Magnetic field assisted laser fabrication and electrical characterizations of metal dry Biolectrode with surface microstructures.

Magnetic field assisted laser fabrication is proposed to process metal dry bioelectrode with surface microstructures. The effects of magnetic flux density on the geometrical dimension of surface microstructures of bioelectrode is investigated. The electrode-skin contact impedance is then studied using the two-electrode measurement method. Finally, electromyography (EMG) signal is recorded using bioelectrodes processed in different magnetic flux density. Our results show that the magnetic field has obvious influences on the height and bottom width of microstructure of bioelectrode. When a magnetic field of 100 mT is selected, larger height-width ratio of microstructures is obtained, which provides a stronger ability to penetrate stratum corneum. Consequently, much lower contact impedance is obtained. Signal-noise ratio (SNR) of EMG signal shows a correlation coefficient of 0.9836 with height-width ratio of microstructures on the surface of metal dry bioelectrodes. Raw EMG signals recorded by metal dry bioelectrodes in 100 mT magnetic field show a high SNR up to 27.350, which is slightly higher than that of traditional Ag/AgCl wet bioelectrodes (26.689). By stationary wavelet transform (SWT) de-noising, noise interfused in raw EMG signals is suppressed effectively. Moreover, the de-noised EMG signal recorded using metal dry bioelectrodes processed in 100 mT magnetic field still remains a fairly high SNR.

Influence of the shielding effect on the formation of a micro-texture on the cermet with nanosecond pulsed laser ablation.

The degree of laser pulse overlapping in a laser scanning path has a significant impact on the ablation regime in the laser machining of a micro-texture. In this Letter, a nanosecond pulsed laser is used to prepare the micro-scaled groove on WC-8Co cermet under different scanning speeds. It is observed that as the scanning speed increases, the ablated trace morphology in the first scanning pass transits from a succession of intermittent deep dimples to the consecutive overlapped shallow pits. The test result also indicates that ablated trace morphology with respect to the low scanning speed stems from a plume shielding effect. Moreover, the ablation regime considering the shielding effect in micro-groove formation process is clarified. The critical scanning speed that can circumvent the shielding effect is also summarized with respect to different laser powers.

Fabrication of Composite Microneedle Array Electrode for Temperature and Bio-Signal Monitoring.

Body temperature and bio-signals are important health indicators that reflect the human health condition. However, monitoring these indexes is inconvenient and time-consuming, requires various instruments, and needs professional skill. In this study, a composite microneedle array electrode (CMAE) was designed and fabricated. It simultaneously detects body temperature and bio-signals. The CMAE consists of a 6 × 6 microneedles array with a height of 500 µm and a base diameter of 200 µm. Multiple insertion experiments indicate that the CMAE possesses excellent mechanical properties. The CMAE can pierce porcine skin 100 times without breaking or bending. A linear calibration relationship between temperature and voltage are experimentally obtained. Armpit temperature (35.8 °C) and forearm temperature (35.3 °C) are detected with the CMAE, and the measurements agree well with the data acquired with a clinical thermometer. Bio-signals including EII, ECG, and EMG are recorded and compared with those obtained by a commercial Ag/AgCl electrode. The CMAE continuously monitors bio-signals and is more convenient to apply because it does not require skin preparation and gel usage. The CMAE exhibits good potential for continuous and repetitive monitoring of body temperature and bio-signals.

Fabrication of Flexible Microneedle Array Electrodes for Wearable Bio-Signal Recording.

Laser-direct writing (LDW) and magneto-rheological drawing lithography (MRDL) have been proposed for the fabrication of a flexible microneedle array electrode (MAE) for wearable bio-signal monitoring. Conductive patterns were directly written onto the flexible polyethylene terephthalate (PET) substrate by LDW. The microneedle array was rapidly drawn and formed from the droplets of curable magnetorheological fluid with the assistance of an external magnetic field by MRDL. A flexible MAE can maintain a stable contact interface with curved human skin due to the flexibility of the PET substrate. Compared with Ag/AgCl electrodes and flexible dry electrodes (FDE), the electrode-skin interface impedance of flexible MAE was the minimum even after a 50-cycle bending test. Flexible MAE can record electromyography (EMG), electroencephalography (EEG) and static electrocardiography (ECG) signals with good fidelity. The main features of the dynamic ECG signal recorded by flexible MAE are the most distinguishable with the least moving artifacts. Flexible MAE is an attractive candidate electrode for wearable bio-signal monitoring.

