Implantable arterial blood pressure sensor

Although blood pressure measurements are well developed, the existing technology in the field of Arterial Blood Pressure (ABP) measurements is not sufficient in terms of long-term ABP waveform assessment. To overcome existing limitations this dissertation proposes, models, designs and tests a new technique of ABP measurements: implantable arterial tonometry.The scope of this dissertation is to study how the geometry of the tonometer and its mechanical properties influence sensor output and stress/strain distribution inside the arterial wall. Two models of tonometer, analytical and numerical, are developed. The relationship between the tonometer response and its effective stiffness is calculated using a lumped parameter model. The contact pressure between the artery and the tonometer as well as the arterial wall stress/strain distribution is studied using a Finite Element numerical model.Based on the theoretical results three prototypes are developed. The piezoelectric dual mode transducer is designed to measure the tonometer-arterial wall contact pressure.The series of in-vitro and in-vivo experiments test the static and dynamic responses of the tonometer.The results indicate the tonometer’s effective stiffness necessary to achieve less than 1% error in the dynamic response of the sensor. The geometry of the tonometer’s measurement area is found, which results in less than 1% of error in quasi-static response of the sensor. In effort to find potential tissue remodeling areas, the internal arterial wall stress/strain distribution generated by the tonometer is found.The experimental results complement the numerical analysis. The static and dynamic characteristics of the prototype tonometer obtained in-vitro and in-vivo are presented. The explanted tunica media remodeling effect is compared with FE analysis results.The presented work states and solves basic problems of implantable arterial tonometry. In addition it provides the in-vitro and in-vivo examination of the theoretical results. The thesis develops tools of modeling, designs, and testing procedures for future researchers willing to develop implantable tonometers.The thesis concludes with a novel design of the implantable tonometer.Ph.D., Biomedical Engineering -- Drexel University, 200

