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A Review of microcantilevers for sensing applications

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 A Review of Microcantilevers for Sensing Applications

A Review of Microcantilevers for Sensing Applications

Sandeep Kumar Vashist

Copyright AZoM.com Pty Ltd.
This is an AZo Open Access Rewards System (AZo-OARS) article distributed under the terms of the AZo–OARS
http://www.azonano.com/oars.asp which permits unrestricted use provided the original work is properly cited but is
limited to non-commercial distribution and reproduction.

Submitted: May 22nd, 2007

Posted: June 18th, 2007

DOI: 10.2240/azojono0115

Topics Covered
Abstract
Keywords
Introduction
Mass Sensitive Detection by Microcantilevers
Microcantilever Deflection Detection Methods
The Piezoresistive Deflection Detection Method
The Optical Deflection Detection Method
The Capacitive Deflection Detection Method
The Interferometry Deflection Detection Method
The Optical Diffraction Grating Deflection Detection Method
The Charge Coupled Device (CCD) Detection Method
Mechanical Properties of Cantilever
Bending Behavior of Cantilever Beams
Microcantilever Sensors
Materials Used in Commercial Cantilevers
Cantilevers Use in Non-Contact Modes
Advantages of Microcantilever-Based Sensors
Types of Sensors Based on Micro and Nanocantilevers
Sensing Applications of Microcantilevers in Physics and Chemistry
Humidity Sensors
Herbicide Sensors
Metal Ion Sensors
Temperature Sensors / Heat Sensors
Viscosity Sensors
Calorimetry Sensors
Sensor Detecting Magnetic Beads
Cantilever Based Telemetry Sensors
Microsensors to Monitor Missile Storage and Maintenance Needs
Remote Infrared Radiation Detection Sensors
Explosives Detection Devices
Sensing Applications of Microcantilevers in the Field of Disease Diagnosis
Cancer Detecting Microchips
Myoglobin Detection Sensors
Biosensor for Coronary Heart Disease
Cantilever Based Sensors to Detect Single-Nucleotide Polymorphisms
Biochips
Nanocantilevers: A Major Breakthrough in Sensors
Conclusions
References
Contact Details

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 Sandeep Kumar Vashist

Abstract

Microelectromechanical Systems (MEMS) [1,2] have come into existence only in the last
decade. Microcantilevers are the most simplified MEMS based devices. Diverse applications of
microcantilevers in the field of sensors have been explored by many researchers. Several
groups have also shown the possibility of using microcantilevers for the diagnosis of prostate
cancer [3], myocardial infarction [4] and glucose monitoring [5]. Scientists are chasing the
vision of making miniaturized biochips based on an array of microcantilevers, which can detect
several routinely diagnosed diseases simultaneously in the clinical laboratory. Recently the
development of nanocantilevers have scaled down the technology further with the capability of
ultra sensitive detection of analytes combined with high throughput.

Keywords
Microcantilevers, sensors, diagnostics, MEMS

Introduction

Molecular diagnostic devices are getting smaller with the advancement of miniaturization
technologies. There is increasing interest in the field of biosensor research on miniaturized
platforms. Miniaturization is essential for in vivo physiological monitoring, multiple specificity
sensor arrays, sensor portability and minimized sample volumes. Conventional biosensors
need extensive packaging, complex electronic interfacing and regular maintenance. These
drawbacks could be reduced by the use of MEMS devices that integrate electronics and
micromechanical structures on chips.
Microcantilevers have been employed for physical, chemical and biological sensing. They have
also have wide applications in the field of medicine, specifically for the screening of diseases,
detection of point mutations, blood glucose monitoring and detection of chemical and biological
warfare agents. These sensors have several advantages over the conventional analytical
techniques in terms of high sensitivity, low cost, simple procedure, low analyte requirement (in
µl), non-hazardous procedures and quick response. Moreover, the technology has been
developed in the last few years for the fabrication and use of nanocantilevers for sensing
applications, thereby giving rise to nanoelectromechanical systems (NEMS). This development
has increased the sensitivity limit up to the extent that researchers can now visualize the
counting of molecules. With the ability of high throughput analysis of analytes and ultra
sensitive detection, this technology holds tremendous promise for the next generation of
miniaturized and highly sensitive sensors.

