Adaptive Wireless Biomedical Capsule Localization and Tracking

Wireless capsule endoscopy systems have been shown as a gold step to develop future wireless biomedical multitask robotic capsules, which will be utilized in micro surgery, drug delivery, biopsy and multitasks of the endoscopy. In such wireless capsule endoscopy systems, one of the most challenging problems is accurate localization and tracking of the capsule inside the human body. In this thesis, we focus on robotic biomedical capsule localization and tracking using range measurements via electromagetic wave and magnetic strength based sensors. First, a literature review of existing localization techniques with their merits and limitations is presented. Then, a novel geometric environmental coefficient estimation technique is introduced for time of flight (TOF) and received signal strength (RSS) based range measurement. Utilizing the proposed environmental coefficient estimation technique, a 3D wireless biomedical capsule localization and tracking scheme is designed based on a discrete adaptive recursive least square algorithm with forgetting factor. The comparison between localization with novel coefficient estimation technique and localization with known coefficient is provided to demonstrate the proposed technique’s efficiency. Later, as an alternative to TOF and RSS based sensors, use of magnetic strength based sensors is considered. We analyze and demonstrate the performance of the proposed techniques and designs in various scenarios simulated in Matlab/Simulink environment

In-body to On-body Experimental UWB Channel Characterization for the Human Gastrointestinal Area

