Microcantilever Sensors Research Articles

Monitoring swelling and deswelling of thin polymer films by microcantilever sensors

Microcantilever based sensors are promising devices because they are fast, low cost, portable and allow measuring extremely small quantities of substances in gas or liquid phase that are not detectable by other methods. In this work we investigate the swelling and deswelling behavior of poly(hydroxyl ethyl methacrylate), PHEMA, films with three different average molecular masses deposited onto bare silicon microcantilevers, a hydrophilic substrate, and onto polystyrene (PS) coated microcantilevers, which is a hydrophobic substrate, under humidity cycles by monitoring the deflections resulting from differential surface stress. The results found in the present study demonstrate that the micromechanical response observed are related not only to the polymer molecular weight, but also to the polymer-interface phenomena and environment–polymer interface that can play a crucial role on the signal transduction. Ellipsometric measurements evidenced that the swelling of PHEMA films with intermediate molecular weight at 80% RH follows Fickian diffusion mechanism. Nevertheless, due to the weak optical contrast or film homogeneity shorter or longer chains than PHEMA-300 could not be investigated by ellipsometry. PHEMA films deposited onto PS surfaces presented dewetting, which limited the ellipsometric measurements. In comparison to ellipsometry, monitoring swelling behavior of PHEMA by nanomechanical responses is more advantageous because it is faster and less restricted.

Miniaturization of Photothermal Cantilever Deflection Spectroscopy with an Electrical Readout

The chemical selectivity challenge of microcantilever sensors can be overcome by photothermal cantilever deflection spectroscopy (PCDS). A bi-material cantilever responds to heat generated by non-radiative decay process when the adsorbed molecules are resonantly excited with infrared (IR) light. The variation in cantilever deflection amplitude as a function of illuminating IR wavelength corresponds to the conventional IR absorption spectrum of the adsorbed molecules. In addition, the mass of the adsorbed molecules can be determined by measuring the resonance frequency shift of the cantilever for the quantitative analysis. This technique offers unprecedented opportunities for highly selective as well as sensitive chemical sensing without relying on chemoselective interfaces. However, conventional optical signal readout schemes employed for microcantilever sensors pose challenges on miniaturization and system level integration. Here, we demonstrate PCDS using a piezoresistive cantilever which can be easily miniaturized and integrated into a portable sensor platform.

Photothermal cantilever deflection spectroscopy

Microcantilever sensors offer high sensitivity in the detection of adsorbed molecules based either on resonance frequency shift or changes in cantilever deflection, as both of these signals can be detected with very high resolution. Despite the high sensitivity offered by this platform, cantilevers suffer from poor selectivity due to the lack of sufficiently selective interfacial layers which can be immobilized on cantilever surfaces. This problem can be overcome by using photothermal cantilever deflection spectroscopy (PCDS), which exploits the high thermomechanical sensitivity of bi-material microcantilevers. A bi-material cantilever responds to heat generated by the nonradiative decay process when the adsorbed molecules are resonantly excited with infrared (IR) light. The variation in the cantilever deflection as a function of illuminating IR wavelength corresponds to the conventional IR absorption spectrum of the adsorbed molecules. In addition, the mass of the adsorbed molecules can be determined by measuring the resonance frequency shift of the cantilever as an orthogonal signal for the quantitative analysis. This multi-modal PCDS offers unprecedented opportunities for obtaining very high selectivity in chemical and biological sensing without using selective interfacial layers or extrinsic labels.