Mass Sensitive Detection by Microcantilevers

A microcantilever is a device that can act as a physical, chemical or biological sensor by
detecting changes in cantilever bending or vibrational frequency. It is the miniaturized
counterpart of a diving board that moves up and down at a regular interval. This movement
changes when a specific mass of analyte is specifically adsorbed on its surface similar to the
change when a person steps onto the diving board. But microcantilevers are a million times
smaller than the diving board having dimensions in microns and different shapes as shown in
figure 1.

Figure 1. Different types of microcantilevers (top view) (a) Rectangular (b) Double-legged (c)
Triangular.
Molecules adsorbed on a microcantilever cause vibrational frequency changes and deflection of
the microcantilever. Viscosity, density, and flow rate can be measured by detecting changes in
the vibrational frequency.

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 A Review of Microcantilevers for Sensing Applications

Another way of detecting molecular adsorption is by measuring deflection of the cantilever due
to adsorption stress on just one side of the cantilever. Depending on the nature of chemical
bonding of the molecule, the deflection can be up or down. Biochips with mechanical detection
systems commonly use microcantilever bi-material (e.g. Au–Si) beams as sensing elements.
The Au side is usually coated with a certain receptor. Upon the binding of the analyte (e.g.
biological molecules, such as proteins or biological agents) with the receptor, the receptor
surface is either tensioned or relieved. This causes the microcantilever to deflect, usually in
nanometers, which can be measured using optical techniques. The deflection is proportional to
the analyte concentration. The concept has been employed in screening certain diseases such
as cancer and detecting specific chemical and biological warfare agents.

Microcantilever Deflection Detection Methods

The Piezoresistive Deflection Detection Method

The piezoresistive method [6-8] involves the embedding of a piezoresistive material near the
top surface of the cantilever to record the stress change occurring at the surface of the
cantilever. As the microcantilever deflects, it undergoes a stress change that will apply strain
to the piezoresistor, thereby causing a change in resistance that can be measured by electronic
means. The advantage of the piezoresistive method is that the readout system can be
integrated on the chip. The disadvantage is that the deflection resolution for the piezoresistive
readout system is only one nanometer compared with one Angstrom by optical detection
method. Another disadvantage with the method is that a piezoresistor has to be embedded in
the cantilever. The fabrication of such a cantilever with a composite structure is more
complicated.
The piezoresistor material in the beam must be localized as close to one surface of the
cantilever as possible for maximum sensitivity. The type of doping being used for fabrication
of the piezoresistive material is an important factor. The piezoresistive coefficient of N-type
silicon is greater than that for P-type. The resistance of a piezoresistive material changes when
strain is applied to it. The relative change in resistance as function of applied strain can be
written as:
ΔR
= Κ lδ l Κ tδ t
R
where K denotes the Gage Factor, which is a material parameter. The subscripts l and t refer
to the longitudinal and the transversal part of the Gage Factor.
The sensitivity of a piezoresistor varies proportionally to the thickness t and the radius of
curvature. The Gage Factor is proportional to Young’s Modulus, E, which is the intrinsic
characteristic of material. The gage factor can also be calculated directly by straining the
cantilevers and measuring the resistance change.
ΔR
GF .δ =
R
where δ is the strain in the material and R is the resistance. For a sensitive device, the gage
factor should be of the order of 100.
The piezoresistive cantilever beam can be used as an arm of the Wheatstone Bridge circuit as
shown in figure 2.

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 Sandeep Kumar Vashist

Figure 2. The Wheatstone Bridge Circuit used for the piezoresistive microcantilever.

The resistance of the variable resistance arm ( R0 + ΔR ) in the above figure can be determined
by using the common Voltage divider formula and is shown as below:

There would be a resistance change whenever the cantilever is subjected to a deflection.

The Optical Deflection Detection Method

The optical method [8], as shown in figure 3, employs a laser beam of very low power of the
order that does not affect the biomolecules coated on the surface of the microcantilever and a
position sensitive detector (PSD). The laser beam falls on the cantilever and gets reflected as
the gold layer coated on the surface of the cantilever gives it an almost mirror like finish. The
reflected beam falls on the PSD. When the cantilever is undeflected i.e. it is not coated with
any molecule, the laser beam would fall on a particular spot on the PSD. As the cantilever
deflects, the position of the beam changes, which, in turn, is calculated using appropriate
electronics. The advantage of this detection system is that it is capable of detecting deflection
in the sub-nanometer range. But this method also has its own disadvantages. The presence of
a focused laser beam in a liquid cell environment can result in additional thermal management
issues giving rise to extraneous readings. Secondly, the alignment system is expensive and
involves great precision, which can ultimately raise the cost of the whole diagnostic kit. In
addition, it also reduces the kit’s portability.

