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Hypoxia plays a crucial role in cell physiology. Defining the oxygen level that induces cell death within 3D tissues is vital for understanding tissue hypoxia; however, obtaining accurate measurements has been technically challenging. In this study, we introduce a non-invasive, high-throughput methodology to quantify critical survival partial oxygen pressure (pO₂) with high spatial resolution within spheroids by employing a combination of controlled hypoxic conditions, semi-automated live/dead cell imaging, and computational oxygen modeling. The oxygen-permeable, micro-pyramid patterned culture plates created a precisely controlled oxygen condition around the individual spheroid. Live/dead cell imaging provided the geometric information of the live/dead boundary within spheroids. Finally, computational oxygen modeling calculated the pO₂ at the live/dead boundary within spheroids. As proof of concept, we determined the critical survival pO₂ in two types of spheroids: isolated primary pancreatic islets and tumor-derived pseudo-islets (2.43 ± 0.08 vs. 0.84 ± 0.04 mmHg), indicating higher hypoxia tolerance in pseudo-islets due to their tumorigenic origin. We also applied this method for evaluating graft survival in cell transplantations for diabetes therapy, where hypoxia is a critical barrier to successful transplantation outcomes; thus, designing oxygenation strategies is required. Based on the elucidated critical survival pO₂, 100% viability could be maintained in a typically sized primary islet under the tissue pO₂ above 14.5 mmHg. This work presents a valuable tool that is potentially instrumental for fundamental hypoxia research. It offers insights into physiological responses to hypoxia among different cell types and may refine translational research in cell therapies.

The need for maintaining cell-spheroid viability and function within high-density cultures is unmet for various clinical and experimental applications, including cell therapies. One immediate application is for transplantation of pancreatic islets, a clinically recognized treatment option to cure type 1 diabetes; islets are isolated from a donor for subsequent culture prior to transplantation. However, high seeding conditions cause unsolicited fusion of multiple spheroids, thereby limiting oxygen diffusion to induce hypoxic cell death. Here we introduce a culture dish incorporating a micropyramid-patterned surface to prevent the unsolicited fusion and oxygen-permeable bottom for optimal oxygen environment. A 400µm-thick, oxygen-permeable polydimethylsiloxane sheet topped with micropyramid pattern of 400µm-base and 200µm-height was fabricated to apply to the 24-well plate format. The micropyramid pattern separated the individual pancreatic islets to prevent the fusion of multiple islets. This platform supported the high oxygen demand of islets at high seeding density at 260 islet equivalents cm-2, a 2-3-fold higher seeding density compared to the conventional islet culture used in a preparation for the clinical islet transplantations, demonstrating improved islet morphology, metabolism and function in a 4 d-culture. Transplantation of these islets into immunodeficient diabetic mice exhibited significantly improved engraftment to achieve euglycemia compared to islets cultured in the conventional culture wells. Collectively, this simple design modification allows for high-density cultures of three-dimensional cell spheroids to improve the viability and function for an array of investigational and clinical replacement tissues.

ObjectiveAtherosclerosis is a chronic immuno-inflammatory condition emerging in arteries and considered the cause of a myriad of cardiovascular diseases. Atherosclerotic lesion characterization through invasive imaging modalities is essential in disease evaluation and determining intervention strategy. Recently, electrical properties of the lesions have been utilized in assessing its vulnerability mainly owing to its capability to differentiate lipid content existing in the lesion, albeit with limited detection resolution. Electrical impedance tomography is the natural extension of conventional spectrometric measurement by incorporating larger number of interrogating electrodes and advanced algorithm to achieve imaging of target objects and thus provides significantly richer information. It is within this context that we develop Outward Electrical Impedance Tomography (OEIT), aimed at intravascular imaging for atherosclerotic lesion characterization.MethodsWe utilized flexible electronics to establish the 32-electrode OEIT device with outward facing configuration suitable for imaging of vessels. We conducted comprehensive studies through simulation model and ex vivo setup to demonstrate the functionality of OEIT.ResultsQuantitative characterization for OEIT regarding its proximity sensing and conductivity differentiation was achieved using well-controlled experimental conditions. Imaging capability for OEIT was further verified with phantom setup using porcine aorta to emulate in vivo environment.ConclusionWe have successfully demonstrated a novel tool for intravascular imaging, OEIT, with unique advantages for atherosclerosis detection.SignificanceThis study demonstrates for the first time a novel electrical tomography-based platform for intravascular imaging, and we believe it paves the way for further adaptation of OEIT for intravascular detection in more translational settings and offers great potential as an alternative imaging tool for medical diagnosis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson's correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = -0.69, p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.

The elimination of integrated batteries in biomedical implants holds great promise for improving health outcomes in patients with implantable devices. However, despite extensive research in wireless power transfer, achieving efficient power transfer and effective operational range have remained a hindering challenge within anatomical constraints.ObjectiveWe hereby demonstrate an intravascular wireless and batteryless microscale stimulator, designed for (1) low power dissipation via intermittent transmission and (2) reduced fixation mechanical burden via deployment to the anterior cardiac vein (ACV, ∼3.8 mm in diameter).MethodsWe introduced a unique coil design circumferentially confined to a 3 mm diameter hollow-cylinder that was driven by a novel transmitter-based control architecture with improved power efficiency.ResultsWe examined wireless capacity using heterogenous bovine tissue, demonstrating >5 V stimulation threshold with up to 20 mm transmitter-receiver displacement and 20° of misalignment. Feasibility for human use was validated using Finite Element Method (FEM) simulation of the cardiac cycle, guided by pacer phantom-integrated Magnetic Resonance Images (MRI).ConclusionThis system design thus enabled sufficient wireless power transfer in the face of extensive stimulator miniaturization.SignificanceOur successful feasibility studies demonstrated the capacity for minimally invasive deployment and low-risk fixation.

Large‐area graphene is typically synthesized on rolled‐annealed copper foils, which require transferring to other substrates for applications. This study examines large‐area graphene growth on electrodeposited (ED) copper foils—used in lithium‐ion batteries and printed circuit boards—via plasma‐enhanced chemical vapor deposition (PECVD). It reveals that, for a set plasma power, a minimum growth time ensures full graphene coverage, leading to monolayer and then multilayer graphene, showing PECVD growth on ED copper is not self‐limited. The process also beneficially modifies the ED copper substrate, like removing the surface zinc layer and changing copper grain size and orientation, thus improving graphene growth. Additionally, the study includes high‐frequency scattering parameter (S‐parameter) measurements in a coplanar waveguide (CPW) system. This involves graphene on a sapphire substrate with a silver electrode. The S‐parameter data indicate that the CPW with graphene shows reduced insertion losses in high‐frequency circuits compared to those without graphene. This underscores graphene's role in reducing insertion losses between metallic and dielectric layers in high‐frequency settings, offering valuable insights for industrial and technological applications. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements.Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²).Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome.

Blood viscosity provides the rheological basis to elucidate shear stress underlying developmental cardiac mechanics and physiology. Zebrafish is a high throughput model for developmental biology, forward-genetics, and drug discovery. The micro-scale posed an experimental challenge to measure blood viscosity. To address this challenge, a microfluidic viscometer driven by surface tension was developed to reduce the sample volume required (3μL) for rapid (500 s-1), at which the power law exponent (n) of zebrafish blood was nearly 1 behaving as a Newtonian fluid. The measured values of whole blood from the micro-channel (4.17cP) and the vacuum method (4.22cP) at 500 s-1 were closely correlated at 27 °C. A calibration curve was established for viscosity as a function of hematocrits to predict a rise and fall in viscosity during embryonic development. Thus, our rapid capillary pressure-driven micro-channel revealed the Newtonian fluid behavior of zebrafish blood at high shear rates and the dynamic viscosity during development.

We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes.

