Characterization of ligand-functionalized microcantilevers for metal ion sensing

A sensor for metal cations is demonstrated using single and binary mixtures of different thiolated ligands as self-assembled monolayers (SAMs) functionalized on silicon microcantilevers (MCs) with gold nanostructured surfaces. Binding of charged metal ions to the active surface of a cantilever induces an apparent surface stress, thereby causing static bending of the MC that is detected in this work by a beam-bending technique. A MC response mechanism based on changes in surface charge is discussed. The monodentated ligands arranged as SAMs on the MC surface are not expected to fully satisfy the coordination sphere of the detected metals. This leads to lower binding constants than would be expected for chelating ligands, but reversible responses. The modest binding constants are compensated in terms of the magnitudes of responses by the inherent higher sensitivity of the nanostructured approach as opposed to more traditional smooth surface MCs. Response characteristics are optimized in terms of SAM formation time, concentration of ligand solution, and pH of working buffer solution. Limits of detection for the tested mono-, di-, and trivalent metal ions are in low to submicromolar range. The results indicated that shapes and magnitudes of response profiles are characteristics of the metal ions and type of SAM. The response factors for a given SAM with the tested metal ions, or for a given metal with the tested SAMs, varied by roughly 1 order of magnitude. While the observed selectivity is not large, it is anticipated that sufficient ionic recognition contrast is available for selective metal ion identification when differentially functionalized arrays of MCs (different ligands on different cantilevers in the array) are used in conjunction with pattern recognition techniques.     

Detection of Hg2+ using microcantilever sensors

Trace amounts of Hg2+ are detected by using a microcantilever coated with gold. The microcantilever undergoes bending due to accumulation of Hg2+ on the gold surface. It is found that a concentration of 10(-11) M Hg2+ can be detected using this technology. Other cations, such as K+, Na+, Pb2+, Zn2+, Ni2, Cd2+, Cu2+, and Ca2+ have little or no effect on the deflection of the cantilever. The selectivity of the Hg2+ sensor could be improved by coating the gold surface of microcantilever with a self-assembled monolayer of a long-chain thiol compound.     

Label-free detection of amyloid growth with microcantilever sensors

We present an approach for sensing protein aggregation using microcantilever systems. Results?from both single cantilever experiments with internal reference and multicantilever array measurements with dedicated reference cantilevers are discussed. We show that in both?cases protein aggregation on the sensor can be detected through associated changes in surface?stress.     

Design of High-Sensitivity Cantilever and Its Monolithic Integration With CMOS Circuits

Rectangular piezoresistive cantilevers with stress concentration holes opened were designed and fabricated in order to increase the response signals of piezoresistive cantilever first. Both the simulations and the measurements on the cantilever sensitivity show that this design can obviously result in an improvement on the displacement sensitivity of the piezoresistive cantilever. After a characterization study on the piezoresistive cantilever, a monolithic integration of the microcantilever array with a complementary metal-oxide-semiconductor (CMOS) readout circuitry based on the silicon-on-insulator (SOI) CMOS and the SOI micromachining technologies was designed. A cantilever array, a digital controlled multiplexer, and an instrumentation amplifier compose the integrated sensor system, and post-CMOS process was designed to fabricate the integrated system. The measurement results on the SOI CMOS circuitry of the integrated system prove a feasibility of the integration design     

Micromechanical detection of proteins using aptamer-based receptor molecules

We report label-free protein detection using a microfabricated cantilever-based sensor that is functionalized with DNA aptamers to act as receptor molecules. The sensor utilizes two adjacent cantilevers that constitute a sensor/reference pair and allows direct detection of the differential bending between the two cantilevers. One cantilever is functionalized with aptamers selected for Taq DNA polymerase while the other is blocked with single-stranded DNA. We have found that the polymerase-aptamer binding induces a change in surface stress, which causes a differential cantilever bending that ranges from 3 to 32 nm depending on the ligand concentration. Protein recognition on the sensor surface is specific and has a concentration dependence that is similar to that in solution.     

Liquid-phase chemical and biochemical detection using fully integrated magnetically actuated complementary metal oxide semiconductor resonant cantilever sensor systems

A novel resonant cantilever sensor system for liquid-phase applications is presented. The monolithic system consists of an array of four electromagnetically actuated cantilevers with transistor-based readout, an analog feedback circuit, and a digital interface. The biochemical sensor chip with a size of 3 mm x 4.5 mm is fabricated in an industrial complementary metal oxide semiconductor (CMOS) process with subsequent CMOS-compatible micromachining. A package, which protects the electrical components and the associated circuitry against liquid exposure, allows for a stable operation of the resonant cantilevers in liquid environments. The device is operated at the fundamental cantilever resonance frequency of approximately 200 kHz in water with a frequency stability better than 3 Hz. The use of the integrated CMOS resonant cantilever system as a chemical sensor for the detection of volatile organic compounds in liquid environments is demonstrated. Low concentrations of toluene, xylenes, and ethylbenzene in deionized water have been detected by coating the cantilevers with chemically sensitive polymers. The liquid-phase detection of analyte concentrations in the single-ppm range has been achieved. Furthermore, the application of this sensor system to the label-free detection of biomarkers, such as tumor markers, is shown. By functionalizing the cantilevers with anti-prostate-specific antigen antibody (anti-PSA), the corresponding antigen (PSA) has been detected at concentration levels as low as 10 ng/mL in a sample fluid.     

Glucose oxidase multilayer modified microcantilevers for glucose measurement

We report a novel enzyme-based microcantilever sensor by using layer-by-layer nanoassembly modification. A glucose oxidase (GOx) functionalized microcantilever underwent bending when it was exposed to glucose solutions. The magnitudes of bending were proportional to the concentrations of glucose. The cantilever bending was specific toward glucose, but not to other sugars such as mannose, fructose, or galactose. The flow rate effect on the cantilever bending response is also discussed. The bending mechanism was investigated, and the kinetic and thermodynamic analysis and experimental results showed that the conformational change of GOx and gluconic formation were the origin of cantilever deflection.     

Fabrication,calibration, and preliminary testing of microcantilever‐based piezoresistive sensor for BioMEMS applications

In this study, the authors demonstrate the fabrication, calibration, and testing of a piezoresistive microcantilever‐based sensor for biomedical microelectromechanical system (BioMEMS) application. To use any sensor in BioMEMS application requires surface modification to capture the targeted biomolecules. The surface alteration comprises self‐assembled monolayer (SAM) formation on gold (Au)/chromium (Cr) thin films. So, the Au/Cr coating is essential for most of the BioMEMS applications. The fabricated sensor uses the piezoresistive technique to capture the targeted biomolecules with the SAM/Au/Cr layer on top of the silicon dioxide layer. The stiffness (k) of the cantilever‐based biosensor is a crucial design parameter for the low‐pressure range and also influence the sensitivity of the microelectromechanical system‐based sensor. Based on the calibration data, the average stiffness of the fabricated microcantilever with and without Au/Cr thin film is 141.39 and 70.53 mN/m, respectively, which is well below the maximum preferred range of stiffness for BioMEMS applications. The fabricated sensor is ultra‐sensitive and selective towards Hg²⁺ ions in the presence of other heavy metal ions (HMIs) and good enough to achieve a lower limit of detection 0.75 ng/ml (3.73 pM/ml).Inspec keywords: molecular biophysics, bioMEMS, chemical sensors, microfabrication, cantilevers, microsensors, self‐assembly, monolayers, gold, piezoresistive devices, calibration, chromium, thin film sensors, mercury (metal), silicon compoundsOther keywords: microcantilever‐based piezoresistive sensor, BioMEMS application, biomedical microelectromechanical system application, targeted biomolecules, piezoresistive technique, cantilever‐based biosensor, microelectromechanical system‐based sensor, microcantilever fabrication, calibration, surface modification, surface alteration, self‐assembled monolayer, SAM, coating, thin films, HMI, heavy metal ion, Au‐Cr‐SiO₂ , Hg     

Novel microcantilever design for versatile mass sensor application

This study presents a new microcantilever design for versatile mass sensor application. The novel comb-type cantilever provides a sensitive microcantilever structure for normal sensor application, and its sensing responses are compared with those of a commercial cantilever. While the comb-type cantilever has a similar total surface area to the commercial cantilever, there is a distinct difference in the design of the regional surface area. The results for a static charge interaction, used to compare the sensitivity of normal sensor applications, show a significant resonant frequency change for the comb-type cantilever when compared with that for the commercial cantilever, indicating the importance of the large surface area in the highly sensitive cantilever region. Thus, a schematic structure of a microcantilever for fabricating a highly sensitive mass sensor is proposed.     

