in recording spontaneous action potentials from wider area than commercial multi electrode arrays.

In this work we present the dielectrophoretic structure fabricated using two glass wafers and one 0.5 mm thick and highly conductive silicon wafer. In fabricated device the DEP force extends uniformly across the volume of the microfluidic device in the direction normal to the wafer plane. This is achieved by fabricating microfluidic channel walls from doped silicon so that they can also function as DEP electrodes. The advantages of the structure are: electrical leadouts that are free from the fluid leakage usually associated with the lead out recesses, a volume DEP force for deep chambers compared with the surface forces achieved by planar electrodes, no electrical dead volumes as encountered above the thin planar electrodes of alternative technologies, biocompatible silicon oxide passivated surfaces, and no electrochemical effects that arise from edge effects in multi-metal electrodes such as Ti/Au or Cr/Au.

Current methods used to study neural communication have not been able to achieve both good spatial and temporal resolution of recordings. There are two ways to record synaptic potentials from nerve endings: recordings using single or dual intracellular or extra cellular metal electrodes give good temporal resolution but poor spatial resolution, and recording activity with fluorescent dyes gives good spatial resolution but poor temporal resolution. Such medical research activity in the area of neurological signal detection has thus identified a requirement for the design of a CMOS circuit that contains an array of independent sensors. As both spatial and temporal distribution of acquired data is required in this application, the circuit must be capable of continuous measurement of synaptic potentials from an array of points on a tissue sample, with a 10 μm separation between sensor points. The major requirement for the circuit is that it is capable of sensing synaptic potentials of the order of several mV, with a resolution of 0.05 mV. For data recording purposes, the circuit must amplify these synaptic potentials and digitise them together with their locations in the sensor array. Finally, the circuit must be biologically inert, to avoid specimen deterioration. This paper presents the design of a prototype single-chip circuit, which provides a 6 x 3 array of independent synaptic potential sensors. The signal from each of the sensors is amplified and time-multiplexed into an on-chip A/D converter. The circuit provides an 8-bit synaptic potential value, together with an 8-bit field containing array location and trigger signals suitable for external data acquisition instrumentation. Our test circuit is implemented in a low-cost 0.5 um, 5 V CMOS process. The fabricated die is mounted in a standard 40 pin DIP ceramic package, with no lid to allow direct contact of the die surface with the tissue sample. The only post-processing step required for these packages is to encapsulate the exposed bond wires to ensure that the device is biologically inert. No further processing of the silicon die is required. Both the circuit design and the chip performance will be presented in the seminar.

Recently, a novel crown-shaped microneedle array fabricated by deep X-ray lithography so called, quadruplets-microneedle array was reported. The microneedle requires no hole-fabrication whilst still can be used for a blood extraction system. Due to its quadruped tip, a deep channel formed by the space between each spike is used for storing blood by a capillary force. The particular shape of the microneedle is unrealizable by other microfabrication technology apart from PCT(Plain-pattern to Cross-section Transfer) technique. Nanoscaled tips and sloped side-wall of the structure ease a smooth skin-penetration. A model for simulating the capillary height of the extracted blood for this specific shape has been developed since the typical capillary theory is suitable for the only tube shape of liquid channel. The result of simulation conforms to the practical extraction test of the microneedle. The amount of blood retained inside the microneedle can be predicted by the height obtained from the simulation. Besides the PCT technique, the electroforming of Nickel has been demonstrated in order to fabricate the mold. The injections of polycarbonate is then performed for final structures. The cost of each microneedle array after a large volume-production has been dumped to be less than a US dollar. In this paper, the fabrication process and capillary models for individual simulation of the quadruplets-microneedle will be reported.