[ES] La población mundial en países desarrollados está envejeciendo y con ello existe un aumento de enfermedades en gran medida causadas por la edad. Las nuevas tecnologías médicas pueden ayudar a detectar, diagnosticar y tratar estas enfermedades y con ello ahorrar dinero, tiempo y recursos de los sistemas sanitarios. Las tecnologías inalámbricas implantables han abierto un nuevo panorama para la próxima generación de tecnologías médicas. Frecuencias como la Ultra Wide-Band (UWB) de 3.1 a 10.6 GHz están siendo consideradas para la nueva generación de dispositivos inalámbricos para dentro del cuerpo humano. Las características como el reducido tamaño de las antenas, la baja potencia de transmisión y la alta velocidad de datos son las más buscadas en este tipo de dispositivos. El problema surge porque el cuerpo humano depende de la frecuencia de modo que a mayores frecuencias, mayores son las pérdidas por propagación. Conociendo el canal de transmisión se puede solventar el problema de las altas pérdidas. Esta tesis tiene como objetivo caracterizar el canal de radio frecuencia (RF) para la nueva generación de dispositivos médicos implantables. Para caracterizar el canal se han empleado tres diferentes metodologías: simulaciones numéricas, medidas en phantom y experimentos en animales vivos. Las medidas en phantom fueron realizadas en un nuevo sistema de medidas expresamente disen¿ados para medidas de dentro a fuera del cuerpo humano en la banda de frecuencias UWB. Además, se utilizó un novedoso recipiente con dos capas de phantom imitando la zona gastrointestinal del cuerpo. Estos phantoms fueron creados para este tipo de medidas y son extremadamente precisos a las frecuencias UWB. Para los experimentos en animales se utilizaron cerdos y se intentó reproducir en ellos las medidas previamente realizadas en phantom. Las simulaciones software se realizaron con la intención de replicar ambas metodologías. Una vez realizados los experimentos se realizó un extensivo estudio del canal en dominio frecuencial y temporal. Mas en detalle, se compararon las antenas usadas en la recepción y transmisión, el efecto de la grasa en el canal, la formas del recipiente contenedor de phantom y las componentesmulticamino. Como resultado se ha propuesto un modelo de propagación del canal para la banda baja de las frecuencias UWB (3.1 -5.1 GHz) para la zona gastrointestinal del cuerpo humano. Este modelo de propagación ha sido validado utilizando las tres metodologías previamente descritas y comparada con otros estudios existentes en literatura. Finalmente, se midió el canal de propagación para una determinada aplicación a bajas frecuencias con señales UWB. También se realizaron medidas del canal de propagación en la zona cardíaca del cuerpo humano desde un punto de vista de seguridad de datos. Los resultados obtenidos en esta tesis confirman los beneficios que tendría la utilización de frecuencias UWB para las futuras generaciones de dispositivos médicos implantables.[CA] La població mundial a països desenvolupats està envellint-se i enfrontant-se a un augment d'infermetats principalment causades per la edat. Les noves tecnologies mèdiques poden ajudar a detectar, diagnosticar i tractar aquestes malalties, estalviant diners, temps i recursos sanitaris. Els dispositius implantables sense fils han generat un nou panorama per a les noves generacions de dispositius mèdics. Les freqüències com la banda de UWB estan sent considerades per a les futures tecnologies implantables. La reduïda grandària de les antenes, la baixa potència de transmissió i les altes velocitats de dades son característiques buscades per als dispositius implantables. Per contra, els éssers humans depenen de la freqüència en el sentit que a majors freqüències, majors les pèrdues per propagació quan el senyal travessa el cos humà d'interior a exterior. Per solventar aquestes pèrdues el canal de propagació s'ha d'entendre i conèixer de la millor manera possible. Aquesta tesi doctoral te com a objectiu caracteritzar el canal de radio freqüència (RF) per a la nova generació de dispositius mèdics implantables. S'han emprat tres metodologies diferents per a realitzar aquesta caracterització: simulacions software, mesures amb fantomes i experiments amb animals vius. Els experiments amb fantomes es van realitzar a un sistema de mesures dissenyat expressament per a les transmissions de dins a fora del cos humà a les freqüències UWB. També es van utilitzar un contenidor per als fantomes de dues capes, imitant l'area gastrointestinal dels humans. Per als experiments a animals es van emprar porcs, replicant els experiments al laboratori en fantomes de la forma més semblant possible. Les simulacions software foren dissenyades per a imitar les experiments amb fantomes i animals. Després dels experiments el canal de propagació es va investigar exhaustivament des del domini freqüèncial i temporal. S'ha observat com les antenes en transmissió i recepció afecten al senyal, la influència de la grassa, la forma del contenidor de fantoma i les possibles contribucions multicamí. Finalment es proposa un nou model de propagació per a les baixes freqüències UWB (3.1 a 5.1 GHz) per a la zona GI del cos humà. El model es va validar utilitzant les tres metodologies abans esmentades i també foren comparades amb model ja existents a la literature. Finalment des d'un punt de vista aplicat, el canal es va avaluar per al senyal UWB a baixes freqüències (60 MHz). A més a més, per a la nova generació de marcapassos sense fil es va investigar el canal des d'un punt de vista de seguretat de dades. Els resultats obtinguts a aquesta tesi confirmen els avantatges d'emprar la banda de freqüències UWB per a la nova generació de dispositius médics implantables.[EN] The current global population in developed countries is becoming older and facing an increase in diseases mainly caused by age. New medical technologies can help to detect, diagnose and treat illness, saving money, time, and resources of physicians. Wireless in-body devices opened a new scenario for the next generation of medical devices. Frequencies like the Ultra Wide-band (UWB) frequency band (3.1 - 10.6 GHz) are being considered for the next generation of in-body wireless devices. The small size of the antennas, the low power transmission, and the higher data rate are desirable characteristics for in-body devices. However, the human body is frequency ependent, which means higher losses of the radio frequency (RF) signal from in- to out-side the body as the frequency increases. To overcome this, the propagation channel has to be understood and known as much possible to process the signal accordingly. This dissertation aims to characterize the (RF) channel for the future of in-body medical devices. Three different methodologies have been used to characterize the channel: numerical simulations, phantom measurements, and living animals experiments. The phantom measurements were performed in a novel testbed designed for the purpose of in-body measurements at the UWB frequency band. Moreover, multi-layer high accurate phantoms mimicking the gastrointesintal (GI) area were employed. The animal experiments were conducted in living pigs, replicating in the fairest way as possible the phantom measurement campaigns. Lastly, the software simulations were designed to replicate the experimental measurements. An in-depth and detail analysis of the channel was performed in both, frequency and time domain. Concretely, the performance of the receiving and transmitting antennas, the effect of the fat, the shape of the phantom container, and the multipath components were evaluated. Finally, a novel path loss model was obtained for the low UWB frequency band (3.1 - 5.1 GHz) at GI scenarios. The model was validated using the three methodologies and compared with previous models in literature. Finally, from a practical case point of view, the channel was also evaluated for UWB signals at lower frequencies (60 MHz) for the GI area. In addition, for the next generation of leadless pacemakers the security link between the heart and an external device was also evaluated. The results obtained in this dissertation reaffirm the benefits of using the UWB frequency band for the next generation of wireless in-body medical devices.Pérez Simbor, S. (2019). In-body to On-body Experimental UWB Channel Characterization for the Human Gastrointestinal Area [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/133034TESI

Drug Delivery Technology Development in Canada

Canada continues to have a rich history of ground-breaking research in drug delivery within academic institutions, pharmaceutical industry and the biotechnology community

Wireless capsule endoscope for targeted drug delivery

The diagnosis and treatment of pathologies of the gastrointestinal (GI) tract are performed routinely by gastroenterologists using endoscopes and colonoscopes, however the small intestinal tract is beyond the reach of these conventional systems. Attempts have been made to access the small intestines with wireless capsule endoscopes (WCE). These pill-sized cameras take pictures of the intestinal wall and then relay them back for evaluation. This practice enables the detection and diagnosis of pathologies of the GI tract such as Crohn's disease, small intestinal tumours such as lymphoma and small intestinal cancer. The problems with these systems are that they have limited diagnostic capabilities and they do not offer the ability to perform therapy to the affected areas leaving only the options of administering large quantities of drugs or surgical intervention. To address the issue of administering therapy in the small intestinal tract this thesis presents an active swallowable microrobotic platform which has novel functionality enabling the microrobot to treat pathologies through a targeted drug delivery system. This thesis first reviews the state-of-the-art in WCE through the evaluation of current and past literature. A review of current practises such as flexible sigmoidoscopy, virtual colonoscopy and wireless capsule endoscopy are presented. The following sections review the state-of-the-art in methods of resisting peristalsis, drug targeting systems and drug delivery. A review of actuators is presented, in the context of WCE, with a view to evaluate their acceptability in adding functionality to current WCEs. The thesis presents a novel biologically-inspired holding mechanism which overcomes the issue of resisting natural peristalsis in the GI tract. An analysis of the two components of peristaltic force, circumferential and longitudinal peristaltic contractions, are presented to ensure correct functionality of the holding mechanism. A detailed analysis of the motorised method employed to deploy the expanding mechanism is described and a 5:1 scale prototype is presented which characterises the gearbox and validates the holding mechanism. The functionality of WCE is further extended by the inclusion of a novel targeting mechanism capable of delivering a metered dose of medication to a target site of interest in the GI tract. A solution to the problem of positioning a needle within a 360 degree envelope, operating the needle and safely retracting the needle in the GI tract is discussed. A comprehensive analysis of the mechanism to manoeuvre the needle is presented and validation of the mechanism is demonstrated through the evaluation of scale prototypes. Finally a drug delivery system is presented which can expel a 1 ml dose of medication, stored onboard the capsule, into the subcutaneous tissue of the GI tract wall. An analysis of the force required to expel the medication in a set period of time is presented and the design and analysis of a variable pitch conical compression spring which will be used to deliver the medication is discussed. A thermo mechanical trigger mechanism is presented which will be employed to release the compressed conical spring. Experimental results using 1:1 scale prototype parts validate the performance of the mechanisms.Open Acces

