Nanoenabled Direct Contact Interfacing of Syringe-Injectable Mesh Electronics.

Polymer-based electronics with low bending stiffnesses and high flexibility, including recently reported macroporous syringe-injectable mesh electronics, have shown substantial promise for chronic studies of neural circuitry in the brains of live animals. A central challenge for exploiting these highly flexible materials for in vivo studies has centered on the development of efficient input/output (I/O) connections to an external interface with high yield, low bonding resistance, and long-term stability. Here we report a new paradigm applied to the challenging case of injectable mesh electronics that exploits the high flexibility of nanoscale thickness two-sided metal I/O pads that can deform and contact standard interface cables in high yield with long-term electrical stability.

Advanced One- and Two-Dimensional Mesh Designs for Injectable Electronics.

The unique structure and mechanical properties of syringe-injectable mesh electronics have enabled seamless tissue integration and stable chronic recording of the activities of the same neurons on a year scale. Here, we report studies of a series of structural and mechanical mesh electronics design variations that allow injection using needles at least 4-fold smaller than those previously reported to minimize the footprint during injection of the electronics in soft matter and tissue. Characterization of new ultraflexible two-dimensional (2D) and one-dimensional (1D) probes has demonstrated reproducible injection of the newly developed mesh electronics designs via needles as small as 100 μm in inner diameter (ID) with reduced injection volumes.

Bioinspired neuron-like electronics.

As an important application of functional biomaterials, neural probes have contributed substantially to studying the brain. Bioinspired and biomimetic strategies have begun to be applied to the development of neural probes, although these and previous generations of probes have had structural and mechanical dissimilarities from their neuron targets that lead to neuronal loss, neuroinflammatory responses and measurement instabilities. Here, we present a bioinspired design for neural probes-neuron-like electronics (NeuE)-where the key building blocks mimic the subcellular structural features and mechanical properties of neurons.

A method for single-neuron chronic recording from the retina in awake mice.

The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice.

Tissue-like Neural Probes for Understanding and Modulating the Brain.

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized.

Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology.

Implantable electrical probes have led to advances in neuroscience, brain-machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain.

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain.

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes.

Stable long-term chronic brain mapping at the single-neuron level.

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning.

Alkaline and ultrasonic dissolution of biological materials for trace silicon determination.

A simple method for trace elemental determination in biological tissue has been developed. Novel nanomaterials with biomedical applications necessitate the determination of the fate of the materials to understand their toxicological profile. Hollow iron-doped calcined silica nanoshells have been used as a model to demonstrate that potassium hydroxide and bath sonication at 50 °C can extract elements from alkaline-soluble nanomaterials.

Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.

Background: High intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues.