6 research outputs found
Scalable Fabrication Framework of Implantable Ultrathin and Flexible Probes with Biodegradable Sacrificial Layers
For long-term biocompatibility
and performance, implanted probes
need to further reduce their size and mechanical stiffness to match
that of the surrounding cells, which, however, makes accurate and
minimally invasive insertion operations difficult due to lack of rigidity
and brings additional complications in assembling and surgery. Here,
we report a scalable fabrication framework of implantable probes utilizing
biodegradable sacrificial layers to address this challenge. Briefly,
the integrated biodegradable sacrificial layer can dissolve in physiological
fluids shortly after implantation, which allows the in situ formation
of functional ultrathin film structures off of the initial small and
rigid supporting backbone. We show that the dissolution of this layer
does not affect the viability and excitability of neuron cells in
vitro. We have demonstrated two types of probes that can be used out
of the box, including (1) a compact probe that spontaneously forms
three-dimensional bend-up devices only after implantation and (2)
an ultraflexible probe as thin as 2 Ī¼m attached to a small silicon
shaft that can be accurately delivered into the tissue and then get
fully released in situ without altering its shape and position because
the support is fully retracted. We have obtained a >93% yield of
the
bend-up structure, and its geometry and stiffness can be systematically
tuned. The robustness of the ultraflexible probe has been tested in
tissue-mimicking agarose gels with <1% fluctuation in the test
resistance. Our work provides a general strategy to prepare ultrasmall
and flexible implantable probes that allow high insertion accuracy
and minimal surgical damages with the best biocompatibility
Multiplexed Free-Standing Nanowire Transistor Bioprobe for Intracellular Recording: A General Fabrication Strategy
Recent
advance in free-standing nanowire transistor bioprobes opens
up new opportunities of accurately interfacing spatially unobstructed
nanoscale sensors with live cells. However, the existing fabrication
procedures face efficiency and yield limitations when working with
more complex nanoscale building blocks to integrate, for example,
multiplexed recordings or additional functionalities. To date, only
single-kinked silicon nanowires have been successfully used in such
probes. Here we establish a general fabrication strategy to mitigate
such limitations with which synthetically designed complex nanoscale
building blocks can be readily used without causing significant penalty
in yield or fabrication time, and the geometry of the probe can be
freely optimized based on the orientation and structure of the building
blocks. Using this new fabrication framework, we demonstrate the first
multiplexed free-standing bioprobe based on w-shaped silicon kinked
nanowires that are synthetically integrated with two nanoscale field-effect
transistor devices. Simultaneous recording of intracellular action
potentials from both devices have been obtained of a single spontaneously
beating cardiomyocyte
Design and Synthesis of Diverse Functional Kinked Nanowire Structures for Nanoelectronic Bioprobes
Functional kinked nanowires (KNWs) represent a new class
of nanowire
building blocks, in which functional devices, for example, nanoscale
field-effect transistors (nanoFETs), are encoded in geometrically
controlled nanowire superstructures during synthesis. The bottom-up
control of both structure and function of KNWs enables construction
of spatially isolated point-like nanoelectronic probes that are especially
useful for monitoring biological systems where finely tuned feature
size and structure are highly desired. Here we present three new types
of functional KNWs including (1) the zero-degree KNW structures with
two parallel heavily doped arms of U-shaped structures with a nanoFET
at the tip of the āUā, (2) series multiplexed functional
KNW integrating multi-nanoFETs along the arm and at the tips of V-shaped
structures, and (3) parallel multiplexed KNWs integrating nanoFETs
at the two tips of W-shaped structures. First, U-shaped KNWs were
synthesized with separations as small as 650 nm between the parallel
arms and used to fabricate three-dimensional nanoFET probes at least
3 times smaller than previous V-shaped designs. In addition, multiple
nanoFETs were encoded during synthesis in one of the arms/tip of V-shaped
and distinct arms/tips of W-shaped KNWs. These new multiplexed KNW
structures were structurally verified by optical and electron microscopy
of dopant-selective etched samples and electrically characterized
using scanning gate microscopy and transport measurements. The facile
design and bottom-up synthesis of these diverse functional KNWs provides
a growing toolbox of building blocks for fabricating highly compact
and multiplexed three-dimensional nanoprobes for applications in life
sciences, including intracellular and deep tissue/cell recordings
Synthetically Encoded Ultrashort-Channel Nanowire Transistors for Fast, Pointlike Cellular Signal Detection
Nanostructures, which have sizes comparable to biological
functional
units involved in cellular communication, offer the potential for
enhanced sensitivity and spatial resolution compared to planar metal
and semiconductor structures. Silicon nanowire (SiNW) field-effect
transistors (FETs) have been used as a platform for biomolecular sensors,
which maintain excellent signal-to-noise ratios while operating on
lengths scales that enable efficient extra- and intracellular integration
with living cells. Although the NWs are tens of nanometers in diameter,
the active region of the NW FET devices typically spans micrometers,
limiting both the length and time scales of detection achievable with
these nanodevices. Here, we report a new synthetic method that combines
gold-nanocluster-catalyzed vaporāliquidāsolid (VLS)
and vaporāsolidāsolid (VSS) NW growth modes to produce
synthetically encoded NW devices with ultrasharp (<5 nm) n-type
highly doped (n<sup>++</sup>) to lightly doped (n) transitions along
the NW growth direction, where n<sup>++</sup> regions serve as source/drain
(S/D) electrodes and the n-region functions as an active FET channel.
Using this method, we synthesized short-channel n<sup>++</sup>/n/n<sup>++</sup> SiNW FET devices with independently controllable diameters
and channel lengths. SiNW devices with channel lengths of 50, 80,
and 150 nm interfaced with spontaneously beating cardiomyocytes exhibited
well-defined extracellular field potential signals with signal-to-noise
values of ca. 4 independent of device size. Significantly, these āpointlikeā
devices yield peak widths of ā¼500 Ī¼s, which is comparable
to the reported time constant for individual sodium ion channels.
Multiple FET devices with device separations smaller than 2 Ī¼m
were also encoded on single SiNWs, thus enabling multiplexed recording
from single cells and cell networks with device-to-device time resolution
on the order of a few microseconds. These short-channel SiNW FET devices
provide a new opportunity to create nanoscale biomolecular sensors
that operate on the length and time scales previously inaccessible
by other techniques but necessary to investigate fundamental, subcellular
biological processes
Outside Looking In: Nanotube Transistor Intracellular Sensors
Nanowire-based field-effect transistors, including devices
with
planar and three-dimensional configurations, are being actively explored
as detectors for extra- and intracellular recording due to their small
size and high sensitivities. Here we report the synthesis, fabrication,
and characterization of a new needle-shaped nanoprobe based on an
active silicon nanotube transistor, ANTT, that enables high-resolution
intracellular recording. In the ANTT probe, the source/drain contacts
to the silicon nanotube are fabricated on one end, passivated from
external solution, and then time-dependent changes in potential can
be recorded from the opposite nanotube end via the solution filling
the tube. Measurements of conductance versus water-gate potential
in aqueous solution show that the ANTT probe is selectively gated
by potential changes within the nanotube, thus demonstrating the basic
operating principle of the ANTT device. Studies interfacing the ANTT
probe with spontaneously beating cardiomyocytes yielded stable intracellular
action potentials similar to those reported by other electrophysiological
techniques. In addition, the straightforward fabrication of ANTT devices
was exploited to prepare multiple ANTT structures at the end of single
probes, which enabled multiplexed recording of intracellular action
potentials from single cells and multiplexed arrays of single ANTT
device probes. These studies open up unique opportunities for multisite
recordings from individual cells through cellular networks
Fixed-Gap Tunnel Junction for Reading DNA Nucleotides
Previous measurements of the electronic conductance of DNA nucleotides or amino acids have used tunnel junctions in which the gap is mechanically adjusted, such as scanning tunneling microscopes or mechanically controllable break junctions. Fixed-junction devices have, at best, detected the passage of whole DNA molecules without yielding chemical information. Here, we report on a layered tunnel junction in which the tunnel gap is defined by a dielectric layer, deposited by atomic layer deposition. Reactive ion etching is used to drill a hole through the layers so that the tunnel junction can be exposed to molecules in solution. When the metal electrodes are functionalized with recognition molecules that capture DNA nucleotides <i>via</i> hydrogen bonds, the identities of the individual nucleotides are revealed by characteristic features of the fluctuating tunnel current associated with single-molecule binding events