Gregory Kovacs
Professor of Electrical Engineering, Emeritus
Bio
Professor Kovacs' research areas include the development of non-invasive instruments for cardiovascular medicine; sensors for prediction of epileptic seizures; cell-based systems for drug discovery and testing of stem-cell cardiac therapies; titration of medical care via embedded systems; and remote delivery of laboratory electronics education. He teaches hands-on undergraduate courses in analog circuit design and medical instrument design. He is led the initial development of the Bioengineering graduate core curriculum sequence. He has extensive industry experience, including the co-founding of Cepheid, which has shipped more than 25 million DNA diagnostic assays. He has a long history of government service for DARPA, NASA and other agencies. In 2003 he was the Investigation Scientist for the debris team investigating the loss of the space shuttle Columbia and was Director of the Microsystems Technology Office at DARPA from 2008 through 2010.
Academic Appointments
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Emeritus Faculty, Acad Council, Electrical Engineering
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Member, Cardiovascular Institute
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Member, Wu Tsai Neurosciences Institute
Honors & Awards
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Young Investigator (NYI) Award, National Science Foundation (1993)
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Undergraduate Summer Research Award, Natural Sciences and Engineering Research Council of Canada (1982, 1983)
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Hector MacLeod Scholarship in Electrical Engineering, University of British Columbia (1984)
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Peter J. Gingrass, M.D., Memorial Award, Plastic Surgery Research Council (1990)
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Robert N. Noyce Family Faculty Scholar Chair, Stanford (1992-1994)
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Terman Fellow, Stanford (1994-1997)
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University Fellow, Stanford (1996-1998)
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Fellow National, Explorer's Club (2001)
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Fellow, American Institute for Medical and Biological Engineering (2003)
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Group Achievement Award for Columbia Accident Investigation, NASA (2003)
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Thomas V. Jones Faculty Development Scholar, Thomas V. Jones (2003 - 2005)
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Fellow, IEEE (2008)
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Group Achievement Award for Columbia Investigation Medical Forensics, NASA (2008)
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Secretary of Defense Medal for Exceptional Public Service, Department of Defense (2010)
Professional Education
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M.D., Stanford, Medicine (1992)
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Ph.D., Stanford, Electrical Engineering (1990)
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M.S., U.C. Berkeley, Bioengineering (1985)
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B.A.Sc., University of British Columbia, Electrical Engineering (1984)
Current Research and Scholarly Interests
Kovacs is a long-standing member of the Defense Sciences Research Council (DARPA), and has served as Associate Chair and Chairman. He also has extensive industry experience including co-founding several companies, including Cepheid in Sunnyvale, CA.
His present research areas include biomedical instruments and sensors, miniaturized spaceflight hardware, and biotechnology. He is the Director of Medical Device Technologies for the Astrobionics Program at the NASA Ames Research Center, and Principal Investigator of the Stanford-NASA National Center for Space Biological Technologies. He helps direct a variety of projects spanning wearable physiologic monitors, biosensor instruments for detection of chemical and biological warfare agents and space biology applications, and free-flyer experiment payloads.
In 2003, he served as the Investigation Scientist for the debris team of the Columbia Accident Investigation Board, having worked for the first four months after the accident at the Kennedy Space Center, Florida. In this role, he carried out physical, photographic, x-ray, chemical and other analyses on selected items from the nearly 90,000 pounds of recovered debris and worked toward understanding the nature of the accident. He currently serves as Engineering/Medical Liason on the Spacecraft Crew Survival Integration Investigation Team (SCSIIT) of the Johnson Space Center.
He is a Fellow of the American Institute for Medical and Biological Engineering. Kovacs is a private pilot, scuba diver, and a Fellow National of the Explorers Club. He was a member of a NASA and National Geographic Society sponsored team that climbed Licancabur volcano (19,734 ft.) on the Chile/Bolivia border in November of 2003, serving as medical, physiologic research, and photography lead. In November of 2004, he served the same role on a return expedition to Licancabur, and carried out medical research and underwater videography in the summit lake.
2023-24 Courses
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Independent Studies (8)
- Bioengineering Problems and Experimental Investigation
BIOE 191 (Aut) - Directed Investigation
BIOE 392 (Aut, Win, Spr, Sum) - Directed Study
BIOE 391 (Aut, Win, Spr, Sum) - Master's Thesis and Thesis Research
EE 300 (Win, Spr, Sum) - Special Studies and Reports in Electrical Engineering
EE 391 (Spr, Sum) - Special Studies and Reports in Electrical Engineering (WIM)
EE 191W (Spr) - Special Studies or Projects in Electrical Engineering
EE 190 (Spr) - Special Studies or Projects in Electrical Engineering
EE 390 (Spr, Sum)
- Bioengineering Problems and Experimental Investigation
All Publications
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Characterisation of electrophysiological conduction in cardiomyocyte co-cultures using co-occurrence analysis
COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING
2013; 16 (2): 185-197
Abstract
Cardiac arrhythmias are disturbances of the electrical conduction pattern in the heart with severe clinical implications. The damage of existing cells or the transplantation of foreign cells may disturb functional conduction pathways and may increase the risk of arrhythmias. Although these conduction disturbances are easily accessible with the human eye, there is no algorithmic method to extract quantitative features that quickly portray the conduction pattern. Here, we show that co-occurrence analysis, a well-established method for feature recognition in texture analysis, provides insightful quantitative information about the uniformity and the homogeneity of an excitation wave. As a first proof-of-principle, we illustrate the potential of co-occurrence analysis by means of conduction patterns of cardiomyocyte-fibroblast co-cultures, generated both in vitro and in silico. To characterise signal propagation in vitro, we perform a conduction analysis of co-cultured murine HL-1 cardiomyocytes and murine 3T3 fibroblasts using microelectrode arrays. To characterise signal propagation in silico, we establish a conduction analysis of co-cultured electrically active, conductive cardiomyocytes and non-conductive fibroblasts using the finite element method. Our results demonstrate that co-occurrence analysis is a powerful tool to create purity-conduction relationships and to quickly quantify conduction patterns in terms of co-occurrence energy and contrast. We anticipate this first preliminary study to be a starting point for more sophisticated analyses of different co-culture systems. In particular, in view of stem cell therapies, we expect co-occurrence analysis to provide valuable quantitative insight into the integration of foreign cells into a functional host system.
View details for DOI 10.1080/10255842.2011.615310
View details for PubMedID 21970595
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Microfluidic impedance cytometer for platelet analysis
LAB ON A CHIP
2013; 13 (4): 722-729
Abstract
We present the design and performance characteristics of a platelet analysis platform based on a microfluidic impedance cytometer. Dielectrophoretic focusing is used to centre cells in a fluid stream, which then forms the core of a two-phase flow (dielectric focusing). This flow then passes between electrodes for analysis by differential impedance spectroscopy at multiple frequencies from 280 kHz to 4 MHz. This approach increases the signal-to-noise ratio relative to a single-phase, unfocused stream, while minimising the shear forces to which the cells are subjected. The percentage of activated platelets before and after passage through the chip was measured using flow cytometry, and no significant change was measured. Measuring the in-phase amplitude at a single frequency is sufficient to distinguish platelets from erythrocytes. Using multi-frequency impedance measurements and discriminant analysis, resting platelets can be discriminated from activated platelets. This multifrequency impedance cytometer therefore allows ready determination of the degree of platelet activation in blood samples.
View details for DOI 10.1039/c2lc40896a
View details for Web of Science ID 000313971300028
View details for PubMedID 23282651
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Extracting respiratory information from seismocardiogram signals acquired on the chest using a miniature accelerometer
PHYSIOLOGICAL MEASUREMENT
2012; 33 (10): 1643-1660
Abstract
Seismocardiography (SCG) is a non-invasive measurement of the vibrations of the chest caused by the heartbeat. SCG signals can be measured using a miniature accelerometer attached to the chest, and are thus well-suited for unobtrusive and long-term patient monitoring. Additionally, SCG contains information relating to both cardiovascular and respiratory systems. In this work, algorithms were developed for extracting three respiration-dependent features of the SCG signal: intensity modulation, timing interval changes within each heartbeat, and timing interval changes between successive heartbeats. Simultaneously with a reference respiration belt, SCG signals were measured from 20 healthy subjects and a respiration rate was estimated using each of the three SCG features and the reference signal. The agreement between each of the three accelerometer-derived respiration rate measurements was computed with respect to the respiration rate derived from the reference respiration belt. The respiration rate obtained from the intensity modulation in the SCG signal was found to be in closest agreement with the respiration rate obtained from the reference respiration belt: the bias was found to be 0.06 breaths per minute with a 95% confidence interval of -0.99 to 1.11 breaths per minute. The limits of agreement between the respiration rates estimated using SCG (intensity modulation) and the reference were within the clinically relevant ranges given in existing literature, demonstrating that SCG could be used for both cardiovascular and respiratory monitoring. Furthermore, phases of each of the three SCG parameters were investigated at four instances of a respiration cycle-start inspiration, peak inspiration, start expiration, and peak expiration-and during breath hold (apnea). The phases of the three SCG parameters observed during the respiration cycle were congruent with existing literature and physiologically expected trends.
View details for DOI 10.1088/0967-3334/33/10/1643
View details for Web of Science ID 000309506400008
View details for PubMedID 22986375
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Noninvasive Measurement of Physiological Signals on a Modified Home Bathroom Scale
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2012; 59 (8): 2137-2143
View details for DOI 10.1109/TBME.2012.2186809
View details for Web of Science ID 000306593000006
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Noninvasive measurement of physiological signals on a modified home bathroom scale.
IEEE transactions on bio-medical engineering
2012; 59 (8): 2137-2143
Abstract
A commercial bathroom scale with both handlebar and footpad electrodes was modified to enable measurement of four physiological signals: the ballistocardiogram (BCG), electrocardiogram (ECG), lower body impedance plethysmogram (IPG), and lower body electromyogram (EMG). The BCG, which describes the reaction of the body to cardiac ejection of blood, was measured using the strain gauges in the scale. The ECG was detected using handlebar electrodes with a two-electrode amplifier. For the lower body IPG, the two electrodes under the subject's toes were driven with an ac current stimulus, and the resulting differential voltage across the heels was measured and demodulated synchronously with the source. The voltage signal from the same two footpad electrodes under the heels was passed through a passive low-pass filter network into another amplifier, and the output was the lower body EMG signal. The signals were measured from nine healthy subjects, and the average signal-to-noise ratio (SNR) while the subjects were standing still was estimated for the four signals as follows: BCG, 7.6 dB; ECG, 15.8 dB; IPG, 10.7 dB. During periods of motion, the decrease in SNR for the BCG signal was found to be correlated to the increase in rms power for the lower body EMG (r = 0.89, p <; 0.01). The EMG could, thus, be used to flag noise-corrupted segments of the BCG, increasing the measurement robustness. This setup could be used for monitoring the cardiovascular health of patients at home.
View details for DOI 10.1109/TBME.2012.2186809
View details for PubMedID 22318479
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High-Frequency Electrical Stimulation of Cardiac Cells and Application to Artifact Reduction
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2012; 59 (5): 1381-1390
Abstract
A novel modality for the electrical stimulation of cardiac cells is described. The technique is based on HF stimulation-burst of HF (1-25 kHz) biphasic square waves-to depolarize the cells and trigger action potentials (APs). HF stimulation was demonstrated in HL-1 cardiomyocyte cultures using microelectrode arrays, and the underlying mechanisms were investigated using single-cell model simulations. Current thresholds for HF stimulation increased at higher frequencies or shorter burst durations, and were typically higher than thresholds for single biphasic pulses. Nonetheless, owing to the decreasing impedance of metal electrodes with increasing frequencies, HF bursts resulted in reduced electrode voltages (up to four fold). Such lowered potentials might be beneficial in reducing the probability of irreversible electrochemical reactions and tissue damage, especially for long-term stimulation. More significantly, stimulation at frequencies higher than the upper limit of the AP power spectrum allows effective artifact reduction by low-pass filtering. Shaping of the burst envelope provides further reduction of the remaining artifact. This ability to decouple extracellular stimulation and recording in the frequency domain allowed detection of APs during stimulation-something previously not achievable to the best of our knowledge.