An implantable analog front-end for human nerve signal sensors is presented. The front-end is composed of a low-noise, high-gain pre-amplifier and an analog-to-digital converter (ADC) for quantizing the recorded nerve signal. The front-end is implemented in a 0.35um CMOS technology. The circuit draws 196uA from a 1.8V supply, thus consuming approximately 350uW excluding bias circuitry and buffers. As the signal provided by the nerve signal only has a magnitude of a few microvolts, the pre-amplifier intrinsic noise has to be minimized in order to retain a sufficient signal-to-noise ratio (SNR). A two-stage design for achieving an overall gain of 74dB is employed. For low thermal noise, the first stage is biased at a relatively high current and employs MOS transistors (MOSTs) biased in the weak inversion region. The chopper modulation technique is utilized for shifting low frequency 1/f-noise out of the signal band leaving thermal noise dominant in-band. The measured noise is approximately 7nV/sqrt(Hz) input referred, for a chopping frequency of 20kHz, while the measured gain is 72.5dB over a 4kHz bandwidth. The measured power supply rejection ratio (PSRR) is above 90dB and the common-mode rejection ratio (CMRR) exceeds 105dB inband. The implemented ADC is of the sigma-delta type, and uses a third order continuous-time loop-filter. The loop-filter is implemented using Gm-C integrators, and uses CMOS only for the transconductor implementation. The measured resolution of the manufactured ADC is 10 bits and features a dynamic range (DR) of 67dB at a sampling rate of 1.4MHz.

As the population ages, health management will be one of the important issues. The development of a safe medical machine based on MEMS technologies for the human body will be the primary research project in the future. We have developed the glucose sensor, as one of the medical based devices, for use in the Health Monitoring System (HMS). HMS is the device that continuously monitors human health conditions. For example, blood is the monitoring target of HMS. The glucose sensor specifically detects the glucose levels of the blood and monitors the glucose concentration as the blood sugar level. This glucose sensor has a "separated Au electrode", which immobilizes GOx. In our previous work, GOx was immobilized onto Au electrode by the SAMs (Self-Assembled Monolayer) method, and the sensor, using this working electrode, detected the glucose concentration of an aqueous glucose solution. In this report, we used a Pt electrode, which immobilized GOx, as a working electrode. Au electrode, which was used previously, was dissolved by the application of current in the presence of chloride ions. Based on the above-mentioned fact, a new working electrode, which immobilized GOx, was produced using Pt, which did not possess such characteristics. These Pt working electrodes were produced using the covalent binding method and the cross-link method, and both the electrodes displayed a good sensing property. In addition, the electrode using glutaraldehyde (GA) and bovine serum albumin (BSA) as crosslinking agents was produced, and it displayed better characteristics as compared with those displayed by the electrode that used only GA. Based on the above-mentioned techniques, the improvement in performance of the sensor was confirmed.

In this paper, we present the design of an endoscope probe, which can image the inner cavity walls as well as collect fluorescence emission from the same cavity inner surfaces, for disease diagnosis in body cavities. The probe makes use of a single coherent laser illumination / excitation source for both modalities. An imaging lens at the probe end collects the fluorescence emission as well as the image from the test surface. Two types of imaging lens are used in the probe and their fluorescence collection efficiencies and imaging capabilities are compared with each other. An eyepiece at the end of the probe directs the transmitted light into a CCD camera / Monochromator through selected filters to display the image / analyze the emission spectrum. The developed probe has been tested in a phantom colon model, where cancerous growths and fluorophores are simulated, so as to illustrate the probe diagnostic efficiency.