Towards tactile sensing active capsule endoscopy

Examination of the gastrointestinal(GI) tract has traditionally been performed using tethered endoscopy tools with limited reach and more recently with passive untethered capsule endoscopy with limited capability. Inspection of small intestines is only possible using the latter capsule endoscopy with on board camera system. Limited to visual means it cannot detect features beneath the lumen wall if they have not affected the lumen structure or colour. This work presents an improved capsule endoscopy system with locomotion for active exploration of the small intestines and tactile sensing to detect deformation of the capsule outer surface when it follows the intestinal wall. In laboratory conditions this system is capable of identifying sub-lumen features such as submucosal tumours.Through an extensive literary review the current state of GI tract inspection in particular using remote operated miniature robotics, was investigated, concluding no solution currently exists that utilises tactile sensing with a capsule endoscopy. In order to achieve such a platform, further investigation was made in to tactile sensing technologies, methods of locomotion through the gut, and methods to support an increased power requirement for additional electronics and actuation. A set of detailed criteria were compiled for a soft formed sensor and flexible bodied locomotion system. The sensing system is built on the biomimetic tactile sensing device, Tactip, \cite{Chorley2008, Chorley2010, Winstone2012, Winstone2013} which has been redesigned to fit the form of a capsule endoscopy. These modifications have required a $360^{o}$ cylindrical sensing surface with $360^{o}$ panoramic optical system. Multi-material 3D printing has been used to build an almost complete sensor assembly with a combination of hard and soft materials, presenting a soft compliant tactile sensing system that mimics the tactile sensing methods of the human finger. The cylindrical Tactip has been validated using artificial submucosal tumours in laboratory conditions. The first experiment has explored the new form factor and measured the device's ability to detect surface deformation when travelling through a pipe like structure with varying lump obstructions. Sensor data was analysed and used to reconstruct the test environment as a 3D rendered structure. A second tactile sensing experiment has explored the use of classifier algorithms to successfully discriminate between three tumour characteristics; shape, size and material hardness. Locomotion of the capsule endoscopy has explored further bio-inspiration from earthworm's peristaltic locomotion, which share operating environment similarities. A soft bodied peristaltic worm robot has been developed that uses a tuned planetary gearbox mechanism to displace tendons that contract each worm segment. Methods have been identified to optimise the gearbox parameter to a pipe like structure of a given diameter. The locomotion system has been tested within a laboratory constructed pipe environment, showing that using only one actuator, three independent worm segments can be controlled. This configuration achieves comparable locomotion capabilities to that of an identical robot with an actuator dedicated to each individual worm segment. This system can be miniaturised more easily due to reduced parts and number of actuators, and so is more suitable for capsule endoscopy. Finally, these two developments have been integrated to demonstrate successful simultaneous locomotion and sensing to detect an artificial submucosal tumour embedded within the test environment. The addition of both tactile sensing and locomotion have created a need for additional power beyond what is available from current battery technology. Early stage work has reviewed wireless power transfer (WPT) as a potential solution to this problem. Methods for optimisation and miniaturisation to implement WPT on a capsule endoscopy have been identified with a laboratory built system that validates the methods found. Future work would see this combined with a miniaturised development of the robot presented. This thesis has developed a novel method for sub-lumen examination. With further efforts to miniaturise the robot it could provide a comfortable and non-invasive procedure to GI tract inspection reducing the need for surgical procedures and accessibility for earlier stage of examination. Furthermore, these developments have applicability in other domains such as veterinary medicine, industrial pipe inspection and exploration of hazardous environments

Soft and flexible bioelectronic micro-systems for electronically controlled drug delivery

The concept of targeted and controlled drug delivery, which directs treatment to precise anatomical sites, offers benefits such as fewer side effects, reduced toxicity, optimized dosages, and quicker responses. However, challenges remain to engineer dependable systems and materials that can modulate host tissue interactions and overcome biological barriers. To stay aligned with advancements in healthcare and precision medicine, novel approaches and materials are imperative to improve effectiveness, biocompatibility, and tissue compliance. Electronically controlled drug delivery (ECDD) has recently emerged as a promising approach to calibrated drug delivery with spatial and temporal precision. This article covers recent breakthroughs in soft, flexible, and adaptable bioelectronic micro-systems designed for ECDD. It overviews the most widely reported operational modes, materials engineering strategies, electronic interfaces, and characterization techniques associated with ECDD systems. Further, it delves into the pivotal applications of ECDD in wearable, ingestible, and implantable medical devices. Finally, the discourse extends to future prospects and challenges for ECDD

