Mesh electronics: a new paradigm for tissue-like brain probes

Abstract

Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies.

Figure 1

Challenges of state-of-the-art neural probes and original conception of mesh electronics. (a) Comparison of feature size and bending stiffness between existing neural probes [–,,–17] and a 20~100 μm thick slice of brain tissue. Ideal brain probes should have critical feature sizes and bending stiffness values similar to or smaller than those of the brain tissue to afford ‘tissue-like probes’. (b) Original page from Lieber’s notebook in 2008 showing key idea leading to free-standing 3D neuron-like nanoelectronic devices to interface with neurons in a biological manner. (c) Schematic drawings presented in 2007/2008 talks and NIH proposal illustrating the key concept leading to mesh electronics with porosity that enables interpenetration and integration of neural networks with electronics structure [24].

Figure 2

Syringe delivery of mesh electronics into the brain to yield neuron interpenetration without a chronic immune response. (a) Unique structural and mechanical properties of mesh electronics allow for syringe delivery into the brain, highlighting a photograph of multiple mesh electronics probes (green arrow) floating in an aqueous saline solution similar to colloidal particles (I), a bright-field microscope image showing partially ejected mesh electronics with significant expansion in solution (II), and a schematic of controlled stereotaxic injection (III) that allows precisely targeted delivery of mesh electronics using a motorized translational stage for controlling needle withdrawal (blue arrow), a syringe pump for controlling the injection rate (green arrow), and a camera for visualizing the mesh during injection (red arrow) [14,36]. (b) Time-dependent immunohistochemical staining images of horizontal brain slices at 2 weeks (hippocampus), 6 weeks (cortex), 12 weeks (cortex) and 1 year (cortex) post injection. In all images of panel (b), red, green and blue colors correspond to neuron axons (Neurofilament antibody), neuron nuclei (NeuN antibody) and mesh elements. (c) Normalized fluorescence intensities plotted versus distance from the mesh/brain tissue interface at different time points; the intensities were normalized versus background far from the probe (black dashed horizontal lines). The pink shaded regions indicate the interior of mesh electronics [40].

Figure 3

Electrical I/O connection and long-term stable recording at the single-neuron level using mesh electronics. (a) Quantitative and scalable high throughput I/O connection by a plug-and-play interface: structural design of the plug-and-play mesh electronics (I), insertion of I/O pads of plug-and-play mesh electronics into a ZIF connector (II), and compact headstage comprising mesh electronics inserted into the ZIF connector (red arrows) on a PCB that provides an interface to a standard Omnetics connector (yellow arrows) for recording (III) [45]. (b) 16-channel multiplexed recording of LFP (background heat map) and single-unit firing (foreground black traces) from the same mouse brain at 2 and 4 months post injection. The relative positions of all 16 recording electrodes are marked by red dots in the schematic (leftmost panel), and span the somatosensory cortex to hippocampus. (c) Chronic tracking of same individual neurons by time-dependent PCA (I) and firing rate analysis (II) that allows for study of brain aging on the single-neuron level by tracking firing rate evolution of the same three individual neurons from 35 to 57 weeks of age (III) [40].

Figure 4

Outlook and three basic areas of opportunity for mesh electronics neural probes, including neuroscience opportunities, neurotechnology developments, and neurology applications.