Focused Epicranial Brain Stimulation by Spatial Sculpting of Pulsed Electric Fields Using High Density Electrode Arrays.

Transcranial electrical neuromodulation of the central nervous system is used as a non-invasive method to induce neural and behavioral responses, yet targeted non-invasive electrical stimulation of the brain with high spatial resolution remains elusive. This work demonstrates a focused, steerable, high-density epicranial current stimulation (HD-ECS) approach to evoke neural activity. Custom-designed high-density (HD) flexible surface electrode arrays are employed to apply high-resolution pulsed electric currents through skull to achieve localized stimulation of the intact mouse brain.

Residual voltage as an ad-hoc indicator of electrode damage in biphasic electrical stimulation.

We derive and demonstrate how residual voltage (RV) from a biphasic electrical stimulation pulse can be used to recognize degradation at the electrode-tissue interface.Using a first order model of the electrode-tissue interface and a rectangular biphasic stimulation current waveform, we derive the equations for RV as well as RV growth over several stimulation pulses. To demonstrate the use of RV for damage detection, we simulate accelerated damage on sputtered iridium oxide film (SIROF) electrodes using potential cycling.

Hydrogel-based electrodes for selective cervical vagus nerve stimulation.

Electrical vagus nerve stimulation (VNS) has the potential to treat a wide variety of diseases by modulating afferent and efferent communication to the heart, lungs, esophagus, stomach, and intestines. Although distal vagal nerve branches, close to end organs, could provide a selective therapeutic approach, these locations are often surgically inaccessible. In contrast, the cervical vagus nerve has been targeted for decades using surgically implantable helix electrodes to treat epileptic seizures and depression; however, to date, clinical implementation of VNS has relied on an electrode with contacts that fully wrap around the nerve, producing non-selective activation of the entire nerve.

Inkjet Printing of Curing Agent on Thin PDMS for Local Tailoring of Mechanical Properties.

Rapid prototyping of thin, stretchable substrates with engineered stiffness gradients at desired locations has potential impact in the robustness of skin-wearable electronics, as the gradients can inhibit cracking of interconnect and delamination of embedded electronic chips. Drop-on-demand inkjetting of thinned polydimethylsiloxane (PDMS) curing agent onto a spin-cast 80 µm-thick 20:1 (base: curing agent) PDMS substrate sets the elastic modulus of the subsequently cured film with sub-millimeter accuracy. The inkjet process creates digitally defined stiffness gradient spans as small as 100 µm for single droplets.

Parylene neural probe with embedded CMOS multiplexing amplifier.

We present a method for embedding integrated circuit chips in parylene neural probes where Anisotropic Conductive Film (ACF) electrically and physically connects the chip to the probe. Adequate insulation of the assembly is verified up to 150 h in vitro (testing ongoing). A custom-designed 8-to-1 multiplexing amplifier for neural application was fabricated in a 0.

Insulation of thin-film parylene-C/platinum probes in saline solution through encapsulation in multilayer ALD ceramic films.

The long-term electrical leakage performance of parylene-C/platinum/parylene-C (Px/Pt/Px) interconnect in saline is evaluated using electrochemical impedance spectroscopy (EIS). Three kinds of additional ceramic encapsulation layers between the metal and Px are characterized: 50 nm-thick alumina (AlO), 50 nm-thick titania (TiO), and 80 nm-thick AlO-TiO nanolaminate (NL). The AlO and TiO encapsulation layers worsen the overall insulation properties.

The role of hierarchical design and morphology in the mechanical response of diatom-inspired structures via simulation.

Diatoms are microscopic algae with intricate shell morphologies and features ranging from the nanometer to the micrometer scale, which have been proposed as templates for drug delivery carriers, optical devices, and metamaterials design. Several studies have found that diatom shells show unique mechanical properties such as high specific strength and resilience. One hypothesis is that these properties stem from the structural arrangement of the material at the nanometer and micrometer length scales, challenging the concept between what constitutes a "material" versus a "structure".

A silicon neural probe fabricated using DRIE on bonded thin silicon.

A silicon neural probe fabricated using a deep reactive ion etching based process on 250 μm thin silicon wafers was developed. The fabricated probes replicate the design of soft parylene-C based probes embedded in dissolvable needles and can therefore also be used to test the encapsulation properties of parylene-C in-vivo without introducing additional effects introduced by the dissolvable gel. The process also demonstrates the possibility of performing conventional photolithography on substrates bonded to a handle wafer using a backgrinding liquid wax (BGL7080) as an adhesive.

Elastic ribbon-like piezoelectric energy harvester for wearable devices with stretchable surfaces.

This paper presents an elastic ribbon-like piezoelectric energy harvester which is targeted for skin-wearable devices by harnessing the movements of stretchable surfaces. The device aims to power up smart thin stick-on devices for healthcare monitoring. By embedding a ribbon-like PVDF film in a flexible elastomer, Ecoflex, the device is potentially able to stretch 34%, while maintaining internal strain of the film below its plastic deformation limit.

Ultra-miniature ultra-compliant neural probes with dissolvable delivery needles: design, fabrication and characterization.

Stable chronic functionality of intracortical probes is of utmost importance toward realizing clinical application of brain-machine interfaces. Sustained immune response from the brain tissue to the neural probes is one of the major challenges that hinder stable chronic functionality. There is a growing body of evidence in the literature that highly compliant neural probes with sub-cellular dimensions may significantly reduce the foreign-body response, thereby enhancing long term stability of intracortical recordings.

Material Gradients in Stretchable Substrates toward Integrated Electronic Functionality.

The approach toward a stretchable electronic substrate employs multiple soft polymer layers patterned around silicon chips, which act as surrogates for conventional electronics chips, to create a controllable stiffness gradient. Adding just one intermediate polymer layer results in a six-fold increase in the strain failure threshold enabling the substrate to be stretched to over twice its length before delamination occurs.

Chronic tissue response to carboxymethyl cellulose based dissolvable insertion needle for ultra-small neural probes.

Implantable neural electrodes must drastically improve chronic recording stability before they can be translated into long-term human clinical prosthetics. Previous studies suggest that sub-cellular sized and mechanically compliant probes may result in improved tissue integration and recording longevity. However, currently these design features are restricted by the opposing mechanical requirements needed for minimally damaging insertions.

Characterization of a CMOS sensing core for ultra-miniature wireless implantable temperature sensors with application to cryomedicine.

In effort to improve thermal control in minimally invasive cryosurgery, the concept of a miniature, wireless, implantable sensing unit has been developed recently. The sensing unit integrates a wireless power delivery mechanism, wireless communication means, and a sensing core-the subject matter of the current study. The current study presents a CMOS ultra-miniature PTAT temperature sensing core and focuses on design principles, fabrication of a proof-of-concept, and characterization in a cryogenic environment.

Ultra-compliant neural probes are subject to fluid forces during dissolution of polymer delivery vehicles.

Ultra-compliant neural probes implanted into tissue using a molded, biodissolvable sodium carboxymethyl cellulose (Na-CMC)-saccharide composite needle delivery vehicle are subjected to fluid-structure interactions that can displace the recording site of the probe with respect to its designed implant location. We applied particle velocimetry to analyze the behavior of ultra-compliant structures under different implantation conditions for a range of CMC-based materials and identified a fluid management protocol that resulted in the successful targeted depth placement of the recording sites.

Ultra-miniature wireless temperature sensor for thermal medicine applications.

This study presents a prototype design of an ultra-miniature, wireless, battery-less, and implantable temperature-sensor, with applications to thermal medicine such as cryosurgery, hyperthermia, and thermal ablation. The design aims at a sensory device smaller than 1.5 mm in diameter and 3 mm in length, to enable minimally invasive deployment through a hypodermic needle.

Robust gold nanoparticles stabilized by trithiol for application in chemiresistive sensors.

