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1.
Adv Sci (Weinh) ; : e2103331, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34747140

RESUMO

Nutrients play critical roles in maintaining core physiological functions and in preventing diseases. Technologies for delivering these nutrients and for monitoring their concentrations can help to ensure proper nutritional balance. Eccrine sweat is a potentially attractive class of biofluid for monitoring purposes due to the ability to capture sweat easily and noninvasively from nearly any region of the body using skin-integrated microfluidic technologies. Here, a miniaturized system of this type is presented that allows simple, rapid colorimetric assessments of the concentrations of multiple essential nutrients in sweat, simultaneously and without any supporting electronics - vitamin C, calcium, zinc, and iron. A transdermal patch integrated directly with the microfluidics supports passive, sustained delivery of these species to the body throughout a period of wear. Comparisons of measurement results to those from traditional lab analysis methods demonstrate the accuracy and reliability of this platform. On-body tests with human subjects reveal correlations between the time dynamics of concentrations of these nutrients in sweat and those of the corresponding concentrations in blood. Studies conducted before and after consuming certain foods and beverages highlight practical capabilities in monitoring nutritional balance, with strong potential to serve as a basis for guiding personalized dietary choices.

2.
J Vis Exp ; (176)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34747395

RESUMO

Peripheral nerve interfaces are frequently used in experimental neuroscience and regenerative medicine for a wide variety of applications. Such interfaces can be sensors, actuators, or both. Traditional methods of peripheral nerve interfacing must either tether to an external system or rely on battery power that limits the time frame for operation. With recent developments of wireless, battery-free, and fully implantable peripheral nerve interfaces, a new class of devices can offer capabilities that match or exceed those of their wired or battery-powered precursors. This paper describes methods to (i) surgically implant and (ii) wirelessly power and control this system in adult rats. The sciatic and phrenic nerve models were selected as examples to highlight the versatility of this approach. The paper shows how the peripheral nerve interface can evoke compound muscle action potentials (CMAPs), deliver a therapeutic electrical stimulation protocol, and incorporate a conduit for the repair of peripheral nerve injury. Such devices offer expanded treatment options for single-dose or repeated dose therapeutic stimulation and can be adapted to a variety of nerve locations.

3.
Chem Rev ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739219

RESUMO

Advances in materials chemistry and engineering serve as the basis for multifunctional neural interfaces that span length scales from individual neurons to neural networks, neural tissues, and complete neural systems. Such technologies exploit electrical, electrochemical, optical, and/or pharmacological modalities in sensing and neuromodulation for fundamental studies in neuroscience research, with additional potential to serve as routes for monitoring and treating neurodegenerative diseases and for rehabilitating patients. This review summarizes the essential role of chemistry in this field of research, with an emphasis on recently published results and developing trends. The focus is on enabling materials in diverse device constructs, including their latest utilization in 3D bioelectronic frameworks formed by 3D printing, self-folding, and mechanically guided assembly. A concluding section highlights key challenges and future directions.

4.
Digit Biomark ; 5(2): 167-175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34723069

RESUMO

Introduction: Difficulty swallowing (dysphagia) occurs frequently in patients with neurological disorders and can lead to aspiration, choking, and malnutrition. Dysphagia is typically diagnosed using costly, invasive imaging procedures or subjective, qualitative bedside examinations. Wearable sensors are a promising alternative to noninvasively and objectively measure physiological signals relevant to swallowing. An ongoing challenge with this approach is consolidating these complex signals into sensitive, clinically meaningful metrics of swallowing performance. To address this gap, we propose 2 novel, digital monitoring tools to evaluate swallows using wearable sensor data and machine learning. Methods: Biometric swallowing and respiration signals from wearable, mechano-acoustic sensors were compared between patients with poststroke dysphagia and nondysphagic controls while swallowing foods and liquids of different consistencies, in accordance with the Mann Assessment of Swallowing Ability (MASA). Two machine learning approaches were developed to (1) classify the severity of impairment for each swallow, with model confidence ratings for transparent clinical decision support, and (2) compute a similarity measure of each swallow to nondysphagic performance. Task-specific models were trained using swallow kinematics and respiratory features from 505 swallows (321 from patients and 184 from controls). Results: These models provide sensitive metrics to gauge impairment on a per-swallow basis. Both approaches demonstrate intrasubject swallow variability and patient-specific changes which were not captured by the MASA alone. Sensor measures encoding respiratory-swallow coordination were important features relating to dysphagia presence and severity. Puree swallows exhibited greater differences from controls than saliva swallows or liquid sips (p < 0.037). Discussion: Developing interpretable tools is critical to optimize the clinical utility of novel, sensor-based measurement techniques. The proof-of-concept models proposed here provide concrete, communicable evidence to track dysphagia recovery over time. With refined training schemes and real-world validation, these tools can be deployed to automatically measure and monitor swallowing in the clinic and community for patients across the impairment spectrum.