View details for DOI 10.1109/TBME.2012.2188136
View details for PubMedID 22345525
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Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation
PLOS ONE
2012; 7 (4)
Abstract
Methods for the electrical inhibition of cardiac excitation have long been sought to control excitability and conduction, but to date remain largely impractical. High-amplitude alternating current (AC) stimulation has been known to extend cardiac action potentials (APs), and has been recently exploited to terminate reentrant arrhythmias by producing reversible conduction blocks. Yet, low-amplitude currents at similar frequencies have been shown to entrain cardiac tissues by generation of repetitive APs, leading in some cases to ventricular fibrillation and hemodynamic collapse in vivo. Therefore, an inhibition method that does not lead to entrainment - irrespective of the stimulation amplitude (bound to fluctuate in an in vivo setting) - is highly desirable.We investigated the effects of broader amplitude and frequency ranges on the inhibitory effects of extracellular AC stimulation on HL-1 cardiomyocytes cultured on microelectrode arrays, using both sinusoidal and square waveforms. Our results indicate that, at sufficiently high frequencies, cardiac tissue exhibits a binary response to stimulus amplitude with either prolonged APs or no effect, thereby effectively avoiding the risks of entrainment by repetitive firing observed at lower frequencies. We further demonstrate the ability to precisely define reversible local conduction blocks in beating cultures without influencing the propagation activity in non-blocked areas. The conduction blocks were spatiotemporally controlled by electrode geometry and stimuli duration, respectively, and sustainable for long durations (300 s).Inhibition of cardiac excitation induced by high-frequency AC stimulation exhibits a binary response to amplitude above a threshold frequency, enabling the generation of reversible conduction blocks without the risks of entrainment. This inhibition method could yield novel approaches for arrhythmia modeling in vitro, as well as safer and more efficacious tools for in vivo cardiac mapping and radio-frequency ablation guidance applications.
View details for DOI 10.1371/journal.pone.0036217
View details for Web of Science ID 000305340200050
View details for PubMedID 22558389
View details for PubMedCentralID PMC3340354
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Preliminary Results from BCG and ECG Measurements in the Heart Failure Clinic
34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS)
IEEE. 2012: 3780–3783
Abstract
We report on the preliminary deployment of a bathroom scale-based ballistocardiogram (BCG) system for the in-hospital monitoring of patients with heart failure. These early trials provided valuable insights into the challenges and opportunities for such monitoring. In particular, the need for robust algorithms and adapted BCG metric is suggested. The system was designed to be robust and user-friendly, with dual ballistocardiogram (BCG) and electrocardiogram (ECG) capabilities. The BCG was measured from a modified bathroom scale, while the ECG (used as timing reference) was measured using dry handlebar electrodes. The signal conditioning and digitization circuits were USB-powered, and data acquisition performed using a netbook. Four patients with a NYHA class III at admission were measured daily for the duration of their treatment at Stanford hospital. A measure of BCG quality, in essence a quantitative implementation of the BCG classes originally defined in the 1950s, is proposed as a practical parameter.
View details for Web of Science ID 000313296504002
View details for PubMedID 23366751
- Microfluidic platelet analysis platform based on impedance spectroscopy 2012
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Determination of low bacterial concentrations in hyperarid Atacama soils: comparison of biochemical and microscopy methods with real-time quantitative PCR
CANADIAN JOURNAL OF MICROBIOLOGY
2011; 57 (11): 953-963
Abstract
Hyperarid Atacama soils are reported to contain significantly reduced numbers of microbes per gram of soil relative to soils from other environments. Molecular methods have been used to evaluate microbial populations in hyperarid Atacama soils; however, conflicting results across the various studies, possibly caused by this low number of microorganisms and consequent biomass, suggest that knowledge of expected DNA concentrations in these soils becomes important to interpreting data from any method regarding microbial concentrations and diversity. In this paper we compare the number of bacteria per gram of Atacama Desert soils determined by real-time quantitative polymerase chain reaction with the number of bacteria estimated by the standard methods of phospholipids fatty acid analysis, adenine composition (determined by liquid chromatography - time-of-flight mass spectrometry), and SYBR-green microscopy. The number determined by real-time quantitative polymerase chain reaction as implemented in this study was several orders of magnitude lower than that determined by the other three methods and probably underestimates the concentrations of soil bacteria, most likely because of soil binding during the DNA extraction methods. However, the other methods very possibly overestimate the bacteria concentrations owing to desiccated, intact organisms, which would stain positive in microscopy and preserve both adenine and phospholipid fatty acid for the other methods.
View details for DOI 10.1139/W11-091
View details for Web of Science ID 000298015800010
View details for PubMedID 22035208
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Rapid Assessment of Cardiac Contractility on a Home Bathroom Scale
IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
2011; 15 (6): 864-869
Abstract
Analyzing systolic time intervals-specifically the preejection-period (PEP)-is widely accepted as one of the few methods for the noninvasive assessment of cardiac contractility. In this paper, we investigated the ballistocardiogram (BCG) as a way to noninvasively measure myocardial contractility when combined with the ECG. Specifically, we derived a parameter from the BCG and ECG that we hypothesized would be highly correlated to PEP. This is the time delay between the J-wave peak of the BCG and the R-wave of the ECG, which we refer to as the RJ interval. The RJ interval was correlated to PEP (r(2) = 0.86) for 2126 heartbeats across ten subjects, with a y-intercept of 138 ms and slope of 1.05. This suggests that the RJ interval can be reliably used as a noninvasive assessment of cardiac contractility.
View details for DOI 10.1109/TITB.2011.2161998
View details for Web of Science ID 000297355000008
View details for PubMedID 21843998
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A portable system for monitoring the behavioral activity of Drosophila
JOURNAL OF NEUROSCIENCE METHODS
2011; 202 (1): 45-52
Abstract
We describe a low-cost system for monitoring the behavioral activity of the fruit fly, Drosophila melanogaster. The system is readily adaptable to one or more cameras for simultaneous recordings of behavior from different angles and can be used for monitoring multiple individuals in a population at the same time. Signal processing allows discriminating between active and inactive periods during locomotion or flying, and quantification of subtler movements related to changes in position of the wings or legs. The recordings can be taken continuously over long periods of time and can thus provide information about the dynamics of a population. The system was used to monitor responses to caffeine, changes in temperature and g-force, and activity in a variable size population.
View details for DOI 10.1016/j.jneumeth.2011.08.039
View details for Web of Science ID 000296414900006
View details for PubMedID 21907735
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Automatic detection of motion artifacts in the ballistocardiogram measured on a modified bathroom scale
MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING
2011; 49 (2): 213-220
Abstract
Ballistocardiography (BCG) is a non-invasive technique used to measure the ejection force of blood into the aorta which can be used to estimate cardiac output and contractility change. In this work, a noise sensor was embedded in a BCG measurement system to detect excessive motion from standing subjects. For nine healthy subjects, the cross-correlation of the motion signal to the BCG noise--estimated using a simultaneously acquired electrocardiogram and statistics of the BCG signal--was found to be 0.94 and 0.87, during periods of standing still and with induced motion artifacts, respectively. In a separate study, where 35 recordings were taken from seven subjects, a threshold-based algorithm was used to flag motion-corrupted segments of the BCG signal using only the auxiliary motion sensor. Removing these flagged segments enhanced the BCG signal-to-noise ratio (SNR) by an average of 14 dB (P < 0.001). This integrated motion-sensing technique addresses a gap in methods available to identify and remove noise in standing BCG recordings due to movement, in a practical manner that does not require user intervention or obtrusive sensing.
View details for DOI 10.1007/s11517-010-0722-y
View details for Web of Science ID 000286835100009
View details for PubMedID 21153058
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Multi-Signal Electromechanical Cardiovascular Monitoring on a Modified Home Bathroom Scale
33rd Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS)
IEEE. 2011: 2472–2475
Abstract
A commercially available bathroom scale was modified to enable unobtrusive and robust cardiovascular monitoring in the home. Handlebar electrodes were interfaced to an ultra-low power, two-electrode electrocardiogram (ECG) acquisition circuit providing consistent and clean heartbeat timing information. In addition, the footpad electrodes were used to detect lower-body electromyogram (EMG) and lower-body impedance plethysmogram (IPG) signals using two parallel circuits. The lower-body EMG signal was used as an indication of excessive motion of the subject on the scale. The lower-body IPG signal is related to blood flow through the legs, and will be investigated further in future studies. Finally, the component of bodyweight that varies with time--the ballistocardiogram (BCG) signal--was amplified from the existing strain gauges built into the scale. A preliminary validation was completed on five healthy subjects of varying sizes. The average signal-to-noise ratio (SNR) values computed over all five subjects for the ECG, IPG, and BCG signals were 17.2, 12.0, and 9.0 dB, respectively.
View details for Web of Science ID 000298810002053
View details for PubMedID 22254842
- Ballistocardiography – A method worth revisiting 2011
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Ballistocardiography - A Method Worth Revisiting
33rd Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS)
IEEE. 2011: 4279–4282
Abstract
The field of ballistocardiography seems to be enjoying a recent resurgence, most notably through the development of novel technologies and signal processing methods for measurement and analysis. After the method almost vanished in the late 80's and 90's, it is reasonable to wonder what is different this time, and if the technique has now more chances of becoming what its pioneer always wanted - a widespread clinical tool. This paper is an effort to compare and contrast this novel wave of research (notably in the context of the authors' own work). It also suggests that the new approaches have several key differences with past embodiments that place them in a good position to address some specific issues such as cardiac resynchronization therapy device optimization or congestive heart failure monitoring. This optimism is largely fed by the recent technological advances enabling the measurement of the BCG unobtrusively, frequently, at home or in a hospital, and by a re-focus on monitoring and trending applications.
View details for Web of Science ID 000298810003154
View details for PubMedID 22255285
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Evaluating the Lower-Body Electromyogram Signal Acquired From the Feet As a Noise Reference for Standing Ballistocardiogram Measurements
IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
2010; 14 (5): 1188-1196
Abstract
The ballistocardiogram (BCG) is a measure of the reaction force of the body to cardiac ejection of blood. A variety of systems can be used for BCG detection, including beds, tables, chairs, and weighing scales. Weighing scales, in particular, have several practical advantages over the alternatives: low cost, small size, unobtrusiveness, and familiarity to the user; one disadvantage is that the subject must stand during the recording, rather than sit or lay supine, resulting in a higher susceptibility to motion artifacts in the measured signal. This paper evaluates the electromyogram (EMG) signal acquired from the feet of the subject during BCG recording as a noise reference for standing BCG measurements. As a subject moves while standing on the scale, muscle contractions in the feet are detected by the EMG signal, and used to flag segments of the BCG signal that are corrupted by elevated noise. For the purposes of evaluating this method, estimates of the BCG noise-to-signal ratio (NSR) were independently calculated with an ensemble average method, using the R-wave of a simultaneously-acquired chest ECG as a timing reference. The linear correlation between EMG power alone and BCG NSR from 14 subjects was found to be moderate ( r = 0.58, F-statistic p -value 0.05); combined with body-mass index (BMI), multiple linear regression yielded a stronger correlation ( r = 0.73, F -statistic p-value = 0.01). Additionally, an example usage of the lower-leg EMG for improving BCG measurement robustness is provided.
View details for DOI 10.1109/TITB.2010.2044185
View details for Web of Science ID 000282474800007
View details for PubMedID 20371416
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A Device for Separated and Reversible Co-Culture of Cardiomyocytes
BIOTECHNOLOGY PROGRESS
2010; 26 (4): 1164-1171
Abstract
A novel technique is introduced for patterning and controllably merging two cultures of adherent cells on a microelectrode array (MEA) by separation with a removable physical barrier. The device was first demonstrated by separating two cardiomyocyte populations, which upon merging synchronized electrical activity. Next, two applications of this co-culture device are presented that demonstrate its flexibility as well as outline different metrics to analyze co-cultures. In a differential assay, the device contained two distinct cell cultures of neonatal wild-type and beta-adrenergic receptor (beta-AR) knockout cardiomyocytes and simultaneously exposed them with the beta-AR agonist isoproterenol. The beat rate and action potential amplitude from each cell type displayed different characteristic responses in both unmerged and merged states. This technique can be used to study the role of beta-receptor signaling and how the corresponding cellular response can be modulated by neighboring cells. In the second application, action potential propagation between modeled host and graft cell cultures was shown through the analysis of conduction velocity across the MEA. A co-culture of murine cardiomyocytes (host) and murine skeletal myoblasts (graft) demonstrated functional integration at the boundary, as shown by the progression of synchronous electrical activity propagating from the host into the graft cell populations. However, conduction velocity significantly decreased as the depolarization waves reached the graft region due to a mismatch of inherent cell properties that influence conduction.
View details for DOI 10.1002/btpr.431
View details for PubMedID 20730771
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A low-noise ac-bridge amplifier for ballistocardiogram measurement on an electronic weighing scale
PHYSIOLOGICAL MEASUREMENT
2010; 31 (7): N51-N59
Abstract
Ballistocardiography is a non-invasive technique for evaluating cardiovascular health. This note presents an ac-bridge amplifier for low-noise ballistocardiogram (BCG) recording from a modified weighing scale. The strain gauges in a commercial scale were excited by an ac source-square or sine wave-and the differential output voltage resulting from the BCG was amplified and demodulated synchronously with the excitation waveform. A standard BCG amplifier, with a simple dc-bridge excitation, was also built and the performance was compared to both the square- and sine-wave excited ac-bridge amplifiers. The total input-referred voltage noise (rms) integrated over the relevant BCG bandwidth of 0.3-10 Hz was found to be 30 nV (square wave source) or 25 nV (sine-wave source) for the ac-bridge amplifier and 52 nV for the standard amplifier: an improvement of 4.8 dB or 6 dB, respectively. These correspond to input-referred force noise (rms) values of 5 mN, 4 mN and 8.3 mN. The improvement in SNR was also observed in recorded waveforms from a seated subject whose BCG signal was measured with both dc- and ac-bridge circuits.