Fabrication of a Micro-Needle Array Electrode by Thermal Drawing for Bio-Signals Monitoring.

A novel micro-needle array electrode (MAE) fabricated by thermal drawing and coated with Ti/Au film was proposed for bio-signals monitoring. A simple and effective setup was employed to form glassy-state poly (lactic-co-glycolic acid) (PLGA) into a micro-needle array (MA) by the thermal drawing method. The MA was composed of 6 × 6 micro-needles with an average height of about 500 µm. Electrode-skin interface impedance (EII) was recorded as the insertion force was applied on the MAE. The insertion process of the MAE was also simulated by the finite element method. Results showed that MAE could insert into skin with a relatively low compression force and maintain stable contact impedance between the MAE and skin. Bio-signals, including electromyography (EMG), electrocardiography (ECG), and electroencephalograph (EEG) were also collected. Test results showed that the MAE could record EMG, ECG, and EEG signals with good fidelity in shape and amplitude in comparison with the commercial Ag/AgCl electrodes, which proves that MAE is an alternative electrode for bio-signals monitoring.

Fabrication of Micro-Needle Electrodes for Bio-Signal Recording by a Magnetization-Induced Self-Assembly Method.

Micro-needle electrodes (MEs) have attracted more and more attention for monitoring physiological electrical signals, including electrode-skin interface impedance (EII), electromyography (EMG) and electrocardiography (ECG) recording. A magnetization-induced self-assembling method (MSM) was developed to fabricate a microneedle array (MA). A MA coated with Ti/Au film was assembled as a ME. The fracture and insertion properties of ME were tested by experiments. The bio-signal recording performance of the ME was measured and compared with a typical commercial wet electrode (Ag/AgCl electrode). The results show that the MA self-assembled from the magnetic droplet array under the sum of gravitational surface tension and magnetic potential energies. The ME had good toughness and could easily pierce rabbit skin without being broken or buckling. When the compression force applied on the ME was larger than 2 N, ME could stably record EII, which was a lower value than that measured by Ag/AgCl electrodes. EMG signals collected by ME varied along with the contraction of biceps brachii muscle. ME could record static ECG signals with a larger amplitude and dynamic ECG signals with more distinguishable features in comparison with a Ag/AgCl electrode, therefore, ME is an alternative electrode for bio-signal monitoring in some specific situations.

Ultra-low frequency magnetic energy focusing for highly effective wireless powering of deep-tissue implantable electronic devices.

The limited lifespan of batteries is a challenge in the application of implantable electronic devices. Existing wireless power technologies such as ultrasound, near-infrared light and magnetic fields cannot charge devices implanted in deep tissues, resulting in energy attenuation through tissues and thermal generation. Herein, an ultra-low frequency magnetic energy focusing (ULFMEF) methodology was developed for the highly effective wireless powering of deep-tissue implantable devices. A portable transmitter was used to output the low-frequency magnetic field (<50 Hz), which remotely drives the synchronous rotation of a magnetic core integrated within the pellet-like implantable device, generating an internal rotating magnetic field to induce wireless electricity on the coupled coils of the device. The ULFMEF can achieve energy transfer across thick tissues (up to 20 cm) with excellent transferred power (4-15 mW) and non-heat effects in tissues, which is remarkably superior to existing wireless powering technologies. The ULFMEF is demonstrated to wirelessly power implantable micro-LED devices for optogenetic neuromodulation, and wirelessly charged an implantable battery for programmable electrical stimulation on the sciatic nerve. It also bypassed thick and tough protective shells to power the implanted devices. The ULFMEF thus offers a highly advanced methodology for the generation of wireless powered biodevices.

Advances in Multifunctional Electronic Catheters for Precise and Intelligent Diagnosis and Therapy in Minimally Invasive Surgery.

