Dependence of Skin-Electrode Contact Impedance on Material and Skin Hydration.

Dry electrodes offer an accessible continuous acquisition of biopotential signals as part of current in-home monitoring systems but often face challenges of high-contact impedance that results in poor signal quality. The performance of dry electrodes could be affected by electrode material and skin hydration. Herein, we investigate these dependencies using a circuit skin-electrode interface model, varying material and hydration in controlled benchtop experiments on a biomimetic skin phantom simulating dry and hydrated skin. Results of the model demonstrate the contribution of the individual components in the circuit to total impedance and assist in understanding the role of electrode material in the mechanistic principle of dry electrodes. Validation was performed by conducting in vivo skin-electrode contact impedance measurements across ten normative human subjects. Further, the impact of the electrode on biopotential signal quality was evaluated by demonstrating an ability to capture clinically relevant electrocardiogram signals by using dry electrodes integrated into a toilet seat cardiovascular monitoring system. Titanium electrodes resulted in better signal quality than stainless steel electrodes. Results suggest that relative permittivity of native oxide of electrode material come into contact with the skin contributes to the interface impedance, and can lead to enhancement in the capacitive coupling of biopotential signals, especially in dry skin individuals.

A miniaturized 3D printed pressure regulator (µPR) for microfluidic cell culture applications.

Well-defined fluid flows are the hallmark feature of microfluidic culture systems and enable precise control over biophysical and biochemical cues at the cellular scale. Microfluidic flow control is generally achieved using displacement-based (e.g., syringe or peristaltic pumps) or pressure-controlled techniques that provide numerous perfusion options, including constant, ramped, and pulsed flows. However, it can be challenging to integrate these large form-factor devices and accompanying peripherals into incubators or other confined environments. In addition, microfluidic culture studies are primarily carried out under constant perfusion conditions and more complex flow capabilities are often unused. Thus, there is a need for a simplified flow control platform that provides standard perfusion capabilities and can be easily integrated into incubated environments. To this end, we introduce a tunable, 3D printed micro pressure regulator (µPR) and show that it can provide robust flow control capabilities when combined with a battery-powered miniature air pump to support microfluidic applications. We detail the design and fabrication of the µPR and: (i) demonstrate a tunable outlet pressure range relevant for microfluidic applications (1-10 kPa), (ii) highlight dynamic control capabilities in a microfluidic network, (iii) and maintain human umbilical vein endothelial cells (HUVECs) in a multi-compartment culture device under continuous perfusion conditions. We anticipate that our 3D printed fabrication approach and open-access designs will enable customized µPRs that can support a broad range of microfluidic applications.

A biomimetic skin phantom for characterizing wearable electrodes in the low-frequency regime.

Advances in the integration of wearable devices in our daily life have led to the development of new electrode designs for biopotential monitoring. Historically, the development and testing of wearable electrodes for the acquisition of biopotential signals has been empirical, relying on experiments on human volunteers. However, the lack of explicit control on human variables, the intra-, and inter-subject variability complicates the understanding of the performance of these wearable electrodes. Herein, phantom mimicking the electrical properties of the skin in the low-frequency range (1 Hz-1000 Hz), which has the potential to be used as a platform for controlled benchtop experiments for testing electrode functionality, is demonstrated. The fabricated phantom comprises two layers representing the deeper tissues and stratum corneum. The lower layer of the phantom mimicking deeper tissues was realized using polyvinyl alcohol cryogel (PVA-c) prepared with 0.9% W/W saline solution by a freeze-thaw technique. The properties of the upper layer representing the stratum corneum were simulated using a 100µm thick layer fabricated by spin-coating a mixture of polydimethylsiloxane (PDMS), 2.5% W/W carbon black (CB) for conductance, and 40% W/W barium titanate (BaTiO3) as a dielectric. The hydration of the stratum corneum was modeled in a controlled way by varying porosity of the phantom's upper layer. Impedance spectroscopy measurements were carried out to investigate the electrical performance of the fabricated phantom and validated against the impedance response obtained across a physiological skin impedance range of five human subjects. The results indicated that the Bode plot depicting the impedance response obtained on the phantom was found to lie in the human skin range. Moreover, it was observed that the change of porosity provides control over the hydration and the phantom can be tuned as per the skin ranges among different individuals. Also, the phantom was able to mimic the impact of dry and hydrated skin on a simulated ECG signal in the time domain. The developed skin phantom is affordable, fairly easy to manufacture, stable over time, and can be used as a platform for benchtop testing of new electrode designs.

