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This PDF file contains the front matter associated with SPIE Proceedings Volume 9107, including the Title Page, Copyright information, Table of Contents, Invited Panel Discussion, and Conference Committee listing.
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Advances in Fiber Optic Sensing for Biomedical Applications
The all-glass optical fibre pressure and temperature sensor (OFPTS), present here is a combination of an extrinsic Fabry Perot Interferometer (EFPI) and an fiber Bragg gratings (FBG), which allows a simultaneously measurement of both pressure and temperature. Thermal effects experienced by the EFPI can be compensated by using the FBG. The sensor achieved a pressure measurement resolution of 0.1mmHg with a frame-rate of 100Hz and a low drift rate of < 1 mmHg/hour drift. The sensor has been evaluated using a cardiovascular simulator and additionally has been evaluated in-vivo in a urodynamics application under medical supervision.
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Photonic nanosensors (e.g. PEBBLES, quantum dots-based sensors, etc.) have begun to allow the study of these
previously inaccessible environments. Unfortunately, many current techniques suffer from biocompatibility issues,
limited ability to monitor multiple species simultaneously and/or complicated fabrication chemistries. Recently SERS
immuno-nanoprobes have demonstrated the capability to overcome many of these limitations. Such intracellular SERS
nanosensors require optimized substrate geometry to achieve the sensitivity necessary to detect the trace analyte
concentrations present. To address this, we have developed a novel multilayered SERS substrate nanoarchitecture that is
capable of enhancing SERS signals by over two orders of magnitude relative to comparable single layer substrates.
These structures are fabricated using different deposition techniques (PVD, ALD, etc) in which multiple films of Ag
(between 10-125 nm thick) are alternately deposited with ultrathin dielectric layers (tens of Å). This geometry allows
surface plasmons from different metal layers to be generated. The resulting multilayer enhancement increases the
sensitivity while also improving the robustness of the nanoprobes. In this paper, we investigate and characterize SERS
immuno-nanoprobes fabricated using this multilayered geometry and discuss the effect of the dielectric spacer (Ag2O,
TiO2, Ta2O5) work functions and conductive band offsets on the multilayer enhancement.
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One of the greatest dangers of drug use is in combination with driving. According to the most recent National
Highway Traffic Safety Administration (NHTSA) studies, more than 11% of drivers tested positive for illicit drugs,
while 18% of drivers killed in accidents tested positive for illicit, prescription or over-the-counter drugs.
Consequently, there is a need for a rapid, noninvasive, roadside drug testing device, similar to the breathalyzers used
by law enforcement officials to estimate blood alcohol levels of impaired drivers. In an effort to satisfy this need we
have been developing a sampling kit that allows extraction of drugs from 1 mL of saliva and detection by surfaceenhanced
Raman spectroscopy using a portable Raman analyzer. Here we describe the development of the sampling
kit and present measurements of diazepam at sub μg/mL concentrations measured in ~15 minutes.
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Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes major infection not only in Cystic Fibrosis
patients but also in chronic obstructive pulmonary disease and in critically ill patients in intensive care units. Successful
antibiotic treatment of the infection relies on accurate and rapid identification of the infectious agents. Conventional
microbiological detection methods usually take more than 3 days to obtain accurate results. We have developed a rapid
diagnostic technique based on surface-enhanced Raman scattering to directly identify PA from biological fluids. P.
aeruginosa strains, PAO1 and PA14, are cultured in lysogeny broth, and the SERS spectra of the broth show the
signature Raman peaks from pyocyanin and pyoverdine, two major biomarkers that P. aeruginosa secretes during its
growth, as well as lipopolysaccharides. This provides the evidence that the presence of these biomarkers can be used to
indicate P. aeruginosa infection. A total of 22 clinical exhaled breath condensates (EBC) samples were obtained from
subjects with CF disease and from non-CF healthy donors. SERS spectra of these EBC samples were obtained and
further analyzed by both principle component analysis and partial least square-discriminant analysis (PLS-DA). PLS-DA
can discriminate the samples with P. aeruginosa infection and the ones without P. aeruginosa infection at 99.3%
sensitivity and 99.6% specificity. In addition, this technique can also discriminate samples from subject with CF disease
and healthy donor with 97.5% sensitivity and 100% specificity. These results demonstrate the potential of using SERS of
EBC samples as a rapid diagnostic tool to detect PA infection.