The advent of catheter-based minimally invasive surgical instruments has provided an effective means of diagnosing and treating human disease. However, conventional medical catheter devices are limited in functionalities, hindering their ability to gather tissue information or perform precise treatment during surgery. Recently, electronic catheters have integrated various sensing and therapeutic technologies through micro/nanoelectronics, expanding their capabilities. As micro/nanoelectronic devices become more miniaturized, flexible, and stable, electronic surgical catheters are evolving from simple tools to multiplexed sensing and theranostics for surgical applications. The review on multifunctional electronic surgical catheters is lacking and thus is not conducive to the reader's comprehensive understanding of the development trend in this field. This review covers the advances in multifunctional electronic catheters for precise and intelligent diagnosis and therapy in minimally invasive surgery. It starts with the summary of clinical minimally invasive surgical instruments, followed by the background of current clinical catheter devices for sensing and therapeutic applications. Next, intelligent electronic catheters with integrated electronic components are reviewed in terms of electronic catheters for diagnosis, therapy, and multifunctional applications. It highlights the present status and development potential of catheter-based minimally invasive surgical devices, while also illustrating several significant challenges that remain to be overcome.

A smartphone-based fluorospectrophotometer and ratiometric fluorescence nanoprobe for on-site quantitation of pesticide residue.

Cost-effective and user-friendly quantitation at points-of-need plays an important role in food safety inspection, environmental monitoring, and biomedical analysis. This study reports a stand-alone smartphone-based fluorospectrophotometer (the SBS) installed with a custom-designed application (the SBS-App) for on-site quantitation of pesticide using a ratiometric sensing scheme. The SBS can collect fluorescence emission spectra in the wavelength range of 380-760 nm within 5 s. A ratiometric fluorescence probe is facilely prepared by directly mixing the blue-emissive carbon nanodots (the Fe3+-specific fluorometric indicator) and red-emissive quantum dots (the internal standard) at a ratio of 11.6 (w/w). Based on the acetylcholinesterase/choline oxidase dual enzyme-mediated cascade catalytic reactions of Fe2+/Fe3+ transformation, a ratiometric fluorescence sensing scheme is developed. The practicability of the SBS is validated by on-site quantitation of chlorpyrifos in apple and cabbage with a comparable accuracy to the GC-MS method, offering a scalable solution to establish a cost-effective surveillance system for pesticide pollution.

Development of Smartphone-Controlled and Microneedle-Based Wearable Continuous Glucose Monitoring System for Home-Care Diabetes Management.

Continuous glucose monitoring (CGM) can mini-invasively track blood glucose fluctuation and reduce the risk of hyperglycemia and hypoglycemia, and this is is in great demand for diabetes management. However, cost-effective manufacture of CGM systems with continuously improved convenience and performance is still the persistent goal. Herein, we developed a smartphone-controlled and microneedle (MN)-based wearable CGM system for long-term glucose monitoring. The CGM system modified with a sandwich-type enzyme immobilization strategy can satisfy the clinical requirement of interstitial fluid (ISF) glucose monitoring for 14 days with a mean absolute relative difference of 10.2% and a cost of less than $15, which correlated well with the commercial glucometer and FDA-approved CGM system FreeStyle Libre (Abbott Inc., Illinois, USA). The self-developed CGM system is demonstrated to accurately monitor glucose fluctuations and provide abundant clinical information. It is better to find the cause of individual blood glucose changes and beneficial for the guide of precise glucose control. On the whole, the intelligently wearable CGM system may provide an alternative solution for home-care diabetes management.

Coaxially printed magnetic mechanical electrical hybrid structures with actuation and sensing functionalities.

Soft electromagnetic devices have great potential in soft robotics and biomedical applications. However, existing soft-magneto-electrical devices would have limited hybrid functions and suffer from damaging stress concentrations, delamination or material leakage. Here, we report a hybrid magnetic-mechanical-electrical (MME) core-sheath fiber to overcome these challenges. Assisted by the coaxial printing method, the MME fiber can be printed into complex 2D/3D MME structures with integrated magnetoactive and conductive properties, further enabling hybrid functions including programmable magnetization, somatosensory, and magnetic actuation along with simultaneous wireless energy transfer. To demonstrate the great potential of MME devices, precise and minimally invasive electro-ablation was performed with a flexible MME catheter with magnetic control, hybrid actuation-sensing was performed by a durable somatosensory MME gripper, and hybrid wireless energy transmission and magnetic actuation were demonstrated by an untethered soft MME robot. Our work thus provides a material design strategy for soft electromagnetic devices with unexplored hybrid functions.