Miniaturization of Photothermal Cantilever Deflection Spectroscopy with an Electrical Readout

Detection, differentiation, and quantification of trace amounts of chemical analytes with a portable device are of great interest in many applications such as energy, environment, law-enforcement, national security, and health. With the recent progress of micro/nanofabrication and system integration technologies, micro/nanoelectromechanical systems are regarded as very strong candidates to satisfy the current requirements of portable sensors such as high sensitivity, miniature size, multiple detection, low-cost, and low-power consumption. The enhancement in quality of life and economic growth are anticipated by realizing and exploiting high-performance portable chemical sensing systems in the near future. However, achieving this goal using the current approach based on the development of chemoselective interfaces is proving to be a challenging task, especially for the realization of reversible sensors at room temperature. Responses from a sensor with immobilized chemoselective interfaces often show interference due to the presence of other similar molecules and give false signals. This chemical selectivity challenge can be overcome by photothermal cantilever deflection spectroscopy (PCDS), which exploits the high thermomechanical sensitivity of a bi-material microcantilever. A bi-material cantilever responds to heat generated by non-radiative decay process when the adsorbed molecules are resonantly excited with infrared (IR) light. Monitoring the variation in cantilever deflection amplitude as a function of illuminating IR wavelength corresponds to the conventional IR absorption spectrum of the adsorbed molecules. In addition, the mass of the adsorbed molecules can be determined by measuring the resonance frequency shift of the cantilever for the quantitative analysis. This photothermal spectroscopy technique offers unprecedented opportunities for highly selective as well as sensitive chemical sensing without relying on chemoselective interfaces. However, conventional optical signal readout schemes employed for microcantilever sensors limit miniaturization and system level integration. Here, we demonstrate PCDS using a piezoresistive cantilever which can be easily miniaturized and integrated into a portable sensor platform.

Detection of calcium ions using gold-coated micro-cantilever sensors using upper- and lower-rim functionalized calix[4]arenes

The use of a bimodal calix[4]arene 2, was investigated as a potential host/guest sensing layer for microcantilever sensors for detecting selected ions in dilute aqueous solutions. It was found that the sensing layers gave the highest microcantilever sensitivity when microcantilevers coated with 5nm of Inconel and 40nm of Au were incubated for 1h in a 1.0μM dichloromethane:ethanol (1:9) solution of calix[4]arene 2. This calix[4]arene 2 was observed to form well-ordered self-assembled monolayers (SAM) on Au-coated substrates with no sign of bare areas or etch pits. Microcantilever sensor measurements showed that the calix[4]arene 2-functionalized cantilevers were able to detect Ca2+ ions in aqueous solutions of CaCl2 at concentrations as low as 10−12M. Although this receptor was shown to have a high affinity for CaCl2 in aqueous solutions, it was also found to be able to detect other ionic compounds, however only producing microcantilever deflections ranging from 10% to 30% of those obtained for CaCl2.

An ultra-sensitive piezoresistive polymer nano-composite microcantilever platform for humidity and soil moisture detection

Simultaneous monitoring of soil moisture at different soil levels or near plant roots and relative humidity are crucial for optimizing the crop yield. In the present paper, we demonstrate a novel, compact and inexpensive polymer nano-composite piezoresistive microcantilever sensor platform for the measurement of relative humidity (% RH) and soil moisture. A piezoresistive microcantilever is realized using SU-8 and carbon black based nano-composite. Its surface is further modified by Poly-aniline (PANI) nanofibers as a sensing layer. The surface functionalization is confirmed by FTIR, SEM and contact angle measurements. The sensor exhibited a maximum response of 28mV toward 93% RH with sensitivity of 64μV/0.1% RH. Sensitivity values of 43.6, 275 and 78.6μV/0.1% change in the moisture content for bentonite soil, white clay and sand, respectively, are achieved. Such high sensitivity values coupled with the low cost can be utilized further for the realization of rugged, portable and handheld devices with wireless networking facility.

