Artificial Organs and Devices - Posters

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Poster Presentations 25 PREDICTION OF PHYSIOLOGIC SIGNALS IN SLEEP APNEA Joel Bock and David Gough, Department of Bioengineering, University of California San Diego, La Jolla, CA Obstructive sleep apnea is successfully managed using a mechanical ventilation technique known as nasal continuous positive airway pressure, but long-term patient compliance is problematic. A device that continuously adapts applied pressure according to dynamic physiological state may produce greater long-term compliance. A timedomain neural network model of nonlinear, time-lagged interactions between heart rate, ventilation, and oxygen saturation time series was developed that implicitly synthesizes the effects of the respiration and cardiovascular control systems and produces a representation of dynamic state trajectory useful for prediction and control. A prototypicai recurrent network was modified to enhance depth of memory in learning long-time lagged relationships inherent in the data. Multiple future time scales (1, 4, and 17 minutes) were enforced on the network during training to explore the limits of the prediction horizon, Respiration time series prediction results on out-of-sample data will be presented in terms of metrics expressing model dispersion and goodness-of-fit. Clinically useful respiration waveform predictions can be obtained using this methodology.

26 COMPARISON OF LINEAR AND NONLINEAR OTOACOUSTIC EMISSIONS Hekimoglu, Y. and Ozdamar, O. Department of Biomedical Engineering, University of Miami, Coral Gables, FL 33156 Transient evoked otoacoustic emissions (TEOAEs) are very low level sounds produced by the inner ear in response to transient acoustic stimuli. TEOAEs recorded from the external ear canal using the conventional averaging method are called linear (LNR) responses. At mid-to-high click levels, LNR responses are obscured by the overlapping stimulus artifact. At low-to-mid intensities, the degrading effects of the stimulus artifact can be reduced by filtering and windowing. At high click levels, however, the degrading effects of the stimulus artifact is still dominant and can only be reduced by using the derived nonlinear (DNL) method which utilizes the nonlinear saturation characteristic of TEOAEs. The purpose of this study is to explore the advantages and the limitations of both techniques and develop a new method called the scaled template subtraction (STS) method to overcome those limitations. In this study, single sweep responses to click stimuli presented in a novel non-linear alternating (NLA) mode are recorded from 10 ears and processed off-line with all three methods. Results show that the DNL method reduces the stimulus artifact to a large extent, but also lowers the response power at all click levels, effectively raising detection thresholds compared to the LNR method. The STS method, on the other hand, can reduce the stimulus artifact better than the DNL method while preserving the response amplitude at low intensities, thus yielding low detection levels as the LNR method. 27 DOSE-DEPENDENCE OF LITHOTRIPSY-INDUCED C A V I T A T I O N

I. Cioanta #, P. Zhong#, *, F. H. Cocks # and G. M. Preminger* Depts. of#Mech. Engr. & Mat. Sci. and *Urology, Duke University Acoustic emission (AE) associated with lithotripsy-induced cavitation in water and renal parenchyma of a swine model, were measured using various doses of shock wave treatment (Table 1). At each output voltage, the damping ratio of the bubbles (collapse/ringing time) was found to be almost unchanged in water, but varies significantly with increased number of shocks delivered in renal parenchyma. Physically, the damping ratio represents the influence of tissue constraining, hemorrhage and hematomas developed in the kidney on bubble oscillation. The maximum damping in parenchyma was achieved at 1,500 pulses at 16 kV, and was reduced to 500 pulses at 20 kV, indicating an increased tissue injury at high lithotripter output voltages. These results suggest that AE measurements may be used to assess the dose-dependence of tissue injury in vivo during lithotripsy. (Supported by the Wbitaker Foundation and NIH PO1 DK 20543). Table 1 The dampingratio oflithotripsy-inducedcavitationbubbles

28 SEVERE LOCAL HYPOTHERMAL FROM LAPAROSCOPIC GAS, EVAPORATIVE JET COOLING: A POSSIBLE MECHANISM TO E XPLAIN WIDESPREAD CLINICAL OBSERVATIONS R.I. Gray, AC. Henderson, & D.E. Ott Mercer University, Dept of BME, Macon, GA. Past theoretical mechanisms have failed to explain widely observed, postoperative hypothermia in laparoscopic surgery patients. Mismatch of tissue and inflation gas thermal capacities rule out any substantial global tissue temperature reduction during laparoscopic procedures. Overlooked, however, is the possibility of severe hypothermia due to local super-cooling of tissue due to evaporation into a dry jet of insufflation gas (LSFGJE). This mechanism has been examined analytically and experimentally and has been found both feasible and profound. At high gas flow rates (10 l/m), theoretical analysis o f LSFGJE, subject to very sensitive jet size/tissue orientation assumptions, gave local tissue cooling rates of 10 to 25~ Even at low insufflation flows (>1 I/m), cooling rates as high as 3 to 8~ were calcuated. Preliminary lab experiments have shown cooling rates in excess of 2.5~ for large jets in normal orientation and moderate flow (4 I/m). Such super-cooling, if experienced in clinical practice, could result in severe local tissue damage and/or necrosis during laparoscopic insuflation.

29 COX SURVIVAL-TIME MODEL FOR THE RESUMPTION OF OVULATORY ACTIVITY FOLLOWING CHILDBIRTH B. Taylor and S.J. Samuels New Mexico Highlands University, Department of Engineering, Las Vegas, NM and University of California Davis, School of Reproductive Medicine, Davis, CA. The hypothesis that suckling behavior and other factors may be causally related to the month-specific rate of return of ovarian cyclicity after childbirth was tested for 117 lactating women. We used survival analysis for time-dependent covariates, with the first postpartum menses and ovulatory symptoms taken as the dependent responses. We detected a strong influence on the timing of suckling bouts on the rate of postpartum ovarian recrudescence and menstrual cycles recovery, probably mediated through inhibition of the ovarian-hypothalamic axis. We found also that the risk of ovulating during amenorrhea increases after the sixth month postpartum, although the fertility-suppressing effect of lactation continues past postpartum amenorrhea.

30 DEVELOPMENT OF A FUZZY LOGIC CONTROLLER FOR CONTROLLED ECOLOGICAL LIFE SUPPORT SYSTEMS (CELSS) B. Taylor, E. Leyderman and A. Maestas New Mexico Highlands University, Department of Engineering, Las Vegas, NM. We have designed a stand-alone fuzzy logic controller to supervise environmental conditions in a CELSS. We modified MATLAB Fuzzy Logic C code in order to use it with our QED C Control System downloaded on the M68HCI 1 microcontroller. The controller then was used to monitor such inputs as temperature, relative humidity, water level and CO2 concentration in the chamber. The controller outputs actuate such climate control devices as heaters, blowers, pumps, humidifier, CO2 source and lighting. The controller can provide automatic control of the environment of any plant growth chamber; the controller makes control decisions based upon up to eight inputs and then, by fuzzy inference, maps them to as many as eight outputs. The software is designed so that the user can readily change the fuzzy logic rules through the MATLAB Fuzzy Logic Toolbox and also make specific non-fuzzy changes in the software, if necessary. The controller can be calibrated to the appropriate input sensors and the user can change the desired threshold level for each input without switching off the controller.

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Artificial Organs and Devices - Posters

31 ON RANDOM CENSORSHIP MODELS G. Dikta Aachen University of Applied Science, Dept. of Chemistry and Biotechnology, D-52428 Juelich, Germany In lifetime analysis one frequently observes data with incomplete information due to censoring. We discuss the Kaplan-Meier estimator and a new semiparametric procedure for the estimation of the survival time under the random censorship model. Furthermore, the results of a small simulation study are presented. In this study the estimated expected lifetimes due to the two estimators are compared.

32 PROTAMINE BIOREACTOR FOR HEPAR/N REMOVAL: DESIGN USING TWO-COMPARTMENT ELIMINATION TANK MODEL Tanya Wang, Dr. Youngro Byun, Jae-Seung Kim, and Dr. Victor Yang University of Michigan, Biomedical Engineering Dept., Ann Arbor, MI To sidestep the adverse effects resulting from protamine administration for clinical reversal of heparin, we have proposed the placement of a hollowfiber bioreactor with immobilized protamine after the blood perfusion unit in order to extracorporeally remove heparin before it returns to the body. Preliminary in vitro and in vivo results show promise in demonstrating the feasibility of this approach. Presented herein is a two-compartment elimination tank model developed from preliminary results to optimize the bioreactor for target clinical applications of cardiopulmonary bypass and hemodialysis. In vitro studies revealed that the association rate constant between heparin and immobilized protamine is approximately 4xl0S/M rain. In vivo studies showed that heparin disappearance in dogs followed a two-compartment elimination. Bioreactor design factors are (1) capacity which depends on initial concentration and reactor size, and (2) time, dependent on flow rate. Applying our model, a bioreactor of 150g is projected to reduce initial blood heparin to 10% in 5 minutes and 60 minutes for cardiopnlmonary bypass and hemodialysis, respectively. To reduce bioreactor size, we are currently attempting to increase capacity by alternating flow between two bioreactors and by enhancing protamine immobilization. Tanya Wang is currently a recipient of the Whitaker Foundation Graduate Student Fellowship in Biomedical Engineering.

