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1.
Adv Mater ; 36(18): e2311154, 2024 May.
Article in English | MEDLINE | ID: mdl-38174953

ABSTRACT

Bioelectronic implants delivering electrical stimulation offer an attractive alternative to traditional pharmaceuticals in electrotherapy. However, achieving simple, rapid, and cost-effective personalization of these implants for customized treatment in unique clinical and physical scenarios presents a substantial challenge. This challenge is further compounded by the need to ensure safety and minimal invasiveness, requiring essential attributes such as flexibility, biocompatibility, lightness, biodegradability, and wireless stimulation capability. Here, a flexible, biodegradable bioelectronic paper with homogeneously distributed wireless stimulation functionality for simple personalization of bioelectronic implants is introduced. The bioelectronic paper synergistically combines i) lead-free magnetoelectric nanoparticles (MENs) that facilitate electrical stimulation in response to external magnetic field and ii) flexible and biodegradable nanofibers (NFs) that enable localization of MENs for high-selectivity stimulation, oxygen/nutrient permeation, cell orientation modulation, and biodegradation rate control. The effectiveness of wireless electrical stimulation in vitro through enhanced neuronal differentiation of neuron-like PC12 cells and the controllability of their microstructural orientation are shown. Also, scalability, design flexibility, and rapid customizability of the bioelectronic paper are shown by creating various 3D macrostructures using simple paper crafting techniques such as cutting and folding. This platform holds promise for simple and rapid personalization of temporary bioelectronic implants for minimally invasive wireless stimulation therapies.


Subject(s)
Absorbable Implants , Magnetics , Precision Medicine , Wireless Technology , Paper , Precision Medicine/instrumentation , Humans , Male , Animals , Rats , Brain , Electronics, Medical/instrumentation
2.
Biomaterials ; 301: 122271, 2023 10.
Article in English | MEDLINE | ID: mdl-37619262

ABSTRACT

In the past few decades, stem cell-based regenerative engineering has demonstrated its significant potential to repair damaged tissues and to restore their functionalities. Despite such advancement in regenerative engineering, the clinical translation remains a major challenge. In the stance of personalized treatment, the recent progress in bioelectronic medicine likewise evolved as another important research domain of larger significance for human healthcare. Over the last several years, our research group has adopted biomaterials-based regenerative engineering strategies using innovative bioelectronic stimulation protocols based on either electric or magnetic stimuli to direct cellular differentiation on engineered biomaterials with a range of elastic stiffness or functional properties (electroactivity/magnetoactivity). In this article, the role of bioelectronics in stem cell-based regenerative engineering has been critically analyzed to stimulate futuristic research in the treatment of degenerative diseases as well as to address some fundamental questions in stem cell biology. Built on the concepts from two independent biomedical research domains (regenerative engineering and bioelectronic medicine), we propose a converging research theme, 'Regenerative Bioelectronics'. Further, a series of recommendations have been put forward to address the current challenges in bridging the gap in stem cell therapy and bioelectronic medicine. Enacting the strategic blueprint of bioelectronic-based regenerative engineering can potentially deliver the unmet clinical needs for treating incurable degenerative diseases.


Subject(s)
Electronics, Medical , Precision Medicine , Precision Medicine/instrumentation , Precision Medicine/methods , Nanostructures , Electronics, Medical/instrumentation , Electronics, Medical/methods , Biocompatible Materials/chemistry , Magnetics
3.
Nature ; 614(7948): 456-462, 2023 02.
Article in English | MEDLINE | ID: mdl-36792740

ABSTRACT

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.