5.
Proc Natl Acad Sci U S A ; 118(43)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34663725

RESUMO

Early identification of atypical infant movement behaviors consistent with underlying neuromotor pathologies can expedite timely enrollment in therapeutic interventions that exploit inherent neuroplasticity to promote recovery. Traditional neuromotor assessments rely on qualitative evaluations performed by specially trained personnel, mostly available in tertiary medical centers or specialized facilities. Such approaches are high in cost, require geographic proximity to advanced healthcare resources, and yield mostly qualitative insight. This paper introduces a simple, low-cost alternative in the form of a technology customized for quantitatively capturing continuous, full-body kinematics of infants during free living conditions at home or in clinical settings while simultaneously recording essential vital signs data. The system consists of a wireless network of small, flexible inertial sensors placed at strategic locations across the body and operated in a wide-bandwidth and time-synchronized fashion. The data serve as the basis for reconstructing three-dimensional motions in avatar form without the need for video recordings and associated privacy concerns, for remote visual assessments by experts. These quantitative measurements can also be presented in graphical format and analyzed with machine-learning techniques, with potential to automate and systematize traditional motor assessments. Clinical implementations with infants at low and at elevated risks for atypical neuromotor development illustrates application of this system in quantitative and semiquantitative assessments of patterns of gross motor skills, along with body temperature, heart rate, and respiratory rate, from long-term and follow-up measurements over a 3-mo period following birth. The engineering aspects are compatible for scaled deployment, with the potential to improve health outcomes for children worldwide via early, pragmatic detection methods.

7.
J Reconstr Microsurg ; 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553344

RESUMO

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are limited to flaps which carry a cutaneous paddle. As such, this useful and reliable technology has not previously been applicable to muscle-only free flaps where other modalities with substantial limitations continue to be utilized. METHODS: We present the first NIRS probe which allows continuous monitoring of local tissue oxygen saturation (StO2) directly within the substance of muscle tissue. This probe is flexible, subcentimeter in scale, waterproof, biocompatible, and is fitted with resorbable barbs which facilitate temporary autostabilization followed by easy atraumatic removal. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. During these experiments, the T.Ox device was affixed to the skin paddle, while the novel probe was within the muscle component of the same flap. RESULTS: The intramuscular NIRS device and skin-mounted ViOptix T.Ox devices produced very similar StO2 tracings throughout the vascular clamping events, with obvious and parallel changes occurring upon vascular clamping and release. The normalized cross-correlation at zero lag describing correspondence between the novel intramuscular NIRS and T.Ox devices was >0.99. CONCLUSION: This novel intramuscular NIRS probe offers continuous monitoring of oxygen saturation within muscle flaps. This experiment demonstrates the potential suitability of this intramuscular NIRS probe for the task of muscle-only free flap monitoring, where NIRS has not previously been applicable. Testing in the clinical environment is necessary to assess durability and reliability.

