Resonant Micro-cantilever Sensor Research Articles

Highly Sensitive Self-Actuated Zinc Oxide Resonant Microcantilever Humidity Sensor.

A resonant microcantilever sensor is fabricated from a zinc oxide (ZnO) thin film, which serves as both the structural and sensing layers. An open-air spatial atomic layer deposition technique is used to deposit the ZnO layer to achieve a ∼200 nm thickness, an order of magnitude lower than the thicknesses of conventional microcantilever sensors. The reduction in the number of layers, in the cantilever dimensions, and its overall lower mass lead to an ultrahigh sensitivity, demonstrated by detection of low humidity levels. A maximum sensitivity of 23649 ppm/% RH at 5.8% RH is observed, which is several orders of magnitude larger than those reported for other resonant humidity sensors. Furthermore, the ZnO cantilever sensor is self-actuated in air, an advantageous detection mode that enables simpler and lower-power-consumption sensors.

An in-situ TEM microreactor for real-time nanomorphology & physicochemical parameters interrelated characterization

In-situ quantitative structure-property relationship (QSPR) characterization between nanomorphology and physicochemical parameters is essential for revealing the growth mechanism and guiding the optimization of functional nanomaterials. However, extracting the interrelated physicochemical parameters in the process of nanomorphology observation is still challenging. Herein, this paper demonstrates an advanced chip-scale platform for in-situ QSPR characterization by integrating a gravimetric resonant microcantilever sensor within a transmission electron microscopy (TEM) microreactor. The microcantilever measures the thermodynamic and kinetic parameters, such as enthalpy (ΔH°), activation energy (Ea) and reaction rate (v), by monitoring the reaction-induced mass change of functional nanomaterials. Simultaneously, the low-stress SiNx films as electron transparent windows allow in-situ nanomorphology observation. Using such a QSPR characterization platform, the three-stage sulfuration mechanism based on nano Kirkendall effect for the gas-solid reaction of H2S and Cu nanowires is revealed, and the different molecule-interaction behaviors of SO2 on ZnO nanowires at various temperatures are distinguished for the first time. It is believed that the in-situ QSPR microreactor can be widely used for elucidating the underlying interfacial thermodynamic/kinetic reaction mechanism, and guiding the controllable synthesis and precise optimization of functional nanomaterials.

Resonant-Cantilever-Detected Kinetic/Thermodynamic Parameters for Aptamer-Ligand Binding on a Liquid-Solid Interface.

Nucleic acid aptamers have been widely used as recognition elements on various biosensing interfaces, but quantitative kinetic/thermodynamic analysis for revealing the aptamer-ligand binding mechanism, which occurs on a liquid-solid interface, has not been realized due to a lack of usable biophysical tools. Herein we apply a resonant microcantilever sensor to continuously record the frequency shift according to the binding-induced mass change on the liquid-solid interface. The frequency-shift curve is used for tracing the reaction process and is fitted with classic equations to calculate a set of kinetic/thermodynamic parameters, such as rate constants (ka = 902.95 M-1 s-1, kd = 0.000141 s-1), equilibrium constants (KD = 1.55 μM), the Gibbs free energy (ΔG° = -32.57 kJ/mol), and the activation energy (Ea = 38.03 kJ/mol) for the immobilized aptamer and free ATP. This quantitative analysis method is label-free, calibration-free, and highly sensitive. The kinetic/thermodynamic parameter detection method provides new resolution to the in-depth understanding of the ligand-aptamer interaction on the liquid-solid interface for biosensing or lab-on-a-chip applications.

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

Detection of trace-level hydrogen sulfide (H2S) gas is of great importance whether in industrial production or disease diagnosis. This research presents a novel H2S gas sensor based on integrated resonant dual-microcantilevers which can identify and detect trace-level H2S in real-time. The sensor consists of two integrated resonant microcantilever sensors with different functions. One cantilever sensor can identify H2S by outputting positive frequency shift signals, while the other cantilever sensor will detect H2S as a normally used cantilever sensor with negative frequency shifts. Combined the two cantilever sensors, the proposed gas sensor can distinguish H2S from a variety of common gases, and the detection limit to H2S of the sensor is as sensitive as below 1 ppb.

