13/8/2016 A Review of Microcantilevers for Sensing Applications

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A Review of Microcantilevers for Sensing Applications

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Keywords
Introduction
Mass Sensitive Detection by Microcantilevers
Microcantilever De ection Detection Methods
The Piezoresistive De ection Detection Method
The Optical De ection Detection Method
The Capacitive De ection Detection Method
The Interferometry De ection Detection Method
The Optical Di raction Grating De ection 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
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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

Abstract
Microelectromechanical Systems (MEMS) [1,2] have come into existence only in the last decade. Microcantilevers are the most
simpli ed MEMS based devices. Diverse applications of microcantilevers in the eld 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
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Keywords
Microcantilevers, sensors, diagnostics, MEMS

Introduction
Molecular diagnostic devices are getting smaller with the advancement of miniaturization technologies. There is increasing
interest in the eld of biosensor research on miniaturized platforms. Miniaturization is essential for in vivo physiological
monitoring, multiple speci city 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
eld of medicine, speci cally 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 l), 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 speci c mass of analyte is speci cally 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 di erent shapes as shown in gure 1.

Figure 1. Di erent types of microcantilevers (top view) (a) Rectangular (b) Double-legged (c) Triangular.

Molecules adsorbed on a microcantilever cause vibrational frequency changes and de ection of the microcantilever. Viscosity,
density, and ow rate can be measured by detecting changes in the vibrational frequency.

Another way of detecting molecular adsorption is by measuring de ection 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 de ection can be up or down. Biochips
with mechanical detection systems commonly use microcantilever bi-material (e.g. AuSi) 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
de ect, usually in nanometers, which can be measured using optical techniques. The de ection is proportional to the analyte
concentration. The concept has been employed in screening certain diseases such as cancer and detecting speci c chemical and
biological warfare agents.

Microcantilever De ection Detection Methods

The Piezoresistive De ection 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 de ects, 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
de ection 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
coe cient 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:

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 Youngs 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.

where 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 gure 2.

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

The resistance of the variable resistance arm ( ) in the above gure 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 de ection.

The Optical De ection Detection Method

The optical method [8], as shown in gure 3, employs a laser beam of very low power of the order that does not a ect the
biomolecules coated on the surface of the microcantilever and a position sensitive detector (PSD). The laser beam falls on the
cantilever and gets re ected as the gold layer coated on the surface of the cantilever gives it an almost mirror like nish. The
re ected beam falls on the PSD. When the cantilever is unde ected i.e. it is not coated with any molecule, the laser beam would
fall on a particular spot on the PSD. As the cantilever de ects, 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 de ection 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 kits
portability.

Figure 3. Schematic of an optical detection system for detecting microcantilever de ection. The re ected laser light from the
de ected microcantilever falls at a di erent position on the PSD. Depending on the distance between the two positions of the
laser beam on the PSD, the de ection of the microcantilever is determined.

The Capacitive De ection Detection Method

The capacitive method [9] is based on the principle that when the cantilever de ection 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
de ection 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 De ection Detection Method

This optical detection method [10,11] is based on the interference of a reference laser beam with the laser beam re ected by the
cantilever. The cleaved end of an optical ber is brought close to the cantilever surface. One part of the light is re ected at the
interface between ber and surrounding media, and the other part is re ected at the cantilever back into the ber. These two
beams interfere inside the ber, 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 re ected light. Optical ber few microns away from the free end of the microcantilever could
measure de ection in 0.01 range. However, the positioning of the bers is a di cult task. The method works well for small
displacements but is less sensitive in liquids and hence, of limited use in biosensor applications.

The Optical Di raction Grating De ection Detection Method

The re ected laser light from the interdigitated cantilevers forms a di raction pattern in which the intensity is proportional to the
cantilever de ection [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 de ection 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 de ected 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 Hookes law.
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relation is called Hookes law.