Prevalence, Fate and Effects of Plastic in Freshwater Environments

Plastic (and microplastic) pollution has been described as one of the greatest environmental challenges of our time, and a hallmark of the human-driven epoch known as the Anthropocene. It has gained the attention of the general public, governments, and environmental scientists worldwide. To date, the main focus has been on plastics in the marine environment, but interest in the presence and effects of plastics in freshwaters has increased in the recent years. The occurrence of plastics within inland lakes and rivers, as well as their biota, has been demonstrated. Experiments with freshwater organisms have started to explore the direct and indirect effects resulting from plastic exposure. There is a clear need for further research, and a dedicated space for its dissemination. This book is devoted to highlighting current research from around the world on the prevalence, fate, and effects of plastic in freshwater environments

Endoscopic Optical Coherence Tomography: Design and Application

This thesis presents an investigation on endoscopic optical coherence tomography (OCT). As a noninvasive imaging modality, OCT emerges as an increasingly important diagnostic tool for many clinical applications. Despite of many of its merits, such as high resolution and depth resolvability, a major limitation is the relatively shallow penetration depth in tissue (about 2∼3 mm). This is mainly due to tissue scattering and absorption. To overcome this limitation, people have been developing many different endoscopic OCT systems. By utilizing a minimally invasive endoscope, the OCT probing beam can be brought to the close vicinity of the tissue of interest and bypass the scattering of intervening tissues so that it can collect the reflected light signal from desired depth and provide a clear image representing the physiological structure of the region, which can not be disclosed by traditional OCT. In this thesis, three endoscope designs have been studied. While they rely on vastly different principles, they all converge to solve this long-standing problem. A hand-held endoscope with manual scanning is first explored. When a user is holding a hand- held endoscope to examine samples, the movement of the device provides a natural scanning. We proposed and implemented an optical tracking system to estimate and record the trajectory of the device. By registering the OCT axial scan with the spatial information obtained from the tracking system, one can use this system to simply ‘paint’ a desired volume and get any arbitrary scanning pattern by manually waving the endoscope over the region of interest. The accuracy of the tracking system was measured to be about 10 microns, which is comparable to the lateral resolution of most OCT system. Targeted phantom sample and biological samples were manually scanned and the reconstructed images verified the method. Next, we investigated a mechanical way to steer the beam in an OCT endoscope, which is termed as Paired-angle-rotation scanning (PARS). This concept was proposed by my colleague and we further developed this technology by enhancing the longevity of the device, reducing the diameter of the probe, and shrinking down the form factor of the hand-piece. Several families of probes have been designed and fabricated with various optical performances. They have been applied to different applications, including the collector channel examination for glaucoma stent implantation, and vitreous remnant detection during live animal vitrectomy. Lastly a novel non-moving scanning method has been devised. This approach is based on the EO effect of a KTN crystal. With Ohmic contact of the electrodes, the KTN crystal can exhibit a special mode of EO effect, termed as space-charge-controlled electro-optic effect, where the carrier electron will be injected into the material via the Ohmic contact. By applying a high voltage across the material, a linear phase profile can be built under this mode, which in turn deflects the light beam passing through. We constructed a relay telescope to adapt the KTN deflector into a bench top OCT scanning system. One of major technical challenges for this system is the strong chromatic dispersion of KTN crystal within the wavelength band of OCT system. We investigated its impact on the acquired OCT images and proposed a new approach to estimate and compensate the actual dispersion. Comparing with traditional methods, the new method is more computational efficient and accurate. Some biological samples were scanned by this KTN based system. The acquired images justified the feasibility of the usage of this system into a endoscopy setting. My research above all aims to provide solutions to implement an OCT endoscope. As technology evolves from manual, to mechanical, and to electrical approaches, different solutions are presented. Since all have their own advantages and disadvantages, one has to determine the actual requirements and select the best fit for a specific application.</p

Spatial frequency domain imaging towards improved detection of gastrointestinal cancers

