Microcantilever sensors for biochemical detection

Microcantilever is one of the most popular miniaturized structures in micro-electromechanical systems(MEMS).Sensors based on microcantilever are ideal for biochemical detection,since they have high sensitivity,high throughput,good specification,fast response,thus have attracted extensive attentions.A number of devices that are based on static deflections or shifts of resonant frequency of the cantilevers responding to analyte attachment have been demonstrated.This review comprehensively presents state of art of microcantilever sensors working in gaseous and aqueous environments and highlights the challenges and opportunities of microcantilever biochemical sensors.

Piezoelectric and flexoelectric effects of DNA adsorbed films on microcantilevers

DNA-based biosensors have played a huge role in many areas,especially in current global coronavirus outbreak.However,there is a great difficulty in the characterization of piezoelectric and flexoelectric coefficients of the nanoscale DNA film,because the existing experimental methods for hard materials are almost invalid.In addition,the relevant theoretical models for DNA films only consider a single effect without clarifying the difference between the two electromechanical effects on device detection signals.This work aims to present multiscale models for DNA-microcantilever experiments to clarify the competitive mechanism in piezoelectric and flexoelectric effects of DNA films on detection signals.First,a Poisson-Boltzmann(PB)equation is used to predict the potential distribution due to the competition between fixed phosphate groups and mobile salt ions in DNA films.Second,a macroscopic piezoelectric/flexoelectric constitutive equation of the DNA film and a mesoscopic free energy model of the DNA solution are combined to analytically predict the electromechanical coefficients of the DNA film and the relevant microcantilever signals by the deformation equivalent method and Zhang’s two-variable method.Finally,the effects of detection conditions on microscopic interactions,electromechanical coupling coefficients,and deflection signals are studied.Numerical results not only agree well with the experimental observations,but also reveal that the piezoelectric and flexoelectric effects of the DNA film should be equivalently modeled when interpreting microcantilever detection signals.These insights might provide opportunities for the microcantilever biosensor with high sensitivity.

Mechanical and electronic approaches to improve the sensitivity of microcantilever sensors

Advances in the field of micro electro mechanical systems and their uses now offer unique opportunities in the design of ultrasensitive analytical tools. The analytical community continues to search for cost-effective, reliable, and even portable analytical techniques that can give reliable and fast response results for a variety of chemicals and biomolecules. Microcantilevers （MCLs） have emerged as a unique platform for label-free chem-sensor or bioassay. Several electronic designs, including piezoresistive, piezoelectric, and capacitive approaches, have been applied to measure the bending or frequency change of the MCLs upon exposure to chemicals. This review summarizes mechanical, fabrication, and electronics approaches to increase the sensitivity of MCL sensors.

Clamped-end effect on static detection signals of DNA-microcantilever

Boundary constraint induced inhomogeneous effects are important for mechanical responses of nano/micro-devices.For microcantilever sensors,the clamped-end constraint induced inhomogeneous effect of static deformation,so called the clamped-end effect,has great influence on the detection signals.This paper is devoted to developing an alternative mechanical model to characterize the clamped-end effect on the static detection signals of the DNA-microcantilever.Different from the previous concentrated load models,the DNA adsorption is taken as an equivalent uniformly distributed tangential load on the substrate upper surface,which exactly satisfies the zero force boundary condition at the free-end.Thereout,a variable coefficient differential governing equation describing the non-uniform deformation of the DNA-microcantilever induced by the clamped-end constraint is established by using the principle of minimum potential energy.By reducing the order of the governing equation,the analytical solutions of the curvature distribution and static bending deflection are obtained.By comparing with the previous approximate surface stress models,the clamped-end effect on the static deflection signals is discussed,and the importance of the neutral axis shift effect is also illustrated for the asymmetric laminated microcantilever.

Resonance-mode effect on piezoelectric microcantilever performance in air,with a focus on the torsional modes

A high quality factor is preferred for a microresonator sensor to improve the sensitivity and resolution. In this paper we systematically investigate the performance of the microcantilever in different resonance modes, which are the first three flexural modes, the first lateral mode, and the first and the second torsional modes. An aluminum nitride-based piezoelectric cantilever is fabricated and tested under controlled pressure from an ultra-high vacuum to a normal atmosphere, using a custom-built vacuum chamber. From the experiment results, it can be seen that the torsional modes exhibit better quality factors than those of the flexural and lateral ones. Finally, an analytical model for the air damping characteristics of the torsional mode cantilever is derived and verified by comparing with experimental results.

