Bio

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


Honors & Awards


  • Secretary of Defense Medal for Exceptional Public Service, Department of Defense (2010)
  • Group Achievement Award for Columbia Investigation Medical Forensics, NASA (2008)
  • Fellow, IEEE (2008)
  • Thomas V. Jones Faculty Development Scholar, Thomas V. Jones (2003 - 2005)
  • Group Achievement Award for Columbia Accident Investigation, NASA (2003)
  • Fellow, American Institute for Medical and Biological Engineering (2003)
  • Fellow National, Explorer's Club (2001)
  • University Fellow, Stanford (1996-1998)
  • Terman Fellow, Stanford (1994-1997)
  • Robert N. Noyce Family Faculty Scholar Chair, Stanford (1992-1994)
  • Peter J. Gingrass, M.D., Memorial Award, Plastic Surgery Research Council (1990)
  • Hector MacLeod Scholarship in Electrical Engineering, University of British Columbia (1984)
  • Undergraduate Summer Research Award, Natural Sciences and Engineering Research Council of Canada (1982, 1983)
  • Young Investigator (NYI) Award, National Science Foundation (1993)

Professional Education


  • M.D., Stanford, Medicine (1992)
  • Ph.D., Stanford, Electrical Engineering (1990)
  • M.S., U.C. Berkeley, Bioengineering (1985)
  • B.A.Sc., University of British Columbia, Electrical Engineering (1984)

Research & Scholarship

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.

Publications

Journal Articles


  • Characterisation of electrophysiological conduction in cardiomyocyte co-cultures using co-occurrence analysis COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING Chen, M. Q., Wong, J., Kuhl, E., Giovangrandi, L., Kovacs, G. T. 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 Web of Science ID 000314564900007

    View details for PubMedID 21970595

  • Extracting respiratory information from seismocardiogram signals acquired on the chest using a miniature accelerometer PHYSIOLOGICAL MEASUREMENT Pandia, K., Inan, O. T., Kovacs, G. T., Giovangrandi, L. 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

  • Spatiotemporally Controlled Cardiac Conduction Block Using High-Frequency Electrical Stimulation PLOS ONE Dura, B., Kovacs, G. T., Giovangrandi, L. 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

  • A portable system for monitoring the behavioral activity of Drosophila JOURNAL OF NEUROSCIENCE METHODS Inan, O. T., Marcu, O., Sanchez, M. E., Bhattacharya, S., Kovacs, G. T. 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

  • Automatic detection of motion artifacts in the ballistocardiogram measured on a modified bathroom scale MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING Wiard, R. M., Inan, O. T., Argyres, B., Etemadi, M., Kovacs, G. T., Giovangrandi, L. 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

  • 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 Inan, O. T., Kovacs, G. T., Giovangrandi, L. 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

  • A Device for Separated and Reversible Co-Culture of Cardiomyocytes BIOTECHNOLOGY PROGRESS Chen, M. Q., Whittington, R. H., Day, P. W., Kobilka, B. K., Giovangrandi, L., Kovacs, G. T. 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 Web of Science ID 000281045100030

    View details for PubMedID 20730771

  • A low-noise ac-bridge amplifier for ballistocardiogram measurement on an electronic weighing scale PHYSIOLOGICAL MEASUREMENT Inan, O. T., Kovacs, G. T. 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

  • Adaptive Cancellation of Floor Vibrations in Standing Ballistocardiogram Measurements Using a Seismic Sensor as a Noise Reference IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Inan, O. T., Etemadi, M., Widrow, B., Kovacs, G. T. 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

  • Current-Controlled Electrical Point-Source Stimulation of Embryonic Stem Cells CELLULAR AND MOLECULAR BIOENGINEERING Chen, M. Q., Xie, X., Wilson, K. D., Sun, N., Wu, J. C., Giovangrandi, L., Kovacs, G. T. 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 PubMedID 20652088

  • Evolving Point-of-Care Diagnostics Using Up-Converting Phosphor Bioanalytical Systems ANALYTICAL CHEMISTRY Ouellette, A. L., Li, J. J., Cooper, D. E., Ricco, A. J., Kovacs, G. T. 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

  • Non-invasive cardiac output trending during exercise recovery on a bathroom-scale-based ballistocardiograph PHYSIOLOGICAL MEASUREMENT Inan, O. T., Etemadi, M., Paloma, A., Giovangrandi, L., Kovacs, G. T. 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

  • A Miniaturized Video System for Monitoring the Locomotor Activity of Walking Drosophila Melanogaster in Space and Terrestrial Settings IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Inan, O. T., Etemadi, M., Sanchez, M. E., Marcu, O., Bhattacharya, S., Kovacs, G. T. 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

  • Robust ballistocardiogram acquisition for home monitoring PHYSIOLOGICAL MEASUREMENT Inan, O. T., Etemadi, M., Wiard, R. M., Giovangrandi, L., Kovacs, G. T. 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

  • Optical scanner for immunoassays with up-converting phosphorescent labels IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Li, J. J., Ouellette, A. L., Giovangrandi, L., Cooper, D. E., Ricco, A. J., Kovacs, G. T. 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

  • Non-invasive Measurement of Valsalva-induced Hemodynamic Changes on a Bathroom Scale Ballistocardiograph 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 Inan, O. T., Etemadi, M., Wiard, R. M., Kovacs, G. T., Giovangrandi, L. 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

  • Cardiac Differentiation of Embryonic Stem Cells with Point-Source Electrical Stimulation 2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 Chen, M. Q., Xie, X., Whittington, R. H., Kovacs, G. T., Wu, J. C., Giovangrandi, L. 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 Web of Science ID 000262404501031

    View details for PubMedID 19163013

  • A discrete-time control algorithm applied to closed-loop pacing of HL-1 cardiomyocytes IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Whittington, R. H., Kovacs, G. T. 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

  • Robust neural-network-based classification of premature ventricular contractions using wavelet transform and timing interval features IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Inan, O. T., Giovangrandi, L., Kovacs, G. T. 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

  • 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 Whittington, R. H., Chen, M. Q., Giovangrandi, L., Kovacs, G. T. 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

  • A multiparameter wearable physiologic monitoring system for space and terrestrial applications IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE Mundt, C. W., Montgomery, K. N., Udoh, U. E., Barker, V. N., Thonier, G. C., Tellier, A. M., Ricks, R. D., Darling, R. B., Cagle, Y. D., Cabrol, N. A., Ruoss, S. J., Swain, J. L., Hines, J. W., Kovacs, G. T. 2005; 9 (3): 382-391

    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

  • A closed-loop electrical stimulation system for cardiac cell cultures IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Whittington, R. H., Giovangrandi, L., Kovacs, G. T. 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

  • Sensitivity of cell-based biosensors to environmental variables BIOSENSORS & BIOELECTRONICS Gilchrist, K. H., Giovangrandi, L., Whittington, R. H., Kovacs, G. T. 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

  • 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) Montgomery, K., Mundt, C., Thonier, G., Tellier, A., Udoh, U., Barker, V., Ricks, R., Davies, P., Cagle, Y., Swain, J., Hines, J., Kovacs, G. 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 Droitcour, A. D., Boric-Lubecke, O., Lubecke, V. M., Lin, J., Kovacs, G. T. A. 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 Droitcour, A.D., Boric-Lubecke, O., Lubecke, V. M., Lin, J., Kovacs, G. T. A. 2004; E87-C (9): 1524 - 1531
  • Electronic Sensors with Living Cellular Components Proceedings of the IEEE Kovacs, G. T. A. 2003; 91 (6): 915 ? 929
  • Retinal ganglion cells do not extend axons by default: Promotion by neurotrophic signaling and electrical activity NEURON Goldberg, J. L., Espinosa, J. S., Xu, Y. F., Davidson, N., Kovacs, G. T., Barres, B. A. 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

  • Stimulus Representation in Rat Primary Visual Cortex: Multi-Electrode Recordings with Micromachined Silicon Probes and Estimation Theory Neurocomputing Freiwald, W. A., Stemmann, H., Wannig, A., Kreiter, A. K., Hofmann, U. G., Hills, M. D., Kovacs, G. T. A., Kewley, D. T., Bower, J. M. 2002; 44 - 46: 407 - 416
  • An In-Line Osmometer for Application to a Cell-Based Biosensor System Sensors and Actuators B: Chemical Mourlas, N. J., Gilchrist, K. H., Giovangrandi, L., Maluf, N. I., Kovacs, G. T. A. 2002; 83: 41 - 47
  • Retinal Ganglion Cells Do Not Extend Axons by Default: Promotion by Neurotrophic Signaling and Electrical Activity Neuron Goldberg, J. L., Espinosa, J. S., Xu, Y., Davidson, N., Kovacs, G. T. A., Barres, B. A. 2002; 33: 689-702
  • A genetically engineered cell-based biosensor for functional classification of agents BIOSENSORS & BIOELECTRONICS Aravanis, A. M., DeBusschere, B. D., Chruscinski, A. J., Gilchrist, K. H., Kobilka, B. K., Kovacs, G. T. 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

  • General purpose, field-portable cell-based biosensor platform BIOSENSORS & BIOELECTRONICS Gilchrist, K. H., Barker, V. N., Fletcher, L. E., DeBusschere, B. D., Ghanouni, P., Giovangrandi, L., Kovacs, G. T. 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

  • Portable cell-based biosensor system using integrated CMOS cell-cartridges BIOSENSORS & BIOELECTRONICS DeBusschere, B. D., Kovacs, G. T. 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