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The tympanic membrane (ear drum) is a thin tissue film that is stretched between the outer and middle ear. Sound waves travel from outside the ear, and strike the tympanic membrane resulting in its vibration. These vibrations amplify the sound waves and transmit them to the ossicles (auditory bones). The magnitude of amplification is directly proportional to vibrating area of tympanic membrane. Hence a perforation in this membrane would result in hearing loss.
Pure-tone audiometry is the traditional procedure used to detect the amount of hearing loss in a patient. However, it is lengthy and less efficient, as it largely depends on the response of the patient to sound intensity and frequency of pure-tones.
We present a relatively more efficient approach to determine hearing loss due to perforated tympanic membrane using image processing techniques. We describe an algorithm that uses unsharp masking to sharpen images of the perforations as well as the tympanic membrane. Then, it converts the image into a binary image using thresholding. A median filter is applied to get rid of the noise component in the image. The ratio of the area of perforation and total area of tympanic membrane will define the percentage of hearing loss. Our approach will eliminate the error introduced due to patient dependency as in the traditional method.
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Optical coherence tomography (OCT) is a high resolution imaging technology that is rapidly being adopted as the
standard of care for medical applications such as ocular and intravascular imaging. However, clinical translation has
been hampered by the lack of standardized test methods for performance evaluation as well as consensus standards
analogous to those that have been developed for established medical imaging modalities (e.g., ultrasound). In this study,
we address low contrast detectability, specifically, the ability of systems to differentiate between regions exhibiting small
differences in scattering coefficient. Based on standard test methods for established medical imaging modalities, we
have developed layered phantoms with well-characterized scattering properties in a biologically relevant range. The
phantoms consisted of polydimethylsiloxane (PDMS) doped with varying concentrations of BaSO4 microparticles.
Microfabrication processes were used to create layered and channel schemes. Two spectral domain OCT systems - a
Fourier domain system at 855 nm and a swept-source device at 1310 nm - were then used to image the phantoms. The
detectability of regions with different scattering levels was evaluated for each system by measuring pixel intensity
differences. Confounding factors such as the inherent attenuation of the phantoms, signal intensity decay due to focusing
and system roll-off were also encountered and addressed. Significant differences between systems were noted. The
minimum differences in scattering coefficient that the Fourier domain and swept source systems could differentiate was
1.50 and 0.46 mm-1 respectively. Overall, this approach to evaluating low contrast detectability represents a key step
towards the development of standard test methods to facilitate clinical translation of novel OCT systems.
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Micro/Nanofluidic for Biomedical Sensing and Treatment
A model of transient flow with memory in a nanocapillar is formulated and anallitically solved. Nanofluidics behavior
is described by Navier-Stokes Equation when viscosity is a radially modulated parameter and by a border condition
corresponding with hysteretic sliding on the nanocapillar wall. Solution is obtained using the Laplace Transform, and
Bromwich Integral and the Residue Theorem for the Inverse Laplace Transform; with the final result being expressed
as an infinite series of Bessel Functions. The analytic solution for the case with material memory is compared with the
analytic solution for the case with no material memory and with constant viscosity. A formula for the development of
nanodynamic impedance is deduced. Analytic results are shown to be relevant in the design of nanofluidics devices
with applications in general nanotechnologies and pharmaceutical engineering in particular. Future lines of research
are also suggested.
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Consider the case of a microcapillary of radius R with two microfluidic immiscible. The micro-capillary region 0 < r <
R1 is occupied by the microfluidic less dense and less viscous; while the microcapillary region R1 <0 < R is occupied by
the microfluidic more dense and more viscous. Determine the characteristic impedance of the microcapillary in this case
when both microfluidics are driven by the same pressure gradient as the boundary condition at the wall of the
microcapillary is of the non-Newtonian slip. The Navier Stokes equation is solved for both microfluidic methods using
the Laplace transform. The velocity profiles are expressed in terms of Bessel functions. Similarly, the characteristic
impedance of the microcapillary is expressed by a complex formula Bessel functions. Obtain the analytical results are
important for designing engineering microdevices with applications in pharmaceutical, food engineering,
nanotechnology and biotechnology in general in particular. For future research it is interesting to consider the case of
boundary conditions with memory effects.