F = -kz

The spring constant yields the sti ness of the cantilever. For a rectangular cantilever of length l, the spring constant can be
written as

where E is the Youngs 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

where 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

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

where mass, m=.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 de ection 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 gure 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 Youngs modulus and I is the moment of inertia given by the following equation for rectangular beams

The change in the surface stress at one side of the beam will cause static bending, and the bending moment can be calculated as:

= 1 2 is the di erential surface stress with 1 and 2 as surface stress at the upper and lower side of the cantilever
respectively ( gure 5). Inserting these values of I and M in the rst equation yields Stoneys formula [15]:

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 de ection of the cantilever beam. (b) Tensile surface stress due
to attraction between molecules leads to upward/positive de ection of the cantilever beam.

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Figure 5. Lateral view of a thin cantilever beam of thickness t subjected to compressive stress. 1 is the stress at the upper
surface and 2 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:

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 coe cients of the two materials are
di erent.

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 ful lled by micromachined cantilever sensors, which are
therefore ideal candidates for biosensing applications. The various applications of microcantilever based sensors are
summarized in Figure 6.

Figure 6. Applications of microcantilever-based sensors.

Microcantilever based sensors [16] are the simplest MEMS devices that o er 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 de ection 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
di erent 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 e ect, 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
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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 speci city, high sensitivity, simplicity, low cost, low
analyte requirement (in l), non-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, uid pressures and ow 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 speci c for the particular
biotoxin. The e ects of small atmospheric-pressure changes can be felt in the resonance of the vibrating cantilever. E ects 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 de ection. Sensitivity of
microcantilevers can be increased by coating its surface with materials having a high a nity 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 speci c 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 ow 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 di erent thermal expansion coe cients by the
bimetallic e ect. 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 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 speci cally 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 m size magnetic bead sticking onto the
functionalized cantilever surface by applying an external magnetic eld and measuring the de ection of the microcantilever. An
extremely sensitive sensor can be made by labelling the analyte with magnetic beads.

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Cantilever Based Telemetry Sensors

Cantilever based telemetry sensors [28] will deploy eldable 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 di erent 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 speci c 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 di erential 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 di erent material, which causes the bimetallic
e ect 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 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 sni ng 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 dogs nose. In this nose-on-a-chip device [32,33], a microcantilever array could be used in which each
cantilever will be coated di erently to pick up a speci c 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 570C 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 speci c to prostate speci c 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 uorescent 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 de ection 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 ow conditions and it was demonstrated that the common interferences for
glucose detection had no e ect on the measurement of blood glucose.

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 di erentiated by measuring the surface stress employing biosensing microcantilevers.
The ability to di erentiate these two species is of interest because their uptake from plasma principally favoured the oxidised

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form, which is believed to be responsible for the accumulation of cholesterol in the aorta in time and is associated with the rst
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 bu er environment. This
phenomenon is of crucial importance in biomedical applications involving solid surfaces, but has been di cult 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, Alzheimers disease etc. Therefore,
e orts 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 e ective and reliable way of detecting such single base pair mismatches is by using
microcantilevers which are extremely sensitive to speci c 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
speci c 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 de ection of the cantilever. Net positive de ection is a result of
reduction in the con gurational 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 de ection of the cantilever due to increased repulsive forces exerted on the gold-coated surface of the microcantilever.
The de ection 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 de ection assays would be a boon to the eld of pharmacogenomics, which will develop drugs
speci cally 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 de ection
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 bu er and room temperature (25C). 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. AuSi) 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 de ect and the de ection was found to be proportional to the analyte concentration.
Examples of bindings in biomolecular (receptor/analyte) applications are: antibodyantigen 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 uorescent molecules or signal transduction for their
operation. These types of biochips can be used in screening certain diseases such as cancer and detecting speci c chemical and
biological warfare agents such as botulinum toxin, anthrax, and a atoxin. 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 sul de-modi ed
double-stranded DNA. But in principle, gold nanodots could be used to capture any biomolecule having a free sul de 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 ampli cation for the detection of de ned DNA
sequences, thereby simplifying methods used to screen for speci c 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 eld 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 l), 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.

