1.4 Nanoelectronics in Biology: Interfacing with Living
Tissues and Organs
Progress in nanotechnology has already significantly advanced our ability to
interrogate tissue structure. For examples, nanoparticles have been used to image
tissue structure and activity in vitro and in vivo [ 100 , 101 ], and as drug delivery
materials to control the release of drugs in tissue [ 102 , 103 ]; micro- and nanofluidic
channels have been used to deliver or inject biomolecules and virus vectors to the
targeted tissue region [ 104 ] and 3D macroporous materials with micro- and
nanoscopic features have been developed to build synthetic tissue scaffolds [ 105 ].
While interfacing electronic units with individual cells has been progressed,
building electronics-tissues interface is still challenge due to the complicated and
compact 3D cellular structure, dynamic movement in behaving objects and
molecular responses from tissue to the implanted foreign objects. The emerge of
flexible nanoelectronics shows great opportunities for interfacing electronics with
living tissues and organs due to: (1) nanoscale feature size of nanoelectronic unit
will introduce minimal interrupting to the internal tissue structures and cellular
networks, (2) geometry and composition of nanoelectronics engineered to mimic
the chemical and physical properties of biomaterials can further facilitate the
seamless integration with tissue, (3) unique optical and electrical performances that
allow millions to billions functional units to be addressed simultaneously will
greatly enhance our capability for tissue activity monitoring, especially for brain
mapping, (4) ultraflexibility that eliminates the mechanical mismatch between the
living tissue and electronics will enhance the working life and efficiency of those
units inside tissue and (5) the unprecedented integration of multiple functions in a
small volume (e.g. the volume of one millionflexible interconnected nanosensors
array will only occupy much less than 1 thousandth volume of a living mice brain)
could possibly allow us to seamlessly integrate nanoelectronics within behaving
animals to create a true cyborg system.
However, very few works have been done in interfacing nanoelectronics to
cellular networks, tissues and organs. The challenges are that (1) tissue has a 3D
and heterogeneous structure and (2) in contrast to single cells, cells in tissues
closely pack in 3D networks surrounded by dense extracellular matrix which are
inaccessible to nanoelectronic units. Someflexible electronics have been used to
interface to the top surface of tissue to facilitate attachment and adhesion [ 16 , 17 ,
106 , 107 ]. However, the surface of tissue provides only limited information that can
also be acquired by optical methods [ 108 ]. To be delivered into the interior space of
tissues, currently nanoelectronic systems need sensors fabricated on the rigid
substrates to provide mechanical strength for penetrating though the dense cellular
structure and attach functional units targeted cells [ 109 – 113 ]. The dimensions of
this rigid substrate need to be micro- to millimeter scale to maintain enough
mechanical strength. This approach introduces large acute damage from inserting a
significantly large volume of substrate materials (vs. nanoelectronics) into the living
system. In addition, the mechanical mismatch between the nanoelectronics and
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