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- Front Matter: Volume 6465
- Lab-on-a-Chip I
- Microfluidics I
- Sensors
- Lab-on-a-Chip II
- Fabrication Technologies
- Microfluidics II
- Plenary Paper
Front Matter: Volume 6465
Front Matter: Volume 6465
Show abstract
This PDF file contains the front matter associated with Proceedings of SPIE Volume 6465, including the Title Page, Copyright information, Table of Contents, Introduction, and the Conference Committee listing.
Lab-on-a-Chip I
Methods and instruments for continuous-flow PCR on a chip
Show abstract
PCR is the most commonly used method to identify DNA segments. Several methods have been used to miniaturize PCR
and perform it in a microfluidic chip. A unique approach is the continuous-flow PCR, where the conventional
thermocycling is replaced by pumping the sample through a channel which meanders over stationary temperature zones,
allowing fast temperature changes in the sample due to the low thermal mass as well as a continuous production of PCR
products. In this paper we present a system comprising a polymer microfluidic chip, a thermocycler unit and the
protocols necessary to perform fast continuous-flow PCR including experimental results in comparison with a
conventional PCR system.
Micro-devices for rapid continuous separation of suspensions for use in micro-total-analysis-systems (μTAS)
Show abstract
Planar micro-devices capable of continuously separating large volumes of dilute suspensions were designed and
modeled using a commercial CFD package. The devices consist of a single high aspect ratio spiral micro channel
with a bifurcation at the exit. The device exploits small inertial and hydrodynamic differences between particles of
dissimilar size, which arise as a result of the curvature of the flow through the device. The channel length and
location of the bifurcation were found to affect the separation achievable by the devices. Devices of varying
geometries were fabricated using conventional silicon micro fabrication processes and were tested by flowing dilute
aqueous suspensions of polystyrene particles (diameters of 1&mgr;m, 8&mgr;m and 10&mgr;m) through the devices at various
flow rates. A 3.5 fold concentration enhancement of 10&mgr;m particles was achieved in the longer devices at flow rates
of 2 ml/min, whereas the 1&mgr;m particles showed negligible concentration increases at similar flow rates. The devices
may be used as a sample preparation stage in a complex &mgr;TAS, where rapid, continuous concentration of dilute
suspensions is often required.
Thermal gradient PCR in a continuous-flow microchip
Show abstract
A new continuous-flow PCR microchip has been developed that operates by cycling a prepared sample within a spatial
temperature gradient. This design allows for minimal thermal residence times - a key feature of the protocols used by
the fastest commercial PCR equipment. Since thermal gradients are a natural effect of heat dissipation, the appropriate
temperature distribution for PCR can be generated by a minimum of one heater held at a steady state temperature. With a
thermal gradient of more than 3°C/mm across the width of the chip, each complete PCR cycle requires approximately
2cm of channel length. These glass chips were manufactured using standard glass microfabrication methods as well as
the Xurographic rapid prototyping technique. Targets of 110bp and 181bp were amplified from &Fgr;X174 plasmid DNA on
these thermal gradient chips as well as on commercial PCR equipment, then subsequently analyzed by gel
electrophoresis. Visual inspection of fluorescent images of the stained gels shows that the amplicon size and yield for the
systems are comparable.
A hyper-step DNA computing system based on surface plasmon resonance
Show abstract
We reported a reusable DNA computing platform for solving satisfiability (SAT) problem based on surface
plamon resonance (SPR) technology in this paper. Three different sequences of 18-mer ssDNAs with thiol
terminal were first immobilized on the gold surface and then hybridized with their complementary sequences at
specific sites via microfluidic channels under room temperature. We also conjugated monoclonal antibody
(human IgG) to these complementary pairs chemically to amplify the hybridization signal and thus enhance the
noise margin to distinguish Boolean value of true and false. In order to keep the reaction temperature and SPR
measurement stable, repeated DNA annealing and denaturing is doned by varying salt concentration (by
adding NaOH to denature DNA) of reaction solution rather than changing reaction temperature. The
experimental results successfully demonstrated a multi-channel microfluidic DNA computation system to solve
a three variables (X, Y, Z) Boolean SAT problem (formula) with reusability and specificity
using protein-ssDNA conjugates to link to complementary ssDNA SAM surface under room temperature within
one hour. This technique provide a feasible solution to miniaturize the DNA computation platform for possible
iterated hyperstep computing processes.
Microfluidics I
Diffusion dynamics in microfluidic dye lasers
Show abstract
We have investigated the bleaching dynamics that occur in opto-fluidic dye lasers, where the liquid laser dye
in a channel is locally bleached due to optical pumping. Our studies suggest that for micro-fluidic devices, the
dye bleaching may be compensated through diffusion of dye molecules alone. By relying on diffusion rather
than convection to generate the necessary dye replenishment, our observation potentially allows for a significant
simplification of opto-fluidic dye laser device layouts, omitting the need for cumbersome and costly external
fluidic handling or on-chip micro-fluidic pumping devices.
A novel electrolysis-bubble-actuated micropump
Show abstract
A novel electrolysis-bubble-actuated micropump has been successfully developed by utilizing a specific roughness
gradient design on the hydrophobic lateral breather which could achieve a net pumping flow. The micropump is
implemented by means of electrolysis, surface tension effect and the periodic electrolysis-bubble generation. The
advantages of this proposed micropump design not only achieve a net pumping flow but also resolve the disadvantages
that exist in the early proposed electrochemical micropumps, such as the complicated time-sequence power control on
many pairs of electrodes, the need of large/long nozzle-diffuser structure and the limitation of the sealed reservoir inside
the fluidic chip. This micropump with a simple circuit control and without moving parts is suitable for the development
of low power-consumption and compact micropumps. Experimental results successfully demonstrate the pumping
function of our micropump to continuously push liquid forward via the gradient roughness design and the periodic
generation of electrolytic bubbles in a microchannel. Furthermore, experimental results also show that the liquid
displacement and pumping rate could be easily and accurately controlled by adjusting the applied voltage with specific
operating frequency. A maximum pumping rate of 114 nl/min is achieved for our micropump #1 with a microchannel
cross section of 100 µm × 20 µm. In this paper, we describe the theoretical analysis, design, micromachining process, and
operating principles, as well as the experimental demonstration of this micropump.
Using a CD-like microfluidic platform for uniform calcium alginate drug carrier generation
Ming-Kai Liu,
Keng-Shiang Huang,
Jia-Yaw Chang,
et al.
Show abstract
In this paper the manipulation of monodisperse Ca-alginate microparticles using a polymer-based CD-like microfluidic
platform and a reaction of external gelation is presented. Our strategy was based on associating the rapid injection
molding process for cross-junction microchannel with the sheath focusing effect to form uniform water-in-oil (w/o)
emulsions. These fine emulsions, consisting of 1.5% w/v Na-alginate, were then dripped into an oil solution containing
20% w/v calcium chloride (CaCl2) to accomplish Ca-alginate microspheres in an efficient manner. We have
demonstrated that one can control the size of Ca-alginate microparticles from 20 µm to 50 µm in diameter (with a
variation less than 10%) by altering the relative sheath/sample flow rate ratio. Experimental data showed that for a given
fixed dispersed phase flow (sample flow), the emulsion size decreased as the average velocity of the continuous phase
(oil flow) increased. The proposed CD-like microfluidic platform is capable of generating relatively uniform microdroplets
and has the advantages of active control of droplet diameter, simple and low cost process, and high throughput.
Set-up of a biological monitoring module realized in LTCC technology
Show abstract
Low temperature co-fired ceramic (LTCC) technology was originally developed for the realization of multilayer circuits
of high reliability. It was recognized that LTCC technology is a valuable development in thick film technology, which
launches new application areas as it becomes evident that complex three-dimensional structures can easily be realized.
When considered for biological applications ceramic tape material must be proved with regard to its biocompatibility. A
selection of appropriate commercially available ceramic tapes has been characterized in respect to the influence on
proliferation, viability and adherence of cells. Aspects of realization of a complex biological monitoring module
comprising a three-dimensional network of channels and cavities will be demonstrated.
A simple planar micromixer with low-pressure drop for disposable lab-on-a-chip (LOC) systems
Show abstract
In this work the design and fabrication of a novel passive microfluidic mixer capable of achieving mixing in shorter
distances and lower Reynolds numbers (Re) is reported. Passive mixers typically rely on the channel geometry to
mix fluids, and many previously reported designs work efficiently only at moderate to high Re and are often difficult
to fabricate as they incorporate complex 3-D structures within the channel. The mixer design discussed in this work
achieves good mixing at low Re, has planar geometry and thus is simpler to fabricate and integrate with existing labon-
a-chip (LOC) technologies. The design incorporates triangular notches patterned along the channel walls to
laminate the flow, thus enhancing mixing. Numerical and experimental studies to determine the effect of the notch
dimensions and placement within the microchannel were carried out to optimize the mixing performance. Results
show that the final mixer design is efficient at mixing fluids at low Re. The mixer is fabricated in
polydimethylsiloxane (PDMS) bonded to glass slides and tested using fluorescence dyes. Results show that the new
design exhibit complete mixing at Re < 0.1 within 7 mm and thus will benefit a wide range of LOC applications
where space is limited.
