Most rural areas of developing countries are faced with problems like shortage of doctors in hospitals, illiteracy and poor power supply. Because of these issues, Information and Communication Technology (ICT) is often sees as a useful solution for these areas. Unfortunately, the social environment is often ignored. This leads to inappropriate systems being developed for these areas. The aims of this thesis were firstly, to learn how a communication system can be built for a rural telehealth environment in a developing country, secondly to learn how users can be supported to use such a system.

Tissues constituting mammalian organisms are finitely organised 3-D multicellular structures where cell-cell and cell-matrix interactions are important modulators of functionality. The liver, being the site of metabolism in mammals, is extensively employed in in-vitro studies such as toxicology, drug testing and liver replacement. Most existing liver models have been static, homogenous 2-D models which have shown limited morphological and functional characteristics of in-vivo liver. With the improved understanding of the liver, these models became more sophisticated to comprise various liver and non-liver cell types, various configurations of extracellular matrix and complex scaffold supports, including fluidic systems. Fluidic supports for liver cells in-vitro are reported in this work and two different types were investigated. The first one was a glass based micro fluidic system with hexagonal structure to mimic the liver lobule. The second one was a standard flatplate fluidic chamber made of plastic (Ibidi channel). For the purpose of improving the attachment of the cells and the performance of the bioreactors examined, various substrate coating procedures were evaluated. The main coating techniques employed were collagen in two forms, adsorbed and gel, and plasma polymerised allylamine (ppAAm). The plasma coating procedures utilised in this work changed the surface properties of the substrate used by increasing the levels of nitrogen and improving hydrophilicity as demonstrated by x-ray photoelectron spectroscopy and contact angle measurements. The ppAAm penetrated both etched glass channels of the hexagonal bioreactor and the flat-plate chamber. The ppAAm films on etched glass channels had similar properties to the films produced on the glass surrounding the channels and coverslips. The ppAAm films obtained in the flat-plate chamber were different and they were characterised with a gradient of chemicals and hydrophilicity. This was because the Ibidi chamber is a closed environment and the plasma vapour infiltrated through the inlet and outlet at the ends of the channel. The attachment and functionality of primary rat hepatocytes seeded onto ppAAm films were evaluated using ppAAm coated coverslips and compared to coverslips coated with collagen gel. This demonstrated that both collagen gel and ppAAm improved the attachment, albumin secretion and 7-Ethoxyresorufin-O-deethylase (EROD) activity of the cells compared to uncoated glass. The hexagonal glass bioreactor showed poor attachment of liver cells and this was enhanced with ppAAm coating. The Huh-7 cells incubated into ppAAm coated hexagonal bioreactor died and detached after incubation with media flow. One of the reasons for this was poor cellular attachment. An improved attachment, but not viability, was observed when the cells were seeded using the biotin-avidin technique. The ppAAm coated flat-plate chamber demonstrated low adhesion of primary rat hepatocytes. However, these channels showed good attachment when collagen type I was adsorbed onto the surface. The viability and functionality, when measured using albumin secretion and EROD, of primary rat hepatocytes were maintained for 5 days in closed fluidic circuit in mono-culture and co-culture with 3T3 cells. These promising results could be exploited to further develop these systems for in-vitro culture of liver cells.

