1. technology and computing

73
Development of Micro/Nano Electro
Mechanical System based Sensors for
Societal Applications
M. S. VINCHURKAR1, V. SEENA1,3, D. AGARWAL1,
NEHUL GULLAIYA1, S. MUKHERJI2 and V. RAMGOPAL
RAO1
1 Centre of Excellence in Nanoelectronics, Department of
Electrical Engineering
2 Department of Biosceiences and Bio-engineering Indian
Institute of Technology, Bombay, India – 400 076
3 Indian Institute of
Thiruvananthapuram
Space
Science
and
Technology,
*Email: [email protected]
Abstract
Using surface functionalized piezoresistive polymer composite
cantilevers, prototypes of systems have recently been demonstrated at IIT
Bombay for point of care cardiac diagnostics and for vapour phase
explosive detection. Prototypes of these systems are currently being tested
in the field conditions with the help of NanoSniff Technologies Pvt. Ltd., a
company incubated at IIT Bombay based on this technology.
Keywords : biosensor, microsensor, biofunctionalization SU-8-CB, cantilever.
1. Introduction
Microsensors based on Micro/nano electro mechanical
systems are among the first examples when the investigation of
microelectronic application of microfabrication technology was
started.
Electronic
sensor
applications
require
fast,
comprehensible, economical and ultra sensitive methods for
74
recognition of target analytes. MEMS applications with
‘‘Microcantilever’’ transducers have emerged from the increasing
demand for these miniaturized high throughput sensors supported
by advancement in microfabrication. MEMS devices based on
micromechanical cantilevers offer an enhanced sensitivity and an
exceptional dynamic range which lead to their diverse sensing
applications. Many physical1, 2, chemical3, and biological4–6
microcantilever based sensors have been reported till date. MEMS
sensors with microcantilever as a transducer work on the basis of
conversion of physical parameters such as temperature changes
around them or chemical or biomolecular interactions occurring
directly on their surface into either static displacements (static
mode) or a change in resonance frequency (dynamic mode) of the
microcantilever beam6–8. Depending on the sensor application, the
microcantilever design needs to be optimized differently with
respect to the transduction modes used. Either optical (external) or
electrical (integrated) transduction techniques are applied to
monitor the nanomechanical motion. An external optical readout
mechanism like a laser beam needs extra device alignment step
which can be eliminated by incorporation of a transduction
mechanism within the mechanical element. The practical
limitations of external transduction method are overcome by
employing self-sensing microcantilevers with integrated electrical
transduction mechanisms. In a microcantilever with an integrated
piezoresistor, electrical transduction of strain is performed by
measuring the corresponding resistance change. When a surface
functionalized microcantilever with molecules or thin film coatings
that are specific to the target molecules is exposed to the ambient
containing analyte, the selective molecular adsorption creates a
differential surface stress between the top and bottom surfaces of
the microcantilever. This differential surface stress leads to a
change in resistance of the piezoresistive layer. The surface stress
sensitivity is proportional to the the ratio of the gauge factor (K) of
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the piezoresistive film to the Young’s modulus (E) of the cantilever
structural material. Stable polymers such as SU-8 (glycidylether of
bis-phenol A) with low E values are favored as structural layers for
microcantilevers over the conventional materials like silicon. SU- 8
microcantilevers with piezoresistive layers such as gold and
polysilicon have been reported earlier9,10,11. Performance improvement of the piezoresistive SU-8 microcantilever sensorshas been
achieved by integrating SU-8-carbon black (CB) nanocomposite as
the strain sensitive layer12-16.
2. Device Design and Fabrication
The dimensions of the microcantilevers are decided based on
their stiffness which reflects in their sensitivity in static mode and
the resonance frequency of the microcantilever, which determines
their stability under external vibrations.14. The piezoresistive SU-8
microcantilever device has a set of measurement and reference
microcantilever beams as depicted in the schematics of the
polymer device die (Fig. 1)14.
Fig. 1 : Device design of the SU-8-CB peizoresistive micro-cantilever; planar
schematic (A); Cross sectional schematic (B)14
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The fabrication of these microcantilevers with SU-8/CB
nanocomposite piezoresistive layers sandwiched between two SU8 layers involves five levels of lithography15. The process sequence
for fabricating this composite microcantilever is shown in Fig. 2
13,11,16
.