  • A Genetically Engineered Cell-Based Biosensor for Functional Classification of Agents Biosensors and Bioelectronics Aravanis, A. M., DeBusschere, B. D., Chruscinski, A. J., Gilchrist, K. H., Kobilka, B. K., Kovacs, G. T. A. 2001; 16: 571 - 577
  • Lysing Bacterial Spores by Sonication Through a Flexible Interface in a Microfluidic System Analytical Chemistry Taylor, M. T., Belgrader, P., Furman B. J., Pourahmadi, F., Kovacs, G. T. A., Northrup, M. A. 2001; 73 (3): 492-496
  • Integration of Sputtered Silicon Microstrutures with Pre-Fabricated CMOS Circuitry Sensors and Actuators A: Physical Honer, K. A., Kovacs, G. T. A. 2001; 91 (3): 492-496
  • A Docking System for Microsatellites Based on MEMS Actuator Arrays Smart Materials and Structures Terry, M., Reiter, J., Bhringer, K. F., Suh, J. W., Kovacs, G. T. A. 2001; 10 (6): 1176 - 1184
  • General Purpose, Field-Portable Cell-Based Biosensor Platform Biosensors and Bioelectronics Gilchrist, K. H., Barker, V. N., Fletcher, L. E., DeBusschere, B. D., Ghanouni, P., Giovangrandi, L., Kovacs, G. T. A. 2001; 16: 557 - 564
  • Portable Cell-Based Biosensor System Using Integrated CMOS Cell-Cartridges Biosensors and Bioelectronics DeBusschere, B. D., Kovacs, G. T. A. 2001; 16: 543 - 556
  • A Traction Stress Sensor Array for Use in High-Resolution Robotic Tactile Imaging IEEE/ASME Journal of Microelectromechanical Systems Kane, B. J., Cutkosky, M. R., Kovacs, G. T. A. 2000; 9 (4): 425-434
  • Thermo-Bimorph Microcilia Arrays for Small Spacecraft Docking MEMS 2000 - ASME International Mechanical Congress and Exposition, Orlando, FL Reiter, J., Terry, M., Bohringer, K., F., Suh, J., W., Kovacs, G., T. A. 2000: 57 - 63
  • An Integrated Controller for Tunnel Sensors IEEE Journal of Solid State Circuits Partridge, A., Reynolds, J. K., Grade, J. D., Kane, B. J., Maluf, N. I., Kovacs, G. T. A., Kenny, T. W. 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 Suh, J. W., Darling, R. B., Bhringer, K.-F., Donald, B. R., Baltes, H., Kovacs, G. T. A. 1999; 8 (4): 483 - 496
  • Novel Interconnection Technologies for Integrated Microfluidic Systems Sensors and Actuators A Gray, B. L., Jaeggi, D., Mourlas, N. J., van Drienhuizen, B. P., Williams, K. R., Maluf, N. I., Kovacs, G. T. A. 1999; 77 (1): 57 - 65
  • A Minisonicator to Rapidly Disrupt Bacterial Spores for DNA Analysis Analytical Chemistry Belgrader, P., Hansford, D., Kovacs, G. T. A., Venkateswaran, K., Mariella, R., Milanovich, F., Nasarabadi, S., Okuzumi, M., Pourahmadi, F., Northrup, M. A. 1999; 71 (19): 4232 - 4236
  • Biological Warfare Agent Decontamination Defense Sciences Research Council Study Report Series Kovacs, G., Scannon, P., Giroir, B. 1999
  • Ciliary Microactuator Array for Scanning Electron Microscope Positioning Stage Journal of Vacuum Science & Technology A (Vacuum, Surfaces, and Films) Darling, R. B., Suh, J. W., Kovacs, G. T. A. 1998; 16 (3): 1998-2002
  • Description and Demonstration of a CMOS Amplifier-Based-System with Measurement and Stimulation Capability for Bioelectrical Signal Transduction Biosensors and Bioelectronics Pancrazio, J. J., Bey, P. P., Loloee, A., Manne, S., Chau, H.-C., Howard, L. H., Gosney, W. M., Borkholder, D. A., Kovacs, G. T. A., Manos, P., Cuttino, D. S., Stenger, D. A. 1998; 13: 971-979
  • Field Evaluation of an Electrochemical Probe for In Situ Screening of Heavy Metals in Groundwater Environmental Science and Technology Herdan, J., Feeney, R., Kounaves, S. P., Flannery, A. F., Storment, C. W., Kovacs, G. T. A., Darling, R. B. 1998; 32 (1): 131-136
  • Toward Next Generation Clinical Diagnostic Instruments: Scaling and New Processing Paradigms Journal of Biomedical Microdevices Petersen, K. E., McMillan, W. A., Kovacs, G. T. A., Northrup, M. A., Christel, L. A., Pourahmadi, F. 1998; 1 (1): 71 - 79
  • PECVD Silicon Carbide as a Chemically Resistant Material for Micromachined Transducers Sensors and Actuators A Flannery, A. F., Mourlas, N. J., Storment, C. W., Tsai, S., Tan, S. H., Heck, J., Monk, D., Gogoi, B., Kovacs, G. T. A. 1998; 70 (1 - 2): 48 - 55
  • Bulk Micromachining of Silicon Proceedings of the IEEE Kovacs, G. T. A., Maluf, N. I., Petersen, K. E. 1998; 86 (8): 1536 - 1551
  • Portable Cell-Based Biosensor System for Toxin Detection Sensors and Actuators B: Chemical Pancrazio, J. J., Bey, P. P., Jr., Cuttino, D. S., Kusel, J. K., Borkholder, D. A., Shaffer, K. M., Kovacs, G. T. A., Stenger, D. A. 1998; 53 (3): 179 - 185
  • 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) Jung, D. R., Cuttino, D.S., Pancrazio, J. J., Manos, P., Cluster, T., Sathanoori, R. S., Aloi, L. E., Coulombe, M. G., Bey, P., Czarnaski, M. A., Borkholder, D. A., Kovacs, G. T. A., Bey, P., Stenger, D. A., Hickman, J. J. 1998; 16 (3): 1183-1188
  • Electrically Floating Conductivity Detection System for Capillary Electrophoresis Journal of Chromatography A Zhao, H., Dadoo, R., Reay, R. J., Kovacs, G. T. A., Zare, R. N. 1998; 813 (1): 205 - 208
  • Microelectrode arrays for stimulation of neural slice preparations JOURNAL OF NEUROSCIENCE METHODS Borkholder, D. A., Bao, J., Maluf, N. I., Perl, E. R., Kovacs, G. T. 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