View details for DOI 10.1088/0967-3334/31/7/N02
View details for Web of Science ID 000279269900016
View details for PubMedID 20526027
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Thermally Actuated Omnidirectional Walking Microrobot
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
2010; 19 (3): 433-442
View details for DOI 10.1109/JMEMS.2010.2041897
View details for Web of Science ID 000278537900001
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An 11 mu W, Two-Electrode Transimpedance Biosignal Amplifier With Active Current Feedback Stabilization
IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS
2010; 4 (2): 93-100
View details for DOI 10.1109/TBCAS.2009.2032096
View details for Web of Science ID 000276036900003
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Adaptive Cancellation of Floor Vibrations in Standing Ballistocardiogram Measurements Using a Seismic Sensor as a Noise Reference
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2010; 57 (3): 722-727
Abstract
An adaptive noise canceller was used to reduce the effect of floor vibrations on ballistocardiogram (BCG) measurements from a modified electronic bathroom scale. A seismic sensor was placed next to the scale on the floor and used as the noise reference input to the noise canceller. BCG recordings were acquired from a healthy subject while another person stomped around the scale, thus causing increased floor vibrations. The noise canceller substantially eliminated the artifacts in the BCG signal due to these vibrations without distorting the morphology of the measured BCG. Additionally, recordings were obtained from another subject standing inside a parked bus while the engine was running. The artifacts due to the vibrations of the engine, and the other vehicles moving on the road next to the bus, were also effectively eliminated by the noise canceller. The system with automatic floor vibration cancellation could be used to increase BCG measurement robustness in home monitoring applications. Additionally, the noise cancellation approach may enable BCG recording in ambulances-or other transport vehicles-where noninvasive hemodynamic monitoring may otherwise not be feasible.
View details for DOI 10.1109/TBME.2009.2018831
View details for Web of Science ID 000274990800025
View details for PubMedID 19362900
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Physical Modeling of Low-Frequency Sound Propagation through Human Thoracic Tissue
32nd Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBC 10)
IEEE. 2010: 2455–2458
Abstract
This work aims at modeling, in the presence of simplifying physical and geometrical assumptions, acoustic wave propagation through human thoracic tissue. Presented here are preliminary modeling results that are indicative of dominant lung resonances at specific frequencies. These resonant modes strongly impact pressure distribution in the tissue as well as the pressure and acceleration at the tissue-air interface. Under the modeling conditions, the effect of these lung resonant modes outweighs that of bones on acoustic waves at these frequencies.
View details for Web of Science ID 000287964002211
View details for PubMedID 21096159
- Signal Improvement by Dielectric Focusing in Microfluidic Impedance Cytometers 2010
- Chest-Acclerometery for Hemodynamic Trending During Valsalva-Recovery 2010
- Motion artifact cancelation to obtain heart sounds from a single chest-worn accelerometer 2010
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Current-Controlled Electrical Point-Source Stimulation of Embryonic Stem Cells
CELLULAR AND MOLECULAR BIOENGINEERING
2009; 2 (4): 625-635
Abstract
Stem cell therapy is emerging as a promising clinical approach for myocardial repair. However, the interactions between the graft and host, resulting in inconsistent levels of integration, remain largely unknown. In particular, the influence of electrical activity of the surrounding host tissue on graft differentiation and integration is poorly understood. In order to study this influence under controlled conditions, an in vitro system was developed. Electrical pacing of differentiating murine embryonic stem (ES) cells was performed at physiologically relevant levels through direct contact with microelectrodes, simulating the local activation resulting from contact with surrounding electroactive tissue. Cells stimulated with a charged balanced voltage-controlled current source for up to 4 days were analyzed for cardiac and ES cell gene expression using real-time PCR, immunofluorescent imaging, and genome microarray analysis. Results varied between ES cells from three progressive differentiation stages and stimulation amplitudes (nine conditions), indicating a high sensitivity to electrical pacing. Conditions that maximally encouraged cardiomyocyte differentiation were found with Day 7 EBs stimulated at 30 microA. The resulting gene expression included a sixfold increase in troponin-T and a twofold increase in beta-MHCwithout increasing ES cell proliferation marker Nanog. Subsequent genome microarray analysis revealed broad transcriptome changes after pacing. Concurrent to upregulation of mature gene programs including cardiovascular, neurological, and musculoskeletal systems is the apparent downregulation of important self-renewal and pluripotency genes. Overall, a robust system capable of long-term stimulation of ES cells is demonstrated, and specific conditions are outlined that most encourage cardiomyocyte differentiation.
View details for DOI 10.1007/s12195-009-0096-0
View details for Web of Science ID 000272671600015
View details for PubMedCentralID PMC2905819
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Signal-to-Noise Ratio in Doppler Radar System for Heart and Respiratory Rate Measurements
IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES
2009; 57 (10): 2498-2507
View details for DOI 10.1109/TMTT.2009.2029668
View details for Web of Science ID 000271100300004
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Evolving Point-of-Care Diagnostics Using Up-Converting Phosphor Bioanalytical Systems
ANALYTICAL CHEMISTRY
2009; 81 (9): 3216-3221
Abstract
Up-converting phosphors promise simpler readout systems with less background at a given signal level than many other popular approaches. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs.acs.org/journal/ancham.).
View details for DOI 10.1021/ac900475u
View details for Web of Science ID 000265632400007
View details for PubMedID 19368339
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Non-invasive cardiac output trending during exercise recovery on a bathroom-scale-based ballistocardiograph
PHYSIOLOGICAL MEASUREMENT
2009; 30 (3): 261-274
Abstract
Cardiac ejection of blood into the aorta generates a reaction force on the body that can be measured externally via the ballistocardiogram (BCG). In this study, a commercial bathroom scale was modified to measure the BCGs of nine healthy subjects recovering from treadmill exercise. During the recovery, Doppler echocardiogram signals were obtained simultaneously from the left ventricular outflow tract of the heart. The percentage changes in root-mean-square (RMS) power of the BCG were strongly correlated with the percentage changes in cardiac output measured by Doppler echocardiography (R(2) = 0.85, n = 275 data points). The correlation coefficients for individually analyzed data ranged from 0.79 to 0.96. Using Bland-Altman methods for assessing agreement, the mean bias was found to be -0.5% (+/-24%) in estimating the percentage changes in cardiac output. In contrast to other non-invasive methods for trending cardiac output, the unobtrusive procedure presented here uses inexpensive equipment and could be performed without the aid of a medical professional.
View details for DOI 10.1088/0967-3334/30/3/003
View details for Web of Science ID 000264813200003
View details for PubMedID 19202234
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A Miniaturized Video System for Monitoring the Locomotor Activity of Walking Drosophila Melanogaster in Space and Terrestrial Settings
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2009; 56 (2): 522-524
Abstract
A novel method is presented for monitoring movement of Drosophila melanogaster (the fruit fly) in space. Transient fly movements were captured by a $60, 2.5-cm-cubed monochrome video camera imaging flies illuminated by a uniform light source. The video signal from this camera was bandpass filtered (0.3-10 Hz) and amplified by an analog circuit to extract the average light changes as a function of time. The raw activity signal output of this circuit was recorded on a computer and digitally processed to extract the fly movement "events" from the waveform. These events corresponded to flies entering and leaving the image and were used for extracting activity parameters such as interevent duration. The efficacy of the system in quantifying locomotor activity was evaluated by varying environmental temperature and measuring the activity level of the flies. The results of this experiment matched those reported in the literature.
View details for DOI 10.1109/TBME.2008.2006018
View details for Web of Science ID 000265372700039
View details for PubMedID 19272912
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Robust ballistocardiogram acquisition for home monitoring
PHYSIOLOGICAL MEASUREMENT
2009; 30 (2): 169-185
Abstract
The ballistocardiogram (BCG) measures the reaction of the body to cardiac ejection forces, and is an effective, non-invasive means of evaluating cardiovascular function. A simple, robust method is presented for acquiring high-quality, repeatable BCG signals from a modified, commercially available scale. The measured BCG waveforms for all subjects qualitatively matched values in the existing literature and physiologic expectations in terms of timing and IJ amplitude. Additionally, the BCG IJ amplitude was shown to be correlated with diastolic filling time for a subject with premature atrial contractions, demonstrating the sensitivity of the apparatus to beat-by-beat hemodynamic changes. The signal-to-noise ratio (SNR) of the BCG was estimated using two methods, and the average SNR over all subjects was greater than 12 for both estimates. The BCG measurement was shown to be repeatable over 50 recordings taken from the same subject over a three week period. This approach could allow patients at home to monitor trends in cardiovascular health.
View details for DOI 10.1088/0967-3334/30/2/005
View details for Web of Science ID 000263031400005
View details for PubMedID 19147897
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Conduction Analysis in Mixed Cardiomyocytes-Fibroblasts Cultures using Microelectrode Arrays
Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2009: 4250–4253
Abstract
Models for cardiac arrhythmia currently exist primarily in in-vivo and computer simulation form. Towards the development of such a model in-vitro, a better understanding of electrical conduction in heterogeneous cultures is required. Increasing ratios of cardiomyocytes and fibroblasts were cultured on 500x500 microm arrays of 36 microelectrodes to study the emergence and properties of action potential propagation in mixed cultures. A minimum ratio of 70% cardiomyocytes to 30% fibroblasts was found to be necessary for detection of electrical activity. However, the establishment of a continuous, homogeneous depolarization wave across the culture required a higher proportion of cardiomyocytes; even a 90:10 ratio was unable to consistently produce a unidirectional, uniform depolarization wave as is seen in controls. This model underlines the importance and sensitivity of tissue homogeneity in supporting electrical conduction, and is especially relevant to studies of arrhythmia (reentry) and stem cell grafts.
View details for PubMedID 19964347
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Non-Invasive Assessment of Cardiac Contractility on a Weighing Scale
Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2009: 6773–6776
Abstract
Myocardial contractility, the intrinsic ability of the heart muscle to produce force, has been difficult to quantify non-invasively. Pre-ejection-period (PEP), the time the ventricles spend in isovolumetric contraction, is widely accepted as a way to measure contractility. This work presents a way by which the ballistocardiogram - a readily accessible non-invasive cardiovascular signal - can be used in tandem with the electrocardiogram to obtain a parameter highly correlated to PEP and thus to myocardial contractility. This parameter is the delay from the electrocardiogram R-wave to the peak (the J-wave) of the ballistocardiogram. In this work, we showed that this delay, the RJ interval, was correlated to PEP (r(2) = 0.75) for 709 heartbeats across 4 subjects, with a slope of 1.11, and a y-intercept of 151 ms. This suggests that the RJ interval can be used in place of the PEP for a reliable, practical, and non-invasive assessment of myocardial contractility.
View details for Web of Science ID 000280543605152
View details for PubMedID 19963690
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Novel Methods for Estimating the Ballistocardiogram Signal Using a Simultaneously Acquired Electrocardiogram
Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2009: 5344–5347
Abstract
The ballistocardiogram (BCG) signal represents the movements of the body in response to cardiac ejection of blood. Recently, many groups have developed low-cost instrumentation for facilitating BCG measurement in the home. The standard method used in the literature for estimating the BCG pulse response has generally been ensemble averaging over several beats. Unfortunately, since the BCG pulse response is likely longer than a typical heartbeat interval, this standard approach does not yield a full-length estimate of the response. This paper describes a simple, novel algorithm for estimating the full-length BCG pulse response using the R-wave timing of a simultaneously acquired electrocardiogram (ECG). With this pulse response, the full signal can be reconstructed, enabling the analysis of slow transient effects in the BCG signal, and of the measurement noise. Additionally, while this paper focuses only on the BCG signal, the same algorithm could be applied to other biomedical signals such as the phonocardiogram or impedance cardiogram, particularly when the heartbeat interval is shorter than the duration of the pulse response.
View details for Web of Science ID 000280543604063
View details for PubMedID 19964385
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Modeling Conduction in Host-Graft Interactions Between Stem Cell Grafts and Cardiomyocytes
Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2009: 6014–6017
Abstract
Cell therapy has recently made great strides towards aiding heart failure. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. A model using microelectrode array technology that maps the electrical interactions between host and graft tissues in co-culture is presented and sheds light on the effects of having a mismatch of conduction properties at the boundary. Skeletal myoblasts co-cultured with cardiomyocytes demonstrated that conduction velocity significantly decreases at the boundary despite electromechanical coupling. In an attempt to improve the uniformity of conduction with host cells, differentiating human embryonic stem cells (hESC) were used in co-culture. Over the course of four to seven days, synchronous electrical activity was observed at the hESC boundary, implying differentiation and integration. Activity did not extend far past the boundary, and conduction velocity was significantly greater than that of the host tissue, implying the need for other external measures to properly match the conduction properties between host and graft tissue.