The potential effects of introducing bone regeneration strategies into environments of disease and damage are often overlooked, despite the fact that many of the signalling pathways in inflammation have effects on bone development and healing. Embryonic stem cells (ESCs) are increasingly being used to develop models of disease and have potential in osteogenic-cell based therapies. Osteogenic differentiation strategies for ESCs are well established, but the response of these cells to tissue damage and inflammation has not yet been investigated, particularly in comparison to primary osteoblasts. Here, proinflammatory cytokines were used as part of an in vitro model to mimic elements of skeletal disease, such as rheumatoid arthritis and non-union fractures. The response of osteogenically differentiated mouse embryonic stem cells (osteo-mESCs) to the proinflammatory cytokines interleukin 1-β (IL-1β), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), was compared to that of primary mouse calvarial osteoblasts, already well-described in literature and used as a “benchmark” in this study. Although histology, immunocytochemistry and PCR showed similarities in osteogenic differentiation of the osteo-mESCs and the primary calvarial cells, over 21 days in culture, there were marked differences in the response to the proinflammatory cytokines. Viability of the osteo-mESCs was maintained in response to cytokines, whereas viability of primary cells was significantly reduced. There were marked increases in nitric oxide (NO) and prostaglandin E2 (PGE2) production in primary calvarial cells over the entire 21-day culture period, but this was not seen with osteo-mESCs until day 21. The study then went on to look at the effects of proinflammatory signalling on the in vitro bone formation of the two cell types. Significant differences in the effects of proinflammatory cytokines on bone nodule formation and matrix production were seen when comparing the osteo-mESCs and the calvarial cells. This study demonstrates that while osteo-mESCs share phenotypic characteristics with primary osteoblasts, there are some distinct differences in their biochemistry and response to cytokines. This is relevant to understanding differentiation of stem cells, developing in vitro models of disease, testing new drugs and developing cell therapies. An additional objective in this investigation was to look at tissue engineering strategies as a means of controlling inflammation in bone disease. The primary calvarial osteoblasts were utilised as an in vitro inflammation model, and used to study the effects of anti-inflammatory mediators. Anti-inflammatory-releasing porous scaffolds were manufactured from poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG). The calvarial osteoblast inflammation model was used successfully to show successful release of diclofenac sodium from the PLGA/PEG scaffolds. This study demonstrates that there is much to consider in the development of regenerative strategies for bone disease, particularly the role that the effect and control of inflammation will play in bone healing.

In total knee replacement (TKR) surgery, mobile bearing (MB) total knee prostheses were designed to more closely mimic the function of the normal knee than traditional fixed bearing (FB) designs by allowing axial mobility between the polyethylene insert and tibial tray. Despite the hypothetical benefits of the MB design, few studies have objectively analysed knee biomechanics during activities of daily living (ADLs) in the laboratory compared to FB designs. This thesis aimed to substantiate the theoretical advantages of MB implantation during ADLs in the laboratory as well as during free living conditions, in addition to investigating previous claims of instability in MB knees. Sixteen patients undergoing primary unilateral total knee replacement (TKR) surgery were randomised to receive either a FB (n=8) or MB (n=8) total knee prosthesis and were tested at pre-surgery, three months post-surgery, and nine months post-surgery using three dimensional motion analysis in the laboratory and electrogoniometry and accelerometry during free living conditions. No differences were found between FB and MB groups during walking at post-surgery that could not be explained by differences at pre-surgery. There were also no differences between FB and MB groups during the more biomechanically demanding activities of stair negotiation and sit to stand and stand to sit activities, as well as no differences during free living conditions away from the laboratory. There appears to be no evidence based rationale for the widespread use of MBs with regards to optimising knee function during ADLs. This thesis was the first to compare FB and MB designs using the same implant range, posterior cruciate ligament (PCL) scenario, posterior stabilising strategy, and patella strategy over a range of ADLs, as well as being the first to combine testing in the laboratory with testing during free living conditions away from the laboratory.