Subject(s)
Electromyography , Electronics, Medical , Nanostructures , Pliability , Polymers , Prostheses and Implants , Wearable Electronic Devices , Humans , Nanostructures/chemistry , Polymers/chemistry , Skin , Monitoring, Physiologic , Electronics, Medical/instrumentation , Electronics, Medical/methods , Electromyography/instrumentation
4.
Radiat Oncol ; 16(1): 232, 2021 Dec 04.
Article in English | MEDLINE | ID: mdl-34863229

ABSTRACT

BACKGROUND: Intensity-modulated radiation therapy (IMRT) and volume-modulated arc therapy (VMAT) are rather complex treatment techniques and require patient-specific quality assurance procedures. Electronic portal imaging devices (EPID) are increasingly used in the verification of radiation therapy (RT). This work aims to develop a novel model to predict the EPID transmission image (TI) with fluence maps from the RT plan. The predicted TI is compared with the measured TI for in vivo treatment verification. METHODS: The fluence map was extracted from the RT plan and corrections of penumbra, response, global field output, attenuation, and scatter were applied before the TI was calculated. The parameters used in the model were calculated separately for central axis and off-axis points using a series of EPID measurement data. Our model was evaluated using a CIRS thorax phantom and 20 clinical plans (10 IMRT and 10 VMAT) optimized for head and neck, breast, and rectum treatments. RESULTS: Comparisons of the predicted and measured images were carried out using a global gamma analysis of 3%/2 mm (10% threshold) to validate the accuracy of the model. The gamma pass rates for IMRT and VMAT were greater than 97.2% and 94.5% at 3%/2 mm, respectively. CONCLUSION: We have developed an accurate and straightforward EPID-based quality assurance model that can potentially be used for in vivo treatment verification of the IMRT and VMAT delivery.


Subject(s)
Diagnostic Imaging/methods , Electronics, Medical/instrumentation , Image Processing, Computer-Assisted/methods , Neoplasms/radiotherapy , Phantoms, Imaging , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Algorithms , Humans , Neoplasms/diagnostic imaging , Neoplasms/pathology , Organs at Risk/radiation effects , Radiotherapy Dosage
5.
PLoS One ; 16(12): e0261793, 2021.
Article in English | MEDLINE | ID: mdl-34969050

ABSTRACT

Disinvestment is the removal or reduction of previously provided practices or services, and has typically been undertaken where a practice or service has been clearly shown to be ineffective, inefficient and/or harmful. However, practices and services that have uncertain evidence of effectiveness, efficiency and safety can also be considered as candidates for disinvestment. Disinvestment from these practices and services is risky as they may yet prove to be beneficial if further evidence becomes available. A novel research approach has previously been described for this situation, allowing disinvestment to take place while simultaneously generating evidence previously missing from consideration. In this paper, we describe how this approach can be expanded to situations where three or more conditions are of relevance, and describe the protocol for a trial examining the reduction and elimination of use of mobilisation alarms on hospital wards to prevent patient falls. Our approach utilises a 3-group, concurrent, non-inferiority, stepped wedge, randomised design with an embedded parallel, cluster randomised design. Eighteen hospital wards with high rates of alarm use (≥3%) will be paired within their health service and randomly allocated to a calendar month when they will transition to a "Reduced" (<3%) or "Eliminated" (0%) mobilisation alarm condition. Dynamic randomisation will be used to determine which ward in each pair will be allocated to either the reduced or eliminated condition to promote equivalence between wards for the embedded parallel, cluster randomised component of the design. A project governance committee will set non-inferiority margins. The primary outcome will be rates of falls. Secondary clinical, process, safety, and economic outcomes will be collected and a concurrent economic evaluation undertaken.


Subject(s)
Accidental Falls/prevention & control , Clinical Alarms , Hospitalization , Hospitals , Monitoring, Ambulatory/instrumentation , Patient Safety , Beds , Computer Simulation , Electronics, Medical/instrumentation , Humans , Outcome Assessment, Health Care , Randomized Controlled Trials as Topic , Research Design , Statistics as Topic , Uncertainty
6.
IEEE Pulse ; 12(3): 14-17, 2021.
Article in English | MEDLINE | ID: mdl-34156928

ABSTRACT

An estimated ten million people in the United States have a condition known as essential tremor (ET). Yet although it's been recognized for over a century-it was originally known as senile tremor-there is relatively little awareness of it as a distinct medical condition. Sometimes mistaken for Parkinson's disease, ET can lead to shaking of the arms and hands, and sometimes the head or torso. When severe, it can interfere with eating or drinking, writing, dressing, and even make some tasks impossible. Now, new approaches for treating the condition are emerging, potentially offering options to many patients whose life activities have been curtailed by ET.