Early detection and treatment of gastrointestinal cancers has been shown to drastically improve patients survival rates. However, wide population based screening for gastrointestinal cancers is not feasible due to its high cost, risk of potential complications, and time consuming nature. This thesis forms the proposal for the development of a cost-effective, minimally invasive device to return quantitative tissue information for gastrointestinal cancer detection in-vivo using spatial frequency domain imaging (SFDI). SFDI is a non-invasive imaging technique which can return close to real time maps of absorption and reduced scattering coefficients by projecting a 2D sinusoidal pattern onto a sample of interest. First a low-cost, conventional bench top system was constructed to characterise tissue mimicking phantoms. Phantoms were fabricated with specific absorption and reduced scattering coefficients, mimicking the variation in optical properties typically seen in healthy, cancerous, and pre-cancerous oesophageal tissue. The system shows accurate retrieval of absorption and reduced scattering coefficients of 19% and 11% error respectively. However, this bench top system consists of a bulky projector and is therefore not feasible for in-vivo imaging. For SFDI systems to be feasible for in-vivo imaging, they are required to be miniaturised. Many conditions must be considered when doing this such as various illumination conditions, lighting conditions and system geometries. Therefore to aid in the miniaturisation of the bench top system, an SFDI system was simulated in the open-source ray tracing software Blender, where the capability to simulate these conditions is possible. A material of tunable absorption and scattering properties was characterised such that the specific absorption and reduced scattering coefficients of the material were known. The simulated system shows capability in detecting optical properties of typical gastrointestinal conditions in an up-close, planar geometry, as well in a non-planar geometry of a tube simulating a lumen. Optical property imaging in the non-planar, tubular geometry was done with the use of a novel illumination pattern, developed for this work. Finally, using the knowledge gained from the simulation model, the bench top system was miniaturised to a 3 mm diameter prototype. The novel use of a fiber array producing the necessary interfering fringe patterns replaced the bulky projector. The system showed capability to image phantoms simulating typical gastrointestinal conditions at two wavelengths (515 and 660 nm), measuring absorption and reduced scattering coefficients with 15% and 6% accuracy in comparison to the bench top system for the fabricated phantoms. It is proposed that this system may be used for cost-effective, minimally invasive, quantitative imaging of the gastrointestinal tract in-vivo, providing enhanced contrast for difficult to detect cancers

Spatial frequency domain imaging towards improved detection of gastrointestinal cancers

Early detection and treatment of gastrointestinal cancers has been shown to drastically improve patients survival rates. However, wide population based screening for gastrointestinal cancers is not feasible due to its high cost, risk of potential complications, and time consuming nature. This thesis forms the proposal for the development of a cost-effective, minimally invasive device to return quantitative tissue information for gastrointestinal cancer detection in-vivo using spatial frequency domain imaging (SFDI). SFDI is a non-invasive imaging technique which can return close to real time maps of absorption and reduced scattering coefficients by projecting a 2D sinusoidal pattern onto a sample of interest. First a low-cost, conventional bench top system was constructed to characterise tissue mimicking phantoms. Phantoms were fabricated with specific absorption and reduced scattering coefficients, mimicking the variation in optical properties typically seen in healthy, cancerous, and pre-cancerous oesophageal tissue. The system shows accurate retrieval of absorption and reduced scattering coefficients of 19% and 11% error respectively. However, this bench top system consists of a bulky projector and is therefore not feasible for in-vivo imaging. For SFDI systems to be feasible for in-vivo imaging, they are required to be miniaturised. Many conditions must be considered when doing this such as various illumination conditions, lighting conditions and system geometries. Therefore to aid in the miniaturisation of the bench top system, an SFDI system was simulated in the open-source ray tracing software Blender, where the capability to simulate these conditions is possible. A material of tunable absorption and scattering properties was characterised such that the specific absorption and reduced scattering coefficients of the material were known. The simulated system shows capability in detecting optical properties of typical gastrointestinal conditions in an up-close, planar geometry, as well in a non-planar geometry of a tube simulating a lumen. Optical property imaging in the non-planar, tubular geometry was done with the use of a novel illumination pattern, developed for this work. Finally, using the knowledge gained from the simulation model, the bench top system was miniaturised to a 3 mm diameter prototype. The novel use of a fiber array producing the necessary interfering fringe patterns replaced the bulky projector. The system showed capability to image phantoms simulating typical gastrointestinal conditions at two wavelengths (515 and 660 nm), measuring absorption and reduced scattering coefficients with 15% and 6% accuracy in comparison to the bench top system for the fabricated phantoms. It is proposed that this system may be used for cost-effective, minimally invasive, quantitative imaging of the gastrointestinal tract in-vivo, providing enhanced contrast for difficult to detect cancers