Figure 3. Schematic of an optical detection system for detecting microcantilever deflection.

The reflected laser light from the deflected microcantilever falls at a different position on the
PSD. Depending on the distance between the two positions of the laser beam on the PSD, the
deflection of the microcantilever is determined.

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 A Review of Microcantilevers for Sensing Applications

The Capacitive Deflection Detection Method

The capacitive method [9] is based on the principle that when the cantilever deflection takes
place due to the adsorption of the analyte, the capacitance of a plane capacitor is changed.
Here the microcantilever is one of the two capacitor plates. This deflection technique is highly
sensitive and provides absolute displacement. But this technique is not suitable for measuring
large displacements. Moreover, it does not work in electrolyte solutions due to the faradic
currents between the capacitive plates. Therefore, it is limited in its sensing applications.

The Interferometry Deflection Detection Method

This optical detection method [10,11] is based on the interference of a reference laser beam
with the laser beam reflected by the cantilever. The cleaved end of an optical fiber is brought
close to the cantilever surface. One part of the light is reflected at the interface between fiber
and surrounding media, and the other part is reflected at the cantilever back into the fiber.
These two beams interfere inside the fiber, and the interference signal can be measured with a
photodiode. Interferometry is a highly sensitive method providing a direct and absolute
measurement of displacement. In this method, light has to be brought close to the cantilever
surface to get enough reflected light. Optical fiber few microns away from the free end of the
microcantilever could measure deflection in 0.01 Å range. However, the positioning of the
fibers is a difficult task. The method works well for small displacements but is less sensitive in
liquids and hence, of limited use in biosensor applications.

The Optical Diffraction Grating Deflection Detection Method

The reflected laser light from the interdigitated cantilevers forms a diffraction pattern in which
the intensity is proportional to the cantilever deflection [12]. This can be used for atomic force
microscopy, infrared detection, and chemical sensing.

The Charge Coupled Device (CCD) Detection Method

A CCD camera for measuring the deflection of the cantilever in response to analyte was used
by Kim and co-workers [13]. The position sensitive detector here is the CCD camera that
records the laser beam deflected from the cantilever.

Mechanical Properties of Cantilevers

The basic mechanical parameters of a cantilever are the spring constant and the resonance
frequency.
The spring constant k is the proportionality factor between applied force, F and the resulting
bending of the cantilever, z. This relation is called Hooke’s law.
F = -kz
The spring constant yields the stiffness of the cantilever. For a rectangular cantilever of length
l, the spring constant can be written as
3 .E .I .
k=
l3
where E is the Young’s modulus and I is the moment of inertia. A typical spring constant for a
stress sensitive cantilever is in the range of 1 mN/m to 1 N/m.
The resonance frequency fres for a simple rectangular cantilever can be expressed as

0.162 E. h 3 . W
f res =
ρ .l 2
where ρ is the mass density, h and w denotes the height and the width of the cantilever
respectively. The moment of inertia for a rectangular cantilever can be written as

w. h 3
I= 3
l

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 Sandeep Kumar Vashist

A simpler expression for the resonance frequency can be written as a function of the spring
constant as

0.32 k
f res =
m
where mass, m=ρ.h.l.w. The relation shows that the resonance frequency increases as a
function of increasing spring constant and of decreasing cantilever mass.
The use of microcantilevers has been understood worldwide but the biomechanics [14] and the
underlying mechanism of microcantilever deflection is not yet fully established.