Subject(s)
Electric Stimulation/instrumentation , Tremor , Wearable Electronic Devices , Electronics, Medical/instrumentation , Humans , Tremor/diagnosis , Tremor/therapy
7.
Sci Rep ; 11(1): 9815, 2021 05 10.
Article in English | MEDLINE | ID: mdl-33972649

ABSTRACT

Lab-on-Chip is a technology that aims to transform the Point-of-Care (PoC) diagnostics field; nonetheless a commercial production compatible technology is yet to be established. Lab-on-Printed Circuit Board (Lab-on-PCB) is currently considered as a promising candidate technology for cost-aware but simultaneously high specification applications, requiring multi-component microsystem implementations, due to its inherent compatibility with electronics and the long-standing industrial manufacturing basis. In this work, we demonstrate the first electrolyte gated field-effect transistor (FET) DNA biosensor implemented on commercially fabricated PCB in a planar layout. Graphene ink was drop-casted to form the transistor channel and PNA probes were immobilized on the graphene channel, enabling label-free DNA detection. It is shown that the sensor can selectively detect the complementary DNA sequence, following a fully inkjet-printing compatible manufacturing process. The results demonstrate the potential for the effortless integration of FET sensors into Lab-on-PCB diagnostic platforms, paving the way for even higher sensitivity quantification than the current Lab-on-PCB state-of-the-art of passive electrode electrochemical sensing. The substitution of such biosensors with our presented FET structures, promises further reduction of the time-to-result in microsystems combining sequential DNA amplification and detection modules to few minutes, since much fewer amplification cycles are required even for low-abundance nucleic acid targets.


Subject(s)
Biosensing Techniques/instrumentation , DNA/isolation & purification , Graphite/chemistry , Lab-On-A-Chip Devices , Microtechnology/instrumentation , DNA/chemistry , Electronics, Medical/instrumentation , Nucleic Acid Amplification Techniques/instrumentation , Nucleic Acid Amplification Techniques/methods
8.
J Orthop Surg Res ; 16(1): 305, 2021 May 08.
Article in English | MEDLINE | ID: mdl-33964958

ABSTRACT

BACKGROUND: Soft tissue balancing is essential for the success of total knee arthroplasty (TKA) and is mainly dependent on surgeon-defined assessment (SDA) or a gap-balancer (GB). However, an electronic sensor has been developed to objectively measure the gap pressure. This study aimed to evaluate the accuracy of soft tissue balancing using SDA and GB compared with a sensor. METHODS: Forty-eight patients undergoing TKA (60 knees) were prospectively enrolled. Soft tissue balancing was sequentially performed using SDA, a GB, and an electronic sensor. We compared the SDA, GB, and sensor data to calculate the sensitivity, specificity, and accuracy at 0°, 45°, 90°, and 120° flexion. Cumulative summation (CUSUM) analysis was performed to assess the surgeon's performance during the sensor introductory phase. RESULTS: The sensitivity of SDA was 63.3%, 68.3%, 80.0%, and 80.0% at 0°, 45°, 90°, and 120°, respectively. The accuracy of the GB compared with sensor data was 76.7% and 71.7% at 0° and 90°, respectively. Cohen's kappa coefficient for the accuracy of the GB was 0.406 at 0° (moderate agreement) and 0.227 at 90° (fair agreement). The CUSUM 0° line achieved good prior performance at case 45, CUSUM 90° and 120° showed a trend toward good prior performance, while CUSUM 45° reached poor prior performance at case 8. CONCLUSION: SDA was a poor predictor of knee balance. GB improved the accuracy of soft tissue balancing, but was still less accurate than the sensor, particularly for unbalanced knees. SDA improved with ongoing use of the sensor, except at 45° flexion.


