Our work focuses on the implementation of microfluidic network (μFN) platforms for the
development of new bioassays and diagnositics in micro total
analytical systems (μTAS).
Several examples of ongoing research are highlighted below, along with
contact information for participating faculty members.
Prospective graduate students are encouraged to contact us for information
regarding research opportunities leading to MS and PhD degrees in
chemical engineering,
chemistry, and
electrical engineering. We particularly invite undergraduate students
to work in our laboratories as members of vibrant, interdisciplinary research teams.
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A local, evanescent, array-coupled (LEAC)
sensor based on a compact,
single-mode optical waveguide (IOW) is being developed
by the Dandy, Lear, and Henry groups for multianalyte
sensing of targets ranging from small molecules to virus and bacteria
particles. The LEAC sensor mechanism relies on specific binding of
analytes to one of several localized regions of immobilized
biological molecule probes, to modify the waveguide cross section
and, thus, the local evanescent field.
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An array of poly-silicon detector elements
along the length of the silicon nitride waveguide, each opposite a region of specific
capture ligand type, can sense the modification in the evanescent field due
to local adlayers of bound targets. To sense multiple adlayers at
different positions along the waveguide, the optical field
disturbance from one sensor element needs to be minimized or at least
controlled before light is incident on the next one.
However, each
adlayer perturbs the local mode structure, thus exciting leaky modes
in addition to the single bound mode. Transient optical interference
or mode-beating between the bound and leaky modes, which
have different propagation constants, causes subsequent
oscillations in the evanescent field that damp as the leaky mode
field dissipates. This behavior is shown in the figure to the right,
in which near-field scanning optical microscopy has been used to measure
the response of the evanescent field to a 17 nm thick region on the sensor
surface.
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It is recognized that mixing plays an important role in the growing
use of microfluidic devices for lab-on-a-chip applications. For
applications ranging from DNA separation and amplification to protein
crystallization and kinetics studies, the performance of a
lab-on-a-chip device is directly related to the rate at which two or
more fluids can be mixed. Due to the small dimensions of microchannels
as well as the limited range of obtainable linear flow rates, flow in
microchannels is confined to the laminar regime and mixing is
dominated by molecular diffusion.
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Perhaps the
best known examples pertaining to passive microfluidic mixing are the
staggered herringbone mixer (SHM) and the slanted groove micromixer
(SGM).
The SGM consists of diagonal grooves embedded into the floor
of a microchannel situated at an angle θ with respect to the axial
direction. The Dandy group is
carrying out a systematic study of the SGM geometry using computational
fluid dynamics (CFD) to determine optimal geometrical configurations associated with
groove depth, length, and spacing. As seen in the figure to the right,
a significant enhancement in mixing may be achieved through manipulation of
the groove length to ridge height ratio. Studies are ongoing to determine
correlations arising from the CFD simulations that may be used to guide
microchannel design.
With the goal of further simplifying fabrication of a micromixer,
we are developing a new method for achieving chaotic advection through
application of a localized electric field perpendicular to the mean
flow direction driven by a pressure gradient in a planar rectangular
microchannel. The electric field, created by a potential
drop across an integrated electrode gap, drives
electro-osmotic flow (EOF) perpendicular to
the main flow direction, thereby creating a secondary recirculation
flow profile.
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Through control of the electrode geometry-gap width, gap
location, and axial separation, it is possible to induce rapid mixing
in short axial distances. This device, a superposition of transverse
electro-osmotic and axial pressure driven flow, is referred to as an
electro-osmotic chaotic advection micromixer (eCAM).
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The Reardon group has developed fiber optic biosensors based on pH
changes caused by enzymatic reaction with the analyte. In particular,
we have focused on hydrolytic dehalogenases, which add water to a
halogenated organic and release a halogen ion and a proton.
A layer of pH-sensitive fluorophore is immobilized on the tip of a
1-mm diameter optical fiber and coated with dehalogenase-containing
bacteria (or purified dehalogenase), as shown here. Protons from the
dehalogenation reaction are detected as a pH change in at the end of
the optical fiber, and thus as a change in the fluorescence intensity.
Since the change in fluorescence depends on the
contaminant concentration, these sensors provide quantitative output.