8.
Adv Mater ; 33(44): e2103974, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34510572

RESUMO

Continuous monitoring of vital signs is an essential aspect of operations in neonatal and pediatric intensive care units (NICUs and PICUs), of particular importance to extremely premature and/or critically ill patients. Current approaches require multiple sensors taped to the skin and connected via hard-wired interfaces to external data acquisition electronics. The adhesives can cause iatrogenic injuries to fragile, underdeveloped skin, and the wires can complicate even the most routine tasks in patient care. Here, materials strategies and design concepts are introduced that significantly improve these platforms through the use of optimized materials, open (i.e., "holey") layouts and precurved designs. These schemes 1) reduce the stresses at the skin interface, 2) facilitate release of interfacial moisture from transepidermal water loss, 3) allow visual inspection of the skin for rashes or other forms of irritation, 4) enable triggered reduction of adhesion to reduce the probability for injuries that can result from device removal. A combination of systematic benchtop testing and computational modeling identifies the essential mechanisms and key considerations. Demonstrations on adult volunteers and on a neonate in an operating NICUs illustrate a broad range of capabilities in continuous, clinical-grade monitoring of conventional vital signs, and unconventional indicators of health status.

9.
Microsyst Nanoeng ; 7: 62, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567774

RESUMO

Implantable deep brain stimulation (DBS) systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic pain. However, long-term efficacy of DBS is limited, and chronic neuroplastic changes and associated therapeutic mechanisms are not well understood. Fundamental and mechanistic investigation, typically accomplished in small animal models, is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise insight. To overcome these challenges, we demonstrate a fully implantable, wireless, battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real time. The devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance, surface-engineered platinum electrodes. The devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid dissemination. Efficacy of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days.

10.
Nature ; 597(7877): 503-510, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34552257

RESUMO

Large, distributed collections of miniaturized, wireless electronic devices1,2 may form the basis of future systems for environmental monitoring3, population surveillance4, disease management5 and other applications that demand coverage over expansive spatial scales. Aerial schemes to distribute the components for such networks are required, and-inspired by wind-dispersed seeds6-we examined passive structures designed for controlled, unpowered flight across natural environments or city settings. Techniques in mechanically guided assembly of three-dimensional (3D) mesostructures7-9 provide access to miniature, 3D fliers optimized for such purposes, in processes that align with the most sophisticated production techniques for electronic, optoelectronic, microfluidic and microelectromechanical technologies. Here we demonstrate a range of 3D macro-, meso- and microscale fliers produced in this manner, including those that incorporate active electronic and colorimetric payloads. Analytical, computational and experimental studies of the aerodynamics of high-performance structures of this type establish a set of fundamental considerations in bio-inspired design, with a focus on 3D fliers that exhibit controlled rotational kinematics and low terminal velocities. An approach that represents these complex 3D structures as discrete numbers of blades captures the essential physics in simple, analytical scaling forms, validated by computational and experimental results. Battery-free, wireless devices and colorimetric sensors for environmental measurements provide simple examples of a wide spectrum of applications of these unusual concepts.

11.
J Reconstr Microsurg ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404105

RESUMO

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

12.
ACS Sens ; 6(8): 2787-2801, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34351759

RESUMO

Skin-interfaced wearable systems with integrated colorimetric assays, microfluidic channels, and electrochemical sensors offer powerful capabilities for noninvasive, real-time sweat analysis. This Perspective details recent progress in the development and translation of novel wearable sensors for personalized assessment of sweat dynamics and biomarkers, with precise sampling and real-time analysis. Sensor accuracy, system ruggedness, and large-scale deployment in remote environments represent key opportunity areas, enabling broad deployment in the context of field studies, clinical trials, and recent commercialization. On-body measurements in these contexts show good agreement compared to conventional laboratory-based sweat analysis approaches. These device demonstrations highlight the utility of biochemical sensing platforms for personalized assessment of performance, wellness, and health across a broad range of applications.