Subject(s)
Arthroplasty, Replacement, Knee/methods , Connective Tissue/physiology , Electronics, Medical/instrumentation , Knee Prosthesis , Osteoarthritis, Knee/physiopathology , Osteoarthritis, Knee/surgery , Range of Motion, Articular , Surgeons , Biomechanical Phenomena , Cohort Studies , Humans , Learning Curve , Sensitivity and Specificity , Treatment Outcome
9.
Nat Commun ; 12(1): 2399, 2021 04 23.
Article in English | MEDLINE | ID: mdl-33893292

ABSTRACT

Energy autonomy and conformability are essential elements in the next generation of wearable and flexible electronics for healthcare, robotics and cyber-physical systems. This study presents ferroelectric polymer transducers and organic diodes for imperceptible sensing and energy harvesting systems, which are integrated on ultrathin (1-µm) substrates, thus imparting them with excellent flexibility. Simulations show that the sensitivity of ultraflexible ferroelectric polymer transducers is strongly enhanced by using an ultrathin substrate, which allows the mounting on 3D-shaped objects and the stacking in multiple layers. Indeed, ultraflexible ferroelectric polymer transducers have improved sensitivity to strain and pressure, fast response and excellent mechanical stability, thus forming imperceptible wireless e-health patches for precise pulse and blood pressure monitoring. For harvesting biomechanical energy, the transducers are combined with rectifiers based on ultraflexible organic diodes thus comprising an imperceptible, 2.5-µm thin, energy harvesting device with an excellent peak power density of 3 mW·cm-3.


Subject(s)
Bioelectric Energy Sources , Biosensing Techniques/instrumentation , Electronics, Medical/instrumentation , Transducers , Wearable Electronic Devices , Biosensing Techniques/methods , Electronics, Medical/methods , Humans , Micro-Electrical-Mechanical Systems/instrumentation , Micro-Electrical-Mechanical Systems/methods , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Reproducibility of Results , Robotics/instrumentation , Robotics/methods
10.
Lancet Digit Health ; 3(4): e266-e273, 2021 04.
Article in English | MEDLINE | ID: mdl-33640306

ABSTRACT

Globally, neonatal mortality remains unacceptability high. Physiological monitoring is foundational to the care of these vulnerable patients to assess neonatal cardiopulmonary status, guide medical intervention, and determine readiness for safe discharge. However, most existing physiological monitoring systems require multiple electrodes and sensors, which are linked to wires tethered to wall-mounted display units, to adhere to the skin. For neonates, these systems can cause skin injury, prevent kangaroo mother care, and complicate basic clinical care. Novel, wireless, and biointegrated sensors provide opportunities to enhance monitoring capabilities, reduce iatrogenic injuries, and promote family-centric care. Early validation data have shown performance equivalent to (and sometimes exceeding) standard-of-care monitoring systems in premature neonates cared for in high-income countries. The reusable nature of these sensors and compatibility with low-cost mobile phones have the future potential to enable substantially lower monitoring costs compared with existing systems. Deployment at scale, in low-income countries, holds the promise of substantial improvements in neonatal outcomes.


Subject(s)
Critical Care/methods , Electronics, Medical/instrumentation , Infant Care/methods , Monitoring, Physiologic/instrumentation , Wireless Technology/instrumentation , Developing Countries , Humans , Infant , Infant, Newborn
11.
J Manipulative Physiol Ther ; 44(1): 42-48, 2021 01.
Article in English | MEDLINE | ID: mdl-33248749

