Ranglow Review of Different Sensing and Actuation Afm Microcantilever
Molecular diagnostic devices are getting smaller with the advancement of miniaturization technologies. In that location 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 employ of MEMS devices that integrate electronics and micromechanical structures on chips.
Microcantilevers have been employed for concrete, chemical and biological sensing. They have besides have broad applications in the field of medicine, specifically for the screening of diseases, detection of indicate mutations, blood glucose monitoring and detection of chemic and biological warfare agents. These sensors accept several advantages over the conventional analytical techniques in terms of high sensitivity, low cost, simple procedure, low analyte requirement (in µl), not-chancy procedures and quick response. Moreover, the engineering has been developed in the terminal few years for the fabrication and use of nanocantilevers for sensing applications, thereby giving ascension to nanoelectromechani cal systems (NEMS). This development has increased the sensitivity limit upwards 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 applied science holds tremendous hope for the next generation of miniaturized and highly sensitive sensors.
Mass Sensitive Detection past Microcantilevers
A microcantilever is a device that tin deed equally a physical, chemic or biological sensor by detecting changes in cantilever bending or vibrational frequency. It is the miniaturized counterpart of a diving board that moves upwardly 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 one thousand thousand 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.
Some other manner of detecting molecular adsorption is by measuring deflection of the cantilever due to adsorption stress on just ane side of the cantilever. Depending on the nature of chemical bonding of the molecule, the deflection can be up or downward. Biochips with mechanical detection systems commonly employ microcantilever bi-material (due east.thou. 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 every bit 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 fabric virtually the top surface of the cantilever to record the stress alter occurring at the surface of the cantilever. Equally the microcantilever deflects, it undergoes a stress modify that volition employ strain to the piezoresistor, thereby causing a change in resistance that tin can be measured by electronic ways. The advantage of the piezoresistive method is that the readout system can exist integrated on the scrap. The disadvantage is that the deflection resolution for the piezoresistive readout system is just 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 exist localized as close to i surface of the cantilever as possible for maximum sensitivity. The type of doping being used for fabrication of the piezoresistive fabric is an important factor. The piezoresistive coefficient of N-blazon 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 every bit role of practical strain can exist written every bit:
where Yard denotes the Gage Cistron, which is a material parameter. The subscripts 50 and t refer to the longitudinal and the transversal part of the Gage Gene.
The sensitivity of a piezoresistor varies proportionally to the thickness t and the radius of curvature. The Gage Factor is proportional to Immature'southward Modulus, E, which is the intrinsic characteristic of material. The gage factor tin as well be calculated directly by straining the cantilevers and measuring the resistance change.
where δ is the strain in the material and R is the resistance. For a sensitive device, the gage factor should be of the guild of 100.
The piezoresistive cantilever axle can be used every bit an arm of the Wheatstone Bridge circuit equally shown in figure 2.
Figure 2. The Wheatstone Span Circuit used for the piezoresistive microcantilever.
The resistance of the variable resistance arm ( 
) in the higher up effigy tin be determined by using the common Voltage divider formula and is shown every bit below:
There would be a resistance modify 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 social club that does not affect the biomolecules coated on the surface of the microcantilever and a position sensitive detector (PSD). The laser axle falls on the cantilever and gets reflected every bit the golden 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 axle would fall on a detail spot on the PSD. Every bit the cantilever deflects, the position of the beam changes, which, in turn, is calculated using appropriate electronics. The advantage of this detection organization 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 prison cell environs tin can upshot in boosted thermal management issues giving rise to inapplicable readings. Secondly, the alignment system is expensive and involves corking precision, which can ultimately raise the toll 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 light amplification by stimulated emission of radiation light from the deflected microcantilever falls at a unlike position on the PSD. Depending on the altitude betwixt the 2 positions of the light amplification by stimulated emission of radiation axle on the PSD, the deflection of the microcantilever is determined.
The Capacitive Deflection Detection Method
The capacitive method [9] is based on the principle that when the cantilever deflection takes identify due to the adsorption of the analyte, the capacitance of a plane capacitor is inverse. Here the microcantilever is one of the ii capacitor plates. This deflection technique is highly sensitive and provides absolute displacement. But this technique is non 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,eleven] is based on the interference of a reference laser beam with the laser beam reflected by the cantilever. The broken 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 office is reflected at the cantilever back into the fiber. These two beams interfere inside the fiber, and the interference betoken tin can exist measured with a photodiode. Interferometry is a highly sensitive method providing a straight and absolute measurement of displacement. In this method, light has to be brought close to the cantilever surface to get enough reflected lite. Optical fiber few microns away from the free cease of the microcantilever could mensurate deflection in 0.01 Å range. Nonetheless, the positioning of the fibers is a difficult chore. The method works well for pocket-sized displacements merely 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 Accuse Coupled Device (CCD) Detection Method
A CCD photographic 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 photographic camera that records the laser beam deflected from the cantilever.
