1.3 Nanoelectronics in Biology: Interfacing with Living
Cells
Applications of nanoelectronics in biomolecule detection and electrophysiological
recording have been highly successful, which offer advantages such as high
throughput, scalability and low cost leading to novel analytical devices for
disease-marker detection, DNA sequencing and other applications [ 71 – 73 ]. For
example, electrophysiological recording of cellular activity is central to areas
ranging from basic biophysical study to medical applications [ 74 – 88 ]. In past
decades, glass micropipette intracellular probes and sharp electrode probes have
been predominantly used to interface with the internal environment of cells [ 74 –
77 ], and multi-electrode arrays [ 78 – 81 ] and planar FETs [ 81 – 88 ] have been used to
interface to and record from electrogenic cells. However, these technologies are
either invasive or lack the ability to record signals in the intracellular and subcel-
lular regions. Moreover, metal-based electrical recording suffers from the limitation
of liquid-solid input impedance, which precludes further decrease of detector size
[ 89 ].
Recently, there have been several advances using nanowire-based nanoelec-
tronics to interface with single cells. One has been the use of metallic vertical
nanowires as detectors to interface with the cells cultured directly on them. Through
localized electroporation, the nanowires can break the cell membrane to form a
temporary connection between detectors and the intracellular environment [ 90 , 91 ].
However, this technique is still invasive to cells despite some modifications which
allow longer intracellular detection time. Moreover, as mentioned above,
metal-based electrical recording probes cannot be made smaller and less invasive
without increasing the input impedance. In addition, the amplitude of signal,
temporal resolution and signal-to-noise (S/N) are all limited by the sub-microscale
size of the detector [ 89 ]. Importantly, those vertical metallic nanowires all fail to
identify the subthreshold voltage change in action potential recording [ 90 , 91 ]. On
the contrary, the FET has proved to be an“active”detector, in which the sensitivity
will drop with decreasing detector size [ 71 , 92 ]. In an FET device, the potential is
recorded by measuring the conductance between the source and drain electrodes.
The potential applied to the channels of the FET serves as a gate potential changing
the carrier density in the FET channels, which leads to conductance change. This
process is independent of the input impedance of the FET channels and
source-drain electrodes; therefore, the size of the detector does not affect the sen-
sitivity of the FET. As an example of such an FET detector, Tian et al. synthesized
kinked nanowire with ca. 80-nm diameter and modulated its axial doping to localize
a lightly doped nanoscale FET region on the tip of the kink with two metallic arms.
Stressed metal contacts were formed to leverage the nanowire into a 3D probe.
Phospholipid bilayers were coated on the surface of the kinked nanowire to facil-
itate the penetration of the nanowire into the cell. Using this nanoFET probe, a full
amplitude cardiomyocyte action potential with 75–100 mV was recorded
(Fig.1.2a–c) [ 18 ]. Moreover, Duan et al. [ 93 ] fabricated a silica nanotube, coated
1.3 Nanoelectronics in Biology: Interfacing with Living Cells 5