Measurements with the biosensor are simple and require no reagent or
pretreatment: the tip of the biosensor is simply placed in the sample
to be measured. For cases in which the original sample matrix
contains species that interfere with the measurement, a simple
dilution into a saline solution has proven effective.
To date, we
have developed fiber optic biosensors for atrazine, 1,2-dichloroethane
(DCA), ethylene dibromide (EDB), dichloromethane, 1-chlorohexane,
Lindane (γ-hexachlorocyclohexane), Endosulfan, and paraoxon.
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Using other dehalogenases and enzymes that create pH changes,
new sensors can be created for a wide range of chemicals,
including not only halogenated organics but also organophosphates.
These enzymes do not require energy or cofactors, so the cells in
which they are immobilized need not be living. In principle,
immobilized enzymes could be used but we have found cell
immobilization to be simple and effective.
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Work is underway in the Lear group to develop
a passive cavity approach to performing optofluidic intracavity
spectroscopy
that greatly simplifies the sensor system relative to previous
external cavity laser implementations. The device is based on the
treatment of cells in an aqueous environment as lenses due to their
higher index and curved interface with the fluid. Paul Gourley and
colleagues at Sandia National Laboratories demonstrated that placing
cells in the cavity of a photopumped VCSEL generated unique spectral
features such as the number, spacing, and offset of multimode spectra
that could be used to distininguish different types of cells.
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The Lear
optoelectronics group subsequently demonstrated an electrically driven
laser diode version. A Fabry-Perot cavity is
fabricated in a microfluidic channel by depositing
gold mirror coatings on the channel bottom and lid and bonding
the pieces together (a). A top view, looking through a channel
containing polystyrene beads is shown in (b).
However, the active cavity sensors place
relatively high demands on the laser to overcome the loss associated
with the fluid filled external cavity, and to integrate the laser
diode with the microfluidics system. These challenges motivated the
passive cavity system that relies on the transmission spectra of a
cavity taken using an external LED as the continuum light source.
This system has been used to obtain spectra of red and white blood
cells, yeast, and polystyrene spheres. The spectra of red blood cells in
particular were found to be well correlated and allowed their
quantitative differentiation with respect to white blood cells. Thus,
this technology may be appropriate applications such as unstained
whole blood counts in a lab-on-a-chip environment. The nigh finesse
transmission spectrum measured for a channel using a LED as the source
is seen to the right.
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bioanalytical detection
Microchip capillary electrophoresis and related techniques have the
potential to change the way chemical analysis is preformed. The
benefits over conventional instruments are attributed to the small
size, high speed, and the low amount of sample needed to run an
experiment. We are developing and implementing electrochemical
detection techniques for micro devices to provide a greater set
detectable analytes.
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The main goal of the Henry group
is to be able to separate and
detect biologically important compounds from whole blood samples such
as neurotransmitters, metabolic markers, markers of redox and
oxidative damage, and chemotherapy agents.
The complex natures of
blood as well as the low concentrations of analytes require a system
with high sensitivity and efficiency. We are developing methods to
improve separation efficiency of PDMS microchip capillary
electrophoresis devices as well as working with other materials to
improve separation efficiency. Our microchips are fabricated with
microwire working electrodes which have shown detection limits in the
low nanomolar range. These developments should let us detect and
quantify a number of biologically important analytes.
environmental detection
Analysis of atmospheric aerosols is an important area of
research. Aerosol composition is known to affect weather by causing
temperature shifts or by acting as cloud condensation
nuclei. Additionally, they can negatively affect the human respiratory
and cardiovascular systems. Of particular interest are the
fluctuations in concentration of inorganic and organic ions.
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The
current analysis methods of gas chromatography-mass spectrometry and
ion chromatography require time-consuming derivatization and/or
relatively large sample sizes, making them unsuitable for routine
analysis on small spatial and temporal scales. The goal of our
research is develop a microchip capillary electrophoresis system
capable of quickly separating and quantifying the major organic and
inorganic ions present in atmospheric aerosols. The system will be
portable, inexpensive, easy-to-build, and allow routine monitoring on
much smaller temporal and spatial scales than current methods. This
technology should allow for a better understanding of the sources of
atmospheric aerosols, as well as the severity of their effects on the
environment and human health. The spectrum above shows the successful
separation
of 26 acids found in atmospheric aerosols.
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