Bending Behaviour of Cantilever Beams

A uniform surface stress acting on an isotropic material increases (in the case of compressive
stress) or decreases (in case of tensile stress) the surface area as shown in figure 4. If this
stress is not compensated at the opposite side of a thin plate or beam, the whole structure will
bend. Between the areas of compressive stress and tensile stress, there is a neutral plane
which is not deformed. Due to bending, a force F is acting at a distance of x in the neutral
plane results in a bending moment M=F.x. Therefore, the radius of curvature R is given by:
1/R = d2z/dx2 = M/EI
where E is the apparent Young’s modulus and I is the moment of inertia given by the following
equation for rectangular beams

bh 3
I=
12
The change in the surface stress at one side of the beam will cause static bending, and the
bending moment can be calculated as:
Δσ bh
M=
2
Δσ = σ1 – σ2 is the differential surface stress with σ1 and σ2 as surface stress at the upper and
lower side of the cantilever respectively (figure 5). Inserting these values of I and M in the first
equation yields Stoney’s formula [15]:
6(1 - υ ) Δσ
1/R =
Eh 2

Figure 4. Bending of a cantilever beam in response to compressive and tensile stresses. (a)
Compressive surface stress due to repulsion between the biomolecules leads to
downward/negative deflection of the cantilever beam. (b) Tensile surface stress due to
attraction between molecules leads to upward/positive deflection of the cantilever beam.

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 A Review of Microcantilevers for Sensing Applications

Figure 5. Lateral view of a thin cantilever beam of thickness t subjected to compressive

stress. σ1 is the stress at the upper surface and σ2 is the stress at the lower surface of the
cantilever. The cantilever beam bends with a constant radius of curvature R.
Taking into account the boundary conditions of a cantilever (R » L), the above equation can be
solved and the displacement of the cantilevers can be written as:

3L2 (1 - υ ) Δσ
s=
Eh 2
Changes in surface stress can be the result of adsorption process or electrostatic interactions
between charged molecules on the surface as well as changes in the surface hydrophobicity
and conformational changes of the adsorbed molecules.
In addition to surface stress-induced bending, the volume expansion of bimaterial cantilevers
can result in a static bending. A bimaterial cantilever undergoes bending due to gas adsorption
if the volume expansion coefficients of the two materials are different.

Microcantilever Sensors
Biosensing applications demand fast, easy-to-use, cheap and highly sensitive methods for
detecting analytes along with the capability for high-throughput screening. All these points can
be fulfilled by micromachined cantilever sensors, which are therefore ideal candidates for
biosensing applications. The various applications of microcantilever based sensors are
summarized in Figure 6.

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 Sandeep Kumar Vashist

Figure 6. Applications of microcantilever-based sensors.

Microcantilever based sensors [16] are the simplest MEMS devices that offer a very promising
future for the development of novel physical, chemical and biological sensors. They are the
most recent and most advanced analyte detection systems with the detection limit far lower
than the most advanced techniques currently employed. The adsorbed mass of the analytes
causes the nanomechanical bending of the microcantilever. The change in mass on the
microcantilever surface due to the binding of the analyte molecules is directly proportional to
the deflection of the microcantilever. Thus, qualitative as well as quantitative detection of
analytes can be performed.

Materials Used in Commercial Cantilevers

The commercial cantilevers are typically made of silicon, silicon nitride, or silicon oxide and are
available in a wide variety of different shapes, dimensions, and force sensitivities. Recent
developments combine the latest integrated circuit (IC) and complementary metal oxide
semiconductor (CMOS) technologies to produce intelligent extremely small cantilevers in the
form of an array.

Cantilevers Use in Non-Contact Modes

Recent years have witnessed a second evolutionary step in the use of cantilevers whereby they
are no longer brought into contact with a surface. They are now used in sensor systems
providing a completely new type of miniaturized transducer based on fundamental principles of
physics like the bimetallic effect, surface stress, or the harmonic oscillator.

Advantages of Microcantilever-Based Sensors

Microcantilever based sensors have enormous potential for the detection of various analytes in
gaseous, vacuum and liquid medium. They have aroused considerable interest because of their
high specificity, high sensitivity, simplicity, low cost, low analyte requirement (in µl), non-
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 A Review of Microcantilevers for Sensing Applications

hazardous procedure with fewer steps, quick response and low power requirement. Substances
at trace levels are currently detected by various techniques like high performance liquid
chromatography (HPLC), thin layer chromatography (TLC), gas chromatography (GC), gas
liquid chromatography (GLC) etc. However, these techniques are complex, time consuming,
costly and require bulky instrumentation. Also sample preparation is a prolonged complex
procedure and requires skilled personnel. But the microcantilever-based sensors can detect
trace amounts of substances in parts-per-billion (ppb) and parts-per-trillion (ppt). They
translate biomolecular recognition into nanomechanical bending of the microcantilever [17].
Intermolecular forces arising from the adsorption of analyte molecules onto the microcantilever
induce surface stress, directly resulting in nanomechanical bending of the microcantilever.

