1,721,022 research outputs found
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Empowering disease management with non- and minimally- invasive wearable sensing system
No full textPersonalized medicine aims to optimize therapeutic strategies by accounting for individual physiological differences, including both inter- and intra-subject variability. Yet, current clinical practices largely depend on nonspecific physical parameters and labor-intensive biochemical assays, which fail to capture the dynamic fluctuations and molecular complexity of an individual's health state. Recent advances in micro-electromechanical systems (MEMS) and electrochemical sensors have enabled the development of portable and wearable platforms capable of accessing molecular-level biochemical information in a non- or minimally invasive manner. These technologies, with their high temporal resolution, allow for continuous, real-time monitoring of clinically relevant molecular markers, supporting more precise and adaptive medical interventions. Despite this promise, significant barriers remain to the widespread clinical translation of wearable biochemical sensors. Challenges persist in biofluid sampling, sensing fidelity, system integration, and data interpretation. This thesis addresses these translational barriers by proposing generalizable, system-level solutions to support the development of wearable biosensing platforms. Emphasizing immediate applications in therapeutic monitoring and diagnostics, the sensor systems described herein are designed to detect disease-associated biomarkers and pharmaceutical compounds. Chapter 1 introduces the background of non- and minimally invasive biosensing technologies, with a focus on electrochemical sensing mechanisms. Chapter 2 details a hydrogel patch for concurrent analyte sampling and detection from natural sweat, also enabling multi-modal human-machine interfacing. Chapter 3 presents an organohydrogel-based, one-touch sensing platform for lithium therapy monitoring. Chapter 4 explores a microneedle-based aptamer sensor targeting interstitial fluid analytes, while Chapter 5 advances this concept with a resilient nanostructured microneedle for high-fidelity sensing and organ function assessment. Chapter 6 introduces a sensor based on cofactor-immobilized single-walled carbon nanotubes, establishing a framework for broad-spectrum in vivo enzymatic sensing
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Ferrobotic Platform for Decentralized Diagnostics
No full textDecentralized diagnostics, pivotal in shifting healthcare paradigms, play a crucial role in enabling accessible and frequent health monitoring outside traditional central laboratory confines. This approach, by facilitating early detection of health issues, enhances treatment outcomes and significantly reduces healthcare costs. Key requirements for effective decentralized diagnostics include a small footprint, automated liquid handling, high multiplexity, and minimal reagent and sample usage.We present an innovative ferrobotic platform to address the challenges. This system comprises a network of individually addressable robots, each performing designated micro-/nano-fluidic manipulation tasks in collaboration toward a unified objective. The platform leverages addressable electromagnetic actuation of mobile magnets for fluidic operations, manipulating aqueous droplets containing biocompatible magnetic nanoparticles. The robustness and individual addressability of the ferrobots underpin their capability for efficient cross-collaborative logistics. This, coupled with the system's reconfigurability, allows the integration of passive/active functional components for versatile lab-equivalent operations.
The ferrobotic platform we developed marks a substantial advancement in medical diagnostics. It is adept at streamlining and automating a wide array of assays. This platform significantly extends beyond our previous viral diagnostics, transitioning from simple nucleic acid amplification tests with binary readouts to comprehensive, multi-reagent and multi-step assay workflows. It incorporates advanced multiplexing strategies, enhancing diagnostic spectrum and adaptability. This innovation represents a pivotal step in evolving point-of-care diagnostic capabilities.
In biomedical applications, the ferrobotic platform excels, particularly in quantifying active matrix metallopeptidases in human plasma, a key biomarker for cancer and inflammation. This cross-collaborative robotic function facilitates fully automated assays. Its efficacy extends to detecting SARS-CoV-2 in clinical samples, with results matching traditional methods. Notably, the platform employs a square matrix pooled testing algorithm for efficient viral testing, potentially reducing reagent costs by up to 300-fold, depending on viral prevalence. Additionally, in neonatal intensive care unit settings, it significantly reduces blood draw volumes and sample costs, demonstrating its utility in sensitive medical environments. This versatility underscores the platform's significant impact in advancing biomedical diagnostics. The concluding section also lists the challenges to enhance the platform for practical application and anticipates the potential fields beyond diagnostics where the ferrobotic platform could be impactful
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A Magnetic Digital Microfluidic Platform for Point-of-care Diagnostics
No full textAutomated technologies that can perform massively parallelized and sequential fluidic operations at small length scales can resolve major bottlenecks encountered in various fields, including medical diagnostics, -omics, drug development, and chemical/material synthesis. Inspired by the transformational impact of automated guided vehicle systems on manufacturing, warehousing, and distribution industries, here, we devise a ferrobotic system which employs a network of individually addressable robots, each performing designated micro/nano-fluid manipulation-based tasks in cooperation with other robots toward a shared objective. The underlying robotic mechanism facilitating fluidic operations is realized by addressable electromagnetic actuation of miniature mobile magnets that exert localized magnetic body forces on aqueous droplets filled with biocompatible magnetic nanoparticles. The contactless and high-strength nature of the actuation mechanism inherently renders it rapid (~10 cm/s), repeatable (> 10,000 cycles), and robust (> 24 hours). The robustness and individual addressability of ferrobots provide a foundation for the deployment of a network of ferrobots to carry out cross-collaborative logistics efficiently. These traits, together with the reconfigurability of the system, are exploited to devise and integrate passive/active advanced functional components (e.g., droplet dispensing, generation, filtering, and merging), enabling versatile system-level functionalities. By applying this ferrobotic system within the framework of a microfluidic architecture, the ferrobots were tasked to work cross-collaboratively toward the quantification of active matrix metallopeptidases (a biomarker for cancer malignancy and inflammation) in human plasma, where various functionalities converged to achieve a fully automated assay
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Development methodologies of wearable biosensors for personalized health monitoring
No full textWearable biomarker sensors have made significant strides in the realm of personalized healthcare, permitting the seamless acquisition of physiological data from non-invasively sourced biofluids. This research delves deeper into this frontier, investigating the potential of these sensors to monitor specific molecular biomarkers that provide granular insights into an individual's physiological and psychological states. In this thesis, three principal domains were particularly addressed: native electroactive biomarker detection, electroenzymatic detection of metabolites, and aptamer detection of xenobiotics and hormones.In chapter 2, we addressed the inherent challenges of employing voltammetry for the analysis of native electroactive biomarkers like uric acid. By introducing a fouling-resistant sensing interface that combines a boron-doped diamond electrode with a hydrophilic chitosan membrane, we provided an effective solution to the biofouling challenges that typically plague the analysis of untreated biofluids.
In chapter 3 and chapter 4, our research tapped into the capabilities of oxidoreductase enzymes for indirectly reactive biomarker electroenzymatic detection. In chapter 3, we revealed the inherent limitations of the traditionally used mediator-free sensing interface for wearable applications, and devised an alternative that incorporates a permselective membrane and a platinum/carbon-nanotube-based electroanalysis layer. This approach is adaptable to measure a wide range of vital metabolites like glucose, lactate, and choline. Furthermore, in chapter 4, our design of a unique cofactor-integrated biosensing framework, utilizing cofactor immobilized single-wall carbon nanotubes, laid the foundation for broad in vivo enzymatic sensing, specifically capitalizing on nicotinamide adenine dinucleotide-based enzymatic reactions.
In chapter 5 and chapter 6, we shifted the focus to the aptamer detection of xenobiotics and hormones. In chapter 5, by integrating an aptamer functionalized field-effect-transistor sensing system, our research demonstrated continuous wearable sweat cortisol monitoring. In chapter 6, our innovative microneedle-based electrochemical aptamer biosensor patch offers real-time insights into the pharmacokinetics of drugs in interstitial fluid circulation. Demonstrated through in vivo tests on specific antibiotics such as tobramycin and vancomycin, our advancements in wearable biosensors stand to revolutionize potential applications in healthcare, furnishing users with accurate, prompt, and insightful data about their health metrics
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An Autonomous 3D Biofluid Management and Analysis Lab-on-the-Body Platform for Point-of-Person Biomarker Monitoring Applications
No full textPersonal biomarker sensors are poised to transform personalized medicine by providing frequent and real-time measures of biomarker molecules, thus catalyzing the transition from point-of-lab and point-of-care testing to near-continuous monitoring at the point-of-person. To realize the full range of possibilities offered by such wearable and mobile sensors, in-situ active microfluid management capabilities are fundamentally required. Previously reported non-invasive wearable and mobile biomarker sensors rely on the in-situ analysis of biofluid samples that are passively collected in absorbent pads or 2D microfluidic housings. The spatial constraints of these platforms and their lack of active control on biofluid inherently limit the efficiency, diversity and frequency of end-point assessments. Here, by devising a suite of programmable electro-fluidic interfaces, integrated within a multi-layer flexible microfluidic device, we demonstrate key biofluid management functionalities, including biofluid flow actuation and compartmentalization, for autonomous lab-on-the-body sample analysis. System-level functionality is achieved by interfacing the microfluidic device with a wireless circuit board. The desired operations are validated on-body through human subject testing. The versatility of these unprecedented lab-on-the-body methodologies enables a wide-ranging complex sample processing and analysis operations that can converge to realize point-of-person monitoring platforms
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Materials design of flexible bioelectronics for reliable electrochemical signal transduction and electrical signal transmission
No full textBoth sophisticated electronic systems and human biological systems rely on signal transduction and transmission to achieve all operations and complex tasks. However, there are many fundamental differences between these two systems. For example, the human biological system contains deformable and soft organs/tissues under solution environments, mainly based on chemical reactions to transduce/transmit bio-signals. In comparison, electronics contain non-deformable rigid components under ambient environment mainly, based on electrons to transduce/transmit electrical signals. Even though it is difficult to merge gaps between these two systems, translation of existing electronics to be compliant with our biological tissues will render a wide panel of applications such as wearable health and wellness monitoring platforms, implantable/ingestible devices, artificial prosthesis, surgery robots, etc. As a researcher in materials science and engineering, I am applying reductionism to approach this complicated question by firstly decomposing electronic materials’ properties into chemical, electrical, and mechanical domains, then engineering material properties in each domain to be compatible with biological systems as needed. However, the most difficult part is that materials’ chemical, electrical and mechanical properties are always coupled and interacted with one another, thus rarely allowing us to independently tune each of them. For example, highly conductive materials (e.g. Au) are normally mechanically fragile (low crack onset strain), which will lead to distorted electrical signal transmission under strain imposed by organ/tissue movement. To improve mechanical compliance of these materials, it normally needs to compensate for their electrical properties (e.g. lower conductivity). As another example of materials for electrochemical bio-signal transduction, it requires to apply voltage to transduce target bio-signals into electrical signals, while also inevitably oxidizing non-target electroactive species to generate noise. In this case, applying lower voltage will simultaneously lower both the target bio-signal and unwanted noise. In this thesis, as the building block towards envisioned applications, Chapter 1 