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Microfluidics have revolutionized the field of radiopharmaceuticals in allowing for the rapid optimization of
chemical processes and increased productivity in the preparation of radiotracers used in the development of imaging
agents for clinical research and the study of biological processes. This presentation will cover the rapid preparation
of radiotracers including simultaneous and sequential syntheses as well as the preparation of clinically useful
amounts of radiotracers, as well as the rapid purification of such materials.
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After analyzing the behavior of a fluid using an electroosmosis transport system, it was shown that the analysis of a
constant electric permittivity could also be extended to a medium in which its electrical properties are space dependent.
Using the hydrodynamic analysis with the Navier-Stookes equation in a high symmetric stationary environment and by
solving the Maxwell’s equations for only electrical charge sources within a micro channel, in the case where the
electrical properties of the fluid changed along the space. In this case, it was considered a linear and a quadratic relation
of the spatially modulated electric permittivity. For the first case, the solution was obtained in the terms of the Heun
functions and in the second case the solution was given in terms of the Legendre polynomials. For both cases, the
analytical solutions were obtained using the Maple software. After evaluating these results with the solutions obtained
with the Bessel’s special functions, it provided a close approximation of the behavior of the fluid under the
electroosmosis effect with constant permittivity. With the development of this comparison between these solutions for
the non-constant fluid’s electric characteristics, the analysis could be brought into the field of non-single-phase fluids, so
it might allow a further analysis of the electroosmosis within a more realistic fluid, in which properties changes among
the space inside a micro channel.
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One foundational motivation for chemical sensing is that knowledge of the presence and level of a chemical agent
informs decisions about treatment of the agent, for example by sequestration, separation or chemical conversion to a less
harmful substance. Commonly the sensing and treatment steps are separate. However, the disjoint detection/treatment
approach is neither optimal, nor required. Thus, we are investigating how nanostructured architectures can be
constructed so that molecular transport (analyte/reagent delivery), chemical sensing (optical or electrochemical) and
subsequent treatment can all be coupled in the same physical space during the same translocation event. Chemical
sensors that are uniquely well-poised for integration into 3-D micro-/nanofluidic architectures include those based on
plasmonics and impedance. Following detection, treatment can be substantially enhanced if mass transport limitations
can be overcome. In this context, in situ generation of reactive species within confined geometries, such as nanopores or
nanochannels, is of significant interest, because of its potential utility in overcoming mass transport limitations in
chemical reactivity. Solvent electrolysis in electrochemically coupled nanochannels supporting electrokinetic flow for
the generation of reactive species, can produce arbitrarily tunable quantities of reagents, such as O2 or H2, in situ in close proximity to the site of a hydrogenation catalyst, for example. Semi-quantitative estimates of the local H2 concentration are obtained by comparing the spatiotemporal fluorescence behavior and current measurements with finite element simulations accounting for electrolysis and subsequent convection and diffusion within the confined geometry. H2 saturation can easily be achieved at modest overpotentials.
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Lab-on-a-Chip Technologies for Biosensing Applications
A heat transfer model on a microfluidic is resolved analytically. The model describes a fluid at rest between two parallel
plates where each plate is maintained at a differentially specified temperature and the thermal conductivity of the
microfluidic is spatially modulated. The heat transfer model in such micro-hydrostatic configuration is analytically
resolved using the technique of the Laplace transform applying the Bromwich Integral and the Residue theorem. The
temperature outline in the microfluidic is presented as an infinite series of Bessel functions. It is shown that the result for
the thermal conductivity spatially modulated has as a particular case the solution when the thermal conductivity is
spatially constant. All computations were performed using the computer algebra software Maple. It is claimed that the
analytical obtained results are important for the design of nanoscale devices with applications in biotechnology.
Furthermore, it is suggested some future research lines such as the study of the heat transfer model in a microfluidic
resting between coaxial cylinders with radially modulated thermal conductivity in order to achieve future developments
in this area.
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Solidification and melting modeling on microfluidics are solved using Lambert W’s function and error’s functions.
Models are formulated using the heat’s diffusion equation. The generic posed case is the melting of a slab with time
dependent surface temperature, having a micro or nano-fluid liquid phase. At the beginning the solid slab is at melting
temperature. A slab’s face is put and maintained at temperature greater than the melting limit and varying in time.