View details for PubMedID 19964687
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Estimation of Central Aortic Forces in the Ballistocardiogram under Rest and Exercise Conditions
Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2009: 2831–2834
Abstract
The ballistocardiogram (BCG) signal represents the movements of the body in response to cardiac ejection of blood. The BCG signal can change considerably under various physiological states; however, little information exists in literature describing how these forces are generated. A physical analysis is presented using a finite element model of thoracic aortic vasculature to quantify forces generated by the blood flow during the cardiac cycle. The traction at the fluid-solid interface of this deformable wall model generates a Central Aortic Force (CAF) which appears of similar magnitude to recorded BCG forces. The increased pulse pressure in an exercise simulation caused a significant increase in CAF, which is consistent with recent BCG measurements in exercise recovery.
View details for Web of Science ID 000280543602072
View details for PubMedID 19964271
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Optical scanner for immunoassays with up-converting phosphorescent labels
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2008; 55 (5): 1560-1571
Abstract
A 2-D optical scanner was developed for the imaging and quantification of up-converting phosphor (UCP) labels in immunoassays. With resolution better than 500 microm, a scan rate of 0.4 mm/s, and a 1-2% coefficient of variation for repeatability, this scanner achieved a detection limit of fewer than 100 UCP particles in an 8.8. x 10(4) microm(2) area and a dynamic range that covered more than three orders of magnitude. Utilizing this scanner, a microfluidic chip immunoassay for the cytokine interferon-gamma (IFN-gamma) was developed: concentrations as low as 3 pM (50 pg/mL) were detected from 100 microL samples with a total assay time of under an hour, including the 8 min readout. For this UCP-based assay, 2-D images of the capture antibody lines were scanned, image processing techniques were employed to extract the UCP emission signals, a response curve that spanned 3-600 pM IFN-gamma was generated, and a five-parameter logistic mathematical model was fitted to the data for determination of unknown IFN-gamma concentrations. Relative to common single-point or 1-D scanning optical measurements, our results suggest that a simple 2-D imaging system can speed assay development, reduce errors, and improve accuracy by characterizing the spatial distribution and uniformity of surface-captured optical labels as a function of assay conditions and device parameters.
View details for DOI 10.1109/TBME.2007.914674
View details for Web of Science ID 000255148600011
View details for PubMedID 18440902
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Non-invasive Measurement of Valsalva-induced Hemodynamic Changes on a Bathroom Scale Ballistocardiograph
30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2008: 674–677
Abstract
Unobtrusive and compact methods for monitoring time varying hemodynamic trends can allow physicians to monitor heart failure of outpatients at home. In this paper, the ballistocardiogram (BCG), measured on a modified commercial bathroom scale, is proposed as a viable option for this important need. The BCG measures the reaction force of the body to cardiac ejection of blood and is a non-invasive tool for evaluating cardiovascular function. The Valsalva maneuver was used to modulate the hemodynamics in a well documented manner, and BCG signals were acquired from 15 subjects. The electrocardiogram (ECG) was simultaneously obtained to measure the electrical to mechanical delay in ventricular contraction: the interval from the ECG R-wave peak to the BCG J-wave peak. This interval, called the RJ interval, decreased for all subjects following the release of intrathoracic strain compared to the resting value, suggesting that it is inversely correlated to cardiac contractility. The power spectrum magnitude of the BCGs showed that the high frequency content increased after release, also consistent with increased contractility (faster ejection). Additionally, J-wave amplitudes increased following release, suggesting that it is correlated to stroke volume. Since RJ interval computation required the ECG, BCG J-wave rise time was proposed as an alternative for evaluating cardiac contractility. The correlation between this rise time and RJ interval was high (R2=0.78).
View details for Web of Science ID 000262404500169
View details for PubMedID 19162745
- Point-Source Electrical Stimulation of Embryonic Stem Cells for Cardiac Repair 2008
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High electromechanical performance of electroelastomers based on interpenetrating polymer networks
Conference on Electroactive Polymer Actuators and Devices (EAPAD 2008)
SPIE-INT SOC OPTICAL ENGINEERING. 2008
View details for DOI 10.1117/12.778282
View details for Web of Science ID 000257246800074
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Evaluating the foot electromyogram signal as a noise reference for a bathroom scale ballistocardiogram recorder
21st IEEE International Symposium on Computer-Based Medical Systems
IEEE COMPUTER SOC. 2008: 70–74
View details for DOI 10.1109/CBMS.2008.78
View details for Web of Science ID 000257577600014
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A discrete-time control algorithm applied to closed-loop pacing of HL-1 cardiomyocytes
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2008; 55 (1): 21-30
Abstract
Electrical stimulation represents a useful tool for electrophysiologic investigation of electrically excitable cells such as cardiomyocytes. The stimulation threshold and electrophysiologic response to precisely timed pulses yields valuable information regarding physiologic processes. However, determining these parameters accurately, while simultaneously resolving time-dependent or transient effects has been difficult or impossible with previous methods. This paper presents a discrete-time algorithmic controller used for closed-loop electrical stimulation of HL-1 clonal cardiomyocytes cultured on, and stimulated using, a planar microelectrode array. We introduce the temporal error-controlled algorithm (TECA), that is well-suited to control using capture fraction, a low data rate, highly quantized feedback parameter describing stimulation efficacy. HL-1 cardiomyocytes were electrically stimulated and resulting parameters were used to develop a representative model of partial capture, enabling extensive analysis of the algorithm. The performance of this approach is compared via computer simulation to a previously introduced conditional convergence algorithm to quantify its performance and relative advantages. Operation of the TECA is demonstrated by tracking the real-time biological response of stimulation threshold to a rapid increase in extracellular potassium concentration in four independent cell cultures. This work enables the use of stimulation threshold as a real-time, continuously monitored parameter with considerable utility in cardiac pharmacology, electrophysiology, and cell-based biosensing.
View details for DOI 10.1109/TBME.2007.910641
View details for Web of Science ID 000251908300003
View details for PubMedID 18232343
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Cardiac Differentiation of Embryonic Stem Cells with Point-Source Electrical Stimulation
30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2008: 1729–1732
Abstract
The use of pluripotent stem cells as a means to repair damaged heart tissue has recently emerged as a promising, yet controversial therapy. Despite the different approaches and the variety of cell types used, many of these procedures have been met with mixed success. The lack of understanding of the differentiation and integration process, notably with respect to electrical signaling, significantly hampers the development of these therapies. A system was thus developed allowing the use of point source electrical stimulation on embryonic stem (ES) cells to study the effect of physiologically-relevant electrical stimulus. When modulating the amplitude of the stimulus over various differentiation stages of embryonic stem cells, differences in the proportions of cardiomyocytes to embryonic stem cells were observed through quantitative PCR. The use of this technique might have larger applications in understanding molecular pathways towards the regeneration process.
View details for PubMedID 19163013
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Robust neural-network-based classification of premature ventricular contractions using wavelet transform and timing interval features
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2006; 53 (12): 2507-2515
Abstract
Automatic electrocardiogram (ECG) beat classification is essential to timely diagnosis of dangerous heart conditions. Specifically, accurate detection of premature ventricular contractions (PVCs) is imperative to prepare for the possible onset of life-threatening arrhythmias. Although many groups have developed highly accurate algorithms for detecting PVC beats, results have generally been limited to relatively small data sets. Additionally, many of the highest classification accuracies (> 90%) have been achieved in experiments where training and testing sets overlapped significantly. Expanding the overall data set greatly reduces overall accuracy due to significant variation in ECG morphology among different patients. As a result, we believe that morphological information must be coupled with timing information, which is more constant among patients, in order to achieve high classification accuracy for larger data sets. With this approach, we combined wavelet-transformed ECG waves with timing information as our feature set for classification. We used select waveforms of 18 files of the MIT/BIH arrhythmia database, which provides an annotated collection of normal and arrhythmic beats, for training our neural-network classifier. We then tested the classifier on these 18 training files as well as 22 other files from the database. The accuracy was 95.16% over 93,281 beats from all 40 files, and 96.82% over the 22 files outside the training set in differentiating normal, PVC, and other beats.
View details for DOI 10.1109/TBME.2006.880879
View details for Web of Science ID 000242363400011
View details for PubMedID 17153208
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Low-cost microelectrode array with integrated heater for extracellular recording of cardiomyocyte cultures using commercial flexible printed circuit technology
SENSORS AND ACTUATORS B-CHEMICAL
2006; 113 (1): 545-554
View details for DOI 10.1016/j.snb.2005.03.059
View details for Web of Science ID 000234626900072
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Temporal resolution of stimulation threshold: a tool for electrophysiologic analysis.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
2006; 1: 3891-3894
Abstract
Electrical stimulation of cardiac cultures with closed-loop control permits the determination of threshold in real time. The temporal response of stimulation threshold and underlying cell membrane excitability is valuable information for understanding the complex electrophysiologic processes within cardiac cells and can aid in understanding the mechanisms and effects of pharmaceuticals or other stimuli. This work presents the temporal response of stimulation threshold measured using HL-1 cardiac myocytes when exposed to changes in temperature and extracellular potassium concentration. These changes mimic systemic alteration of excitability and conditions that can result from ischemia in the heart. The results demonstrate the efficacy of stimulation threshold as a physiologic indicator and illustrate transient effects with both fast and slow time constants that can be resolved using a system that determines stimulation threshold in real time.
View details for PubMedID 17945812
- Micro and Nanoscale Education at Stanford University 2006
- Modeling and Control of a 3-Degree of Freedom Walking Microrobot 2006
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Temporal resolution of stimulation threshold: A tool for electrophysiologic analysis
28th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2006: 813–816
View details for Web of Science ID 000247284700202
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A multiparameter wearable physiologic monitoring system for space and terrestrial applications
International Workshop on New Generation of Smart Wearable Health Systems and Applications
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2005: 382–91
Abstract
A novel, unobtrusive and wearable, multiparameter ambulatory physiologic monitoring system for space and terrestrial applications, termed LifeGuard, is presented. The core element is a wearable monitor, the crew physiologic observation device (CPOD), that provides the capability to continuously record two standard electrocardiogram leads, respiration rate via impedance plethysmography, heart rate, hemoglobin oxygen saturation, ambient or body temperature, three axes of acceleration, and blood pressure. These parameters can be digitally recorded with high fidelity over a 9-h period with precise time stamps and user-defined event markers. Data can be continuously streamed to a base station using a built-in Bluetooth RF link or stored in 32 MB of on-board flash memory and downloaded to a personal computer using a serial port. The device is powered by two AAA batteries. The design, laboratory, and field testing of the wearable monitors are described.
View details for DOI 10.1109/TITB.2005.854509
View details for Web of Science ID 000231747500010
View details for PubMedID 16167692
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A closed-loop electrical stimulation system for cardiac cell cultures
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2005; 52 (7): 1261-1270
Abstract
An integrated electrical stimulation and recording system was designed for closed-loop control and analysis of cardiac cultures on planar microelectrode arrays. Stimulated action potentials from HL-1 clonal myocyte cultures were digitized, stimulation artifacts were removed using nulling and filtering methods, and analysis was performed to determine stimulation efficacy in real time. Results of this analysis were used to determine future stimulation waveform parameters such as polarity, amplitude, pulse duration, and rate or pattern. Algorithms were designed utilizing real-time analysis and control to maintain a desired electrophysiological response of the culture, such as an arbitrary capture fraction value. This paper presents the hardware and software design of the stimulus pulse circuitry, artifact extraction, analysis, and control components of the system. Applications of this technology include the study of cardiac cell physiology, improving the speed and accuracy of traditional open-loop stimulation protocols, pharmacological screening, and improving the performance of biosensors based on sensing electrical activity in cardiac cultures.
View details for DOI 10.1109/TBME.2005.847539
View details for Web of Science ID 000229978500011
View details for PubMedID 16041989
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A microfluidic shadow imaging system for the study of the nematode Caenorhabditis elegans in space
SENSORS AND ACTUATORS B-CHEMICAL
2005; 107 (2): 904-914
View details for DOI 10.1016/j.snb.2004.12.039
View details for Web of Science ID 000229567400054
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Sensitivity of cell-based biosensors to environmental variables
BIOSENSORS & BIOELECTRONICS
2005; 20 (7): 1397-1406
Abstract
Electrically active living cells cultured on extracellular electrode arrays are utilized to detect biologically active agents. Because cells are highly sensitive to environmental conditions, environmental fluctuations can elicit cellular responses that contribute to the noise in a cell-based biosensor system. Therefore, the characterization and control of environmental factors such as temperature, pH, and osmolarity is critical in such a system. The cell-based biosensor platform described here utilizes the measurement of action potentials from cardiac cells cultured on electrode arrays. A recirculating fluid flow system is presented for use in dose-response experiments that regulates temperature within +/-0.2 degrees C, pH to within +/-0.05 units, and allows no significant change in osmolarity. Using this system, the relationship between the sensor output parameters and environmental variation was quantified. Under typical experimental conditions, beat rate varied approximately 10% per degree change in temperature or per 0.1 unit change in pH. Similar relationships were measured for action potential amplitude, duration, and conduction velocity. For the specific flow system used in this work, the measured environmental sensitivity resulted in an overall beat rate variation of +/-4.7% and an overall amplitude variation of +/-3.3%. The magnitude of the noise due to environmental sensitivity has a large impact on the detection capability of the cell-based system. The significant responses to temperature, pH, and osmolarity have important implications for the use of living cells in detection systems and should be considered in the design and evaluation of such systems.