Fig. 2: Process sequence for SU-8-CB microcantilevers (a) First layer of SU-8
(b) Cr/Au for contacts (c) strain sensitive composite layer (d) encapsulating SU8 (e) Thick SU-8 (f) Release of cantilever die from the substrate15
Silcon wafer used as the dummy susbstrate has been RCA
cleaned and silicon dioxide which acts as a sacrificial layer has been
deposited. The piezoresistive layer is a polymer nanocomposite of
Carbon Black (CB) Conductex 7067 Ultra in SU-8. For this, optimum
carbon black filler loading in the range of 8–9 vol% was used13,14. By
adjusting the lithographic parameters, this nanocomposite was
successfully patterned just like any other negative UV resist. Wet
etching of the silicon dioxide layer releases the polymer device chips
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from silicon substrate. The photograph of the unreleased and released
devices along with an SEM image of one of the fabricated devices are
shown in Fig. 3.
Fig. 3: Photograph of strips of different polymer nanocomposite microcantilever device chips after the release process (A); SEM image of one type of
SU-8/CB nanocomposite microcantilevers (B); Optical micrographs of SU-8/CB
nanocomposite microcantilevers devices on the wafer (C and D);13,14,16
3. Device Characterization
Electromechanical characterization of the fabricated
microcantilevers was performed for verifying the piezoresistive
transduction and extracting the sensor sensitivity. These devices
showed deflection sensitivity ( R/R for unit deflection) of 1.1
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ppm nm−1. Using the ‘Polytek Doppler’ vibrometer the resonance
frequency of these microcantilevers was extracted (Fig. 4). The
resonance frequency was found to be well above the lower limit
needed for external vibrational noise immunity.
Fig. 4: Resonance frequency plot of SU-8-CB microcantilever.23
4. Sensor Applications
In recent years, microcantilevers have been identified to be
suitable for developing chemical and biological sensors because of
their advantages such as small size, high sensitivity, label free
detection, low power consumption and versatility for incorporating
sensors arrays in a single miniature package.17-24. Among the
transduction schemes for these sensors, optical readout schemes
are known to be sensitive and simple. However, this class of
sensors suffer from practical limitations such as incompatibility
with opaque solutions, time consuming laser alignment, difficulty
in integration with sensor electronics etc. Hence, for the
biomolecular sensing applications, microcantilever sensors with
sensitive electrical transduction schemes would be a better
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candidate as compared to their optical counterpart. Application of
the peizoresistive polymeric (SU-8-CB) microcantilevers as
cardiac biosensor and explosive detector are described in the
following sections.
5. Cardiac Biosensor
According to the World Health Organization (WHO) survey,
by 2030, Cardiovascular Diseases (CVDs) will cause 23.6 million
deaths around the world25.There is an urgent need for a sensor
which can detect the cardiac markers at an early stage of Acute
Myocardial Infarction (AMI). Authors have combined the
advantages of polymeric microcantilevers and piezoresistive
readout into an inexpensive and highly sensitive platform for point
of care applications. The integrated system called "infarcSens" or
"iSens", is a peizoresistive microcantilever based affinity biosensor
array for sensing myocardial infarction and subsequent cardiac
status prognosis, using a suite of molecular markers. It is
particularly useful in detecting heart attacks that go unnoticed
before a major or fatal attack occurs. The target cardiac biomarkers
are Human fatty acid binding protein (hFABP), Troponin,
Myoglobin and CK-MB.
6. Bio-functionalization
In order to use the peizoresistive SU-8-CB microcantilevers
for biosensor applications, the cantilever should be biofunctionalized with biomolecules specific to the target analyte such
as an antibody. The protocol for the bio-functionalization has been
developed earlier26,27.