References
1. Grayson, A.C.R., Shawgo, R.S., Johnson, A.M., Flynn, N.T., Li, Y., Cima, M.J. & Langer, R. (2004) A BioMEMS Review: MEMS

http://www.azonano.com/article.aspx?ArticleID=1927 8/12
13/8/2016 A Review of Microcantilevers for Sensing Applications
technology for physiologically integrated devices. Proc. IEEE, 92(1), 6-21.

2. Polla, D.L., Erdman, E., Robbins, W.P., Markus, D.T., Diaz, J.D., Rinz, R., Nam, Y. & Brickner, H.T. (2000) Microdevices in Medicine.
Ann. Rev. Biomed. Eng., 2, 551-76.

3. Wu, G.H., Datar, R.H., Hansen, K.M., Thundat, T., Cote, R.J. & Majumdar, A. (2001) Bioassay of prostate-speci c antigen (PSA)
using microcantilever. Nat. Biotechnol., 19, 856-60.

4. Arntz, Y., Seelig, J.D., Lang, H.P., Zhang, J., Hunziker, P., Ramseyer, J.P., Meyer, E., Hegner, M. & Gerber, C. (2003) Label-free
protein assay based on a nanomechanical cantilever array. Nanotechnology, 14, 86-90.

5. Subramanian, A., Oden, P.I., Kennel, S.J., Jacobson, K.B., Warmack, R.J., Thundat, T., Doktycz, M.J. (2002) Glucose biosensing
using an enzyme-coated microcantilever. Appl. Phys. Lett., 81, 385-87.

6. Thaysen, J., Boisen, A., Hansen, O. & Bouwstra, S. (2000) Atomic force microscopy probe with piezoresistive read-out and
highly symmetrical Wheatstone bridge arrangement. Sens. Actuators A, 83, 47-53.

7. Yang, M., Zhang, X., Vafai, K. & Ozkan, C.S. (2003) High sensitivity piezoresistive cantilever design and optimization for analyte-
receptor binding. J. Micromech. Microeng., 13, 864-72.

8. Meyer, G. & Amer, N.M. (1988) Novel optical approach to atomic force microscopy. Appl. Phys. Lett., 53(12), 1045-47.

9. Blanc, N., Brugger, J., Rooij, N.F.D. & Durig, U. (1996) Scanning Force Microscopy in the Dynamic Mode Using Microfabricated
Capacitive Sensors. J Vac. Sci. Technol. B, 14(2), 901-05.

10. Erlandsson, R., McClelland, G.M., Mate, C.M. & Chiang, S. (1988) Atomic force microscopy using optical interferometry. J. Vac.
Sci. Technol. A, 6(2), 266-70.

11. Rugar, D., Mamin, H.J. & Guethner, P. (1989) Improved ber-optic interferometer for atomic force microscopy. Appl. Phys.
Lett., 55(25), 2588-90.

12. Manalis, S.R., Minne, S.C., Atalar, A. & Quate, C.F. (1996) Interdigital cantilevers for atomic force microscopy. Appl. Phys. Lett.,
69, 3944-46.

13. Kim, B.H., Mader, O., Weimar, U., Brock, R. & Kern, D.P. (2003) Detection of antibody peptide interaction using
microcantilevers as surface stress sensors. J. Vac. Sci. Technol. B, 21(4), 1472-1475.

14. Lavrik, N.V., Tipple, C.A., Sepaniak, M.J. & Datskos, P.G. (2001) Gold Nano-structures for transduction of biomolecular
interactions into micrometer scale movements. Biomed. Microdevices, 3(1), 35-44.

15. Stoney, G.G. (1909) The tension of metallic lms deposited by electrolysis. Proc. Roy. Soc. London A Mater., 82, 172-75.

