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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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-C_ab) 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.

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.

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.

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.

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.

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 V_max, K_M, and K_cat/K_M 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.