Fabrication of a microfluidic system with integrated electrochemical pump and valves
Show abstract
An integrated microfluidic system with a check valve and a micropump based on electrochemical actuation was
designed and fabricated using UV-LIGA microfabrication technologies. The main components of the system include
two electrochemical (ECM) actuators, a polydimethylsiloxane (PDMS) membrane, and multi levels of covers. The
thickness of the membrane is 100 &mgr;m thick and the thickness of the PDMS structure is 1000 &mgr;m. Hydrogen gas bubbles
were generated from Pt black electrodes with 1M of NaCl solution in the valve chamber. Experimental results proved
that the system can be operated by controlling the electrical signals supplied to the ECM actuators.
Sensors
Assembly and testing of microparticle and microcapsule smart tattoo materials
Show abstract
Microscale biochemical sensors are attractive for in vitro diagnostics and disease management, as well as medical and
biological research applications. Fluorescent sensors, coupling specific glucose-binding proteins with fluorescent readout
methods, have been developed for this purpose. Our work has focused on the development of assembly and packaging
systems for producing micro- and nanoscale sensing components that can be used as implants, intracellular reporters, or
as elements in larger systems. Both hybrid organic/inorganic particles and hollow microshells have been developed to
physically couple the sensing materials together in biocompatible, semipermeable packages. Fabrication details and
sensor characterization are used to demonstrate the potential of these sensor concepts.
An integrated microsystem for multiplex processing of encoded silicon microbeads
Show abstract
A novel integrated microsystem for multiplex processing of encoded microbeads on a single microchip
is presented. Conventional bio-analysis of proteins and DNA requires a combination of different
techniques including: accurate delivery of reagents, mixing, then reaction at controlled temperature to
yield a detectable product. Standard laboratory bio-assays require intervention at several stages to
manipulate samples. Furthermore, ultra sensitive quantification with a colorimetric or fluorescent label
is required to obtain the necessary results. This process is time consuming and labour intensive.
However the new multiplex microsystem reported here enhances logical bio-assay development due to
the integration of a compact optical detection system with customized analysis software in an enclosed
microfluidic environment. The bioassay was realised by careful integration of a Peltier cell and
associated control electronics which enabled specific identification of a hybridized DNA sequence
from a 4 x 4 cDNA library at a fixed temperature of 42oC. The multiple fluorescence measurements of
complementary hybridised DNA at the surface of encoded microbeads was confirmed. Thus, the
complete integration of the different bio-assay components on a single multiplex assay platform
provides distinct advantages of reduced sample volume, rapid analysis and low cost.
Lasing droplets in a microfluidic T-junction device with integrated optics
Show abstract
Lasing from spherical microdroplets ejected into a liquid medium with lower refractive index is observed in a
microchannel. A microfabricated device that combines the droplet production and excitation/detection has been
utilized. Droplets of 50 µm-diameter containing a fluorescent dye were first detected and then excited through
multimode fibers after their production at a T-junction. Images show intense lasing emission around the droplet rim.
Spectra from the droplets exhibit morphology dependent resonances (MDRs) which are red shifted relative to the
bulk fluorescence emission from the dyes. The dependence of resonant peak intensities on the pump beam power is
nonlinear.
Hybrid microfluidic systems: combining a polymer microfluidic toolbox with biosensors
Show abstract
In this paper we present polymer based microfluidic chips which contain functional elements (electrodes, biosensors) made out of a different material (metals, silicon, organic semiconductors). These hybrid microfluidic devices allow the integration of additional functionality other than the simple manipulation of liquids in the chip and have been developed as a reaction to the increasing requirement for functional integration in microfluidics.
Specific immobilization of human immunoglobulin G on gold-coated silicon microcantilever array
Show abstract
We demonstrate a procedure for immobilizing human immunoglobulin G (IgG) on an array of gold-coated silicon microcantilevers. The procedure employed protein A for the specific immobilization of human IgG on the gold surface. Protein A bound specifically to the gold-coated upper surface of the silicon microcantilever and had no interaction with the silicon surface. It binds to the constant Fc regions of human IgG keeping the antigen binding sites on the variable Fab region free to bind to antigens. Fluorescent microscopy was done to analyze qualitatively the biomolecular binding of human IgG using FITC labeled goat anti-human IgG. The immobilization densities of protein A and human IgG were 112±19 ng/cm2 and 629±23ng/cm2, as determined employing horse radish peroxidase (HRP) labeled biomolecules by 3, 3', 4, 4'-tetramethyl benzidine (TMB) substrate assay. The uniformness of the biomolecular coatings was further determined by atomic force microscopy (AFM). Surface plasmon resonance (SPR) was used to cross-validate the immobilization density of functional human IgG molecules immobilized on the gold surface w.r.t. that obtained by TMB substrate assay.
