Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues

Abstract

Nanobioelectronics represents a rapidly developing field with broad-ranging opportunities in fundamental biological sciences, biotechnology, and medicine. Despite this potential, seamless integration of electronics has been difficult due to fundamental mismatches, including size and mechanical properties, between the elements of the electronic and living biological systems. In this Account, we discuss the concept, development, key demonstrations, and future opportunities of mesh nanoelectronics as a general paradigm for seamless integration of electronics within synthetic tissues and live animals. We first describe the design and realization of hybrid synthetic tissues that are innervated in three dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a tissue scaffold and as a platform of addressable electronic devices for monitoring and manipulating tissue behavior. Specific examples of tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac patches, and vascular constructs, where the nanoelectronic devices have been used to carry out real-time 3D recording of electrophysiological and chemical signals in the tissues. This novel platform was also exploited for time-dependent 3D spatiotemporal mapping of cardiac tissue action potentials during cell culture and tissue maturation as well as in response to injection of pharmacological agents. The extension to simultaneous real-time monitoring and active control of tissue behavior is further discussed for multifunctional mesh nanoelectronics incorporating both recording and stimulation devices, providing the unique capability of bidirectional interfaces to cardiac tissue. In the case of live animals, new challenges must be addressed, including minimally invasive implantation, absence of deleterious chronic tissue response, and long-term capability for monitoring and modulating tissue activity. We discuss each of these topics in the context of implantation of mesh nanoelectronics into rodent brains. First, we describe the design of ultraflexible mesh nanoelectronics with size features and mechanical properties similar to brain tissue and a novel syringe-injection methodology that allows the mesh nanoelectronics to be precisely delivered to targeted brain regions in a minimally invasive manner. Next, we discuss time-dependent histology studies showing seamless and stable integration of mesh nanoelectronics within brain tissue on at least one year scales without evidence of chronic immune response or glial scarring characteristic of conventional implants. Third, armed with facile input/output interfaces, we describe multiplexed single-unit recordings that demonstrate stable tracking of the same individual neurons and local neural circuits for at least 8 months, long-term monitoring and stimulation of the same groups of neurons, and following changes in individual neuron activity during brain aging. Moving forward, we foresee substantial opportunities for (1) continued development of mesh nanoelectronics through, for example, ...

Cellular-scale silicon probes for high-density, precisely-localized neurophysiology

“…Neural probes made using flexible polymer substrates 20,22,30,33 can also produce recordings with high longevity. Furthermore, their mechanical flexibility prevents breaking, and they may also be sliced-in-place 34 .…”

Hybrid Silicon Nanowire Devices and Their Functional Diversity

“…Otherwise, the spreading of the bubble can also be continued onto a flat surface (e.g., a silicon wafer) until the surface is covered by the polymer film. [26] The biocompatibility and mechanical deformation capability are very high and enable injection into tissues using a syringe, as it has been demonstrated in mice brains with minimal immune response, [25] obtaining above 30 simultaneous measuring points in real time ( Figure 3e). Some defects still may appear due to trapped gas during film transfer.…”

“…The acceptor substrate does not necessarily need to be another wafer, the possibility of printing the nanowires on potentially any surface opens the way to build electronic devices at a low cost on flexible plastic foils (Figure 3d). [26] Copyright 2018, ACS Publications. Sci.…”

“…[16][17][18][19] During the last decade 1D nanostructures, and in particular semiconductor silicon nanowires (SiNWs), have attracted attention as highly efficient elements of transistor elements due to their high level of complementary metal-oxide semiconductor (CMOS) compatibility, [20] compactness of the resulting device architecture, and high surface-to-volume ratio. However, current commercial transistors and the most advanced research examples are being manufactured using silicon as semiconducting channel material, [25][26][27] while the technologies and knowledge in relation to the other materials are still in their infancy in comparison, not being ready yet to fully replace Si. However, current commercial transistors and the most advanced research examples are being manufactured using silicon as semiconducting channel material, [25][26][27] while the technologies and knowledge in relation to the other materials are still in their infancy in comparison, not being ready yet to fully replace Si.…”

Conducting Polymer-Based Composite Materials for Therapeutic Implantations: From Advanced Drug Delivery System to Minimally Invasive Electronics

“…The longitudinal elements may have composite structures, consisting of gold interconnects sandwiched between two layers of the biocompatible photoresist SU-8 [101]. One end of the longitudinal element is connected to a sensor or stimulator such as a metal electrode [94][95][96][97][98]102] or nanowire transistor [95,102,103], and the other end is connected to an input/output (I/O) pad. The transverse elements may consist of two SU-8 layers with a total thickness of approximately 800 nm and a width of 20 μm [95].…”