33 Animal Laboratory Virtual Notebook System Joalin P-K Lim, Wendy Steger and Jerome Abrams University of Minnesota, Dept. of Surgery & BioMed Eng. Institute As computerized information technology has evolved to become the zenith of the 21st century, the Iraditional laboratory notebook may almost be over. Scientists do more and more of their work on computers; therefore, the task of keeping data in a handwritten notebook has become cumbersome and impractical. How can one enter a complex, three-dimensional color model into a notebook ? In this report, our research group designed and developed an electronic animal laboratory notebook that allows collection, implementation, storage and analysis of data in an efficient, organized manner. All the data storage is done using a Professional version of Paradox 7.0. The schema of the system is a 3rd normal form relational database management system that runs under Microsoft Windows 95. This software allows us to record data while performing the animal operation and to store and organize it in a database library. It not only has the capability to analyze data in a user- defined graphical format but also has a research expenditure application that allows us to compute the amount spent on a particular experiment. Since all the experiment's data is collected in a database, variables of the selected experiment can be traced and studied easily by a touch of the button.

34 IN VITRO DEGRADATION OF A CROSSLINKED POLY(ETHYLENE GLYCOL) COPOLYESTER L.J. Suggs, R.S. Krishnan, S.J. Peter, and A.G. Mikos Institute of Biosciences and Bioengineering, Rice University, 6100 South Main, Houston, TX 77005 We have developed a block copolymer of poly(propylene fumarate-coethylene glycol), P(PF-co-EG), in order to address problems with currently used cardiovascular stenting materials. P(PF-co-EG) is crosslinkable through the fumarate double bonds forming a mechanically stable hydrogel which degrades into fumaric acid, propylene glycol, and PEG. Because of these properties, P(PF-co-EG) has potential for use as an injectable, biodegradable implant. We have examined the degradation of this copolymer over a 12 week time course in phosphate-buffered saline at 37~ pH 7.4. Properties which were evaluated include: tensile strength and modulus, dynamic flexural modulus, molecular weight between crosslinks, weight loss, and dimensional and morphological changes. In addition, gas chromatography was performed on the media to identify the degradation products after 12 weeks. This material was shown to degrade primarily by bulk degradation. The dimensional changes and weight loss were negligible over the course of the study, excluding an initial weight loss due to leaching of the sol fraction. The ultimate tensile strength, however, decreased by an average of 88.5% for copolymers with PEG content between 25% and 50%. These data suggest that P(PF-co-EG) could provide mechanical stability to the vessel wall during initial implantation.

35 ADHESION MEASUREMENTS BETWEEN SOFT BIOMATERIALS Angela K. Dillow and Matthew Tirrell Department of Chemical Engineering and Materials Science University of Minnesota; Minneapolis, MN 55455 A technique that utilizes the JKR theory of contact mechanics is used to measure the intrinsic strength of adhesion between soft biomaterials and a variety of polymeric and amphiphilic molecules which may be useful in the formulation of pharmaceuticals and implant materials. The complex nature of soft biomaterials (i.e., hydrogels such as gelatin and mucin), and the number of variables upon which their physical and chemical properties depend, makes tests of adhesion for these materials challenging. The bioadhesive properties between many natural and synthetic bioeompatible polymers, or between the biocompatible polymers and cell or tissue samples, has not been investigated thoroughly due to the extreme difficulty in the experimental procedures. Utilizing our experimental technique, various components contributing to adhesion (i.e., non-specific interactions, interchain diffusion, hydrogen bonding, ligand/receptor interactions) between complex biomaterials may be quantified.