View details for DOI 10.1016/j.bios.2004.06.007
View details for Web of Science ID 000226344100019
View details for PubMedID 15590295
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Chest motion sensing with modified silicon base station chips
IEEE Topical Conference on Wireless Communication Technology/2nd Wireless Grantees Workshop
IEICE-INST ELECTRONICS INFORMATION COMMUNICATIONS ENG. 2004: 1524–31
View details for Web of Science ID 000223794700019
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Range correlation and I/Q performance benefits in single-chip silicon Doppler radars for noncontact cardiopulmonary monitoring
IEEE MTT-S International Microwave Symposium
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC. 2004: 838–48
View details for DOI 10.1109/TMTT.2004.823552
View details for Web of Science ID 000220177500013
- LifeGuard- A Personal Physiological Monitor for Extreme Environments Proceedings of the 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (ISBN 0-7803-8439-3-04, Ed: RJ Jaeger) 2004: pp. 2192-2195.
- Range Correlation and I/Q Performance Benefits in Single-Chip Silicon Doppler Radars for Noncontact Cardiopulmonary Monitoring IEEE Transactions on Microwave Theory and Techniques 2004; 52 (3): 838 ? 848
- Chest motion sensing with modified silicon base station chips IEICE Transactions on Electronics, Special Issue on Wave Technologies for Wireless and Optical Communications 2004; E87-C (9): 1524 - 1531
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Lifeguard--a personal physiological monitor for extreme environments.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference
2004; 3: 2192-2195
Abstract
Monitoring vital signs in applications that require the subject to be mobile requires small, lightweight, and robust sensors and electronics. A body-worn system should be unobtrusive, noninvasive, and easy-to-use. It must be able to log vital signs data for several hours as well as transmit it on demand in real-time using secure wireless technologies. The NASA Ames Research Center (Astrobionics) and Stanford University (National Center for Space Biological Technologies) are currently developing a wearable physiological monitoring system for astronauts, called LifeGuard, that meets all of the above requirements and is also applicable to clinical, home-health monitoring, first responder and military applications.
View details for PubMedID 17272160
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Lifeguard - A personal physiological monitor for extreme environments
26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2004: 2192–2195
View details for Web of Science ID 000225461800566
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Electronic sensors with living cellular components
PROCEEDINGS OF THE IEEE
2003; 91 (6): 915-929
View details for DOI 10.1109/JPROC.2003.813580
View details for Web of Science ID 000183692500010
- Electronic Sensors with Living Cellular Components Proceedings of the IEEE 2003; 91 (6): 915 ? 929
- Wireless IC Doppler Radars for Sensing of Heart and Respiration Activity 2003
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A multi-parameter, feedback-based electrical stimulation system for cardiomyocyte cultures
12th International Conference on Solid-State Sensors, Actuators and Microsystems (TRANSDUCERS 03)
IEEE. 2003: 983–986
View details for Web of Science ID 000184567300247
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Range correlation effect on ISM band I/Q CMOS radar for non-contact vital signs sensing
IEEE MTT-S International Microwave Symposium
IEEE. 2003: 1945–1948
View details for Web of Science ID 000184045100506
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Modiried silicon base station chips as biomedical sensors
IEEE Topical Conference on Wireless Communication Technology/2nd Wireless Grantees Workshop
IEEE. 2003: 210–211
View details for Web of Science ID 000222673800082
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Stimulus representation in rat primary visual cortex: multi-electrode recordings with micro-machined silicon probes and estimation theory
10th Computational Neuroscience Meeting (CSN 01)
ELSEVIER SCIENCE BV. 2002: 407–416
View details for Web of Science ID 000176839200060
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An in-line osmometer for application to a cell-based biosensor system
Transducers 2001 Conference/Eurosensor XVth Conference
ELSEVIER SCIENCE SA. 2002: 41–47
View details for Web of Science ID 000174823900007
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Microfabricated solid-state dissolved oxygen sensor
Transducers 2001 Conference/Eurosensor XVth Conference
ELSEVIER SCIENCE SA. 2002: 138–48
View details for Web of Science ID 000174823900021
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Retinal ganglion cells do not extend axons by default: Promotion by neurotrophic signaling and electrical activity
NEURON
2002; 33 (5): 689-702
Abstract
We investigate the signaling mechanisms that induce retinal ganglion cell (RGC) axon elongation by asking whether surviving neurons extend axons by default. We show that bcl-2 overexpression is sufficient to keep purified RGCs alive in the absence of any glial or trophic support. The bcl-2-expressing RGCs do not extend axons or dendrites unless signaled to do so by single peptide trophic factors. Axon growth stimulated by peptide trophic factors is remarkably slow but is profoundly potentiated by physiological levels of electrical activity spontaneously generated within embryonic explants or mimicked on a multielectrode silicon chip. These findings demonstrate that these surviving neurons do not constitutively extend axons and provide insight into the signals that may be necessary to promote CNS regeneration.
View details for Web of Science ID 000174286200006
View details for PubMedID 11879647
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Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer
CANCER RESEARCH
2002; 62 (4): 957-960
Abstract
Array-based comparative genomic hybridization (CGH) uses multiple genomic clones arrayed on a slide to detect relative copy number of tumor DNA sequences. Application of array CGH to tumor specimens makes genetic diagnosis of cancers possible and may help to differentiate relevant subsets of tumors, biologically and clinically, which would allow better prognostic and therapeutic decision making. In this study, we have used array-based CGH to detect DNA copy number alterations in distinct types of renal cell carcinomas for diagnostic purposes. We were able to correctly diagnose 33 of 34 malignant tumors by automated computational means and to group together eight benign neoplasms and normal kidney samples. These results indicate that array-based CGH is capable of diagnosing the vast majority of renal cell carcinomas based on their genetic profiles.
View details for Web of Science ID 000173969400002
View details for PubMedID 11861363
- Retinal Ganglion Cells Do Not Extend Axons by Default: Promotion by Neurotrophic Signaling and Electrical Activity Neuron 2002; 33: 689-702
- Active SOI-Based Neural Probes 2002
- Measurement of Changes in Tissue Metabolism Using a Clark-Type Oxygen Sensor 2002
- Stimulus Representation in Rat Primary Visual Cortex: Multi-Electrode Recordings with Micromachined Silicon Probes and Estimation Theory Neurocomputing 2002; 44 - 46: 407 - 416
- An In-Line Osmometer for Application to a Cell-Based Biosensor System Sensors and Actuators B: Chemical 2002; 83: 41 - 47
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A docking system for microsatellites based on MEMS actuator arrays
SMART MATERIALS & STRUCTURES
2001; 10 (6): 1176-1184
View details for Web of Science ID 000173555900007
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A genetically engineered cell-based biosensor for functional classification of agents
BIOSENSORS & BIOELECTRONICS
2001; 16 (7-8): 571-577
Abstract
Cell-based biosensors (CBBs) utilize whole cells to detect biologically active agents. Although CBBs have shown success in detecting the presence of biological agents, efforts to classify the type of agent based on functional activity have proven difficult because multiple biochemical pathways can lead to the same cellular response. However, a new approach using a genetically-engineered cell-based biosensor (GECBB) described in this paper translates this cross-talk noise into common-mode noise that can be rejected. The GECBB operates by assaying for an agent's ability to differentially activate two populations of cells, wild-type (WT) cells and cells genetically engineered to lack a specific receptor, knockout (KO) cells. Any biological agent that targets the knocked out receptor will evoke a response in the WT but not in the KO. Thus, the GECBB is exquisitely sensitive to agents that effect the engineered pathway. This approach provides the benefits of an assay for specific functional activity while simplifying signal analysis. The GECBB implemented was designed to be sensitive to agents that activate the beta 1-adrenergic receptor (beta 1-AR). This was achieved by using mouse cardiomyocytes in which the beta 1-AR had been knocked out. The cellular signal used in the GECBB was the spontaneous beat rate of the two cardiomyocyte syncitia as measured with microelectrode arrays. The GECBB was able to detect the beta-AR agonist isoproterenol (ISO) at a concentration of 10 microM (P<0.005).
View details for Web of Science ID 000171257900017
View details for PubMedID 11544051
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General purpose, field-portable cell-based biosensor platform
BIOSENSORS & BIOELECTRONICS
2001; 16 (7-8): 557-564
Abstract
There are several groups of researchers developing cell-based biosensors for chemical and biological warfare agents based on electrophysiologic monitoring of cells. In order to transition such sensors from the laboratory to the field, a general-purpose hardware and software platform is required. This paper describes the design, implementation, and field-testing of such a system, consisting of cell-transport and data acquisition instruments. The cell-transport module is a self-contained, battery-powered instrument that allows various types of cell-based modules to be maintained at a preset temperature and ambient CO(2) level while in transit or in the field. The data acquisition module provides 32 channels of action potential amplification, filtering, and real-time data streaming to a laptop computer. At present, detailed analysis of the data acquired is carried out off-line, but sufficient computing power is available in the data acquisition module to enable the most useful algorithms to eventually be run real-time in the field. Both modules have sufficient internal power to permit realistic field-testing, such as the example presented in this paper.
View details for Web of Science ID 000171257900015
View details for PubMedID 11544049
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Portable cell-based biosensor system using integrated CMOS cell-cartridges
BIOSENSORS & BIOELECTRONICS
2001; 16 (7-8): 543-556
Abstract
The use of cell-based biosensors outside of the laboratory has been limited due to many issues including preparation of the sample, maintenance of the biological environment, and integration of the electronics for data collection and analysis. This paper describes a system that addresses several of these issues with the development of an integrated silicon-polydimethylsiloxane cell-cartridge. The cell-cartridge contains a CMOS silicon chip that incorporates a digital interface, temperature control system, microelectrode electrophysiology sensors, and analog signal buffering. Additionally, the cell-cartridge supports two separate cell populations in two 10 microl sealed chambers that have independent fluidic channels for sample injection. A portable, microcontroller-based electronics system capable of monitoring the action potential (AP) activity within the cell-cartridges was also developed. The AP activities of cardiomyocyte syncytia in the two chambers differentially responded to the flow of a control medium versus the flow of a biochemical agent. The cell-cartridges and portable electronics system were used to successfully record AP activity from cardiomyocytes outside of the laboratory under realistic application conditions.
View details for Web of Science ID 000171257900014
View details for PubMedID 11544048
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Integration of sputtered silicon microstructures with pre-fabricated CMOS circuitry
Solid-State Sensors and Actuators Workshop
ELSEVIER SCIENCE SA. 2001: 386–97
View details for Web of Science ID 000169970700019
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Lysing bacterial spores by sonication through a flexible interface in a microfluidic system
ANALYTICAL CHEMISTRY
2001; 73 (3): 492-496
Abstract
Cell disruptions using ultrasonic energy transmitted through a flexible interface into a liquid region has limitations because the motion of the vibrating tip is not completely transferred into the liquid. To ensure that some degree of contact will be maintained between the ultrasonic horn tip and the flexible interface, the liquid must be pressurized. The pressure conditions that yield consistent coupling between the ultrasonic horn tip and the liquid region were explored in this study by using an analytical model of the system and test fixture experiments. The nature of the interaction between the horn tip and the flexible interface creates pulses of positive pressure rises, increase in temperature, streaming flow, and almost no cavitation in the liquid. There was sufficient energy to create a cloud of microspheres, or beads, that maintain a consistent pattern of ballistic motion in the liquid. The sonication was found to be repeatable by studying video recordings of bead motion and was shown to be statistically consistent using measurements of temperature rise. Sonication of bacterial spores to obtain measurements of released nucleic acid and SEM images of damaged spores were used to verify the effects of liquid pressure on the horn-interface-liquid coupling.