A Wirelessly Controlled Scalable 3D-Printed Microsystem for Drug Delivery.

Here we present a 3D-printed, wirelessly controlled microsystem for drug delivery, comprising a refillable microreservoir and a phase-change peristaltic micropump. The micropump structure was inkjet-printed on the back of a printed circuit board around a catheter microtubing. The enclosure of the microsystem was fabricated using stereolithography 3D printing, with an embedded microreservoir structure and integrated micropump. In one configuration, the microsystem was optimized for murine inner ear drug delivery with an overall size of 19 × 13 × 3 mm3. Benchtop results confirmed the performance of the device for reliable drug delivery. The suitability of the device for long-term subcutaneous implantation was confirmed with favorable results of implantation of a microsystem in a mouse for six months. The drug delivery was evaluated in vivo by implanting four different microsystems in four mice, while the outlet microtubing was implanted into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion, demonstrating similar results with syringe pump infusion. Although demonstrated for one application, this low-cost design and fabrication methodology is scalable for use in larger animals and humans for different clinical applications/delivery sites.

Microengineered 3D Collagen Gels with Independently Tunable Fiber Anisotropy and Directionality.

Cellular processes, including differentiation, proliferation, and migration, have been linked to the alignment (anisotropy) and orientation (directionality) of collagen fibers in the native extracellular matrix (ECM). Given the critical role that biophysical cell-matrix interactions play in regulating biological functions, several microfluidic-based methods have been used to establish 3D collagen gels with defined fiber properties; these gels have helped to establish quantitative relationships between structural ECM cues and observed cell responses. Although existing microfluidic fabrication methods provide excellent definition over collagen fiber anisotropy, they have not demonstrated the independent control over fiber anisotropy and directionality necessary to replicate in vivo collagen architecture. Therefore, to advance collagen microengineering capabilities, we present a user-friendly technology platform that uses controlled fluid flows within a non-uniform microfluidic channel network to create collagen landscapes that can be tuned as a function of extensional strain rate. Herein, we demonstrate capabilities to i) control the degree of fiber anisotropy, ii) create spatial gradients in fiber anisotropy, iii) independently define fiber directionality, and iv) generate multi-material interfaces within a 3D environment. We then address the practical issue of integrating cells into microfluidic systems by using a peel-off template technique to provide direct access to microengineered collagen gels, and demonstrate that cells respond to the defined properties of the landscape. Finally, the platform's modular capability is highlighted by integrating a sub-micrometer thick porous parylene membrane onto the microengineered collagen as a method to define cell-substrate interactions.

A review of peristaltic micropumps.

This report presents a review of progress on peristaltic micropumps since their emergence, which have been widely used in many research fields from biology to aeronautics. This paper summarizes different techniques that have been used to mimic this elegant physiological transport mechanism that is commonly found in nature. The analysis provides definitions of peristaltic micropumps and their different features, distinguishing them from other mechanical micropumps. Important parameters in peristalsis are presented, such as the operating frequency, stroke volume, and various actuation sequences, along with introducing design rules and analysis for optimizing actuation sequences. Actuation methods such as piezoelectric, motor, pneumatic, electrostatic, and thermal are discussed with their advantages and disadvantages for application in peristaltic micropumps. This review evaluates research efforts over the past 30 years with comparison of key features and outputs, and suggestions for future development. The analysis provides a starting point for researchers designing peristaltic micropumps for a broad range of applications.

Deep Volumetric Segmentation of Murine Cochlear Compartments from Micro-Computed Tomography Images.

Local drug delivery to the inner ear via micropump implants has the potential to be much more effective than oral drug delivery for treating patients with sensorineural hearing loss and to protect hearing from ototoxic insult due to noise exposure or cancer treatments. Designing micropumps to deliver appropriate concentrations of drugs to the necessary cochlear compartments is of paramount importance; however, directly measuring local drug concentrations over time throughout the cochlea is not possible. Recent approaches for indirectly quantifying local drug concentrations in animal models capture a series of magnetic resonance (MR) or micro computed tomography (µCT) images before and after infusion of a contrast agent into the cochlea. These approaches require accurately segmenting important cochlear components (scala tympani (ST), scala media (SM) and scala vestibuli (SV)) in each scan and ensuring that they are registered longitudinally across scans. In this paper, we focus on segmenting cochlear compartments from µCT volumes using V-Net, a convolutional neural network (CNN) architecture for 3-D segmentation. We show that by modifying the V-Net architecture to decrease the numbers of encoder and decoder blocks and to use dilated convolutions enables extracting local estimates of drug concentration that are comparable to those extracted using atlas-based segmentation (3.37%, 4.81%, and 19.65% average relative error in ST, SM, and SV), but in a fraction of the time. We also test the feasibility of training our network on a larger MRI dataset, and then using transfer learning to perform segmentation on a smaller number of µCT volumes, which would enable this technique to be used in the future to characterize drug delivery in the cochlea of larger mammals.

Microtechnologies for inner ear drug delivery.

PURPOSE OF REVIEW: Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and pharmacokinetic profile control. This review examines recent developments in the field for clinical and animal research environments. RECENT FINDINGS: Micropump technologies are being developed for dynamic control of flow rates with refillable reservoirs enabling timed delivery of multiple agents for protection or regeneration therapies. These micropumps can be combined with cochlear implants with integral catheters or used independently with cochleostomy or round window membrane (RWM) delivery modalities for therapy development in animal models. Sustained release of steroids with coated cochlear implants remains an active research area with first-time-in-human demonstration of reduced electrode impedances. Advanced coatings containing neurotrophin producing cells have enhanced spiral ganglion neuron survival in animal models, and have proven safe in a human study. Microneedles have emerged for controlled microperforation of the RWM for significant enhancement in permeability, combinable with emerging matrix formulations that optimize biological interaction and drug release kinetics. SUMMARY: Microsystem technologies are providing enhanced and more controlled access to the inner ear for advanced drug delivery approaches, alone and in conjunction with cochlear implants.

A 3D-Printed Modular Microreservoir for Drug Delivery.

Reservoir-based drug delivery microsystems have enabled novel and effective drug delivery concepts in recent decades. These systems typically comprise integrated storing and pumping components. Here we present a stand-alone, modular, thin, scalable, and refillable microreservoir platform as a storing component of these microsystems for implantable and transdermal drug delivery. Three microreservoir capacities (1, 10, and 100 µL) were fabricated with 3 mm overall thickness using stereolithography 3D-printing technology, enabling the fabrication of the device structure comprising a storing area and a refill port. A thin, preformed dome-shaped storing membrane was created by the deposition of parylene-C over a polyethylene glycol sacrificial layer, creating a force-free membrane that causes zero forward flow and insignificant backward flow (2% of total volume) due to membrane force. A septum pre-compression concept was introduced that enabled the realization of a 1-mm-thick septa capable of ~65000 leak-free refill punctures under 100 kPa backpressure. The force-free storing membrane enables using normally-open micropumps for drug delivery, and potentially improves the efficiency and precision of normally-closed micropumps. The ultra-thin septum reduces the thickness of refillable drug delivery devices, and is capable of thousands of leak-free refills. This modular and scalable device can be used for drug delivery in different laboratory animals and humans, as a sampling device, and for lab-on-a-chip and point-of-care diagnostics applications.

Cochlear pharmacokinetics - Micro-computed tomography and learning-prediction modeling for transport parameter determination.

Inner ear disorders such as sensorineural deafness and genetic diseases may one day be treated with local drug delivery to the inner ear. Current pharmacokinetic models have been based on invasive methods to measure drug concentrations, limiting them in spatial resolution, and restricting the research to larger rodents. We developed an intracochlear pharmacokinetic model based on an imaging, learning-prediction (LP) paradigm for learning transport parameters in the murine cochlea. This was achieved using noninvasive micro-computed tomography imaging of the cochlea during in vivo infusion of a contrast agent at the basal end of scala tympani through a cochleostomy. Each scan was registered in 3-D to a cochlear atlas to segment the cochlear regions with high accuracy, enabling concentrations to be extracted along the length of each scala. These spatio-temporal concentration profiles were used to learn a concentration dependent diffusion coefficient, and transport parameters between the major scalae and to clearance. The LP model results are comparable to the current state of the art model, and can simulate concentrations for cases involving different infusion molecules and different drug delivery protocols. Forward simulation results with pulsatile delivery suggest the pharmacokinetic model can be used to optimize drug delivery protocols to reduce total drug delivered and the potential for toxic side effects. While developed in the challenging murine cochlea, the processes are scalable to larger animals and different drug infusion paradigms.

Magnetic Field Patterning of Nickel Nanowire Film Realized by Printed Precursor Inks.

This paper demonstrates an easily prepared novel material and approach to producing aligned nickel (Ni) nanowires having unique and customizable structures on a variety of substrates for electronic and magnetic applications. This is a new approach to producing printed metallic Ni structures from precursor materials, and it provides a novel technique for nanowire formation during reduction. This homogeneous solution can be printed in ambient conditions, and it forms aligned elemental Ni nanowires over large areas upon heating in the presence of a magnetic field. The use of templates or subsequent purification are not required. This technique is very flexible, and allows the preparation of unique patterns of nanowires which provides opportunities to produce structures with enhanced anisotropic electrical and magnetic properties. An example of this is the unique fabrication of aligned nanowire grids by overlaying layers of nanowires oriented at different angles with respect to each other. The resistivity of printed and cured films was found to be as low as 560 µΩ∙cm. The saturation magnetization was measured to be 30 emu∙g-1, which is comparable to bulk Ni. Magnetic anisotropy was induced with an axis along the direction of the applied magnetic field, giving soft magnetic properties.

A nanoliter resolution implantable micropump for murine inner ear drug delivery.

Advances in protective and restorative biotherapies have created new opportunities to use site-directed, programmable drug delivery systems to treat auditory and vestibular disorders. Successful therapy development that leverages the transgenic, knock-in, and knock-out variants of mouse models of human disease requires advanced microsystems specifically designed to function with nanoliter precision and with system volumes suitable for implantation. Here we present results for a novel biocompatible, implantable, scalable, and wirelessly controlled peristaltic micropump. The micropump configuration included commercially available catheter microtubing (250 µm OD, 125 µm ID) that provided a biocompatible leak-free flow path while avoiding complicated microfluidic interconnects. Peristaltic pumping was achieved by sequentially compressing the microtubing via expansion and contraction of a thermal phase-change material located in three chambers integrated adjacent to the microtubing. Direct-write micro-scale printing technology was used to build the mechanical components of the micropump around the microtubing directly on the back of a printed circuit board assembly (PCBA). The custom PCBA was fabricated using standard commercial processes providing microprocessor control of actuation and Bluetooth wireless communication through an Android application. The results of in vitro characterization indicated that nanoliter resolution control over the desired flow rates of 10-100 nL/min was obtained by changing the actuation frequency. Applying 10× greater than physiological backpressures and ±â€¯3 °C ambient temperature variation did not significantly affect flow rates. Three different micropumps were tested on six mice for in vivo implantation of the catheter microtubing into the round window membrane niche for infusion of a known ototoxic compound (sodium salicylate) at 50 nL/min for 20 min. Real-time shifts in distortion product otoacoustic emission thresholds and amplitudes were measured during the infusion. There were systematic increases in distortion product threshold shifts during the 20-min perfusions; the mean shift was 15 dB for the most basal region. A biocompatibility study was performed to evaluate material suitability for chronic subcutaneous implantation and clinical translational development. The results indicated that the micropump components successfully passed key biocompatibility tests. A micropump prototype was implanted for one month without development of inflammation or infection. Although tested here on the small murine cochlea, this low-cost design and fabrication methodology is scalable for use in larger animals and for clinical applications in children and adults by appropriate scaling of the microtubing diameter and actuator volume.

In-Home Cardiovascular Monitoring System for Heart Failure: Comparative Study.

