With ANY BRAINS AT ALL in stroke leadership, this would have immediately started research using this to listen in on neuron signalling in neuroplasticity. We need to know why and how a neighboring neuron gives up its current task and takes on a neighboring task. Without that knowledge neuroplasticity will never be made repeatable and made into a stroke protocol. Hell, this has been out since July 2015 so more proof that the stroke medical world is completely incompetent.
Syringe injectable electronics
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Associated Data
Abstract
Seamless
and minimally-invasive three-dimensional (3D) interpenetration of
electronics within artificial or natural structures could allow for
continuous monitoring and manipulation of their properties. Flexible
electronics provide a means for conforming electronics to non-planar
surfaces, yet targeted delivery of flexible electronics to internal
regions remains difficult. Here, we overcome this challenge by
demonstrating syringe injection and subsequent unfolding of
submicrometer-thick, centimeter-scale macroporous mesh electronics
through needles with a diameter as small as 100 micrometers. Our results
show that electronic components can be injected into man-made and
biological cavities, as well as dense gels and tissue, with > 90%
device yield. We demonstrate several applications of syringe injectable
electronics as a general approach for interpenetrating flexible
electronics with 3D structures, including (i) monitoring of internal
mechanical strains in polymer cavities, (ii) tight integration and low
chronic immunoreactivity with several distinct regions of the brain, and
(iii) in vivo multiplexed neural recording. Moreover, syringe
injection enables delivery of flexible electronics through a rigid
shell, delivery of large volume flexible electronics that can fill
internal cavities and co-injection of electronics with other materials
into host structures, opening up unique applications for flexible
electronics.
The
emergence of flexible electronics has significantly extended the
applications of electronics by allowing intimate interfaces between
electronic units and non-planar surfaces for better monitoring and
manipulation of their properties1-3. A variety of electronic devices1-8 has been integrated on flexible and stretchable substrates to enable applications from foldable display to electronic skin3-8.
3D interpenetration of flexible electronics within existing structures
could further broaden and open up new applications by directly
interfacing devices with the internal structures of man-made and
biological materials.
Recent work has shown that flexible electronics can be placed into 3D structures through surgical processes9-12 or by being attached to and subsequently released from a rigid delivery substrates13-14
for biological and biomedical applications. However, direct 3D
interpenetration of electronics within these structures is limited by
the intrinsic thin-film 14
supporting substrates. We have introduced a macroporous mesh paradigm
that allow electronics to be combined, for example, with polymer
precursors and cells to yield 3D interpenetration15, 16,
although controlled delivery and/or non-surgical placement of these
ultraflexible open electronic networks into structures with seamless 3D
integration and interpenetration has not been possible.
Here,
we describe the design and demonstration of macroporous flexible mesh
electronics that allow electronics to be precisely delivered into 3D
structures by syringe injection and subsequently relax and
interpenetrate within the internal space of man-made and biological
materials. Distinct from previous reports3, 17, 18,
syringe injection requires complete release of the mesh electronics
from a substrate so that the electronics can be driven by solution
through a needle. The syringe injectable electronics concept involves
(i) loading the mesh electronics into a syringe and needle, (ii)
insertion of the needle into the material or internal cavity and
initiation of mesh injection (Fig. 1a), (iii) simultaneous mesh injection and needle withdrawal to place the electronics through the targeted region (Fig. 1b), and (iv) delivery of the input/output (I/O) region of the mesh outside of the material (Fig. 1c) for subsequent bonding and measurements.
Syringe injectable electronics
a to c,
Schematics of injectable electronics. The red-orange lines highlight
the overall mesh structure and indicate the regions of supporting and
passivating polymer mesh layers; the yellow lines indicate metal
interconnects between I/O pads (green filled circles) and recording
devices (blue filled circles). d, Schematic of the mesh
electronics design (upper image), where the orange and red lines
represent polymer encapsulated metal interconnects and supporting
polymer elements, respectively, and W is the total width of the
mesh. The dashed black box (lower image) highlights the structure of
one unit cell (white dashed lines), where α is the angle deviation from rectangular. e, Longitudinal mesh bending stiffness, DL, and transverse mesh bending stiffness, DT, as a function of α defined in d. f and g, Images of mesh electronics injection through a glass needle, ID = 95 μm, into 1x PBS solution. Bright-field microscopy image f
of the mesh electronics immediately prior to injection into solution;
the red arrow indicates the end of the mesh inside the glass needle. 3D
reconstructed confocal fluorescence image g recorded
following injection of ca. 0.5 cm mesh electronics into 1x PBS solution.
The blue and white dashed boxes correspond to regions shown in Supplementary Fig. 3a and b. h, Optical image of an injectable mesh electronics structure unfolded on a glass substrate. W
is the total width of the mesh electronics. The red dashed polygon
highlights the position of electrochemical devices or FET devices. Green
and black dashed boxes highlighted metal interconnect lines and metal
I/O pads, respectively. i and j,
Yields and change with ±1 standard deviation (±1SD) in properties
post-injection for single-terminal electrochemical and two-terminal
field-effect transistor (FET) devices. i, Yield (blue)
and impedance change (red) of the metal electrodes from the mesh
electronics injected through 32, 26 and 22 gauge metal needles. Inset:
bright field image of a representative metal electrode on mesh
electronics, where the sensing electrode is highlighted by a red arrow.
Scale Bar: 20 μm. j, Yield (blue) and conductance
change (red) of silicon nanowire FETs following injection through 32,
26, 24, 22 and 20 gauge needles. Inset: scanning electron microscopy
(SEM) image of a representative nanowire FET device in the mesh
electronics; the nanowire is highlighted by the red arrow. Scale bar: 2
μm.
Design and implementation of electronics for syringe injection
The
mechanical properties of the free-standing mesh electronics are
important to the injection process. The basic mesh structure (Fig. 1d and Supplementary Fig. 1, a and b)
consists of longitudinal polymer/metal/polymer elements, which function
as interconnects between exposed electronic devices and I/O pads, and
transverse polymer elements. The mesh longitudinal and transverse
bending stiffness, DL and DT,
are determined by the mesh unit cell and corresponding widths and
thickness of the longitudinal and transverse elements, and the angle, α, 15, 16. Simulations of DT and DL versus α(Fig. 1e) show that DT (DL) decreases (increases) for increasing α. Hence, increasing α facilitates bending along the transverse direction (reduced DT) and should allow for rolling-up of the mesh electronics within a needle constriction, while at the same time increasing DL, which should reduce bending and potential buckling along the injection direction.
The mesh electronics were fabricated, fully-released from substrates using reported methods15, 16 and loaded into glass needles connected to a microinjector (details see, Supplementary Information Sections 2 and 3 and Supplementary Figs. 2 and 3).
Images of injection of a 2 mm wide sample through a 95 μm inner
diameter (ID) glass needle show the compressed mesh ca. 250 μm from the
needle opening (Fig. 1f), and then injected ca. 0.5 cm into 1x phosphate-buffered saline (PBS) solution (Fig. 1g),
where the 3D image highlights the unfolding of the mesh structure from
the point of the needle constriction (blue dashed box). Higher
resolution images (Supplementary Fig. 4, a and b)
show that the mesh structure is continuous as it unfolds. Similar
results were obtained for injection of a 1.5 cm width sample through a
20 gauge (600 μm ID) metal needle (Supplementary Fig. 4c) demonstrating the generality of this injection through common glass and metal syringe needles.
To
test further electrical continuity and functionality of the mesh
electronics post-injection, we used anisotropic conductive film (ACF)19 to connect the I/O pads of theelectronics post-injection to flexible cables that are interfaced to measurement electronics (Supplementary Fig. 5, a-d).
Studies of the electrical performance and yield of devices following
injection into 1x PBS solution through 100-600 μm ID needles (Fig. 1, i and j)
highlight several points. First, metal electrochemical devices had an
average device >94% and an average device impedance change, which
represents an important characteristic for voltage sensing applications20, 21, of <7% post injection (Fig. 1i).
Second, silicon nanowire field-effect transistor (FET) devices had a
yield > 90% for needle IDs from 260 to 600 μm, only dropped to 83%
for the smallest 100 μm ID needles, and exhibited < 12% conductance
change on average post injection (Fig. 1j).
Together these results demonstrate the robustness of our mesh
electronics design and the capability of maintaining good device
performance following injection through a wide-range of needle IDs.
We
have characterized the structures of different mesh electronics within
glass needle-like constrictions to understand design parameters for
successful injection (Fig. 2, a and b).
Bright field microscopy images of mesh electronics with different
structural parameters recorded from the central region of different ID
glass channels (Fig. 2c) highlight two important features. First, mesh electronics with α
= 45° and widths substantially larger than the constriction ID can be
smoothly injected. Relatively straight longitudinal elements are seen in
Fig. 2c, I and II,
where the 5 mm 2D mesh widths are 11- and 20-times larger than the
respective 450 and 250 μm ID needle constrictions. Second, even 1.5 cm
width mesh electronics (Fig. 2c, III) can be injected smoothly through a 33-times smaller ID (450 μm) constriction.
More plus pictures at link.
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