Sensing Applications of Microcantilevers in Physics and Chemistry

The cantilever-based sensors have extensive applications in physics and chemistry. They can
be used to measure sound wave velocities, fluid pressures and flow rates, and can be tuned to
selectively pick up acoustic vibrations. Biotoxins could be detected with sensitivity at the ppt
level by coating one side of the cantilever with monoclonal antibodies specific for the particular
biotoxin. The effects of small atmospheric-pressure changes can be felt in the resonance of the
vibrating cantilever. Effects of exposure to ultraviolet radiations can be sensed by choosing the
proper polymeric coating. It has been observed that silicon nitride cantilevers coated with gold
on one side are quite sensitive to pH changes. Based on this, cantilever based sensors can be
made to detect the pH change. They have also been used to detect mercury vapor, humidity,
natural gas, gas mixtures, toluene and lead in water.

Types of Sensors Based on Micro and Nanocantilevers

Humidity Sensors
The humidity in the environment can be measured if one side of microcantilever is coated with
gelatin [18]. Gelatin binds to the water vapors present in the atmosphere, thereby causing the
bending of the cantilever. Researchers at Oak Ridge National Laboratory (ORNL), USA showed
that cantilevers coated with hygroscopic materials such as phosphoric acid can be used as a
sensor for detecting water vapour with picogram mass resolution [19]. When water vapors are
adsorbed on the coated surface of the cantilever, there is change in the resonance frequency
of microcantilevers and cantilever deflection. Sensitivity of microcantilevers can be increased
by coating its surface with materials having a high affinity for the analyte.

Herbicide Sensors
Microcantilevers have been used to detect the concentration of herbicides in the liquid
environment by Roberto Raiteri and co-workers [20]. The herbicide 2,4-dichlorophenoxyacetic
acid (2,4-D) was coated on the upper surface of the cantilever. The monoclonal antibody
against 2,4-D was then provided to the cantilever. The specific interaction between the
monoclonal antibody and the herbicide caused the bending of the cantilever. A lot of research
is going on to develop antibody coated cantilever immunobiosensors for the detection of
organochlorine and organophosphorous pesticides and herbicides present at ng/l concentration
in aqueous media. Alvarez and Co-workers demonstrated the use of microcantilevers for the
detection of pesticide dichloro dipheny trichloroethane (DDT) [21].

Metal Ion Sensors

Microcantilever sensors have been employed to detect a concentration of 10-9 M CrO42- in a
flow cell [22]. In this device, a self-assembled layer of triethyl-12-mercaptododecyl ammonium
bromide on the gold-coated microcantilever surface was used. Microcantilevers could be used
for the chemical detection of a number of gaseous analytes. A multielement sensor array
device employing microcantilevers can be made to detect various ions simultaneously.

Temperature Sensors / Heat Sensors

Changes in temperature and heat bend a cantilever composed of materials with different
thermal expansion coefficients by the bimetallic effect. Microcantilever based sensors can
measure changes in temperature as small as 10-5 K and can be used for photo thermal
measurement. They can be used as microcalorimeters to study the heat evolution in catalytic
chemical reactions and enthalpy changes at phase transitions. Bimetallic microcantilevers can
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 Sandeep Kumar Vashist

perform photothermal spectroscopy [23] with a sensitivity of 150 fJ and a sub-millisecond time
resolution. They can detect heat changes with attojoule sensitivity.

Viscosity Sensors
Changes in the medium viscoelasticity shift the cantilever resonance frequency. A highly
viscous medium surrounding the cantilever as well as an added mass will damp the cantilever
oscillation lowering its fundamental resonance frequency. Cantilevers can therefore be vibrated
by piezoelectric actuators to resonate and used as viscosity meters [24].

Calorimetry Sensors
In these sensors, only the temperature changes are to be measured [25,26]. Most of the
chemical reactions are associated with a change in heat. So, calorimetry has got tremendous
potential to identify a wide range of compounds. Enzymes like glucose oxidase can be
immobilized and coated on the surface of the microcantilever, which will react specifically with
glucose in the solution producing a recognizable calorimetric signal. Due to the tiny thermal
mass and sensitivity of the cantilever, calorimetry sensors employing cantilevers will be next
generation of sensors for detecting temperature changes.