It is known that rapid mixing in microchannels overcomes the inherent diffusion-limited mixing of laminar flow. Consequently, many techniques that enhance microfluidic mixing are under development: slanted wells, shallow grooves, electrokinetic instability mixing and surface layers, etc. The long-term goal of this work is the optimization of surface-property distributions to control mixing and provide surface-directed flows. In this work, binary fluid mixing is explored using the lattice Boltzmann Method (LBM) to simulate flows in two-dimensional, microfluidic channels having surface temperature variations. Previous work has shown the advantages of controlled wall temperature distributions (i.e., flow-through PCR devices). Over 100 mixing scenarios were simulated by varying the Reynolds number, wall temperature distributions, binary fluid density ratios and interaction strengths, and the coupling strength between momentum and temperature. If one adds channel geometry variations, we are optimizing a mixing function over a multidimensional parameter space of large dimension. This vector-valued mixing function contains two scalar-valued objective functions. Each objective function measures the mixing obtained for fluid 1 and fluid 2. The optimization problem is to find designs that simultaneously attain an optimal mix of both fluids. Consequently, we have a massive, computationally-intensive, multiobjective optimization problem. In multiobjective optimization problems, many acceptable designs can be obtained by trading one objective function against the other. For example, one might accept a slightly worse mixing of fluid 1 for a much better mix of fluid 2. We demonstrate optimal mixing as a function of these designs, that is the variation of the wall temperatures and the heater lengths.

This work describes an innovative approach to preparation of the highly controlled drug delivery materials that involves a self-assembly process at the molecular level based upon the silicified L₃ phase silicates and thermoresponsive PNIPAm integrated L₃ phase silicates. The materials designed by the integration of thermosensitive polymer have been prepared and demonstrated for the highly controlled drug releasing system over a longer period of time due to their high degree of continuity and contigunity in 3-D interconnected porous structure. This approach is suitable for long term drug delivery systems with constant release in hard tissue engineering due to nanodiffusion mechanism. The structural characterization was achieved by TEM, SEM, SAXD, solid-state ²⁹Si NMR, and BET.

This paper describes chemically functionalized mesoporous silica as a novel catalyst for the rapid hydrolysis of a phenyl ester. Work demonstrates a very simple and flexible approach to control surface reactivity on the nanometer scale using a self-assembled organic monolayer consisting of polar, (dihydroxyl, carboxyl, ethylene-diamine, and dihydroimidazole), and non-polar (isobutyl) groups. All five functional groups are an essential requirement in preparing an enzyme-like catalyst because of the synergistic effect and hydrophobic partitioning, which has been verified by a 13C CP- MAS solid-state NMR technique. Catalytic activities were obtained from the catalytic efficiency constant and specificity constant using Michaelis-Menten kinetics. Catalytic activities were close to those of a natural enzyme when 12% of the surface was covered by hydrophobic isobutyl silane. The rate of enzyme catalyzed activity was dependent on the energy of the transition state as defined in terms of an energy barrier derived from the relationship between transfer free energy and specificity constant.

A self-priming and bubble tolerant planar micro-pump, which is fabricated by traditional technology, has been demonstrated and characterized. The micro-pump has a simple three-layered structure. Its two pump housings are made of polycarbonate and they are fabricated by computer numerical control (CNC) machine. The actuation membrane, which acts as the inlet and outlet valve membrane is cast in polydimethylsiloxane (PDMS). Using the PDMS membrane to act as the actuation membrane and valve membrane, we have solved the problem of sealing and poor compression ratio that most silicon based micro-pump faced. From the model of the membrane stroke volume, the flow rate of the pump is insensitive to the pump output pressure, and the output flow rate is linearly varying with actuating frequency. Flow rate up to 1000 ul/min of liquid has been achieved. More than 2m pump-head has been obtained when using water as the pumping medium. The robustness of the pump makes it suitable for disposable applications like biochip system.