Lambert W function and error function are applied via Maple to obtain the analytic solution evolution of the front of
microfluidic-solid interface, it is analytically computed and slab’s corresponding melting time is determined. It is
expected to have analytical results to be useful for food engineering, cooking engineering, pharmaceutical engineering,
nano-engineering and bio-medical engineering.
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In case of transplantation or the identification of special metabolic diseases like coeliac disease, HLA typing has to be done
fast and reliably with easy-to-handle devices by using limited amount of sample. Against this background a lab-on-a-chip
device was realized enabling a fast HLA typing via miniaturized Real-time PCR. Hereby, two main process steps were
combined, namely the extraction of DNA from whole blood and the amplification of the target DNA by Real-time PCR
giving rise-to a semi-quantitative analysis. For the implementation of both processes on chip, a sample preparation and a
real-time module were used. Sample preparation was carried out by using magnetic beads that were stored directly on chip
as dry powder, together with all lysis reagents. After purification of the DNA by applying a special buffer regime, the
sample DNA was transferred into the PCR module for amplification and detection. Coping with a massively increased
surface-to-volume ratio, which results in a higher amount of unspecific binding on the chip surface, special additives
needed to be integrated to compensate for this effect. Finally the overall procedure showed a sensitivity comparable to
standard Real-time PCR but reduced the duration of analysis to significantly less than one hour. The presented work
demonstrates that the combination of lab-on-a-chip PCR with direct optical read-out in a real-time fashion is an extremely
promising tool for molecular diagnostics.
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Today, nucleic amplification plays a key role in modern molecular biology allowing fast and specific laboratory
diagnostics testing. An ultrafast microfluidic module (allowing 30 polymeric chain reaction (PCR) cycles in 6 minutes)
based on an oscillating fluid plug concept was previously developed[1]. This system allows the amplification of native
genomic deoxyribonucleic acid molecules (DNA) even from whole blood samples but still lacks some functionality
compared to commercial bench top systems. This work presents the actual status of the renewed and advanced system,
permitting the automated optical detection of not only the fluid plug position but also fluorescence detection. The system
uses light emitting diodes (LED) for illumination and a low cost CMOS web-camera for optical detection. Image data
processing allows the automated process control of the overall system components. Therefore, the system enables the
performance of rapid and robust nucleic acid amplifications together with the integration of real time measurement
technology. This allows the amplification and simultaneous quantification of the DNA molecules. The possibility to
integrate swift nucleic amplification and optical detection into complex sample-to-answer analysis platforms opens up
new pathways towards fast and transportable low-cost point of care devices.
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Lab-on-a-chip systems are innovative tools for the detection and identification of microbial pathogens in human and
veterinary medicine. The major advantages are small sample volume and a compact design. Several fluidic modules have
been developed to transform analytical procedures into miniaturized scale including sampling, sample preparation, target
enrichment, and detection procedures.
We present evaluation data for single modules that will be integrated in a chip system for the detection of pathogens.
A microfluidic chip for purification of nucleic acids was established for cell lysis using magnetic beads. This assay was
evaluated with spiked environmental aerosol and swab samples. Bacillus thuringiensis was used as simulant for Bacillus
anthracis, which is closely related but non-pathogenic for humans. Stationary PCR and a flow-through PCR chip module
were investigated for specific detection of six highly pathogenic bacteria. The conventional PCR assays could be
transferred into miniaturized scale using the same temperature/time profile.
We could demonstrate that the microfluidic chip modules are suitable for the respective purposes and are promising tools
for the detection of bacterial pathogens. Future developments will focus on the integration of these separate modules to
an entire lab-on-a-chip system.
