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1.
Nanotechnology ; 32(37)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34049305

RESUMO

Wearable skin sensors is a promising technology for real-time health care monitoring. They are of particular interest for monitoring glucose in diabetic patients. The concentration of glucose in sweat can be more than two orders of magnitude lower than in blood. In consequence, the scientific and technological efforts are focused in developing new concepts to enhance the sensitivity, decrease the limit of detection (LOD) and reduce the response time (RT) of glucose skin sensors. This work explores the effect of adsorbed superparamagnetic magnetite nanoparticles (MNPs) and conductive nanoparticles (CNPs) on carbon nanotube substrates (CNTs) used to immobilize glucose oxidase enzyme in the working electrode of skin sensors. MNPs and CNPs are made of magnetite and gold, respectively. The performance of the sensors was tested in standard buffer solution, artificial sweat, fresh sweat and on the skin of a healthy volunteer during an exercise session. In the case of artificial sweat, the presence of MNPs accelerated the RT from 7 to 5 s at the expense of increasing the LOD from 0.017 to 0.022 mM with slight increase of the sensitivity from 4.90 to 5.09µAm M-1cm-2. The presence of CNPs greatly accelerated the RT from 7 to 2 s and lowered the LOD from 0.017 to 0.014 mM at the expense of a great diminution of the sensitivity from 4.90 to 4.09µAm M-1cm-2. These effects were explained mechanistically by analyzing the changes in the concentration of free oxygen and electrons promoted by MNPs and CNPs in the CNTs and its consequences on the the glucose oxidation process.

2.
Sci Transl Med ; 13(587)2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790027

RESUMO

The concentration of chloride in sweat remains the most robust biomarker for confirmatory diagnosis of cystic fibrosis (CF), a common life-shortening genetic disorder. Early diagnosis via quantitative assessment of sweat chloride allows prompt initiation of care and is critically important to extend life expectancy and improve quality of life. The collection and analysis of sweat using conventional wrist-strapped devices and iontophoresis can be cumbersome, particularly for infants with fragile skin, who often have insufficient sweat production. Here, we introduce a soft, epidermal microfluidic device ("sweat sticker") designed for the simple and rapid collection and analysis of sweat. Intimate, conformal coupling with the skin supports nearly perfect efficiency in sweat collection without leakage. Real-time image analysis of chloride reagents allows for quantitative assessment of chloride concentrations using a smartphone camera, without requiring extraction of sweat or external analysis. Clinical validation studies involving patients with CF and healthy subjects, across a spectrum of age groups, support clinical equivalence compared to existing device platforms in terms of accuracy and demonstrate meaningful reductions in rates of leakage. The wearable microfluidic technologies and smartphone-based analytics reported here establish the foundation for diagnosis of CF outside of clinical settings.


Assuntos
Fibrose Cística , Suor , Cloretos , Fibrose Cística/diagnóstico , Fibrose Cística/terapia , Humanos , Lactente , Qualidade de Vida , Smartphone
3.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33731359

RESUMO

Three-dimensional (3D), submillimeter-scale constructs of neural cells, known as cortical spheroids, are of rapidly growing importance in biological research because these systems reproduce complex features of the brain in vitro. Despite their great potential for studies of neurodevelopment and neurological disease modeling, 3D living objects cannot be studied easily using conventional approaches to neuromodulation, sensing, and manipulation. Here, we introduce classes of microfabricated 3D frameworks as compliant, multifunctional neural interfaces to spheroids and to assembloids. Electrical, optical, chemical, and thermal interfaces to cortical spheroids demonstrate some of the capabilities. Complex architectures and high-resolution features highlight the design versatility. Detailed studies of the spreading of coordinated bursting events across the surface of an isolated cortical spheroid and of the cascade of processes associated with formation and regrowth of bridging tissues across a pair of such spheroids represent two of the many opportunities in basic neuroscience research enabled by these platforms.

6.
Nat Neurosci ; 23(12): 1522-1536, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33199897

RESUMO

Interest in deciphering the fundamental mechanisms and processes of the human mind represents a central driving force in modern neuroscience research. Activities in support of this goal rely on advanced methodologies and engineering systems that are capable of interrogating and stimulating neural pathways, from single cells in small networks to interconnections that span the entire brain. Recent research establishes the foundations for a broad range of creative neurotechnologies that enable unique modes of operation in this context. This review focuses on those systems with proven utility in animal model studies and with levels of technical maturity that suggest a potential for broad deployment to the neuroscience community in the relatively near future. We include a brief summary of existing and emerging neuroscience techniques, as background for a primary focus on device technologies that address associated opportunities in electrical, optical and microfluidic neural interfaces, some with multimodal capabilities. Examples of the use of these technologies in recent neuroscience studies illustrate their practical value. The vibrancy of the engineering science associated with these platforms, the interdisciplinary nature of this field of research and its relevance to grand challenges in the treatment of neurological disorders motivate continued growth of this area of study.


