A calorimetria indireta para análise do metabolismo humano tem se mostrado um método não invasivo de crescente importância no estudo mais preciso das respostas metabólicas e cardio-respiratórias. Entretanto, o alto custo dos equipamentos aliado à falta de conhecimento das técnicas tem impedido a disseminação do uso de analisadores metabólicos no Brasil. Este trabalho foi desenvolvido com o intuito de oferecer uma visão global dos procedimentos de calorimetria indireta aplicados à avaliação do metabolismo humano sob a abordagem de Engenharia Biomédica. Foram avaliados três transdutores tipicamente utilizados em equipamentos de calorimetria indireta para análise metabólica humana: um transdutor eletroquímico de oxigênio, um transdutor de dióxido de carbono por radiação infravermelha e um transdutor de fluxo em volume tipo turbina. O transdutor de oxigênio mostrou-se bastante confiável, mas com um tempo de resposta bastante elevado para aplicações em análises de respiração a respiração. A principal deficiência do transdutor de dióxido de carbono está no fato de sua configuração proporcionar um aumento significativo na resistência à respiração do indivíduo. Verificou-se que o transdutor de fluxo em volume apresenta um melhor comportamento para um fluxo em torno de 20 litros/minuto. Apesar das limitações apresentadas pelos transdutores, os resultados dos ensaios foram úteis e representativos para a compreensão do funcionamento de um analisador metabólico humano porcalorimetria indireta, evidenciando quais deficiências devem ser sanadas em pesquisas futuras e os cuidados a serem considerados na implantação do laboratório para análise metabólica/respiratória sendo instalado no Laboratório de Engenharia Biomédica da Escola Politécnica da Universidade de São Paulo. / The indirect calorimetry for analysis of the human metabolism has been a no invasive method of increasing importance in the study of metabolic and cardiorespiratory responses. However, the high cost of the equipment ally to the lack of knowledge of the techniques have been obstacles to the use of metabolic analysers in Brazil. This research was developed with the intention to offer a global vision of the applied procedures of indirect calorimetry to the evaluation of the human metabolism under the prism of the Biomedical Engineering. Three transducers typically used in equipment of indirect calorimetry for metabolic analysis had been evaluated: an electrochemical transducer of oxygen, a carbon dioxide transducer by infrared absorption and a turbine flowmeter. The oxygen transducer revealed sufficiently trustworthy, but a too high response time for applications in breath by breath analyses. The main deficiency of the transducer of carbon dioxide is to provide a significant increase in the flow resistance. It was verified that the flowmeter presents one better behavior for a stream around 20 litres/minute. Despite the limitations presented for the transducers, the results of the assays had been useful and representative for the understanding of the functioning of a human metabolic analyser for indirect calorimetry, evidencing which points have to be improved in future researches and to be considered in the implantation of the laboratory for metabolic and respiratory analysis being installed in the Laboratório de Engenharia Biomédica da Escola Politécnica da Universidade de São Paulo.

Soft materials have gained increasing prominence in science and technology over the last few decades. This shift from traditional rigid materials to soft, compliant materials have led to the emergence of a new class of devices which can interact with humans safely, as well as reduce the disparity in mechanical compliance at the interface of soft human tissue and rigid devices.<br><br>One of the largest application of soft materials has been in the field of flexible electronics, especially in wearable sensors. While wearable sensors for physical attributes such as strain, temperature, etc. have been popular, they lack applications and significance from a healthcare perspective. Point-of-care (POC) devices, on the other hand, provide exceptional healthcare value, bringing useful diagnostic tests to the bedside of the patient. POC devices, however, have been developed for only a limited number of health attributes. In this dissertation I propose and demonstrate wireless, wearable POC devices to measure and communicate the level of various analytes in and the properties of multiple biofluids: blood, urine, wound exudate, and sweat.<br><br>Along with sensors, another prominent area of soft materials application has been in actuators and robots which mimic biological systems not only in their action but also in their soft structure and actuation mechanisms. In this dissertation I develop design strategies to improve upon current soft robots by programming the storage of elastic strain energy. This strategy enables us to fabricate soft actuators capable of programmable and low energy consuming, yet high speed motion. Collectively, this dissertation demonstrates the use of soft compliant materials as the foundation for developing new sensors and actuators for human use and interaction.