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Advances in Electrochemical Biosensing Materials and Devices
In this paper, we report on fabrication of a label free, highly sensitive and selective electrochemical cortisol
immunosensors using one dimensional (1D) ZnO nanorods (ZnO-NRs) and two dimensional nanoflakes (ZnO-NFs)
as immobilizing matrix. The synthesized ZnO nanostructures (NSs) were characterized using scanning electron
microscopy (SEM), selective area diffraction (SAED) and photoluminescence spectra (PL) which showed that both
ZnO-NRs and ZnO-NFs are single crystalline and oriented in [0001] direction. Anti-cortisol antibody (Anti-Cab) are
used as primary capture antibodies to detect cortisol using electrochemical impedance spectroscopy (EIS). The
charge transfer resistance increases linearly with increase in cortisol concentration and exhibits a sensitivity of 3.078
KΩ. M-1 for ZnO-NRs and 540 Ω. M -1 for ZnO-NFs. The developed ZnO-NSs based immunosensor is capable of
detecting cortisol at 1 pM. The observed sensing parameters are in physiological range. The developed sensors can
be integrated with microfluidic system and miniaturized potentiostat to detect cortisol at point-of-care.
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In this study, we have designed an electrochemical biosensor for real-time detection of specific biomarkers of bacterial
metabolism related to meat spoilage (hypoxanthine and xanthine). The selective biosensor was developed by assembling
a ‘sandwich’ of nanomaterials and enzymes on a platinum-iridium electrode (1.6 mm tip diameter). The materials
deposited on the sensor tip include amorphous platinum nanoclusters (i.e. Pt black), reduced graphene oxide, nanoceria,
and xanthine oxidase. Xanthine oxidase was encapsulated in laponite hydrogel and used for the biorecognition of
hypoxanthine and xanthine (two molecules involved in the rotting of meat by spoilage microorganisms). The developed
biosensor demonstrated good electrochemical performance toward xanthine with sensitivity of 2.14 ± 1.48 μA/mM,
response time of 5.2 ± 1.5 sec, lower detection limit of 150 ± 39 nM, and retained at least 88% of its activity after 7 days of continuous use.
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Advances in Luminescent Biosensing and Biomolecular Logic
Fluorescent probes suitable for the selective detection of DNA sequences are important in genomic research, disease
diagnostics, and pathogen detection, among many other applications. The unique optical properties of semiconductor
quantum dots (QDs) have proven to be highly valuable for development of fluorescent probes and biosensors. We
describe preliminary work toward combining QDs with monomeric thiazole dyes for the detection of nucleic acid
hybridization. BO, TO, BO3, and TO3 dyes, which span the visible spectrum, were synthesized with undecanoic acid
linkers to permit bioconjugation and their fluorescent enhancements in response to DNA oligonucleotides was evaluated.
Contrast ratios between single-stranded probe oligonucleotide and double-stranded probe/target hybrids were between
2.5 and 7.5. BO3 and TO3 were used to label a polyhistidine-appended peptide that self-assembled to QDs and were
found to be suitable acceptor dyes for Förster resonance energy transfer (FRET) with QD donors that had their peak
emission at 540 nm and 625 nm, respectively. We further conjugated a probe oligonucleotide to a polyhistidineappended
peptide at an internal site, and this probe also self-assembled to QDs. Mixing these conjugates with BO3 and
either complementary DNA target or non-complementary DNA could induce quenching of the QD emission via FRET,
but no FRET-sensitized BO3 emission was observed. Experiments suggested that binding of BO3 to the interface of the
QDs was in competition with binding to DNA. Our results provide insight into important criteria (e.g., QD surface
chemistry) for designing and optimizing a QD-FRET probe for DNA detection that utilizes the fluorescent properties of
monomeric thiazole intercalating dyes.
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The “spectroscopic ruler” based on fluorescence resonance energy transfer (FRET) is explored as a method for detailed
structural characterization of DNA nanostructures in solution. The approach is most directly useful for assessing the
positional relationships among chromophores organized by the DNA, but it can also be used to characterize the geometry
and kinematics of the DNA scaffold itself. By accumulating data for the distances separating various donor-acceptor
pairs, and correlating them with the expected distances, one can quantify the shape and deformability of the structure. A
8x16nm “mini-origami” rectangle is used as the model test structure and the dye-pairs are chosen to investigate
anisotropy in the origami’s mechanical properties. Not unexpectedly, our analysis finds a strong anisotropy in the
stiffness, with the measured spacing across the origami weave deviating much more from expectation than the spacing
aligned along the weave pattern.
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The paper presents an overview of recent advances in biosensors and bioactuators based on the biocomputing concept.
