Proceedings Volume 6036

BioMEMS and Nanotechnology II

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Proceedings Volume 6036

BioMEMS and Nanotechnology II

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Volume Details

Date Published: 12 January 2006
Contents: 9 Sessions, 53 Papers, 0 Presentations
Conference: Microelectronics, MEMS, and Nanotechnology 2005
Volume Number: 6036

Table of Contents

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Table of Contents

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  • Nanotechnology: Molecules and Molecular Surfaces
  • Nanotechnology: Nanoparticles, CNTs, and Nanomaterials
  • Microfluidics and Micro/Nanomanipulation I
  • Microfluidics and Micro/Nanomanipulation II
  • Biomedical Microdevices
  • Sensors and Biosensors I
  • Sensors and Biosensors II
  • Biomedical Engineering
  • Poster Session
Nanotechnology: Molecules and Molecular Surfaces
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Ge/Si island nucleation and ordering on naturally and artificially patterned substrates
Nunzio Motta, A. Sgarlata, A. Balzarotti, et al.
Quantum dots (QDs) grown on semiconductors surfaces are actually the main researchers' interest for applications in the forecoming nanotechnology era. New frontiers in nanodevice technology rely on the precise positioning of the nucleation site and on controlling the shape and size of the dots. Novel approaches to form ordered patterns of homogeneous nanostructures are explored: natural patterning induced by surface instabilities (as step bunching of Si(111) or misoriented Si(001) surfaces), standard patterning with high resolution lithographic techniques, implantation of Ga+ ions by Focused Ion Beam (FIB), or in situ substrate patterning by Scanning Tunneling Microscopy (STM). Based on the analysis of STM images we report on growth and arrangement of Ge islands on Si(001) substrates nanopatterned using several different approaches. The first is a natural method based on the regular step bunching that occurs on Si(111) surfaces with different annealing treatments. The second is based on the self organization of a Si(001) misoriented surface covered by a thin layer of a GeSi alloy. The third exploit an array of holes produced by STM lithography. The forth is a tight pattern created by FIB. We analyze the resulting distribution of islands resulting from all these approaches.
Actomyosin motility detection using quartz crystal microbalance
Kristi L. Hanson, Viswanathan Viidyanathan, Dan V. Nicolau
A 5 MHz Quartz Crystal Microbalance was used to investigate changes in resonant frequency and motional resistance of the protein film during in vitro actomyosin motility on a poly (tert-butyl methacrylate) surface. QCM crystal frequency was found to decrease with adsorption of heavy meromyosin (HMM) to the crystal surface, and with binding of additional protein during the standard BSA blocking step. The frequency and resistance signals after binding of dead HMM heads in actin rigor complexes were consistent with those expected for a film becoming more rigid, but suggested that little mass was added during this step. Addiion of the low concentration of actin used for motility did not cause a significant signal response, but addition of ATP to initiate actin filament movement caused both frequency and resistance signals to increase slightly, consistent with a less rigid protein film of lower apparent mass, suggesting that moving filaments are felt with a lower effective mass than strongly bound static filaments. The frequency signal also fluctuated significantly during motility, consistent with a dynamic process occurring on the crystal surface.
Electron tunneling through alkanedithiol molecules
R. C. Hoft, J. Liu, M. B. Cortie, et al.
We report on first principles calculations of the tunneling current across n-alkanedithiol molecules (n = 4,6,8,10,12) sandwiched between two Au {111} electrodes. The conductance drops exponentially with increased chain length with decay parameter βn = 0.9. The results are compared with scanning tunneling microscopy measurements on decanedithiol and with other n-alkanedithiol (n = 6,8,10) results in the literature. The theoretical results are found to be an order of magnitude larger than experimental values but follow the same trend. However, two additional, more realistic, geometries are modeled by changing the bond type and by combining the first-principles results with a Wentzel-Kramer-Brillouin (WKB) expression for tunneling across the air gap that is invariably present during scanning tunneling microscopy (STM) measurements. These results are more compatible with the experimental data.
How reliable are scanning tunneling microscopy measurements of electron transport in molecules?
Michael J. Ford, Les Kirkup, Angus Gentle, et al.
Scanning tunneling microscopy measurements of tunneling through molecules adsorbed on a surface have been simulated using a standard empirical model based upon the Wentzel-Kramer-Brillouin method applied to tunneling through a barrier. The Gaussian noise inherent in these experiments has been added to the model data using a Monte Carlo technique. By generating multiple sets of current-voltage curves and fitting these to the model we have evaluated how reliably barrier height can be determined as a function of noise level. The results suggest that for constant percentage standard deviation in the noise greater than 5% the barrier height cannot be determined reliably. At this level, the standard deviation in the estimate of the barrier height is about 10%. Weighted fits give more reliable estimates of the barrier height. If the height of the tip above the molecule is known, so that the fit is only a single parameter the barrier height can be determined reliably even at percentage noise levels as high as 20%. However, in this case unweighted fits must be used otherwise the estimated value deviates by up to 15% from the true value. Data with constant absolute noise give similar results. The effects of experimental resolution have been evaluated in a similar manner and are shown to have a significant influence on the reliability. At a resolution of about 0.1% of full scale the standard deviation in the estimate of barrier height is only about 2% but increases rapidly to 10% for a resolution of about 1%.
Investigation of ssDNA molecule using clustered atomistic method and its application to the dsDNA analysis
Cheng-Nan Han, Cadmus Yuan, Kuo-Ning Chiang
A novel single-stranded DNA (ssDNA) model based on the clustered atomistic method is conducted to simulate the meso-mechanics of ssDNA molecule. Through the validation of the single molecular experiment, the proposed ssDNA model could represent the ssDNA molecule in different counter length, and the mechanical characteristic of the ssDNA molecule in external tensile loading could be elucidated. Furthermore, the characteristic of the validated ssDNA model is adapted in the double-stranded DNA (dsDNA) model. The simulation result of the dsDNA model under external loading reveals mechanical behavior of the dsDNA B-S structural transition. Good agreement is achieved between the numerical simulation and single molecular manipulation experimental result, and the mechanical behavior of stretching nicked dsDNA could be revealed.
Nanotechnology: Nanoparticles, CNTs, and Nanomaterials
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Self-organization in composites of poly(3-hexylthiophene) and single-walled carbon nanotubes designed for use in photovoltaic applications
A detailed study of poly(alkylthiophene) self-assembly and organization on single-walled carbon nanotubes (SWNTs) is presented. Experimental evidence for self-assembly and organization of regioregular poly(3-hexyl thiophene) (rrP3HT) on single-walled carbon nanotubes was obtained using scanning tunneling microscopy (STM) and transmission electron microscopy (TEM). TEM images of drop-cast rrP3HT/SWNT composites displayed strong evidence that SWNTs were isolated from each other in a polymer matrix and coated with between 1-3 layers rrP3HT. STM measurements of adsorbed monolayers of rrP3HT on SWNT surfaces were compared to rrP3HT monolayer deposition on highly ordered pyrolytic graphite (HOPG) surfaces. The results show that average inter-lamellar distances of adsorbed polymer are greater for rrP3HT monolayers adsorbed onto the curved surfaces of SWNTs than on the flat surfaces of HOPG samples. Analysis of STM images yielded the chiral angles at which the thiophene polymer chains wrap around individual carbon nanotubes (41-48° with respect to nanotube axis) while the interchain spacings of adsorbed macromolecules was 1.68 ± 0.02 nm. Comparisons between the native polymer deposited on graphite and the composite structure confirmed that the presence of carbon nanotubes in rrP3HT produces a material with a high degree of order at the molecular level. This high level of order and close coupling of the two components of the composite are prerequisites for its use as the active layer of an organic photovoltaic.
