Smart Hydrogel Swelling State Detection Based on a Power-Transfer Transduction Principle.

Stimulus-responsive (smart) hydrogels are a promising sensing material for biomedical contexts due to their reversible swelling change in response to target analytes. The design of application-specific sensors that utilize this behavior requires the development of suitable transduction concepts. The presented study investigates a power-transfer-based readout approach that is sensitive to small volumetric changes of the smart hydrogel.

Development of a feline model for preclinical research of a new translabyrinthine auditory nerve implant.

Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers.

Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy.

Objective: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity.

Physics-Based Circuit Modeling of the Impedance Characteristics of a Smart Hydrogel-Actuated Bending Sensor.

Smart hydrogels are stimuli-responsive polymers which exhibit a volume-phase transition in response to external influences. This makes them promising candidates for sensing elements, especially in a biomedical context due to their easily achievable biocompatibility. The main challenge in harnessing the smart polymer's potential for sensor applications lies in a reliable transduction of the swelling change into an electrical signal.

Flexural bending to approximate cortical forces exerted by electrocorticography (ECoG) arrays.

The force that an electrocorticography (ECoG) array exerts on the brain manifests when it bends to match the curvature of the skull and cerebral cortex. This force can negatively impact both short-term and long-term patient outcomes. Here we provide a mechanical characterization of a novel liquid crystal polymer (LCP) ECoG array prototype to demonstrate that its thinner geometry reduces the force potentially applied to the cortex of the brain.

Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue.

Catheter-mounted smart hydrogel ultrasound resonators for intravenous analyte monitoring.

Continuous monitoring of drug concentrations in blood plasma can be beneficial to guide individualized drug administration. High interpatient variability in required dosage and a small therapeutic window of certain drugs, such as anesthetic medications, can cause risks and challenges in accurate dosing during administration. In this work, we present a sensing platform concept using a smart hydrogel micro resonator sheet with medical ultrasound readout that is integrated on the top of a catheter.

Monitoring of Glucose Using Ultrasound-Induced Resonance in Implantable Smart Hydrogel Microstructures.

A novel glucose sensor is presented using smart hydrogels as biocompatible implantable sensing elements, which eliminates the need for implanted electronics and uses an external medical-grade ultrasound transducer for readout. The readout mechanism uses resonance absorption of ultrasound waves in glucose-sensitive hydrogels. glucose concentration changes in the interstitial fluid lead to swelling or deswelling of the gels, which changes the resonance behavior.

Flexible, high-resolution thin-film electrodes for human and animal neural research.

Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans.

Smart Hydrogel Micromechanical Resonators with Ultrasound Readout for Biomedical Sensing.

One of the main challenges for implantable biomedical sensing schemes is obtaining a reliable signal while maintaining biocompatibility. In this work, we demonstrate that a combination of medical ultrasound imaging and smart hydrogel micromechanical resonators can be employed for continuous monitoring of analyte concentrations. The sensing principle is based on the shift of the mechanical resonance frequencies of smart hydrogel structures induced by their volume-phase transition in response to changing analyte levels.

Advances in Penetrating Multichannel Microelectrodes Based on the Utah Array Platform.

The Utah electrode array (UEA) and its many derivatives have become a gold standard for high-channel count bi-directional neural interfaces, in particular in human subject applications. The chapter provides a brief overview of leading electrode concepts and the context in which the UEA has to be understood. It goes on to discuss the key advances and developments of the UEA platform in the past 15 years, as well as novel wireless and system integration technologies that will merge into future generations of fully integrated devices.

Low-Cost Microfluidic Sensors with Smart Hydrogel Patterned Arrays Using Electronic Resistive Channel Sensing for Readout.

There is a strong commercial need for inexpensive point-of-use sensors for monitoring disease biomarkers or environmental contaminants in drinking water. Point-of-use sensors that employ smart polymer hydrogels as recognition elements can be tailored to detect almost any target analyte, but often suffer from long response times. Hence, we describe here a fabrication process that can be used to manufacture low-cost point-of-use hydrogel-based microfluidics sensors with short response times.

Neural electrode resilience against dielectric damage may be improved by use of highly doped silicon as a conductive material.

Background: Dielectric damage occurring in vivo to neural electrodes, leading to conductive material exposure and impedance reduction over time, limits the functional lifetime and clinical viability of neuroprosthetics. We used silicon micromachined Utah Electrode Arrays (UEAs) with iridium oxide (IrO) tip metallization and parylene C dielectric encapsulation to understand the factors affecting device resilience and drive improvements.

New Method: In vitro impedance measurements and finite element analyses were conducted to evaluate how exposed surface area of silicon and IrO affect UEA properties.

Long term performance of porous platinum coated neural electrodes.

Over the last several years, there has been a growing interest in neural implants for the study and diagnostics of neurological disorders as well as for the symptomatic treatment of central nervous system related diseases. One of the major challenges is the trade-off between small electrode sizes for high selectivity between single neurons and large electrode-tissue interface areas for excellent stimulation and recording properties. This paper presents an approach of increasing the real surface area of the electrodes by creating a surface microstructure.

Analysis of AlO-parylene C bilayer coatings and impact of microelectrode topography on long term stability of implantable neural arrays.