  • Microelectrode Arrays for Stimulation of Neural Slice Preparations Journal of Neuroscience Methods Borkholder, D. A., Bao, J., Maluf, N. I., Perl, E. R., Kovacs, G. T. A. 1997; 77 (1): 61-66
  • Computational Methods for Design and Control of MEMS Micromanipulator Arrays IEEE Computational Science and Engineering Bohringer, K. F., Donald, B. R., MacDonald, N. C., Kovacs, G. T. A., Suh, J. W. 1997; 4 (1): 17-29
  • Micromachined Thermally Isolated Circuits Sensors and Actuators A Klaassen, E. H., Reay, R. J., Storment, C. W., Kovacs, G. T. A. 1997; 58 (1): 43-50
  • Multi-Unit Recording from Regenerated Bullfrog Eighth Nerve Using Implantable Silicon-Substrate Microelectrodes Journal of Neuroscience Methods Della Santina, C. C., Kovacs, G. T. A., Lewis, E. R. 1997; 72 (1): 71-86
  • Miniature Spectrometers for Biochemical Analysis Sensors and Actuators A Yee, G. M., Maluf, N. I., Hing, P. A., Albin, M. I., Kovacs, G. T. A. 1997; 58 (1): 61-66
  • Plasma-Etched Neural Probes Sensors and Actuators A Kewley, D. T., Hills, M. D., Borkholder, D. A., Opris, I. E., Maluf, N. I., Storment, C. W., Bower, J. M., Kovacs, G. T. A. 1997; 58 (1): 27-35
  • Integrated Thermal Conductivity Vacuum Sensor Sensors and Actuators A Klaassen, E. H., Kovacs, G. T. A. 1997; 58 (1): 37-42
  • DSRC Report on Improving Human Performance Defense Sciences Research Council Report Kovacs, G. 1997
  • Organic Thermal and Electrostatic Ciliary Microactuator Array for Object Manipulation Sensors and Actuators A Suh, J. W., Glander, S. F., Darling, R. B., Storment, C. W., Kovacs, G. T. A. 1997; 58 (1): 51-60
  • CMOS-Compatible Traction Stress Sensor for Use In High-Resolution Tactile Imaging Sensors and Actuators A Kane, B. J., Cutkosky, M. R., Kovacs, G. T. A. 1996; 54: 511-516
  • Silicon Micromachining Analytical Chemistry Kovacs, G. T. A., Petersen, K., Albin, M. 1996; 68: 407A-412A
  • Characterizing Deflectable Microstructures Via a High-Resolution Laser-Based Measurement System Sensors and Actuators A Honer, K. A., Maluf, N. I., Martinez, E., Kovacs, G. T. A. 1996; 52 (1-3): 12-17
  • Microfabricated Electrochemical Analysis System for Heavy Metal Detection Sensors and Actuators B Reay, R. J., Storment, C. W., Flannery, A. F., Kounaves, S. P., Kovacs, G. T. A. 1996; 34 (1-3): 450-455
  • Silicon Fusion Bonding and Deep Reactive Ion Etching Sensors and Actuators A Klaassen, E. H., Petersen, K., Noworolski, J. M., Logan, J., Maluf, N. I., Brown, J., Storment, C., McCulley, W., Kovacs, G. T. A. 1996; 52 (1-3): 132-139
  • High-Voltage Devices and Circuits Fabricated Using Foundry CMOS for Use With Electrostatic MEM Actuators Sensors and Actuators A Maluf, M. I., Reay, R. J., Kovacs, G. T. A. 1996; 52 (1-3): 187-192
  • A Rail-to-Rail Ping-Pong Op-Amp IEEE Journal of Solid-State Circuits Opris, I. E., Kovacs, G. T. A. 1996; 31 (9): 1320-1324
  • Diode-Based Thermal RMS Converter with On-Chip Circuitry Fabricated Using Standard CMOS Technology Sensors and Actuators A Klaassen, E. H., Reay, R. J., Kovacs, G. T. A. 1996; 52 (1): 33-40
  • DSRC Tissue Engineering Workshop Summary Report Defense Sciences Research Council Report Kovacs, G. 1996
  • Characterizing Deflectable Microstructures Via a High-Resolution Laser-Based Measurement System Sensors and Actuators A Honer, K., A., Maluf, N., I., Martinez, E., Kovacs, G., T. A. 1996; 52 (1-3): 12 - 17
  • Biosensors Utilizing Neural Cells as Sensing Elements Society for Neuroscience 26th Annual Meeting Abstracts, Washington, D.C. Hickman, J., J., Stenger, D., A., Kovacs, G., T. A. 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 Mohan, J., Maluf, N., I., Petersen, K., E., Kovacs, G., T. A. 1996: 21-22
  • Advanced Technologies for Defense Against Biological Warfare Agents Defense Sciences Research Council Report Whitesides, G., Kovacs, G. 1996
  • New Materials for MEMS Defense Sciences Research Council Report Heuer, A., Cross, E., Kovacs, G. 1996
  • Mesoscopic Machines Defense Sciences Research Council Report Kovacs, G. 1996
  • FORCE-SENSING MICROPROBE FOR PRECISE STIMULATION OF MECHANOSENSITIVE TISSUES IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Kane, B. J., Storment, C. W., CROWDER, S. W., Tanelian, D. L., Kovacs, G. T. 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