Fabrication and characterization of piezoelectric driven microdiaphragm resonating sensor for a biosensing application

The detection capability of microresonating sensors is decided by the resonant properties (mass sensitivity and quality factor) because the microresonating sensors have detection principle that the target material of small amount quantitatively detect by measuring the resonant properties change of microresonators. Mass sensitivity is important factor to evaluate minimum detectable mass of microresonating sensors. For the biomolecule detection in liquid, microresonaotrs have to keep the quality factor that can discriminate small frequency change when the liquid sample injected on the microresonating sensors. In order to study mass sensitivity and quality factor of the fabricated microdiaphragm sensors, Pt thin film with different thicknesses are deposited on the our Pb(Zr0.52Ti0.48)O3 layer-embedded microdiaphragm sensors. Increasing the mass sensitivity ranging from 1.68 to 36.61 Hz/ng which is found with the decreasing the width of squared microdiaphragms ranging 900 to 300 μm. The mass sensitivity of our microdiaphragm sensor stands comparison with microcantilever sensor of length scale of 200 ~ 300 μm. Moreover, we find that the quality factor is kept on more than 23 that was ten times better than microcantilever resonating sensor with length scale of 200 μm.

Effect of non-specific species competition from total RNA on the static mode hybridization response of nanomechanical assays of oligonucleotides

We investigate here the nanomechanical response of microcantilever sensors in real-time for detecting a range of ultra-low concentrations of oligonucleotides in a complex background of total cellular RNA extracts from cell lines without labeling or amplification. Cantilever sensor arrays were functionalized with probe single stranded DNA (ssDNA) and reference ssDNA to obtain a differential signal. They were then exposed to complementary target ssDNA strands that were spiked in a fragmented total cellular RNA background in biologically relevant concentrations so as to provide clinically significant analysis. We present a model for prediction of the sensor behavior in competitive backgrounds with parameters that are indicators of the change in nanomechanical response with variation in the target and background concentration. For nanomechanical assays to compete with current technologies it is essential to comprehend such responses with eventual impact on areas like understanding non-coding RNA pharmacokinetics, nucleic acid biomarker assays and miRNA quantification for disease monitoring and diagnosis to mention a few. Additionally, we also achieved a femtomolar sensitivity limit for online oligonucleotide detection in a non-competitive environment with these sensors.

First-principles surface stress calculations and multiscale deformation analysis of a self-assembled monolayer adsorbed on a micro-cantilever.

Micro-cantilever sensors are widely used to detect biomolecules, chemical gases, and ionic species. However, the theoretical descriptions and predictive modeling of these devices are not well developed, and lag behind advances in fabrication and applications. In this paper, we present a novel multiscale simulation framework for nanomechanical sensors. This framework, combining density functional theory (DFT) calculations and finite element method (FEM) analysis, is capable of analyzing molecular adsorption-induced deformation and stress fields in the sensors from the molecular scale to the device scale. Adsorption of alkanethiolate self-assembled monolayer (SAM) on the Au(111) surface of the micro-cantilever sensor is studied in detail to demonstrate the applicability of this framework. DFT calculations are employed to investigate the molecular adsorption-induced surface stress upon the gold surface. The 3D shell elements with initial stresses obtained from the DFT calculations serve as SAM domains in the adsorption layer, while FEM is employed to analyze the deformation and stress of the sensor devices. We find that the micro-cantilever tip deflection has a linear relationship with the coverage of the SAM domains. With full coverage, the tip deflection decreases as the molecular chain length increases. The multiscale simulation framework provides a quantitative analysis of the displacement and stress fields, and can be used to predict the response of nanomechanical sensors subjected to complex molecular adsorption.

Microgripping force measuring device based on SU-8 microcantilever sensor

For the direct measurement of microgripper gripping force and the calibration of microgripper jaw stiffness, this paper presents a new microforce measuring device based on low-cost SU-8 microcantilever sensors with integrated copper piezoresistive strain gauge. On the basis of the deduced equations, the geometric parameters of the microcantilever sensor are determined. Then, the fabrication of the sensors is carried out using a simple process. One fabricated sensor is calibrated by measuring the output voltage and the applied vertical force simultaneously. The calibration result of the microcantilever stiffness is 2.99 N/m and the output sensitivity is 0.51 V/N . The performance test results of the calibrated sensor show that the force sensing range is 405 μN and the maximum nonlinearity is 11 μN. Finally, the microgripping forces of two different microgrippers are measured by the developed device, and jaw stiffness calibrations are also carried out. According to the experiment results, the normally closed SU-8 microgripper has a jaw stiffness of ∼2.83 N/m and the jaw stiffness of the normally open SU-8 microgripper is ∼7.22 N/m .