New methods for continuous non-invasive blood pressure measurement

Hlavním cílem této práce je nalezení nové metodiky pro měření kontinuálního neinvazivního krevního tlaku na základě rychlosti šíření pulzní vlny v krevním řečišti. Práce se opírá o rešerši zabývající se základním modelem pro stanovení kontinuálního neinvazivního krevního tlaku na základě měření zpoždění pulzní vlny a jeho rozšířením. Z informací získaných z rešerše se upravila metodika měření doby zpoždění pulzní vlny / rychlosti šíření pulzní vlny, aby bylo možné docílit přesnějších výsledků a omezit tak lidský faktor, který způsobuje významnou nepřesnost vlivem nedokonalého rozmístění senzorů. Rešerše se rovněž podrobně zabývá modely pro stanovení kontinuálního neinvazivního krevního tlaku a jejich úprav zajištujících zvýšení přesnosti. Mezi úpravy modelů zejména patří vstupní parametry popisující krevní oběh - systémový cévní odpor, elasticita cév, tuhost cév. Práce se taky zabývá úpravami stávajícího modelu krevního řečiště pro bližší přizpůsobení fyzického modelu k reálnému cévnímu systému lidského těla. Mezi tyto úpravy patří i funkce baroreflexu či simulace různé tvrdosti stěny umělých cévních segmentů. Protože se jedná o simulační model krevního řečiště, důležitým krokem je také měření tlakové a objemové pulzní vlny, kde není možné využít konvenční senzory pro fotopletysmografii kvůli absenci částic pohlcující světlo. Na základě experimentálního měření pro různé nastavení modelu krevního řečiště bylo provedeno měření pulzní vlny pomocí tlakových a kapacitních senzorů s následným zpracováním měřených signálů a detekcí příznaků charakterizující pulzní vlnu. Na základě příznaku byly stanoveny predikční regresní modely, které vykazovaly dostatečnou přesnost jejich určení, a tak následovaly dvě metody pro získání parametru o tvrdosti cévní stěny na základě měřitelných parametrů. První metodou byl predikční regresní model, který vykazoval přesnost 74,1 % a druhou metodou byl adaptivní neuro-fuzzy inferenční systém, který vykazoval přesnost 98,7 %. Tyto stanovení rychlosti pulzní vlny bylo ověřeno dalším přímým měřením pulzní vlny a výsledky byly srovnány. Výsledkem disertační práce je určení rychlosti šíření pulzní vlny s využitím pouze jednoho pletysmografického senzoru bez nutnosti měření na dvou různých místech s přesným měřením vzdálenosti a možnosti aplikace v klinické praxi.The main objective of this work is to find a new methodology for measuring continuous non-invasive blood pressure based on the pulse wave velocity in the vascular system. The work is based on the literature research of the basic model for the determination of non-invasive continuous blood pressure based on the measurement of pulse transit time. From the information obtained from the review, the methodology of measuring the pulse transit time/pulse wave velocity was modified in order to achieve more accurate results and to reduce the human factor that causes significant inaccuracy due to imperfect sensor placement. The review discusses in detail the models for continuous non-invasive blood pressure estimation and their modifications to ensure increased accuracy. In particular, model modifications include input parameters describing blood circulation - systemic vascular resistance, vascular elasticity, and vascular stiffness. The thesis deals with modifications to the existing physical vascular model to more closely mimic the real vascular system of the human body. These modifications include the baroreflex function or the simulation of different wall hardness of artificial arterial segments. As this is a simulation model of the vascular system, the measurement of pressure and volume pulse wave is also an important step, where it is not possible to use photoplethysmography method due to the absence of light absorbing particles. Based on the experimental measurements for different settings of the vascular model, pulse wave measurements were performed using pressure and capacitive sensors with subsequent processing of the measured signals and detection of the pulse wave features. Predictive regression models were established based on the pulse wave features and showed sufficient accuracy in their determination, followed by two methods for obtaining the parameter on the hardness of the vascular wall based on the measurable parameters. The first method was a predictive regression model, which showed an accuracy of 74.1 %, and the second method was an adaptive neuro-fuzzy inference system, which showed an accuracy of 98.7 %. These pulse wave velocity determinations were verified by further direct pulse wave measurements and the results were compared. The dissertation results in the determination of pulse wave propagation velocity using only one plethysmographic sensor without the need for measurements at two different locations with accurate distance measurements and the possibility of application in clinical practice.450 - Katedra kybernetiky a biomedicínského inženýrstvívyhově

Modeling, Simulation and Validation of a Bio-Inspired and Self-Powered Miniature Pressure Sensing System for Monitoring Cerebral Intra Aneurysmal Pressure

Intracranial aneurysm rupture is one of the main cause for the intracranial bleeding. A brain aneurysm is an abnormal focal bulging of the arteries in the brain. As an aneurysm grows, its wall becomes thinner and weaker, which is more prone to rupture. Rupture of the intracranial aneurysm leads to releasing blood into the spaces around the brain - called a subarachnoid hemorrhage (SAH). 10 to 15% of the patients with subarachnoid hemorrhage die immediately. To prevent aneurysmal bleeding, it is essential to seclude the aneurysm from the blood circulation. This can be done with open craniotomy with microsurgical clipping and minimally invasive endovascular surgery. One of endovascular surgical technique is to place stent/flow-diverter across the neck of the aneurysm. The stent across the aneurysm reduces the flow within the aneurysm and help to form the thrombus within the aneurysm. However, approximately 3% people with the flow- diverter treatment may have delayed aneurysm bleeding after the stent placement. Short-term studies show that the stents can reduce the flow within the aneurysm but not the pressure. Currently there is no other device available to measure the intracranial intraaneurysmal pressure. This work is on designing a bio-inspired, self-powered, passively operated PVDF pressure sensor that can be deployed within the aneurysm, during flow diverting endovascular treatment that is very sensitive to small changes in pressure. The design utilizes the ear mechanics benefits by consisting of the circular vibrating membrane which vibrates based on the intraaneursymal pressure changes. This mimic the tympanic membrane part of the ear. The design continues to follow the middle ear’s mechanical advantage mechanism by incorporating the surface area increase and leverage mechanism, by the other side of the vibrating membrane been connected to three pole-links structures similar to the three bones of the middle ear to perform the middle ear’s amplification mechanism. This is followed by a composite cantilever beam structure with the sensor strips, which mimics the coiled cochlea of the inner ear in elongated form. This piezoelectric sensor strips are responsible for the passive mechanoelectrical conversion and generation of electric voltage, for the intraaneursymal pressure change application. Simulation, experiments and analysis at every level are done. Simulation and experimental result correlate and match the modeling

A novel approach to bioelectrical impedance plethysmography for the assessment of arterial and venous circulatory problems in the forearm

Peripheral vascular disease (PVD) and/or peripheral arterial disease (PAD) are sicknesses known to inadequate delivery of either arterial or venous blood towards the extremities. Such sickness may trigger complications owing to the lack of transport of oxygen and nutrients, thus causing hypoxic events that may eventually prompt to ischaemic tissue or even the loss of the compromised limb. One of the most prominent indicators of prosperous health is blood volume and flow. The basic information within these health parameters may show cardiovascular problems or the advance of further complications related to other diseases like diabetes. In clinical setting, there effective methods to measure these parameters like Doppler ultrasound, photoplethysmography or venous occlusion plethysmography. These methods take measurements from either single vessels and/or small volume of tissue. However, it is difficult to establish a relation between the obstruction of arterial and/or venous circulation and the amount of blood received by the tissue. Bioelectrical impedance plethysmography (iPG) measures blood changes by driving a small amount of AC current into the body and after measuring the potential created by fluids flowing through tissue. This technique apart from taking measures within defined volumes of tissue, it is easy to use as only needs four electrodes on the skin. Hence, a bespoken bioelectrical impedance device including hardware and software was built ready to measure changes in blood volume/flow in the upper limbs. The system was assessed in an in-vivo controlled environment with 8 participants. The blood flow towards their left arms was altered by constricting the upper arm with a cuff at three levels: 1) below venous pressure 2) amongst venous and arterial pressure and 3) during total occlusion. Simultaneously, measurements from various instruments like ECG, Doppler ultrasound, laser Doppler flowmetry and PPG were taken and compared to the measurements obtained from the iPG instrument and defining its correlation with the impedimetric signal. The results from the experiments showed that the bioelectrical impedance signal changed in basal and arterial pulses showing specific characteristics for each kind of occlusion. The data indicated that it is possible to differentiate between a venous and arterial occlusion by examining both components of the impedance signal. The impedance during venous occlusion dropped in average 0.658±0.230% from the baseline. On the other hand, during arterial occlusion the base impedance dropped in a higher rate approximately 1.13±04.82%, indicating a differentiator during both type of blood flow disruption. Furthermore, the impedance plethysmography waveform morphology also reshaped during these occlusive periods. The whole waveform during artificial venous obstruction increased in magnitude, the systolic peak rose 31.80%, the dicrotic notch 47.73% and the diastolic point 31.92%, where the value of the latter was higher than the dicrotic notch point. In contrast, in the time of partial arterial occlusion the waveform also increased in size at all these points, but its shape was altered. The impedance magnitude at the diastolic point went below the ones at the dicrotic notch. These fluctuations provided additional further information that it might be possible to differentiate amongst venous and arterial occlusions. By consolidating the data obtained by the iPG device, it is possible to produce an index ratio between the basal impedance and these three reference points which may help to identify early circulatory problems in the arterial and/or venous systems