  • Microfabricated Electrochemical Analysis System for Heavy Metal Detection Digest of Technical Papers from Transducers ?95/Eurosensors IX Stockholm, Sweden Reay, R., J., Storment, C., W., Flannery, A., F., Kounaves, S., P., Kovacs, G., T. A. 1995; 2: 932 - 935
  • Force-Sensing Microprobe for Precise Stimulation Of Mechanosensitive Tissues IEEE Transactions on Biomedical Engineering Kane, B. J., Storment, C. W., Crowder, S. W., Tanelian, D. L., Kovacs, G. T. A. 1995; 42 (8): 745-750
  • A Feedback Controlled Silicon Microprobe for Quantitative Mechanical Stimulation of Nerve and Tissue Journal of Neuroscience Methods Jackson, D., Kane, B. J., Monroe, S., Li, J., Storment, C. W., Kovacs, G. T. A., Tanelian, D. L. 1995; 60 (12): 157-163
  • Large-Signal Subthreshold CMOS Transconductance Amplifier Electronics Letters Opris, I., Kovacs, G. T. A. 1995; 31 (9): 718-720
  • A Micromachined Low-Power Temperature-Regulated Bandgap Voltage Reference IEEE Journal of Solid-State Circuits Reay, R. J., Klaassen, E. H., Kovacs, G. T. A. 1995; 30 (12): 1374-1381
  • Microfabricated Heavy Metal Ion Sensor Sensors and Actuators B: Chemical Kovacs, G. T. A., Storment, C. W., Kounaves, S. P. 1995; 23 (1): 41-47
  • An Unconditionally Stable Two-Stage CMOS Amplifier IEEE Journal of Solid-State Circuits Reay, R. J., Kovacs, G. T. A. 1995; 30 (5): 591-594
  • 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 Klaassen, E., H., Reay, R., J., Kovacs, G., T. A. 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 Honer, K., A., Maluf, N., I., Martinez, E., Kovacs, G., T. A. 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 Kane, B., J., Kovacs, G., T. A. 1995; 1: 648 - 651
  • On-Chip Chemical Analysis Defense Sciences Research Council Report Wyatt, J., Whitesides, G., Kovacs, G. 1995
  • Microfabricated Heavy Metal Ion Sensor Sensors and Actuators B: Chemical Kovacs, G., T. A., Storment, C., W., Kounaves, S., P. 1995; 23 (1): 41 - 47
  • A THERMAL SIGNAL GENERATOR PROBE FOR THE STUDY OF NEURAL THERMAL TRANSDUCTION IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Maluf, N. I., MCNUTT, E. L., Monroe, S., Tanelian, D. L., Kovacs, G. T. 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

  • SILICON-SUBSTRATE MICROELECTRODE ARRAYS FOR PARALLEL RECORDING OF NEURAL ACTIVITY IN PERIPHERAL AND CRANIAL NERVES IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Kovacs, G. T., Storment, C. W., HALKSMILLER, M., BELCZYNSKI, C. R., DELLASANTINA, C. C., Lewis, E. R., Maluf, N. I. 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