A new fabrication process of silicon nanotips: NERCOM
Francis E. H. Tay, Ciprian Iliescu, Guolin Xu, et al.
This paper presents a new fabrication process for nanotips array using notching effect of reflected charges on mask (NERCOM). The NERCOM fabrication process is based on two phenomena: flowing of thick photoresist mask after bake and the notching effect of the reflected charges from the photoresist mask in a plasma etching process. Heating the photoresist at different temperature and time will generate different profile of the masking layer walls. During the plasma etching process, the charges (ions and radicals) are reflected by the oblique profile of the masking layer walls and generate an undercut. This phenomenon is utilized with an isotropic etching process in a Deep RIE system to produce tips. Due to the isotropy of the process, the tips are generated. The results indicate that the radii of the tips are in the range of 40 to 60 nm.
Formation of a xerogel in reduced gravity using the acid catalysed silica sol-gel reaction
An acid catalysed silica sol-gel reaction was used to create a xerogel in reduced gravity. Samples were formed in a special apparatus which utilised vacuum and heating to speed up the gelation process. Testing was conducted aboard NASA's KC-135 aircraft which flies a parabolic trajectory, producing a series of 25 second reduced gravity periods. The samples formed in reduced gravity were compared against a control sample formed in normal gravity. 29Si NMR and nitrogen adsorption/desorption techniques yielded information on the molecular and physical structure of the xerogels. The microstructure of the reduced gravity samples contained more Q4 groups and less Q3 and Q2 groups than the control sample. The pore size of the reduced gravity samples was also larger than the control sample. This indicated that in a reduced gravity environment, where convection is lessened due to the removal of buoyancy forces, the microstructure formed through cyclisation reactions rather than bimolecularisation reactions. The latter requires the movement of molecules for reactions to occur whereas cyclisation only requires a favourable configuration. Q4 groups are stabilised when contained in a ring structure and are unlikely to undergo repolymerisation. Thus reduced gravity favoured the formation of a xerogel through cyclisation, producing a structure with more highly coordinated Q groups. The xerogel formed in normal gravity contained both chain and ring structures as bimolecularisation reactions were able to effectively compete with cyclisation.
Mechanical properties of MWCNT-reinforced polymeric composites
Yi-Wei Chang, N. Yu
Due to its excellent stiffness and strength, carbon nanotubes (CNTs) are considered as candidates for reinforcement in composites. In the present work, the epoxy resin is used as the matrix whereas multi-walled carbon nanotubes (MWCNTs) with various diameters are used as the reinforcement. The composite is subjected to uniaxial tension and the effects of CNT weight fraction and CNT diameter on the mechanical properties of the composite are studied. Micromechanics models are employed to predict the Young modulus of MWCNT-reinforced composites. The predicted Young moduli are benchmarked with the experimental data of MWCNT-reinforced composites. The Young modulus and tensile strength of epoxy containing 5 wt% MWCNTs with a diameter less than 20 nm increase from 2.83 GPa and 25.67 MPa of pure epoxy to 4.56 GPa and 52.89 MPa, respectively.
Porous hydroxyapatite-gelatin composites with functions of bone substitutes and drug releasing agents: A preliminary study
I. Sopyan, N. S. Sulaiman, D. Gustiono, et al.
Biomedical composites made of porous hydroxyapatite (HA) bonded with a biodegradable polymeric matrix gelatin have been prepared. This device is expected to be useful as an excellent bone graft with bioactive hydroxyapatite which will facilitate new bone formation and at the same time it could functions as drug delivery with a controlled release rate. In this preliminary report, we wish to present preparation and physical characterization of the biomedical composite and the non-biodegradable porous hydroxyapatite composing the matrix of the composite. Porous hydroxyapatite was prepared via polymeric sponge method using hydroxyapatite nanopowders which were prepared via sol-gel procedure. Suspensions of the sol-gel derived hydroxyapatite powder was prepared with an adjusted loading of hydroxyapatite, using a dispersant. After soaking cellulosic sponges into the suspension, the sponges were dried and then subjected to heat-treatment at 600°C, followed by sintering at 1250°C for 1h. Three types of porous hydroxyapatite samples have been prepared in various composition of hydroxyapatite suspension. Porous hydroxyapatite bodies produced from slurry with less hydroxyapatite powder content and more dispersant amount yielded higher porosity and thus causing weaker compressive strength. Compressive strengths varied between 0.67 and 1.94 MPa depending on the porosity of the sample. Porosity plays important role in gelatin loading; the amount of gelatin coated on the porous hydroxyapatite bodies depend on porosity and the gelatin concentration in water solution. The higher porosity the more gelatin can be absorbed by the porous body.
Microfluidics and Micro/Nanomanipulation I
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Cell separation technique in dilectrophoretic chip with bulk electrode
Ciprian Iliescu, Francis E. H. Tay, Guolin Xu, et al.
This paper presents a new technique for separation of two cell populations in a dielectrophoretic chip with bulk silicon electrode. A characteristic of the dielectrophoretic chip is its "sandwich" structure: glass/silicon/glass that generates a unique definition of the microfluidic channel with conductive walls (silicon) and isolating floor and ceiling (glass). The structure confers the opportunity to use the electrodes not only to generate a gradient of the electric field but also to generate a gradient of velocity of the fluid inside the channel. This interesting combination gives rise to a new solution for dielectrophoretic separation of two cell populations. The separation method consists of four steps. First, the microchannel is field with the cells mixture. Second, the cells are trapped in different locations of the microfluidic channel, the cell population which exhibits positive dielectrophoresis is trapped in the area where the distance between the electrodes is the minimum whilst, the other population that exhibit negative dielectrophoresis is trapped where the distance between electrodes is the maximum. In the next step, increasing the flow in the microchannel will result in an increased hydrodynamic force that sweeps the cells trapped by positive dielectrophoresis out of the chip. In the last step, the electric field is removed and the second population is sweep out and collected at the outlet. The device was tested for separation of dead yeast cells from live yeast cells. The paper presents analytical aspects of the separation method a comparative study between different electrode profiles and experimental results.
Laser-based manipulation of growth direction and intracellular processes in fungal hyphae
Fungal growth is concentrated in elongated tips, called hyphae, which have the tendency to maintain their direction of growth. Hyphal tips exhibit a number of tropisms in response to various factors e.g. nutrients, light, physical contact.Irradiation in the area of hyphal tips with a 1064 nm laser affected shown a sensing mechanism within the fungal tip. The result of this was a change of growth direction caused by Spitzenkoerper's tendency to move away from the trap. The manipulation of the growth orientation of fungi in microstructures using focused laser beam has the potential to help the understanding of space search algorithms used by microorganisms.
Finite element analysis of fluid behaviour under micro surface waves
Yanru Shi, Weimin Gao, Zhenxian Yu, et al.
The wide utilisation of micro-systems has brought increasing attention into micro-fluidics in recent years. When the size and mass of a device are scaled down, forces which used to be ignored may become dominant in the performance of a micro system. This paper studies the behaviour of fluid responding to travelling sinusoidal waves imposed by a micro actuator. The thickness of the fluid between the wave surface and the substrate is 20 microns, and the wavelength is 50 microns. The model is developed and implemented in ANSYS. The nonlinearities of the flow exist in both X and Y directions. A stable thrust force can be generated by the moving waves. The direction of the thrust force is opposite to the direction of the travelling wave. The magnitude of the thrust force is related to fluid viscosity, wave amplitude, and wave frequency. As this force is highly predictable and controllable, it can be used to propel a micro device working in thin tubes filled with fluid. The principle could also be applied to non-Newtonian fluid, although the flow will be more complicate.
Conception and design of a thermal valveless micropump
G. Manzoni, S. Heisig, T. Takano, et al.
This paper describes the conception and design of a micropump for gas, with no moving or deformable parts, for use on the future sensor network system, which includes environment monitoring. This design is original because of the complete absence of moving parts for the pumping of gas. In fact, fluid movement was obtained by means of repetitive heating and cooling cycles of the gas, in the pump chamber. The prototyping work is on going and the first results are presented with particular emphasis on thermal characterization.
Development of microfluidic device for a cell counter using electrical impedance method
Jun Lee, Hyun-Seok Choi, Deok-Won Yun, et al.
Many previous researches related with the cell-counter have measured transit of cells by the electrical-impedance method. Most of devices using electrical-impedance method have electrodes which are made by metal deposition process. In this study, the micro channel takes the place of metallic electrodes. The electric current is passed through the micro channel which is filled with PBS solution. The proposed device helps to save the time of fabrications of micro fluidic device. The process for metal deposition and fine alignment process between micro fluidic channel and base of electrodes can be canceled in proposed device. The signal for counting of a red blood cell of human and polymer microspheres were successfully measured.
Microfluidics and Micro/Nanomanipulation II
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Mixing in microchannels based on hydrodynamic focusing and time-interleaved segmentation: modeling and experiment
Nam-Trung Nguyen, Xiaoyang Huang
This paper reports a new mixing concept in microscale using hydrodynamic focusing and sequential segmentation. Both focusing and segmentation were used in the present study to reduce mixing path, to shorten mixing time, and to enhance mixing quality. Transversal mixing path is reduced by hydrodynamic focusing, while sequential segmentation shortens the axial mixing path. Assuming the same viscosity in the different streams, the focused width can be adjusted by the flow rate ratio. The axial mixing path can be controlled by the switching frequency of the inlet valves and the mean velocity of the flow. Both flow rate ratio and pulse width modulation of the switching signal can adjust the desired mixing ratio. This paper first presents a time-dependent two-dimensional analytical model for the mixing concept. This model considers an arbitrary mixing ratio between solute and solvent as well as the axial Taylor-Aris dispersion. A polymeric micromixer was designed and fabricated by CO2 laser micromachining and hot lamination. Sequential segmentation was realized by two piezoelectric valves. The sheath streams for hydrodynamic focusing are introduced through other two inlets. We also designed a measurement system that can synchronize of the mixer's switching signal with the camera's trigger signal. The system allows our relatively slow and low-resolution CCD camera to freeze and to capture a large transient concentration field. The concentration profile along the mixing channel agrees qualitatively well with the analytical model.
A microfluidic sensor for dynamic surface tension measurement
This paper reports on a hybrid polymeric microfluidic device with optical detection for droplet-based systems. The optical part of the device is integrated by a hybrid concept. The microfluidic structures were fabricated using CO2 laser on PMMA (poly methylmethacrylate) substrate. The microfluidic network consists of two microchannels for forming droplets of an aqueous liquid in an immiscible carrier liquid. The optical component consists of two optical fibers for guiding laser light from the source, through the detection point, to a photo diode. The formed droplets pass the detection point and diffract the incoming laser light. The detected signal at the photo diode can be used for evaluating droplet size, droplet shape, and droplet formation frequency. The device can detect very high formation frequencies, which are not detectable using a conventional CCD camera/microscope setup.
Passive control of two merging streams for microfluidic devices
Sung-Jin Kim, Yong Taik Lim, Haesik Yang, et al.
This paper describes the pure passive scheme that manipulates the multiple streams using microfluidic device. This device relies on capillarity to control merging of two streams and to regulate the volumetric flow rate (VFR). This sophisticated manipulation of the capillarity is, however, nontrivial due to the lack of the passive and precise means. Here, we control the capillarity precisely and rapidly through the geometry of the junction of two streams and the hydrophilicity of the substrate. Additionally, we use the relative flow resistance to control the VFR ratio of the merged two streams. This passive scheme leads to the significant simplification of the control of the multistream without sacrificing the rapidity and precision. When combined with the microfluidic components such as mixers, reaction chambers, and detectors, this passive scheme offer the possibility of designing disposable and integrated microfluidic systems.
Biomedical Microdevices
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Development of wearable medical device for Bio-MEMS
Naoyuki Nakanishi, Hidetake Yamamoto, Kazuyoshi Tsuchiya, et al.
Biomedical Micro Electro Mechanical Systems (Bio-MEMS) have been applied to the development of a variety of health care related products including health Monitoring Systems (HMS) and Drug Delivery Systems (DDS). We focus on research to develop the new type compact medical device used for blood sugar control. The new type compact medical device comprises (1) a micropump system to extract blood using a pressure change occurred by electrolysis, (2) a platinum (Pt) electrode as a blood sugar sensor immobilized Glucose Oxidase (GOx) and attached to the gate electrode of Metal-Oxide-Semiconductor Field Effect Transistor (MOSFET) to detect the amount of glucose in extracted blood, and (3) a micropump system to inject insulin using a pressure change occurred by electrolysis. The device can extract blood in a few microliter through a painless microneedle with the micropump, which used the pressure change occurred by electrolysis. The liquid extraction ability of the micropump system through a microneedle, which is 3.8 mm in length and 100 μm in internal diameter, was measured. The wearable medical device with using the micropump controlled by electrolysis could extract human blood at the speed of 0.15 μl/sec. If the wearable medical device extracts human blood for 6 seconds, it is enough human blood volume to measure a glucose level, compared to the amount of commercial based glucose level monitor. The compact medical device with the air bubble that occurred by electrolysis could inject insulin at the speed of 6.15μl/sec.
Microfabricated silicon array of microneedles: prediction of its behaviour during insertion through the skin
Baron N., V. Guicheret-Retel, J.-R. Coudevylle, et al.
Transdermal drug delivery is a novel alternative painless way to inject medicine and therapic agents through skin. Our study investigates an array of out-of-plane microneedles to pierce the permeability barrier without reaching the nerves in the deeper layers. To the best of our knowledge, the skin behavior during the insertion of a microneedle array through its different layers has not up to now been fully dealt with. In this paper, we assume skin to be similar to a stratified material, and approximate it as composed of three layers: the stratum corneum is described by a linear isotropic material model while a hyperelastic material model (Ogden) is used for the two deeper layers. The choice of the model is all the more important since we work at a microscopic scale. We prove that differences exist between the insertion of one microneedle and the insertion of an array of microneedles in terms of the skin deformation and value of the insertion force due to the interaction among microneedles. We simulate the insertion of a micro needles array using a finite element method and the results show a relation between the microneedle diameter, the array density and the microneedle length. Our arrays of microneedles are fabricated by deep reacting ion etching (DRIE) and coated by titanium out of biocompatibility concerns. In this paper, the dimensions of the microneedles are: 500 microns in length, 30-60 microns in inner channel diameter and 100-150 microns in outer diameter in order to be in agreement with our analytically analysis. Some experimental validations are given.
Acoustic characteristics improvement of PZT ceramic sounder for sound source of artificial larynx
Katsutoshi Ooe, Ryota Kanetake, Akimitsu Tanaka
For utterance handicapped persons, various speech production substitutes which aim to reconstruct speech functions have been developed and used practically. But conventional speech production substitutes have various problems, therefore perfect speech production substitutes expect to be developed. We focused to PZT ceramics sounder as a sound source of an electric drive artificial larynx. We first produced the artificial larynx which uses PZT ceramic sounder, and then evaluated its performance. The voice of the power spectrum of the artificial larynx user is similar to that of the speaking person's voice. The vocalized sound of the artificial larynx user shows good characteristics at formant frequency which is important for vowel discrimination. The feature of our artificial larynx is its own structure, and the typical structure means that the sound source and the implant are separated. This structure gives high biocompatibility in our artificial larynx. In this report, the acoustic characteristics improvement of the sound source is described. The characteristics improvement is achieved by optimization of the electric control and its structure. Until now, we have researched about the enzyme immobilization method onto gold or platinum substrate using biomoleculer immobilization technology. By biomoleculer immobilization onto the sound source surface, it is thought that the biocompatibility of it improves. In the future, we aim at the realization of implantable sound source which applied biomoleculer immobilization technology.
Sensors and Biosensors I
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Interaction and intelligence in living neuronal networks interfaced with moving robot
Neurons form complex networks and it seems that the living neuronal network can perform certain type of information processing. We are interested in intelligence autonomously formed in vitro. The most important features of the two-dimensional culture neural network are that it is a system in which the information processing is autonomously carries out. We reported previously that 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. Certain types of feedback stimulation caused suppression of spontaneous network electrical activities and drastic re-organization of functional connections between neurons, when these activities are initially almost synchronized. The result suggests that neurons in dissociated culture autonomously re-organized their functional neuronal networks interacted with their environment. The spatio-temporal pattern of activity in the networks may be a reflection of their external environment. We also interfaced the cultured neuronal network with moving robot. The planar microelectrodes can be used for detecting neuronal electrical signals from the living neuronal network cultured on a 2-dimensional electrode array. The speed of actuators of moving robot was determined by these detected signals. Our goal is reconstruction of the neural network, which can process "thinking" in the dissociated culture system.
Spray pyrolysis synthesis of particles possessing magnetic and luminescent properties: Application of magnetic/luminescent particles in immunoassays
D. Dosev, M. Nichkova, R. K. Dumas, et al.
Many types of fluorescent nanoparticles have been investigated as alternatives to conventional organic dyes in biochemistry. In addition, magnetic beads are another type of particle that have a long history of biological applications. In this work we apply flame spray pyrolysis in order to engineer a novel type of nanoparticle that has both luminescent and magnetic properties. The particles have magnetic cores of iron oxide doped with cobalt and neodymium and luminescent shells of europium-doped gadolinium oxide (Eu:Gd2O3). Measurements on a Vibrating Sample Magnetometer showed an overall paramagnetic response of these composite particles. Fluorescence spectroscopy showed spectra typical of the Eu ion in a Gd2O3 host; a narrow emission peak centered near 615 nm. Our synthesis method offers low-cost, high-rate synthesis allowing a wide range of biological applications of magnetic/fluorescent core/shell particles. We demonstrate an immunoassay using the magnetic and fluorescent properties of the particles for separation and detection purposes.
Microcontact printing trapping air: A versatile tool for protein microarray fabrication
The present work introduces a new method for the fabrication of protein micro-patterns, microcontact printing trapping air. The method is based on microcontact printing, a well-established soft-lithographic technique for printing bioactive protein patterns. Usually, the stamp used is made of poly(dimethylsiloxane) obtained by replicating a lithographically microfabricated silicon master. In microcontact printing, the dimensions of the features in the stamp are critical, since the high compressibility of poly(dimethylsiloxane) causes high aspect ratio features to collapse, leading to the printing of undesired areas. In most cases, this is an unwanted effect, which interferes with the printing quality. In this work we used a poly(dimethylsiloxane)stamp bearing an array of micro-posts which, when placed over a flat surface, collapses with consequent formation of an air gap around the entire array. This effect is linked to the distance between the posts that form the array and can be exploited for the fabrication of protein microarrays having a remarkably low background noise for fluorescence detection.
Development of the MOSFET hybrid biosensor for self-monitoring of blood glucose
Kazuyoshi Tsuchiya, Tatsuro Kuroda, Yasutomo Hirai, et al.
We focus on the research to develop a compact Self Monitoring of Blood Glucose (SMBG). The SMBG consists of (1) a micro electrical pumping system for blood extraction, (2) a painless microneedle as same size as a female mosquito's labium and (3) a biosensor to detect and evaluate an amount of glucose in extracted blood, by using enzyme such as glucose oxidase (GOx). A gold (Au) plate immobilized GOx was used as a biosensor and attached to the gate electrode of MOSFET. GOx was immobilized on a self-assembled spacer combined with an Au electrode by the cross-link method using BSA (bovine serum albumin) as an additional bonding material. The electrode could detect electrons generated by the hydrolysis of hydrogen peroxide produced by the reaction between GOx and glucose using the constant electric current measurement system of the MOSFET type hybrid biosensor system. The system can measure the change of gate voltage. The extracting speed for whole blood using the micro electrical pumping system was about 2 μl/min. The extracted volume was sufficient to determine the glucose level in the blood; it was comparable to the volume extracted in a commercial glucose level monitor. In the functional evaluation of the biosensor system using hydrogen peroxide solution, it is shown that the averaged output voltage increases in alignment to hydrogen peroxide concentration. The linear value was shown with the averaged output voltage in corresponding hydrogen peroxide concentration with the averaged output voltage obtained from the biosensor system by glucose solution concentration. Furthermore, it is confirmed that the averaged output voltage from the biosensor system obtained by whole blood showed the same voltage in corresponding glucose solution concentration. The hybrid biosensor obtained the useful performance for the SMBG.
Review of bioinspired real-time motion analysis systems
Flying insects are able to manoeuvre through complex environments with remarkable ease and accuracy despite their simple visual system. Physiological evidence suggests that flight control is primarily guided by a small system of neurons tuned to very specific types of complex motion. This system is a promising model for bio-inspired approaches to low-cost artificial motion analysis systems, such as collision avoidance devices. A number of models of motion detection have been proposed, with the basic model being the Reichardt Correlator. Electrophysiological data suggest a variety of non-linear elaborations, which include compressive non-linearities and adaptive feedback of local motion detector outputs. In this paper we review a number of computational models for motion detection from the point of view of ease of implementation in low cost VLSI technology. We summarise the features of biological motion analysis systems that are important for the design of real-time artificial motion analysis systems. Then we report on recent progress in bio-inspired analog VLSI chips that capture properties of biological neural computation.
Sensors and Biosensors II
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Silicon-on-glass based microchip for protein sensing and analysis by confocal microscopy and MALDI-TOF
M. S. Kim, S. H. Cho, B. G. Kim, et al.
We propose a prototype of silicon-on-glass microchip for protein detection by bead-based affinity chromatography. The microchip has five channels integrated by composing one beads reactor per one channel. Especially, an effective protein analysis mechanism is presented where the three protein-pretreatment processes are simultaneously performed on a single beads reactor: selective detection (purification / sensing), pre-concentration and protein digestion. Since the five channels are closely spaced in parallel on the microchip, it is possible to inspect the five different detection results on real-time in a single microscope image. The microchip is fabricated on silicon-on-glass (SiOG) to make a mechanically strong and vertically transparent structure for efficient fluid interconnection and fluorescence detection, respectively. Within the microchip, the grid-type filter is formed on channel output to physically trap 38 ~ 50 μm diameter microbeads. The dimension of one grid is 30 × 30 μm2. The volume flow rate was investigated experimentally on the case of bead-packed chamber, and the resulted value was compared to that of the case of hollow chamber. In this research, we used self-cleavage free aptazymes as detection ligands immobilized on polystyrene microbeads. The target proteins are firstly on-chip concentrated and fluorescence-detected (confocal microscopy), and secondly checked off-chip by using MALDI-TOF. If the two analyses are used cooperatively, it is expected that the accuracy in diagnostic analysis will be enhanced in biosensing system. Especially by using this free aptazymes system, we don't need to consider the requirement of fluorescence tagging and the difficulty of eluting antibody-bound proteins from microbeads without bad effects of harsh elution conditions in protease treatment. We analyzed the on-bead detection of HCV replicase and HCV helicase respectively by measuring fluorescence intensities at different concentrations, and also performed a selectively detection of HCV helicase from protein mixtures.
Enhanced electrokinetic manipulation and impedance sensing using FPGA digital signal processing
Steven N. Higginbotham, Denis R. Sweatman
Electrokinetic manipulation of microscopic biological particles, such as bacteria and other cells, is useful in the technology of lab-on-a-chip devices and micro-total-analysis systems (μTAS). In electrokinetic manipulation, non-uniform electric fields are used to exploit the dielectric properties of suspended biological microparticles, to induce forces and torques on the particles. The electric fields are produced by planar electrode arrays patterned on electrically-insulating substrates. Biological microparticles are dielectrically-heterogeneous structures. Each different type of biological cell has a distinct dielectric frequency response signature. This dielectric distinction allows specificity when manipulating biological microparticles using electrokinetics. Electrokinetic microbiological particle manipulation has numerous potential applications in biotechnology, such as the separation and study of cancerous cells, determining the viability of cells, as well as enabling more automation and parallelization in microbiological research and pathology. This paper presents microfabricated devices for the manipulation of biological microparticles using electrokinetics. Methods of impedance sensing for determining microparticle concentration and type are also discussed. This paper also presents methods of using digital signal processing systems to enhance the manipulation and sensing of the microbiological particles. A Field-Programmable Gate Array (FPGA) based system is demonstrated which is used to digitally synthesize signals for electrokinetic actuation, and to process signals for impedance sensing.
Joule heating in polymer microfluidic chip
Y. Zhu, S. Nahavandi, A. Bui, et al.
Joule heating is a significant problem for microfluidic chips with electrokinetically driven flows. In this paper, we will present the modeling results of the Joule heating of a Polymethylmethacrylate (PMMA) polymer separation chip using both experimental and computational methods. The temperature distributions on the surface of the chip were measured by an advanced thermograph system. The numerical study was carried out using the multiphysics computational fluid dynamics (CFD) package CFD-Ace+. Different solutions and operating conditions were studied. Both the measurements and CFD data revealed that the heat generation was approximately uniform and the subsequent temperature increase was also uniform along the channel except for regions near the liquid ports. The highest temperature increase was observed along the centerline of the channel and the temperature reduced significantly away from the channel. At an electrical field of 45kV/m, the Joule heating effect was negligible for the solution used, even though at such a high electric field significant heating effect has been observed for micro capillary flows in literature. At a higher electrical field (68-120kV/m), the Joule heating could cause an increase of temperature of up to 40°C.
Biomedical Engineering
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Bio-inspired analog circuitry model of insect photoreceptor cells
This paper describes the implementation of a robust adaptive photodetector circuit that mimics the characteristics of insect photoreceptors. The implementation of the photodetector circuit is an elaborated version of the mathematical model initially developed by van Hateren and Snippe. It consists of a linear photodetector, two divisive feedback loops and a static non-linearity stage. The photoreceptor circuit was rigorously tested under both steady-state and dynamic (natural scenes) conditions and the circuit parameters optimized such that the output was highly correlated to results obtained from fly photoreceptors observing an identical stimulus. The results show that this adaptive non-linear photoreceptor circuit is ideally suited to mimic the biological photoreceptors found in insects.
Use of accelerometers for detecting foot-ground contact time during running
A biomechanical variable of interest to sprint coaches is foot-ground contact time. Contact time can be easily measured in a laboratory environment using a force platform, but is difficult to measure in the field. The focus of this paper is on the development and validation of an accelerometer-based method for estimating contact time during sprinting that could be used in the field. Tri-axial accelerometers were mounted on the tibia of the right leg of 6 subjects who performed maximal running trials from a stationary start, and running trials at a range of steady state speeds (jog, run and sprint). Ground contact times were measured using a force platform, and estimated from 3D accelerometer data. The mean error between the force plate and accelerometer-based measures of contact time were 0 ± 12 ms, 2 ± 3 ms, and 1 ± 1 ms for the jog, run and sprint. For steps 1, 3 and 5 of the acceleration phase of the maximal sprint the mean errors were 8 ± 9 ms, 2 ± 5 ms, and 0 ± 1 ms respectively. Overall it was concluded from our analysis that close estimates of contact time during running can be obtained using body mounted accelerometers, with the best estimates obtained in conditions associated with the highest accelerations.
Determination of rotational kinematics of the lower leg during sprint running using accelerometers
Justin Channells, Brendan Purcell, Rod Barrett, et al.
Motion analysis systems measure and calculate the position of markers fixed to the body but generally restrict measurement to the laboratory environment. In contrast, inertial measurement devices are small, lightweight and self-contained and data collection is not restricted to a laboratory. Most research using inertial measurement in human locomotion studies has focused on walking. This paper describes a wireless accelerometer-based method for measuring shank angular velocity during sprint running. The system consists of body-mounted electronics with a wireless connection to a PC programmed with the necessary equations to interpret the acceleration data. The hardware incorporates two sets of accelerometers measuring acceleration in each of the three axes. The two 3D accelerometers are fixed to a frame so that their axes are aligned and they are separated by a prescribed distance. By calculating the difference in acceleration between the two 3D sensors, the gravitational component and linear acceleration components are cancelled leaving the rotational acceleration components. An onboard microcontroller digitises the accelerometer signals and the data is transmitted wirelessly to a PC to calculate the angular velocity with minimal latency. Tests were conducted on several subjects running at a constant velocity for several different speeds. The angular rate output from the accelerometer-based system was compared to data obtained from an optical motion analysis system. Validation test results indicate an accurate result was obtained. The design's suitability for acquiring data during elite athlete sprint training is examined and other applications considered. Error reduction strategies will also be discussed.
Poster Session
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A 16 pixel yaw sensor for velocity estimation
The insect visual system, with its simplicity and efficiency has gained widespread attention and many biologically inspired models are being used for motion detection and velocity estimation tasks. One of the earliest and most efficient models among them is the Reichardt correlator model. In this paper, we have elaborated the basic Reichardt correlator to include spatial and temporal pre-filtering and additional non-linearites which are believed to be present in the fly visual system to develop a simple yaw sensor. We have used just 16 elaborated EMDs and it is seen that this sensor can detect rotational motion at angular velocities up to several thousand degrees per second. The modelling of these sensors make us realize that the VLSI implementation of such simple detectors can have varied applications for flight control in different fields.
Elucidating the structure and function of S100 proteins in membranes
Stella M. Valenzuela, Mark Berkahn, Donald K. Martin, et al.
S100 proteins are important Ca2+-binding proteins involved in vital cellular functions including the modulation of cell growth, migration and differentiation, regulation of intracellular signal transduction/phosphorylation pathways, energy metabolism, cytoskeletal interactions and modulation of ion channels. Furthermore, they are implicated in oncogenesis and numerous other disease states. Three S100 proteins: S100A8, S100A9 and S100A12 are constitutively expressed in neutrophils and monocytes. At low levels of intracellular Ca2+, S100A8 and S100A9 are located predominantly in the cytosol but when Ca2+ concentrations are elevated as a consequence of activation, they translocate to membranes and complex with cytoskeletal components such as vimentin. The functions of S100A8 and S100A9 at the plasma membrane remain unclear. A possible role may be the regulation of ion channel proteins. The current study uses the techniques of Atomic Force Microscopy and production of artificial lipid membranes in the form of liposomes to investigate possible mechanisms for the insertion of these proteins into membranes in order to elucidate their structure and stoichiometry in the transmembrane state. We have successfully imaged the liposomes as a lipid bilayer, the S100A8/A9 protein complex in solution and the S100A8/A9 complex associating with lipid, using tapping-mode atomic force microscopy, in buffer.