Using microneedle array electrodes for non-invasive electrophysiological signal acquisition and sensory feedback evoking.

Introduction: Bidirectional transmission of information is needed to realize a closed-loop human-machine interaction (HMI), where electrophysiological signals are recorded for man-machine control and electrical stimulations are used for machine-man feedback. As a neural interface (NI) connecting man and machine, electrodes play an important role in HMI and their characteristics are critical for information transmission. Methods: In this work, we fabricated a kind of microneedle array electrodes (MAEs) by using a magnetization-induced self-assembly method, where microneedles with a length of 500-600 µm and a tip diameter of ∼20 µm were constructed on flexible substrates. Part of the needle length could penetrate through the subjects' stratum corneum and reach the epidermis, but not touch the dermis, establishing a safe and direct communication pathway between external electrical circuit and internal peripheral nervous system. Results: The MAEs showed significantly lower and more stable electrode-skin interface impedance than the metal-based flat array electrodes (FAEs) in various testing scenarios, demonstrating their promising impedance characteristics. With the stable microneedle structure, MAEs exhibited an average SNR of EMG that is more than 30% higher than FAEs, and a motion-intention classification accuracy that is 10% higher than FAEs. The successful sensation evoking demonstrated the feasibility of the MAE-based electrical stimulation for sensory feedback, where a variety of natural and intuitive feelings were generated in the subjects and thereafter objectively verified through EEG analysis. Discussion: This work confirms the application potential of MAEs working as an effective NI, in both electrophysiological recording and electrical stimulation, which may provide a technique support for the development of HMI.

Iontophoresis-driven microneedle patch for the active transdermal delivery of vaccine macromolecules.

COVID-19 has seriously threatened public health, and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles (MNs) can damage the stratum corneum to allow passive diffusion of vaccine macromolecules, but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of the stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecule delivery. Polyacrylamide/chitosan hydrogels with good biocompatibility, excellent conductivity, high elasticity, and a large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is "press and poke, iontophoresis-driven delivery, and immune response". We demonstrated that the synergistic effect of MN puncture and iontophoresis significantly promoted transdermal vaccine delivery efficiency. In vitro experiments showed that the amount of ovalbumin delivered transdermally using the iontophoresis-driven MN patch could be controlled by the iontophoresis current. In vivo immunization studies in BALB/c mice demonstrated that transdermal inoculation of ovalbumin using an iontophoresis-driven MN patch induced an effective immune response that was even stronger than that of traditional intramuscular injection. Moreover, there was little concern about the biosafety of the iontophoresis-driven MN patch. This delivery system has a low cost, is user-friendly, and displays active delivery, showing great potential for vaccine self-administration at home.

Implantable magnetically-actuated capsule for on-demand delivery.

Many implantable drug delivery systems (IDDS) have been developed for long-term, pulsatile drug release. However, they are often limited by bulky size, complex electronic components, unpredictable drug delivery, as well as the need for battery replacement and consequent replacement surgery. Here, we develop an implantable magnetically-actuated capsule (IMAC) and its portable magnetic actuator (MA) for on-demand and robust drug delivery in a tether-free and battery-free manner. IMAC utilizes the bistable mechanism of two magnetic balls inside IMAC to trigger drug delivery under a strong magnetic field (|Ba| > 90 mT), ensuring precise and reproducible drug delivery (9.9 ± 0.17 µg per actuation, maximum actuation number: 180) and excellent anti-magnetic capability (critical trigger field intensity: ∼90 mT). IMAC as a tetherless robot can navigate to and anchor at the lesion sites driven by a gradient magnetic field (∇ Bg = 3 T/m, |Bg| < 60 mT), and on-demand release drug actuated by a uniform magnetic field (|Ba| = âˆ¼100 mT) within the gastrointestinal tract. During a 15-day insulin administration in vivo, the diabetic rats treated with IMAC exhibited highly similar pharmacokinetic and pharmacodynamic profiles to those administrated via subcutaneous injection, demonstrating its robust and on-demand drug release performance. Moreover, IMAC is biocompatible, batter-free, refillable, miniature (only Φ 6.3 × 12.3 mm3), and lightweight (just 0.8 g), making it an ideal alternative for precise implantable drug delivery and friendly patient-centered drug administration.

Development of enzyme-inorganic hybrid nanoflower-modified electrodes and a smartphone-controlled electrochemical analyzer for point-of-care testing of salivary amylase in saliva.

Quantitation of salivary alpha-amylase (sAA) plays a significant role in not only theoretical studies but also clinical practice. This study reports a quantitative point-of-care testing (POCT) system for sAA quantitation anywhere, anytime and by anyone, which consists of customized electrodes and a smartphone-controlled electrochemical analyzer. Organic-inorganic hybrid nanoflowers (NFs) encapsulating α-glucosidase (AG) and glucose dehydrogenase (GDH) have been synthesized and modified onto screen-printed electrodes (SPCEs) to fabricate the customized electrodes. The SPCEs integrated with the smartphone-controlled electrochemical analyzer exhibit good analytical performance for sAA with a low detection limit of 5.02 U mL-1 and a wide dynamic range of 100-2000 U mL-1 using chronoamperometry. The reported POCT system has been successfully demonstrated for quantitation of sAA in clinical saliva samples, and the quantitation results correlated well with those of the Bernfeld method which is extensively used in clinics. More importantly, this study reveals the great potential of sAA as an early warning indicator of abnormal glucose metabolism in obese individuals. Considering the non-invasive saliva sampling process as well as the easy-to-use and cost-effectiveness features of this quantitative POCT system, quantitation of salivary sAA at home by laypersons might become an appealing choice for obese individuals to monitor their glucose metabolism status anytime.

Ferromagnetic Flexible Electronics for Brain-Wide Selective Neural Recording.

Flexible microelectronics capable of straightforward implantation, remotely controlled navigation, and stable long-term recording hold great promise in diverse medical applications, particularly in deciphering complex functions of neural circuits in the brain. Existing flexible electronics, however, are often limited in bending and buckling during implantation, and unable to access a large brain region. Here, an injectable class of electronics with stable recording, omnidirectional steering, and precise navigating capabilities based on magnetic actuation is presented. After simple transcriptional injection, the rigid coatings are biodegraded quickly and the bundles of magnetic-nanoparticles-coated microelectrodes become separated, ultra-flexible, and magnetic actuated for further minimally invasive three-dimensional interpenetration in the brain. As proof of concept, this paradigm-shifting approach is demonstrated for selective and multiplexed neural activities recording across distant regions in the deep rodent brains. Coupling with optogenetic neural stimulation, the unique capabilities of this platform in electrophysiological readouts of projection dynamics in vivo are also demonstrated. The ability of these miniaturized, remotely controllable, and biocompatible ferromagnetic flexible electronics to afford minimally invasive manipulations in the soft tissues of the mammalian brain foreshadows applications in other organ systems, with great potential for broad utility in biomedical science and engineering.

3D Bioprinting of Living Materials for Structure-Dependent Production of Hyaluronic Acid.

3D bioprinting of living materials represents an interesting paradigm toward the efficacy enhancement for the biosynthesis of various functional compounds in microorganisms. Previous studies have shown the success of 3D-printed bioactive systems in the production of small molecular compounds. However, the feasibility of such a strategy in producing macromolecules and how the geometry of the 3D scaffold influences the productivity are still unknown. In this study, we printed a series of 3D gelatin-based hydrogels immobilized with fermentation bacteria that can secrete hyaluronic acid (HA), a very useful natural polysaccharide in the fields of biomedicine and tissue engineering. The 3D-printed bioreactor was capable of producing HA, and an elevated yield was obtained with the system bearing a grid structure compared to that either with a solid structure or in a scaffold-free fermentation condition. As for the grid structure, bioreactors with a 90° strut angel and a median interfilament distance displayed the highest HA yield. Our findings highlighted the significant role of 3D printing in the spatial control of microorganism-laden hydrogel structures for the enhancement of biosynthesis efficiency.