In recent years, a number of reports have focused on the use of polyesters in drug delivery due to their intrinsic biocompatibility and biodegradability. In this thesis, aliphatic polyesters were synthesized by polycondensation reaction and ring opening polymerization reactions. The properties of the polymers and drug delivery potential of the resultant materials were evaluated. In the polycondensation reactions, a series of aliphatic polyesters of similar molecular weight were synthesized by reacting 1,10-decanediol with different ratios of succinic acid/phenylsuccinic acid and the effects of phenyl group side-chain substitution on polymer properties was investigated. A solvent-free melt polycondensation method using scandium (III) triflate as catalyst at an industrially relevant temperature (120 °C) was used. As the phenyl content increased, the polymers changed from semicrystalline to amorphous in state. The loading capability of polymers was checked by formulating nanoparticles containing coumarin 6 as a fluorescent dye analogue of active drugs. A polymer with a 70/30 ratio of succinic acid and phenylsuccinic acid showed the highest dye loading among the set of materials synthesised. This polymer was found to be degradable over time under selected experimental conditions. Amphiphilic block co-polymers from the PluronicTM class were used to stabilize, in PBS, nanoparticles formed from these polyesters by nanoprecipitation routes. The metabolic activity, cell membrane integrity and lysosomal functions of C3A cells dosed with the polymers were determined to observe the cytocompatibility of the highest dye-loaded nanoparticles. Activity relative to undosed C3A cells was retained at more than 80% in the all of the assays. Imaging of Pluronic coated and uncoated nanoparticles in C3A cells suggested that both types of the nanoparticles were endocytosed in the early stage of the study (within 10 min). The internalization of nanoparticles was increased progressively over the study time. These results indicated the possible utility of the selected polymers in diagnostic and delivery applications. Ring opening polymerization (ROP) reactions were used for the synthesis of a diblock (mPEG-b-PεDL) and a triblock (PεDL-b-PEG-b-PεDL) copolymer from a seven membered ε-decalactone (ε-DL) monomer obtained from renewable sources. A diblock (mPEG-b-PεDL) copolymer was compared with structurally similar mPEG-b-PCL copolymer synthesized via ROP of ε-caprolactone (ε-CL) monomer, which can be considered as a non-renewable monomer. A six membered δ-decalactone (δ-DL) was also used for the synthesis of a diblock copolymer (mPEG-b-PδDL) to compare the reaction kinetics and properties of the copolymers. The copolymers were prepared via bulk polymerisation using 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) as a metal-free catalyst to replace the conventionally used stannous octoate [Sn(Oct)2]. A higher polymerization efficiency was achived with TBD compared to Sn(Oct)2 catalyst. However, a notable difference in the reaction temperature required for ε-DL and δ-DL polymerization was observed. The comparison with a structural analogue, i.e. ε-CL, demonstrated that the ε-DL polymerization was inhibited due to the presence of the alkyl chain of ε-DL monomer. However, a higher reaction time (12 h for TBD and 24 h for Sn(Oct)2) in CROP of ε-DL was addressed by using microwave based ring opening polymerization (MROP) reaction. The MROP was adopted as a ‘green’ and cheap heating method alternative to conventional heating (CROP) for the synthesis of mPEG-b-PεDL diblock copolymers using TBD as a catalyst. All the reactions were conducted in bulk. The MROP was designed based on the dielectric properties of all the reacting materials, as it was found that ε-DL monomers showed good absorption of MW radiation (tanδ>0.5). Accordingly, MROP resulted in a higher rate of ε-DL polymerization compared to CROP but comparison of the synthesis of mPEG-b-PCL copolymer by MROP indicated that the presence of the alkyl chain in ε-DL monomer significantly reduced the rate of polymerization. The synthesized mPEG-b-PεDL copolymer was investigated as a potential drug delivery vehicle for solubilization and controlled delivery of indomethacin. The indomethacin loading and release from mPEG-b-PεDL micelles (amorphous core) was compared against well-established mPEG-b-PCL micelles (semicrystalline core). The drug-polymer compatibility was also determined through a predictive computational approach to access the drug solubilisation (or drug loading) into hydrated micelles. The micelles were prepared by solvent evaporation method and characterized for size, morphology, indomethacin (IND) loading and release. Both of the micelle formulations showed a uniform distribution of spherical micelles with size <60 nm. However, a significantly higher size of empty mPEG-b- PεDL micelle was observed compared to mPEG-b-PCL micelles. A higher compatibility of the drug was predicted with PCL core as determined by modified Flory-Huggins interaction parameters (sp) using the Hanson solubility parameter (HSP) approach. The compatibility of the drug was determined for both of the segments (hydrophilic and hydrophobic) of the copolymers and found to be in the order of sp (PεDL)> sp (mPEG)> sp (PCL). The predictions suggested that more IND should encapsulate within the micelles with PCL core compared to PDL core, but the IND loading experiments revealed an overall higher loading in PεDL core (6.55 wt%) compared