  • Neural Microsensors for Automated Toxicity and Pharmacology Assays Society for Neuroscience Annual Meeting Abstracts, Miami Beach, FL Kowtha, V., C., Stenger, D., A., Beay, P., P., Borkholder, D., Kovacs, G., T., Foster, K., E. 1994; 20 (1-2): 642
  • Silicon-Substrate Microelectrode Arrays for Parallel Recording of Neural Activity in Peripheral and Cranial Nerves IEEE Transactions on Biomedical Engineering Kovacs, G. T. A., Storment, C. W., Halks-Miller, M., Belczynski, C. R., Della Santina, C. C., Lewis, E. R., Maluf, N. I. 1994; 41 (6): 567 - 577
  • A Fast Precision Voltage Rectifier Electronics Letters Opris, I., Kovacs, G. T. A. 1994; 30 (16): 1269-1270
  • Thermally and Electrically Isolated Single Crystal Silicon Structures in CMOS Technology IEEE Electron Device Letters Reay, R. J., Klaassen, E. H., Kovacs, G. T. A. 1994; 15 (10): 399-401
  • Voltage-Mode Defuzzification Circuits International Journal of Electronics Opris, I. E., Kovacs, G. T. A. 1994; 77 (6): 1043-1057
  • An Analogue Median Circuit Electronics Letters Opris, I., Kovacs, G. T. A. 1994; 30 (17): 1369-1370
  • An Improved Analogue Median Filter Electronics Letters Opris, I., Kovacs, G. T. A. 1994; 30 (4): 284 - 285
  • A Thermal Signal Generator Probe for the Study of Neural Thermal Transduction IEEE Transactions on Biomedical Engineering Maluf, N. I., McNutt, E. L., Monroe, S., Tanelian, D. L., Kovacs, G. T. A. 1994; 41 (7): 649 - 655
  • Flexible, Dry-Released Process for Aluminum Electrostatic Actuators IEEE/ASME Journal of Microelectromechanical Systems Storment, C. W., Borkholder, D. A., Westerlind, V., Suh, J. W., Maluf, N. I., Kovacs, G. T. A. 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 Kounaves, S. P., Deng, W., Kovacs, G. T. A., Storment, C. W. 1994; 66 (3): 418 - 423
  • A New Silicon Microelectrode Array Technology for Multichannel Extracellular Recording Society for Neuroscience 24th Annual Meeting Abstracts, Miami Beach, FL Kewley, D., T., Borkholder, D., A., Storment, C., W., Bower, J., M., Kovacs, G., T. A. 1994; 20 (1-2): 1745
  • Current-Mode Fuzzy Memory Element Electronics Letters Balteanu, F., Opris, I., Kovacs, G. 1993; 29 (2): 236-237
  • A General-Purpose System for Long-Term Recording from a Microelectrode Array Coupled to Excitable Cells Journal of Neuroscience Methods Martinoia, S., Bove, M., Carlini, G., Ciccarelli, C., Grattarola, M., Storment, C., Kovacs, G. 1993; 48 (1-2): 115-121
  • A Silicon Microprobe Closed-Loop Feedback Controlled Mechanical Stimulator System Society for Neuroscience 23rd Annual Meeting Abstracts, Washington, D.C. Kane, B., Jackson, D., Li, J., Storment, C., Tanelian, D., Kovacs, G. 1993; 19: 105
  • Response Characteristics of Thermal Sensitive Corneal Nociceptors Society for Neuroscience 23rd Annual Meeting Abstracts, Washington, D.C. Monroe, S., Maluf, N., Kovacs, G., Tanelian, D., L. 1993; 19: 323
  • REGENERATION MICROELECTRODE ARRAY FOR PERIPHERAL-NERVE RECORDING AND STIMULATION IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Kovacs, G. T., Storment, C. W., Rosen, J. M. 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

  • Micromechanical Probe for Stimulation of Corneal Afferents Society for Neuroscience 22nd Annual Meeting Abstracts, Anaheim, CA Kane, B., J., Kovacs, G., T. A., Storment, C., W., Tanelian, D., L. 1992; 18: 830
  • Regeneration Microelectrode Array for Peripheral Nerve Recording and Stimulation IEEE Transactions on Biomedical Engineering Kovacs, G. T. A., Storment, C. W., Rosen, J. M. 1992; 39 (9): 893-902
  • Actively-Scanned Microelectrode Arrays Society for Neuroscience 22nd Annual Meeting Abstracts, Anaheim, CA Whitehurst, T., K., Storment, C., W., Belczynski, C., R., Kovacs, G., T. A. 1992; 18: 38
  • A METHOD FOR EVALUATING THE SELECTIVITY OF ELECTRODES IMPLANTED FOR NERVE SIMULATION IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Liang, D. H., Kovacs, G. T., Storment, C. W., White, R. L. 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

  • Thin-Film Microelectrode Array for Peripheral Nerve Recording and Stimulation Society for Neuroscience Abstracts, New Orleans, LA Kovacs, G., T. A., Storment, C., W., Belczynski, C., R., Nguyen, K., D., Rosen, J., M. 1991; 17: 567
  • A Method for Evaluating the Selectivity of Electrodes Implanted for Nerve Stimulation IEEE Transactions on Biomedical Engineering Liang, D. H., Kovacs, G. T. A., Storment, C. W., White, R. L. 1991; 38 (5): 443-449
  • Regeneration Microelectrode Arrays for Direct Interface to Nerves Digest of Technical Papers, Transducers ?91v Kovacs, G., T. A. 1991: 116-119
  • In Vitro Networks of Neurons: Technological and Cytometric Aspects Medical and Biological Engineering & Computing Grattarola, M., Kovacs, G., Martinoia, S., Belczynski, C., Cambiaso, A., Storment, C. 1991; 29: 664

Books and Book Chapters


  • CMOS Integrated Organic Ciliary Actuator Arrays for General-Purpose Micromanipulation Tasks Distributed Manipulation Suh, J., W., Darling, R., B., Bohringer, K., F., Donald, B., R., Baltes, H., Kovacs, G., T. A. edited by Bohringer, K., F., Choset, H. Kluwer Academic Publishers, Norwell, MA. 2000: 191-215
  • Micromachined Transducers Sourcebook Kovacs, G., T. A. McGraw-Hill, Inc., New York, NY. 1998
  • Thoughts on Becoming and Being an Analog Circuit Designer The Art and Science of Analog Circuit Design Kovacs, G., T. A. edited by Williams, J. Butterworth-Heinemann, Boston, MA. 1995: 41-54
  • Introduction to the Theory, Design and Modeling of Thin-Film Microelectrodes for Neural Interfaces Enabling Technologies for Cultured Neural Networks Kovacs, G., T. A. edited by Stenger, D., A., McKenna, T. Academic Press. 1994: 121 - 166
  • Regeneration-Type Peripheral Nerve Interfaces for Direct Man/Machine Communication Robots and Biological Systems: Towards a New Bionics? Kovacs, G., T. A., Rosen, J., M. edited by Sandini, G., Dario, P., Aebischer, P. 1993: 637-665