36 MODULATION OF PROTEIN-LIGAND RECOGNITION BY GENETIC INCORPORATION OF AN ENVIRONMENTALLYSENSITIVE PEPTIDE SWITCH R. T. Piervincenzi and A. Chilkoti Duke University, Biomedical Engineering, Durham, NC The molecular recognition capabilities of proteins are of great interest in the fields of biosensors, affinity bioseparation and targeted drug delivery. A novel approach involves the introduction of molecular switches within a protein's scaffold to modulate its ligand binding. In particular, the polypentapeptide of elastin, which displays an inverse temperature transition, will be incorporated into the enzyme inhibitor tendamistat in a way as to allow for the modulation of binding with temperature. The synthetic gene for tendamistat was synthesized and expressed. The recombinant wild-type (WT) tendamistat was to inhibit porcine pancreatic alpha-amylase in a colorimetric kinetic assay. A circularly permuted tendamistat variant with new C- and N-termini was determined to have an inhibition constant within two-fold of WT tendamistat. Introduction of elastin pepfides at the new c-terminus of the permuted tendamistat will be tested for their ability to modulate proteinprotein binding.

Artificial Organs and D e v i c e s - Posters

37 SPATIO-TEMPORAL ASPECTS OF TRANSPORT IN TUMORS: A PERCOLATION MODEL James W. Baish*, Joshua H. Smith*, Leena Hamberg**, Rakesh K. Jain*** *Department of Mechanical Engineering, Bucknell University, Lewisburg, PA, **Center for Imaging and Pharmaceutical Research, ***Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA Delivery of drags to tumors is complicated by the seemingly chaotic architecture of the tumor vasculature. Recent studies indicate that, unlike capillaries in healthy tissues which exhibit fairly regular spacing, tumor blood vessels grow in patterns that have percolation-like scaling. In the present study, we investigate the implications of this finding for the spatial and temporal aspects of drag delivery. We have developed a model that simulates the growth, flow and transient transport characteristics of tumor vasculature. Concentration histories are modeled by coupling a multi-path drug or tracer transport model to a percolationbased flow model. We predict highly heterogeneous transport in the tumor which is clinically significant because some 'out of the way' regions of tumor may receive drug significantly later than most of the tumor and retain drug for longer than average.

38 DEVELOPMENT OF PERCUTANEOUS CIRCULATORY ASSIST D E V I C E - - I N - V I V O AND IN-VITRO ANALYSES Hai Zhang', Kaoru Inaanishi*', Kou Imachf', Yakashi Isoyama'*, Tetsou Fujimoto'*', Mitsuo Umezu"* * University of Missouri-Columbia, USA *, Institute of Medical Electronics, University of Tokyo, Japan ,,, Dept. of Mechanical Engineering, Waseda University, Japan A new percutaneous circulatory assist device (PCAD) was developed. It consists of a cannula which was incorporated a truncated conical jellyfish valve as the inlet valve and a skirt valve as the outlet valve, and a single-port valveless sac type blood pump made ofpolyvinyl chloride paste which was connected to a pneumatic driver. Tire haemodynamic characteristics of the PCAD were tested in an animal experiment and a mock circulatory system. Experiment results show that the PCAD increases the aortic flow and aortic pressure effectively. It also increases the coronary flow significantly during pacing cnndition. Flow-pressure curve of the PCAD is smooth, which makes it easy to control the flow rate by changing the driving condition. The leakage flow rate was low. It makes the circulatory assist more effective.

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40 AN AUTOMATED 1NTELLEGENT MICROSCOPE SYSTEM - DEVELOPMENT AND APPLICATIONS D. Harrington, H. Zhang, B. Decker, P.C. Kirkitelos, R.A. O'Neal, C. Priddy, J.W. Douglass, T.Riding, M.Schneider, S. Harver ChromaVision Medical Systems, Inc. San Juan Capistrano, CA. An automated intelligent microscope system (AIMS) has been developed for scanning slides in bright field. AIMS consists of a color CCD camera, a bright field microscope with a moving xy stage, automatic carrier feeder and a personal computer with image processing capabilities. AIMS is able to scan up to 25 slide carriers (I 00 slides) each time without human intervention. It reads routinely prepared slide using a variety of substrates, and automatically locates and counts suspected tumor and normal cells presented on a slide by analyzing their color, size, and morphological characteristics. After scanning is completed, all stored images for each slide can be reviewed by pathologists to decide which of the detected objects are true tumor cells. Upon completion of this review, a report may be produced. Preliminary studies show that AIMS is highly sensitive and reproducible. AIMS can be used for cancer research, Down's syndrome diagnosis and other biomedical applications.