Assuntos
Suor , Dispositivos Eletrônicos Vestíveis , Microfluídica , Pele
13.
Adv Mater ; 33(39): e2103857, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34369002

RESUMO

Wireless, skin-integrated devices for continuous, clinical-quality monitoring of vital signs have the potential to greatly improve the care of patients in neonatal and pediatric intensive-care units. These same technologies can also be used in the home, across a broad spectrum of ages, from beginning to end of life. Although miniaturized forms of such devices minimize patient burden and improve compliance, they represent life-threatening choking hazards for infants. A materials strategy is presented here to address this concern. Specifically, composite materials are introduced as soft encapsulating layers and gentle adhesives that release chemical compounds designed to elicit an intense bitter taste when placed in the mouth. Reflexive reactions to this sensation strongly reduce the potential for ingestion, as a safety feature. The materials systems described involve a non-toxic bitterant (denatonium benzoate) as a dopant in an elastomeric (poly(dimethylsiloxane)) or hydrogel matrix. Experimental and computational studies of these composite materials and the kinetics of release of the bitterant define the key properties. Incorporation into various wireless skin-integrated sensors demonstrates their utility in functional systems. This simple strategy offers valuable protective capabilities, with broad practical relevance to the welfare of children monitored with wearable devices.

14.
Curr Opin Biotechnol ; 72: 1-7, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34358775

RESUMO

Recent advances in bio-interface technologies establish a rich range of electronic, optoelectronic, thermal, and chemical options for probing and modulating the behaviors of small-scale three dimensional (3D) biological constructs (e.g. organoids, spheroids, and assembloids). These approaches represent qualitative advances over traditional alternatives due to their ability to extend broadly into volumetric spaces and/or to wrap tightly curved surfaces of natural or artificial tissues. Thin deformable sheets, filamentary penetrating pins, open mesh structures and 3D interconnected networks represent some of the most effective design strategies in this emerging field of bioelectronics. This review focuses on recent developments, with an emphasis on multimodal interfaces in the form of tissue-embedding scaffolds and tissue-surrounding frameworks.

15.
Nat Mater ; 20(11): 1559-1570, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34326506

RESUMO

Flexible electronic/optoelectronic systems that can intimately integrate onto the surfaces of vital organ systems have the potential to offer revolutionary diagnostic and therapeutic capabilities relevant to a wide spectrum of diseases and disorders. The critical interfaces between such technologies and living tissues must provide soft mechanical coupling and efficient optical/electrical/chemical exchange. Here, we introduce a functional adhesive bioelectronic-tissue interface material, in the forms of mechanically compliant, electrically conductive, and optically transparent encapsulating coatings, interfacial layers or supporting matrices. These materials strongly bond both to the surfaces of the devices and to those of different internal organs, with stable adhesion for several days to months, in chemistries that can be tailored to bioresorb at controlled rates. Experimental demonstrations in live animal models include device applications that range from battery-free optoelectronic systems for deep-brain optogenetics and subdermal phototherapy to wireless millimetre-scale pacemakers and flexible multielectrode epicardial arrays. These advances have immediate applicability across nearly all types of bioelectronic/optoelectronic system currently used in animal model studies, and they also have the potential for future treatment of life-threatening diseases and disorders in humans.

16.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34301889

RESUMO

Wireless, battery-free, and fully subdermally implantable optogenetic tools are poised to transform neurobiological research in freely moving animals. Current-generation wireless devices are sufficiently small, thin, and light for subdermal implantation, offering some advantages over tethered methods for naturalistic behavior. Yet current devices using wireless power delivery require invasive stimulus delivery, penetrating the skull and disrupting the blood-brain barrier. This can cause tissue displacement, neuronal damage, and scarring. Power delivery constraints also sharply curtail operational arena size. Here, we implement highly miniaturized, capacitive power storage on the platform of wireless subdermal implants. With approaches to digitally manage power delivery to optoelectronic components, we enable two classes of applications: transcranial optogenetic activation millimeters into the brain (validated using motor cortex stimulation to induce turning behaviors) and wireless optogenetics in arenas of more than 1 m2 in size. This methodology allows for previously impossible behavioral experiments leveraging the modern optogenetic toolkit.

