A population-based microbial oscillator

Genetic oscillators are a major theme of interest in the emerging field of synthetic biology. Until recently, most work has been carried out using intra-cellular oscillators, but this approach restricts the broader applicability of such systems. Motivated by a desire to develop large-scale, spatially-distributed cell-based computational systems, we present an initial design for a population-level oscillator which uses three different bacterial strains. Our system is based on the client-server model familiar to computer science, and uses quorum sensing for communication between nodes. We present the results of extensive in silico simulation tests, which confirm that our design is both feasible and robust.Comment: Submitte

Quantitative assessment of reflex blood pressure regulation using a dynamic model of the cardiovascular system

A quantitative understanding of the changes in coronary, pulmonary and systemic hemodynamic variables and their effects on the regulation mechanism is important to the better postoperative management of patients with impaired cardiac function. The arterial baroreflex plays a key role in blood pressure homeostasis, and its impairment may result in exaggerated blood pressure fluctuations and an increased risk of cardiovascular morbid events. The objective of this work was to construct a mathematical model of the cardiovascular system, which will allow us to simulate the effects of the baroreceptor reflex regulation on sudden changes in blood pressure, caused by sudden changes in one or more hemodynamic parameters. These parameters include heart rate, peripheral resistance and ventricular contractility. A comprehensive model of the baroreflexfeedback mechanism regulating the heart rate, the contractility of the ventricle and the peripheral vascular resistance is presented. The model used is a combination of several models, which have been reported in literature, along with our own modifications. The important feature of the model is that it is dynamic in nature and thus it is helpful in real time analysis. The model is also useful to conceptualize the problem and test relationships, helping researchers frame hypotheses and design experiments

3D spatio-temporal analysis for compressive sensing in magnetic resonance imaging of the murine cardiac cycle

This thesis consists of two major contributions, each of which has been prepared in a conference paper. These papers will be submitted for publication in the SPIE 2013 Medical Imaging Conference and the ASEE 2013 Annual Conference. The first paper explores a three-dimensional compressive sensing (CS) technique for reducing measurement time in MR imaging of the murine (mouse) cardiac cycle. By randomly undersampling a single 2D slice of a mouse heart at regular time intervals as it expands and contracts through the stages of a heartbeat, a CS reconstruction algorithm can be made to exploit transform sparsity in time as well as space. For the purposes of measuring the left ventricular volume in the mouse heart, this 3D approach offers significant advantages against classical 2D spatial compressive sensing. The second paper describes the modification and testing of a set of laboratory exercises for developing an undergraduate level understanding of Simulink. An existing partial set of lab exercises for Simulink was obtained and improved considerably in pedagogical utility, and then the completed set of pilot exercises was taught as a part of a communications course at the Missouri University of Science and Technology in order to gauge student responses and learning experiences. In this paper, the content of the laboratory exercises with corresponding educational approaches are discussed, along with student feedback and future improvements. --Abstract, page iv

Cycle Assist

The senior engineering design project presented in the paper that succeeds this, outlines the steps taken to design and implement an electronic bicycle that is able to keep a user’s heart-rate in a selected “intensity zone” though the use of an electronic motor and custom control circuitry. My portion of this project was to allow for safe and consistent power delivery to the rest of the electronics. That is to say, I built a battery pack and battery management system (BMS) to safely supply sufficient power to the rest of the electronics that were required for this project. In order to design a BMS for a project, the theoretical battery specifications first need to be established. To come up with these specifications, three key aspects were analyzed: voltage level, capacity, and size. The voltage and capacity had to be large enough to supply the necessary power to the motor, while also minimizing the size so that unnecessary weight was not added to the bike. Next, the BMS was able to be designed to protect the battery mentioned above. When designing a BMS, three key aspects of the battery have to be continuously monitored: cell voltage, cell temperature, and total battery pack current. In order to get adequate measurements for cell temperatures and current, custom circuitry was designed to enable accurate measurements through the use of a central microcontroller’s analog-to-digital converter. To measure the pack voltage, an integrated-circuit was used as it allowed for quick measurements of every battery cell, effective passive balancing to elongate the lifespan of the battery pack, and could communicate with the central microcontroller through the use of the serial-peripheral-interfacing communication protocol. These three systems combined allowed for quick and accurate measurements of the battery, so that the BMS could determine if it was operating safely or not. There were many takeaways from this project that relate both to this specific project, and what would be changed in the next iteration, as well as how to handle future design based projects. For this specific project, the design included two power MOSFETs on the BMS to enable and disable power flow to and from the battery. The way the MOSFET’s were oriented allowed for continual power flow to or from the batter, regardless of whether or not the BMS deemed it safe to do so. To solve this issue, one MOSFET was removed to make it possible for the BMS to disable discharging, but not charging (someone has to always watch the batteries while they are charging to ensure everything is safe). In the next iteration of this project, it would make sense to design for the use of an external relay instead. This would allow for easy customization of the BMS for use with different battery packs that have different power requirements, as well as more efficiently allowing bidirectional power flow, and being able to disable charging and discharging if the operation is deemed unsafe by the BMS. Also, the next iteration would implement active balancing instead of just passive balancing. This would allow the redistribution of charge around the battery pack so that the weakest cells could be propped up by the stronger cells, allowing the battery pack to last longer on a single charge. A final takeaway of this project was how to test and implement future design based projects. In this project, the various subsystems were tested on breadboards before a final PCB was ordered and implemented. This lead to unforeseen errors with the PCB manufacturing process as well as things that were overlooked on the PCB schematic. In the future, it would make sense to instead design and order a cheap, low power, version of the PCB to test with. Then, all of the issues could be diagnosed and dealt with on that board prior to ordering the final PCB. All in all, this design project lead to a lot of learning about not only the BMS design process, but the design process as a whole