Nonlinear Response of Multi-Segmented Photodetectors Used for Measurements of Microcantilever Motion over Large Dynamic Ranges

The use of multi-segmented Position Sensitive Photodiodes (PSD) to measure microcantilever deflections have been found to produce nonlinear signal output, especially when the dynamic range is large. The reflected beam of the microcantilever may undergo intensity and shape modifications prior to reaching the PSD. In a multi-microcantilever sensor system the variation in the size of the individual spots plays an additional role contributing to the nonlinearities of detector output. Irrespective of the range of operation the merits of intensity normalization have been discussed. We show that the output is proportional to the width of the spot along the split line of the detector. This enables the determination of the shape of a spot. We show that the microcantilever vibrational spectrum can be obtained just using a single segment photodetector instead of using multiple segmented PSDs. These concepts will greatly facilitate interpretation of sensor data acquired from either single or multi-microcantilever experimental platforms.

Measurement of Temperature Induced Unfolding of DNA Hairpins by Microcantilever Sensors

The technical feasibility of monitoring DNA melting and cooling transitions using a microcantilever substrate has been demonstrated and these results were compared with those measured in solution by circular dichroism. DNA hairpins have been immobilized on the surface of gold-coated microcantilever surfaces and their DNA melting and cooling transitions were monitored by nanomechanical deflections. The hairpins comprised of a 16 base-pair GACA repeat motif stem duplex with a 29 nucleotide variable region. Microcantilever deflection profiles, measured by the microcantilever response as a function of temperature, were unique to different hairpins indicative of the molecules’ general stability and denaturation characteristics. The major melting and cooling transition temperatures for all three immobilized oligonucleotides were between 41。C - 52。C. The composition and flexibility of the DNA stem loops were shown to influence the thermal transitions.

Microcantilever-based Nanomechanical Studies of the Orphan Nuclear Receptor Pregnane X Receptor-Ligand Interactions

Human pregnane X receptor (PXR) is of vital importance in pharmaceutical and exogenous compound metabolism within the body. This provides strong motivation for investigating this orphan receptor’s activation by various pharmaceuticals, xenobiotics, and endocrine disrupting chemicals (EDCs). A nanomechanical transducer is developed to study xenobiotic and EDC interactions with the bioreceptor PXR’s ligand binding domain (LBD). The combination of immobilized LBD PXR with a nanostructured microcantilever (MC) platform allows for the sensitive, label-free study of ligand interaction with the receptor. PXR shows real-time, reversible responses when exposed to a specific pharmaceutical, EDCs, and xenobiotic ligands. Three EDCs binding interactions are tested, which include phthalic acid, nonylphenol, and bisphenol A, with PXR. PXR LBD was exposed to rifampicin, a potent PXR activator, with various injection and recovery times to study their interaction. A two protein array of PXR and estrogen receptor ? (ER-?) directly compares the nanomechanical responses of these receptors with rifampicin on a single platform.

A ZnO thin-film driven microcantilever for nanoscale actuation and sensing

Zinc oxide(ZnO)thin film as a piezoelectric material for microelectromechanical system(MEMS)actuators and sensors was evaluated.ZnO thin films were deposited using radio frequency(RF)magnetron sputtering.Process parameters such as gas ratio,working pressure,and RF power were optimized for crystalline structure.The ZnO thin films were characterized by X-ray diffraction(XRD)and scanning electron microscopy(SEM).Good quality of ZnO thin films was further confirmed by a high transverse piezoelectric coefficient d31.A microcantilever was then designed,fabricated,and characterized.Design formulas of resonant frequency,actuation,and sensing sensitivities were derived.The resonant frequency was determined by an impedance analyzer.Tip deflection on nanometer level was demonstrated with the cantilever used as an actuator.The actuation sensitivity was found to be 12.2 nm/V.As a sensor,the cantilever was calibrated against a reference accelerometer.The sensing sensitivity was characterized to be 46 mV/g.The characterization results were compared with design specifications.The differences were caused mainly by thickness control in etching.This study showed that ZnO is a promising piezoelectric material for MEMS actuators and sensors in terms of excellent process compatibility and good piezoelectric performance.

Performance analysis of microcantilever array sensing

Array sensing is increasingly important in the development of microcantilever(MC) sensors, and response consistency is the foundation for MC array sensing. In the present work, we investigated the response consistency of MC array sensing. The responses of two types of commercially available MC arrays were studied under conditions of temperature change, solution replacement and biochemical molecular interaction. For the thermal response, the deflections of both arrays were found to be proportional to temperature, and the responses of the MCs in both arrays were consistent with each other. The thermal response sensitivity for each MC during temperature increase and decrease also showed good consistency. Moreover, the MC array showed good consistency for the response induced by solution replacement. Finally, we also demonstrated that the MC array had good consistency in biochemical detection, exemplified by aflatoxin antibody-anti gen binding. The good response consistency makes this technology reliable and accurate for biochemical sensing.

Design and realization of 3D printed fiber-tip microcantilever probes applied to hydrogen sensing

Cantilevers in microelectromechanical systems have the advantages of non-labeling,real-time detection,positioning,and specificity.Rectangular solid,rectangular hollow,and triangular microcantilevers were fabricated on an optical fiber tip via two-photon polymerization.The mechanical properties were characterized using finite element simulations.Coating the microcantilever with a palladium film enabled high sensitivity and rapid hydrogen detection.The shape of the cantilever determines the sensitivity,whereas the thickness of the palladium film determines the response time.Additional microelectromechanical systems can be realized via polymerization combined with optical fibers.