Solid-Liquid State Transformable Magnetorheological Millirobot.

Magnetically actuated soft millirobots (magneto-robot) capable of accomplishing on-demand tasks in a remote-control manner using noninvasive magnetic fields are of great interest in biomedical settings. However, the solid magneto-robots are usually restricted by the limited deformability due to the predesigned shape, while the liquid magneto-robots are capable of in situ shape reconfiguration but limited by the low stiffness and geometric instability due to the fluidity. Herein, we propose a magneto-active solid-liquid state transformable millirobot (named MRF-Robot) made from a magnetorheological fluid (MRF). The MRF-Robot can transform freely and rapidly between the Newtonian fluid in the liquid state upon a weak magnetic field (∼0 mT) and the Bingham plasticity in the solid state upon a strong magnetic field (∼100 mT). The MRF-Robot in the liquid state can realize diverse behaviors of large deformation, smooth navigation, in situ splitting, merging, and gradient pulling actuated by a weak magnetic field with a high gradient. The MRF-Robot in the solid state is distinguished for the controllable locomotion with reconfigured shapes and versatile object manipulations (including pull, push, and rotate the objects) driven by a strong magnetic field with a high gradient. Moreover, the MRF-Robot could continuously maneuver to accomplish diverse tasks in the comprehensive scenes and achieve liquid-drug delivery, thrombus clearance, and fluid-flow blockage in the phantom vascular model under magnetic actuation.

Recent Progress in Microneedles-Mediated Diagnosis, Therapy, and Theranostic Systems.

Theranostic system combined diagnostic and therapeutic modalities is critical for the real-time monitoring of disease-related biomarkers and personalized therapy. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. They have shown attractive properties including painless skin penetration, easy self-administration, prominent therapeutic effects, and good biosafety. Herein, an overview of the microneedles-based diagnosis, therapies, and theranostic systems is given. Four microneedles-based detection methods are concluded based on the sensing mechanism: i) electrochemistry, ii) fluorometric, iii) colorimetric, and iv) Raman methods. Additionally, robust microneedles are suitable for implantable drug delivery. Microneedles-assisted transdermal drug delivery can be primarily classified as passive, active, and responsive drug release, based on the release mechanisms. Microneedles-assisted oral and implantable drug delivery mechanisms are also presented in this review. Furthermore, the key frontier developments in microneedles-mediated theranostic systems as the major selling points are emphasized in this review. These systems are classified into open-loop and closed-loop theranostic systems based on the indirectness and directness of feedback between the transdermal diagnosis and therapy, respectively. Finally, conclusions and future perspectives for next-generation microneedles-mediated theranostic systems are also discussed. Taken together, microneedle-based systems are promising as the new avenue for diagnosis, therapy, and disease-specific closed-loop theranostic applications.

Masticatory system-inspired microneedle theranostic platform for intelligent and precise diabetic management.

Integrated systems for diabetic theranostics present advanced technology to regulate diabetes yet still have critical challenges in terms of accuracy, long-term monitoring, and minimal invasiveness. Inspired by the feature and functions of animal masticatory system, we presented a biomimetic microneedle theranostic platform (MNTP) for intelligent and precise management of diabetes. The MNTP was supported by a miniatured circuit, which used microneedle arrays for on-demand skin penetration, enabling interstitial fluid exudation for simultaneous detection of glucose and physiological ions, and subcutaneous insulin delivery. Interstitial fluid exudation enabled sensing in oxygen-rich environment via the incorporated epidermal sensor functionalized with hybrid carbon nanomaterials. This feature addressed the biosafety issues due to implanted electrodes and the "oxygen-deficit" issues in vivo. The MNTP was demonstrated to accurately detect glucose and ions and deliver insulin to regulate hyperglycemia. The biomimetic and intelligent features of the MNTP endowed it as a highly advanced system for diabetes therapy.