Objective: Performance of many dielectric coatings for neural electrodes degrades over time, contributing to loss of neural signals and evoked percepts. Studies using planar test substrates have found that a novel bilayer coating of atomic-layer deposited (ALD) AlO and parylene C is a promising candidate for neural electrode applications, exhibiting superior stability to parylene C alone. However, initial results from bilayer encapsulation testing on non-planar devices have been less positive.

Different methods to alter surface morphology of high aspect ratio structures.

In various applications such as neural prostheses or solar cells, there is a need to alter the surface morphology of high aspect ratio structures so that the real surface area is greater than geometrical area. The change in surface morphology enhances the devices functionality. One of the applications of altering the surface morphology is of neural implants such as the Utah electrode array (UEA) that communicate with single neurons by charge injection induced stimulation or by recording electrical neural signals.

Local release of masitinib alters in vivo implantable continuous glucose sensor performance.

Continuous glucose monitoring (CGM) sensors are often advocated as a clinical solution to improve long-term glycemic control in the context of diabetes. Subcutaneous sensor inflammatory response, fouling and fibrous encapsulation resulting from the host foreign body response (FBR) reduce sensor sensitivity to glucose, eventually resulting in sensor performance compromise and device failure. Several combination device strategies load CGM sensors with drug payloads that release locally to tissue sites to mitigate FBR-mediated sensor failure.

Effect of bias voltage and temperature on lifetime of wireless neural interfaces with Al ₂O₃ and parylene bilayer encapsulation.

The lifetime of neural interfaces is a critical challenge for chronic implantations, as therapeutic devices (e.g., neural prosthetics) will require decades of lifetime.

SELF ALIGNED TIP DEINSULATION OF ATOMIC LAYER DEPOSITED ALO AND PARYLENE C COATED UTAH ELECTRODE ARRAY BASED NEURAL INTERFACES.

The recently developed alumina and Parylene C bi-layer encapsulation improved the lifetime of neural interfaces. Tip deinsulation of Utah electrode array based neural interfaces is challenging due to the complex 3D geometries and high aspect ratios of the devices. A three-step self-aligned process was developed for tip deinsulation of bilayer encapsulated arrays.

Long-term reliability of Al2O3 and Parylene C bilayer encapsulated Utah electrode array based neural interfaces for chronic implantation.

Objective: We focus on improving the long-term stability and functionality of neural interfaces for chronic implantation by using bilayer encapsulation.

Approach: We evaluated the long-term reliability of Utah electrode array (UEA) based neural interfaces encapsulated by 52 nm of atomic layer deposited Al2O3 and 6 µm of Parylene C bilayer, and compared these to devices with the baseline Parylene-only encapsulation. Three variants of arrays including wired, wireless, and active UEAs were used to evaluate this bilayer encapsulation scheme, and were immersed in phosphate buffered saline (PBS) at 57 °C for accelerated lifetime testing.

Collaborative approach in the development of high-performance brain-computer interfaces for a neuroprosthetic arm: translation from animal models to human control.

Our research group recently demonstrated that a person with tetraplegia could use a brain-computer interface (BCI) to control a sophisticated anthropomorphic robotic arm with skill and speed approaching that of an able-bodied person. This multiyear study exemplifies important principles in translating research from foundational theory and animal experiments into a clinical study. We present a roadmap that may serve as an example for other areas of clinical device research as well as an update on study results.

Deep-tissue light delivery via optrode arrays.

We establish performance characteristics of needle-type waveguides in three-dimensional array architectures as light delivery interfaces into deep tissue for applications, such as optogenetic and infrared (IR) neural stimulation. A single optrode waveguide achieves as high as 90% transmission efficiency, even at tissue depths >1  mm. Throughout the visible and near-IR spectrum, the effective light attenuation through the waveguide is ∼3 orders of magnitude smaller than attenuation in tissue/water, as confirmed by both simulation and experimental results.

Foreign body response to subcutaneous biomaterial implants in a mast cell-deficient Kit(w-Sh) murine model.

Mast cells (MCs)_are recognized for their functional role in wound-healing and allergic and inflammatory responses - host responses that are frequently detrimental to implanted biomaterials if extended beyond acute reactivity. These tissue reactions impact especially on the performance of sensing implants such as continuous glucose monitoring (CGM) devices. Our hypothesis that effective blockade of MC activity around implants could alter the host foreign body response (FBR) and enhance the in vivo lifetime of these implantable devices motivated this study.

Lifetime assessment of atomic-layer-deposited Al2O3-Parylene C bilayer coating for neural interfaces using accelerated age testing and electrochemical characterization.

The lifetime and stability of insulation are critical features for the reliable operation of an implantable neural interface device. A critical factor for an implanted insulation's performance is its barrier properties that limit access of biological fluids to the underlying device or metal electrode. Parylene C is a material that has been used in FDA-approved implantable devices.

Modulation of the foreign body response to implanted sensor models through device-based delivery of the tyrosine kinase inhibitor, masitinib.

The host foreign body response (FBR) adversely effects the performance of numerous implanted biomaterials especially biosensors, including clinically popular glucose-monitoring sensors. Reactive formation of a fibrous capsule around implanted sensors hinders the transport of essential analytes to the sensor from the surrounding tissue, resulting in loss of glucose response sensitivity and eventual sensor failure. Several strategies have sought to mitigate the foreign body response's effects on CGM sensors through the use of local delivery of pharmaceuticals and biomolecules with limited success.