SURFACE STRESS PROPERTIES OF DNA-MICROCANTILEVER SYSTEMS

For the first time, the connection between surface stress and nanoscopic interac- tions of DNA adsorbed on microcantilever is established by combining Strey＇s mesoscopic liquid crystal theory and Stoney＇s formula. It is shown that surface stress depends not only on biomolec- ular interactions of DNA biofilm but also on mechanical properties of cantilever. Considering the correlativity between grafting density and chain length of DNA chain, we discuss the differences between DNA-microcantilever system and DNA solution system. The major theoretical achieve- ment of this model is to identify the main contributions to surface stress under different detection conditions. This provides guidelines for designing new biosensors with high sensitivity and improved reliability.

H2S gas sensor based on integrated resonant dual-microcantilevers with high sensitivity and identification capability

Detection of trace-level hydrogen sulfide(H2 S)gas is of great importance whether in industrial production or disease diagnosis.This research presents a novel H2 S gas sensor based on integrated resonant dual-microcantilevers which can identify and detect trace-level H2 S in real-time.The sensor consists of two integrated resonant microcantilever sensors with different functions.One cantilever sensor can identify H2 S by outputting positive frequency shift signals,while the other cantilever sensor will detect H2 S as a normally used cantilever sensor with negative frequency shifts.Combined the two cantilever sensors,the proposed gas sensor can distinguish H2 S from a variety of common gases,and the detection limit to H2 S of the sensor is as sensitive as below 1 ppb.

Electrothermal Driving Microcantilever Resonator as a Platform for Chemical Gas Sensing

In the current research,the use of a micromachined cantilever resonator as a platform for chemical gas sensing was examined.The microcantilever resonator integrates an electrothermal driving unit and a piezoresistive detecting unit,and it is fabricated by direct bonding a silicon-on-insulator（SOI） wafer.With a particular polymer layer coated on the surface of the microcantilever,a gas sensor for volatile organic components（VOCs） detection can be realized.The operation mechanism provides the microcantilever resonator with integrated circuit（IC） compatibility in terms of both the fabrication process and operating voltage.The configuration of the microcantilever resonator can optimize the performance of the gas sensor.The SOI wafer provides a solution for the integrated fabrication of the microstructure,transducers,electronics,and the precise control of the resonator parameters.In this paper,the principles,design,analysis,process,and demonstration of the gas sensor based on the microcantilever resonator are presented.The experimental results provide confirmation that the polymer-coated microcantilever resonator has excellent performance with regard to VOC detection.

3D printed fiber-optic nanomechanical bioprobe

Ultrasensitive nanomechanical instruments,e.g.atomic force microscopy(AFM),can be used to perform delicate biomechanical measurements and reveal the complex mechanical environment of biological processes.However,these instruments are limited because of their size and complex feedback system.In this study,we demonstrate a miniature fiber optical nanomechanical probe(FONP)that can be used to detect the mechanical properties of single cells and in vivo tissue measurements.A FONP that can operate in air and in liquids was developed by programming a microcantilever probe on the end face of a single-mode fiber using femtosecond laser two-photon polymerization nanolithography.To realize stiffness matching of the FONP and sample,a strategy of customizing the microcantilever’s spring constant according to the sample was proposed based on structure-correlated mechanics.As a proof-of concept,three FONPs with spring constants varying from 0.421 N m^(−1)to 52.6 N m^(−1)by more than two orders of magnitude were prepared.The highest microforce sensitivity was 54.5 nmμN^(−1)and the detection limit was 2.1 nN.The Young’s modulus of heterogeneous soft materials,such as polydimethylsiloxane,muscle tissue of living mice,onion cells,and MCF-7 cells,were successfully measured,which validating the broad applicability of this method.Our strategy provides a universal protocol for directly programming fiber-optic AFMs.Moreover,this method has no special requirements for the size and shape of living biological samples,which is infeasible when using commercial AFMs.FONP has made substantial progress in realizing basic biological discoveries,which may create new biomedical applications that cannot be realized by current AFMs.

Residual Strains in a Nanometer Thick Cr Film Measured on Micromachined Beams

A Cr film with a 75 nm thickness sputtered on a Si substrate was used to fabricate microbridge and microcantilever samples with the MEMS （microelectromechanical system） technique. The profile of the buckled beams was measured by using the interference technique with white light and fitted with a theoretical result. The uniform residual strain in the bridge samples was deduced from the variation of buckling amplitude with the beam length. On the other hand, the gradient residual strain was determined from the deflection profile of the cantilever. The residual uniform and gradient strain in the Cr film are about 4.96×10^-3 and 4.2967×10^-5, respectively.