ABSTRACT

OBJECTIVE: The purpose this study was to investigate the reliability of a handheld myotonometer in measuring the mechanical properties of the neck and orofacial muscles in asymptomatic individuals. METHODS: The study included 16 healthy participants. The mechanical properties (frequency, decrement, stiffness, relaxation time, and creep) of the selected muscles were measured with a MyotonPRO myotonometer (Mumeetria Ltd, Tallinn, Estonia). The sternocleidomastoid, upper trapezius, cervical extensor, and masseter muscles were selected to determine the reliability of the device. Measurements were performed by 2 examiners to determine interrater reliability; for intrarater reliability, an examiner repeated the measurements 1 week after the first measurements. RESULTS: The results revealed moderate to excellent intrarater and interrater reliability (intraclass correlation coefficients: 0.50-0.95) in measuring muscle mechanic properties. The standard error of measurement in the tested muscles ranged from 0.3 to 0.8 Hz for frequency, from 7.4 to 20.9 N/m for stiffness, from 0.1 to 0.2 for decrement, and from 0.8 to 1.4 ms for relaxation time. The minimum detectable change ranged from 0.8 to 2.2 Hz for frequency, from 20.5 to 57.9 N/m for stiffness, from 0.2 to 0.6 for decrement, from 2.2 to 3.9 ms for relaxation time, and from 0.2 to 0.3 for creep. In addition, the coefficients of variation were below 9.1% for all the assessed parameters. CONCLUSION: The obtained results demonstrate that the MyotonPRO device is a reliable and repeatable tool to quantify the frequency, stiffness, decrement, relation time, and creep of the neck and orofacial muscles in asymptomatic individuals.


Subject(s)
Electronics, Medical/instrumentation , Neck Muscles/physiology , Superficial Back Muscles/physiology , Adult , Humans , Male , Manometry/standards , Middle Aged , Observer Variation , Reproducibility of Results , Young Adult
12.
IEEE Trans Biomed Circuits Syst ; 14(6): 1218-1229, 2020 12.
Article in English | MEDLINE | ID: mdl-33170783

ABSTRACT

This paper presents a millimeter-scale crystal-less wireless transceiver for volume-constrained insertable pills. Operating in the 402-405 MHz medical implant communication service (MICS) band, the phase-tracking receiver-based over-the-air carrier recovery has a ±160 ppm coverage. A fully integrated adaptive antenna impedance matching solution is proposed to calibrate the antenna impedance variation inside the body. A tunable matching network (TMN) with single inductor performs impedance matching for both transmitter (TX) and receiver (RX) and TX/RX mode switching. To dynamically calibrate the antenna impedance variation over different locations and diet conditions, a loop-back power detector using self-mixing is adopted, which expands the power contour up to 4.8 VSWR. The transceiver is implemented in a 40-nm CMOS technology, occupying 2 mm2 die area. The transceiver chip and a miniature antenna are integrated in a 3.5 × 15 mm2 area prototype wireless module. It has a receiver sensitivity of -90 dBm at 200 kbps data rate and delivers up to - 25 dBm EIRP in the wireless measurement with a liquid phantom.


Subject(s)
Electronics, Medical/instrumentation , Gastroscopy/instrumentation , Wireless Technology/instrumentation , Equipment Design , Humans , Models, Biological , Phantoms, Imaging , Signal Processing, Computer-Assisted/instrumentation , Stomach/diagnostic imaging
13.
IEEE Trans Biomed Circuits Syst ; 14(6): 1263-1273, 2020 12.
Article in English | MEDLINE | ID: mdl-33216718

ABSTRACT

This paper presents the body-coupled power transmission and ambient energy harvesting ICs. The ICs utilize human body-coupling to deliver power to the entire body, and at the same time, harvest energy from ambient EM waves coupled through the body. The ICs improve the recovered power level by adapting to the varying skin-electrode interface parasitic impedance at both the TX and RX. To maximize the power output from the TX, the dynamic impedance matching is performed amidst environment-induced variations. At the RX, the Detuned Impedance Booster (DIB) and the Bulk Adaptation Rectifier (BAR) are proposed to improve the power recovery and extend the power coverage further. In order to ensure the maximum power extraction despite the loading variations, the Dual-Mode Buck-Boost Converter (DM-BBC) is proposed. The ICs fabricated in 40 nm 1P8M CMOS recover up to 100 µW from the body-coupled power transmission and 2.5 µW from the ambient body-coupled energy harvesting. The ICs achieve the full-body area power delivery, with the power harvested from the ambiance via the body-coupling mechanism independent of placements on the body. Both approaches show power sustainability for wearable electronics all around the human body.