<div>Rare circulating cells are becoming a subject of interest due to their potential clinical applications to replace invasive procedures. Due their low presence in blood (as low as 1 in 1 ml of blood) various platforms are developed to capture and isolate them. Common limitations of current platforms include the inability to process large volumes of blood without an initial volume reduction step such as centrifugation, reliance on a single antibody for the capture, and the difficulty of releasing and retrieving the captured cells with high purity. A rare cell retrieval platform with high throughput operation and high purity retrieval is needed to capture these rare cells by processing large volumes of blood.</div><div><br></div><div>In this thesis study, we have developed a two-tiered microchip system to capture and retrieve rare cells from blood samples with high purity. The first module of the system is a high throughput microfluidic interface that is used to immunomagnetically isolate targeted rare cells from whole blood, and discard > 99.999% of the unwanted leukocytes. The second module is a microwell array that furthers the purification by magnetically guiding each cell into a separate well concurrently, and allows individual retrieval of each cell. Even though the system we have developed is applicable to many fields pertaining to rare cell capture, here we demonstrate the proof-of-concept using model cell lines that represent circulating fetal trophoblasts. We describe the design, operation as well as the experimental characterization of the system. Our characterization results show that the process can be completed within 145 minutes from the very beginning till the retrieval of a target cell, and can provide efficiencies and purities that are as high as 100%. </div><div><br></div><div>In order to demonstrate a real-world use case for our device, we present preliminary experiments done with blood samples from pregnant women. We show that we are able to retrieve candidate fetal cells under 167 minutes. Future work will be focused on sequencing the candidate fetal cells retrieved from maternal samples to confirm their fetal origin as well as enhancing system performance in maximizing the number of cells captured.</div><div><br></div>

<p>Textiles have gained popularity in wearable products due to their potential for wearability, comfort, flexibility, breathability, and seamless fit to the human body. The growing demand for remote telehealth monitoring has led to advancements in the field of e-textiles. Various approaches, such as dip coating, screen printing, inkjet printing, and vapor deposition, are utilized to overcoat fabrics with active nanomaterials. However, practical deployment still faces challenges due to a lack of rapid prototyping for scalable and customizable e-textiles. To meet the requirements of large-scale batch production, high-resolution electrode line width, and long-term durability, new platform technologies have been established to convert existing textiles into multifunctional e-textiles. These studies have also revealed the process-structure-property relationships of various e-textiles.</p> <p>Chapter I overviews the recent results and current limitations of e-textiles in wearable sensing and display. Since people stay and work in various circumstances, continuous monitoring of physical, electrophysiological signals on skin in ambulatory manners is necessary to evaluate hazardous situation or chronicle symptoms. For these reasons, fabrication of smart e-textiles is crucial. In this chapter, various conductive materials, overcoating methods, and sensor structures for physical and electrophysiological sensors are reviewed. In addition, as a useful user communication tool with different sensor system, e-textile formats of displays are developed. The comprehensive e-textile displays from DC-driven to AC-driven are presented.</p> <p>Chapter II introduces a dual-regime spray technique that enables the direct writing of functional nanoparticles onto commercial 4-way stretchable textiles up to a meter scale with high-resolution mask-free patterning. The resulting e-textiles maintain the intrinsic properties of the fabric and can conform to various body shapes, enabling high-fidelity recording of physiological and electrophysiological signals under ambulatory conditions. Field tests have shown the potential of these e-textiles for minimally obtrusive remote telehealth monitoring of large animals.</p> <p>Chapter III presents an in-situ polymerization and patterning technique that utilizes the dual-regime spray method to synthesize conductive polymers directly onto commercial stretch textiles. The resulting e-textiles are utilized for strain sensors that conform closely to the human body, providing exceptional measurement accuracy and fidelity in capturing physical signals and motion detections.</p> <p>Conclusion section summarizes this dissertation with pointing out important results and discussions of each study. As an innovative additive manufacturing technology, dual-regime spray system, was established and developed to open new field in manufacture of e-textile. At last of this section, the potential research opportunities and perspectives are addressed. </p>