Mechanical Properties of Cantilevers
The basic mechanical parameters of a cantilever are the bound 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'south police.
F = -kz
The spring constant yields the stiffness of the cantilever. For a rectangular cantilever of length fifty, the spring constant can be written as
where E is the Young'south modulus and I is the moment of inertia. A typical spring abiding for a stress sensitive cantilever is in the range of 1 mN/m to 1 Northward/chiliad.
The resonance frequency fres for a elementary rectangular cantilever tin exist expressed as
where ρ is the mass density, h and due west denotes the pinnacle and the width of the cantilever respectively. The moment of inertia for a rectangular cantilever can be written every bit
A simpler expression for the resonance frequency can exist written as a function of the spring abiding as
where mass, g=ρ.h.l.w. The relation shows that the resonance frequency increases as a function of increasing spring abiding and of decreasing cantilever mass.
The use of microcantilevers has been understood worldwide but the biomechanics [14] and the underlying machinery of microcantilever deflection is not withal fully established.
Bending Behaviour of Cantilever Beams
A uniform surface stress acting on an isotropic fabric increases (in the case of compressive stress) or decreases (in case of tensile stress) the area as shown in figure 4. If this stress is non compensated at the opposite side of a thin plate or beam, the whole structure will bend. Betwixt the areas of compressive stress and tensile stress, in that location is a neutral plane which is non deformed. Due to bending, a force F is acting at a altitude of x in the neutral plane results in a bending moment One thousand=F.ten. Therefore, the radius of curvature R is given past:
i/R = d 2 z/dx 2 = M/EI
where Due east is the apparent Young'southward modulus and I is the moment of inertia given by the post-obit equation for rectangular beams
The change in the surface stress at one side of the beam will cause static angle, and the bending moment tin can exist calculated as:
Δσ = σi – σii is the differential surface stress with σ1 and σ2 as surface stress at the upper and lower side of the cantilever respectively (figure five). Inserting these values of I and M in the first equation yields Stoney'southward formula [15]:
Effigy four. Angle of a cantilever axle in response to compressive and tensile stresses. (a) Compressive surface stress due to repulsion between the biomolecules leads to down/negative deflection of the cantilever beam. (b) Tensile surface stress due to allure between molecules leads to upward/positive deflection of the cantilever beam.
Figure five. 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 axle bends with a abiding radius of curvature R.
Taking into account the boundary conditions of a cantilever (R » Fifty), the above equation can be solved and the deportation of the cantilevers can be written every bit:
Changes in surface stress can be the upshot of adsorption process or electrostatic interactions between charged molecules on the surface likewise as changes in the surface hydrophobicity and conformational changes of the adsorbed molecules.
In add-on 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 ii materials are different.
Microcantilever Sensors
Biosensing applications demand fast, easy-to-use, cheap and highly sensitive methods for detecting analytes along with the adequacy for loftier-throughput screening. All these points can be fulfilled past micromachined cantilever sensors, which are therefore ideal candidates for biosensing applications. The various applications of microcantilever based sensors are summarized in Figure 6.
Figure half dozen. Applications of microcantilever-based sensors.
Microcantilever based sensors [sixteen] are the simplest MEMS devices that offer a very promising hereafter for the development of novel physical, chemical and biological sensors. They are the near contempo and nigh avant-garde analyte detection systems with the detection limit far lower than the near advanced techniques currently employed. The adsorbed mass of the analytes causes the nanomechanical angle of the microcantilever. The modify in mass on the microcantilever surface due to the binding of the analyte molecules is direct proportional to the deflection of the microcantilever. Thus, qualitative as well as quantitative detection of analytes tin 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 minor cantilevers in the form of an array.
Cantilevers Utilize in Non-Contact Modes
Recent years accept witnessed a 2nd 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 similar 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 involvement because of their high specificity, high sensitivity, simplicity, low cost, low analyte requirement (in µl), non-hazardous procedure with fewer steps, quick response and low power requirement. Substances at trace levels are currently detected by various techniques like loftier operation liquid chromatography (HPLC), sparse layer chromatography (TLC), gas chromatography (GC), gas liquid chromatography (GLC) etc. Notwithstanding, these techniques are complex, time consuming, costly and require bulky instrumentation. Also sample preparation is a prolonged circuitous 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, straight 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 tin can be used to measure sound wave velocities, fluid pressures and menses rates, and tin can be tuned to selectively choice up acoustic vibrations. Biotoxins could be detected with sensitivity at the ppt level past blanket one side of the cantilever with monoclonal antibodies specific for the item biotoxin. The furnishings of minor atmospheric-pressure changes can be felt in the resonance of the vibrating cantilever. Effects of exposure to ultraviolet radiations can exist 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 observe the pH change. They take also been used to detect mercury vapor, humidity, natural gas, gas mixtures, toluene and pb in water.