Assuntos
Neurociências/tendências , Tecnologia/tendências , Animais , Encéfalo/fisiologia , Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Humanos , Neurociências/métodos , Optogenética/tendências , Farmacologia/métodos , Pesquisa
7.
Lab Chip ; 20(23): 4391-4403, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33089837

RESUMO

Important insights into human health can be obtained through the non-invasive collection and detailed analysis of sweat, a biofluid that contains a wide range of essential biomarkers. Skin-interfaced microfluidic platforms, characterized by soft materials and thin geometries, offer a collection of capabilities for in situ capture, storage, and analysis of sweat and its constituents. In ambulatory uses cases, the ability to provide real-time feedback on sweat loss, rate and content, without visual inspection of the device, can be important. This paper introduces a low-profile skin-interfaced system that couples disposable microfluidic sampling devices with reusable 'stick-on' electrodes and wireless readout electronics that remain isolated from the sweat. An ultra-thin capping layer on the microfluidic platform permits high-sensitivity, contactless capacitive measurements of both sweat loss and sweat conductivity. This architecture avoids the potential for corrosion of the sensing components and eliminates the need for cleaning/sterilizing the electronics, thereby resulting in a cost-effective platform that is simple to use. Optimized electrode designs follow from a combination of extensive benchtop testing, analytical calculations and FEA simulations for two sensing configurations: (1) sweat rate and loss, and (2) sweat conductivity, which contains information about electrolyte content. Both configurations couple to a flexible, wireless electronics platform that digitizes and transmits information to Bluetooth-enabled devices. On-body field testing during physical exercise validates the performance of the system in scenarios of practical relevance to human health and performance.


Assuntos
Técnicas Biossensoriais , Suor , Eletrônica , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica , Pele
8.
Sci Adv ; 6(35): eabb1093, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32923633

RESUMO

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

9.
Biosens Bioelectron ; 168: 112493, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889394

RESUMO

Enzymatic biofuel cell (EBFC)-based self-powered biochemical sensors obviate the need for external power sources thus enabling device miniaturization. While recent efforts driven by experimentalists illustrate the potential of EBFC-based sensors for real-time monitoring of physiologically relevant biochemicals, a robust mathematical model that quantifies the contributions of sensor components and empowers experimentalists to predict sensor performance is missing. In this paper, we provide an elegant yet simple equivalent circuit model that captures the complex, three-dimensional interplay among coupled catalytic redox reactions occurring in an EBFC-based sensor and predicts its output signal with high correlations to experimental observations. The model explains the trade-off among chemical design parameters such as the surface density of enzymes, various reaction constants as well as electrical parameters in the Butler-Volmer relationship. The model shows that the linear dynamic range and sensitivity of the EBFC-based sensor can be independently fine-tuned by changing the surface density of enzymes and electron mediators at the anode and by enhancing reductant concentrations at the cathode. The mathematical model derived in this work can be easily adapted to understand a wide range of two-electrode systems, including sensors, fuel cells, and energy storage devices.


Assuntos
Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Eletricidade , Eletrodos , Limite de Detecção
10.
Nat Commun ; 10(1): 5513, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31797921

RESUMO

Recently introduced classes of thin, soft, skin-mounted microfluidic systems offer powerful capabilities for continuous, real-time monitoring of total sweat loss, sweat rate and sweat biomarkers. Although these technologies operate without the cost, complexity, size, and weight associated with active components or power sources, rehydration events can render previous measurements irrelevant and detection of anomalous physiological events, such as high sweat loss, requires user engagement to observe colorimetric responses. Here we address these limitations through monolithic systems of pinch valves and suction pumps for purging of sweat as a reset mechanism to coincide with hydration events, microstructural optics for reversible readout of sweat loss, and effervescent pumps and chemesthetic agents for automated delivery of sensory warnings of excessive sweat loss. Human subject trials demonstrate the ability of these systems to alert users to the potential for dehydration via skin sensations initiated by sweat-triggered ejection of menthol and capsaicin.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Pele/metabolismo , Suor/metabolismo , Biomarcadores/metabolismo , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Retroalimentação Fisiológica , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Estado de Hidratação do Organismo , Reprodutibilidade dos Testes , Pele/química , Suor/química
11.
Adv Mater ; 31(32): e1902109, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31206791

