tissue can cause continuously chronic damage to the surrounding cells during
long-term implantation and recording, resulting in severe immunoreactivity, which
degrades the quality and efficiency of recording and stimulation.
Although we have many challenges for building electronics-tissue interface, the
necessity to deliver and seamlessly integrate nanoelectronic units within tissue in
3D, from subcellular scale to throughout the whole tissue is ever-increasing. For
example, the integration of billions of sensing units within brain tissue in behaving
animals at single-cell level to minimal-invasively monitor the activity from statis-
tically significant amount of neurons is the key for precise brain activity mapping
[ 114 , 115 ]. Other examples include a smart drug release system coupled with ability
to sense microenvironment changes throughout our body [ 116 , 117 ], a 3D in situ
sequencing technique based on the integration of nanopore enabled sequencing
technique with 3D tissue [ 118 – 120 ], and the development of a completely cyborg
system for robotics. These advances would significantly impact the fields of
biomedical devices, tissue engineering and neuroscience and lead to fundamental
new understanding of biological systems and its integration with digital systems.
1.5 Overview of Thesis
In this thesis, Ifirst propose a fundamentally new idea for the interfacing and
integrating nanoelectronics with tissue in vitro and in vivo. This new approach
involves stepwise incorporation of biomimetic and biological elements into a net-
work with addressable, nanoscale-feature units assembled on a centimeter-size scale
in a 3D structure. This electronic network mimics theflexible and macroporous
structure of the extracellular matrix as nanoelectronic scaffold (nanoES), which
allows its integration with other soft materials and biomaterials without affecting
their physical and chemical properties. Then, I introduce the in vitro culture of cells
within tissue scaffolds that is hybridized with nanoES to build synthetic tissues, in
which nanoelectronic units have been intrinsically embedded as cyborg tissues.
Finally, I show that the completely freestanding nanoES can be delivered and
integrated into in vivo rodent brain systems through a minimally invasive
syringe-injection. The injected nanoES can unfold within tissue to distribute
nanosensors three-dimensionally into the largest possible volume for localfield and
action potential recording, and act as tissue scaffolds to actively guide stem cell
growth.
In Chap. 2 ,Ifirst introduce a new method to pattern and fabricate a real 3D
nanoelectronic network. This 3D network is initially fabricated on a 2D sacrificial
layer. Using a contact printing technique and lithography patterning,
single-nanowire based nanoelectronics are then patterned into regular arrays formed
by polymers. Removing the underlying sacrificial layer allows the 2D nanoelec-
tronics to be organized into 3D structures by either external manipulation or internal
stress control.
8 1 Introduction