Functionalization layer effect on the mechanical properties of silicon based micro-cantilever mass sensors: A theoretical study

In this paper we calculate the surface stress and surface elastic constants of a model functionalized Si(111) surface by means of ab initio Density Functional Theory calculations. Subsequently these values are used in Finite Element Method simulations to predict the resonance frequency shift induced in a silicon cantilever by surface functionalization; this “multiscale” approach considers both changes in mass and elasticity of the microstructure induced by molecular adsorption. Interestingly our results show that the change in surface elastic constants, often ignored in experimental analysis, may account for 50% of the frequency shift and thus lead to a large overestimation of the attached mass.

Microcantilevers Bend to the Pressure of Clustered Redox Centers

The redox-activated deflection of microcantilevers has attracted interest for nanoactuation and chemical sensing. Microcantilever sensors are devices that transduce (bio)chemical reactions into a quantifiable nanomechanical motion via surface stress changes. Despite promising applications in analytical science, poor signal-to-noise ratios and a limited understanding of the molecular origins of the surface stress changes that cause the observed deflections remain obstacles to cantilever-based sensing becoming an established (bio)detection method, such as surface plasmon resonance and electrochemistry. We use phase-separated, binary self-assembled monolayers (SAMs) of ferrocenyldodecanethiolate and n-undecanethiolate as a model system to study the effect of the steric crowding of the redox centers on the surface stress change and cantilever deflection produced by the electrochemical oxidation of the surface-tethered ferrocene to ferrocenium. We correlate the measured surface stress change to the fraction of the clustered ferrocenyldodecanethiolate phase in the binary SAMs. The pairing of anions with the sterically crowded clustered ferroceniums induces a collective molecular reorientation which drives the cantilever deflection. The results provide fundamental insights into the response mechanism of microcantilever-based actuating and sensing technologies.

Real-time enzyme-digesting identification of double-strand DNA in a resonance-cantilever embedded micro-chamber

A novel direct identification of double-strand DNA is proposed by using real-time enzyme-digestion in a resonant-cantilever embedded microfluidic chip. The new gene-level detection method is expected to replace the conventional DNA-hybridization based gene-detection that suffers from not only nonspecific adsorption induced false-positives but also complicated single-strand DNA preparation and hybridization. Since a detected DNA chain features a unique cutting site for a certain restriction-enzyme, the accurately cut-off mass (representing the length of the digested segment) can be online recorded by the frequency-shift signal of the resonant micro-cantilever sensor. This enzyme-digestion technique is confirmed by experimental identification of the stx2 gene of E. coli O157:H7. The direct-PCR sample is directly analyzed by using our lab-made cantilever-embedded microfluidic-chip. The 3776 bp DNA is immobilized via biotin-streptavidin binding and the added mass is recorded by a frequency-decrease of 15.9 kHz within 10 min. Then, with EcoRV-enzyme digestion at the site of 2635 bp, the cut-off mass is real-time detected by a frequency-increase of 10.2 kHz within 6 min. The detected frequency-shift ratio of 15.9/10.2 = 64.2% is consistent with the length ratio between the cut-off fragment and the whole DNA chain (2635/3776 = 69.8%). Hence, the simple and accurate double-strand detection method is verified experimentally.