Novel biosensors digitally process multiple biochemical signals through Boolean logic networks of coupled
biomolecular reactions and produce output in the form of YES/NO response. Compared to traditional single-analyte
sensing devices, biocomputing approach enables a high-fidelity multi-analyte biosensing, particularly beneficial for
biomedical applications. Multi-signal digital biosensors thus promise advances in rapid diagnosis and treatment of
diseases by processing complex patterns of physiological biomarkers. Specifically, they can provide timely detection and
alert to medical emergencies, along with an immediate therapeutic intervention. Application of the biocomputing concept
has been successfully demonstrated for systems performing logic analysis of biomarkers corresponding to different
injuries, particularly exemplified for liver injury. Wide-ranging applications of multi-analyte digital biosensors in
medicine, environmental monitoring and homeland security are anticipated. “Smart” bioactuators, for example for
signal-triggered drug release, were designed by interfacing switchable electrodes and biocomputing systems. Integration
of novel biosensing and bioactuating systems with the biomolecular information processing systems keeps promise for
further scientific advances and numerous practical applications.
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Luminescent semiconductor nanocrystals or quantum dots (QDs) hold tremendous
promise for in vivo biosensing, cellular imaging, theranostics, and smart molecular sensing
probes due to their small size and favorable photonic properties such as resistance to
photobleaching, size-tunable PL, and large effective Stokes shifts. Herein, we demonstrate how
QD-based bioconjugates can be used to enhance enzyme kinetics. Enzyme-substrate kinetics are
analyzed for solutions containing both alkaline phosphatase enzymes and QDs with enzyme-to-
QD molar ratios of 2, 12, and 24 as well as for a solution containing the same concentration of
enzymes but without QDs. The enzyme kinetic paramters Vmax, KM, and Kcat/KM are extracted from the enzyme progress curves via the Lineweaver-Burk plot. Results demonstrate an
approximate increase in enzyme efficiency of 5 - 8% for enzymes immobilized on the QD
versus free in solution without QD immobilization.
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Advanced Smart Materials for Potential Biosensing/Bioimaging Applications
Current biodetection assays that employ monoclonal antibodies as primary capture agents exhibit limited
fieldability, shelf life, and performance due to batch-to-batch production variability and restricted thermal stability. In
order to improve upon the detection of biological threats in fieldable assays and systems for the Army, we are
investigating protein catalyzed capture (PCC) agents as drop-in replacements for the existing antibody technology
through iterative in situ click chemistry. The PCC agent oligopeptides are developed against known protein epitopes and
can be mass produced using robotic methods. In this work, a PCC agent under development will be discussed. The
performance, including affinity, selectivity, and stability of the capture agent technology, is analyzed by
immunoprecipitation, western blotting, and ELISA experiments. The oligopeptide demonstrates superb selectivity
coupled with high affinity through multi-ligand design, and improved thermal, chemical, and biochemical stability due
to non-natural amino acid PCC agent design.
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A polymer pellet-based sensor device comprised of polypyrrole (PPy), polymethyl methacrylate (PMMA) and
polyethylene glycol (PEG), its fabrication methods, and the experimental results for low-concentration acetone detection
are presented. The design consists of a double layer pellet, where the top layer consists of PPy/PMMA and the bottom
layer is composed of PPy/PMMA/PEG. Both sets of material compositions are synthesized by readily realizable
chemical polymerization techniques. The mechanism of the sensor operation is based on the change in resistance of PPy
and the swelling of PMMA when exposed to acetone, thereby changing the resistance of the layers. The resistances
measured on the two layers, and across the pellet, are taken as the three output signals of the sensor. Because the
PPy/PMMA and PPy/PMMA/PEG layers respond differently to acetone, as well as to other volatile organic compounds,
it is demonstrated that the three output signals can allow the presented sensor to have a better sensitivity and selectivity
than previously reported devices. Materials characterizations show formation of new composite with PPy/PMMA/PEG.
Material response at various concentrations of acetone was conducted using quartz crystal microbalance (QCM). It was
observed that the frequency decreased by 98 Hz for 290 ppm of acetone and by 411 Hz for 1160 ppm. Experimental
results with a double layer pellet of PPy/PMMA and PPy/PMMA/PEG show an improved selectivity of acetone over
ethanol. The reported acetone sensor is applicable for biomedical and other applications.