BACKGROUND: There is a pressing need to reduce the hospitalization rate of heart failure patients to limit rising health care costs and improve outcomes. Tracking physiologic changes to detect early deterioration in the home has the potential to reduce hospitalization rates through early intervention. However, classical approaches to in-home monitoring have had limited success, with patient adherence cited as a major barrier. This work presents a toilet seat-based cardiovascular monitoring system that has the potential to address low patient adherence as it does not require any change in habit or behavior. OBJECTIVE: The objective of this work was to demonstrate that a toilet seat-based cardiovascular monitoring system with an integrated electrocardiogram, ballistocardiogram, and photoplethysmogram is capable of clinical-grade measurements of systolic and diastolic blood pressure, stroke volume, and peripheral blood oxygenation. METHODS: The toilet seat-based estimates of blood pressure and peripheral blood oxygenation were compared to a hospital-grade vital signs monitor for 18 subjects over an 8-week period. The estimated stroke volume was validated on 38 normative subjects and 111 subjects undergoing a standard echocardiogram at a hospital clinic for any underlying condition, including heart failure. RESULTS: Clinical grade accuracy was achieved for all of the seat measurements when compared to their respective gold standards. The accuracy of diastolic blood pressure and systolic blood pressure is 1.2 (SD 6.0) mm Hg (N=112) and -2.7 (SD 6.6) mm Hg (N=89), respectively. Stroke volume has an accuracy of -2.5 (SD 15.5) mL (N=149) compared to an echocardiogram gold standard. Peripheral blood oxygenation had an RMS error of 2.3% (N=91). CONCLUSIONS: A toilet seat-based cardiovascular monitoring system has been successfully demonstrated with blood pressure, stroke volume, and blood oxygenation accuracy consistent with gold standard measures. This system will be uniquely positioned to capture trend data in the home that has been previously unattainable. Demonstration of the clinical benefit of the technology requires additional algorithm development and future clinical trials, including those targeting a reduction in heart failure hospitalizations.

Inkjet Printed Polyethylene Glycol as a Fugitive Ink for the Fabrication of Flexible Microfluidic Systems.

This paper demonstrates a novel and simple processing technique for the realization of scalable and flexible microfluidic microsystems by inkjet-printing polyethylene-glycol (PEG) as a sacrificial template, followed by embedding in a structural layer (e.g. soft elastomers). The printing technology allows production of an array of PEG droplets simultaneously, reducing cost and manufacturing time. The PEG can be removed through heating above its phase-change temperature after the formation of the structural layer, with hydraulic flow removing the material. The developed technique allows easy modulation of the shape and dimensions of the pattern with the ability to generate complex architectures without using lithography. The method produces robust planar and multilayer microfluidic structures that can be realized on wide range of substrates. Moreover, microfluidics can be realized on other systems (e.g. electrodes and transducers) directly without requiring any bonding or assembling steps, which often limit the materials selection in conventional microfluidic fabrication. Multilayer Polydimethylsiloxane (PDMS) microfluidic channels were created using this technique to demonstrate the capability of the concept to realize flexible microfluidic electronics, drug delivery systems, and lab-on-a-chip devices. By utilizing conductive liquid metals (i.e. EGaIn) as the filling material of the channels, flexible passive resistive components and sensors have been realized.

Nontraditional Electrocardiogram and Algorithms for Inconspicuous In-Home Monitoring: Comparative Study.