RESUMO

Comprehensive analysis of sweat chemistry provides noninvasive health monitoring capabilities that complement established biophysical measurements such as heart rate, blood oxygenation, and body temperature. Recent developments in skin-integrated soft microfluidic systems address many challenges associated with standard technologies in sweat collection and analysis. However, recording of time-dependent variations in sweat composition requires bulky electronic systems and power sources, thereby constraining form factor, cost, and modes of use. Here, presented are unconventional design concepts, materials, and device operation principles that address this challenge. Flexible galvanic cells embedded within skin-interfaced microfluidics with passive valves serve as sweat-activated "stopwatches" that record temporal information associated with collection of discrete microliter volumes of sweat. The result allows for precise measurements of dynamic sweat composition fluctuations using in situ or ex situ analytical techniques. Integrated electronics based on near-field communication (NFC) protocols or docking stations equipped with standard electronic measurement tools provide means for extracting digital timing results from the stopwatches. Human subject studies of time-stamped sweat samples by in situ colorimetric methods and ex situ techniques based on inductively coupled plasma mass spectroscopy (ICP-MS) and chlorodimetry illustrate the ability to quantitatively capture time-dynamic sweat chemistry in scenarios compatible with field use.


Assuntos
Desenho de Equipamento/instrumentação , Dispositivos Lab-On-A-Chip , Pele/química , Suor/química , Técnicas Biossensoriais/instrumentação , Colorimetria , Teste de Esforço , Humanos , Smartphone , Fatores de Tempo , Dispositivos Eletrônicos Vestíveis
12.
Lab Chip ; 19(9): 1545-1555, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-30912557

RESUMO

The rich range of biomarkers in sweat and the ability to collect sweat in a non-invasive manner create interest in the use of this biofluid for assessments of health and physiological status, with potential applications that range from sports and fitness to clinical medicine. This paper introduces two important advances in recently reported classes of soft, skin-interfaced microfluidic systems for sweat capture and analysis: (1) a simple, broadly applicable means for collection of sweat that bypasses requirements for physical/mental exertion or pharmacological stimulation and (2) a set of enzymatic chemistries and colorimetric readout approaches for determining the concentrations of creatinine and urea in sweat, throughout ranges that are physiologically relevant. The results allow for routine, non-pharmacological capture of sweat for patient populations, such as infants and the elderly, that cannot be expected to sweat through exercise, and they create potential opportunities in the use of sweat for kidney disease screening/monitoring. Studies on human subjects demonstrate these essential capabilities, with quantitative comparisons to standard methods. The results expand the range of options available in microfluidic sampling and sensing of sweat for disease diagnostics and health monitoring.


Assuntos
Colorimetria/instrumentação , Nefropatias/metabolismo , Dispositivos Lab-On-A-Chip , Suor/metabolismo , Biomarcadores/metabolismo , Humanos
13.
ACS Sens ; 4(2): 379-388, 2019 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-30707572

RESUMO

Real-time measurements of the total loss of sweat, the rate of sweating, the temperature of sweat, and the concentrations of electrolytes and metabolites in sweat can provide important insights into human physiology. Conventional methods use manual collection processes (e.g., absorbent pads) to determine sweat loss and lab-based instrumentation to analyze its chemical composition. Although such schemes can yield accurate data, they cannot be used outside of laboratories or clinics. Recently reported wearable electrochemical devices for sweat sensing bypass these limitations, but they typically involve on-board electronics, electrodes, and/or batteries for measurement, signal processing, and wireless transmission, without direct means for measuring sweat loss or capturing and storing small volumes of sweat. Alternative approaches exploit soft, skin-integrated microfluidic systems for collection and colorimetric chemical techniques for analysis. Here, we present the most advanced platforms of this type, in which optimized chemistries, microfluidic designs, and device layouts enable accurate assessments not only of total loss of sweat and sweat rate but also of quantitatively accurate values of the pH and temperature of sweat, and of the concentrations of chloride, glucose, and lactate across physiologically relevant ranges. Color calibration markings integrated into a graphics overlayer allow precise readout by digital image analysis, applicable in various lighting conditions. Field studies conducted on healthy volunteers demonstrate the full capabilities in measuring sweat loss/rate and analyzing multiple sweat biomarkers and temperature, with performance that quantitatively matches that of conventional lab-based measurement systems.


Assuntos
Colorimetria/instrumentação , Dispositivos Lab-On-A-Chip , Pele , Suor/química , Temperatura , Biomarcadores/análise , Humanos , Limite de Detecção , Fenômenos Mecânicos
14.
Annu Rev Anal Chem (Palo Alto Calif) ; 12(1): 1-22, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-30786214

RESUMO

Sweat is a largely unexplored biofluid that contains many important biomarkers ranging from electrolytes and metabolites to proteins, cytokines, antigens, and exogenous drugs. The eccrine and apocrine glands produce and excrete sweat through microscale pores on the epidermal surface, offering a noninvasive means for capturing and probing biomarkers that reflect hydration state, fatigue, nutrition, and physiological changes. Recent advances in skin-interfaced wearable sensors capable of real-time in situ sweat collection and analytics provide capabilities for continuous biochemical monitoring in an ambulatory mode of operation. This review presents a broad overview of sweat-based biochemical sensor technologies with an emphasis on enabling materials, designs, and target analytes of interest. The article concludes with a summary of challenges and opportunities for researchers and clinicians in this swiftly growing field.


Assuntos
Técnicas Biossensoriais/instrumentação , Suor/química , Dispositivos Eletrônicos Vestíveis , Animais , Biomarcadores/análise , Técnicas Biossensoriais/métodos , Desenho de Equipamento , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos
15.
Sci Adv ; 5(1): eaau6356, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30746456

RESUMO

Noninvasive, in situ biochemical monitoring of physiological status, via the use of sweat, could enable new forms of health care diagnostics and personalized hydration strategies. Recent advances in sweat collection and sensing technologies offer powerful capabilities, but they are not effective for use in extreme situations such as aquatic or arid environments, because of unique challenges in eliminating interference/contamination from surrounding water, maintaining robust adhesion in the presence of viscous drag forces and/or vigorous motion, and preventing evaporation of collected sweat. This paper introduces materials and designs for waterproof, epidermal, microfluidic and electronic systems that adhere to the skin to enable capture, storage, and analysis of sweat, even while fully underwater. Field trials demonstrate the ability of these devices to collect quantitative in situ measurements of local sweat chloride concentration, local sweat loss (and sweat rate), and skin temperature during vigorous physical activity in controlled, indoor conditions and in open-ocean swimming.


Assuntos
Técnicas Biossensoriais/instrumentação , Epiderme/metabolismo , Dispositivos Lab-On-A-Chip , Microfluídica/instrumentação , Água do Mar , Suor/química , Termografia/instrumentação , Dispositivos Eletrônicos Vestíveis , Biomarcadores/análise , Cloretos/análise , Desenho de Equipamento , Humanos , Pele/metabolismo , Natação/fisiologia , Temperatura
16.
Sci Adv ; 5(1): eaav3294, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30746477

RESUMO

Wearable sweat sensors rely either on electronics for electrochemical detection or on colorimetry for visual readout. Non-ideal form factors represent disadvantages of the former, while semiquantitative operation and narrow scope of measurable biomarkers characterize the latter. Here, we introduce a battery-free, wireless electronic sensing platform inspired by biofuel cells that integrates chronometric microfluidic platforms with embedded colorimetric assays. The resulting sensors combine advantages of electronic and microfluidic functionality in a platform that is significantly lighter, cheaper, and smaller than alternatives. A demonstration device simultaneously monitors sweat rate/loss, pH, lactate, glucose, and chloride. Systematic studies of the electronics, microfluidics, and integration schemes establish the key design considerations and performance attributes. Two-day human trials that compare concentrations of glucose and lactate in sweat and blood suggest a potential basis for noninvasive, semi-quantitative tracking of physiological status.


Assuntos
Técnicas Biossensoriais/instrumentação , Colorimetria/métodos , Dispositivos Lab-On-A-Chip , Microfluídica/métodos , Pele/metabolismo , Suor/química , Dispositivos Eletrônicos Vestíveis , Fontes de Energia Bioelétrica , Cloretos/análise , Glucose/análise , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/análise , Masculino
17.
Chem Rev ; 119(8): 5461-5533, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30689360