An ultra-sensitive piezoresistive polymer nano-composite microcantilever sensor electronic nose platform for explosive vapor detection

In the present paper, we demonstrate a compact, nonoptical, and inexpensive polymer nano-composite microcantilever sensor platform for the detection of 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-triazine (RDX) and pentaerythritol tetranitrate (PETN) vapors at room temperature. In order to achieve sufficient selectivity, the piezoresistive polymer nano-composite microcantilevers coated with gold surfaces are modified with self-assembled monolayers (SAM) of 4-mercaptobenzoic acid (4-MBA), 6-mercaptonicotonic acid (6-MNA) and 2-mercaptonicotonic acid (2-MNA). The SAMs formation is confirmed by FTIR and contact angle measurements. The ultrahigh sensitive piezoresistive polymer nano-composite microcantilever provides detection sensitivities in the below parts-per-trillion level within few seconds of exposure under ambient conditions. Maximum bending of the microcantilever is achieved within 20s with response and recovery time of ∼3s and 4s, respectively. The cross selectivity of 4-MBA and 6-MNA coated microcantilevers is confirmed by investigating exposure to different organic compounds. We also demonstrate that the polymer nano-composite microcantilever is ideally suited for “electronic nose” applications. Further, the ultra-high sensitivity and low cost of polymer nano-composite microcantilever can lead to the development of a rugged portable, handheld device for rapid and sensitive detection of explosive vapors.

The Specific Binding between Aptamer and its Target Molecules Investigated by Microcantilever Sensor

Cantilever with modified aptamers on the gold surface was employed to detect platelet-derived growth factor-BB (PDGF-BB) and cocaine. The deflection increased when PDGF-BB and cocaine were added into the flowing cell, respectively. The defection depended on the concentration of PDGF-BB and cocaine. It was also found the microcantiver went back to the same position as without cocaine after adding cocaine aptamer in situ, which proved that the cantilever could be reused. The deflection arose from the specific interaction between aptamer and its target.

Atomic force microscope microcantilevers used as sensors for monitoring humidity

A microcantilever sensor is presented. Functionalization of the cantilever with a polyaniline (PANI) sensitive layer and its use as a humidity sensor were investigated. Polyaniline was produced by interfacial synthesis and the sensitive layer was deposited on the microcantilever surface by the spin-coating method. The microcantilever deflection at various levels of relative humidity (RH) was read by means of the optical lever of an atomic force microscope (AFM Veeco Dimension V). A range of RH from 20% to 70% was introduced into the AFM chamber by mixing streams of dry and wet nitrogen. The sensitivity and reversibility of the sensors were assessed at various RH and temperatures (10, 20 and 30°C). A large deflection was observed in the coated microcantilever sensors, with faster response time at 10°C and better sensitivity and reversibility at 30°C. These results demonstrate that the spin-coated microcantilever can be used as a sensor to detect relative humidity at various different temperatures.

Electrical detection of C-reactive protein using a single free-standing, thermally controlled piezoresistive microcantilever for highly reproducible and accurate measurements.

This study demonstrates a novel method for electrical detection of C-reactive protein (CRP) as a means of identifying an infection in the body, or as a cardiovascular disease risk assay. The method uses a single free-standing, thermally controlled piezoresistive microcantilever biosensor. In a commonly used sensing arrangement of conventional dual cantilevers in the Wheatstone bridge circuit, reference and gold-coated sensing cantilevers that inherently have heterogeneous surface materials and different multilayer structures may yield independent responses to the liquid environmental changes of chemical substances, flow field and temperature, leading to unwanted signal disturbance for biosensing targets. In this study, the single free-standing microcantilever for biosensing applications is employed to resolve the dual-beam problem of individual responses in chemical solutions and, in a thermally controlled system, to maintain its sensor performance due to the sensitive temperature effect. With this type of single temperature-controlled microcantilever sensor, the electrical detection of various CRP concentrations from 1 μg/mL to 200 μg/mL was performed, which covers the clinically relevant range. Induced surface stresses were measured at between 0.25 N/m and 3.4 N/m with high reproducibility. Moreover, the binding affinity (KD) of CRP and anti-CRP interaction was found to be 18.83 ± 2.99 μg/mL, which agreed with results in previous reported studies. This biosensing technique thus proves valuable in detecting inflammation, and in cardiovascular disease risk assays.

Microcantilever sensors coated with doped polyaniline for the detection of water vapor

In the present work, PANI (polyaniline) emeraldine salt (doped) and base (dedoped) were used as the sensitive layer of a silicon microcantilever, and the mechanical response (deflection) of the bimaterial (coated microcantilever) was investigated under the influence of humidity. PANI in the emeraldine base oxidation state was obtained by interfacial synthesis and was deposited on the microcantilever surface by spin-coating (dedoped). Next, the conducting polymer was doped with 1 M HCl (hydrochloric acid). A four-quadrant AFM head with an integrated laser and a position-sensitive detector (AFM Veeco Dimension V) was used to measure the optical deflection of the coated microcantilever. The deflection of the coated (doped and undoped PANI) and uncoated microcantilever was measured under different humidities (in triplicate) at room pressure and temperature in a closed chamber to evaluate the sensor's sensitivity. The relative humidity (RH) in the chamber was varied from 20% to 70% using dry nitrogen as a carrier gas, which was passed through a bubbler containing water to generate humidity. The results showed that microcantilevers coated with sensitive layers of doped and undoped PANI films were sensitive (12,717 ± 6% and 6,939 ± 8%, respectively) and provided good repeatability (98.6 ± 0.015% and 99 ± 0.01%, respectively) after several cycles of exposure to RH. The microcantilever sensor without a PANI coating (uncoated) was not sensitive to humidity. The strong effect of doping on the sensitivity of the sensor was attributed to an increased adsorption of water molecules dissociated at imine nitrogen centers, which improves the performance of the coated microcantilever sensor. Moreover, microcantilever sensors coated with a sensitive layer provided good results in several cycles of exposure to RH (%).

Effect of Adsorption Stress-Induced Change in Neutral Layer Position on Static Behavior of Microcantilever Gas Sensor

The static bending model of microcantilever with monolayer molecules has been established based on energy method, in which the change in neutral layer position caused by adsorption-induced stress is introduced. On this basis, we have analyzed the relationship between the bending curvature radius of a microcantilever with its thickness, Young’s modulus and molecule-molecule distance of adsorbed molecules when it is adsorbed with monolayer water molecules. Additionally, we have investigated the effect of change in neutral layer position on the static behavior of microcantilever sensors. The results show that 1)the bending curvature radius of microcantilever is the linear, quadratic and eight approximation function of its Young’s modulus, thickness and distance of adsorbed molecules, respectively; 2)the predicted error of bending curvature radius caused by the change in neutral layer position slightly increases with decreasing Young’s modulus and thickness, whereas the effect of distance between adsorbed molecules on the error is significant; 3)the change in neutral layer position can cause a significant effect on the sensitivity and surface strain of the microcantilever

Highly sensitive nanomechanical assay for the stress transmission of carbon chain

Here, we report the first quantitative experimental study into the molecular basis of the transmission of mechanical signal that originates from biochemical reaction focusing on the length of carbon chain. We designed an experiment by using n-alkanethiols with a same carboxyl group and different chain lengths (n=1, 5, 10 and 15) to immobilize a same receptor molecule on the gold surface of a microcantilever, and detected the nanomechanical response of biochemical reaction. The sensitivity of the microcantilever was found to be greatly influenced by the chain length of linker that is between the receptor molecule and the microcantilever surface. The efficiency of stress transmission increases significantly with decreasing length of carbon chain. At the same time, we develop a label-free microcantilever sensor for highly sensitive detection of Glycyrrhizic acid (GL). The detection limit of the microcantilever sensor for GL is found to be as low as 20pg/mL for the shortest linker (n=1), which is 500 times lower than the longest linker (n=15) and 50 times lower than that of the corresponding icELISA. These findings will provide new insights into the fundamental mechanisms of stress transmission, which may be exploited for biochemical sensor and nanoactuation applications.