41 IMAGING AND ANALYZING STRAIGHTENED DNA MOLECULES FIXED ON A SURFACE Weining Wang, Jieyi Lin, and David C. Schwartz W. M. Keck Laboratory for Biomedical Imaging, Department of Chemistry, New York University, 31 Washington Place, New York, NY 10003 The base sequences of DNA molecules carry the genetic information to determine the construction and function of a living organism. Along a DNA chain, large stretches of noncoding regions separate the biologically important base sequences, or genes, where biological processes, such as replication, transcription, etc., take place. To be able to study and possibly modify these processes on individual DNAs directly, we have combined fluid flow induced DNA elongation and scanning force microscopy to image and analyze individual DNA molecules. Solvent flow was employed to straighten DNA molecules and expose their internal structures. The elongated DNAs were then fixed on a suitable surface and imaged by a scanning force microscope. Intact, nearly fully elongated molecules of lambda DNA were imaged. Replication bubbles in the interior of G DNA were also imaged. This technique can be integrated into our new, powerful genomic analysis approach--optical mapping--for rapid detection of structural or conformational features along a DNA molecule. Potential applications include high throughput clinical diagnostics of diseases.

BIOENGINEERING~INDUSTRYAND SOCIETY Bioengineering History 39 BLOOD-FLOW MODELING IN CLEARANCES OF THE UTAHVIRGINIA CONTINUOUS FLOW ARTIFICIAL HEART. R.S. Awad*, M.S., P.E. Allaire*, Ph.D., and J.S.Lee*, Ph.D. University of Virginia, Depts. of BME* and MANE*, Charlottesville, VA. The Utah-Virginia team has built a prototype continuous flow ventricular assist device (CFVAD) fully supported on magnetic bearings. To predict the blood flow behavior in clearances between the impeller and housing, the three-dimensional Navier-Stokes equations were solved numerically using the FLOW3D | software (AEA Technology). In a preliminary study, the parameter values chosen corresponded to clearances ranging form 0.015" and 0.03", rotational speeds of 2000-2400 rpm, and differential pressures (DP) ranging between 20 and 60 mmHg. Numerical results detail the shear stress and velocity fields within the CFVAD. At 60 mmHg DP, results indicate that the blood would be pressure-driven inward towards the hub with little influence from the Ekman shear-driven flow. At 20 mmHg DP, the flow would move inward for the 0.03" clearance case, but could stagnate at the 0.02" clearance and move outward towards the shroud for a clearance of 0.015". The maximum predicted shear stress in the heart pump is 2200 dyne/cm2. This is only 20% of the brief-exposure value of lytic shear published in the literature. For the high DP, maximum shear stresses of 2000 dyne/cm2 were produced by the pressure-driven flow, while the shear-driven Ekman flow produced shear stresses of 1000 dyne/cm2. This suggests that the magnetically suspended impeller can be used for long-term implantation.

42 BIOMEDICAL AND CHEMICAL ENGINEERING: CONVERGENT EVOLUTION THROUGH MASS TRANSPORT - A HISTORICAL COMMENTARY Edwin N. Lightfoot, Ph.D., Dept. of Chemical Engineering, Univ. of Wisconsin; Kenneth H. Keller, Ph.D., Hubert H. Humphrey Center, Univ. of Minnesota, and Y. C Fung, Ph.D, Dept of Biomedical Engineering, Univ. of California, San Diego. Chair: Paul H. Fagette, Jr., Ph.D., Dept. of Biomedical Engineering, Univ. of Memphis. The publication of the Bird, Stewart, and Lightfoot text, Transport Phenomena, and the later Lighffoot work, TransportPhenomena and Living Systems, marked two key transitional stages in the intellectual development of both chemical and biomedical engineering. Dr. Lightfoot will begin a discussion about the historic setting and influences in which both works appeared. Critical commentary and two additional perspectives will be offered by Drs. Ken Keller and Y. C. Fung about the status of both disciplines and the impact of both works. Crucial to the overall discussion will be how shills in chemical engineering affected the direction of research in the newly emerging biomedical engineering.