Plaque rupture causes acute coronary syndromes and stroke. Intraplaque oxidized low density lipoprotein (oxLDL) is metabolically unstable and prone to induce rupture. We designed an intravascular ultrasound (IVUS)-guided electrochemical impedance spectroscopy (EIS) sensor to enhance the detection reproducibility of oxLDL-laden plaques. The flexible 2-point micro-electrode array for EIS was affixed to an inflatable balloon anchored onto a co-axial double layer catheter (outer diameter = 2 mm). The mechanically scanning-driven IVUS transducer (45 MHz) was deployed through the inner catheter (diameter = 1.3 mm) to the acoustic impedance matched-imaging window. Water filled the inner catheter to match acoustic impedance and air was pumped between the inner and outer catheters to inflate the balloon. The integrated EIS and IVUS sensor was deployed into the ex vivo aortas dissected from the fat-fed New Zealand White (NZW) rabbits (n=3 for fat-fed, n= 5 normal diet). IVUS imaging was able to guide the 2-point electrode to align with the plaque for EIS measurement upon balloon inflation. IVUS-guided EIS signal demonstrated reduced variability and increased reproducibility (p < 0.0001 for magnitude, p < 0.05 for phase at < 15 kHz) as compared to EIS sensor alone (p < 0.07 for impedance, p < 0.4 for phase at < 15 kHz). Thus, we enhanced topographic and EIS detection of oxLDL-laden plaques via a catheter-based integrated sensor design to enhance clinical assessment for unstable plaque.

Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 µm in diameter and separated by 400 µm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy.

Epidural electrostimulation has shown promise for spinal cord injury therapy. However, finding effective stimuli on the multi-electrode stimulating arrays employed requires a laborious manual search of a vast space for each patient. Widespread clinical application of these techniques would be greatly facilitated by an autonomous, algorithmic system which choses stimuli to simultaneously deliver effective therapy and explore this space. We propose a method based on GP-BUCB, a Gaussian process bandit algorithm. In n = 4 spinally transected rats, we implant epidural electrode arrays and examine the algorithm's performance in selecting bipolar stimuli to elicit specified muscle responses. These responses are compared with temporally interleaved intra-animal stimulus selections by a human expert. GP-BUCB successfully controlled the spinal electrostimulation preparation in 37 testing sessions, selecting 670 stimuli. These sessions included sustained autonomous operations (ten-session duration). Delivered performance with respect to the specified metric was as good as or better than that of the human expert. Despite receiving no information as to anatomically likely locations of effective stimuli, GP-BUCB also consistently discovered such a pattern. Further, GP-BUCB was able to extrapolate from previous sessions' results to make predictions about performance in new testing sessions, while remaining sufficiently flexible to capture temporal variability. These results provide validation for applying automated stimulus selection methods to the problem of spinal cord injury therapy.

Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this chapter, we outline the use of a multisite electrode array in the spinal rat model to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats. The results demonstrate that spinal rats can stand and step when the spinal cord is stimulated tonically via electrodes located at specific sites on the spinal cord. The quality of stepping and standing was dependent on the location of the electrodes on the spinal cord, the specific stimulation parameters, and the orientation of the cathode and anode. The spinal motor evoked potentials in selected muscles during standing and stepping are shown to be critical tools to study selective activation of interneuronal circuits via responses of varying latencies. The present results provide further evidence that the assessment of functional networks in the background of behaviorally relevant functional states is likely to be a physiological tool of considerable importance in developing strategies to facilitate recovery of motor function after a number of neuromotor disorders.

Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrate the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display an electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights into long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients. © 2014 the Partner Organisations.

Flexible electronics have enabled catheter-based intravascular sensing. However, real-time interrogation of unstable plaque remains an unmet clinical challenge. Here, we demonstrate the feasibility of stretchable electrochemical impedance spectroscopy (EIS) sensors for endoluminal investigations in New Zealand White (NZW) rabbits on diet-induced hyperlipidemia. A parylene C (PAC)-based EIS sensor mounted on the surface of an inflatable silicone balloon affixed to the tip of an interrogating catheter was deployed (1) on the explants of NZW rabbit aorta for detection of lipid-rich atherosclerotic lesions, and (2) on live animals for demonstration of balloon inflation and EIS measurements. An input peak-to-peak AC voltage of 10 mV and sweeping-frequency from 300 kHz to 100 Hz were delivered to the endoluminal sites. Balloon inflation allowed EIS sensors to be in contact with endoluminal surface. In the oxidized low-density-lipoprotein (oxLDL)-rich lesions from explants of fat-fed rabbits, impedance magnitude increased significantly by 1.5-fold across the entire frequency band, and phase shifted ~5° at frequencies below 10 kHz. In the lesion-free sites of the normal diet-fed rabbits, impedance magnitude increased by 1.2-fold and phase shifted ~5° at frequencies above 30 kHz. Thus, we demonstrate the feasibility of stretchable intravascular EIS sensors for identification of lipid rich lesions, with a translational implication for detecting unstable lesions.

Abstract Background Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. Methods We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1–100 Hz and 1–10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. Results In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Conclusions Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles.

Although many sensors (e.g., temperature, light level, acceleration, etc.) that are compatible with sensor networks (i.e., sensitive, small, low power, etc.) are now commercially available, two important classes of sensors are not as technologically mature and remain an area of active research: chemical sensors and biological sensors. The sensor-technology-development efforts in the CENS center are focused on these very challenging classes of sensors. Successful development of chemical and biological sensors will enable wireless-sensor-network technology to span the full range of possible classes of measurements. In addition to better performance, the technological emphases are miniaturization and automation of the developed sensors. Specific sensor-technology-development efforts include: (1) amperometric and potentiometric electrochemical sensors for monitoring nitrate-ion detection in ground water; (2) lab-on-a-chip aquatic microorganism analysis system; and (3) ultra sensitive field operational sensor for marine environmental monitoring.

This is a project that aims to expedite research in marine biology using chip-based and state-of-the-art detection technology. The project is a joint effort that will incorporate the expertise of three different groups, Dr. Chih-Ming Ho at UCLA, Dr. David Caron at USC and Dr. Yu-Chong Tai at Caltech. One main focus of the project is to develop Lab-on-a-chip devices that reduce total sample volume and detection time. Also, the chips can be fabricated in large quantities with minimal cost so many experiments can be run in parallel. Here at Caltech, a chip will be developed to culture a small number of algae and screen for factors inducing toxin production. Algal bloom and toxins produced by different algae have always caused problems to the environment and marine ecology. Pseudo-nitzschia is one type of algae that produces a neural toxin called Domoic Acid, which when transferred through the food chain causes sickness and mortality in marine mammals and seabirds. However, during Pseudo-nitzschia bloom, Domoic Acid is not always produced. In another word, growth of algae does not equal Domoic Acid production. Studies done by other groups have suggested that many factors (such as trace metal, macronutrient, or ionic concentration) might induce or suppress algae to produce toxin. Yet, exact causes are unclear. To completely elucidate the causes of toxin production, many potential compounds will have to be screened. This leads to an enormous amount of experiments to be performed and large quantity of reagents and cells to be used. To speed up the process of screening for possible factors inducing toxin production, we would like to make a chip to culture Pseudo-nitzschia under different growing conditions. At the same time, an Ultra Sensitive Electrochemical Sensor will be developed for detection of Domoic Acid at Dr. Chih-Ming Ho’s lab at UCLA. The current state-of-the-art detection technology indicates that per cell toxin load may range over 2 or 3 orders of magnitude but its sensitivity is limited since a sample size of at least 100 cells/mL is required. The new sensor will be able to push the sensitivity to 10 cells/mL or to even single molecules of Domoic Acid. This sensor will not only enable the detection of Domoic Acid produced by algae cells inside the culture chip, such sensor will also have the broad application of detecting Domoic Acid from field samples.

We present an integrated method to fabricate 3-D microfluidic networks and fabricated the first on-chip cell culture device with an integrated combinatorial mixer. The combinatorial mixer is designed for screening the combinatorial effects of different compounds on cells. The monolithic fabrication method with parylene C as the basic structural material allows us to avoid wafer bonding and achieves precise alignment between microfluidic channels. As a proof-of-concept, we fabricated a device with a three-input combinatorial mixer and demonstrated that the mixer can produce all the possible combinations. Also, we demonstrated the ability to culture cells on-chip and performed a simple cell assay on-chip using trypan blue to stain dead cells.

The exponential progress of technology development, driven in many cases by Moore’s Law, has enabled the combination of sensing, computation and wireless communication in small, low-power devices that can be embedded directly in the physical environment. Recent research has resulted in several new classes of embedded networked sensing systems that can be rapidly distributed in the environment to study phenomena with unprecedented detail. Embedded networked sensing systems are transforming the way in which physical, biological and chemical changes are detected and quantified. These results are leading to new mechanistic understanding of the environment and, consequently, to new models and predictions for better assessment and management of environmental challenges.This white paper describes the emerging technologies used in distributed sensing systems and the opportunities these systems present for environmental management, and in particular, water quality protection. A team of faculty, students, and staff at the Center for Embedded Networked Sensing (CENS) wrote the report. CENS is a National Science Foundation sponsored Science and Technology Center, headquartered at the University of California, Los Angeles (UCLA). In addition to UCLA, the California Institute of Technology, the Riverside and Merced campuses of the University of California, and the University of Southern California are partners in the center. CENS is developing embedded networked sensing systems and applying this technology to critical scientific and social applications. The Foresight and Governance Project at the Woodrow Wilson International Center for Scholars edited and finalized this document for the U.S. Environmental Protection Agency’s Office of Water.This paper first briefly describes the potential applications of sensing systems to four common water quality management problems. This potential includes: (1) providing early warning for septic systems, (2) allowing for the trading of credits for non-point source runoff, (3) monitoring beach water quality, and (4) management of combined sewer overflows. Section 4 describes these scenarios in further detail.Section 1 provides an overview of sensors (i.e., the devices that convert environmental phenomena into an electronic response) and actuators (i.e., the devices that convert electrical signals into mechanical responses). Sensors have the potential to detect physical, chemical, biological, and radiation properties in the environment. A variety of sensors is currently available for networked environmental sensing, while others are still in early research and development phases. Physical sensors for water quality monitoring are generally the most field-ready and scalable to distributed applications, followed by chemical and then biological sensors. The costs for these sensors depend on the physical, chemical, or biological parameter of interest. Indicator sensors and event-triggering sampling can be used when direct detection sensors are not ready for field deployment. To more extensively detect environmental properties, even more sophisticated sensors and sensing strategies are needed, including: (1) hardening novel sensors types (such as lab-on-a-chip technology) to withstand harsh conditions for extended periods, and (2) devising integrated sensing systems for higher order observations, such as quantifying materials fluxes in the environment.Section 2 on Deployment Platforms discusses three new sensing system classes: static, mobile robotic, and mobile handheld. These sensing systems differ from traditional measurement systems in that sensors are attached to wireless radios that enable real-time communication of the data collected. For any particular situation, the best system class to use depends on the environment’s spatial and temporal variation. Among the three classes of sensing systems, mobile handheld systems are best used when the environmental phenomena of interest cover a broad area and do not require great spatial resolution. Static sensing systems are best used over smaller areas when high spatial resolution is not required, and mobile robotic systems are appropriate for intensive measurement of very small areas. To improve overall sensing efficiency (e.g., time or cost), adaptive sampling allows the system to dynamically adjust its measurement location or frequency to meet spatial or temporal variation in the environment. Sensing platforms can also be combined such that different platforms can provide information at different scales. This type of multi-scale system can also often help improve the efficiency of a monitoring effort. Despite the opportunities these sensing systems present, the ability to deploy them in the field can be limited by power availability and faults that interfere with communication or sensing hardware.To help address some of the challenges facing the effective implementation of sensing systems and the interpretation of the acquired data, section 3 discusses the usefulness of considering the entire “life cycle” of data in a sensing system. This life cycle consists of three distinct phases: design and deployment of the observing system; operation and monitoring; and analysis, modeling and data sharing.The final section of the report offers recommendations for future research. In spite of the substantial success in research and development activities that has given rise to existing sensing systems, relatively few have been deployed in real-world applications. The time is ripe to expand the range of applications where embedded sensing systems are used. Some of the key recommendations outlined in section 5 for novel uses of embedded sensing systems include: Sensors and Actuators • (1) Long-term research and development for sensors where new or improved detection methods are needed and (2) short-term market incentives targeted at moving already well-developed sensing technology from research prototypes (e.g., biological and chemical sensors) to commercially available products. • Long-term research to develop detection methods for carbonaceous compounds, heavy metals, large molecular mass molecules such as dissolved organic compounds and dissolved organic nitrogen compounds, pathogenic organisms, biologically-active compounds, biomarkers, and lab-on-achip sensors. • Research on methods to minimize sensor maintenance in the field. • Investments to bring prototype technologies, such as small robust nitrate sensors that can be deployed for long periods, to market in forms suitable for environmental sensing. Deployment Platforms • Investments in a range of pilot studies to determine specific deployment and analysis methodologies for target systems (e.g., septic system or sewage discharge monitoring). • Definition of requirements of large scale uses of the technology to encourage the production of user-friendly systems. The Data Life Cycle • The encouragement of pilot deployments to test and refine data management tasks for specific applications. • Continued research and testing of tools to improve system robustness and ensure high-quality data. • Additional focus on the integration of sensing systems with external data sources and third-party applications, especially map-based visualization with tools for both rigorous GIS techniques and more public friendly web applications. Training • Training at multiple levels (school systems and professional development) to ensure that a ready workforce exists that is prepared to use these new sensing technologies.Embedded networked sensing systems will form a critical infrastructure resource for society—they will monitor and collect information on such diverse subjects as plankton colonies, endangered species, soil and air contaminants, medical patients, and buildings, bridges and other manmade structures. Investments in further research to help bring the sensing technologies discussed in this report into practice will transform the way we monitor and manage the health of our natural resources and predict and respond to crises.

The characterization of atherosclerotic plaques to predict their vulnerability to rupture remains a diagnostic challenge. Despite existing imaging modalities, none have proven their abilities to identify metabolically active oxidized low‐density lipoprotein (oxLDL), a marker of plaque vulnerability. To this end, we developed a machine learning‐directed electrochemical impedance spectroscopy (EIS) platform to analyze oxLDL‐rich plaques, with immunohistology serving as the ground truth. We fabricated the EIS sensor by affixing a six‐point microelectrode configuration onto a silicone balloon catheter and electroplating the surface with platinum black (PtB) to improve the charge transfer efficiency at the electrochemical interface. To demonstrate clinical translation, we deployed the EIS sensor to the coronary arteries of an explanted human heart from a patient undergoing heart transplant and interrogated the atherosclerotic lesions to reconstruct the 3D EIS profiles of oxLDL‐rich atherosclerotic plaques in both right coronary and left descending coronary arteries. To establish effective generalization of our methods, we repeated the reconstruction and training process on the common carotid arteries of an unembalmed human cadaver specimen. Our findings indicated that our DenseNet model achieves the most reliable predictions for metabolically vulnerable plaque, yielding an accuracy of 92.59% after 100 epochs of training. [ABSTRACT FROM AUTHOR]

This paper presents the first direct delivery of silica beads into separation columns using bead/photoresist mixture for on-chip Liquid Chromatography (LC) – Electrospray Ionization (ESI) applications. Instead of packing beads into an existing column from off-chip, this new method uses photoresist mixed with surface-functionalized LC silica beads for a modified photolithography (including spin-coat, exposure and development) and parylene-channel process, followed by sacrificial photoresist removal (by acetone) to release the silica beads inside the LC column. The substantiation and validation of this new technique is demonstrated on an LC-ESI chip integrated with particle filters, silica-bead LC column, and electrospray nozzle, which has been tested both physically and chemically.

This paper describes a new method and an analytical model for characterizing the surface energy inside a microchannel using the measurement of the marching velocity of a capillary meniscus. This method is based on the fact that surface tension of a liquid meniscus in a hydrophilic case produces pressure to pull liquid into the channel and the velocity of the meniscus is related to the surface energy. Both Parylene and silicon nitride microchannels with different surface conditions were fabricated to perform the liquid-filling experiments. It is shown that our model agrees well with the data and this is a valid method.

The micromachining technology that emerged in the late 1980s can provide micron-sized sensors and actuators. These micro transducers are able to be integrated with signal conditioning and processing circuitry to form micro-electromechanical-systems (MEMS) that can perform real-time distributed control. This capability opens up a new territory for flow control research. On the other hand, surface effects dominate the fluid flowing through these miniature mechanical devices because of the large surface-to-volume ratio in micron-scale configurations. We need to reexamine the surface forces in the momentum equation. Owing to their smallness, gas flows experience large Knudsen numbers, and therefore boundary conditions need to be modified. Besides being an enabling technology, MEMS also provide many challenges for fundamental flow-science research.