BACKGROUND: Wearable and connected in-home medical devices are typically utilized in uncontrolled environments and often measure physiologic signals at suboptimal locations. Motion artifacts and reduced signal-to-noise ratio, compared with clinical grade equipment, results in a highly variable signal quality that can change significantly from moment to moment. The use of signal quality classification algorithms and robust feature delineation algorithms designed to achieve high accuracy on poor quality physiologic signals can prove beneficial in addressing concerns associated with measurement accuracy, confidence, and clinical validity. OBJECTIVE: The objective of this study was to demonstrate the successful extraction of clinical grade measures using a custom signal quality classification algorithm for the rejection of poor-quality regions and a robust QRS delineation algorithm from a nonstandard electrocardiogram (ECG) integrated into a toilet seat; a device plagued by many of the same challenges as wearable technologies and other Internet of Things-based medical devices. METHODS: The present algorithms were validated using a study of 25 normative subjects and 29 heart failure (HF) subjects. Measurements captured from a toilet seat-based buttocks electrocardiogram were compared with a simultaneously captured 12-lead clinical grade ECG. The ECG lead with the highest morphological correlation to buttocks electrocardiogram was used to determine the accuracy of the heart rate (HR), heart rate variability (HRV), which used the standard deviation of the normal-to-normal (SDNN) intervals between sinus beats, QRS duration, and the corrected QT interval (QTc). These algorithms were benchmarked using the MIT-BIH Arrhythmia Database (MITDB) and European ST-T Database (EDB), which are standardized databases commonly used to test QRS detection algorithms. RESULTS: Clinical grade accuracy was achieved for all buttocks electrocardiogram measures compared with standard Lead II. For the normative cohort, the mean was -0.0 (SD 0.3) bpm (N=141 recordings) for HR accuracy and -1.0 (SD 3.4) ms for HRV (N=135). The QRS duration and the QTc interval had an accuracy of -0.5 (SD 6.6) ms (N=85) and 14.5 (SD 11.1) ms (N=85), respectively. In the HF cohort, the accuracy for HR, HRV, QRS duration, and QTc interval was 0.0 (SD 0.3) bpm (N=109), -6.6 (SD 13.2) ms (N=99), 2.9 (SD 11.5) ms (N=59), and 11.2 (SD 19.1) ms (N=58), respectively. When tested on MITDB and EDB, the algorithms presented herein had an overall sensitivity and positive predictive value of over 99.82% (N=900,059 total beats), which is comparable to best in-class algorithms tuned specifically for use with these databases. CONCLUSIONS: The present algorithmic approach to data analysis of noisy physiologic data was successfully demonstrated using a toilet seat-based ECG remote monitoring system. This approach to the analysis of physiologic data captured from wearable and connected devices has future potential to enable new types of monitoring devices, providing new insights through daily, inconspicuous in-home monitoring.

Early uneven ear input induces long-lasting differences in left-right motor function.

How asymmetries in motor behavior become established normally or atypically in mammals remains unclear. An established model for motor asymmetry that is conserved across mammals can be obtained by experimentally inducing asymmetric striatal dopamine activity. However, the factors that can cause motor asymmetries in the absence of experimental manipulations to the brain remain unknown. Here, we show that mice with inner ear dysfunction display a robust left or right rotational preference, and this motor preference reflects an atypical asymmetry in cortico-striatal neurotransmission. By unilaterally targeting striatal activity with an antagonist of extracellular signal-regulated kinase (ERK), a downstream integrator of striatal neurotransmitter signaling, we can reverse or exaggerate rotational preference in these mice. By surgically biasing vestibular failure to one ear, we can dictate the direction of motor preference, illustrating the influence of uneven vestibular failure in establishing the outward asymmetries in motor preference. The inner ear-induced striatal asymmetries identified here intersect with non-ear-induced asymmetries previously linked to lateralized motor behavior across species and suggest that aspects of left-right brain function in mammals can be ontogenetically influenced by inner ear input. Consistent with inner ear input contributing to motor asymmetry, we also show that, in humans with normal ear function, the motor-dominant hemisphere, measured as handedness, is ipsilateral to the ear with weaker vestibular input.

Improved Blood Pressure Prediction Using Systolic Flow Correction of Pulse Wave Velocity.

Hypertension is a significant worldwide health issue. Continuous blood pressure monitoring is important for early detection of hypertension, and for improving treatment efficacy and compliance. Pulse wave velocity (PWV) has the potential to allow for a continuous blood pressure monitoring device; however published studies demonstrate significant variability in this correlation. In a recently presented physics-based mathematical model of PWV, flow velocity is additive to the classic pressure wave as estimated by arterial material properties, suggesting flow velocity correction may be important for cuff-less non-invasive blood pressure measures. The present study examined the impact of systolic flow correction of a measured PWV on blood pressure prediction accuracy using data from two published in vivo studies. Both studies examined the relationship between PWV and blood pressure under pharmacological manipulation, one in mongrel dogs and the other in healthy adult males. Systolic flow correction of the measured PWV improves the R2 correlation to blood pressure from 0.51 to 0.75 for the mongrel dog study, and 0.05 to 0.70 for the human subjects study. The results support the hypothesis that systolic flow correction is an essential element of non-invasive, cuff-less blood pressure estimation based on PWV measures.

