A drug-loaded flexible substrate improves the performance of conformal cortical electrodes

Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.

Progress in Mechanical Modeling of Implantable Flexible Neural Probes

Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.

Flexible capacitive pressure sensor based on interdigital electrodes with porous microneedle arrays for physiological signal monitoring

Flexible pressure sensors have many potential applications in the monitoring of physiological signals because of their good biocompatibil-ity and wearability.However,their relatively low sensitivity,linearity,and stability have hindered their large-scale commercial application.Herein,aflexible capacitive pressure sensor based on an interdigital electrode structure with two porous microneedle arrays(MNAs)is pro-posed.The porous substrate that constitutes the MNA is a mixed product of polydimethylsiloxane and NaHCO3.Due to its porous and interdigital structure,the maximum sensitivity(0.07 kPa-1)of a porous MNA-based pressure sensor was found to be seven times higher than that of an imporous MNA pressure sensor,and it was much greater than that of aflat pressure sensor without a porous MNA structure.Finite-element analysis showed that the interdigital MNA structure can greatly increase the strain and improve the sensitivity of the sen-sor.In addition,the porous MNA-based pressure sensor was found to have good stability over 1500 loading cycles as a result of its bilayer parylene-enhanced conductive electrode structure.Most importantly,it was found that the sensor could accurately monitor the motion of afinger,wrist joint,arm,face,abdomen,eye,and Adam’s apple.Furthermore,preliminary semantic recognition was achieved by monitoring the movement of the Adam’s apple.Finally,multiple pressure sensors were integrated into a 33 array to detect a spatial pressure distribu-×tion.Compared to the sensors reported in previous works,the interdigital electrode structure presented in this work improves sensitivity and stability by modifying the electrode layer rather than the dielectric layer.

Smart epidermal electrophysiological electrodes:Materials,structures,and algorithms

Epidermal electrophysiological monitoring has garnered significant attention for its potential in medical diagnosis and healthcare,particularly in continuous signal recording.However,simultaneously satisfying skin compliance,mechanical properties,environmental adaptation,and biocompatibility to avoid signal attenuation and motion artifacts is challenging,and accurate physiological feature extraction necessitates effective signal-processing algorithms.This review presents the latest advancements in smart electrodes for epidermal electrophysiological monitoring,focusing on materials,structures,and algorithms.First,smart materials incorporating self-adhesion,self-healing,and self-sensing functions offer promising solutions for long-term monitoring.Second,smart meso-structures,together with micro/nanostructures endowed the electrodes with self-adaption and multifunctionality.Third,intelligent algorithms give smart electrodes a“soul,”facilitating faster and more-accurate identification of required information via automatic processing of collected electrical signals.Finally,the existing challenges and future opportunities for developing smart electrodes are discussed.Recognized as a crucial direction for next-generation epidermal electrodes,intelligence holds the potential for extensive,effective,and transformative applications in the future.

Flexible polyimide-based hybrid optoelectric neural interface with 16 channels of micro-LEDs and electrodes

In this paper,a polyimide-based flexible device that integrates 16 micro-LEDs and 16 IrO_(x)-modified microelectrodes for synchronous photostimulation and neural signal recording is presented.The 4×4 micro-LEDs(dimensions of 220×270×50μm^(3),700μm pitch)are fixed in the SU-8 fence structure on a polyimide substrate and connected to the leads via a wire-bonding method.The recording electrodes share a similar fabrication process on the polyimide with 16 microelectrode sites(200μm in diameter and 700μm in pitch)modified by iridium oxide(IrO_(x)).These two subparts can be aligned with alignment holes and glued back-to-back by epoxy,which ensures that the light from the LEDs passes through the corresponding holes that are evenly distributed around the recording sites.The long-term electrical and optical stabilities of the device are verified using a soaking test for 3 months,and the thermal property is specifically studied with different duty cycles,voltages,and frequencies.Additionally,the electrochemical results prove the reliability of the IrO_(x)-modified microelectrodes after repeated pressing or friction.To evaluate the tradeoff between flexibility and strength,two microelectrode arrays with thicknesses of 5 and 10μm are evaluated through simulation and experiment.The proposed device can be a useful mapping optogenetics tool for neuroscience studies in small(rats and mice)and large animal subjects and ultimately in nonhuman primates.

Brainmask:an ultrasoft and moist microelectrocorticography electrode for accurate positioning and long-lasting recordings

Bacterial cellulose(BC),a natural biomaterial synthesized by bacteria,has a unique structure of a cellulose nanofiberweaved three-dimensional reticulated network.BC films can be ultrasoft with sufficient mechanical strength,strong water absorption and moisture retention and have been widely used in facial masks.These films have the potential to be applied to implantable neural interfaces due to their conformality and moisture,which are two critical issues for traditional polymer or silicone electrodes.In this work,we propose a micro-electrocorticography(micro-ECoG)electrode named“Brainmask”,which comprises a BC film as the substrate and separated multichannel parylene-C microelectrodes bonded on the top surface.Brainmask can not only guarantee the precise position of microelectrode sites attached to any nonplanar epidural surface but also improve the long-lasting signal quality during acute implantation with an exposed cranial window for at least one hour,as well as the in vivo recording validated for one week.This novel ultrasoft and moist device stands as a next-generation neural interface regardless of complex surface or time of duration.

Stretchable Parylene-C electrodes enabled by serpentine structures on arbitrary elastomers by silicone rubber adhesive

The delicate serpentine structures are widely used in high-performance stretchable electronics over the past decade.The metal interconnects encapsulated in biocompatible polymer Parylene-C film is a superior choice for long-term implantation in vivo,especially as neural interface to acquire electrophysiological signals or apply electrical stimulation.To avoid the physical contact damages from the neural tissues such as the brain or peripheral nerves,serpentine interconnects are utilized as stretchable electrodes and usually bonded to the soft elastomer substrate.The adhesion strength between the serpentine interconnects and the elastomer substrate becomes a considerable issue to ensure reliability and structural integrity.In this paper,the stretchable Parylene-C electrodes can be transfer printed onto arbitrary elastomer substrates by a thin layer of silicone rubber adhesive with low modulus for electrocorticogram(ECoG)recording.Mechanical simulation of serpentine structures consisting of same periodic arcs and different straight segments is investigated by uniaxial stretching.Then,the elastic stretchability of serpentine electrodes is further studied by simulation and experiments.After 5000 repetitive stretching cycles,the electrochemical impedance of microelectrodes remains in steady states.These results prove that the silicone rubber adhesive facilitates the interfacial bonding in the structure of stretchable electrodes as the compliant and reliable neural interface.