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Department of Energy EngineeringElectronic skins (e-skins) enabling to detect various mechanical/chemical stimuli and environmental conditions by converting into various electrical and optical signals have attracted much attentions for various fields including wearable electronics, intelligent/medical robotics, healthcare monitoring devices, and haptic interfaces. Conventional e-skins have been widely used for the realization of these applications, however it is still considered that new e-skins with enhanced sensor performances (i.e. sensitivity, flexibility, multifunctionality, etc.) should be developed. In accordance with these demands, two approaches to explore novel functional materials or to modify device architectures have been introduced for enhancing sensor performance and acquiring multifunctional sensing capabilities. Firstly, a synthesis of multifunctional materials combined with conductive fillers (carbon nanotube, graphene oxide) and functional polymer matrix (i.e. ferroelectric polymer, elastomer) can provide the multimodal sensing capability of various stimuli and stretchability. Secondly, controlling design of device structures into various micro/nanostructures enables a significant improvement on sensing capabilities of e-skins with sensitivity and multidirectional force sensing, resulting from structural advantages such as large surface area, effective stress propagation, and anisotropic deformation. Therefore, a demonstration of e-skin combined with the functional composites and uniquely designed microstructures can offer a powerful platform to realize ideal sensor systems for next generation applications such as wearable electronics, healthcare devices, acoustic sensor, and haptic interface devices. In this thesis, we introduce the novel multifunctional and high performance electronic skins combined with various types of composite materials and nature-inspired 3D microstructures. Firstly, Chapter 1 briefly introduces various types of e-skins and the latest research trends of microstructured e-skins and summarizes the key components for their promising application fields. In chapters 2 and 3, mimicked by interlocking system between epidermal and dermal layers in human skin, we demonstrate the piezoresistive e-skins based on CNT/PDMS composite materials with interlocked microdome arrays for great pressure sensitivity and multidirectional force sensing capabilities. In chapter 4, we conduct in-depth study on giant tunneling piezoresistance in interlocking system and investigate systematically on the geometrical effect of microstructures on multidirectional force sensitivity and selectivity in interlocking sensor systems. In chapter 5, we demonstrate the ferroelectric e-skin that can detect and discriminate the static/dynamic touches and temperature inspired by multi-stimuli detection of various mechanoreceptors in human skin. Using the multifunctional sensing capabilities, we demonstrated our e-skin to the temperature-dependent pressure monitoring of artery vessel, high-precision acoustic sound detection, and surface texture recognition of various surfaces. In chapter 6, we demonstrate the linear and wide range pressure sensor with multilayered composite films having interlocked microdomes. In chapter 7, we present a new-concept of e-skin based on mechanochromic polymer and porous structures for overcoming limitations in conventional mechanochromic systems with low mechanochromic performances and limited stretchability. In addition, our mechanochromic e-skins enable the dual-mode detection of static and dynamic forces without any external power. Our e-skins based on functional composites and uniquely designed microstructures can provide a solid platform for next generation eskin in wearable electronics, humanoid robotics, flexible sensors, and wearable medical diagnostic systems.clos