Characterisation of insect vision based collision avoidance models using a video camera
R. Guzinski, K. Nguyen, Z. H. Yong, et al.
Insects have very efficient vision algorithms that allow them to perform complex manoeuvres in real time, while using a very limited processing power. In this paper we study some of the properties of these algorithms with the aim of implementing them in microchip devices. To achieve this we simulate insect vision using our software, which utilises the Horridge Template Model, to detect the angular velocity of a moving object. The motion is simulated using a number of rotating images showing both artificial constructs and real life scenes and is captured with a CMOS camera. We investigate the effects of texel density, contrast, luminance and chrominance properties of the moving images. Pre and post template filtering and different threshold settings are used to improve the accuracy of the estimated angular velocity. We then further analyse and compare the results obtained. We will then implement an efficient velocity estimation algorithm that produces reliable results. Lastly, we will also look into developing the estimation of time to impact algorithm.
Novel pressure-gradient driven component for blood extraction
Portable blood analysis devices are usually appreciable for applications in blood diagnostic system. We have designed and fabricated a low-cost and simple deal blood extraction device for a biomedical analysis. The device mainly composes of blood extraction tool and a functional bio-chemical analyzing element. In this work, we report the fabrication and pressure-gradient testing results of the blood extraction tool which consists of painless microneedle array and pressure-gradient tank. Microneedle array was fabricated by X-ray lithography using PCT (Plane-pattern to Cross-section Transfer) technique. The idea of our extraction device was simple but capability which is just to hold a sufficient pressure gradient between the tank and blood vessel. The device can draw the volume of blood up to 237 μl. The device was made of low-cost and disposable materials since it is expected to be used for single blood analysis system. In this work, we introduce design, fabrication and mechanism of the pressure gradient driven component including the extraction test results. The fabrication method of microneedle used in our system is also described.
Cell-micropatterning by micromolding in capillary technique based on UV polymerization
Min Ju Park, Won Mook Choi, O. Ok Park
Although optical lithography or photolithography is one of the most well-established techniques for micro, nano-fabrication, its usage with proteins and cells is restricted by steps that must be carried out in harsh organic solvents. Here, we present simple methods for cell-micropatterning using poly(dimethylsiloxane) (PDMS) as a mold. Cell non-adhesive surface or nonfouling surface providing a physico-chemical barrier to cell attachment was introduced for biomaterial pattering, where cells fail to interact with the surface over desired periods of time determined by each application. Poly(ethylene glycol) (PEG) was selected as nonfouling material to inhibit protein adsorption from biological media. The fouling resistance of PEG polymer is often explained by a steric repulsion interaction, resulting from the compression of PEG chains as proteins approach the surface. We also chose fibronectin to direct cell attachment because it is an extracellular matrix protein that is involved in the adhesion and spreading of anchorage-dependent cells. In our experiment, we propose two methods by application of micromolding in capillary (MIMIC) method based on UV polymerization to obtain a surface of alternating PEG and fibronectin. First to fabricate PEG microstructure via MIMIC method, a pre-patterned PDMS mold is placed on a desired substrate, and then the relief structure in the mold forms a network of empty channels. A drop of ethylene glycol monomer solution containing initiator for UV polymerization is placed at the open ends of the network of channels, which is then polymerized by exposure to UV light at room temperature. Once PEG microstructure is fabricated, incubation of the patterned surface in a fibronectin-containing solution allows back-filling of only the bare regions with fibronectin via adsorption. In the alternative method, a substrate is first incubated in a fibronectin-containing solution, leading to the adsorption of fibronectin over the entire surface, and the fibronectin-adsorbed substrate is then micropatterned with the PEG by MIMIC based on UV polymerization. Both methods create reproducible alternating PEG and fibronectin patterns applicable to cell-surface interactions on the microscale.
Thermal denaturation and trypsin digestion of protein on a temperature controllable microchip for MALDI-TOF MS analysis
Tae Seok Sim, Eun-Mi Kim, Hwang Soo Joo, et al.
This paper describes thermal denaturation and trypsin digestion of protein on a microchip as an alternative application of a temperature controllable microchip. Analysis of the protein of small volume and low concentration, which is impossible in macro scale, could be possible with the fairly reduced process time using the proposed temperature controllable microchip. We optimized the parameters concerning thermal denaturation on a microchip such as thermal denaturation temperature, thermal denaturation time, digestion time and concentration of protein using BSA(bovine serum albumin) as a reference sample. Then we applied the optimized parameters to the other proteins (ovalbumin, myoglobin, hemoglobin, cytochrome C, Ubiquitin). The proposed method on a microchip in this paper needed an even shorter reaction time, smaller volume of sample and smaller concentration of sample compared to the previously presented marco scale thermal denaturation and trypsin digestion method. We could successfully acquire the thermally denatured protein in 1 minute at 85°C and the digested peptides in 10 minutes at 37°C with 3 μl/0.2 μM protein. The acquired average sequence coverages are range from 24 to 57% for the test proteins, which are sufficient for the protein identification in practical use.
A microfabricated device with integrated nanoelectrospray source for capillary electrophoresis and mass spectrometry
Min-Su Kim, Hwang-soo Joo, Byung-Gee Kim, et al.
In this study, a new method is described for integrating an electrospray ionization interface to a mass spectrometer with a capillary electrophoresis channel. We have fabricated the ESI-MS device composed of the metal emitter tip, allowing the generation of an efficient nanospray for protein detection, and CE separation channel monolithically in a glass microchip. A triangular-shaped gold emitter tip was formed by electroplating at the end of the separation channel. As an ESI source, this emitter structure aided the formation of a stable Taylor cone. It is easily fabricated by MEMS technology and more robust than that of silica or polymer recently reported. Moreover, this approach is less involved than applying a conductive coating to the exit end to establish electrical contact. As such, the interface is less dependent upon the longevity or durability of such coating, factors that have been consideration in the sheathless interfaces. The spraying stability was evaluated and the ESI-MS experiment was performed by spraying standard peptides for mass spectrometric analysis. The spraying was stable, with a relative standard deviation of 2.9%. The CE/ESI-MS analysis was performed by separating and spraying standard peptide mixture of Bradykinin 1-5, Bradykinin 1-8, and Angiotensin I. Each peptide was separated successfully and singly-charged peaks and doubly-charged peaks of each peptide were detected, respectively. Direct comparisons with conventional ESI-MS system using glass or fused silica emitters showed very similar performance with respect to signal intensity and stability.
Nanocomposite copolymer thin-film sensor for detection of escherichia coli
Prafull Mathur, S. C. K. Misra, Maneesha Yadav, et al.
The majority of human diseases associated with microbial contaminated water are infectious in nature and the associated pathogen includes bacteria, fungi, viruses and protozoa. Water contaminated with bacteria can cause a number of food-borne and water-borne diseases. The waterborne transmission is highly effective means of spreading infectious agents to a large portion of population; this includes water and milk too. Waterborne infections are recognized as resulting either from ingestion of contaminated water or ice, food items, which have, came into contact with microbial contaminated water (occurring through bathing and recreational activities) etc. The detection of E. coli in food and water is normally carried out by culturing methods, which normally take 3-6 days, These methods are complicated and time-consuming in spite of their correctness, and cannot easily meet inspection demands on E. coli. Hence, an establishment of rapid detection methods for E. coli is strongly required. We have developed highly sensitive and cost effective solid sate sensors prepared from vacuum evaporated thin films of nanocomposite copolymer detection of presence of E. coli vapors in the air within 20 seconds. These sensors operate at room temperature. The preparation, optical, electrical, and structural characterization and behavioral acceptance test on the microorganism sensing properties of these sensors are reported here.