Laboratorio virtual para la simulación y el aprendizaje del sistema cardiovascular en estudios de ingeniería biomédica

RESUMEN: La aplicación de la ingeniería al análisis de sistemas es un campo muy importante en los estudios ingeniería Biomédica (BME, por sus siglas en inglés): modelado, simulación y control de los sistemas fisiológicos más importantes. En este documento se presenta un laboratorio virtual para el análisis y el estudio del sistema circulatorio humano. Este laboratorio se basa en la compilación de varios modelos matemáticos descritos en la literatura. Además, algunos parámetros del modelo han sido mejorados por medio de datos experimentales del estímulo de cafeína. Esta herramienta computacional se ha construido utilizando MATLAB / Simulink y EJS, por lo que combina buena capacidad de cálculo con interactividad. El laboratorio virtual ha sido diseñado con el fin de comprender el funcionamiento del sistema circulatorio en condiciones normales, y para predecir variables circulatorias en diferentes tipos y niveles de estímulos y condiciones.ABSTRACT: The application of engineering system analysis is a very important field in biomedical engineering (BME) studies: modeling, simulation and control of the most important physiological systems. A virtual laboratory for the analysis and the study of human circulatory system is presented in this paper. This laboratory is based on the compilation of several mathematical models described in the literature. In addition, some model parameters have been tuned by means of experimental data under caffeine stimulus. The computational tool has been built using MATLAB/SIMULINK and EJS, so it combines good computation capabilities with interactivity. The virtual laboratory has been designed in order to understand the operation of the circulatory system under normal conditions, and to predict circulatory variables at different types and levels of stimuli and conditions

Feasibility assessment of a Kalman filter approach to fault detection and fault-tolerance in a highly unstable system: The RIT heart pump

The purpose of this project is to assess the feasibility of a Kalman Filter approach for fault detection in a highly unstable system, specifically the heart pump currently under development at RIT. Simulations and experimental work were completed to determine the effects of possible position sensor fault conditions on the system; that information was then used in conjunction with a pair of Kalman filters to create a method of detecting faults and providing fault-tolerant operation. The heart pump system was modeled using Simulink and then the fault diagnosis and tolerance system was added to the model and tested via simulation in SIMULINK TM. The simulations showed the filters were able to calculate and remove bias caused by any type of position sensor error, provided the estimated plant model is nearly identical to the actual plant model. Sensitivity analysis showed that the fault detection/fault-tolerance method is extremely sensitive to discrepancies between the estimated plant model and actual pump behavior. Because of this, it is considered unfeasible for implementation on a real system. Experimental results confirmed these findings, demonstrating the drawbacks of model-based fault detection and tolerance methods