Sensor Detecting Magnetic Beads

Baselt and co-workers [27] explained the possibility of using microcantilevers as force
transducers to detect the presence of receptor-coated magnetic beads. It is possible to detect
the presence of single µm size magnetic bead sticking onto the functionalized cantilever
surface by applying an external magnetic field and measuring the deflection of the
microcantilever. An extremely sensitive sensor can be made by labelling the analyte with
magnetic beads.

Cantilever Based Telemetry Sensors

Cantilever based telemetry sensors [28] will deploy fieldable devices to relay pertinent data to
central collection stations. They will enable the use of mobile units worn or carried by
personnel and will replace wired sensors in some applications. Researchers at ORNL are
building a microfabricated chip with built-in electronic processing and telemetry. They are also
working on a method to detect different species.

Microsensors to Monitor Missile Storage and Maintenance Needs

Miniaturized microcantilever based sensors with remote wireless monitoring capability have
been employed to gain insight into stockpile condition [29]. This technology will evaluate
ammunition lifetime based on environmental parameters like humidity, temperature, pressure,
shock and corrosion as well as number of other indicators of propellant degradation including
NOx. Single chip detectors with electronics and telemetry could be developed with several
hundred cantilevers as an array to simultaneously monitor, identify and quantify many
important parameters. Corrosion sensors have limited life in moderate to severe environments.
Systems have to be build to collect environmental data for better knowledge of environmental
conditions. There is a need to develop materials like zeolites [30] for use as sensitizing
coatings for specific detection. Zeolites are thermally stable aluminosilicate framework
structures used commercially as molecular sieves, catalysts, ion-exchangers and chemical
absorbers. They show excellent selectivity and selective thermal desorption properties.

Remote Infrared Radiation Detection Sensors

A remote infrared (IR) radiation detection sensor has been developed by Oden and co-workers
[31]. The sensor is made up of a piezoresistive cantilever coated with a heat absorbing layer.
Piezoresistive microcantilevers represent an important development in uncooled IR detection
technology. The cantilever undergoes bending due to the differential stress between the
coating and the substrate. The cantilever bending causes a change in the piezoresistance,
which is proportional to the amount of the heat absorbed. Temperature variations can be
detected by coating the cantilever with a different material, which causes the bimetallic effect
resulting in the bending of the cantilever. Thus, calorimetric detection of chemical reactions
can be done. Gold-black would serve as the IR absorbing material. High thermal expansion
bimaterial coatings such as Al, Pb and Zn could be used to increase the thermally induced

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 A Review of Microcantilevers for Sensing Applications

bending of the microcantilever. Two dimensional cantilever arrays can be used for IR imaging
as they are simple, highly sensitive and fast responding.

Explosives Detection Devices

It is believed that dogs have got amazing smelling power, the reason they are widely
employed in the detection of explosives. Dogs can detect explosives by sniffing easily
vaporized organic chemicals present at concentration as low as parts-per-billion. Many groups
are conducting active research with the intention of making a ‘nose-on-a-chip’ device having
the smelling power exactly similar to the dog’s nose. In this ‘nose-on-a-chip’ device [32,33], a
microcantilever array could be used in which each cantilever will be coated differently to pick
up a specific organic compound. It can be incorporated in our everyday use item like shoes,
walking cane, purse etc. to detect the explosives without letting the culprits know about the
search operation. The device would be a great achievement from the security point of view and
would prevent large accidents.
A microcantilever coated with platinum or a transition metal can react with trinitrotoluene
(TNT) if it is heated to 570°C and held at that temperature for 0.1 second. The reaction of TNT
with the cantilever coating will cause a mini-explosion. Thundat and his group [34] are
developing a matchbox-size device to detect explosives in airport luggage and landmines
based on this technique.

Sensing Applications of Microcantilevers in the Field of Disease Diagnosis

Cancer Detecting Microchips

Arun Majumdar and co-workers [3] have demonstrated microcantilever based sensitive assay
for the diagnosis of cancer. They coated the surface of the microcantilever with antibodies
specific to prostate specific antigen (PSA), a prostate cancer marker found in the blood of
patients having prostate cancer. When the PSA-coated microcantilever interacted with the
blood sample of the patient having prostate cancer, antigen-antibody complex was formed and
the cantilever bent due to the adsorbed mass of the antigen molecules. The nanometer
bending of cantilever was detected optically by a low power laser beam with sub-nanometer
precision using a photo detector. This microcantilever based assay was more sensitive than
conventional biochemical techniques for detection of PSA as it can detect antigen levels lower
than the clinically relevant threshold value. The technique is as good as and potentially better
than ELISA. Moreover, the cost per assay is lesser as there is no need to attach fluorescent
tags or radiolabel the molecules. The detection of PSA based on the resonant frequency shift of
piezoelectric nanomechanical microcantilever had been demonstrated also by Lee and co-
workers [35].