Fabrication and characterization of SiO2 microcantilever for high sensitive moisture sensor
Show abstract
μThis paper reports a novel design of SiO2 microcantilever for high sensitivity sensor platform.
In order to fabricate this device, a new fabrication process using isotropic combined with
anisotropic dry etching to release the SiO2 microcantilever beam by ICP (Inductively Coupled
Plasma) was developed and investigated. This new process not only obtains a high etch rate at
9.1 &mgr;m per minute, but also provides a good profile controllability, and a flexibility of device
design. To compare the SiO2 and Si cantilever beam, the results of simulation and theoretical
analysis are given. The results predict the SiO2 cantilever can achieve a higher sensitivity than
the Si cantilever. The SiO2 cantilever beams with 1 &mgr;m thickness, 100 &mgr;m width, and 250 &mgr;m
length were fabricated and tested by exposing it to aminoethanethiol solution of low
concentration. The experimental data support the prediction derived from the simulation
results. The moisture sensor based on the surface modified cantilever beam showed a good
response to one percentage relative humidity.
Lab-on-a-Chip II
Nanoparticle analysis using microscale field flow fractionation
Show abstract
Microscale electrical field flow fractionation (FFF) has shown significant progress since it was first reported in early
1997. The first electrical FFF systems were lucky to function for more than a few days and generated only minimal
levels of retention and separation, while current systems now easily function for years and can generate multicomponent
nanoparticle separations. A variety of microscale FFF systems have now been reported including: multiple versions of
normal electrical FFF (ElFFF), cyclical electrical FFF (using oscillating fields), dielectrophoretic FFF, thermal FFF, and
a combined thermal-electric FFF channel. Related microscale electrical SPLITT systems have also been demonstrated.
Microscale ElFFF systems have been used to analyze and separate nanoparticles, DNA, proteins, cells, viruses,
liposomes, large polymers, and other materials. ElFFF clearly improves upon system miniaturization due to the
reduction in sample and carrier volumes, analysis times and more notably an increase in the separation resolution with a
reduction in analysis times. Other advantages of miniaturized FFF include: parallel processing with multiple separation
channels, batch fabrication with reduced costs, high quality manufacturing, and potentially disposable systems.
Additionally, the possibility of on-chip sample injection, detection and signal processing favors the microfabrication of
FFF systems.
Three-dimensional integrated circuits for lab-on-chip dielectrophoresis of nanometer scale particles
Show abstract
In this paper, we present a mixed-technology micro-system for electronically manipulating and optically detecting virusscale
particles in fluids that is designed using 3D integrated circuit technology. During the 3D fabrication process, the
top-most chip tier is assembled upside down and the substrate material is removed. This places the polysilicon layer,
which is used to create geometries with the process' minimum feature size, in close proximity to a fluid channel etched
into the top of the stack. By taking advantage of these processing features inherent to "3D chip-stacking" technology,
we create electrode arrays that have a gap spacing of 270 nm. Using 3D CMOS technology also provides the ability to
densely integrate analog and digital control circuitry for the electrodes by using the additional levels of the chip stack.
We show simulations of the system with a physical model of a Kaposi's sarcoma-associated herpes virus, which has a
radius of approximately 125 nm, being dielectrophoretically arranged into striped patterns. We also discuss how these
striped patterns of trapped nanometer scale particles create an effective diffraction grating which can then be sensed with
macro-scale optical techniques.
Integration of red VCSEL in a versatile microchip for encoding and subsequent detection of encoded beads
Daniel Hoffmann,
John Justice,
Brian Corbett,
et al.
Show abstract
The integration of discrete optical excitation and detection components in a microfluidic platform is an
important pre-requisite for realisation of Lab-on-a-chip devices. This research presents a microfluidic
system made of polymer material with integrated miniaturized vertical cavity surface emitting laser
(VCSEL) source. The light emitted by the VCSEL is detected by a conventional 5 mm diameter
photodiode. The ability to read and detect microbeads encoded with through holes in the silicon
substrate verified successful integration of a functional VCSEL in the polymer microchip.
The microfluidic system was composed of two processed polymer chips that are bonded together. The
substrate contains cavities to accommodate VCSEL components. The second polymer chip
(superstrate) contains the microfluidic channel network. The conventional photodiode detector was
easily mounted on top of the superstrate. Polymer chip substrates and master templates for hot
embossing were fabricated by rapid prototyping technology. Fabricated masters were then moulded
into thermoplastic polycarbonate (PC) substrate by hot embossing. Generated polymer sheets with
embossed structures were diced into polymer chips and subsequently bonded together using a
customised procedure to provide a complementary moulded cavity which accommodates the VCSEL.