From Verified Models to Verified Code for Safe Medical Devices

Medical devices play an essential role in the care of patients around the world, and can have a life-saving effect. An emerging category of autonomous medical devices like implantable pacemakers and implantable cardioverter defibrillators (ICD) diagnose conditions of the patient and autonomously deliver therapies. Without trained professionals in the loop, the software component of autonomous medical devices is responsible for making critical therapeutic decisions, which pose a new set of challenges to guarantee patient safety. As regulation effort to guarantee patient safety, device manufacturers are required to submit evidence for the safety and efficacy of the medical devices before they can be released to the market. Due to the closed-loop interaction between the device and the patient, the safety and efficacy of autonomous medical devices must ultimately be evaluated within their physiological context. Currently the primary closed-loop validation of medical devices is in form of clinical trials, in which the devices are evaluated on real patients. Clinical trials are expensive and expose the patients to risks associated with untested devices. Clinical trials are also conducted after device development, therefore issues found during clinical trials are expensive to fix. There is urgent need for closed-loop validation of autonomous medical devices before the devices are used in clinical trials. In this thesis, I used implantable cardiac devices to demonstrate the applications of model-based approaches during and after device development to provide confidence towards the safety and efficacy of the devices. A heart model structure is developed to mimic the electrical behaviors of the heart in various heart conditions. The heart models created with the model structure are capable of interacting with implantable cardiac devices in closed-loop and can provide physiological interpretations for a large variety of heart conditions. With the heart models, I demonstrated that closed-loop model checking is capable of identifying known and unknown safety violations within the pacemaker design. More importantly, I developed a framework to choose the most appropriate heart models to cover physiological conditions that the pacemaker may encounter, and provide physiological context to counter-examples returned by the model checker. A model translation tool UPP2SF is then developed to translate the pacemaker design in UPPAAL to Stateflow, and automatically generated to C code. The automated and rigorous translation ensures that the properties verified during model checking still hold in the implementation, which justifies the model checking effort. Finally, the devices are evaluated with a virtual patient cohort consists of a large number of heart models before evaluated in clinical trials. These in-silico pre-clinical trials provide useful insights which can be used to increase the success rate of a clinical trial. The work in this dissertation demonstrated the importance and challenges to represent physiological behaviors during closed-loop validation of autonomous medical devices, and demonstrated the capability of model-based approaches to provide safety and efficacy evidence during and after device development

Heart-on-a-Chip: A Closed-loop Testing Platform for Implantable Pacemakers

Implantable cardiac pacemakers restore normal heart rhythm by delivering external electrical pacing to the heart. The pacemaker software is life-critical as the timing of the pulses determine its ability to control the heart rate. Recalls due to software issues have been on the rise with the increasing complexity of pacing algorithms. Open-loop testing remains the primary approach to evaluate the safety of pacemaker software. While this tests how the pacemaker responds to stimulus, it cannot reveal pacemaker malfunctions which drive the heart into an unsafe state over multiple cycles. To evaluate the safety and efficacy of pacemaker software we have developed a heart model to generate different heart conditions and interact with real pacemakers. In this paper, we introduce the closed-loop testing platform which consists of a programmable hardware implementation of the heart that can interact with a commercial pacemaker in closed-loop. The heart-on-a-chip implementation is automatically generated from the Virtual Heart Model in Simulink which models different heart conditions. We describe a case study of Endless Loop Tachycardia to demonstrate potential closed-loop pacemaker malfunctions which inappropriately increase the heart rate. The test platform is part of our model-based design framework for verification and testing of medical devices with the patient--in-the-loop

Design of Control System with Feedback Loop for a Pulsatile Pump

This paper describes the design and implementation of a closed-loop proportional, integral, differential (PID) control system for a custom in-house pulsatile pump apparatus for the University of Arkansas Biomedical Department. The control system is designed to control a MOONS’ PL34HD0L8500 hybrid stepper motor using a dual H-bridge motor driver network with four pulse-width modulated (PWM) inputs to drive a pulsatile pump apparatus at motor stepping frequencies up to 2kHz. The speed of the motor is controlled from a pressure profile transmitted from an external source over RS-232 communication that specifies the motor speed, number of datapoints, and an array of pressure data. Data will be measured from the pump using pressure, flow, and temperature sensors that will output analog data and be read to the control board using analog-to-digital converters (ADCs). A PID controller will be used to match the speed of the motor to the control data by calculating the error between the sensor outputs and the desired profile. The circuit board is separated into two sections for the control board and motor circuit to isolate the 68V and motor circuity from the rest of the control board circuitry. The control system circuitry was tested, and while the control board systems were found to be functional, the motor circuit was found inefficient due to the high L/R time constant of the motor, resulting in greatly reduced speed and torque. A new chopper driver design was proposed to solve this issue and simulations conducted through MATLAB Simulink to prove the feasibility of the design

Pulse patency and oxygenation sensing system development to detect g-induced loss of consciousness

A fighter pilots greatest strength is the weakness of his or her opponent. Commonly, this strength comes down to the maneuverability of the aircraft, particularly the ability to out-climb. Since the 1980\u27s, the thrust produced by these engines have the ability to drain the pilots head of blood causing a state of unconsciousness due to the overwhelming forces of gravity for upwards of 30 seconds; often times having fatal outcomes. This thesis explores the feasibility of detecting of blood flow by means of arterial wall expansion (pulse patency) and blood oxygenation using a microprocessor to continually monitor the signals from this two part sensor where by insight into the development of a g-induced loss of consciousness sensing system can be developed. Results indicate greater than 90% accuracy pulse patency detection using an accelerometer. Simulation and physical models were used as well as human testing to develop a blood oxygenation and pulse patency sensor, or BOPS