A resonant microcantilever sensor for in-plane multi-axis magnetic field measurements

A novel magnetic field sensor is developed based on the microcantilever resonator to realize the parameter measurements of in-plane multi-axis magnetic field under different vibration modes. The working equations of the resonant sensor are established to calculate the strength and direction angle of measured magnetic field based on different resonances. The strength components of magnetic field along x-axis and y -axis are independently measured by the proposed resonant sensor under flexural and torsional resonant modes, respectively. The corresponding outputs of the sensor are linearly related to the magnetic field strength components. The finite element simulations are performed not only to prove the capability of the sensor to measure magnetic field under different modes, but also indicate the mode coupling of microcantilever resonator existed in the measurement. Thus, the coupling compensation method is proposed by amending ouput voltage of the sensor through experiments. The experimental results at atmospheric pressure show that the compensated accuracies of in-plane magnetic field are 3.06% (strength) and 1.59% (angle), and the measuring sensitivities are 98.79 µV mT−1 along x-axis and 92.46 µV mT−1 along y -axis, respectively.

Ni-MOF-74 as sensing material for resonant-gravimetric detection of ppb-level CO

For the first time, ultrasensitive detection of 10 ppb CO has been realized using metal organic framework (MOF) crystals of Ni-MOF-74 as gravimetric-type sensing material with resonant microcantilever sensors. Due to the specific interaction between CO molecules and the active transitional metal centers of Ni2+ in the Ni-MOF-74 crystal, the Ni-MOF-74 material with ultra-high surface area and nanoporous structure possesses large absorption capacity to CO gas. By loading the Ni-MOF-74 material onto the resonant microcantilever, the formed gravimetric sensor exhibits high-performance sensing to CO at trace level. The experimentally obtained limit of detection (LOD) of the sensor to CO reaches finer than 10 ppb (parts per billion in volume), which indicates an extremely high CO-detection sensitivity of the sensor. Besides the excellent sensitivity, the sensor also shows remarkable repeatability and long-term stability. Eight kinds of interfering gases are tested and a fine selectivity of the sensor is verified. This work indicates that MOF materials such as Ni-MOF-74 are promising in gravimetric-type gas sensing applications.

Automated high-throughput viscosity and density sensor using nanomechanical resonators

Most methods used to determine the viscosity and mass density of liquids have two major drawbacks: relatively high sample consumption (∼milliliters) and long measurement time (∼minutes). Resonant nanomechanical cantilevers promise to overcome these limitations. Although sample consumption has already been significantly reduced, the time resolution was rarely addressed to date. We present a method to decrease the time and user interaction required for such measurements. It features (i) a droplet-generating automatic sampler using fluorinated oil to separate microliter sample plugs, (ii) a PDMS-based microfluidic measurement cell containing the resonant microcantilever sensors driven by photothermal excitation, (iii) dual phase-locked loop frequency tracking of a higher-mode resonance to achieve millisecond time resolution, and (iv) signal processing to extract the resonance parameters, namely the eigenfrequency and quality factor. The principle was validated by screening series of 3μL droplets of glycerol solutions separated by fluorinated oil at a rate of ∼6s per sample. An analytical hydrodynamic model (Van Eysden and Sader, 2007 [6]) and a reduced order model (Heinisch et al., 2014 [16]) were employed to calculate the viscosity and mass density of the sample liquids in a viscosity range of 1–10.5mPas and a density range of 998–1154kgm−3.

A Silicon Resonant Micro-Cantilever Biosensor with Closed-Loop Self-Excitation System for Biomacromolecular Detection

A silicon resonant micro-cantilever biosensor was introduced to detect biomacromolecular based on the relationship between the cantilever resonant frequency and the cantilever equivalent mass. A closed-loop self-excitation system was designed to acquire the resonant frequency of micro-cantilever. Two groups of resonant micro-cantilever sensors with different resonant frequencies of 18.192 kHz and 17.688 kHz respectively were tested. The result showed that the detection system can automatically search the resonant frequency of micro-cantilever and locked quickly. To demonstrate the feasibility of this approach, human immunoglobulin G(IgG) as model target biomacromolecular was employed, different concentration of IgG was detected by the resonant micro-cantilever sensors, the mass effect of micro-cantilever was adept and the micro-cantilever was drive by closed-loop circuit. The linearity of micro-cantilever biosensor was very well and the experimental result of sensitivity of micro-cantilever biosensor was about 6.6×106. All the results showed that sensitivity of the presented immunoassay significantly increased by one-order of magnitude and offered great application promises in providing a sensitive, specific, and potent method for real-time detection of biological detection.

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.

A chelating-bond breaking and re-linking technique for rapid re-immobilization of immune micro-sensors

With high sensitivity and specificity to antigen, immune micro-sensors can be used in rapid detection of pathogenic microbial. This study proposes and develops a method for rapidly regeneration of antibody on a resonant micro-cantilever sensor. A nitrilotriacetic acid (NTA) derivative is synthesized with cystine and bromoacetic acid, then added with 2-mercaptoethanol to prepare a mixed self-assembled monolayer (SAM) on Au (111) surface of the cantilever. Ni²⁺ ions are thereafter chelated on the mixed SAM to form a breakable and re-linkable chelating-bond layer. Repeatable cycles of antibody immobilization and erasing are experimentally validated with a detectable marker of synthesized biotinylated poly peptides harboring six histidine residues (named as His-Bio). Two distinguished pathogenic microbial, Escherichia. coli O157:H7 and Bacillus Anthracis, are detected with the rapidly regenerated sensor. The E. coli O157:H7 sensor exhibits a three-time repeated detection to the 10³ CFU/ml concentration microbial. Then, an E. coli O157:H7 sensor is eluted with Tris-HCl (20 mM Tris, 150 mM NaCl, 0.1% Tween 20, pH = 3.0) and rapidly reconstructed into a B. Anthracis sensor by changing the re-immobilized antibody. The cantilever sensor no longer responses to E. coli O157:H7 even in a high concentration of 10⁷ CFU/ml. In contrast, the sensor is experimentally confirmed being resoluble to low concentration B. Anthracis at 10³ spores/ml level. The proposed fast regeneration method is promising in repeatedly or multi-target detection applications of micro/nano immune-sensors, e.g. the resonant micro-cantilevers.

Integrated MEMS/NEMS Resonant Cantilevers for Ultrasensitive Biological Detection

The paper reviews the recent researches implemented in Chinese Academy of Sciences, with achievements on integrated resonant microcantilever sensors. In the resonant cantilevers, the self‐sensing elements and resonance exciting elements are both top‐down integrated with silicon micromachining techniques. Quite a lot of effort is focused on optimization of the resonance mode and sensing structure for improvement of sensitivity. On the other hand, to enable the micro‐cantilevers specifically sensitive to bio/chemical molecules, sensing materials are developed and modified on the cantilever surface with a self‐assembled monolayer (SAM) based bottom‐up construction and surface functionalization. To improve the selectivity of the sensors and depress environmental noise, multiple and localized surface modifications are developed. The achieved volume production capability and satisfactory detecting resolution to trace‐level biological antigen of alpha‐fetoprotein (AFP) give the micro‐cantilever sensors a great promise for rapid and high‐resoluble detection.

Nanogram per milliliter-level immunologic detection of alpha-fetoprotein with integrated rotating-resonance microcantilevers for early-stage diagnosis of heptocellular carcinoma

Nanogram per milliliter-level ultra-low concentration detection of alpha-fetoprotein (AFP), which is an important marker for heptocellular carcinoma, is in favor of early-stage prognosis and disease diagnosis. On-the-spot rapid detection of such antigens as AFP highly requires innovative micro/nano techniques. To meet this requirement, an advanced resonant microcantilever is developed and used for screening the tumor marker at nanogram per milliliter level. The sensing principle of the resonant microcantilever is measuring frequency-shift versus specific-adsorbed mass. With both electromagnetic resonance-exciting and piezoresistive readout elements on-chip integrated, the microcantilever sensor is operated in a rotating resonance mode to improve sensitivity and resolution to specific mass adsorption. Prior to detection of AFP with previously immobilized anti-AFP antibody, the antigen-antibody specific-binding is confirmed with an enzyme linked immunosorbent assay experiment. By implementing the specific reaction in liquid and reading out the sensor signal in lab air environment, the micromechanical sensor has achieved the sensitive scale between 2 and 20 ng/ml. To effectively depress cross-talk signal and improve resolution, the insensitive regions of the cantilever surface are pre-modified with 2-[methoxy (polyethyleneoxy) propyl] trimethoxysilane for nonspecific bio-adsorption minimization. Finally, a better AFP detecting limit than 2 ng/mL is experimentally achieved. The label-free resonant microcantilever sensor is promising in low-cost or even disposable early-stage prognosis and diagnosis of tumors.