<p>In this dissertation, we show three approaches towards selective vagus nerve stimulation (VNS). First, we investigated VNS using microelectrode with circle and Vicsek fractal shape. Our rat study shows that fractal microelectrode can activate C-fibers in cervical vagus nerve with higher energy efficiency compared to circle microelectrode. Secondly, we developed stretchable and adhesive cuff device for a compliant neural interface for a long-term stability. We designed Y-shaped kirigami thin-film device for stretchable neural interface and applied a tissue-adhesive hydrogel to enable tough adhesion of the cuff electrode, which can be potentially used to fix the position of microelectrode for a reliable selective stimulation with minimal mechanical mismatch. Lastly, we developed a microchannel electrode array device to potentially measure high-quality of single fiber action potential (SFAP) from the abdominal vagal trunk of rat to explore natural patterns selective organ activities which can be used for a fine-tuned selective VNS. Our results show the potential of measuring C-fiber activities evoked by cervical VNS.</p>

<div> <p><br></p> </div> Individuals with disabilities and persons operating in inaccessible environments can greatly benefit from the aid of robotic manipulators in performing activities of daily living (ADLs) and other remote tasks. Users relying on robotic manipulators to interact with their environment are restricted by the lack of sensory information available through traditional operator interfaces. These interfaces only allow visual task access and deprive users of somatosensory feedback that would be available through direct contact. Multimodal sensory feedback can bridge these perceptual gaps effectively. Given a set of object properties (e.g. temperature, weight) to be conveyed and sensory modalities (e.g. visual, haptic) available, it is necessary to determine which modality should be assigned to each property for an effective interface design. However, the effectiveness of assigning properties to modalities has varied with application and context. The goal of this study was to develop an effective multisensory interface for robot-assisted pouring tasks, which delivers nuanced sensory feedback while permitting high visual demand necessary for precise teleoperation. To that end, an optimization approach is employed to generate a combination of feedback properties to modality assignments that maximizes effective feedback perception and minimizes cognitive load. A set of screening experiments tested twelve possible individual assignments to form the combination. Resulting perceptual accuracy, load, and user preference measures were input into a cost function. Formulating and solving as a linear assignment problem, a minimum cost combination was generated. Results from experiments evaluating efficacy in practical use cases for pouring tasks indicate that the solution is significantly more effective than no feedback and has considerable advantage over an arbitrary design. <br>

<p>Glaucoma is the leading cause of irreversible blindness worldwide. While current therapies aim to lower elevated intraocular pressure (IOP) to prevent blindness, they often do not provide the desired long-term efficacy, can fail over time, and have systemic side effects. Electroceutical stimulation can be a solution to many of these current issues with glaucoma treatment, as it is believed to have fewer systemic side effects and quicker response times. The goal of this work is to develop and demonstrate a novel system using electrical stimulation to lower intraocular pressure. I present data from a human clinical study and an ongoing clinical trial of the IOPTx™ system, a wearable electroceutical for treating glaucoma, that provides preliminary evidence of efficacy and safety. <a>Furthermore, no current glaucoma treatments allow for closed-loop, continuous monitoring of IOP, requiring more frequent doctor visits or forcing patients and clinicians to operate in the dark. Using an electroceutical therapeutic device with closed-loop feedback and continuous IOP recording can improve glaucoma management. I combined a pressure sensor with this electroceutical therapy, implanted the sensor and stimulation coils in rabbits, and stimulated the eyes. However, to better understand the optimal stimulation parameters, long-term effects, and mechanisms of action, an integrated circuit is designed as part of a fully implantable, closed-loop device. The chip was fabricated in 0.18 </a>µm CMOS process and validated on the benchtop and <i>in vivo</i>. In the future, this electroceutical device has the potential to be a novel treatment for patients suffering from glaucoma.</p>

<p dir="ltr">Since the beginning of the HIV/AIDS epidemic, 85.6 million people worldwide have become infected with HIV; more than half of whom have died from AIDS-related complications.[1] Sustained viral suppression below the clinically relevant threshold (1000 copies per mL) with highly active antiretroviral therapy (HAART) has proven effective at managing and prolonging the life expectancy of people living with HIV (PLHIV). However, in 2022, 11.3 million PLHIV had still not achieved viral suppression and may become susceptible to both HIV transmission and a variety of opportunistic infections. Of particular importance is the complex issue of patient non-compliance in global HIV management due to social, economic, behavioral, and healthcare access barriers, potentially disconnecting many PLHIV from the HIV care continuum. Therefore, to boost patient engagement in clinical care and to improve overall patient outcomes, new approaches to viral load monitoring practices need to be developed to increase access, particularly in regions of high HIV prevalence.</p><p dir="ltr">Nucleic acid amplification tests (NAATs) have emerged as potent tools for monitoring viral load, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) being recognized as the benchmark due to its sensitivity and ability for real-time quantification enabled by fluorescence signal emission. Nevertheless, RT-qPCR is burdened by drawbacks including extended processing times, high operational costs, and the requirement for specialized laboratory facilities. In this study, we propose a novel method for HIV-1 viral load monitoring by integrating reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) with real-time particle diffusometry (PD). This approach allows for the continuous monitoring of changes in the diffusion of 400 nm fluorescent particles during RT-LAMP amplification, targeting the <i>p24</i> gene region of HIV-1 RNA. This enables the real-time detection of amplification curves, achieving a detection sensitivity in water samples as low as 25 virus particles per μL within a short duration of 30 minutes. Additionally, to address challenges related to amplification inhibition in complex human specimens, we developed a power-free sample processing system specifically designed for extracting HIV-1 RNA from both whole blood and plasma.Top of FormBottom of FormThis system modifies a commercially available spin-column protocol by integrating a syringe device and handheld bulb dryer, thus eliminating the requirement for a centrifuge. The adaptation allows for the completion of the entire extraction procedure, encompassing viral lysis, RNA capture, washing, and elution of purified HIV-1 RNA, within a timeframe of less than 16 minutes. Subsequent analyses, including RT-LAMP and RT-qPCR, demonstrate a limit of detection of 100 copies per μL and an average RNA recovery of 32% (for blood) and 70% (for plasma) in the elution fraction. Further investigations emphasize the significant presence of purified RNA in the spin column volume (termed as dead volume), and the cumulative recovered RNA copies align with those obtained using the gold standard centrifugation extraction method. Ultimately, we incorporated the real-time quantitative PD-RT-LAMP assay onto a field-compatible handheld portable platform suitable for field use, featuring built-in quality control measures. This platform enables sample-to-answer viral load testing near the point of care (POC). Subsequently, we undertook essential preparatory steps, such as reagent drying to obviate the need for cold storage, initial device calibration, and hands-on training of laboratory personnel regarding device operation, to validate device performance within a cohort of individuals living with HIV (PLHIV). These innovations facilitate quick and comprehensive viral load determination, offering promise for enhanced HIV management and patient care</p>