to PCL core (5.39 wt%) (P < 0.05, unpaired student’s t-test). However, consideration of the IND loading per unit volume of the micelles revealed that the PCL cored micelles was able to load 1.5 times more compared to the PεDL cored micelles. This result illustrated the higher compatibility of the IND with PCL core in accordance with the solubility parameter calculations. These data also suggested that the overall higher IND loading in PεDL core was attributable to the amorphous nature of the core which increased the core volume by 1.81 times compared to the PCL core. Drug release studies showed the sustained release pattern from both of the micelle systems although the semicrystalline PCL core (80% drug release in 110 h) was able to release the drug for a longer period compared to PεDL core (80% drug release in 72 h). Cell viability tests demonstrated the cytocompatibility of the mPEG-b-PεDL polymer. The micelles were internalized effectively in the early stages of the study and progressively increased with time. The results of the present thesis suggested that novel aliphatic polyester can be good candidates for the drug delivery applications and further studies can explore the possible applications of these polymers in the biomedical field.

Encompassing with fields on engineering and medical image quality, this dissertation proposes a novel framework for diagnostic performance evaluation based on objective image-quality assessment, an important step in the development of new imaging devices, acquisitions, or image-processing techniques being used for clinicians and researchers. The objective of this dissertation is to develop computational modeling tools that allow comprehensive evaluation of task-based assessment including clinical interpretation of images regardless of image dimensionality. Because of advances in the development of medical imaging devices, several techniques have improved image quality where the format domain of the outcome images becomes multidimensional (e.g., 3D+time or 4D). To evaluate the performance of new imaging devices or to optimize various design parameters and algorithms, the quality measurement should be performed using an appropriate image-quality figure-of-merit (FOM). Classical FOM such as bias and variance, or mean-square error, have been broadly used in the past. Unfortunately, they do not reflect the fact that the average performance of the principal agent in medical decision-making is frequently a human observer, nor are they aware of the specific diagnostic task. The standard goal for image quality assessment is a task-based approach in which one evaluates human observer performance of a specified diagnostic task (e.g. detection of the presence of lesions). However, having a human observer performs the tasks is costly and time-consuming. To facilitate practical task-based assessment of image quality, a numerical observer is required as a surrogate for human observers. Previously, numerical observers for the detection task have been studied both in research and industry; however, little research effort has been devoted toward development of one utilized for multidimensional imaging studies (e.g., 4D). Limiting the numerical observer tools that accommodate all information embedded in a series of images, the performance assessment of a particular new technique that generates multidimensional data is complex and limited. Consequently, key questions remain unanswered about how much the image quality improved using these new multidimensional images on a specific clinical task. To address this gap, this dissertation proposes a new numerical-observer methodology to assess the improvement achieved from newly developed imaging technologies. This numerical observer approach can be generalized to exploit pertinent statistical information in multidimensional images and accurately predict the performance of a human observer over the complexity of the image domains. Part I of this dissertation aims to develop a numerical observer that accommodates multidimensional images to process correlated signal components and appropriately incorporate them into an absolute FOM. Part II of this dissertation aims to apply the model developed in Part I to selected clinical applications with multidimensional images including: 1) respiratory-gated positron emission tomography (PET) in lung cancer (3D+t), 2) kinetic parametric PET in head-and-neck cancer (3D+k), and 3) spectral computed tomography (CT) in atherosclerotic plaque (3D+e). The author compares the task-based performance of the proposed approach to that of conventional methods, evaluated based on a broadly-used signal-known-exactly /background-known-exactly paradigm, which is in the context of the specified properties of a target object (e.g., a lesion) on highly realistic and clinical backgrounds. A realistic target object is generated with specific properties and applied to a set of images to create pathological scenarios for the performance evaluation, e.g., lesions in the lungs or plaques in the artery. The regions of interest (ROIs) of the target objects are formed over an ensemble of data measurements under identical conditions and evaluated for the inclusion of useful information from different complex domains (i.e., 3D+t, 3D+k, 3D+e). This work provides an image-quality assessment metric with no dimensional limitation that could help substantially improve assessment of performance achieved from new developments in imaging that make use of high dimensional data.

There is a disproportionate burden of disease (measured in daily-adjusted life years, or DALYs) in low-income countries. Much of this disparity is due to infectious diseases: 53% of DALYs in Africa are due to infectious diseases, compared with only 3% in the American continents. This disparity is largely due to differences in electrical and transport infrastructure as well as access to skilled personnel and monetary resources. Current diagnostic solutions are primarily designed for high-resource settings and therefore these solutions cannot be easily translated to a lower-resource setting. In order to tackle this health disparity, new solutions must be designed specifically for a lower-resource setting. In this dissertation, we take a translational approach to engineering appropriate diagnostics for resource-limited settings. First, we develop a handheld smartphone accessory to perform an assay similar to enzyme-linked immunosorbent assay (ELISA), traditionally a laboratory-based test. In 15 minutes, it provides an objective diagnostic readout important for minimal training, while using an average of 1.6mW of power and costing only $34. We further develop the device to provide a quantitative hemoglobin measurement simultaneously with an HIV immunoassay, for use in antenatal care screening. The multiplexing two assay types that are clinically relevant has the potential to streamline workflow. While specifications can be demonstrated in the laboratory, the true test of the device must be performed in the field. We brought our smartphone accessory to three health centers in Kigali, Rwanda to be used by healthcare workers with no prior experience in ELISA. After a short 30 minute training, the healthcare workers were able to obtain diagnostic results comparable to other immunoassays run under field conditions. With a simple and user-friendly design, we sought to further expand the usage of our device as a self-testing device, having patients test themselves. Lastly, we explore manufacturable thermoplastics as a material for a microfluidic diagnostic for nucleic acid detection. The sum of this work aims to gain insight into methods of design, testing, and implementation of translational design.

Point-of-care (POC) diagnostic technologies aim to expand access to traditional laboratory-based testing to near-patient settings. These settings can range from emergency or intensive care-units (ICUs) in the United States, to remote health posts in sub Saharan Africa. Differences in budget and infrastructure play a role in characterizing the wide array of possible “near patient” settings and must be taken into consideration in the engineering design process. In this dissertation we use translational engineering to develop practical and accessible microfluidic POC immunoassays for diverse settings, that include both provider and consumer facing applications. First, we examined Lyme Disease in the U.S., where existing diagnostic technologies face the challenge of rapid and accurate serodiagnosis in the face of largely non-specific clinical symptoms. We developed a multiplexed rapid test that could replicate enzyme-linked immunosorbent assay (ELISA) performance for Lyme Disease diagnosis. After screening candidate biomarkers, we evaluated performance of the multiplexed microfluidic test against ELISA using clinical serum samples and illustrated the potential to streamline current clinical algorithms requiring two immunoassays (ELISA and Western Blot) into one standalone test suitable for physician’s offices or urgent care clinics in the U.S. We also showed exploratory work towards a similar multiplexed test design for another bacterial spirochete infection, Leptospirosis. Next, we built on previous work towards a POC HIV-syphilis antenatal screening tool, to develop a smartphone-integrated, microfluidic assay for healthcare workers to use in low resource settings. The low-cost ($34), re-usable device (“smartphone dongle”) costs $34 to produce and provides results in 15 minutes. In this work, we focus on assay development efforts undertaken towards development of a fully integrated POC product suitable for deployment in the field, with practical considerations for the use of fingerstick blood, stability, scale-up and transport. We also streamlined the number of manual steps for end-user operation, through the use of lyophilized secondary antibodies, preloaded reagents on cassette, and an automatic result readout. While laboratory demonstration with clinical samples is important for initial characterization of POC devices, field evaluation reveals diagnostic performance under real-world conditions. We tested the device in the hands of minimally trained healthcare workers in Rwanda and saw comparable performance to other immunoassays run under field conditions. We also performed a follow-up pilot field study in Rwanda to evaluate the feasibility of the smartphone dongle platform for self-testing by patients/consumers in a low-resource setting, one of the most challenging use-cases for POC devices. Finally, we sought to integrate intellectual frameworks from behavioral research and user-experience (UX) design in creating a new framework for evaluation of consumer-facing microfluidic devices, specifically towards HIV home-testing in the U.S. While overall rates of HIV are decreasing in the U.S., the population of gay, bisexual and other men who have sex with men (MSM) are disproportionately affected. Self-testing products for sexually transmitted infection (STI) testing could address unmet needs for these target populations in both increasing access and frequency of testing, as well as integrating use with sexual partners for early diagnosis or even prevention. We worked with a cohort of MSMs at high risk for HIV/STI transmission in New York City, and performed for the first time, a structured assessment of completely naïve users interacting with a smartphone interfaced microfluidic diagnostic device (“SMARTtest”). We integrated UX design value model of device usability, credibility, accessibility and acceptability into our evaluation framework, which influence user’s information, knowledge, motivation and behavioral skills towards engaging with a prevention method (“IMB” model). Thus far, such frameworks have rarely been applied to other consumer health monitoring devices, including microfluidic POC devices. As the microfluidic field moves towards more field demonstrations of devices, more untrained and minimally trained users will have access to such tools. It is important to understand how they use devices, what the device failure points are and what the most relevant design features are to spur user adoption and meaningful usage. Underlying our work in creating accessible and practical POC immunoassay tools for infectious disease detection, is the illustration of the translational development roadmap from proof-of-concept assay development to field studies and user-based evaluations for intended end-use settings that range from U.S. based primary care clinics, rural health centers in low-resource settings as well as self-testing environments in both. Incorporating an understanding of the target use-case setting is critical in translating technologies for clinical use, whether in the infrastructure and services that are available, or end-user needs and constraints such as clinical workflow patterns, level of technical expertise and perceptions of usefulness and value. We show how user/use-case focused application of downstream translational engineering and testing informs upstream design choices and accelerates development of POC devices for real-world use. The sum of this work aims to illustrate tenets of translational engineering design and testing to advance insight into building POC products that are poised for greater adoption by target end users, whether they are health providers or consumers.