View details for Web of Science ID 000166780200022
View details for PubMedID 11217752
- A Genetically Engineered Cell-Based Biosensor for Functional Classification of Agents Biosensors and Bioelectronics 2001; 16: 571 - 577
- Omnidirectional Walking Microrobot Realized by Thermal Microactuator Arrays 2001
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An in-line osmometer for application in tissue based bio-sensor systems
11th International Conference on Solid-State Sensors and Actuators
SPRINGER-VERLAG BERLIN. 2001: 370–373
View details for Web of Science ID 000172547800088
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Analysis of microelectrode-recorded signals from a cardiac cell line as a tool for pharmaceutical screening
11th International Conference on Solid-State Sensors and Actuators
SPRINGER-VERLAG BERLIN. 2001: 390–393
View details for Web of Science ID 000172547800093
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Solid-state dissolved oxygen sensor test matrix using a pulsed-plasma deposited PTFE film
11th International Conference on Solid-State Sensors and Actuators
SPRINGER-VERLAG BERLIN. 2001: 1692–1695
View details for Web of Science ID 000172547800393
- Lysing Bacterial Spores by Sonication Through a Flexible Interface in a Microfluidic System Analytical Chemistry 2001; 73 (3): 492-496
- Integration of Sputtered Silicon Microstrutures with Pre-Fabricated CMOS Circuitry Sensors and Actuators A: Physical 2001; 91 (3): 492-496
- A Docking System for Microsatellites Based on MEMS Actuator Arrays Smart Materials and Structures 2001; 10 (6): 1176 - 1184
- General Purpose, Field-Portable Cell-Based Biosensor Platform Biosensors and Bioelectronics 2001; 16: 557 - 564
- Portable Cell-Based Biosensor System Using Integrated CMOS Cell-Cartridges Biosensors and Bioelectronics 2001; 16: 543 - 556
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A traction stress sensor array for use in high-resolution robotic tactile imaging
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
2000; 9 (4): 425-434
View details for Web of Science ID 000166597800003
- A Traction Stress Sensor Array for Use in High-Resolution Robotic Tactile Imaging IEEE/ASME Journal of Microelectromechanical Systems 2000; 9 (4): 425-434
- CMOS Integrated Organic Ciliary Actuator Arrays for General-Purpose Micromanipulation Tasks Distributed Manipulation edited by Bohringer, K., F., Choset, H. Kluwer Academic Publishers, Norwell, MA. 2000: 191–215
- Thermo-Bimorph Microcilia Arrays for Small Spacecraft Docking MEMS 2000 - ASME International Mechanical Congress and Exposition, Orlando, FL 2000: 57 - 63
- Versatile, Adaptable and Programmable Microfluidic Platforms for DNA Diagnostics and Drug Discovery Assays 2000
- Sputtered Silicon for Integrated MEMS Applications 2000
- Fully Programmable MEMS Ciliary Actuator Arrays for Micromanipulation Tasks 2000
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System requirements for a portable cell based sensor
3rd International Symposium on Micro-Total Analysis Systems (mu-TAS'98)
SPRINGER. 2000: 443–446
View details for Web of Science ID 000085854700106
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Novel interconnection and channel technologies for microfluidics
3rd International Symposium on Micro-Total Analysis Systems (mu-TAS'98)
SPRINGER. 2000: 27–30
View details for Web of Science ID 000085854700006
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CMOS integrated ciliary actuator array as a general-purpose micromanipulation tool for small objects
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
1999; 8 (4): 483-496
View details for Web of Science ID 000084225400017
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Novel interconnection technologies for integrated microfluidic systems
SENSORS AND ACTUATORS A-PHYSICAL
1999; 77 (1): 57-65
View details for Web of Science ID 000083733500009
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An integrated controller for tunnel sensors
IEEE JOURNAL OF SOLID-STATE CIRCUITS
1999; 34 (8): 1099-1107
View details for Web of Science ID 000081755500009
- A Minisonicator to Rapidly Disrupt Bacterial Spores for DNA Analysis Analytical Chemistry 1999; 71 (19): 4232 - 4236
- Integrated Clark-Type Oxygen Sensor Array Using a Pulsed Plasma Deposited PTFE-Like Film 1999
- Biological Warfare Agent Decontamination Defense Sciences Research Council Study Report Series 1999
- Genetically Engineered Cell-Based Biosensors for Specific Agent Classification 1999
- A Low-Cost, Micromachined, Integrated CMOS Spectrometer 1999
- Reusable Microfluidic Coupler with PDMS Gasket 1999
- Hybrid Biosensors: Harnessing Living Tissues for Chem/Bio Warfare Agent Detection 1999
- An Integrated Controller for Tunnel Sensors IEEE Journal of Solid State Circuits 1999; 34 (8): 1099-1107
- CMOS Integrated Ciliary Actuator Array as a General-Purpose Micromanipulation Tool for Small Objects IEEE/ASME Journal of Microelectromechanical Systems 1999; 8 (4): 483 - 496
- Novel Interconnection Technologies for Integrated Microfluidic Systems Sensors and Actuators A 1999; 77 (1): 57 - 65
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Portable cell-based biosensor system for toxin detection
SENSORS AND ACTUATORS B-CHEMICAL
1998; 53 (3): 179-185
View details for Web of Science ID 000079908100007
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Description and demonstration of a CMOS amplifier-based-system with measurement and stimulation capability for bioelectrical signal transduction
BIOSENSORS & BIOELECTRONICS
1998; 13 (9): 971-979
Abstract
An extracellular recording system incorporating an electrode array and an amplifier/stimulator CMOS chip is described and characterized. Important features of this custom VLSI chip include 16 instrumentation amplifiers with a gain of 50 and the incorporation of a cross-point array allowing designation of an extracellular microelectrode as either a stimulator or sensor. The planar array consisted of 32 microelectrodes, 14 microns in diameter, and four larger reference electrodes. Microelectrodes, interconnecting traces, and bond pads were patterned with a 500-nm layer of gold. The interconnecting traces were passivated with a 1-micron thick layer of silicon nitride to provide chemical and electrical insulation and microelectrode impedance was lowered utilizing electrode position of platinum black. The amplifier exhibited a nearly flat frequency response with high pass and low pass corner frequencies of 0.7 Hz and 50 kHz, respectively. The input referred noise over the 50 kHz bandwidth was 12-16 microVRMS, well below the magnitude of previously reported extracellular potentials. Crosstalk between neighboring channels resulted in an output signal below the amplifier noise level, even for relatively large extracellular potentials. Using this system, extracellular recording were demonstrated yielding typical peak-to-peak biopotentials of magnitude 0.9-2.1 mV and 100-400 microV for chick cardiac myocytes and rat spinal cord neurons, respectively. The key components of this extracellular recording system can be manufactured using industry standard thin film photolithographic techniques.
View details for Web of Science ID 000076848800006
View details for PubMedID 9839386
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PECVD silicon carbide as a chemically resistant material for micromachined transducers
9th International Conference on Solid-State Sensors and Actuators
ELSEVIER SCIENCE SA. 1998: 48–55
View details for Web of Science ID 000075835900007
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Toward Next Generation Clinical Diagnostic Instruments: Scaling and New Processing Paradigms
BIOMEDICAL MICRODEVICES
1998; 1 (1): 71-79
View details for Web of Science ID 000209019300007
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Bulk micromachining of silicon
PROCEEDINGS OF THE IEEE
1998; 86 (8): 1536-1551
View details for Web of Science ID 000074840200003
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Electrically floating conductivity detection system for capillary electrophoresis
JOURNAL OF CHROMATOGRAPHY A
1998; 813 (1): 205-208
View details for Web of Science ID 000074862100022
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Ciliary microactuator array for scanning electron microscope positioning stage
44th National Symposium of the American-Vacuum-Society
A V S AMER INST PHYSICS. 1998: 1998–2002
View details for Web of Science ID 000074150500108
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Cell-based sensor microelectrode array characterized by imaging x-ray photoelectron spectroscopy, scanning electron microscopy, impedance measurements, and extracellular recordings
44th American-Vacuum-Society Symposium on Flat Panel Displays, Micromechanical Systems, and Quantitative Surface and Analysis
A V S AMER INST PHYSICS. 1998: 1183–88
View details for Web of Science ID 000074150400055
- Electrically Floating Conductivity Detection System for Capillary Electrophoresis Journal of Chromatography A 1998; 813 (1): 205 - 208
- Micromachined Transducers Sourcebook McGraw-Hill, Inc., New York, NY. 1998
- Novel Analytical Technique for On-Line Monitoring of Trace Heavy Metals in Corrosive Chemicals 1998
- An Approach to the Classification of Unknown Biological Agents with Cell Based Sensors 1998
- Design of an Integrated Silicon-PDMS Cell Cartridge 1998
- System Requirements for a Portable Cell Based Sensor 1998
- High Aspect Ratio Silicon Microstructures for Nucleic Acid Extraction 1998
- Ciliary Microactuator Array for Scanning Electron Microscope Positioning Stage Journal of Vacuum Science & Technology A (Vacuum, Surfaces, and Films) 1998; 16 (3): 1998-2002
- Field Evaluation of an Electrochemical Probe for In Situ Screening of Heavy Metals in Groundwater Environmental Science and Technology 1998; 32 (1): 131-136
- Toward Next Generation Clinical Diagnostic Instruments: Scaling and New Processing Paradigms Journal of Biomedical Microdevices 1998; 1 (1): 71 - 79
- PECVD Silicon Carbide as a Chemically Resistant Material for Micromachined Transducers Sensors and Actuators A 1998; 70 (1 - 2): 48 - 55
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Field evaluation of an electrochemical probe for in situ screening of heavy metals in groundwater
ENVIRONMENTAL SCIENCE & TECHNOLOGY
1998; 32 (1): 131-136
View details for Web of Science ID 000071284200040
- Bulk Micromachining of Silicon Proceedings of the IEEE 1998; 86 (8): 1536 - 1551
- Portable Cell-Based Biosensor System for Toxin Detection Sensors and Actuators B: Chemical 1998; 53 (3): 179 - 185
- Description and Demonstration of a CMOS Amplifier-Based-System with Measurement and Stimulation Capability for Bioelectrical Signal Transduction Biosensors and Bioelectronics 1998; 13: 971-979
- Cell-Based Sensor Microelectrode Array Characterized by Imaging X-ray Photoelectron Spectroscopy, Scanning Electron Microscopy, Impedance Measurements, and Extracellular Recordings Journal of Vacuum Science & Technology A (Vacuum, Surfaces, and Films) 1998; 16 (3): 1183-1188
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Microelectrode arrays for stimulation of neural slice preparations
JOURNAL OF NEUROSCIENCE METHODS
1997; 77 (1): 61-66
Abstract
A planar 6 x 6 array of iridium electrodes with four reference electrodes has been developed for use with neural tissue preparations. Precise knowledge of the relative locations of the array elements allows for spatial neurophysiological analyses. The 10 microns diameter platinized iridium electrodes on a 100 microns pitch have been used to stimulate acutely prepared slices of spinal cord from free-ranging rodents. An intracellular recording from a single neuron in the substantia gelatinosa (SG) using the whole-cell, tight-seal technique allowed low noise, high resolution studies of excitatory or inhibitory electrical responses of a given neuron to inputs from the primary afferent fibers or from stimulation by individual electrodes of the array. The resulting maps of responses provide an indication of the interconnectivity of neural processes. The pattern emerging is that of limited interconnectivity in the SG from areas surrounding a recorded neuron but with strong excitatory or inhibitory effects from those oriented in a longitudinal (rostral-caudal) direction relative to the neuron. The observations to date suggest the neurons of the SG are arranged in sets of independent networks, possibly related to sensory modality and input from particular body regions.
View details for Web of Science ID A1997YH55100008
View details for PubMedID 9402558
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A high-speed median circuit
IEEE JOURNAL OF SOLID-STATE CIRCUITS
1997; 32 (6): 905-908
View details for Web of Science ID A1997XA68600015
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Multi-unit recording from regenerated bullfrog eighth nerve using implantable silicon-substrate microelectrodes
JOURNAL OF NEUROSCIENCE METHODS
1997; 72 (1): 71-86
Abstract
Multi-microelectrode silicon devices were developed for extracellular recording from multiple axons in regenerated eighth cranial nerves of American bullfrogs. Each includes a photolithographically defined array of holes and adjacent metal microelectrodes. A device is implanted within a transected eighth nerve; regenerating fibers grow through the holes en route to the brainstem. Multiple spike trains were recorded from two animals at up to 21 weeks after implantation. Single units were tracked for over 8 h. Some responded to sound with tuning typical of fibers innervating the amphibian and basilar papillae. Units of vestibular origin also were recorded. Action potentials were 30-140 microV P-P amid noise of 5 10 microV RMS, an adequate signal-to-noise ratio for spike detection and sorting. Histology confirmed that bundles of myelinated fibers grew through holes near electrodes that recorded activity. The implantation success rate was low, due to surgical morbidity, device extrusion, and lack of nerve regeneration through some devices. Future designs will address these issues and incorporate transistor amplifiers on devices to increase signal-to-noise ratios. The potential of implanted silicon devices to simultaneously record from many axons offers an opportunity for multicellular studies of auditor, vestibular and seismic signal processing in the vertebrate inner ear.