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Biosensing and Therapy for the Central Nervous System
In a computer network there are distinct data channels and control channels where massive amount of visual information
are transported through data channels but the information streams are routed and controlled by intelligent algorithm
through “control channels”. Recent studies on cognition and consciousness have shown that the brain control channels
are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by
brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs
are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to
deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person’s
brain using binaural beats technique and identify the individual’s preferred control channels. The identified control
channels can then be used to influence the subject’s brain executive functions. In the experiment, an EEG measurement
system was used to record and identify a subject’s control channels. After these channels were identified, the subject was
asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject’s
brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the
subject’s executive function performance and reduced the time to complete incongruent tests, while the alpha signal
didn’t seem to be able to slow down the executive function performance.
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Group instruction is the most common delivery method of motor skill training given its cost and time effectiveness. This
is also the case during rehabilitation where therapists divide their attention among several patients. Compared to
dedicated one-on-one instruction, group instruction often suffers from reduced quality and quantity of instruction and
feedback. Further, during rehabilitation programs, patients struggle outside of therapy sessions given the lack of
instruction and feedback found only during clinic visits. We propose a wearable, low-cost motion sensing and actuation
system capable of providing real-time vibrotactile feedback for trainer-defined goal movements and repetitions. The
trainer inputs movement goals for the user, and adapts these values (joint angles, movement speeds) over time for
continued progress. In this paper, we present a novel second generation design, and introduce a flexible vibrotactile strip
to overcome construction challenges of these types of systems. The flexible display is constructed using commercial
LED strips that have been modified by attaching pancake style vibration motors. The flexible display does not require
external microcontrollers to enable or disable motors, and may allow these systems to be expanded to the whole body.
We also summarize two previous studies that have assessed appropriate body sites and pattern designs for vibrotactile
motor instructions and feedback signals.
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Optical Biopsy and Photoacoustic Sensing/Bioimaging
Non-contact photoplethysmography (PPG) has been studied as a method to provide low-cost and non-invasive medical
imaging for a variety of near-surface pathologies and two dimensional blood oxygenation measurements. Dynamic tissue
phantoms were developed to evaluate this technology in a laboratory setting. The purpose of these phantoms was to
generate a tissue model with tunable parameters including: blood vessel volume change; pulse wave frequency; and
optical scattering and absorption parameters. A non-contact PPG imaging system was evaluated on this model and
compared against laser Doppler imaging (LDI) and a traditional pulse oximeter. Results indicate non-contact PPG
accurately identifies pulse frequency and appears to identify signals from optically dense phantoms with significantly
higher detection thresholds than LDI.
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Photoacoustic tomography (PAT) is a maturing imaging technique which combines optical excitation and
acoustic detection to enable deep tissue sensing for biomedical applications. Optical absorption provides biochemical
specificity and high optical contrast while ultrasonic detection provides high spatial resolution and penetration depth.
These characteristics make PAT highly suitable as an approach for vascular imaging. However, standard testing methods
are needed in order to characterize and compare the performance of these systems. Tissue-mimicking phantoms are
commonly used as standard test samples for imaging system development and evaluation due to their repeatable
fabrication and tunable properties. The multi-domain mechanism behind PAT necessitates development of phantoms that
accurately mimic both acoustic and optical properties of tissues. While a wide variety of materials have been used in the
literature, from gelatin and agar hydrogels to silicone, published data indicates that poly(vinyl chloride) plastisol (PVCP)
is a promising candidate material for simulating tissue optical and acoustic properties while also providing superior
longevity and stability. Critical acoustic properties of PVCP phantoms, including sound velocity and attenuation, were
measured using acoustic transmission measurements at multiple frequencies relevant to typical PAT systems. Optical
absorption and scattering coefficients of PVCP gels with and without biologically relevant absorbers and scatterers were
measured over wavelengths from 500 to 1100 nm. A custom PAT system was developed to assess image contrast in
PVCP phantoms containing fluid channels filled with absorbing dye. PVCP demonstrates strong potential as the basis of
high-fidelity polymer phantoms for developing and evaluating PAT systems for vascular imaging applications.