17.
Pain ; 162(12): 2865-2880, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34160168

RESUMO

ABSTRACT: Accumulating evidence suggests hippocampal impairment under the chronic pain phenotype. However, it is unknown whether neuropathic behaviors are related to dysfunction of the hippocampal circuitry. Here, we enhanced hippocampal activity by pharmacological, optogenetic, and chemogenetic techniques to determine hippocampal influence on neuropathic pain behaviors. We found that excitation of the dorsal (DH), but not the ventral (VH) hippocampus induces analgesia in 2 rodent models of neuropathic pain (SNI and SNL) and in rats and mice. Optogenetic and pharmacological manipulations of DH neurons demonstrated that DH-induced analgesia was mediated by N-Methyl-D-aspartate and µ-opioid receptors. In addition to analgesia, optogenetic stimulation of the DH in SNI mice also resulted in enhanced real-time conditioned place preference for the chamber where the DH was activated, a finding consistent with pain relief. Similar manipulations in the VH were ineffective. Using chemo-functional magnetic resonance imaging (fMRI), where awake resting-state fMRI was combined with viral vector-mediated chemogenetic activation (PSAM/PSEM89s) of DH neurons, we demonstrated changes of functional connectivity between the DH and thalamus and somatosensory regions that tracked the extent of relief from tactile allodynia. Moreover, we examined hippocampal functional connectivity in humans and observe differential reorganization of its anterior and posterior subdivisions between subacute and chronic back pain. Altogether, these results imply that downregulation of the DH circuitry during chronic neuropathic pain aggravates pain-related behaviors. Conversely, activation of the DH reverses pain-related behaviors through local excitatory and opioidergic mechanisms affecting DH functional connectivity. Thus, this study exhibits a novel causal role for the DH but not the VH in controlling neuropathic pain-related behaviors.

18.
Nat Biotechnol ; 39(10): 1228-1238, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34183859

RESUMO

Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.


Assuntos
Implantes Absorvíveis , Marca-Passo Artificial , Animais , Bloqueio Atrioventricular/terapia , Modelos Animais de Doenças , Cães , Desenho de Equipamento , Humanos , Camundongos , Coelhos , Ratos , Tecnologia sem Fio
19.
Sci Adv ; 7(20)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33980495

RESUMO

Soft, skin-integrated electronic sensors can provide continuous measurements of diverse physiological parameters, with broad relevance to the future of human health care. Motion artifacts can, however, corrupt the recorded signals, particularly those associated with mechanical signatures of cardiopulmonary processes. Design strategies introduced here address this limitation through differential operation of a matched, time-synchronized pair of high-bandwidth accelerometers located on parts of the anatomy that exhibit strong spatial gradients in motion characteristics. When mounted at a location that spans the suprasternal notch and the sternal manubrium, these dual-sensing devices allow measurements of heart rate and sounds, respiratory activities, body temperature, body orientation, and activity level, along with swallowing, coughing, talking, and related processes, without sensitivity to ambient conditions during routine daily activities, vigorous exercises, intense manual labor, and even swimming. Deployments on patients with COVID-19 allow clinical-grade ambulatory monitoring of the key symptoms of the disease even during rehabilitation protocols.


Assuntos
Acelerometria/instrumentação , Acelerometria/métodos , Eletrocardiografia Ambulatorial/instrumentação , Eletrocardiografia Ambulatorial/métodos , Dispositivos Eletrônicos Vestíveis , Temperatura Corporal , COVID-19 , Exercício Físico/fisiologia , Frequência Cardíaca , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , SARS-CoV-2
20.
Sci Adv ; 7(18)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33931455

RESUMO

Itch is a common clinical symptom and major driver of disease-related morbidity across a wide range of medical conditions. A substantial unmet need is for objective, accurate measurements of itch. In this article, we present a noninvasive technology to objectively quantify scratching behavior via a soft, flexible, and wireless sensor that captures the acousto-mechanic signatures of scratching from the dorsum of the hand. A machine learning algorithm validated on data collected from healthy subjects (n = 10) indicates excellent performance relative to smartwatch-based approaches. Clinical validation in a cohort of predominately pediatric patients (n = 11) with moderate to severe atopic dermatitis included 46 sleep-nights totaling 378.4 hours. The data indicate an accuracy of 99.0% (84.3% sensitivity, 99.3% specificity) against visual observation. This work suggests broad capabilities relevant to applications ranging from assessing the efficacy of drugs for conditions that cause itch to monitoring disease severity and treatment response.

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