The optically encoded microbeads are illuminated with a VCSEL which is operated with a power of 0.7
mW. As the bead flows along the channel (illuminated with the VCSEL), the emitted light from the
VCSEL device is modulated by the bar code and subsequently detected by the photodiode. Signal
measurements confirm that different levels of the VCSEL light can be reproducibly detected by
customized Labview software.
Water-soluble (MUA-coated) quantum dots: physicochemical characterization and application
Chih-Hui Yang,
Keng-Shiang Huang,
Sheng-Ji Lee,
et al.
Show abstract
This paper described the physicochemical characterization and application of quantum dots (CdSe/ZnS, QDs) whose
surface were hydrophilic modified by mercaptoundecanoic acid (MUA). The stability kinetics of MUA-coated QDs
(MUA-QDs) in aqueous solution was studied as a function of MUA-QDs concentration, type of light exposed, pH
conditions and temperatures. The results show that the optimum concentration range of MUA-QDs is 0.5 to 1 mg/mL.
We found that no obvious difference of fluorescence intensity was detected in MUA-QDs stored respectively at 4°C,
24°C and 44°C (8-hour). When they were exposed to UV light (312 nm) for 8 hr, their fluorescence intensity was shown
serious decay. Moreover, the results showed that the pH of maximum stability of MUA-QDs in buffer solutions was 8.
Finally, MUA-QDs had been endocytosis into H9c2 cells, a permanent cell line derived from rat cardiac tissue, for cell
imaging application, the results provided the benefit to apply MUA-QDs in medical areas.
Cross-polarization scheme for fluorescence detection for biochip and biomedical applications
Andrea Pais,
Haichuan Mu,
Erik Peterson,
et al.
Show abstract
The trend in medical equipment is toward compact and integrated low cost medical test devices. Fluorescence-based assays are used to identify specific pathogens through the presence of dyes, but typically require specialized microscopes and narrow-band optical filters to extract information. We present a novel method of using polarizers in cross orientation with each other to filter out excitation light and allow detection of low signal levels of fluorescence with a simple intensity-based detector in the presence of high levels of excitation light. This concept is demonstrated using an inverted microscope fitted with a halogen lamp as the excitation source and an organic photovoltaic (PV) cell as the intensity detector. The excitation light is linearly polarized and used to illuminate a microfluidic device containing a 50µl volume of Rhodamine 6G dye dissolved in water. The detector (with a second polarizer orientated perpendicularly to the first) is placed over the microfluidic device. The resulting emission signal was detected by the organic PV cell down to a concentration of 100 nM This suggests that an integrated microfluidic device, with a PV detector and an organic light emitting excitation source and integrated polarizers, could be fabricated to realize a economical "lab on a chip" device for fluorescence assays.
Fabrication Technologies
Creation of embedded structures in SU-8
Show abstract
Two methods were investigated for the creation of encapsulated micro-fluidic channels and bridges in negative tone
SU-8 photoresist. The first uses two exposures at different wavelengths to create the channel sidewalls and microchannel
encapsulation layer; the other method creates both using a single I-line (365 nm) exposure and a grayscale
photomask. These methods can define structures with vertical dimensions ranging to hundreds of microns and
introduces very little extra processing complexity. For the dual wavelength method, an I-line light source is used to
define the channel walls while a non-collimated deep-UV (254 nm) light source provides a large energy dose to the top
surface of the SU-8 to produce a membrane over all the channels. Using the dual wavelength method allows SU-8 to be
used as the material for the channels and the encapsulation method is self-limiting avoiding the requirement for precise
control over the exposure dose. The rate of UV dose and the post-exposure baking parameters are critical to the quality
and strength of the micro-channels. Properly designed channels have been successfully developed in lengths up to 1 cm.
Alternatively using a grayscale Zn/Al bimetallic photomask and a single I-line exposure, 3D bridge micro-structures
were successfully made on SU-8. The use of grayscale masks for both techniques also provides the possibility of
shaping the channel. With the ability to create micro-bridges, further research will be performed to investigate how well
the single exposure technique can be used to produce micro-channels of various sizes and dimensions.
Two-photon polymerization for fabrication of biomedical devices
Show abstract
Two-photon polymerization (2PP) is a novel technology which allows the fabrication of complex three-dimensional (3D)
microstructures and nanostructures. The number of applications of this technology is rapidly increasing; it includes the
fabrication of 3D photonic crystals [1-4], medical devices, and tissue scaffolds [5-6].
In this contribution, we discuss current applications of 2PP for microstructuring of biomedical devices used in drug
delivery. While in general this sector is still dominated by oral administration of drugs, precise dosing, safety, and
convenience are being addressed by transdermal drug delivery systems. Currently, main limitations arise from low
permeability of the skin. As a result, only few types of pharmacological substances can be delivered in this manner [7].