View details for Web of Science ID A1997WW56200011
View details for PubMedID 9128171
- Microelectrode Arrays for Stimulation of Neural Slice Preparations Journal of Neuroscience Methods 1997; 77 (1): 61-66
- DSRC Report on Improving Human Performance Defense Sciences Research Council Report 1997
- Vector Fields for Task-Level Distributed Manipulation: Experiments with Organic Micro Actuator Arrays 1997
- Force-Balanced Accelerometer with mG Resolution, Fabricated Using Silicon Fusion Bonding and Deep Reactive Ion Etching 1997
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Considerations for the practical use of micromachining technologies
3rd International Symposium on Microstructures and Microfabricated Systems at the 191st Meeting of the Electrochemical-Society
ELECTROCHEMICAL SOCIETY INC. 1997: 20–25
View details for Web of Science ID A1997BH73G00003
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Miniature spectrometers for biochemical analysis
1st SPIE Conference on Microfabricated and Nanofabricated Electro-Optical Mechanical Systems for Biomedical and Environmental Applications
SPIE - INT SOC OPTICAL ENGINEERING. 1997: 75–81
View details for Web of Science ID A1997BH52D00010
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Planar electrode array systems for neural recording and impedance measurements
18th Annual International Conference of IEEE Engineering-in-Medicine-amd-Biology-Society
IEEE. 1997: 106–107
View details for Web of Science ID 000072079000053
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PECVD silicon carbide for micromachined transducers
9th International Conference on Solid-State Sensors and Actuators
I E E E. 1997: 217–220
View details for Web of Science ID A1997BJ35B00052
- Computational Methods for Design and Control of MEMS Micromanipulator Arrays IEEE Computational Science and Engineering 1997; 4 (1): 17-29
- Multi-Unit Recording from Regenerated Bullfrog Eighth Nerve Using Implantable Silicon-Substrate Microelectrodes Journal of Neuroscience Methods 1997; 72 (1): 71-86
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Miniature spectrometers for biochemical analysis
1996 Solid State Sensors and Actuators Workshop (SSSAW-96)
ELSEVIER SCIENCE SA LAUSANNE. 1997: 61–66
View details for Web of Science ID A1997XJ53200008
- Miniature Spectrometers for Biochemical Analysis Sensors and Actuators A 1997; 58 (1): 61-66
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Integrated thermal-conductivity vacuum sensor
1996 Solid State Sensors and Actuators Workshop (SSSAW-96)
ELSEVIER SCIENCE SA LAUSANNE. 1997: 37–42
View details for Web of Science ID A1997XJ53200005
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Plasma-etched neural probes
1996 Solid State Sensors and Actuators Workshop (SSSAW-96)
ELSEVIER SCIENCE SA LAUSANNE. 1997: 27–35
View details for Web of Science ID A1997XJ53200004
- Plasma-Etched Neural Probes Sensors and Actuators A 1997; 58 (1): 27-35
- Integrated Thermal Conductivity Vacuum Sensor Sensors and Actuators A 1997; 58 (1): 37-42
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Micromachined thermally isolated circuits
1996 Solid State Sensors and Actuators Workshop (SSSAW-96)
ELSEVIER SCIENCE SA LAUSANNE. 1997: 43–50
View details for Web of Science ID A1997XJ53200006
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Organic thermal and electrostatic ciliary microactuator array for object manipulation
1996 Solid State Sensors and Actuators Workshop (SSSAW-96)
ELSEVIER SCIENCE SA LAUSANNE. 1997: 51–60
View details for Web of Science ID A1997XJ53200007
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Computational methods for design and control of MEMS micromanipulator arrays
IEEE COMPUTATIONAL SCIENCE & ENGINEERING
1997; 4 (1): 17-29
View details for Web of Science ID A1997WU07300006
- Organic Thermal and Electrostatic Ciliary Microactuator Array for Object Manipulation Sensors and Actuators A 1997; 58 (1): 51-60
- Micromachined Thermally Isolated Circuits Sensors and Actuators A 1997; 58 (1): 43-50
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A rail-to-rail ping-pong op-amp
IEEE JOURNAL OF SOLID-STATE CIRCUITS
1996; 31 (9): 1320-1324
View details for Web of Science ID A1996VE60100012
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Microfabricated electrochemical analysis system for heavy metal detection
8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX)
ELSEVIER SCIENCE SA LAUSANNE. 1996: 450–55
View details for Web of Science ID A1996WC20900043
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Silicon micromachining - Sensors to systems
ANALYTICAL CHEMISTRY
1996; 68 (13): A407-A412
View details for Web of Science ID A1996UW36700002
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CMOS-compatible traction stress sensor for use in high-resolution tactile imaging
8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX)
ELSEVIER SCIENCE SA. 1996: 511–16
View details for Web of Science ID A1996VV39200013
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Characterizing deflectable microstructures via a high-resolution laser-based measurement system
8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX)
ELSEVIER SCIENCE SA. 1996: 12–17
View details for Web of Science ID A1996UR00700003
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High-voltage devices and circuits fabricated using foundry CMOS for use with electrostatic MEM actuators
8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX)
ELSEVIER SCIENCE SA. 1996: 187–92
View details for Web of Science ID A1996UR00700031
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Diode-based thermal rms converter with on-chip circuitry fabricated using CMOS technology
8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX)
ELSEVIER SCIENCE SA. 1996: 33–40
View details for Web of Science ID A1996UR00700006
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Silicon fusion bonding and deep reactive ion etching: A new technology for microstructures
8th International Conference on Solid-State Sensors and Actuators (Eurosensors IX)
ELSEVIER SCIENCE SA. 1996: 132–39
View details for Web of Science ID A1996UR00700022
- CMOS-Compatible Traction Stress Sensor for Use In High-Resolution Tactile Imaging Sensors and Actuators A 1996; 54: 511-516
- Characterizing Deflectable Microstructures Via a High-Resolution Laser-Based Measurement System Sensors and Actuators A 1996; 52 (1-3): 12 - 17
- Biosensors Utilizing Neural Cells as Sensing Elements Society for Neuroscience 26th Annual Meeting Abstracts, Washington, D.C. 1996; 22 (1): 273
- An Integrated Accelerometer As A Demonstration of a New Technology Using Silicon Fusion Bonding and Deep Reactive Ion Etching Late News Poster Session Supplemental Digest of the Solid-State Sensor and Actuator Workshop, Hilton Head, South Carolina 1996: 21-22
- Advanced Technologies for Defense Against Biological Warfare Agents Defense Sciences Research Council Report 1996
- Combined Organic Thermal and Electrostatic Omnidirectional Ciliary Microactuator Array for Object Positioning and Inspection 1996
- New Materials for MEMS Defense Sciences Research Council Report 1996
- Impedance Imaging for Hybrid Biosensor Applications 1996
- Miniaturized Spectrometers for Biochemical Analysis 1996
- DSRC Tissue Engineering Workshop Summary Report Defense Sciences Research Council Report 1996
- Characterizing Deflectable Microstructures Via a High-Resolution Laser-Based Measurement System Sensors and Actuators A 1996; 52 (1-3): 12-17
- Microfabricated Electrochemical Analysis System for Heavy Metal Detection Sensors and Actuators B 1996; 34 (1-3): 450-455
- Silicon Fusion Bonding and Deep Reactive Ion Etching Sensors and Actuators A 1996; 52 (1-3): 132-139
- Silicon Micromachining Analytical Chemistry 1996; 68: 407A-412A
- High-Voltage Devices and Circuits Fabricated Using Foundry CMOS for Use With Electrostatic MEM Actuators Sensors and Actuators A 1996; 52 (1-3): 187-192
- Diode-Based Thermal RMS Converter with On-Chip Circuitry Fabricated Using Standard CMOS Technology Sensors and Actuators A 1996; 52 (1): 33-40
- A Rail-to-Rail Ping-Pong Op-Amp IEEE Journal of Solid-State Circuits 1996; 31 (9): 1320-1324
- Mesoscopic Machines Defense Sciences Research Council Report 1996
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A FEEDBACK-CONTROLLED SILICON MICROPROBE FOR QUANTITATIVE MECHANICAL STIMULATION OF NERVE AND TISSUE
JOURNAL OF NEUROSCIENCE METHODS
1995; 60 (1-2): 157-163
Abstract
The ability to apply and control the force and force velocity of mechanical stimulation is essential for the study of mechanoelectric transduction and adaptation processes. Silicon micromachining technology was used to produce miniature (20-70 microns wide) mechanical microprobes. Passive polysilicon, piezoresistive, force sensing elements were deposited onto the boron-doped epitaxial silicon and the individual devices were chemically etched from the bulk wafer. These microprobes display a linear force versus output voltage relationship. Stimulation forces up to 2 mN can be generated with a measurement resolution of 1.5 microN. The probes were mounted onto circuit board holders and their output sent to a proportional-integral controller which drives an electromagnetic actuator. By using this force-feedback control circuit coupled to a PC it is possible to define any stimulus wave form pattern and independently control and measure the actual stimulus force and velocity. A computer controlled 3-axis stepper motor (0.025 micron step capability) manipulator is used to position the silicon microprobe-actuator assembly relative to the mechanoreceptive field. Sensor feedback control coupled to the 3-axis stepper motor manipulator allows automatic touchdown control and/or preloading of the probe prior to stimulation. Three-dimensional topographic manipulator feedback position control allows automated receptive field mapping.
View details for Web of Science ID A1995RW12000019
View details for PubMedID 8544475
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FORCE-SENSING MICROPROBE FOR PRECISE STIMULATION OF MECHANOSENSITIVE TISSUES
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
1995; 42 (8): 745-750
Abstract
Quantitative study of the transduction mechanisms in mechanically sensitive nerve terminals has been impeded by the lack of instrumentation with which to generate precisely controlled, physically localized mechanical stimuli. We have developed high-resolution force sensing mechanical microprobes for use in the characterization of such nerve terminals. This paper describes their design, fabrication, and testing. A microprobe is comprised of a 0.5- to 2-mm long silicon cantilever beam projecting from a larger supporting silicon substrate. Acting as the variable leg of a Wheatstone bridge circuit, a piezoresistive polysilicon element located at the base of the beam is used to measure the stimulation force applied at the tip. The microprobes exhibit a stable, linear relationship between the stimulation force and the resulting output voltage signal. Stimulation forces up to 3 mN have been generated with a measurement resolution of 10 microN. These microprobes have been used as the force sensing element of a closed loop feedback-controlled stimulation system capable of stimulating the mechanoreceptive nerve terminals of the rabbit corneal epithelium.