16. Thundat, T., Oden, P.I. & Warmack, R.J. (1997) Microcantilevers sensors. Micro. Thermophys. Eng., 1, 185-99.

17. Wu, G., Ji, H., Hansen, K., Thundat, T., Datar, R., Cote, R., Hagan, M.F., Chakraborty, A.K. & Majumdar, A. (2001) Origin of
nanomechanical cantilever motion generated from biomolecular interactions. Proc. Natl. Acad. Sci.USA, 98, 1560-64.

18. http://monet.physik.unibas.ch/nose/

19. http://www.ornl.gov/info/ornlreview/rev29-12/text/instru.htm

20. Raiteri, R., Nelles, G., Butt, H.J., Knoll, W. & Skladal, P. (1999) Sensing of biological substances based on the bending of
microfabricated cantilevers. Sens. Actuators B, 61, 213-17.

21. Alvarez, M., Calle, A., Tamayo, J., Lechuga, L.M., Abad, A. & Montoya A. (2003) Development of nanomechanical biosensors for
detection of the pesticide DDT. Biosens. Bioelectron. 18 (5-6), 649-53.

22. Ji, H.F., Thundat, T., Dabestani, R., Brown, G.M., Britt, P.F. & Bonnesen, P.V. (2001) Ultrasensitive detection of CrO42- using a
microcantilever sensor. Anal. Chem., 73, 1572-76.

23. Barnes, J.R., Stephenson, R.J., Welland, M.E., Gerber, C. & Gimzewski, J.K. (1994) Photothermal spectroscopy with femtojoule
sensitivity using a micromechanical device. Nature, 372, 79-81.

24. Oden, P.I., Chen, G.Y., Steele, R.A., Warmack, R.J. & Thundat, T. (1996) Viscous drag measurements utilizing microfabricated
cantilevers. Appl. Phys. Lett., 68, 3814-16.

25. Berger, R., Gerber, C., Gimzewski, J.K., Meyer, E. & Guntherodt, H.J. (1996) Thermal analysis using a micromechanical
calorimeter. Appl. Phys. Lett., 69, 40-42.

26. Arakawa, E.T., Lavrik, N.V., Rajiv, S. & Datskos, P.G. (2003) Detection and di erentiation of biological species using
microcalorimetric spectroscopy. Ultramicroscopy, 97(1-4), 459-65.

27. Cherian, S. & Thundat, T. (2002) Determination of adsorption-induced variation in the spring constant of a microcantilever.
Appl. Phys. Lett. 80(12), 2219-21.

28. Britton, C.L., Warmack, R.J., Smith, S.F., Wintenberg, A.L., Thundat, T., Brown, G.M., Bryan, W.L., Depriest, J.C., Ericson, M.N.,
Emery, M.S., Moore, M.R., Turner, G.W., Clonts, L.G., Jones, R.L., Threatt, T.D., Hu, Z. & RochelleMarch, J.M. (1999) Battery-
powered, Wireless MEMS sensors for high-sensitivity chemical and biological sensing. Presented at the 1999 Symposium on
Advanced Research in VLSI, Atlanta, GA, 359-68.

29. http://www.osti.gov/bridge/servlets/purl/658232-PJwJRU/webviewable/658232.pdf

30. Scandella, L., Binder, G., Mezzacasa, T., Gobrecht, J., Koegler, J.H., Jansen, J.C., Berger, R., Lang, H.P., Gerber, C. & Gimzewski, J.K.
http://www.azonano.com/article.aspx?ArticleID=1927 9/12
13/8/2016 A Review of Microcantilevers for Sensing Applications
30. Scandella, L., Binder, G., Mezzacasa, T., Gobrecht, J., Koegler, J.H., Jansen, J.C., Berger, R., Lang, H.P., Gerber, C. & Gimzewski, J.K.
(1998) Zeolites: materials for nanodevices. Micropor. Mesopor. Mater., 21, 403-09.

31. Oden, P.I., Thundat, T., Wachter, E.A., Warmack, R.J., Datskos, P.G. & Hunter, S.R. (1996) Remote infrared radiation detection
using piezoresistive microcantilevers. Appl. Phys. Lett., 69, 2986-88.