Myoglobin Detection Sensors

Raiteri and his group [4] employed microcantilevers with anti-myoglobin monoclonal antibody
coated on the upper surface by sulfosuccinimidyl 6-[3-(2-pyridyldithio)-propionamido]
hexanoate (sulfo-LC-SPDP) cross-linker. When the human serum was provided, myoglobin
bound to the anti-myoglobin, thereby causing a deflection of the microcantilever. 85 ng/ml of
myoglobin was easily detected, which is the physiological concentration in the healthy human
serum.
Glucose Biosensors
Pei and co-workers [36] reported a technique for micromechanical detection of biologically
relevant glucose concentrations by immobilization of glucose oxidase onto the microcantilever
surface. The enzyme-functionalized microcantilever undergoes bending due to a change in
surface stress induced by the reaction of glucose oxidase immobilized on the cantilever surface
with glucose in solution. Experiments were carried under flow conditions and it was
demonstrated that the common interferences for glucose detection had no effect on the
measurement of blood glucose.

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 Sandeep Kumar Vashist

Biosensors for Coronary Heart Disease

A clinical biochemical sensor application was presented [37], where the adsorption of low-
density lipoproteins (LDL) and their oxidized form (oxLDL) on heparin were differentiated by
measuring the surface stress employing biosensing microcantilevers. The ability to differentiate
these two species is of interest because their uptake from plasma principally favoured the
oxidised form, which is believed to be responsible for the accumulation of cholesterol in the
aorta in time and is associated with the first stage of coronary heart disease. The method was
also used to detect conformational changes in two plasma proteins, Immunoglobulin G (IgG)
and Albumin (BSA), induced by their adsorption on a solid surface in a buffer environment.
This phenomenon is of crucial importance in biomedical applications involving solid surfaces,
but has been difficult to measure with conventional adsorption techniques.

Cantilever Based Sensors to Detect Single-Nucleotide Polymorphisms

Single nucleotide polymorphisms (SNPs) within the known gene sequences and the genome
are the main concern of the genomics research. Point mutations cause several diseases such
as Thalassemia, Tay Sachs, Alzheimer’s disease etc. Therefore, efforts to detect the single
nucleotide polymorphism will aid in the early diagnosis of these diseases and will help in the
treatment of patients having such disorders. An effective and reliable way of detecting such
single base pair mismatches is by using microcantilevers which are extremely sensitive to
specific biomolecular recognition interactions between the probe DNA sequence and the target
DNA sequence. They can detect concentration in the pico- to femtogram range. Thiolated DNA
probes specific for the particular target DNA sequence are immobilized on the gold-coated
microcantilever. Hybridization with the fully complimentary target DNA sequence will cause the
net positive deflection of the cantilever. Net positive deflection is a result of reduction in the
configurational entropy of dsDNA versus ssDNA, which causes the reduction of compressive
forces on the gold side of the cantilever. Hybridization of the probe DNA with target DNA
having one or two base-pair mismatches results in a net negative deflection of the cantilever
due to increased repulsive forces exerted on the gold-coated surface of the microcantilever.
The deflection is greater for target DNA having two base pair mismatches than for target DNA
having one base pair mismatch. The degree of repulsion increases as the number of base pair
mismatches increase [38]. McKendry [39] demonstrated multiple label-free biodetection and
quantitative DNA-binding assays on a nanomechanical cantilever array.
These DNA based microcantilever deflection assays would be a boon to the field of
pharmacogenomics, which will develop drugs specifically made to target the SNPs. These
assays have a quick response time of less than 30 minutes and are much cheaper than the
other techniques currently used to detect the SNPs. It is a simple procedure and the output i.e.
the cantilever deflection is a simple +/- signal. Current hybridization detection techniques like
Southern blotting require highly stringent reaction conditions while the microcantilever-based
technique requires only a physiological buffer and room temperature (25°C). Details about the
transformation of biomolecular recognition into nanomechanics are given in [40]. Southern
hybridization is very tedious, costly, hazardous and time consuming procedure. On the other
hand, microcantilevers hold a great promise for the medical diagnosis because not only the
presence but the location of the mismatches can be found.