Conference Proceedings


  • Microfluidic platelet analysis platform based on impedance spectroscopy Evander, M., Ricco, A., J., Morser, J., Kovacs, G., T. A., Leung, L. L., K., Giovangrandi, L. 2012
  • Ballistocardiography ? A method worth revisiting Giovangrandi, L., Inan, O., T., Wiard, R., M., Etemadi, M., Kovacs, G., T. A. 2011
  • Motion artifact cancelation to obtain heart sounds from a single chest-worn accelerometer Pandia, K., Vijayraghavan, K., Kovacs, G., T. A., Giovangrandi, L. 2010
  • Physical Modeling of Low-Frequency Sound Propagation through Human Thoracic Tissue Pandia, K., Vijayraghavan, K., Kovacs, G. T., Giovangrandi, L. 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 Evander, M., Dura, B., Ricco, A., J., Kovacs, G., T. A., Giovangrandi, L. 2010
  • Chest-Acclerometery for Hemodynamic Trending During Valsalva-Recovery Pandia, K., Ravindran, S., Kovacs, G., T. A., Giovangrandi, L., Cole, R. 2010
  • Conduction Analysis in Mixed Cardiomyocytes-Fibroblasts Cultures using Microelectrode Arrays Roy, S., Chen, M. Q., Kovacs, G. T., Giovangrandi, L. 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 Web of Science ID 000280543603157

    View details for PubMedID 19964347

  • Modeling Conduction in Host-Graft Interactions Between Stem Cell Grafts and Cardiomyocytes Chen, M. Q., Yu, J., Whittington, R. H., Wu, J. C., Kovacs, G. T., Giovangrandi, L. 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 Web of Science ID 000280543604229

    View details for PubMedID 19964687

  • Estimation of Central Aortic Forces in the Ballistocardiogram under Rest and Exercise Conditions Wiard, R. M., Kim, H. J., Figueroa, C. A., Kovacs, G. T., Taylor, C. A., Giovangrandi, L. 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

  • Non-Invasive Assessment of Cardiac Contractility on a Weighing Scale Etemadi, M., Man, O. T., Wiard, R. M., Kovacs, G. T., Giovangrandi, L. 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

  • Novel Methods for Estimating the Ballistocardiogram Signal Using a Simultaneously Acquired Electrocardiogram Inan, O. T., Etemadi, M., Wiard, R. M., Kovacs, G. T., Giovangrandi, L. 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