RESUMO

Bio-integrated wearable systems can measure a broad range of biophysical, biochemical, and environmental signals to provide critical insights into overall health status and to quantify human performance. Recent advances in material science, chemical analysis techniques, device designs, and assembly methods form the foundations for a uniquely differentiated type of wearable technology, characterized by noninvasive, intimate integration with the soft, curved, time-dynamic surfaces of the body. This review summarizes the latest advances in this emerging field of "bio-integrated" technologies in a comprehensive manner that connects fundamental developments in chemistry, material science, and engineering with sensing technologies that have the potential for widespread deployment and societal benefit in human health care. An introduction to the chemistries and materials for the active components of these systems contextualizes essential design considerations for sensors and associated platforms that appear in following sections. The subsequent content highlights the most advanced biosensors, classified according to their ability to capture biophysical, biochemical, and environmental information. Additional sections feature schemes for electrically powering these sensors and strategies for achieving fully integrated, wireless systems. The review concludes with an overview of key remaining challenges and a summary of opportunities where advances in materials chemistry will be critically important for continued progress.


Assuntos
Técnicas Biossensoriais/instrumentação , Dispositivos Eletrônicos Vestíveis , Técnicas Biossensoriais/métodos , Humanos , Ciência dos Materiais/métodos
18.
Small ; 14(45): e1802876, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30300469

RESUMO

Sweat excretion is a dynamic physiological process that varies with body position, activity level, environmental factors, and health status. Conventional means for measuring the properties of sweat yield accurate results but their requirements for sampling and analytics do not allow for use in the field. Emerging wearable devices offer significant advantages over existing approaches, but each has significant drawbacks associated with bulk and weight, inability to quantify volumetric sweat rate and loss, robustness, and/or inadequate accuracy in biochemical analysis. This paper presents a thin, miniaturized, skin-interfaced microfluidic technology that includes a reusable, battery-free electronics module for measuring sweat conductivity and rate in real-time using wireless power from and data communication to electronic devices with capabilities in near field communications (NFC), including most smartphones. The platform exploits ultrathin electrodes integrated within a collection of microchannels as interfaces to circuits that leverage NFC protocols. The resulting capabilities are complementary to those of previously reported colorimetric strategies. Systematic studies of these combined microfluidic/electronic systems, accurate correlations of measurements performed with them to those of laboratory standard instrumentation, and field tests on human subjects exercising and at rest establish the key operational features and their utility in sweat analytics.


Assuntos
Eletrônica/métodos , Microfluídica/métodos , Animais , Eletrólitos/química , Humanos , Pele/química , Suor/química
19.
Lab Chip ; 18(15): 2178-2186, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-29955754

RESUMO

The rich composition of solutes and metabolites in sweat and its relative ease of collection upon excretion from skin pores make this class of biofluid an attractive candidate for point of care analysis. Wearable technologies that combine electrochemical sensors with conventional or emerging semiconductor device technologies offer valuable capabilities in sweat sensing, but they are limited to assays that support amperometric, potentiometric, and colorimetric analyses. Here, we present a complementary approach that exploits fluorometric sensing modalities integrated into a soft, skin-interfaced microfluidic system which, when paired with a simple smartphone-based imaging module, allows for in situ measurement of important biomarkers in sweat. A network array of microchannels and a collection of microreservoirs pre-filled with fluorescent probes that selectively react with target analytes in sweat (e.g. probes), enable quantitative, rapid analysis. Field studies on human subjects demonstrate the ability to measure the concentrations of chloride, sodium and zinc in sweat, with accuracy that matches that of conventional laboratory techniques. The results highlight the versatility of advanced fluorescent-based imaging modalities in body-worn sweat microfluidics platforms, and they suggest some practical potential for these ideas.


Assuntos
Fluorometria/instrumentação , Dispositivos Lab-On-A-Chip , Imagem Molecular/instrumentação , Pele/química , Smartphone , Suor/química , Cloretos/análise , Humanos , Sódio/análise , Zinco/análise
20.
Small ; 14(12): e1703334, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29394467

RESUMO

This paper introduces super absorbent polymer valves and colorimetric sensing reagents as enabling components of soft, skin-mounted microfluidic devices designed to capture, store, and chemically analyze sweat released from eccrine glands. The valving technology enables robust means for guiding the flow of sweat from an inlet location into a collection of isolated reservoirs, in a well-defined sequence. Analysis in these reservoirs involves a color responsive indicator of chloride concentration with a formulation tailored to offer stable operation with sensitivity optimized for the relevant physiological range. Evaluations on human subjects with comparisons against ex situ analysis illustrate the practical utility of these advances.


Assuntos
Colorimetria/métodos , Microfluídica/métodos , Polímeros/química , Suor/química , Humanos , Dispositivos Lab-On-A-Chip , Pele/metabolismo
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