Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

Abstract

Abstract. Direct electrical recording and stimulation of neural activity using microfabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a 3D macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials (LFPs) and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.Currently, there is intense interest in the development of materials and electronic devices that can extend and/or provide new capabilities for probing neural circuitry and afford long-term minimally-invasive brain-electronics interfaces 1,2,3,4 . Conventional brain probes have contributed extensively to basic neuroscience 5,6 and therapeutic applications 7,8,9,10 , although they suffer from chronic stability and poor neuron-device contacts 4,11,12,13 . Recent studies of smaller 14,15 and more flexible 16,17 probes suggest that addressing size and mechanical factors could help overcome current limitations. 3The most common neural electrical probes are fabricated from metal 18 and silicon 19,20 , materials that have very different structural and mechanical properties compared to brain tissue 21 .Evidence suggests that mechanical mismatch is an important reason leading to abrupt and chronically unstable interfaces within the brain 4,22 . For example, motion of skull-affixed rigid probes in chronic experiments can induce shear stresses and lead to tissue scarring 13,23 , and thereby compromise the stability of recorded signals on the time scale of weeks to months 4,24, 25 .More recent work has shown that flexible probes fabricated on polymer substrates 12,17 and smaller-sized probes 11,14 can reduce deleterious tissue response. More generally, there has also been effort developing flexible bioelectronics 26, 27, 28 and nanoscale devices for single cell recording 29, 30 . We have also shown that 3D macroporous electronic device arrays can function as a scaffold for and allow for 3D interpenetration of cultured neuron cell networks without an adverse effect on cell viability 31 , and such networks can be injected by syringe through needles into materials, including brain tissue 32 . In the latter case, it remains challenging to make electrical in...

Materials and technologies for soft implantable neuroprostheses

“…Such a probe may be either injected through a hollow needle and then deployed in the liquid compartment of the brain (FIG. 3) (that is, the ventricles where the cerebrospinal fluid is produced) 97 or frozen in liquid nitrogen for rapid insertion into the cortex 98 . Cortical tissues carrying the macroporous ultra-flexible implants for several weeks display high biocompatibility as neural tissue invades the macroporous network.…”

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

“…To address the issues of conventional rigid devices we have introduced a paradigm for implantable multielectrode probes based upon an ultraflexible open mesh structure (23)(24)(25)(26), where the mesh has a unique combination of structural and mechanical features. Specifically, the mesh has all size features comparable to or smaller than neuron soma and bending stiffness values of ∼0.1 nN·m, comparable to a 150-μm-thick brain tissue slice (i.e., the same as the overall implanted open mesh diameter), ∼0.4 nN·m (27,28) and orders of magnitude smaller (more flexible) than conventional probes (14,29,30).…”

Flexible and Organic Neural Interfaces: A Review

“…Aside planar graphene electrodes, carbon nanofiber impregnated into conductive polyethylene [120] and graphene oxide microfibers insulated with parylene-C [121] flexible and penetrating electrodes have been developed. These flexible organic and hybrid electrodes can be introduced deep in the brain through releasable injection microneedles [122] or capillary syringe needles [123], can be stereotaxically implanted after rapid freezing in liquid nitrogen [124] or by coating the electrodes with a rigid and dissolvable sucrose carrier needle [121] (Figure 9b). Such techniques allow the insertion of flexible probes able to perform deep brain stimulations by reducing the risk of tissues damaging after the implant due to motions of the implant itself.…”