To recognize the information of ischemia-induced blood vessel permeability would be valuable to formulate the drugs for optimal local delivery, we constructed an implantable needle type fiber-optic microprobe for the monitoring of in vivo fluorescent substances in anesthetized rats. This fiber-optic microprobe was composed of coaxial optical fibers and catheterized using a thin wall tubing of stainless steel (~400 um O.D. and ~300 um I.D.). The central fiber, with 100 um core diameter and 20 um cladding, coated with a 30 um layer of gold, was surrounded by 10 fibers with 50 um cores. The central fiber carried the light from the 488 nm Argon laser to the tissue while the surrounding fibers collected the emitted fluorescence to the detector. When the fiber-optic microprobe was placed in the solutions containing various concentrations of fluorescent nanospheres (20 nm), either with or without 10% lipofundin as optical phantom, nanosphere concentration-dependent responses of the fluorescence intensity were observed. The microprobe was then implanted into the liver and the brain of anesthetized rats to monitor the in situ extravasation of pre-administered fluorescent nanospheres from vasculature following the ischemic insults. Both the hepatic and cerebral ischemic insults showed immediate increases of the extracellular 20 nm fluorescent nanospheres. The implantable fiber-optic microprobe constructed in present study provides itself as a minimally-invasive technique capable of investigating the vascular permeability for in vivo nanosphere delivery in both ischemic liver and brain.

A compact and wearable wristwatch type Bio-MEMS such as a health monitoring system (HMS) to detect blood sugar level for diabetic patient, was newly developed. The HMS consists of (1) a indentation unit with a microneedle to generate the skin penetration force using a shape memory alloy(SMA) actuator, (2) a pumping unit using a bimorph PZT piezoelectric actuator to extract the blood and (3) a gold (Au) electrode as a biosensor immobilized GOx and attached to the gate electrode of MOSFET to detect the amount of Glucose in extracted blood. GOx was immobilized on a self assembled spacer combined with an Au electrode by the cross-link method using BSA as an additional bonding material. The device can extract blood in a few microliter through a painless microneedle with the negative pressure by deflection of the bimorph PZT piezoelectric actuator produced in the blood chamber, by the similar way the female mosquito extracts human blood with muscle motion to flex or relax. The performances of the liquid sampling ability of the pumping unit through a microneedle (3.8mm length, 100μm internal diameter) using the bimorph PZT piezoelectric microactuator were measured. The blood extraction micro device could extract human blood at the speed of 2μl/min, and it is enough volume to measure a glucose level, compared to the amount of commercial based glucose level monitor. The electrode embedded in the blood extraction device chamber could detect electrons generated by the hydrolysis of hydrogen peroxide produced by the reaction between GOx and glucose in a few microliter extracted blood, using the constant electric current measurement system of the MOSFET type hybrid biosensor. The output voltage for the glucose diluted in the chamber was increased lineally with increase of the glucose concentration.

The ability of electrokinetics to manipulate biological microparticles, such as cells and bacteria, has great applications in Lab-on-a-chip devices, and micro-total analysis systems (mTAS). In these methods, non-uniform AC electric fields interact with the dielectric properties of suspended biological microparticles to induce forces and torques on the particles, in order to manipulate them. This is usually done using devices which are planar microelectrode arrays patterned on glass substrates. These devices usually exploit the fact that biological microparticles are dielectrically heterogeneous structures, and that each different type of biological particle has a distinct dielectric frequency response signature. This enables discrimination and selectivity of cells when manipulating electrokinetically. Electrokinetics in the form of Dielectrophoresis (DEP) and Travelling-Wave Dielectrophoresis (TWD) are used to induce rectilinear motion on suspended microparticles, whilst electrorotation is used to induce torques. This paper presents a device for manipulating biological microparticles using electrokinetics. The device consists of planar metal electrode arrays patterned on glass. The device exploits the dielectric frequency response of the microparticles for manipulation as well as sensing.

This research focuses on the use of EIS (electrolyte on insulator on Silicon) structure as a detection platform for DNA binding. The EIS structure (Electrolyte on Insulator on Silicon) provides a novel, label-free and simple to fabricate way to make a field effect DNA detection sensor. The sensor responds to fluctuating capacitances caused by a depletion layer thickness change at the surface of the silicon substrate and also through DNA adsorption onto the dielectric oxide/amino surface. In this paper we present the fundamentals of the Capacitance-Voltage plot technique and how it can be used a method for detecting DNA binding and surface charge transits. The CV plot is a widely used technique in the microelectronics industry for characterizing and profiling capacitor devices. It is mainly used to test the quality of these devices and give an indication of failing processing conditions. Its high sensitivity and ability to provide a wealth of information makes it a suitable choice for our research [11]. We also looked at using 2 types of amino layers and compared their effectiveness as DNA adhesives based on surface charge. The two types we chose to investigate were Poly-L-Lysine and 3-Aminopropylthioxysilane. Their compounds are quite similar in nature in that they contain a NH2 terminated group which is easily protonated in physiological buffers. PolyLysine and APTES are both commonly used in labs to coat slides for adhering cells and also used as monolayer linkers for tethering further compounds. PolyLysine tends to be more expensive than APTES, but safer to use since it isn't as corrosive as APTES. Our results show that APTES was a suitable choice for our experiments.

Electrical interfacing with neural tissue poses significant problems due to host response to the material. This response generally leads to fibrous encapsulation and increased impedance across the electrode. In neural electrodes such as cochlear implants, an elastomeric material like silicone is used as an insulator for the metal electrode. This project ultimately aims to produce a polymer electrode with elastomeric mechanical properties, metal like conductivity and capability. The approach taken was to produce a nanocomposite elastomeric material based on polyurethane (PU) and carbon nanotubes. Carbon nanotubes are ideal due to their high aspect ratio as well as being a ballistic conductor. The choice of PU is based on its elastomeric properties, processability and biocompatibility. Multi-walled nanotubes (MWNTs) were dispersed ultrasonically in various dispersive solutions before being added at up to 20wt% to a 5wt% PU (Pellethane80A) in Dimethylacetamide (DMAc). Films were then solvent cast in a vacuum oven overnight. The resulting films were tested for conductivity using a two-probe technique and mechanically tested using an Instron tensiometer. The percolation threshold (p) of the PU/MWNT films occurred at loadings of between 7 and 10 wt% in this polymer system. Conductivity of the films (above p) was comparable to those for similar systems reported in the literature at up to approximately 7x10^-2 Scm^-1. Although PU stiffness increased with increased %loading of nanotubes, all composites were highly flexible and maintained elastomeric properties. From these preliminary results we have demonstrated electrical conductivity. So far it is evident that a superior percolation threshold is dependent on the degree of dispersion of the nanotubes. This has prompted work into investigating other preparations of the films, including melt-processing and electrospinning.

The design and fabrication of biomedical tools using techniques common in microelectronics is becoming established procedure. In our research, we use gaseous plasma dry etching to form microstructures on silicon wafers. These are intended for use in capturing and binding antibodies and live cells in an array to be used in High Throughput Screening (HTS) and High Content Screening (HCS) of new pharmaceuticals. We call this new arraying plate the "Nanotiter" plate. The benefit of our design (100 x 100 wells in a 25 x 25 mm array) over current 96-, 384- and 1056-well microtiter plates are that the number of samples (wells) that can be tested in one plate scan can be substantially increased, the wells can be rapidly and effectively washed, and the well surfaces can be modified to modulate ligand binding. Simple crowding of wells on a plate can result in cross contamination of samples in adjacent wells during the washing. Furthermore, motile cells may migrate between the wells. 1056 microtiter plates currently cannot be washed, and washing 384 plates is problematic. Our design incorporates plasma-deposited polymers that functionally bind antibodies (or other proteins) in but not between wells. Furthermore, the wells can be shaped to minimize cell migration. Inverting the plate on a wash solution allows unbound cells to simply fall away under gravity thus minimising the contamination of adjacent wells. Thus, our Nanotiter plate represents a substantial improvement over existing technology.