Acoustic sensing as a novel approach for cardiovascular monitoring at the wrist

Cardiovascular diseases are the number one cause of deaths globally. An increased cardiovascular risk can be detected by a regular monitoring of the vital signs including the heart rate, the heart rate variability (HRV) and the blood pressure. For a user to undergo continuous vital sign monitoring, wearable systems prove to be very useful as the device can be integrated into the user's lifestyle without affecting the daily activities. However, the main challenge associated with the monitoring of these cardiovascular parameters is the requirement of different sensing mechanisms at different measurement sites. There is not a single wearable device that can provide sufficient physiological information to track the vital signs from a single site on the body. This thesis proposes a novel concept of using acoustic sensing over the radial artery to extract cardiac parameters for vital sign monitoring. A wearable system consisting of a microphone is designed to allow the detection of the heart sounds together with the pulse wave, an attribute not possible with existing wrist-based sensing methods. Methods: The acoustic signals recorded from the radial artery are a continuous reflection of the instantaneous cardiac activity. These signals are studied and characterised using different algorithms to extract cardiovascular parameters. The validity of the proposed principle is firstly demonstrated using a novel algorithm to extract the heart rate from these signals. The algorithm utilises the power spectral analysis of the acoustic pulse signal to detect the S1 sounds and additionally, the K-means method to remove motion artifacts for an accurate heartbeat detection. The HRV in the short-term acoustic recordings is found by extracting the S1 events using the relative information between the short- and long-term energies of the signal. The S1 events are localised using three different characteristic points and the best representation is found by comparing the instantaneous heart rate profiles. The possibility of measuring the blood pressure using the wearable device is shown by recording the acoustic signal under the influence of external pressure applied on the arterial branch. The temporal and spectral characteristics of the acoustic signal are utilised to extract the feature signals and obtain a relationship with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively. Results: This thesis proposes three different algorithms to find the heart rate, the HRV and the SBP/ DBP readings from the acoustic signals recorded at the wrist. The results obtained by each algorithm are as follows: 1. The heart rate algorithm is validated on a dataset consisting of 12 subjects with a data length of 6 hours. The results demonstrate an accuracy of 98.78%, mean absolute error of 0.28 bpm, limits of agreement between -1.68 and 1.69 bpm, and a correlation coefficient of 0.998 with reference to a state-of-the-art PPG-based commercial device. A high statistical agreement between the heart rate obtained from the acoustic signal and the photoplethysmography (PPG) signal is observed. 2. The HRV algorithm is validated on the short-term acoustic signals of 5-minutes duration recorded from each of the 12 subjects. A comparison is established with the simultaneously recorded electrocardiography (ECG) and PPG signals respectively. The instantaneous heart rate for all the subjects combined together achieves an accuracy of 98.50% and 98.96% with respect to the ECG and PPG signals respectively. The results for the time-domain and frequency-domain HRV parameters also demonstrate high statistical agreement with the ECG and PPG signals respectively. 3. The algorithm proposed for the SBP/ DBP determination is validated on 104 acoustic signals recorded from 40 adult subjects. The experimental outputs when compared with the reference arm- and wrist-based monitors produce a mean error of less than 2 mmHg and a standard deviation of error around 6 mmHg. Based on these results, this thesis shows the potential of this new sensing modality to be used as an alternative, or to complement existing methods, for the continuous monitoring of heart rate and HRV, and spot measurement of the blood pressure at the wrist.Open Acces

Development of biomedical devices for the extracorporeal real-time monitoring and perfusion of transplant organs

The goal of this Thesis is to develop a range of technologies that could enable a paradigm shift in organ preservation for renal transplantation, transitioning from static cold storage to warm normothermic blood perfusion. This transition could enable the development of novel pre-implantation therapies, and even serve as the foundation for a global donor pool. A low-hæmolysis pump was developed, based on a design first proposed by Nikola Tesla in 1913. Simulations demonstrated the theoretical superiority of this design over existing centrifugal pumps for blood recirculation, and provided insights for future avenues of research into this technology. A miniature, battery-powered, multimodal sensor suite for the in-line monitoring of a blood perfusion circuit was designed and implemented. This was named the ‘SmartPipe’, and proved capable of simultaneously monitoring temperature, pressure and blood oxygen saturations over the biologically-relevant ranges of each modality. Finally, the Thesis details the successful implementation and optimisation of a combined microfluidic and microdialysis system for the real-time quantitation of creatinine in blood or urine through amperometric sensing, to act as a live renal function monitor. The range of detection was 4.3μM – 500μM, with the possibility of extending this in both directions. This work also details and explores a novel methodology for functional monitoring in closed-loop systems which avoids the need for sensor calibration, and potentially overcomes the problems of sensor drift and desensitisation.Open Acces

Development of a cell sensing and electrotherapeutic system for a smart stent

Cardiovascular diseases (CVD) is one of the main causes of death worldwide. Coronary heart disease (CHD) and strokes are the highest contributors to CVD deaths (46 % and 26 % respectively) in the UK. The condition which leads to CHD is Coronary artery disease (CAD). The main cause of CAD is coronary atherosclerosis, which involves an inflammatory response of the artery wall to chronic multifactorial injury, which then results into formation of atherosclerotic plaques. One of the main treatment strategies for CAD is Percutaneous Coronary Intervention (PCI). PCI is a procedure during which a balloon mounted catheter with an unexpanded stent is inserted into a peripheral artery and threaded up to the site of stenosis in the coronary artery of the heart to reopen the vessel. PCI usually involves stenting with a Bare Metal Stent (BMS) or Drug Eluting Stent (DES). The 9-month revascularisation rate is 12.32 % with BMS, and this rate has significantly decreased to 4.34 % with early generation DES. The latest generation of DES is associated with revascularisation rates of 2.91 %. Detection of this vascular hyperplasia is a common limitation of these devices which can be found across a number of vascular pathologies. In this project, we developed a new type of biosensor for detecting the changes associated with these blockages that could be mounted on these implantable medical devices. Our design and development led to a comprehensive characterisation of both the sensor and its cell interactions. Proof of concept experiments were performed that legitimised the concept of a smart self-reporting device, as a solution to remote detection of In-stent Restenosis (ISR). The proposed smart stent would have both diagnostic and therapeutic capabilities. Preliminary tests showed that the devices were minimally susceptible to changes in volume and conductivity of culture medium, during baseline measurements. Sensors of different dimensions were fabricated with the best version 16 times smaller but with 4.35 times higher sensitivity in cell detection compared to baseline. Our sensor could also distinguish between different cell types. Indeed the sensor coverage could be remotely monitored intermittently (at 24 h intervals) or continuously (at 15 min intervals) or on demand. Continuous monitoring allowed the gradual changes in cell phenotype to be monitored including cell adherence, proliferation and death which was then correlated with live cell sensor imaging. We found our sensors could be used for both cell detection and therapeutic intervention. As the fabricated biosensors are intended to be integrated onto a future smart stent, this would be implanted in vivo and would be subjected to blood flow. Therefore it was important to test the devices under flow conditions. Our data show that, when incorporated into microfluidic flow chambers, the sensors could exquisitely detect cell adherence under flow and static conditions. Moreover they were also suitable for monitoring the gradual migration and proliferation of vascular cells within a microfluidic channel. Future development of these proof-of-concept biosensors is critical for future commercialisation of this important novel device, which hopefully will provide a new class of diagnostic and therapeutic vascular devices

Nanomechanical characterization of soft bioelectronic interfaces via modeling-informed atomic force microscopy

The field of bioelectronics involves the use of electrodes to exchange electrical signals with biological systems for diagnostic and therapeutic purposes in biomedical devices and healthcare applications. However, the mechanical compatibility of implantable devices with the human body has been a challenge, particularly with long-term implantation into target organs. Current rigid bioelectronics can trigger inflammatory responses and cause unstable device functions due to the mechanical mismatch with the surrounding soft tissue. Recent advances in flexible and stretchable electronics have shown promise in making bioelectronic interfaces more biocompatible. To fully achieve this goal, material science and engineering of soft electronic devices must be combined with quantitative characterization and modeling tools to understand the mechanical issues at the interface between electronic technology and biological tissue. Local mechanical characterization is crucial to understand the activation of failure mechanisms and optimizing the devices. Experimental techniques for testing mechanical properties at the nanoscale are emerging, and the Atomic Force Microscope (AFM) is a good candidate for in situ local mechanical characterization of soft bioelectronic interfaces. In this work, in situ experimental techniques with solely AFM supported by interpretive models for the characterization of planar and three-dimensional devices suitable for in vivo and in vitro biomedical experimentations are reported. The combination of the proposed models and experimental techniques provides access to the local mechanical properties of soft bioelectronic interfaces. The study investigates the nanomechanics of hard thin gold films on soft polymeric substrates (Poly(dimethylsiloxane) PDMS) and 3D inkjet-printed micropillars under different deformation states. The proposed characterization methods provide a rapid and precise determination of mechanical properties, thus giving the possibility to parametrize the microfabrication steps and investigate their impact on the final device