Briefly, functional group modification of either top or bottom
surface of the microcantilever is done as the first step. A dry
method involving the pyrolytic (filament temperature of 1450°C)
dissociation of Ammonia gas inside a hot wire Chemical Vapour
Deposition (CVD) chamber is employed to get surface amine
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groups on the SU-8-CB microcantilevers26. After the CVD
treatment the microcantilevers are mounted in an in-house built
liquid flow cell and the rest of the biofunctionalization steps were
carried out inside the flow cell. The microcantilever surface amine
groups are then reacted with the homo-bifunctional linker
glutaraldehyde for subsequent covalent binding of the antibodies
on the surface. The unsaturated aldehyde sites and nonspecific
adsorption sites on the antibody immobilized surface are blocked
using bovine serum albumin (BSA). The efficiency of the surface
biofunctionalization is monitored by a control experiment using
labeled antibodies and fluorescence microscopy. A typical
fluorescence microscopic image of the biofunctionalized SU-8-CB
microcantilevers is shown in Fig. 5.
Fig. 5: Fluorescence image of biofunctionalized SU-8-CB microcantilever die
7. Read Out Mechanism and Measurement Set-up
A differential microcantilever surface stress is created because
of the binding of the marker protein to the immobilized antibody
causing a bending of the microcantilever, which is in the order of a
few tens of nanometers9. The corresponding change in resistance
of the piezoresistive nanomechanical cantilevers is in the range of
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a few parts per million. An instrumentation setup28 that generates a
voltage signal analogous to the resistance changes down to 14 parts
per million (ppm) with a maximum sensitivity of 2.4 V/ppm
integrated with the peizoresistive microcantilever-liquid flow cell
unit comprises the table-top sensor for cardiac diagnostics. All the
measurements on the biofunctionalized microcantilevers are done
with respect to the nonfunctionalized reference microcantilevers in
the liquid flow cell. A representative example of the sensor signal
in the case of cardiac marker protein h-FABP24 is given in Fig. 6
(A) along with a photograph of the cardiac biosensor prototype
“iSens” Fig. 6 (B).
Fig. 6: Signal recorded as a change in voltage for the detection of cardiac marker
protein FABP. (Baseline was adjusted to zero before analyte introduction) (A);
iSens: A point of care system for cardiac diagnostics (B)24.
It is largely due to the high economical and social value of
modern medical devices that new materials and processes are
incorporated at a very early stage into new products. The point of
care cardiac diagnosis system “iSens” developed at IIT-Bombay is
one such example. As micro machined micro/nano size cantilevers
are batch-fabricated they offer the advantage of parallelization into
sensor arrays which can be used to detect various markers
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simultaneously. Our ultimate aim is to develop a lab on a chip
piezoresistive microcantilever based over-the-counter, field
portable, high-throughput, protein detection systems as a common
platform for characterizing a wide spectrum of diseases. Such a
"protein-chip" would detect multiple markers in a single step in
contrast to the currently available assays which require a separate
reaction for each analyte. The sensing electronics and the
associated data management software for tracking the markers,
with the time required for creating an epidemiological database is
also being developed. This will reduce both the time and cost of
diagnosis.
8. Explosive Detector
Ion mobility spectrometry (IMS) and mass spectrometry are the
conventional explosive detection techniques but their use is limited
due to longer response times besides being bulky and expensive. As
explosives have very low vapour pressures, detectors with ultra high
sensitivity are required for their vapour phase detection. Use of
microcantilever based MEMS devices in explosive detection has
been reported in the literature29,30. In order to use microcantilevers
for explosive detection, functionalization of the cantilever surface
with a chemically selective layer or receptor for the target molecule
is needed. The functionalization procedure is based on the receptor
and microcantilever surface chemistry. Specific receptors like 4MBA (4-mercaptobenzoic acid), SXFA, etc.30,31 have been reported
for the most popular explosives such as TNT, RDX and PETN. In
our case, for the explosive vapour detection, the peizoresistive SU8-CB microcantilevers were functionalized using 4-MBA as a
receptor layer29. The sulfhydryl group 4-MBA forms a stable
monolayer on a gold surface. Thus, for a selective functionalization
with 4-MBA, one of the microcantilever surfaces was coated with
30 nm of gold using titanium as the adhesion layer. The
peizoresistive SU-8-CB microcantilevers with the monolayer of 4MBA were used in the explosive sensor. The functionalized and
non-functionalized (as control) microcantilever devices were stored
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in a humidity controlled chamber. The devices were then connected
to a signal conditioning circuit and kept inside a gas flow cell for
explosive vapour detection. Prolonged dry nitrogen purging of the
device chamber to reduce the humidity levels was done before
starting the measurement. The vapour generator containing the TNT
source was maintained at a constant temperature using a calibrated
temperature controller. The carrier gas for the TNT was dry nitrogen
and the gas flow of 30 sccm was maintained using a mass flow
controller (MFC). The sensor was regenerated with dry nitrogen
purging. The calibrated vapour generator is capable of delivering
TNT vapours with concentrations of less than 10 ppb. A photograph
of the experimental setup along with microcantilever response
recorded during a cycle of exposure to TNT and nitrogen are given
in Fig. 7.
Fig. 7: (a) Experimental set up for explosive vapour experiments (b)Response of
4-MBA coated Microcantilever to TNT vapours (c) A prototype of the explosive
detector system.23
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These devices could detect TNT vapour concentrations down to a
few ppb. Thus an effective chemical sensing application of the
peizoresistive SU-8-CB microcantilevers for the detection of
explosive vapours has been successfully demonstrated.
Acknowledgement
The authors wish to acknowledge the funding received from the
Department of Information Technology, Government of India,
through the Centre of Excellence Nanoelectronics. The cardiac
diagnostics work is supported by the National Programme on Micro
& Smart Systems (NPMASS) while the explosive detector work is
supported by the Principal Scientific Adviser’s office, Govt. of India.
References
1.
Berger R, Lang H P, Gerber Ch, Gimzewski J K, Fabian J H,
Scandella L, Meyer E and G¨untherodt H-J (1998) Micromechanical
thermogravimetry. Chem. Phys. Lett. 294, 363–9.
2.
Chen L T, Lee C Y and Cheng W H (2008) MEMS-based humidity
sensor with integrated temperature compensation mechanism.
Sensors Actuators A 147, 522–8.
3.
Lim S H, Raorane D, Satyanarayana S and Majumdar A (2006)
Nano-chemo-mechanical sensor array platform for high-throughput
chemical analysis. Sensors Actuators B 466–74
4.
Carrascosa L G, Moreno M, A´ lvarez M and Lechuga L M (2006)
Nanomechanical biosensors: a new sensing tool. Trends Anal. Chem.
25, 196–206.
5.
Arntz Y, Seelig J D, Lang H P, Zhang J, Hunziker P, Ramseyer J P,
Meyer E, Hegner M and Gerber C (2003) Label-free protein assay based
on a nanomechanical cantilever array. Nanotechnology 14, 86–90.
6.
Ziegler C (2004) Cantilever-based biosensors. Anal. Bioanal.Chem.
379, 946–59.
7.
Fritz J, Baller M K, Lang H P, Rothuizen H, Vettiger P, Meyer E,
G¨untherodt H, Gerber C and Gimzewski J K (2000) Translating
biomolecular recognition into nanomechanics. Science 288 316–8.
8.
Hosaka S, Chiyoma T, Ikeuchi A, Okano H, Sone H and Izumi T
(2006) Possibility of a femtogram mass biosensor using a selfsensing cantilever.Curr. Appl. Phys. 6, 384–8.
85
9.
Thaysen J, Yalcinkaya A D, Vettiger P and Menon A (2002)
Polymer-based stress sensor with integrated readout. J. Phys.D:
Appl. Phys. 35, 2698–703.
10.
Kale N S, Nag S, Pinto R and Rao V R (2009) Fabrication and
characterization of a polymeric microcantilever with an encapsulated
hotwire CVD polysilicon piezoresistor. J. Microelectromech. Syst.
18, 79–87.
Seena V, Kale N, Nag S, Joshi M, Mukherji S, Rao V R (2009)
Developing a polymeric microcantilever platform technology for
biosensing applications. International Journal of Micro and Nano
Systems 1 (1), 65-70.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
Gammelgaard L, Rasmussen P A, Calleja M, Vettiger P and Boisen
A (2006) Microfabricated photoplastic cantilever with integrated
photoplastic/carbon based piezoresistive strain sensor. Appl. Phys.
Lett. 88, 1508.
Seena V, Rajorya A, Pant P, Mukherji S and Rao V R (2009) Polymer microcantilever biochemical sensors with integrated polymer
composites for electrical detection. Solid State Sci. 11, 1606–11.
Seena V, Fernandes A, Pant P, Mukherji S, and Rao V R (2011)
Polymer nanocomposite nanomechanical cantilever sensors: Material
characterization, device development and application in explosive
vapour detection. Nanotechnology 22, 1–11.
Seena V, Rajorya A, Fernandes A, Dhale K, Pant P,Mukherji S and
Rao V R (2010) Fabrication and characterization of novel polymer
composite microcantilever sensors for explosive detection. IEEE
23rd Int. Conf. MEMS (IEEE MEMS 2010) Tech. Dig. 851–854.
Seena V, Fernandes A, Mukherji S, Rao V R (2011) Photoplastic
Microcantilever Sensor Platform for Explosive Vapour Detection.
International Journal of Nanoscience 10, 739-43.
Fritz J, (2008) Cantilever biosensors Analyst 3 855-63.
Prashanthi K, Miriyala N, Gaikwad R D, Moussa W, Rao V R and
Thundat T (2013) Vibrational energy harvesting using photopatternable piezoelectric nanocomposite cantilevers. Nano Energy
(Elsevier) Accepted for publication.
Raval H N, Sutar D S and Rao V R (2013) Copper(II) phthalocyanine based organic electronic devices for ionizing radiation
dosimetry applications. Organic Electronics (Elsevier) Accepted for
publication.
Raval H N, Sutar D S, Nair P R and Rao V R (2013) Investigation of
effect of ionizing radiation exposure on material properties of
86
organic semiconducting oligomer – Pentacene. Organic Electronics
(Elsevier) Accepted for publication.
21.
Ray P, Rao V R (2013) Al-Doped ZnO thin-film transistor embedded
micro-cantilever as a piezoresistive sensor. Applied Physics Letters
(APL) Accepted for publication.
22.
Reddy C V B, Khaderbad M A, Gandhi S, Kandpal M, Patil S,
Chetty K N, Rajulu K G, Chary P C K, Ravikanth M and Rao V R
(2012) Piezoresistive SU-8 Cantilever with Fe(III)porphyrin coating
for CO Sensing. IEEE Transactions on Nanotechnology 11, 701-6.
23.
Seena V, Dudhe R S, Raval H N, Patil S, Kumar A, Mukherji S, Rao
V R (2011) Organic sensor platforms for environmental and security
applications. Electro-Chemical-Society (ECS) Transactions 35, 6777.
24.
Agarwal D K, Gandhi S I, Narayan Y, Aithal S, Chatterji G, Surya S
G, Seena V, Mukherji S, Rao V R (2012) Detection of heart-type
human Fatty Acid Binding Protein(h-FABP) using piezoresistive
polymer micro-cantilevers. Nano-Mechanical sensors conference
(NMC).
25.
http://www.who.int/mediacentre/factsheets/fs317/en/ index.html.
26.
Joshi M, Kale N, Lal R, Rao V R, Mukherji S (2007) A novel dry
method for surface modification of SU-8 for immobilization of
biomolecules Bio-MEMS. Biosensors and Bioelectronics 22, 2429–
35.
27.
Joshi M, Pinto R, Rao V R, Mukherji S (2007) Silanization and
antibody immobilization on SU-8. Applied Surface Science 253,
3127–32.
28.
Surya S, Nag S, Fernandes A, Gandhi S, Agarwal D, Chatterjee G,
Rao V R (2011). IEEE International Symposium on Electronic
System Design 34.
29.
Pinnaduwage L A, Hawk J E, Boiadjiev V, Yi D and Thundat T
(2003) Use of microcantilevers for the monitoring of molecular
binding to self-assembled monolayers. Langmuir 19, 7841–4.
30.
Senesac L and Thundat T (2008) Nanosensors for trace explosive
detection. Mater. Today 11, 28–33.
31.
Chen Y, Xu P and Li X (2010) Self-assembling siloxane bilayer
directly on SiO2 surface of micro-cantilevers for long-term highly
repeatable sensing to trace explosives. Nanotechnology 21, 265501.