Self-segregation and compartimentalisation are observed experimentally to occur spontaneously on live membranes as well as reconstructed model membranes. It is believed that many of these processes are caused or supported by anomalous diffusive behaviours of biomolecules on membranes due to the complex and heterogeneous nature of these environments. These phenomena are on the one hand of great interest in biology, since they may be an important way for biological systems to selectively localize receptors, regulate signaling or modulate kinetics; and on the other, they provide an inspiration for engineering designs that mimick natural systems. We present an interactive software package we are developing for the purpose of simulating such processes numerically using a fundamental Monte Carlo approach. This program includes the ability to simulate kinetics and mass transport in the presence of either mobile or immobile obstacles and other relevant structures such as liquid-ordered lipid microdomains. We also present preliminary simulation results regarding the selective spatial localization and chemical kinetics modulating power of immobile obstacles on the membrane, obtained using the program.

Micro particle image velocimetry (PIV) measurements of the velocity fields around oscillating gas bubbles in microfluidic geometries were undertaken. Two sets of experiments were performed. The first measured the acoustic microstreaming around a gas bubble with a radius of 195 μm attached to a wall in a chamber of 30 mm× 30 mm× 0.66 mm. Under acoustic excitation, vigorous streaming in the form of a circulation around on the bubble was observed. The streaming flow was highest near the surface of the bubble with velocities around 1mm/s measured. The velocity magnitude decreased rapidly with increasing distance from the bubble. The velocity field determined by micro-PIV matched the streaklines of the fluorescent particles very well. The second set of experiments measured the streaming at the interface between a trapped air bubble and water inside a microchannel of cross section 100 μm × 90 μm. The streaming flow was limited to within a short distance from the interface and was observed as a looping flow, moving towards the interface from the top and being circulated back from the bottom of the channel. The characteristic streaming velocity was in the order of 100 μm/s.

p53 is an important gene, involved in apoptosis (programmed cell death), DNA repair, and cell cycle progression. We explore the selective advantages and disadvantages of mutations in the p53 gene on tumor cells, and the heterogeneity of tumor cell populations. Based on an evolutionary computational approach, our model considers changes in mutation rate caused by lack of DNA repair processes, and the lack of apoptosis caused by mutations in p53. We find that the degree of robustness of p53 to mutations has a significant effect on the tumor heterogeneity and “fitness”, with clinical consequences for people who inherit p53 mutations.

The recent development of living microarrays as novel tools for the analysis of gene expression in an in-situ environment promises to unravel gene function within living organisms. In order to significantly enhance microarray performance, we are working towards electro-responsive DNA transfection chips. This study focuses on the control of DNA adsorption and desorption by appropriate surface modification of highly doped p++ silicon. Silicon was modified by plasma polymerisation of allylamine (ALAPP), a non-toxic surface that sustains cell growth. Subsequent high surface density grafting of poly(ethylene oxide) formed a layer resistant to biomolecule adsorption and cell attachment. Spatially controlled excimer laser ablation of the surface produced micron resolution patterns of re-exposed plasma polymer whilst the rest of the surface remained non-fouling. We observed electro-stimulated preferential adsorption of DNA to the ALAPP surface and subsequent desorption by the application of a negative bias. Cell culture experiments with HEK 293 cells demonstrated efficient and controlled transfection of cells using the expression of green fluorescent protein as a reporter. Thus, these chemically patterned surfaces are promising platforms for use as living microarrays.

A microfluidic device, with a temperature control unit to study the behaviour of temperature sensitive hydrogel, has been designed, simulated and fabricated. The system consists of a PDMS (polydimethylsiloxane) microchannel sealed on a Pyrex substrate with microfabricated titanium electrodes for heating and sensing elements. A thermal insulating layer in-between the electrodes and the substrate was found to increase the heat transfer to the fluid and decrease the lateral heat propagation. The temperature profile and the heat distribution in the system were investigated using the commercial software package CFD-ACE+. The device was electrically and thermally characterised. Such a system, biocompatible and re-usable, could be a potential candidate for biomedical applications such as DNA amplification and protein synthesis.

This paper characterizes factors that affect the probability of success for new startups. These guidelines are derived primarily from Venture Capital industry experience in funding disruptive technology companies. It follows with an overview of Silicon Valley MEMS and MOEMS startups and provides with a summary of Do’s and Don’ts for entrepreneurs.