Health information technology (HIT) has been identified as the fundamental driver to streamline the healthcare delivery processes to improve care quality and reduce operational costs. Of the many facets of HIT is Clinical Decision Support (CDS) which provides the physician with patient-specific inferences, intelligently filtered and organized, at appropriate times. This research has been conducted to develop an agile solution to Clinical Decision Support at the point of care in a healthcare setting as a potential solution to the challenges of interoperability and the complexity of possible solutions. The capabilities of Business Process Management (BPM) and Workflow Management systems are leveraged to support a Service Oriented Architecture development approach for ensuring evidence based medical practice. The aim of this study is to present an architecture solution that is based on SOA principles and embeds clinical guidelines within a healthcare setting. Since the solution is designed to implement real life healthcare scenarios, it essentially supports evidence-based clinical guidelines that are liable to change over a period of time. The thesis is divided into four parts. The first part consists of an Introduction to the study and a background to existing approaches for development and integration of Clinical Decision Support Systems. The second part focuses on the development of a Clinical Decision Support Framework based on Service Oriented Architecture. The CDS Framework is composed of standards based open source technologies including JBoss SwitchYard (enterprise service bus), rule-based CDS enabled by JBoss Drools, process modelling using Business Process Modelling and Notation. To ensure interoperability among various components, healthcare standards by HL7 and OMG are implemented. The third part provides implementation of this CDS Framework in healthcare scenarios. Two scenarios are concerned with the medical practice for diagnosis and early intervention (Chronic Obstructive Pulmonary Disease and Lung Cancer), one case study for Genetic data enablement of CDS systems (New born screening for Cystic Fibrosis) and the last case study is about using BPM techniques for managing healthcare organizational perspectives including human interaction with automated clinical workflows. The last part concludes the research with contributions in design and architecture of CDS systems. This thesis has primarily adopted the Design Science Research Methodology for Information Systems. Additionally, Business Process Management Life Cycle, Agile Business Rules Development methodology and Pattern-Based Cycle for E-Workflow Design for individual case studies are used. Using evidence-based clinical guidelines published by UK's National Institute of Health and Care Excellence, the integration of latest research in clinical practice has been employed in the automated workflows. The case studies implemented using the CDS Framework are evaluated against implementation requirements, conformance to SOA principles and response time using load testing strategy. For a healthcare organization to achieve its strategic goals in administrative and clinical practice, this research has provided a standards based integration solution in the field of clinical decision support. A SOA based CDS can serve as a potential solution to complexities in IT interventions as the core data and business logic functions are loosely coupled from the presentation. Additionally, the results of this this research can serve as an exemplar for other industrial domains requiring rapid response to evolving business processes.

Orientador(a): Rosangela da Silva Leote / Banca: Antônio Pereira Jr / Banca: Fernando Fogliano / Banca: Marco Antonio Corrêa Varella / Banca: Rachel Zuanon Dias / Banca: Osvaldo Pessoa Jr / Resumo: Esta tese parte do pressuposto de que a arte de biofeedback manifesta a mente corporificada de diferentes formas. Considerando essa premissa, propomos a construção de uma epistemologia, sobretudo a partir de abordagens neurocientíficas, com vistas a produzir aportes que permitam avaliar a hipótese de que a arte de biofeedback apresenta modelos de organização e experiência, fora dos quadros naturais, que complementam a investigação científica sobre a mente corporificada. A epistemologia apresentada é alicerçada na fenomenologia, nas teorias tradicionais da mente e da mente corporificada da neurociência e nos fundamentos biológicos e técnicos dos dispositivos de biofeedback. Além disso, a tese conta com uma contextualização histórica que assume que a arte de biofeedback descende de uma tradição imaginativa sobre a interioridade corporal e a localização da mente que se desenvolveu na cultura ocidental. A convergência das abordagens apresentadas na tese originou uma metodologia que confirma a nossa hipótese, a qual é evidenciada por meio da descrição e análise de uma série de implementações poéticas de biofeedback que abrange desde obras de artistas pioneiros criadas nos anos 60 até trabalhos produzidos recentemente / Abstract: This thesis bases itself on the assumption that biofeedback art manifests the embodied mind in different ways. In considering this idea, we propose an epistemology based especially on neuroscientific approaches aimed toward at producing evidence to evaluate the hypothesis that the biofeedback art encompassess models of organization and experience outside of the natural frames that complement the study of the embodied mind. The epistemology presented here is grounded on phenomenology, traditional theories of the mind and embodied mind, and the biological and technical foundations of biofeedback devices. Additionally, the epistemology relies on a historical context that assumes that biofeedback art originated from an imaginative tradition about body interiority and the location of the mind that has developed in Western culture. The convergence of the approaches presented here generated a methodology that confirms our hypothesis, which is evidenced by the description and analysis of a series of poetic biofeedback implementations that cover works by pioneer artists from the 60s to present day / Doutor