Subject(s)
Electric Power Supplies , Electronics, Medical/instrumentation , Wearable Electronic Devices , Electric Impedance , Humans , Signal Processing, Computer-Assisted/instrumentation
14.
Adv Biosyst ; 4(11): e2000055, 2020 11.
Article in English | MEDLINE | ID: mdl-33084251

ABSTRACT

The design and benchtop operation of a wireless miniature epiretinal stimulator implant is reported. The implant is optically powered and controlled using safe illumination at near-infrared wavelengths. An application-specific integrated circuit (ASIC) hosting a digital control unit is used to control the implant's electrodes. The ASIC is powered using an advanced photovoltaic (PV) cell and programmed using a single photodiode. Diamond packaging technology is utilized to achieve high-density integration of the implant optoelectronic circuitry, as well as individual connections between a stimulator chip and 256 electrodes, within a 4.6 mm × 3.7 mm × 0.9 mm implant package. An ultrahigh efficiency PV cell with a monochromatic power conversion efficiency of 55% is used to power the implant. On-board photodetection circuity with a bandwidth of 3.7 MHz is used for forward data telemetry of stimulation parameters. In comparison to implants which utilize inductively coupled coils, laser power delivery enables a high degree of miniaturization and lower surgical complexity. The device presented combines the benefits of implant miniaturization and a flexible stimulation strategy provided by a dedicated stimulator chip. This development provides a route to fully wireless miniaturized minimally invasive implants with sophisticated functionalities.


Subject(s)
Electronics, Medical/instrumentation , Lasers , Visual Prosthesis , Wireless Technology/instrumentation , Diamond , Electric Power Supplies , Electrodes , Equipment Design , Miniaturization/instrumentation
15.
IEEE Trans Biomed Circuits Syst ; 14(4): 811-824, 2020 08.
Article in English | MEDLINE | ID: mdl-32746334

ABSTRACT

This paper presents an 8-channel energy-efficient analog front-end (AFE) for neural recording, with improvements in power supply rejection ratio (PSRR) and dynamic range. The input stage in the low noise amplifier (LNA) adopts low voltage supply (0.35 V) and current-reusing to achieve ultralow power. To maintain a high PSRR performance while using such a low-voltage supply, a replica-biasing scheme is proposed to generate a stable bias current for the input stage of the LNA despite large supply interference. By exploiting the signal characteristics in the tetrode recording, an averaged local field potential (A-LFP) servo loop is introduced to extend the dynamic range without consuming too much extra power and chip area. The A-LFP signal is generated by integrating the four-channel PGA outputs from the same tetrode. Furthermore, the outputs of the programmable gain amplifier (PGA) are level shifted to bias the input nodes of the amplifier through large pseudo resistors, thus increase the maximum output range without distortion under the low-voltage supply. The proof-of-concept prototype is fabricated in a 65 nm CMOS process. Each recording channel including an LNA and a PGA occupies 0.04 mm 2 and consumes 340 nW from the 0.35 V and 0.7 V supply. Each A-LFP servo loop, which is shared by four recording channels, occupies 0.04 mm 2 and consumes 190 nW. The maximum gain of the AFE is 54 dB, and the input-referred noise is 6.7 µV over the passband from 0.5 Hz to 6.5 kHz. Measurement also shows that the 0.35 V replica-biasing input stage can tolerate a large interferer up to 200 mVpp with a PSRR of 74 dB, which has been improved to 110 dB with a silicon respin that shields critical wires in the layout.


Subject(s)
Amplifiers, Electronic , Electronics, Medical/instrumentation , Neurosciences/instrumentation , Semiconductors , Animals , Brain/physiology , Electrodes, Implanted , Equipment Design , Rats , Silicon/chemistry
16.
IEEE Trans Biomed Circuits Syst ; 14(4): 658-670, 2020 08.
Article in English | MEDLINE | ID: mdl-32746351