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Conventional photoacoustic imaging (PAI) employs light pulses to produce a photoacoustic (PA) effect and detects the
resulting acoustic waves using an ultrasound transducer acoustically coupled to the target tissue. The resolution of
conventional PAI is limited by the sensitivity and bandwidth of the ultrasound transducer. We have developed an all-optical
versatile PAI system for characterizing ex vivo and in vivo biological specimens. The system employs noncontact
interferometric detection of the acoustic signals that overcomes limitations of conventional PAI. A 532-nm pump
laser with a pulse duration of 5 ns excited the PA effect in tissue. Resulting acoustic waves produced surface
displacements that were sensed using a 532-nm continuous-wave (CW) probe laser in a Michelson interferometer with a
GHz bandwidth. The pump and probe beams were coaxially focused using a 50X objective giving a diffraction-limited
spot size of 0.48 μm. The phase-encoded probe beam was demodulated using a homodyne interferometer. The detected
time-domain signal was time reversed using k-space wave-propagation methods to produce a spatial distribution of PA
sources in the target tissue. Performance was assessed using PA images of ex vivo rabbit lymph node specimens and
human tooth samples. A minimum peak surface displacement sensitivity of 0.19 pm was measured. The all-optical PAI
(AOPAI) system is well suited for assessment of retinal diseases, caries lesion detection, skin burns, section less
histology and pressure or friction ulcers.
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Transdermal patches are used in medicine to deliver a specific amount of medication through the skin and into the
bloodstream, and then to the injury that will be treated. The diffusion process involved in this method was modeled using
cartesian coordinates and it was solved using Laplace transformation, Bromwich integral and the residue theorem. The
solution obtained in cartesian coordinates was given in terms of Fourier series. The cumulative amount of drug released
at time t was calculated and it is represented as an infinite series of decreasing exponentials. It’s expected that the
analytic results obtained will be useful for pharmaceutical engineering.
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The diffusion rate of a spherical drug delivery device was analyzed using a Laplace transform-based method. The three-dimensional model represented a pharmaceutical agent distributed, not uniformly, in a polymeric matrix. Molecules
could only be transferred to the outside of the matrix through a thin spherical sector of the device. A closed-form
solution was obtained to help study the effects of diffusivity parameters and geometries on the cumulative amount of
drug released. The latter variable increased with the mass transfer and diffusion function and decreased with any
increment in the device’s length. The solution obtained was in terms of the Legendre polynoms, and developed using the
Maple software. It is expected that the results presented help to the future design of devices in pharmaceutical
engineering.
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The dynamics of shrinking drug-loaded microspheres were studied using a diffusion equation in spherical coordinates
and with a radially modulated diffusivity. A movable boundary condition that represents the shrinking was incorporated
using an approximation based on the Laplace transform. The resulting diffusive problem with radially modulated
diffusivity was solved using Laplace transform techniques with the Bromwich integral, the residue theorem and special
functions. Analytical solutions in the form of infinity series of special functions were derived for the general case of
shrinking microspheres and for the particular case with exponential shrinking. All computations were made using
computer algebra, specifically Maple. Some numerical simulations were made in the case of microspheres with
exponential shrinking. The analytical results were used to derive the effective constant time for the shrinking
microsphere. As future line of investigation, it is proposed the analysis of models with boundary condition that shows
the memory effect. It is expected that the obtained analytical results could be very important in pharmaceutical
engineering.
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A diffusion and delivery model of a drug across the skin with diffusivity spatially modulated is formulated and solved
analytically using computer algebra. The model is developed using one-dimensional diffusion equation with a diffusivity
which is a function of position in the skin; with an initial condition which is describing that the drug is initially contained
inside a therapeutic patch; with a boundary condition according to which the change in concentration in the patch is
minimal, such that assumption of zero flux at the patch-skin interface is valid; and with other boundary condition
according to which the microcirculation in the capillaries just below the dermis carries the drug molecules away from the
site at a very fast rate, maintaining the inner concentration at 0. The model is solved analytically by the method of the
Laplace transform, with Bromwich integral and residue theorem. The concentration profile of the drug in the skin is
expressed as an infinite series of Bessel functions. The corresponding total amount of delivered drug is expressed as an
infinite series of decreasing exponentials. Also, the corresponding effective time for the therapeutic patch is determined.
All computations were performed using computer algebra software, specifically Maple. The analytical results obtained
are important for understanding and improving currentapplications of therapeutic patches. For future research it is
interesting to consider more general models of spatial modulation of the diffusivity and the possible application of other
computer algebra software such as Mathematica and Maxima.
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