Detection of streptavidin-biotin protein complexes using a MOSFET-type biosensor with extended gate
Jang-Kyoo Shin, Dong-Sun Kim, Jee-Eun Park
In this paper, we propose a MOSFET-type biosensor in which an extended gate is formed on the bottom of silicon microfluidic channel across the (111) silicon sidewall. Electrical characteristics of the sensor were measured in the solution containing streptavidin-biotin protein complexes. The connection between MOSFET and micro-fluidic channel system could be achieved with the proposed device, offering merits of isolation between the device and solution, compatibility with the integrated circuit technology and applicability in the micro total analysis system. The device was fabricated on the basis of the semiconductor integrated circuit fabrication and micro-electro mechanical system technology. Au was used as the extended gate metal to form a self-assembled monolayer of thiol which was used to immobilize streptavidin and biotin. Atomic force microscopy was used to observe the presence of biomolecules on Au electrode.
Synthesis and bioconjugation of CdSe/CdS core/shell nanoparticles to poly(ethylene glycol) analogues
Kyoungja Woo, Byeong-Seon Kim
CdSe core nanoparticles were synthesized from the stearate complex of Cd and Se powder in octadecene solution containing organic stabilizers. After purification, CdS inorganic shell was made on CdSe core to yield CdSe/CdS core/shell nanostructure using successive ion layer adsorption and reaction method. The outmost half layer of the inorganic CdS shell was designed to be cadmium ion layer. Then, the hydrophobic CdSe/CdS was converted to hydrophilic CdSe/CdS-AET by treating with aminoethanethiol (AET). The cadmium half layer on CdSe/CdS surface was an excellent promoter for the covalent conjugation of CdSe/CdS to thiolate of AET. Finally, CdSe/CdS-AET was bioconjugated to a PEG analogue, poly(ethylene glycol) monomethyl ether mono(succinimidyl succinate) ester. The advantage of using AET compared to mercaptopropionic acid was the stabilization of Cd-thiolate bond during the following bioconjugation process. Investigations of semiconductor nanoparticles with different surface materials are discussed using transmission electron microscopy (TEM), ultraviolet-visible (UV-Vis), photoluminescence (PL), and Fourier transformed-infrared (FT-IR) spectroscopy.
Organic light emitting diodes and photodetectors: Toward applications in lab-on-a-chip portable devices
Xuhua Wang, Oliver Hofmann, Jingsong Huang, et al.
We report that polymer light emitting diodes (pLEDs) and polymer photodetectors can be integrated on disposable polydimethylsiloxane [PDMS] microfluidic flowcells to form hybrid microchips for bioluminescence applications. PLEDs were successfully employed as excitation light sources for microchip based fluorescence detection of microalbuminuria (MAU), an increased urinary albumin excretion indicative of renal disease. To circumvent the use of optical filters, fluorescence was detected perpendicular to the biolabel flow direction using a CCD spectrophotometer. Prior to investigating the suitability of polymer photodiodes as integrated detectors for fluorescence detection, their sensitivity was tested with on-chip chemiluminescence. The polymer photodetector was integrated with a PDMS microfluidic flowcell to monitor peroxyoxalate based chemiluminescence (CL) reactions on the chip. This work demonstrates that our polymer photodetectors exhibit sensitivities comparable to inorganic photodiodes. Here we prove the concept that thin film solution-processed polymer light sources and photodetectors can be integrated with PDMS microfluidic channel structures to form a hybrid microchip enabling the development of disposable low-cost diagnostic devices for point-of-care analysis.
Microfabricated EIS biosensor for detection of DNA
M. Taing, D. Sweatman
This paper focuses on the design of an EIS (electrolyte on insulator on Silicon) structure as a detection method for pathogenic DNA. Current rapid detection methods rely on fluorescent labeling to determine binding affinity. Fluorescent quenching is seen by a change in activity as opposed to non-quenched states. Sensitive optical equipment is required to detect and distinguish these colour changes because they cannot be seen by the naked eye. The disadvantages of this is (1) a portable, independent device cannot be made since samples have to be brought back to the benchtop and (2) the obvious cost of acquiring and maintaining these optical detection systems. A low cost, portable electrical detection method has been investigated. The EIS structure (Electrolyte on Insulator on Silicon) provides a novel, label-free and simple to fabricate way to make a small 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 as a result of DNA adsorption onto the dielectric oxide/APTES (Aminopropylthioxysilane) surface. As DNA molecules diffuse to the sensor surface, they are bound to their complimentary capture probes. The negative charge exhibited by the DNA forces negative charge carriers in the silicon substrate to move away from the surface. This causes a depletion layer in n-type substrate to thicken and for a p-type to thin and can be observed as a change in capacitance. A low ionic solution strength will ensure that counter-ions do not affect the sensor measurements. The EIS sensor is designed to be later integrated into a complete lab on chip solution. A full lab on chip can incorporate the sensor to perform DNA quantity based measurements. Nucleic acids can be amplified by the on chip PCR system and then fed into the sensor to work out the DNA concentration. The sensor surface contains capture probes that will bind to the pathogen. They are held onto the sensor surface by the positively charged layer. The sensor will have onboard electronics to process the signals and determine the result of the measurements. The sensitivity of the sensor is on par with similar capacitance sensing technologies and is expected to be improved with later enhancements.
Structural properties of liposomes from digital holographic microscopy
We have constructed liposomes from L alpha Phosphatidylcholine (PC) lipids, which are biomimetic lipids similar to those present in the membranes of mammalian cells. We propose an advance in the use of liposomes, such as for drug delivery, to incorporate into the liposomal membranes transport proteins that have been extracted from the lipid membranes of mammalian cells. In this paper, we describe the usage of a novel optical microscope to characterize the nanomechanical properties of these liposomes. We have applied the technique of digital holographic microscopy, using an instrument recently developed at the University of Münster, Germany. This system enabled us to measure quantitatively the structural changes in liposomes. We have investigated the deformations of these biomimetic lipids comprising these liposomes by applying osmotic stresses, in order to gain insight into the membrane environment prior to incorporation of cloned membrane transport proteins. This control of the nanomechanical properties is important in the stresses transmitted to mechanosensitive ion channels that we have incorporated into the liposomal membranes. These liposomes provide transporting vesicles that respond to mechanical stresses, such as those that occur during implantation.
Atomic force microscopy in the study of ferrofluids
Comparative study on the ferrophase dimensional distribution within a water ferrofluid was carried out by applying the atomic force microscopy (AFM) scanning and the transmission electron microscopy (TEM). The ferrophase has a magnetite core prepared by chemical co-precipitation and a double layer coating of citric acid. The diameter histograms revealed the main peak at about 9 nm which is concordant with a high degree of stability of the ferrofluid.
Fluoresent bacteria for colloidal iron biosensors
A. Poiata, Al. Vlahovici, D. E. Creanga, et al.
This research was focused on the possibility of iron sensing by means of bacterial cultures. The effect of ferric and ferrous ions on Pseudomonas aeruginosa, which has the ability to uptake the environmental iron in the form of complex iron compositions named siderophores, characterized by luminescent features, was studied. The different sensitivity to the iron from oxide compounds in comparison to the iron from chlorides and sulfate was emphasized by means of fluorescence measurements. It could be stated that Pseudomonas aeruginosa, from human body specimens could be the biological component of an iron biosensor for ferrofluid traces reminiscent after the administration for medical purposes.