The use of gold nanoparticles coated with an organic monolayer of thiol for application in chemiresistive sensors was initiated in the late 1990s; since then, such types of sensors have been widely pursued due to their high sensitivities and reversible responses to volatile organic compounds (VOCs). However, a major issue for chemical sensors based on thiol-capped gold nanoparticles is their poor long-term stability as a result of slow degradation of the monothiol-to-gold bonds. We have devised a strategy to overcome this limitation by synthesizing a more robust system using Au nanoparticles capped by trithiol ligands.

Picogram material dosing of microstructures.

A solution delivery platform comprised of a suspended microcapillary connected to a microwell enables picogram solute deposition on suspended structures. Precision material placement in the capillary from a 100 pl drop inkjetted into the well is achieved without the destruction of the microstructure and adjacent submicron electrostatic gaps. This method scales to smaller structures without the need for drop miniaturization.

Endoscopic optical coherence tomography based on a microelectromechanical mirror.

An endoscopic optical coherence tomography (OCT) system based on a microelectromechanical mirror to facilitate lateral light scanning is described. The front-view OCT scope, adapted to the instrument channel of a commercial endoscopic sheath, allows real-time cross-sectional imaging of living biological tissue via direct endoscopic visual guidance. The transverse and axial resolutions of the OCT scope are roughly 20 and 10.

The effect of a distributed mass loading on the frequency response of a MEMS mesh resonator.

This paper reports on the development of an acoustic-wave biosensor based on integrated MEMS technology that promises high sensitivity and selectively without the need for molecular tagging or external optical equipment. The device works by detecting frequency shifts resulting from the selective binding of target molecules to the surface of a functionalized resonating polymer MEMS-composite membrane. Here, we characterize the frequency response of our metal-oxide MEMS resonators.

Multiple Mycobacterium tuberculosis infections in an HIV-infected patient.

Mycobacterial colonies of two different morphologies were isolated from one sputum sample of a HIV-positive patient. One morphological type was resistant to streptomycin (STR) and susceptible to isoniazid (INH), while the other isolate with different colony morphology was resistant to both of these anti-TB drugs. A mycobacterial isolate of one pus from a lymph node sample was resistant to these two anti-TB drugs, while the other isolate from another pus sample was resistant to STR but susceptible INH.

BioImplantable Bone Stress Sensor.

The clinical management of skeletal trauma and disease relies on radiographic imaging to infer bone quality. However, bone strength does not necessarily correlate well with image intensity. There is a need for a safe and convenient way to measure bone strength in situ.

Volatile organic compound detection using nanostructured copolymers.

Regioregular polythiophene-based conductive copolymers with highly crystalline nanostructures are shown to hold considerable promise as the active layer in volatile organic compound (VOC) chemresistor sensors. While the regioregular polythiophene polymer chain provides a charge conduction path, its chemical sensing selectivity and sensitivity can be altered either by incorporating a second polymer to form a block copolymer or by making a random copolymer of polythiophene with different alkyl side chains. The copolymers were exposed to a variety of VOC vapors, and the electrical conductivity of these copolymers increased or decreased depending upon the polymer composition and the specific analytes.

Endoscopic optical coherence tomography with a modified microelectromechanical systems mirror for detection of bladder cancers.

Experimental results of a modified micromachined microelectromechanical systems (MEMS) mirror for substantial enhancement of the transverse laser scanning performance of endoscopic optical coherence tomography (EOCT) are presented. Image distortion due to buckling of MEMS mirror in our previous designs was analyzed and found to be attributed to excessive internal stress of the transverse bimorph meshes. The modified MEMS mirror completely eliminates bimorph stress and the resultant buckling effect, which increases the wobbling-free angular optical actuation to greater than 37 degrees, exceeding the transverse laser scanning requirements for EOCT and confocal endoscopy.

Acute, painful, and swollen testicle as the presenting feature in polyarteritis nodosa.

A 74-year-old man presented with spiking fever, myalgias, and a painful left testicle. A diagnosis of polyarteritis nodosa (PAN) was made. Corticosteroids, in combination with cyclophosphamide, induced clinical remission.