firstly introduces the background and design rationales for two fundamental units: bio-signal transduction module (e.g. electrochemical biosensing interface) and signal-transmission module (stretchable interconnects). Chapter 2 is focused on describing a material design methodology (based on Pt nanoparticles and p-Phenylenediamine-based permselective membrane), serving as an example of a reliable bio-signal transduction interface to simultaneously improve the sensitivity and selectivity of enzymatic-based electrochemical sensing. In Chapter 3, we devise a wearable freestanding electrochemical system that enables high-fidelity biomarker data acquisition under body movement in daily activities. As the core, it utilizes the anisotropic conductive film as the substrate for the developed sensing interface (in Chapter 2), coupled with microfluidic housing to achieve strain-isolated biomarker information delivery pathway. Subsequently, in Chapter 4, we integrate this technique with miniaturized iontophoresis interfaces and wearable hybrid control/readout electronics to achieve autonomous sweat extracting and glucose tracking in a day. In the end, in Chapter 5, I presented my preliminary research results for two future directions to use anisotropic conductive film to 1): decouple strain-effect on thin-film conductive materials’ conductivity (in bending mode) to achieve compliant electronics and 2) composite with silver-nanowire-based elastomer to achieve strain-resilient stretchable electrochemical sensing materials
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Wearable and Mobile Bioanalytical Systems for Health Monitoring at the Point-of-Person
No full textPoint-of-care testing has greatly improved the accessibility of medical diagnostics and brought it from central laboratory closer to our daily life settings: hospitals, clinics, and pharmacies. The maturity and convergence of micro-device fabrication, sensing methodology development, and low power electronics technologies, in combination with the exponential expansion of internet of things infrastructure have provided an unprecedented opportunity to transform the accessibility of medical testing from the point-of-care to the point-of-person setting. Such transformation would create a paradigm shift in healthcare: moving away from reactive medicine to proactive medicine, which means instead of getting sick and then go to the doctor, the risk of developing disease will be calculated based on our daily measurements, informing timely and preventative actions. To realize point-of-person monitoring, the new generation of personal health monitoring systems should be: 1) portable, allowing for them to be easily distributed and embedded in our lives (e.g., in a wearable or mobile formats); 2) low cost and affordable by the general population; and 3) simple to operate, ideally eliminating the need for user intervention, for example, via automation of the underlying analytical operations. Moreover, the targeted bio-signal domain should be expanded from biophysical signals to biochemical signals to capture insightful health information related to different types of diseases at the molecular level.Aligned with this vision, this dissertation introduces new wearable and mobile bioanalytical systems that are uniquely positioned to support health monitoring at the point-of-person. The first section of this dissertation provides the background and an overview of the point-of-person health monitoring. The second section describes the biofluid-centered operations (e.g., sampling, management, processing, and sensing) that are essential for the realization of complete solutions for point-of-person biochemical monitoring (with the particular focus on wearable format). The third section demonstrates the mobile point-of-person biochemical platforms with specifics in different automated biofluid functionalities and biomarker detection. The final section discusses the remaining challenges and outlines the potential directions to be pursued in order to enable the large-scale deployment of biochemical health monitoring, and catalyze the transition from point-of-lab and point-of-care testing to point-of-person monitoring
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An Autonomous Monolithic Wearable System for Diurnal Sweat Biomarker Data Acquisition and Analysis
No full textTo track dynamically varying and physiologically relevant biomarker profiles in sweat, autonomous wearable platforms are required to periodically sample and analyze sweat with minimal user intervention. Previously reported sweat sensors are functionally limited to capturing biomarker information at one time-point/period, thereby necessitating repeated user intervention to increase the temporal granularity of biomarker data. Accordingly, we present a multi-compartment wearable system, where each compartment can be activated to autonomously induce/modulate sweat secretion (iontophoretically) and analyze sweat at set timepoints. This system was developed following a hybrid-flex design— vertically integrating the required functional modules: miniaturized iontophoresis interfaces, adhesive thin film microfluidic-sensing module, and control/readout electronics. The system was deployed in a human subject study to track the diurnal variation of sweat glucose levels in relation to the daily food intake. The demonstrated autonomous operation for diurnal sweat biomarker data acquisition illustrates the system’s suitability for large-scale and longitudinal personal health monitoring applications
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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