Porous silicon microparticles as an alternative support for solid phase DNA synthesis
Steven McInnes, Sean Graney, Yit-lung Khung, et al.
Current methods to produce short DNA strands (oligonucleotides) involve the stepwise coupling of phosphoramidites onto a solid support, typically controlled pore glass. The full-length oligonucleotide is then cleaved from the solid support using a suitable aqueous or organic base and the oligonucleotide is subsequently separated from the spent support. This final step, albeit seemingly easy, invariably leads to increased production costs due to increased synthesis time and reduced yields. This paper describes the preparation of a dissolvable support for DNA synthesis based on porous silicon (pSi). Initially it was thought that the pSi support would undergo dissolution by hydrolysis upon cleavage of the freshly synthesised oligonucleotide strands with ammonium hydroxide. The ability to dissolve the solid support after completion of the synthesis cycle would eliminate the separation step required in current DNA synthesis protocols, leading to simpler and faster synthesis as well as increased yields, however it was found that the functionalisation of the pSi imparted a stability that impeded the dissolution. This strategy may also find applications for drug delivery where the controlled release of carrier-immobilised short antisense DNA is desired. The approach taken involves the fabrication of porous silicon (pSi) microparticles and films. Subsequently, the pSi is oxidised and functionalised with a dimethoxytrityl protected propanediol to facilitate the stepwise solid phase synthesis of DNA oligonucleotides. The functionalisation of the pSi is monitored by diffuse reflectance infrared spectroscopy and the successful trityl labelling of the pSi is detected by UV-Vis spectroscopy after release of the dimethoxytrityl cation in the presence of trichloroacetic acid (TCA). Oligonucleotide yields can be quantified by UV-Vis spectroscopy.
Characterisation of porous silicon/poly(L-lactide) composites prepared using surface initiated ring opening polymerisation
Inorganic/organic hybrid or composite materials have in the past shown novel and interesting properties, which are not observed for the individual components. In this context, the preparation of inorganic/polymeric composites from biodegradable and biocompatible constituents is a new concept, which may be of interest particularly for tissue engineering and drug delivery applications. We describe here the synthesis of nanostructured porous silicon (pSi) and poly(L-lactide) (PLLA) composites. The composites were produced using tin(II) 2-ethylhexanoate catalysed surface initiated ring opening polymerisation of L-lactide onto silanised porous silicon films and microparticles. The subsequent chemical, physiochemical and morphological characterisation was performed using Diffuse Reflectance Infrared Spectroscopy (DRIFTS), X-ray Photoelectron Spectroscopy (XPS), Atomic Force Microscopy (AFM), Differential Scanning Calorimetery (DSC), Thermogravimetric Analysis (TGA) and Contact Angle measurements. DRIFT spectra of the composites showed the presence of bands corresponding to ester carbonyl stretching vibrations as well as hydrocarbon stretching vibrations. XPS analysis confirmed that a layer of PLLA had been grafted onto pSi judging by the low Si content (ca. 3%) and O/C ratio close to that found for PLLA homopolymers. Comparison of the sessile drop contact angle produced by silanised pSi and PLLA grafted onto pSi showed an increase of ca. 40°. This is comparable to the increase in contact angle seen between blank silicon and spin-coated PLLA of ca. 44°. The AFM surface roughness after surface initiated polymerisation increased significantly and AFM images showed the formation of PLLA nanobrushes.
Thermal modeling of a microheater in a microchannel chip
Y. Zhu, A. Bui, H. Jin, et al.
Integration of microheaters in microfluidic systems has a wide range of applications such as sensing, actuating and biomedical devices. This study focused on the investigation of the thermal performance of a nickel microheater fabricated on a printed circuit board using a LIGA process. Both experimental and computational methods were used in conjunction with preliminary theoretical analysis. The microheater was tested both in air and water. The temperature distributions of the microheater were measured by an advanced thermography system. The numerical study was carried out using the multiphysics CFD package CFD-Ace+. The temperature of the microheater increased approximately linearly with the input power for the experimental conditions. The microheater heated up exponentially at the start of power supply. At a supply of 120mA electrical current, the microheater could heat up at a rate of around 90°C/s. During the cooling stage, the rate was much higher and could reach 800°C/s. When placed in the microchannel with air flow, the heater could heat the flow effectively without causing significant increase in the chip temperature. The CFD results were validated by comparing temperature distributions on the chip surface and on the heater surface. The validated CFD results allowed more detailed investigations of thermal and fluid flow within the microchannel and the whole chip.
Droplet manipulation for lab-on-a-chip using electrowetting
Electrowetting, the phenomena of changing interfacial energy of an interface, has been demonstrated to be an excellent actuation and pumping mechanism for microfluidics and lab-on-a-chip applications. Individual droplets can be moved and deformed on microchips using voltages as low as 15V. In electrowetting, application of a voltage across the electrodes of a micro-droplet causes it to change the interfacial energy of solid-liquid interface which in turn changes the contact angle of the liquid on the solid. The contact angle is a measure of the extent of wetting of the liquid on the surface. In conventional electrowetting, it has been found that the polarity of the applied potential does not affect the contact angle change. However, our experimental results show that the change of polarity across the electrodes of a micro-droplet can reverse the contact angle change. We call this phenomenon 'dewetting'. The actual physics behind this still remains unexplored. In our experiments we used 100 nm of aluminium on a silicon substrate to form the bottom electrode. A 60 nm silicon dioxide or a 1.4 μm thickness strontium doped lead zirconium titanate (PSZT) layer was used as the dielectric and 380 nm of Teflon was used to make a hydrophobic surface. A platinum wire, which was inserted into the micro-droplet, formed the top electrode. The highest dewetting contact angle change was found to be 9o for a 5μl droplet at 60 V. This compared to a maximum of 41o which we obtained for conventional electrowetting.
Acoustic microstreaming applied to batch micromixing
Richard Manasseh, Karolina Petkovic-Duran, Paul Tho, et al.
Experiments are presented in which acoustic microstreaming is investigated and applied to a batch micromixing case appropriate to a point-of-care pathology screening test. The flows presented can be created without complex engineering of contacts or surfaces in the microdevice, which could thus be made disposable. Fundamental flow patterns are measured with a micro-Particle-Image Velocimetry (micro-PIV) system, enabling a quantification of the fluiddynamical processes causing the flows. The design of micromixers based on this principle requires a quantification of the mixing. A simple technique based on digital image processing is presented that enables an assessment of the improvement in mixing due to acoustic microstreaming. The digital image processing technique developed was shown to be non-intrusive, convenient and able to generate useful quantitative data. Preliminary indications are that microstreaming can at least halve the time required to mix quantities of liquid typical of a point-of-care test, and significantly greater improvements seem feasible.
Modeling of the growth of filamentous fungi in artificial microstructures
We present a stochastic and spatial Monte Carlo model for the growth of a fungal colony in microstructures. This model is based on an "L-system-like" representation of filaments as individual objects. Each of these can both grow in space (and be diverted by obstacles) and can send new branches. All parameters in the model such as filament dimensions, the growth speed, behavior at and around obstacles, branching angle and frequency and others are obtained from experimental studies of growth in artificial microstructures. We investigate four different possible "strategies" the colony might use to achieve the tasks of (a) filling the available space and (2) finding its way out of the structures. The simulation results indicate that a combination of directional memory and a stop-and-branch behavior at corners gives the best results and observe that in fact this is similar to the experimentally observed behavior of the fungi. The model is expected to be of use in studying the colonization of microstructures by fungi and in the design of devices either using fungal growth or aiming to inhibit it.