Application of microneedle arrays, whose function is to help overcome the barrier presented by the epidermis layer of
the skin, provides a very promising solution. Using 2PP we have fabricated arrays of hollow microneedles with different
geometries. The effect of microneedle geometry on skin penetration is examined. Our results indicate that microneedles
created using 2PP technique are suitable for in vivo use, and for integration with the next generation of MEMS- and
NEMS-based drug delivery devices.
Mechanically assembled polymer interconnects with dead volume analysis for microfluidic systems
Show abstract
The mechanical and fluidic properties of silicon and polymer peg-in-hole type interconnect structures are analyzed,
tested, and compared in this paper. Microfluidic interconnects composed of interlocking cylindrical posts and holes are
microfabricated of polydimethylsiloxane (PDMS) and SU-8 polymers and are mechanically tested together with existing
silicon interconnects. PDMS cylindrical posts experimentally assemble with lower force (20-81mN) than comparable
SU-8 cylindrical posts (44-227mN) for PDMS, SU-8, and silicon holes. In addition to interconnect fabrication and
experimental demonstration of substrate-to-substrate attachment, fluidic properties of the interconnects are analyzed via
ANSYS simulation to predict whether pressure drop is expected to result in disassembly. Pressures due to simulated
fluid flow at 1mL/min are expected to be 383.6Pa at the interconnect interface. Worst-case interconnect dead volume is
simulated using ANSYS and Matlab. We estimate the dead volume at maximum fluid flow rates (50µL/min and
1mL/min) to range from 5.8 to 33nL. The fluidic analysis predicts sudden expansions should have larger dead volumes
with lower pressure drops, and sudden contractions should have lower dead volumes and higher pressure drops along the
interconnect for the same change in channel width.
Structural and electrical properties of conductive polymeric aligned nanofibers via electrospinning
Show abstract
The fabrication and characterization of conductive and aligned polymeric nanofibers using polypyrrole (PPy) and poly ethylene oxide (PEO) were reported. To improve the structural and electrical properties of the nanofibers, composite materials containing a conducting polymer alloyed with a non-conducting polymer have been proposed. A series of aligned nanofibers using pure PEO and its composite with conducting polymer PPy were produced. By separating the metal target plates, the resultant electric field between the grounded base/collector plates and the charged syringe can be split. This divergence in the electric field facilitates the ordered placement of the nanofibers. Ordered, continuous nanofibers have been realized as large as seven millimeters in separation. The ratio of length to diameter of the aligned fibers can be measured in μm/nm units. Our highest observed value is 46.6μm/nm. The structural properties of these aligned nanofibers have been performed utilizing Scanning Electron Microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR). The characterization of the aligned continuous nanofibers revealed diameters approaching 150 nanometers and the appearance of standard and some new absorption bands for PPy and PEO confirms the composite formation.
Optimization of COC hot embossing with soft PDMS tools
Show abstract
In this paper, Taguchi optimization method was used to investigate a COC (cyclic olefin copolymer) hot embossing
using soft PDMS (polydimethylsiloxane) tools. Because of the PDMS tool's soft intrinsic nature, replication errors
occur due to deformation during the hot embossing. The parameters, which affect on the replication quality, such as
temperature, embossing force, and hold time were selected as the control factors. Four level, L16 (45) orthogonal array of
Taguchi method was use to develop the optimal process. Height and width of the embossed channels were defined as
quality characteristics. The result of the analysis indicated temperature to be the most significant factor that substantially
affects replication fidelity. The optimized embossing process with soft PDMS tools can now be used to rapidly replicate
microfluidic devices having both small and large features with confidence.
Initial investigation of SU-8 photopolymer as a material for noninvasive endothelial cell research platforms
Show abstract
This paper presents a preliminary investigation in the usage of the micromachining polymer material SU-8 for the noninvasive
shape control and functional study of vascular endothelial cells (ECs). We previously demonstrated a silicon
and glass modular microinstrument platform that allowed for a wide range of EC functional response studies. However,
we expect SU-8 to provide a more versatile fabrication technology and material for microchannel fabrication and
instrumentation, since it is capable of achieving high aspect ratio sensor-compatible structures through simple
photopatterning. In this paper, SU-8 microchannels were fabricated on glass slides for straightforward optical
observation and biological sampling. Channel widths ranged from 50 to 210 µm, length varied from 100 to 2100 µm,
with depth fixed at 100 µm. We plated bovine aortic endothelial cells (BAECs) in the microchannels and used image
analysis to determine cellular elongation and orientation. Similar to silicon-on-glass microchannels, the cells become
more elongated and oriented along the microchannel axis as the width of the microchannel decreases. Initial results
indicate cells plate in the microchannels and on the SU-8 surfaces, whereas in a previous silicon microchannel study,
cells plated exclusively on the glass bottom surfaces. This finding has implications for SU-8 as a structural material for
microchannel instrumentation.
Microfluidics II
Concepts for micropneumatic and microhydraulic logic gates
Show abstract
Previously, we proposed novel microvalve structures, amenable to bulk micromachining, which effected fully
complementary behavior in the switching of pneumatic (compressible gas) signals from a high pressure state to a low
state, and vice versa. Using our quantitative relations for the flow of compressible gases in microvalves, we described
mathematically the steady-state behavior of these micro-pneumatic logic gates, and derived the transfer characteristic
for switching between pneumatic states. In this work, we extend the steady-state description to encompass a
mathematical treatment of the transient response of micro-pneumatic logic gates. By analogy to MOSFET scaling in
integrated circuits, we also apply the full transient model to scaled versions of a micro-pneumatic ring oscillator, in
order to illustrate the performance which these devices may afford. As with MOSFETs (which rely on the
compressibility of the electron gas), the ultimate speed of these devices is limited by the velocity of sound of the
compressible gas. Finally, we present structures which can be used to realize micro-hydraulic logic. In micro-hydraulic
logic, because the working fluid is now incompressible, the physical structure must have an alternate means to achieve
capacitance, or storage of mass. Such a means is embodied in a variable-volume component attached to each node in
the logic circuit.
A microfluidic MEMS sensor for the measurement of density and viscosity at high pressure
Show abstract
We present a sensor fabricated with MEMS (Micro-Electro-Mechanical Systems) technology that quickly
measures fluid density and viscosity. This sensor is fabricated inside of a microfluidic channel through which
the fluid to be measured passes. The operational principal involves the influence of the fluid on the
resonance frequency and quality factor of a vibrating plate oscillating normal to its plane. By performing
measurements in liquids we have demonstrated operability in fluids with densities between (0.6 to 1.5) g/cc
and viscosities between (0.4 to 100) cP. Such measurements are required to determine the economic
feasibility of recovering hydrocarbon from subterranean strata. There are numerous examples in the
literature of sensors fabricated by the methods of MEMS that are claimed to measure both density and
viscosity of fluids, but in most cases, the accuracy of such sensors is not been demonstrated in a wide range of
fluids and moreover, their use in non-laboratory environments has not been proven.1,2,3 Here we show that it
is possible to design and package a sensor that can function with high accuracy in extreme environments
while providing useful information.
Visualization of turbid two-fluid flows inside microfluidic conduits
Show abstract
Frequency domain optical coherence tomography (OCT) with phase-resolved algorithm is presented to perform highresolution
(8 &mgr;m), cross-sectional imaging of structure and velocity in turbid gas-liquid slug flow inside a microtube and
turbid liquid-liquid flow inside chaotic mixromixers: a barrier embedded Kenics micromixer and a Kenics micromixer.
Slug flow, the most common flow regime in microfluidic gas-liquid two-phase flow, consists of trails of bubbles
separated by liquid slugs flowing concurrently and provides significant radial heat and mass transfer. Since interfacial
transports are proportional to the interfacial area between two phases, interfacial area concentration defined by
interfacial area per unit mixture volume is an important parameter in a biochip with turbid biofluids. All the en face
image techniques, such as light microscopy, experience errors in the interfacial area concentration measurement due to
light refraction. In addition, they have overlapping depth information from the layers within a laser sheet or a depth of
focus of the objective lens. OCT, however, can provide accurate interfacial area concentration in a microtube because it
is a cross-sectional imaging technique which dispenses with the refraction correction in the radial direction.
Simultaneously, OCT can measure bubble velocity and velocity field inside liquid slugs. The radial liquid velocity was
quantified without refraction correction. Two toroidal vortices per liquid slug were visualized which is the essential
mechanism for radial heat and mass transfers. The barrier embedded Kenics micromixer and Kenics micromixer are
high performance chaotic micromixers with complex three-dimensional geometry. Conventional techniques cannot
visualize a cross-sectional mixing pattern in such a complex micromixer. OCT, however, can image the pattern and,
thereby, show mixing mechanisms. The barrier embedded Kenics micromixer was proven to have a higher performance
by comparison mixing patterns of two micromixers.