Orientador: Rickson Coelho Mesquita / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Física Gleb Wataghin / Made available in DSpace on 2018-08-30T22:43:33Z (GMT). No. of bitstreams: 1 QuirogaSoto_AndresFabian_M.pdf: 7858431 bytes, checksum: cab3b799ea039aaac9d7d8039a9590ed (MD5) Previous issue date: 2016 / Resumo: A espectroscopia óptica de difusão DOS é uma técnica que usa luz no regime do infravermelho próximo (NIR) para extração de informações fisiológicas em tecidos biológicos de forma não invasiva, tais como as concentrações de oxi-hemoglobina (HbO) , desoxi-hemoglobina (Hb) e a saturação de oxigênio no tecido (StO_2). Esta técnica baseia-se no fato de que a luz do infravermelho próximo se propaga difusivamente no tecido biológico, conseguindo se aprofundar alguns centímetros e voltar na superfície de incidência, e sofrendo alterações ao atravessar o meio devido à absorção e ao espalhamento do tecido. Este enfoque utiliza a equação de difusão para o modelamento da luz e suas soluções para conseguir as propriedades ópticas absolutas, que permite inferir as informações fisiológicas do tecido. A técnica experimental DOS utiliza fontes que emitem pulsos ultracurtos (Time Domain DOS) ou intensidades moduladas (Frequency Domain DOS) para extrair tais informações. No entanto, a implementação destas técnicas requerem uma eletrônica avançada, tornando a construção complicada ou a aquisição custosa. Por outro lado, os equipamentos que usam fontes contínuas medem apenas variações relativas dos coeficientes de absorção do tecido. Neste trabalho, estudou-se uma nova metodologia a partir da espectroscopia óptica de difusão usando fontes de onda contínua para vários comprimentos de ondas (CW-DOS) a fim de extrair os valores absolutos de absorção e espalhamento do tecido. A metodologia foi validada com dados ópticos em phantoms e camundongos, conseguindo inferir as propriedades ópticas absolutas para cada estágio. Os resultados refletem que a metodologia é uma boa alternativa para extração de informação fisiológica de forma simples e confiável, e que serve como base para a construção de novos equipamentos de DOS / Abstract: Diffuse Optical Spectroscopy (DOS) is a technique that employs near infrared (NIR) light to noninvasively extract physiological information from biological tissue, such as microvascular oxy-hemoglobin (HbO) and deoxy-hemoglobin (Hb) concentrations, and tissue oxygen saturation (StO_2). DOS is based on the fact that NIR light diffuses through deep tissue and interacts with tissue cells and molecules before returning to the surface. Therefore, the tissue composition can be estimated by the absorption and scattering coefficients, which can be monitored by the intensity detected of scattered light. DOS uses the diffusion equation for modeling light propagation, and its solutions to estimate the absolute optical properties. Typical experimental methods in DOS employ ultrashort-pulsed light sources (Time Domain DOS) or intensity modulated light sources (Frequency Domain DOS) to extract such information. However, the implementation of these techniques requires advanced electronics, which makes its use complicated and/or expensive. Instruments that use continuous-wave (CW- DOS) light sources are limited to estimate relative changes of the absorption coefficient, only. In this dissertation, we analyze a methodology based on continuous-wave diffuse optical spectroscopy with several wavelengths to estimate the absolute values of absorption and scattering coefficients of biological tissue. The methodology was validated in optical phantoms and in mice. Our results suggest that the methodology can be a good approach for estimating physiological information in a simple and reliable way, and it can be used as the basis for the construction of new DOS equipments / Mestrado / Física / Mestre em Física / 1373920/2014 / CAPES

Opioid overdose is a growing epidemic plaguing the United States. Overdose related death has risen from 16,849 in 1999 to 69,029 in 2018. Almost 7 out of 10 of these deaths were due to opioids with 47% being caused by fentanyl or other synthetic opioids. There is a strong need to reduce the amount of overdose-related deaths. Indirect methods should be a first priority, and include counseling and care. For some individuals, this treatment option is unavailable because the drug user may not have the desire or economic means to pursue it. In this case, a more direct preventative approach is needed. This paper presents a novel method of detecting poor peripheral oxygenation, a biomarker linked to opioid overdose. A wristwatch near-infrared spectroscopy device (NIRS) was developed. SPICE simulations were conducted to confirm proper operation of electrical systems. The device was fabricated on a printed circuit board and mounted to a 3D printed enclosure. Absorbance of green, red and infrared (IR) light were measured. Additionally, peripheral capillary oxygen saturation (SpO2) modulation index and changes in concentration of oxyhemoglobin and deoxyhemoglobin were calculated from raw data. A brachial occlusion test was performed to mimic the effects of opioid overdose on peripheral oxygenation. A statistically significant difference (p < 0.05) was observed between pre-occlusion and during-occlusion groups in two subjects for measurement of peak-to-peak values of green raw data, red raw data, IR raw data, oxyhemoglobin concentration change, and deoxyhemoglobin concentration change. Peak-to-peak was observed as a consistent indicator of poor peripheral oxygenation and could serve as a useful metric in the detection of opioid overdose.