ABSTRACT

For mm-sized implants incorporating silicon integrated circuits, ensuring lifetime operation of the chip within the corrosive environment of the body still remains a critical challenge. For the chip's packaging, various polymeric and thin ceramic coatings have been reported, demonstrating high biocompatibility and barrier properties. Yet, for the evaluation of the packaging and lifetime prediction, the conventional helium leak test method can no longer be applied due to the mm-size of such implants. Alternatively, accelerated soak studies are typically used instead. For such studies, early detection of moisture/ion ingress using an in-situ platform may result in a better prediction of lifetime functionality. In this work, we have developed such a platform on a CMOS chip. Ingress of moisture/ions would result in changes in the resistance of the interlayer dielectrics (ILD) used within the chip and can be tracked using the proposed system, which consists of a sensing array and an on-chip measurement engine. The measurement system uses a novel charge/discharge based time-mode resistance sensor that can be implemented using simple yet highly robust circuitry. The sensor array is implemented together with the measurement engine in a standard 0.18  µm 6-metal CMOS process. The platform was validated through a series of dry and wet measurements. The system can measure the ILD resistance with values of up to 0.504 peta-ohms, with controllable measurement steps that can be as low as 0.8 M Ω. The system works with a supply voltage of 1.8 V, and consumes 4.78 mA. Wet measurements in saline demonstrated the sensitivity of the platform in detecting moisture/ion ingress. Such a platform could be used both in accelerated soak studies and during the implant's life-time for monitoring the integrity of the chip's packaging.


Subject(s)
Electronics, Medical/instrumentation , Equipment Design/methods , Prostheses and Implants , Semiconductors , Ions/analysis , Metals/chemistry , Prosthesis Failure , Silicon/chemistry , Water/analysis
17.
IEEE Trans Biomed Circuits Syst ; 14(4): 636-645, 2020 08.
Article in English | MEDLINE | ID: mdl-32746353

ABSTRACT

This paper presents a device for time-gated fluorescence imaging in the deep brain, consisting of two on-chip laser diodes and 512 single-photon avalanche diodes (SPADs). The edge-emitting laser diodes deliver fluorescence excitation above the SPAD array, parallel to the imager. In the time domain, laser diode illumination is pulsed and the SPAD is time-gated, allowing a fluorescence excitation rejection up to O.D. 3 at 1 ns of time-gate delay. Each SPAD pixel is masked with Talbot gratings to enable the mapping of 2D array photon counts into a 3D image. The 3D image achieves a resolution of 40, 35, and 73 µm in the x, y, and z directions, respectively, in a noiseless environment, with a maximum frame rate of 50 kilo-frames-per-second. We present measurement results of the spatial and temporal profiles of the dual-pulsed laser diode illumination and of the photon detection characteristics of the SPAD array. Finally, we show the imager's ability to resolve a glass micropipette filled with red fluorescent microspheres. The system's 420 µm-wide cross section allows it to be inserted at arbitrary depths of the brain while achieving a field of view four times larger than fiber endoscopes of equal diameter.


Subject(s)
Imaging, Three-Dimensional/instrumentation , Neuroimaging/instrumentation , Optical Imaging/instrumentation , Electronics, Medical/instrumentation , Equipment Design
18.
Nat Commun ; 11(1): 4195, 2020 08 21.
Article in English | MEDLINE | ID: mdl-32826916

ABSTRACT

Realizing a clinical-grade electronic medicine for peripheral nerve disorders is challenging owing to the lack of rational material design that mimics the dynamic mechanical nature of peripheral nerves. Electronic medicine should be soft and stretchable, to feasibly allow autonomous mechanical nerve adaptation. Herein, we report a new type of neural interface platform, an adaptive self-healing electronic epineurium (A-SEE), which can form compressive stress-free and strain-insensitive electronics-nerve interfaces and enable facile biofluid-resistant self-locking owing to dynamic stress relaxation and water-proof self-bonding properties of intrinsically stretchable and self-healable insulating/conducting materials, respectively. Specifically, the A-SEE does not need to be sutured or glued when implanted, thereby significantly reducing complexity and the operation time of microneurosurgery. In addition, the autonomous mechanical adaptability of the A-SEE to peripheral nerves can significantly reduce the mechanical mismatch at electronics-nerve interfaces, which minimizes nerve compression-induced immune responses and device failure. Though a small amount of Ag leaked from the A-SEE is observed in vivo (17.03 ppm after 32 weeks of implantation), we successfully achieved a bidirectional neural signal recording and stimulation in a rat sciatic nerve model for 14 weeks. In view of our materials strategy and in vivo feasibility, the mechanically adaptive self-healing neural interface would be considered a new implantable platform for a wide range application of electronic medicine for neurological disorders in the human nervous system.