View details for Web of Science ID A1995RJ14100001
View details for PubMedID 7642187
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LARGE-SIGNAL SUBTHRESHOLD CMOS TRANSCONDUCTANCE AMPLIFIER
ELECTRONICS LETTERS
1995; 31 (9): 718-720
View details for Web of Science ID A1995QY09200024
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FLEXIBLE, DRY-RELEASED PROCESS FOR ALUMINUM ELECTROSTATIC ACTUATORS (VOL 3, PG 90, 1994)
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
1995; 4 (1): 60-60
View details for Web of Science ID A1995QM20000008
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A MICROMACHINED LOW-POWER TEMPERATURE-REGULATED BANDGAP VOLTAGE REFERENCE
1995 IEEE International Solid-State Circuits Conference
I E E E. 1995: 166–167
View details for Web of Science ID A1995BD33W00063
- Thoughts on Becoming and Being an Analog Circuit Designer The Art and Science of Analog Circuit Design edited by Williams, J. Butterworth-Heinemann, Boston, MA. 1995: 41–54
- Diode-Based Thermal RMS Converter with On-Chip Circuitry Fabricated Using Standard CMOS Technology Digest of Technical Papers from Transducers ‘95/Eurosensors IX Stockholm, Sweden 1995; 1: 154 - 157
- A High-Resolution Laser-Based Deflection Measurement System for Characterizing Aluminum Electrostatic Actuators Digest of Technical Papers from Transducers ‘95/Eurosensors IX Stockholm, Sweden 1995; 1: 308 - 311
- A CMOS Compatible Traction Stress Sensing Element for Use In High Resolution Tactile Imaging Digest of Technical Papers from Transducers ‘95/Eurosensors IX Stockholm, Sweden 1995; 1: 648 - 651
- On-Chip Chemical Analysis Defense Sciences Research Council Report 1995
- Microfabricated Heavy Metal Ion Sensor Sensors and Actuators B: Chemical 1995; 23 (1): 41 - 47
- Microfabricated Electrochemical Analysis System for Heavy Metal Detection Digest of Technical Papers from Transducers ‘95/Eurosensors IX Stockholm, Sweden 1995; 2: 932 - 935
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A videobandwidth analog median circuit
IEEE 1995 Custom Integrated Circuits Conference
I E E E. 1995: 555–558
View details for Web of Science ID A1995BD31E00122
- Force-Sensing Microprobe for Precise Stimulation Of Mechanosensitive Tissues IEEE Transactions on Biomedical Engineering 1995; 42 (8): 745-750
- A Feedback Controlled Silicon Microprobe for Quantitative Mechanical Stimulation of Nerve and Tissue Journal of Neuroscience Methods 1995; 60 (12): 157-163
- A Micromachined Low-Power Temperature-Regulated Bandgap Voltage Reference IEEE Journal of Solid-State Circuits 1995; 30 (12): 1374-1381
- Microfabricated Heavy Metal Ion Sensor Sensors and Actuators B: Chemical 1995; 23 (1): 41-47
- Large-Signal Subthreshold CMOS Transconductance Amplifier Electronics Letters 1995; 31 (9): 718-720
- An Unconditionally Stable Two-Stage CMOS Amplifier IEEE Journal of Solid-State Circuits 1995; 30 (5): 591-594
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MICROFABRICATED HEAVY-METAL ION SENSOR
SENSORS AND ACTUATORS B-CHEMICAL
1995; 23 (1): 41-47
View details for Web of Science ID A1995QQ95400006
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VOLTAGE-MODE DEFUZZIFICATION CIRCUITS
INTERNATIONAL JOURNAL OF ELECTRONICS
1994; 77 (6): 1043-1057
View details for Web of Science ID A1994QG89800025
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THERMALLY AND ELECTRICALLY ISOLATED SINGLE-CRYSTAL SILICON STRUCTURES IN CMOS TECHNOLOGY
IEEE ELECTRON DEVICE LETTERS
1994; 15 (10): 399-401
View details for Web of Science ID A1994PL26900010
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FLEXIBLE, DRY-RELEASED PROCESS FOR ALUMINUM ELECTROSTATIC ACTUATORS
JOURNAL OF MICROELECTROMECHANICAL SYSTEMS
1994; 3 (3): 90-96
View details for Web of Science ID A1994RM17600001
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ANALOG MEDIAN CIRCUIT
ELECTRONICS LETTERS
1994; 30 (17): 1369-1370
View details for Web of Science ID A1994PG48100007
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FAST PRECISION VOLTAGE RECTIFIER
ELECTRONICS LETTERS
1994; 30 (16): 1269-1270
View details for Web of Science ID A1994PC86200009
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A THERMAL SIGNAL GENERATOR PROBE FOR THE STUDY OF NEURAL THERMAL TRANSDUCTION
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
1994; 41 (7): 649-655
Abstract
The study of thermal transduction in neural tissues has been impeded by the lack of instrumentation able to generate complex, focal temperature variations. Specifically, we are interested in the study of neural thermal transduction within the cornea, with its homogeneous thermal conductivity and avascularity. We present a thermal signal generator probe that is capable of producing arbitrarily shaped bipolar (heating or cooling) thermal swings in a small volume of corneal tissue with which it is in contact. Heating and cooling of the probe tip are achieved by means of a Peltier effect thermoelectric device. The probe temperature, measured directly at the tip, is controlled using closed-loop control circuitry and waveform generation software on a host computer. Response characteristics of thermally sensitive C-fibers were investigated in an in vitro preparation of the rabbit cornea.
View details for Web of Science ID A1994NY45600005
View details for PubMedID 7927385
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SILICON-SUBSTRATE MICROELECTRODE ARRAYS FOR PARALLEL RECORDING OF NEURAL ACTIVITY IN PERIPHERAL AND CRANIAL NERVES
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
1994; 41 (6): 567-577
Abstract
A new process for the fabrication of regeneration microelectrode arrays for peripheral and cranial nerve applications is presented. This type of array is implanted between the severed ends of nerves, the axons of which regenerate through via holes in the silicon and are thereafter held fixed with respect to the microelectrodes. The process described is designed for compatibility with industry-standard CMOS or BiCMOS processes (it does not involve high-temperature process steps nor heavily-doped etch-stop layers), and provides a thin membrane for the via holes, surrounded by a thick silicon supporting rim. Many basic questions remain regarding the optimum via hole and microelectrode geometries in terms of both biological and electrical performance of the implants, and therefore passive versions were fabricated as tools for addressing these issues in on-going work. Versions of the devices were implanted in the rat peroneal nerve and in the frog auditory nerve. In both cases, regeneration was verified histologically and it was observed that the regenerated nerves had reorganized into microfascicles containing both myelinated and unmyelinated axons and corresponding to the grid pattern of the via holes. These microelectrode arrays were shown to allow the recording of action potential signals in both the peripheral and cranial nerve setting, from several microelectrodes in parallel.
View details for Web of Science ID A1994NX62800007
View details for PubMedID 7927376
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IMPROVED ANALOG MEDIAN FILTER
ELECTRONICS LETTERS
1994; 30 (4): 284-285
View details for Web of Science ID A1994MY75400007
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AN INTEGRATED CMOS POTENTIOSTAT FOR MINIATURIZED ELECTROANALYTICAL INSTRUMENTATION
1994 IEEE International Solid-State Circuits Conference
I E E E. 1994: 162–163
View details for Web of Science ID A1994BA99E00062
- Microfabricated Electrochemical Detector for Capillary Electrophoresis 1994
- A New Silicon Microelectrode Array Technology for Multichannel Extracellular Recording Society for Neuroscience 24th Annual Meeting Abstracts, Miami Beach, FL 1994; 20 (1-2): 1745
- Dry-Released Process for Aluminum Electrostatic Actuators 1994
- Neural Microsensors for Automated Toxicity and Pharmacology Assays Society for Neuroscience Annual Meeting Abstracts, Miami Beach, FL 1994; 20 (1-2): 642
- Introduction to the Theory, Design and Modeling of Thin-Film Microelectrodes for Neural Interfaces Enabling Technologies for Cultured Neural Networks edited by Stenger, D., A., McKenna, T. Academic Press. 1994: 121–166
- An Analog Voltage-Mode Fuzzy Logic Controller 1994
- Silicon-Substrate Microelectrode Arrays for Parallel Recording of Neural Activity in Peripheral and Cranial Nerves IEEE Transactions on Biomedical Engineering 1994; 41 (6): 567 - 577
- Thermally and Electrically Isolated Single Crystal Silicon Structures in CMOS Technology IEEE Electron Device Letters 1994; 15 (10): 399-401
- An Improved Analogue Median Filter Electronics Letters 1994; 30 (4): 284 - 285
- Voltage-Mode Defuzzification Circuits International Journal of Electronics 1994; 77 (6): 1043-1057
- A Fast Precision Voltage Rectifier Electronics Letters 1994; 30 (16): 1269-1270
- A Thermal Signal Generator Probe for the Study of Neural Thermal Transduction IEEE Transactions on Biomedical Engineering 1994; 41 (7): 649 - 655
- An Analogue Median Circuit Electronics Letters 1994; 30 (17): 1369-1370
- Flexible, Dry-Released Process for Aluminum Electrostatic Actuators IEEE/ASME Journal of Microelectromechanical Systems 1994; 3 (3): 90-96
- A Microlithographically Fabricated Iridium-Based Mercury Ultramicroelectrode Array and its Application to SWASV Analysis of Metal Ions in Natural Waters Journal of Analytical Chemistry 1994; 66 (3): 418 - 423
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A GENERAL-PURPOSE SYSTEM FOR LONG-TERM RECORDING FROM A MICROELECTRODE ARRAY COUPLED TO EXCITABLE CELLS
JOURNAL OF NEUROSCIENCE METHODS
1993; 48 (1-2): 115-121
Abstract
A PC-based system for acquisition and processing of data from excitable cells on a microelectrode array is described. Simple and low-cost amplification and filtering custom stages are used. A software package for processing acquired data is proposed.
View details for Web of Science ID A1993LL48400012
View details for PubMedID 8377513
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CURRENT-MODE FUZZY MEMORY-ELEMENT
ELECTRONICS LETTERS
1993; 29 (2): 236-237
View details for Web of Science ID A1993LB76300071
- Current-Mode Fuzzy Memory Element Electronics Letters 1993; 29 (2): 236-237
- Regeneration-Type Peripheral Nerve Interfaces for Direct Man/Machine Communication Robots and Biological Systems: Towards a New Bionics? edited by Sandini, G., Dario, P., Aebischer, P. 1993: 637–665
- A Silicon Microprobe Closed-Loop Feedback Controlled Mechanical Stimulator System Society for Neuroscience 23rd Annual Meeting Abstracts, Washington, D.C. 1993; 19: 105
- BiCMOS Circuits for an Analog Fuzzy Processor 1993
- Response Characteristics of Thermal Sensitive Corneal Nociceptors Society for Neuroscience 23rd Annual Meeting Abstracts, Washington, D.C. 1993; 19: 323
- A General-Purpose System for Long-Term Recording from a Microelectrode Array Coupled to Excitable Cells Journal of Neuroscience Methods 1993; 48 (1-2): 115-121
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REGENERATION MICROELECTRODE ARRAY FOR PERIPHERAL-NERVE RECORDING AND STIMULATION
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
1992; 39 (9): 893-902
Abstract
A microelectrode array capable of recording from and stimulating peripheral nerves at prolonged intervals after surgical implantation has been demonstrated. The microelectrode array, fabricated on a silicon substrate perforated by multiple holes (referred to as via holes), is implanted between the ends of a surgically severed nerve. Regenerating tissue fixes the device in place to provide a stable mapping between the microelectrodes and the axons in the nerve. Processes were developed for the fabrication of thin-film iridium microelectrodes, micromachined via holes, and silicon nitride passivation layers. All fabrication methods were designed to be compatible with standard CMOS/BiCMOS processes to allow for on-chip signal processing circuits in future designs. Such arrays, implanted in the peroneal nerves of rats, were used to record from and stimulate the nerves at up to 13 months postoperatively.
View details for Web of Science ID A1992JK59300003
View details for PubMedID 1473818
- Regeneration Microelectrode Array for Peripheral Nerve Recording and Stimulation IEEE Transactions on Biomedical Engineering 1992; 39 (9): 893-902
- Actively-Scanned Microelectrode Arrays Society for Neuroscience 22nd Annual Meeting Abstracts, Anaheim, CA 1992; 18: 38
- Micromechanical Probe for Stimulation of Corneal Afferents Society for Neuroscience 22nd Annual Meeting Abstracts, Anaheim, CA 1992; 18: 830
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A METHOD FOR EVALUATING THE SELECTIVITY OF ELECTRODES IMPLANTED FOR NERVE SIMULATION
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
1991; 38 (5): 443-449
Abstract
The scale of stimulating electrodes possible for use in functional electrical stimulation to restore motor and sensory function is rapidly approaching that of individual neurons. Although the electrodes may approach the dimensions of single nerve cells, it is unclear if the region of excitation elicited by each electrode will be correspondingly small. Previous techniques for evaluating this have either been tedious or have lacked the resolution necessary. This paper describes a method that uses the refractory interaction of the compound action potentials elicited by a stimulus pulse pair, along with high-resolution recording of those potentials, to achieve measurements of the selectivity of stimulation down to the scale of a few axon diameters. The feasibility of this technique is demonstrated in sciatic nerves of frogs (Rana Catesbiana) acutely implanted with a sapphire electrode array.
View details for Web of Science ID A1991FP65500007
View details for PubMedID 1874526
- A Method for Evaluating the Selectivity of Electrodes Implanted for Nerve Stimulation IEEE Transactions on Biomedical Engineering 1991; 38 (5): 443-449
- Regeneration Microelectrode Arrays for Direct Interface to Nerves Digest of Technical Papers, Transducers ‘91v 1991: 116-119
- In Vitro Networks of Neurons: Technological and Cytometric Aspects Medical and Biological Engineering & Computing 1991; 29: 664
- Monitoring the Electrochemical Activity of Cultured Cells By Means of Solid State Microtransducers 1991
- Monitoring the Electrochemical Activity of Cultured Cells By Means of Solid State Microtransducers 1991
- Thin-Film Microelectrode Array for Peripheral Nerve Recording and Stimulation Society for Neuroscience Abstracts, New Orleans, LA 1991; 17: 567
- Development of a Neural Network Interface for Direct Central Nervous Control of a Prosthetic Limb 1990
- Fabrication Techniques for Directly Implantable Microelectronic Neural Interfaces 1989
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STANFORD-UNIVERSITY GENERAL-PURPOSE MICROELECTRODE FABRICATION PROCESS
1989 ANNUAL INTERNATIONAL CONF OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOC
I E E E. 1988: 1651–1652
View details for Web of Science ID A1988BP88P00850
- Design and Implementation of Two-Dimensional Neural Interfaces 1988
- Advances Toward Development of Microelectronic Axonal Interface Neuroprostheses 1988
- Design of Two-Dimensional Neural Prosthesis Microelectrode Arrays 1987
- Development of Chronic Implant Neural Prosthesis Microelectrode Arrays 1987
- The Development of a Microelectronic Axon Processor Silicon Chip Neuroprosthesis 1987