A physics based approach to the pulse wave velocity prediction in compliant arterial segments.

Pulse wave velocity (PWV) quantification commonly serves as a highly robust prognostic parameter being used in a preventative cardiovascular therapy. Being dependent on arterial elastance, it can serve as a marker of cardiovascular risk. Since it is influenced by a blood pressure (BP), the pertaining theory can lay the foundation in developing a technique for noninvasive blood pressure measurement. Previous studies have reported application of PWV, measured noninvasively, for both the estimation of arterial compliance and blood pressure, based on simplified physical or statistical models. A new theoretical model for pulse wave propagation in a compliant arterial segment is presented within the framework of pseudo-elastic deformation of biological tissue undergoing finite deformation. An essential ingredient is the dependence of results on nonlinear aspects of the model: convective fluid phenomena, hyperelastic constitutive relation, large deformation and a longitudinal pre-stress load. An exact analytical solution for PWV is presented as a function of pressure, flow and pseudo-elastic orthotropic parameters. Results from our model are compared with published in-vivo PWV measurements under diverse physiological conditions. Contributions of each of the nonlinearities are analyzed. It was found that the totally nonlinear model achieves the best match with the experimental data. To retrieve individual vascular information of a patient, the inverse problem of hemodynamics is presented, calculating local orthotropic hyperelastic properties of the arterial wall. The proposed technique can be used for non-invasive assessment of arterial elastance, and blood pressure using direct measurement of PWV, with account of hyperelastic orthotropic properties.

Towards an Implantable, Low Flow Micropump That Uses No Power in the Blocked-Flow State.

Low flow rate micropumps play an increasingly important role in drug therapy research. Infusions to small biological structures and lab-on-a-chip applications require ultra-low flow rates and will benefit from the ability to expend no power in the blocked-flow state. Here we present a planar micropump based on gallium phase-change actuation that leverages expansion during solidification to occlude the flow channel in the off-power state. The presented four chamber peristaltic micropump was fabricated with a combination of Micro Electro Mechanical System (MEMS) techniques and additive manufacturing direct write technologies. The device is 7 mm × 13 mm × 1 mm (<100 mm³) with the flow channel and exterior coated with biocompatible Parylene-C, critical for implantable applications. Controllable pump rates from 18 to 104 nL/min were demonstrated, with 11.1 ± 0.35 nL pumped per actuation at an efficiency of 11 mJ/nL. The normally-closed state of the gallium actuator prevents flow and diffusion between the pump and the biological system or lab-on-a-chip, without consuming power. This is especially important for implanted applications with periodic drug delivery regimens.

Pulse Wave Velocity Prediction and Compliance Assessment in Elastic Arterial Segments.

Pressure wave velocity (PWV) is commonly used as a clinical marker of vascular elasticity. Recent studies have increased clinical interest in also analyzing the impact of heart rate, blood pressure, and left ventricular ejection time on PWV. In this article we focus on the development of a theoretical one-dimensional model and validation via direct measurement of the impact of ejection time and peak pressure on PWV using an in vitro hemodynamic simulator. A simple nonlinear traveling wave model was developed for a compliant thin-walled elastic tube filled with an incompressible fluid. This model accounts for the convective fluid phenomena, elastic vessel deformation, radial motion, and inertia of the wall. An exact analytical solution for PWV is presented which incorporates peak pressure, ejection time, ejection volume, and modulus of elasticity. To assess arterial compliance, the solution is introduced in an alternative form, explicitly determining compliance of the wall as a function of the other variables. The model predicts PWV in good agreement with the measured values with a maximum difference of 3.0%. The results indicate an inverse quadratic relationship ([Formula: see text]) between ejection time and PWV, with ejection time dominating the PWV shifts (12%) over those observed with changes in peak pressure (2%). Our modeling and validation results both explain and support the emerging evidence that, both in clinical practice and clinical research, cardiac systolic function related variables should be regularly taken into account when interpreting arterial function indices, namely PWV.