Numerical simulation of transient nonlinear behaviors of electric-sensitive hydrogel membrane under an external electric field
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A multi-physics model is developed to predict the transient nonlinear behaviors of electric-stimulus-
responsive hydrogels when the hydrogels are immersed into a bathing solution subject to an
externally applied electric field. The presently developed model consists of the transient convection-diffusion
equations for concentration distribution of diffusive ions, the Poisson equation for electric field
and the mechanical equations for deformation. In consideration of the mathematical model involving
chemo-electro-mechanics, a true meshfree, implicit numerical scheme is implemented for solution of the
transient nonlinear partial differential governing equations. The transient responds including the hydrogel
deformation, ionic concentrations and electric potentials interior and exterior the hydrogel are numerically
investigated, in which the simulating results in good agreement with the experimental or published results
validate the presently developed multi-field model.
Stochastic time-of-flight flow rate measurement for microfluidic applications
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We describe a thermal time of flight liquid flow rate measurement based on injection of a pseudo-random sequence of
thermal tracers in a microfluidic flow stream, followed by downstream detection of the temperature variation. The cross
correlation function between the injected sequence and the detected signal displays a peak corresponding to the time of
flight, which in turn provides a sensitive measure of flow rate. We demonstrate the technique by using integrated MEMS
silicon structures suspended across a microfluidic channel for both heating and detection. The encapsulation technique
we use involves 3-layer glass-silicon-glass bonding. We are capable of measuring flow rate over more than three
decades with an accuracy of a few percent (the exact measurement range scales with geometry, in our case
corresponding to 5 - 10,000 µl/min). Our technique shows excellent agreement between measurement, theory and
numerical simulation results; by comparison with other existing methods for microfluidic flow metering (anemometric,
coriolis), ours has the advantage of being largely independent of physical fluid properties. In addition, the suspended
MEMS heaters we fabricate can also be used as regular anemometer probes, extending the measurement possibilities to
gas flow metering and phase detection.
Simple passive micromixer using recombinant multiple flow streams
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A passive microfluidic mixer with high performance is designed and fabricated in this work. Diamond-shaped obstacles
were chosen to split the flow into several streams, which are then guided back together after the obstacle. To keep
pressure drop low, the channel cross-sectional area was maintained equal to the input cross-sectional area, and this was
held constant throughout the device. The proposed design was modeled using computational fluid dynamics (CFD)
software. The effects of channel width, channel length, location of obstructions, and Reynolds Number (Re) were
investigated. The simulated results were verified experimentally. Simulation data showed that the designed micromixer
achieved 90% mixing at a channel length of 4.35 mm with pressure drop of 584 Pa at Re = 1, while experimental data for
Re = 0.1 showed 90% mixing at 7 mm. The mixer functions well especially at the low Re (Re = 0.1).
Numerical simulations and analysis of a micropump actuated by traveling plane waves
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Traveling plane-wave deformations on a solid thin film immersed in a fluid can create viscous propulsion in the direction
opposite to wave propagation. Here, we present modeling and analysis of a valveless dynamic micropump that
incorporates a traveling plane-wave actuator. Our numerical model incorporates direct coupling between solid deforming
boundaries and the fluid by means of a deforming mesh according to Arbitrary Lagrangian Eulerian implementation, and
2D unsteady Stokes equations to solve for the flow realized by the traveling-wave actuator in the channel. A commercial
finite-element package, COMSOL, is used for simulations. Analysis is carried out to identify the effects of operating
conditions such as wavelength, frequency and amplitude of the waves. For specified dimensions of the pump, maximum
time-averaged flow rate, exit pressure, rate-of-work done on the fluid and efficiency of the micropump are calculated for
different operating conditions.
Plenary Paper
MEMS for medical technology applications
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This paper gives an in-depth description of two recent projects at the Royal Institute of Technology (KTH) which utilize MEMS and microsystem technology for realization of components intended for specific applications in medical technology and diagnostic instrumentation.
By novel use of the DRIE fabrication technology we have developed side-opened out-of-plane silicon microneedles intended for use in transdermal drug delivery applications. The side opening reduces clogging probability during penetration into the skin and increases the up-take area of the liquid in the tissue. These microneedles offer about 200µm deep and pain-free skin penetration. We have been able to combine the microneedle chip with an electrically and heat controlled liquid actuator device where expandable microspheres are used to push doses of drug liquids into the skin. The entire unit is made of low cost materials in the form of a square one cm-sized patch.
Finally, the design, fabrication and evaluation of an integrated miniaturized Quartz Crystal Microbalance (QCM) based "electronic nose" microsystem for detection of narcotics is described. The work integrates a novel environment-to-chip sample interface with the sensor element. The choice of multifunctional materials and the geometric features of a four-component microsystem allow a functional integration of a QCM crystal, electrical contacts, fluidic contacts and a sample interface in a single system with minimal assembly effort, a potential for low-cost manufacturing, and a few orders of magnitude reduced in system size (12*12*4 mm3) and weight compared to commercially available instruments. The sensor chip was successfully used it for the detection of 200 ng of narcotics sample.