Subject(s)
Electronics, Medical/instrumentation , Electronics, Medical/methods , Neurosurgery/instrumentation , Neurosurgery/methods , Peripheral Nerves/physiology , Animals , Biomedical Engineering/instrumentation , Biomedical Engineering/methods , Central Nervous System/physiology , Central Nervous System/surgery , Gold , Humans , Male , Materials Testing , Models, Animal , Nerve Tissue/pathology , Nerve Tissue/surgery , Peripheral Nerves/pathology , Peripheral Nerves/surgery , Polymers/chemistry , Prostheses and Implants , Rats , Sciatic Nerve , Wearable Electronic Devices
19.
Nat Commun ; 11(1): 2183, 2020 05 04.
Article in English | MEDLINE | ID: mdl-32366821

ABSTRACT

Coupling myoelectric and mechanical signals during voluntary muscle contraction is paramount in human-machine interactions. Spatiotemporal differences in the two signals intrinsically arise from the muscular excitation-contraction process; however, current methods fail to deliver local electromechanical coupling of the process. Here we present the locally coupled electromechanical interface based on a quadra-layered ionotronic hybrid (named as CoupOn) that mimics the transmembrane cytoadhesion architecture. CoupOn simultaneously monitors mechanical strains with a gauge factor of ~34 and surface electromyogram with a signal-to-noise ratio of 32.2 dB. The resolved excitation-contraction signatures of forearm flexor muscles can recognize flexions of different fingers, hand grips of varying strength, and nervous and metabolic muscle fatigue. The orthogonal correlation of hand grip strength with speed is further exploited to manipulate robotic hands for recapitulating corresponding gesture dynamics. It can be envisioned that such locally coupled electromechanical interfaces would endow cyber-human interactions with unprecedented robustness and dexterity.


Subject(s)
Electromyography/methods , Hand Strength/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Range of Motion, Articular/physiology , Artificial Limbs , Bioengineering/instrumentation , Bioengineering/methods , Biomechanical Phenomena , Electronics, Medical/instrumentation , Electronics, Medical/methods , Fingers/physiology , Forearm/physiology , Hand/physiology , Humans , Prosthesis Design/instrumentation , Prosthesis Design/methods
20.
Nat Biotechnol ; 38(9): 1031-1036, 2020 09.
Article in English | MEDLINE | ID: mdl-32313193

ABSTRACT

Bioelectronics for modulating the nervous system have shown promise in treating neurological diseases1-3. However, their fixed dimensions cannot accommodate rapid tissue growth4,5 and may impair development6. For infants, children and adolescents, once implanted devices are outgrown, additional surgeries are often needed for device replacement, leading to repeated interventions and complications6-8. Here, we address this limitation with morphing electronics, which adapt to in vivo nerve tissue growth with minimal mechanical constraint. We design and fabricate multilayered morphing electronics, consisting of viscoplastic electrodes and a strain sensor that eliminate the stress at the interface between the electronics and growing tissue. The ability of morphing electronics to self-heal during implantation surgery allows a reconfigurable and seamless neural interface. During the fastest growth period in rats, morphing electronics caused minimal damage to the rat nerve, which grows 2.4-fold in diameter, and allowed chronic electrical stimulation and monitoring for 2 months without disruption of functional behavior. Morphing electronics offers a path toward growth-adaptive pediatric electronic medicine.


Subject(s)
Electronics, Medical/instrumentation , Electronics, Medical/methods , Implantable Neurostimulators , Animals , Biocompatible Materials/chemistry , Polymers/chemistry , Rats , Sciatic Nerve/physiology , Viscoelastic Substances/chemistry
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