Biochips
Recent advances in biochips [41,42] have shown that sensors based on the bending of
microfabricated cantilevers have potential advantages over previously used detection methods.
Biochips with mechanical detection systems use microcantilever bimaterial (e.g. Au–Si) beams
as sensing elements. The Au side is usually coated with a certain receptor. Upon the binding of
the analyte (e.g. biological molecules, such as proteins or biological agents) with the receptor,
the receptor surface is either tensioned or relieved. This causes the microcantilever to deflect
and the deflection was found to be proportional to the analyte concentration. Examples of
bindings in biomolecular (receptor/analyte) applications are: antibody–antigen bindings or DNA
hybridization of a pair of DNA strands (receptor/analyte) having complementary sequences
[42]. Biochips having microcantilevers as sensing elements do not require external power,
labelling, external electronics or fluorescent molecules or signal transduction for their
operation. These types of biochips can be used in screening certain diseases such as cancer
and detecting specific chemical and biological warfare agents such as botulinum toxin, anthrax,
Volume 3 | June 2007 Page 12 of 15 DOI: 10.2240/azojono0115
 A Review of Microcantilevers for Sensing Applications

and aflatoxin. A chemical sensor based on a micromechanical cantilever array has been
demonstrated by Battison and co-workers [37].

Nanocantilevers: A Major Breakthrough in Sensors

Nanocantilevers, 90 nm thick and made of silicon nitride, have been used by the group of
researchers led by Harold Craighead, Cornell University to detect a single piece of DNA 1578
base pairs in length [43]. The group claimed that they can accurately determine a molecule
with mass of about 0.23 attograms (1 attogram = 10-18 gram) employing these
nanocantilevers. The researchers placed nanoscale gold dots at the very ends of the
cantilevers, which acted as capture agents for sulfide-modified double-stranded DNA. But in
principle, gold nanodots could be used to capture any biomolecule having a free sulfide group.
Scanning laser beams were used to measure the vibrational frequency of the cantilevers. The
researchers believe that nanodevices based on nanocantilevers would eliminate the need for
PCR amplification for the detection of defined DNA sequences, thereby simplifying methods
used to screen for specific gene sequences and mutations.
Similarly, N. Nelson-Fitzpatrick et al. [44] at the University of Alberta, Canada have made ultra
thin resonant nanocantilevers, of the order of 10 nm, in aluminum-molybdenum composites.
The group claims that the development of NEMS-based devices in metallic materials would
enable new areas of applications for the direct sensing of various chemical compounds thus
obviating the need of intermediate surface derivatization.
Researchers at Purdue University are involved in the creation of nanocantilevers. They
employed an array of nanocantilevers of varying length with thickness of about 30 nm and
functionalized them with antibodies for viruses [45]. They came up with very interesting
results pertaining to the variation in antibody density w.r.t. the length of nanocantilevers.

Conclusions
Microcantilevers have got potential applications in every field of science ranging from physical
and chemical sensing to biological disease diagnosis. The major advantages of employing
microcantilevers as sensing mechanisms over the conventional sensors include their high
sensitivity, low cost, low analyte requirement (in µl), non-hazardous procedure with fewer
steps (obviating the need for labels), quick response and low power requirement. Most
important is the fact that an array of microcantilevers can be employed for the diagnosis of
large numbers of analytes such as various disease biomarkers of a single disease in a single go
thus having tremendous high throughput analysis capabilities. The technology holds the key to
the next generation of highly sensitive sensors. With the development of the technology for
nanocantilevers, sensors have achieved attogram sensitivity, which has until recently only
been a dream for researchers. Further increases in sensitivity will allow researchers the ability
to count the numbers of molecules.

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Volume 3 | June 2007 Page 14 of 15 DOI: 10.2240/azojono0115

 A Review of Microcantilevers for Sensing Applications

Contact Details

Dr. Sandeep Kumar Vashist

National Center for Sensor Research
Dublin City University
Glasnevin, Dublin9
Dublin, Ireland
E-mail: sandeep.vashist@dcu.ie

Volume 3 | June 2007 Page 15 of 15 DOI: 10.2240/azojono0115

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