Types of Sensors Based on Micro and Nanocantilevers
Humidity Sensors
The humidity in the environment tin be measured if one side of microcantilever is coated with gelatin [eighteen]. Gelatin binds to the water vapors present in the atmosphere, thereby causing the bending of the cantilever. Researchers at Oak Ridge National Laboratory (ORNL),
Herbicide Sensors
Microcantilevers have been used to observe the concentration of herbicides in the liquid environment by Roberto Raiteri and co-workers [20]. The herbicide ii,iv-dichlorophenoxyacetic acid (2,4-D) was coated on the upper surface of the cantilever. The monoclonal antibody against two,4-D was then provided to the cantilever. The specific interaction betwixt the monoclonal antibody and the herbicide caused the bending of the cantilever. A lot of research is going on to develop antibiotic 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].
Metallic Ion Sensors
Microcantilever sensors accept been employed to detect a concentration of 10-9 M CrO4 two- in a catamenia 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 assortment device employing microcantilevers can be made to find diverse 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 upshot. Microcantilever based sensors tin can measure changes in temperature equally modest as 10-v K and can be used for photo thermal measurement. They can be used every bit microcalorimeters to study the heat evolution in catalytic chemic reactions and enthalpy changes at phase transitions. Bimetallic microcantilevers can perform photothermal spectroscopy [23] with a sensitivity of 150 fJ and a sub-millisecond fourth dimension resolution. They can observe heat changes with attojoule sensitivity.
Viscosity Sensors
Changes in the medium viscoelasticity shift the cantilever resonance frequency. A highly gluey medium surrounding the cantilever likewise as an added mass will damp the cantilever oscillation lowering its primal resonance frequency. Cantilevers tin can therefore exist 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 chemic reactions are associated with a modify in heat. And so, calorimetry has got tremendous potential to identify a wide range of compounds. Enzymes like glucose oxidase tin be immobilized and coated on the surface of the microcantilever, which will react specifically with glucose in the solution producing a recognizable calorimetric bespeak. Due to the tiny thermal mass and sensitivity of the cantilever, calorimetry sensors employing cantilevers will exist adjacent generation of sensors for detecting temperature changes.
Sensor Detecting Magnetic Chaplet
Baselt and co-workers [27] explained the possibility of using microcantilevers every bit force transducers to find the presence of receptor-coated magnetic beads. It is possible to detect the presence of single µm size magnetic dewdrop sticking onto the functionalized cantilever surface past applying an external magnetic field and measuring the deflection of the microcantilever. An extremely sensitive sensor can exist 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 volition 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 congenital-in electronic processing and telemetry. They are likewise working on a method to detect different species.
Microsensors to Monitor Missile Storage and Maintenance Needs
Miniaturized microcantilever based sensors with remote wireless monitoring adequacy have been employed to gain insight into stockpile status [29]. This technology volition evaluate armament lifetime based on ecology parameters like humidity, temperature, pressure, stupor and corrosion besides as number of other indicators of propellant degradation including NOx. Single bit detectors with electronics and telemetry could exist developed with several hundred cantilevers as an assortment to simultaneously monitor, identify and quantify many important parameters. Corrosion sensors have limited life in moderate to severe environments. Systems take to exist build to collect environmental data for better noesis of environmental conditions. There is a need to develop materials like zeolites [30] for use equally 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 backdrop.
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 oestrus absorbing layer. Piezoresistive microcantilevers correspond an important development in uncooled IR detection engineering science. 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 corporeality of the oestrus absorbed. Temperature variations can exist detected by coating the cantilever with a different cloth, which causes the bimetallic effect resulting in the bending of the cantilever. Thus, calorimetric detection of chemic reactions can be done. Gilt-black would serve as the IR absorbing material. High thermal expansion bimaterial coatings such equally Al, Pb and Zn could exist used to increase the thermally induced bending of the microcantilever. Two dimensional cantilever arrays tin can be used for IR imaging as they are simple, highly sensitive and fast responding.
Explosives Detection Devices
It is believed that dogs accept got astonishing smelling ability, 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 depression as parts-per-billion. Many groups are conducting active research with the intention of making a 'nose-on-a-chip' device having the smelling ability 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. Information technology can exist incorporated in our everyday employ item like shoes, walking pikestaff, purse etc. to notice the explosives without letting the culprits know nigh the search operation. The device would be a keen achievement from the security point of view and would forbid 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.one second. The reaction of TNT with the cantilever coating volition cause a mini-explosion. Thundat and his group [34] are developing a matchbox-size device to notice explosives in aerodrome baggage and landmines based on this technique.
Sensing Applications of Microcantilevers in the Field of Affliction Diagnosis
Cancer Detecting Microchips
Arun Majumdar and co-workers [three] 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 every bit it tin discover antigen levels lower than the clinically relevant threshold value. The technique is as skillful as and potentially better than ELISA. Moreover, the toll 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 [four] employed microcantilevers with anti-myoglobin monoclonal antibiotic coated on the upper surface by sulfosuccinimidyl 6-[3-(ii-pyridyldithio)-propionamido] hexanoate (sulfo-LC-SPDP) cross-linker. When the homo 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 being 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 angle due to a change in surface stress induced past the reaction of glucose oxidase immobilized on the cantilever surface with glucose in solution. Experiments were carried under flow weather condition and it was demonstrated that the mutual interferences for glucose detection had no consequence 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 differentiated past measuring the surface stress employing biosensing microcantilevers. The power to differentiate these two species is of interest because their uptake from plasma principally favoured the oxidised form, which is believed to exist 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 besides used to detect conformational changes in ii plasma proteins, Immunoglobulin G (IgG) and Albumin (BSA), induced past their adsorption on a solid surface in a buffer environment. This phenomenon is of crucial importance in biomedical applications involving solid surfaces, just has been difficult to measure with conventional adsorption techniques.
Cantilever Based Sensors to Detect Single-Nucleotide Polymorphisms
Unmarried nucleotide polymorphisms (SNPs) within the known gene sequences and the genome are the main concern of the genomics research. Point mutations crusade several diseases such as Thalassemia, Tay Sachs, Alzheimer's affliction etc. Therefore, efforts to detect the single nucleotide polymorphism will aid in the early diagnosis of these diseases and will assistance 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 gratis target Dna sequence volition crusade the net positive deflection of the cantilever. Internet positive deflection is a result of reduction in the configurational entropy of dsDNA versus ssDNA, which causes the reduction of compressive forces on the gilt side of the cantilever. Hybridization of the probe Dna with target Dna having one or 2 base of operations-pair mismatches results in a internet 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 of operations pair mismatch. The caste of repulsion increases every bit the number of base pair mismatches increase [38]. McKendry [39] demonstrated multiple characterization-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 volition develop drugs specifically made to target the SNPs. These assays accept a quick response time of less than xxx minutes and are much cheaper than the other techniques currently used to find the SNPs. Information technology is a simple process and the output i.e. the cantilever deflection is a elementary +/- 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 process. On the other hand, microcantilevers hold a great promise for the medical diagnosis because not merely the presence but the location of the mismatches can be constitute.
Biochips
Recent advances in biochips [41,42] take shown that sensors based on the bending of microfabricated cantilevers accept 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 sure receptor. Upon the binding of the analyte (e.m. biological molecules, such equally 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 Deoxyribonucleic acid strands (receptor/analyte) having complementary sequences [42]. Biochips having microcantilevers as sensing elements do non require external power, labelling, external electronics or fluorescent molecules or signal transduction for their operation. These types of biochips can exist used in screening certain diseases such every bit cancer and detecting specific chemical and biological warfare agents such as botulinum toxin, anthrax, 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, xc nm thick and made of silicon nitride, have been used by the group of researchers led by Harold Craighead, Cornell University to notice a unmarried piece of Deoxyribonucleic acid 1578 base pairs in length [43]. The group claimed that they can accurately make up one's mind a molecule with mass of well-nigh 0.23 attograms (one attogram = 10-18 gram) employing these nanocantilevers. The researchers placed nanoscale gold dots at the very ends of the cantilevers, which acted equally capture agents for sulfide-modified double-stranded Deoxyribonucleic acid. But in principle, gold nanodots could be used to capture any biomolecule having a gratis sulfide grouping. 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 cistron sequences and mutations.
Similarly, Due north. Nelson-Fitzpatrick et al. [44] at the University of Alberta ,
Researchers at Purdue University are involved in the creation of nanocantilevers. They employed an array of nanocantilevers of varying length with thickness of about thirty nm and functionalized them with antibodies for viruses [45]. They came upwards with very interesting results pertaining to the variation in antibody density w.r.t. the length of nanocantilevers.
Conclusions
Microcantilevers accept got potential applications in every field of science ranging from physical and chemic 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), not-chancy procedure with fewer steps (obviating the need for labels), quick response and low ability requirement. Most important is the fact that an array of microcantilevers tin be employed for the diagnosis of large numbers of analytes such every bit diverse disease biomarkers of a unmarried affliction in a unmarried go thus having tremendous high throughput assay capabilities. The applied science holds the key to the next generation of highly sensitive sensors. With the development of the engineering science for nanocantilevers, sensors have achieved attogram sensitivity, which has until recently only been a dream for researchers. Further increases in sensitivity will let researchers the ability to count the numbers of molecules.
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