32. Yinon, J. (2003) Detection of explosives by electronic noses. Anal. Chem., 75, 99A-105A.

33. Baller, M.K., Lang, H.P., Fritz, J., Gerber, C., Gimzewski, J.K., Drechsler, U., Rothuizen, H., Despont, M., Vettiger, P., Battison, F.M.,
Ramseyer, J.P., Fornaro, P., Meyer, E. & Guntherodt, H.J. (2000) A cantilever array-based arti cial nose. Ultramicroscopy, 82, 1-
9.

34. http://bio.lsd.ornl.gov/highlights/2000feb2.htmlx

35. Lee, J.H., Hwang, K.S., Park, J., Yoon, K.H., Yoon, D.S. & Kim, T.S. (2005) Immunoassay of prostate-speci c antigen (PSA) using
resonant frequency shift of piezoelectric nanomechanical microcantilever. Biosens. Bioelectron., 20, 2157-62

36. Chen, G.Y., Thundat, T., Wachter, E.A. & Warmack, R.J. (1995) Adsorption-induced surface stress and its e ects on resonance
frequency of microcantilevers. J. Appl. Phys., 77, 3618-22.

37. Battison, F.M., Ramseyer J.-P., Lang, H.P., Baller, M.K., Gerber, C., Gimzewski, J.K., Meyer, E. & Guntherodt, H.-J. (2001) A
chemical sensor based on a microfabricated cantilever array with simultaneous resonance-frequency and bending readout.
Sens. Actuators B, 77, 122-31.

38. Hansen, K.M., Ji, H.F., Wu, G., Datar, R., Cote, R., Majumdar, A. & Thundat T. (2001) Cantilever-based optical de ection assay for
discrimination of DNA single-nucleotide mismatches. Anal. Chem., 73, 1567-71.

39. McKendry, R., Zhang, J., Arntz, Y., Strunz, T., Hegner, M., Lang, H.P., Baller, M.K., Certa, V., Meyer, E., Guntherodt, H.J. & Gerber,
C. (2002) Multiple label-free biodetection and quantitative DNA-binding assays on a nanomechanical cantilever array. Proc.
Natl. Acad. Sci.USA, 99(15), 9783-88.

40. Fritz, J., Baller, M.K., Lang, H.P., Rothuizen, H., Meyer, E., Vettiger, P., Gunterodt, H.J., Gerber, C. & Gimzewski, J.K. (2000)
Translating biomolecular recognition into nanomechanics. Science, 288, 316-18.

41. Fodor, S.P.A., Rava, R.P., Huang, X.C., Pease, A.C., Holmes, C.P. & Adams, C.L. (1993) Multiplexed biochemical assays with
biological chips. Nature, 364, 555-56.

42. Rowe, C.A., Tender, L.M., Feldstein, M.J., Golden, J.P., Scruggs, S.B., MacCraith, B.D., Cras, J.J. & Ligler, F.S. (1999) Array biosensor
for simultaneous identi cation of bacterial, viral, and protein analytes. Anal. Chem., 71(17), 3846-52.

43. Llic, B., Yang, Y., Aubin, K., Reichenbach, R., Krylov, S., Craighead, H.G. (2005) Enumeration of DNA molecules bound to a
nanomechanical oscillator. Nanoletters, 5(5), pp. 925-929.

44. http://www.nsti.org/Nanotech2006/showabstract.html?absno=488

45. Gupta, A.K., Nair, P.R., Akin, D., Ladisch, M.R., Broyles, S., Alam, M.A., Bashir, R. (2006) Anomalous resonance in a
nanomechanical biosensor. Proc. Natl. Acad. Sci.USA, 103(36), 13362-13367.

Contact Details

Dr. Sandeep Kumar Vashist

National Center for Sensor Research

Dublin City University
Glasnevin, Dublin9
Dublin, Ireland

E-mail: sandeep.vashist@dcu.ie (mailto:sandeep.vashist@dcu.ie?subject=AZoJono%20Paper%20Enquiry)

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