  • Point-Source Electrical Stimulation of Embryonic Stem Cells for Cardiac Repair Chen, M., Q., Xie, X., Kovacs, G., T. A., Wu, J., C., Giovangrandi, L. 2008
  • Modeling and Control of a 3-Degree of Freedom Walking Microrobot Chen, Y., M., Suh, J., W., Kovacs, G., T. A., Darling, R., B., Böhringer, K., F. 2006
  • Micro and Nanoscale Education at Stanford University Barlian, A., A., Howe, R., T, Kovacs, G., T. A., Pruitt, B., L. 2006
  • Wireless IC Doppler Radars for Sensing of Heart and Respiration Activity Boric-Lubecke, O., Droitcour, A., D., Lubecke, V., M., Lin, J., Kovacs, G., T. A. 2003
  • Measurement of Changes in Tissue Metabolism Using a Clark-Type Oxygen Sensor Franc, B., Peixoto, N., Giovangrandi, L., McLaughlin, G., Kovacs, G., T. A. 2002
  • Active SOI-Based Neural Probes Hills, M., D., Kewley, D., T., Bower, J., M., Kovacs, G., T. A. 2002
  • Omnidirectional Walking Microrobot Realized by Thermal Microactuator Arrays Mohebbi, M., H., Terry, M., L., Böhringer, K., F., Kovacs, G., T. A., Suh, J., W. 2001
  • Fully Programmable MEMS Ciliary Actuator Arrays for Micromanipulation Tasks Suh, J., W., Darling, R., B., Bohringer, K., F., Donald, B., R., Baltes, H., Kovacs, G., T. A. 2000
  • Versatile, Adaptable and Programmable Microfluidic Platforms for DNA Diagnostics and Drug Discovery Assays Pourahmadi, F., Lloyd, K., Kovacs, G., Chang, R., Taylor, M., Sakai, S. 2000
  • Sputtered Silicon for Integrated MEMS Applications Honer, K., A., Kovacs, G., T. A. 2000
  • Hybrid Biosensors: Harnessing Living Tissues for Chem/Bio Warfare Agent Detection Borkholder, D., A., DeBusschere, B., D., Kovacs, G., T. A. 1999
  • Integrated Clark-Type Oxygen Sensor Array Using a Pulsed Plasma Deposited PTFE-Like Film McLaughlin, G., W., Flannery, A., F., Storment, C., W., Kovacs, G., T. A. 1999
  • Genetically Engineered Cell-Based Biosensors for Specific Agent Classification DeBusschere, B., D., Aravanis, A., M., Chruscinski, A., J., Hedgepath, K., R., Borkholder, D., A., Kobilka, B., K., Kovacs, G. T. 1999
  • A Low-Cost, Micromachined, Integrated CMOS Spectrometer Yee, G., M., Maluf, N., I., Kovacs, G., T. A. 1999
  • Reusable Microfluidic Coupler with PDMS Gasket Mourlas, N., J., Jaeggi, D., Maluf, N., I., Kovacs, G., T. A. 1999
  • High Aspect Ratio Silicon Microstructures for Nucleic Acid Extraction Christel, L., A., Petersen, K., McMillan, W., Kovacs, G., T. A. 1998
  • Novel Analytical Technique for On-Line Monitoring of Trace Heavy Metals in Corrosive Chemicals Tsai, S., Tan, S., H., Flannery, A., F., Storment, C., W., Kovacs, G., T. A. 1998
  • An Approach to the Classification of Unknown Biological Agents with Cell Based Sensors Borkholder, D., A., DeBusschere, B., D., Kovacs, G., T. A. 1998
  • Design of an Integrated Silicon-PDMS Cell Cartridge DeBusschere, B., D., Borkholder, D., A., Kovacs, G., T. A. 1998
  • System Requirements for a Portable Cell Based Sensor DeBusschere, B., D., Borkholder, D., A., Kovacs, G., T. A. 1998
  • Vector Fields for Task-Level Distributed Manipulation: Experiments with Organic Micro Actuator Arrays Bohringer, K., F., Suh, J., Donald, B., R., Kovacs, G. 1997
  • Force-Balanced Accelerometer with mG Resolution, Fabricated Using Silicon Fusion Bonding and Deep Reactive Ion Etching van Drieënhuizen, B., P., Maluf, N., I., Opris, I., E., Kovacs, G., T. A. 1997
  • Combined Organic Thermal and Electrostatic Omnidirectional Ciliary Microactuator Array for Object Positioning and Inspection Suh, J., W., Glander, S., F., Darling, R., B., Storment, C., W., Kovacs, G. T., A. 1996
  • Impedance Imaging for Hybrid Biosensor Applications Borkholder, D., A., Maluf, N., I., Kovacs, G., T. A. 1996
  • Miniaturized Spectrometers for Biochemical Analysis Yee, G., M., Hing, P., A., Maluf, N., I., Kovacs, G., T. A. 1996
  • Microfabricated Electrochemical Detector for Capillary Electrophoresis Reay, R., J., Dadoo, R., Storment, C., W., Zare, R., N., Kovacs, G. T., A. 1994
  • An Analog Voltage-Mode Fuzzy Logic Controller Opris, I., Kovacs, G., T. A. 1994
  • Dry-Released Process for Aluminum Electrostatic Actuators Storment, C., W., Borkholder, D., A., Westerlind, V., A., Suh, J., W., Maluf, N., I., Kovacs, G., T. A. 1994
  • BiCMOS Circuits for an Analog Fuzzy Processor Opris, I., Balteanu, F., Kovacs, G. 1993
  • Monitoring the Electrochemical Activity of Cultured Cells By Means of Solid State Microtransducers Grattarola, M., Martinoia, S., Cambiaso, A., Carlini, G., Tedesco, M., Kovacs, G., T. A. 1991
  • Monitoring the Electrochemical Activity of Cultured Cells By Means of Solid State Microtransducers Grattarola, M., Martinoia, S., Cambiaso, A., Carlini, G., Tedesco, M., Kovacs, G., T. A. 1991
  • Development of a Neural Network Interface for Direct Central Nervous Control of a Prosthetic Limb Wan, E., A., Kovacs, G., T. A., Rosen, J., M., Widrow, B. 1990
  • Fabrication Techniques for Directly Implantable Microelectronic Neural Interfaces Kovacs, G., T. A., Storment, C., W., Hentz, V., R., Rosen, J., M. 1989
  • Advances Toward Development of Microelectronic Axonal Interface Neuroprostheses Kovacs, G., T. A., Storment, C., W., McVittie, J., P., Knapp, W., R., Hentz, V., R., Rosen, J., M. 1988
  • Design and Implementation of Two-Dimensional Neural Interfaces Kovacs, G., T. A., Storment, C., W., Jemes, B., Hentz, V., R., Rosen, J., M. 1988
  • Design of Two-Dimensional Neural Prosthesis Microelectrode Arrays Kovacs, G., T. A., Stephanides, M., C., Knapp, W., R., McVittie, J., P., Rosen, J., M. 1987
  • Development of Chronic Implant Neural Prosthesis Microelectrode Arrays Kovacs, G., T. A., Stephanides, M., C., Knapp, W., R., McVittie, J., P., Hentz, V., R., Rosen, J., M. 1987
  • The Development of a Microelectronic Axon Processor Silicon Chip Neuroprosthesis Rosen, J., M., Kovacs, G., T. A., Stephanides, M., C., Marshall, D., Grosser, M., Hentz, V., R. 1987

Footer Links:

Stanford Medicine Resources: