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Research Article
Fabrication of Patterned Integrated Electrochemical Sensors
Muhammad Mujeeb-U-Rahman, Dvin Adalian, and Axel Scherer
California Institute of Technology, Department of Physics and Applied Physics, Pasadena, CA 91125, USA
Correspondence should be addressed to Muham
mad Mujeeb-U-Rahman; mrahman@caltech.edu
Received 18 March 2015; Revised 15 June 2015; Accepted 25 June 2015
Academic Editor: Carlos R. Cabrera
Copyright © 2015 Muhammad Mujeeb-U-Rahman et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distributio
n, and reproduction in any medium, provided the original work is
properly cited.
Fabrication of integrated electrochemical sensors is an important step towards realizing fully integrated and truly wireless platforms
for many local, real-time sensing applications. Micro/nanoscale patterning of small area electrochemical sensor surfaces enhances
the sensor performance to overcome the limitations resulting from their small surface area and thus is the key to the successful
miniaturization of integrated platforms. We have demonstrated the microfabrication of electrochemical sensors utilizing top-down
lithography and etching techniques on silicon and CMOS substrates. This choice of fabrication avoids the need of bottom-up
techniques that are not compatible with established methods for fabricating electronics (e.g., CMOS) which form the industrial basis
of most integrated microsystems. We present the results of applying microfabricated sensors to various measurement problems, with
special attention to their use for continuous DNA and glucose sensing. Our results demonstrate the advantages of using micro- and
nanofabrication techniques for the miniaturization and optimization of modern sensing platforms that employ well-established
electronic measurement techniques.
1. Introduction
Ultra-small scale integrated electrochemical sensors have
gained considerable interest as solutions to diagnostic mon-
itoring situations requiring a small footprint. One category
of microsensors that benefits from miniaturization is medical
implants which require fully autonomous sensing platforms
along with electronic driving circuitry within the smallest
possible volume [
1
]. Electrochemical sensing technology in
particular is a very attractive solution for health monitoring
as it is possible to integrate electrochemical circuits with
device electronics on a comparatively small size scale [
2
].
Microscale and nanoscale patterning of the sensor surfaces
holds the key to making these devices perform effectively
and to reducing the sensor impedance [
3
]. Such techniques
canalsobeusedtoenhancetheperformanceoflargescale
electrodes made via more conventional methods (e.g., screen
printing) [
4
]. Usual implementations of electrochemical sen-
sors commonly utilize a planar electrode configuration, but
micro/nanoscale patterning of the electrodes provides many
technicaladvantagessuchasahighersurfaceareaandthe
control over the diffusion profile near the electrode surfaces
[
5
]. This surface patterning also allows for more efficient
utilization of functional coatings (e.g., enzyme or binding
coatings) on the electrodes [
6
]. Employing these techniques
to decrease the total area needed per sensor, along with
embedding CMOS electronics underneath the sensor, leads
to reducing the system size to practical dimensions [
7
]. This
size reduction also provides major advantages in reducing
individual device cost and foreign body response to such
devices when used for
in vivo
applications [
8
].
The most common fabrication methods of depositing
electrodes for electrochemical sensors at small (sub-mm) size
scale includes direct Physical Vapor Deposition (PVD) or
Chemical Vapor Deposition (CVD). These techniques, when
used under nonequilibrium conditions, can yield patterned
surfaces [
9
]. However, the resulting structures are typically
not suitable for long-term use because of their deformation
in liquid environments as a result of large capillary forces
acting on the surface nanostructures in a solution [
10
].
This limitation can be overcome by use of liquid deposition
techniques, for example, VLS growth [
11
], porous templates
[
12
], or complex electrochemical plating mechanisms [
13
],
since these methods have better resilience to liquid forces.
However, such deposition approaches are usually not com-
patible with the current CMOS fabrication technologies or
Hindawi Publishing Corporation
Journal of Nanotechnology
Volume 2015, Article ID 467190, 13 pages
http://dx.doi.org/10.1155/2015/467190
2
Journal of Nanotechnology
other vacuum-based fabrication processes. Although it has
been shown that these alternative methods can be adapted
for fabrication on wafer scale, the overall process is generally
complex and expensive. Often, it involves deposition of very
thick (10
m) metal layers as templates [
10
]. In the cases
that nonvacuum (e.g., liquid) processing has been applied
to fabricate nanostructures exact control of the geometry at
the nanometer scale has proven difficult. High temperatures,
corrosive atmospheres, or nonuniform deposition due to
internal stresses during deposition often render such bottom-
up methods troublesome to scale up with consistency over
large areas and over many batches for the reproducible
industrial fabrication of low-impedance electrodes [
9
].
In this work, we present a top-down fabrication method-
ology to fabricate nanoscale patterns on electrodes with very
precise control over the exact geometry and with unifor-
mity over large areas. Our method uses only vacuum-based
processing without the need for making electrical contacts
to the devices to be patterned or any exotic liquid-based
processing. This enables a precise control over the electro-
chemical environment surrounding the sensor electrodes.
Nanofabricated silicon pillars are coated with metal to form
our electrodes and exhibit excellent mechanical resilience
and successfully resist liquid surface tension forces. We
demonstrate deposition of different metals on nanostructures
to render them effective for many different sensing and
actuation applications. The large and controllable surface
area of lithographically patterned surfaces provides a simple
andefficienttechniquetoobtainexcellentandpredictable
sensor performance in medical applications such as when
quantitatively determining the concentrations of metabolites
and when detecting DNA [
14
]. We believe that this is the first
demonstration of metallized nanopillars in fully integrated
electrochemical sensor systems with negligible variation in
sensor properties over many fabrication batches. Metalliza-
tion of etched nanostructures can be easily scaled up through
industrial fabrication approaches to produce high surface
area sensors in existing micro/nanofabrication foundries.
Another advantage of metallization of nanostructures is that
the sensor elements can be shaped in 3D using well-studied
and well-controlled silicon-based fabrication processing. Sil-
icon etching is a very mature and well-understood field,
and three-dimensional structures can be achieved with great
repeatabilityaswellasgeometricaccuracy[
15
].
2. Device Design
The sensor design to test the effects of surface area enhance-
ment on electrochemical performance is based upon a
three-electrode electrochemical sensor configuration with an
optional fourth electrode which can be electrically connected
when needed. The standard three electrodes are the working
electrode (WE), counter electrode (CE), and reference elec-
trode (RE) [
16
]. The optional fourth electrode can be used
as a second working electrode for differential readings or
forbackgroundnormalizationasthesensorages.Allofthe
electrodes are defined by processing a silicon substrate which
allows vacuum-based nanometer scale silicon processing
techniques to be applied. The patterned surface benefits
fromtheexcellentmechanicalelasticityandresilienceof
nanostructures [
17
]. The surface material of the electrodes
canbechosentomatchtherequirementsofaparticular
application. Since the sensing mechanism only depends on
the exposed surface layer and since most electrochemically
active materials are precious metals [
18
], depositing a thin
metal layer on top of an underlying silicon substrate is
economically very beneficial. Using only a thin layer also
provides mechanical integrity since most of the pillar compo-
sition is single crystal silicon. The reference electrode for our
electrochemical measurement consists of Ag/AgCl thin film
bilayer deposited on the RE. The CE is coated with Pt for most
of our applications and the WE material varies based upon the
specific application but is commonly Pt or Au for our devices.
A typical sensor is designed to fit in an area of 500
mby
500
m square. The sensor is connected to large contact pads
via metal contact lines. The contact lines are insulated (using
insulating epoxy, e.g., SU8) to only expose the sensor to test
solutionsduringsensortesting.Thecontactpadsareusedto
connect the sensor to a test instrument (e.g., Potentiostat) to
read its electrical output on a computer. A typical sensor with
contact pads is depicted in
Figure 1
.
The sensor electrodes need to be coated with spe-
cific chemistry (i.e., “functionalized”) to react with specific
molecules for detection in complex biochemical environment
[
19
]. To perform glucose sensing in the presence of many
similar molecules in a complex solution, for example, the
sensor must be coated with a glucose-sensitive layer [
20
].
Many different types of functionalization methods have been
developed to convert nanoscale sensors into sensitive and
specific devices [
19
]. For amperometric measurements with
aredoxenzyme,
in situ
functionalization is a simple and
efficient method which allows the application of function-
alized materials directly to the sensor surface [
21
]. This
method has the benefit that no electrical connections need
to be made to the ultra-small scale devices, which greatly
simplifies the fabrication. However, it is important to note
that electrochemically deposited coatings can be controlled
morepreciselyandcanbeusedforwiredsensors[
22
].
In this work, functionalization is achieved either by
using direct immobilization of a hydrogel containing the
desired chemistry (e.g., glucose-sensitive hydrogel) or by
wetting the electrodes in a solution containing the desired
binding molecules (e.g., nucleic acid strands) depending on
the application. A typical sensor geometry employing based
functionalization layer is illustrated in
Figure 2
.
3. Analysis
The main reason for micro/nanopatterning is to enhance
the sensitivity of the device since it is directly related to
thesurfaceareaavailableforthesensingmechanism.This
advantage of patterned electrodes over planar electrodes can
bequantifiedbycomparingthesurfaceareaofacircularpillar
patterned electrode
(푆)
as compared to a planar electrode
(푆표)
(the derivation for
(1)
and
(2)
isgivenintheAppendix):
푆표
=
1
+
7
.
26
(
)(
).
(1)
Journal of Nanotechnology
3
Sensor electrodes
Contact pads
Figure 1: Patterned electrochemical sensor design with contact pads.
Polymer encapsulation
Functionalization matrix
Figure 2: Nanopatterned electrodes coated with a functionalizing (immobilization) matrix.
Here,
is the radius of the pillars,
istheheightofthe
pillars,
is the separation between the pillars (center to
center distance), and the arrangement is hexagonal closed
pack form. For a standard rectangular array of pillars, this
surface area equation becomes
푆표
=
1
+
6
.
28
(
)(
).
(2)
For practical applications, the difference between hexagonal
and rectangular packing is negligible, and therefore we uti-
lized rectangular arrangements as these are easier to rescale
quickly. The theoretical surface area enhancement from such
patterningisplottedagainstthesizeofthepillarsin
Figure 3
.
Here, pillar aspect ratio is fixed
(ℎ/푟 = 20
)tosignifytheeffect
of reducing pillar radius on surface area.
This shows that higher aspect ratio and higher packing
density result in higher surface area for a given geometric
area. The exact increase depends upon the scale of patterning
andismostlydeterminedbytheapplicationaswellasthecost
of the micro- or nanofabrication. The smaller the pillar, the
more the surface area gain but simultaneously the fabrication
becomes more complex and costly. The feature height of the
devices is also limited by the surface tension forces in the
liquid which can cause sensor damage depending upon both
mechanical and geometrical properties of the pillars. The
deflection
(Δ)
of a pillar due to capillary forces is described
by the following equation [
10
]:
Δ=
푃ℎ
3
3
퐸퐼
.
(3)
0
20
40
60
80
100
0
10
20
30
40
Pillar radius,
r
(nm)
Surface area enhancement (
S
/
So
)
Surface area enhancement as function of pillar radius
a = 250
nm,
h=20×r
Figure 3: Surface area enhancement due to nanopatterning.
Here,
is the capillary force,
is pillar height,
is young’s
modulus, and
is second moment of inertia given by
퐼=
휋푟
4
4
.
(4)
Using
(3)
and
(4)
,
Δ=
4
3
휋퐸푟
(
)
3
.
(5)
4
Journal of Nanotechnology
1.16 휇
m
1.33 휇
m
1.22 휇
m
42.8
nm
(a)
(b)
Figure 4: SEM image of plasma-etched nanopillars demonstrating size-independent etching (a) 1
m pillar beside a 50 nm pillar and (b)
50 nm pillar array.
(a)
151
nm
275
nm
(b)
Figure 5: Nanopillars after oxidation. (a) High voltage imaging to confirm the conformality of the oxide layer (b).
This shows that for a given capillary force, surface tension is
proportional to third power of pillar aspect ratio
(ℎ/푟)
and
is inversely proportional to its Young modulus
(퐸)
.Control
of both of these factors is required to have a safe amount of
deflection due to capillary forces and limit sensor damage.
Control on young’s modulus is achieved by using high purity
materials with high Young’s modulus. Silicon and Pt group
metals have Young’s modulus in GPa range in nanostructures
and can be appropriately flexible [
17
]. Aspect ratio control is
achieved during fabrication by controlling pattern sizes and
etching time, as demonstrated in the next section.
4. Fabrication
The complete fabrication sequence used to define our pat-
terned sensor electrodes consists of the following steps: litho-
graphic patterning, pattern transfer processes (e.g., etching),
interface control methods including deposition of metals and
insulators, isolation coatings between electrodes, and finally,
in some applications, functionalization of the metal contact
surface.
For nanoscale patterning, EUV or electron beam lithog-
raphy can provide the small scale feature resolution. To be
able to rapidly tune the geometries, we have chosen to
useelectronbeamlithographyandusePMMAA4(witha
molecular weight of
950 K) to achieve clean liftoff while
still meeting the required resolution. A 50 nm thick alumina
mask is sputter coated with a Temescal TES BJD-1800 DC
reactive sputter deposition system by depositing aluminum
in the presence of oxygen plasma for 5 minutes. The room
temperature silicon plasma etch recipe for nanoscale features
is described by Henry et al. [
15
]. The etch recipe was iteratively
optimized to achieve uniform etch depth for different pillar
widths and uniform sidewall roughness. Etching results are
shown in
Figure 4
, demonstrating uniformity of etch over
different pillar sizes and over large arrays.
We then thermally oxidized the pillar structures in a
wafer furnace at 1000
C for 90 minutes followed by 15-minute
nitrogen anneal with a gradual return to room temperature.
Theresultsshowaveryuniformandcontinuouslayerof
oxide as seen in
Figure 5
. A FEI Sirion 200 scanning electron
microscope was used for this high contrast imaging. The Si
core and the oxide outer layer can be differentiated due to the
second electron emission imaging contrast between silicon
and its oxide.
For standard CMOS devices, thick top metal (
4.6
m)
aluminum is used for laying out the sensor electrodes