Nanostructured microcantilevers with functionalized cyclodextrin receptor phases: self-assembled monolayers and vapor-deposited films

It is shown that the performance of microcantilver-based chemical sensors in a liquid environment is affected by altering cantilever surface morphology and receptor phase type and thickness. Self-assembled monolayers of thiolated beta-cyclodextrin (HM-beta-CD) and thin films of vapor-deposited heptakis (2,3-O-diacetyl-6-O-tertbutyl-dimethylsilyl)-beta-cyclodextrin (HDATB-beta-CD) were studied on smooth and nanostructured (dealloyed) gold-coated microcantilever surfaces. The dealloyed surface contains nanometer-sized features that enhance the transduction of molecular recognition events into cantilever response, as well as increase film stability for thicker films. Improvements in the limits of detection of the compound 2,3-dihydroxynaphthalene as great as 2 orders of magnitude have been achieved by manipulating surface morphology and film thickness. The observed response factors for the analytes studied varied from 0.02-604 nm/ppm, as determined by cantilever deflection. In general, calibration plots for the analytes were linear up to several hundred nanometers in cantilever deflections.     

Investigation of DNA sensing using piezoresistive microcantilever probes

Piezoresistive microcantilever-based sensors maybe used in a variety of sensing applications, including chemical sensing and biological sensing. In these applications, a sensing material is functionalized so as to undergo a volumetric or dimensional change upon analyte exposure. A piezoresistive microcantilever in contact with, or embedded within, the sensing material records the dimensional change as a simple resistance change in the cantilever as it is strained by the volumetric shift in the sensing layer. Here, we describe the detection of single-strand DNA by utilizing a sensing layer material consisting of thiolated single-strand DNA attached to a gold film substrate. A piezoresistive microcantilever in direct contact with this layer in solution immediately responds to the presence of the complimentary (25 base) single strand.     

Trace detection of peroxides using a microcantilever detector

A microcantilever sensor is reported for the trace detection of peroxide vapors. The sensor features a self-assembled monolayer that undergoes chain polymerization in the presence of peroxide radicals, causing a deflection of the cantilever. The generation of radicals using a heated filament, and the resulting surface polymerization reaction, is based on initiated Chemical Vapor Deposition chemistry. The sensor was successfully demonstrated with hydrogen peroxide and exhibited inherent reversibility and a selective, self-amplified response. Air and water were tested as interferents. This trace peroxide detector has industrial applications and addresses an aviation security need for the reliable detection of homemade explosives.     

Photonic crystal aqueous metal cation sensing materials

We developed a polymerized crystalline colloidal array photonic material that senses metal cations in water at low concentrations (PCCACS). Metal cations such as Cu2+, Co2+, Ni2+, and Zn2+ bind to 8-hydroxyquinoline groups covalently attached to the PCCACS. At low metal concentrations (相似文献   

Silicon made resonant microcantilever: Dependence of the chemical sensing performances on the sensitive coating thickness

A gas sensor based on the use of a resonating microcantilever has been realized by using a polymer sensitive coating. From the theoretical study of the microcantilever sensitivity, it has been deduced that the sensitivity is enhanced when the resonant frequency or the sensitive coating thickness are increased. The sensitive coating thickness influence has then been verified experimentally by using polyetherurethane (PEUT) as sensitive coating for ethanol detection. From these measurements, some drawbacks are shown: the coating thickness increase leads to a sensor response time increase and a frequency noise increase which worsens the limit of detection. Conclusions are then made about the sensitive coating optimization depending on application constraint considerations.     

Nanomechanical detection of cholera toxin using microcantilevers functionalized with ganglioside nanodiscs

The label-free detection of cholera toxin is demonstrated using microcantilevers functionalized with ganglioside nanodiscs. The cholera toxin molecules bind specifically to the active membrane protein encased in nanodiscs, nanoscale lipid bilayers surrounded by an amphipathic protein belt, immobilized on the cantilever surface. The specific molecular binding results in cantilever deflection via the formation of a surface stress-induced bending moment. The nanomechanical cantilever response is quantitatively monitored by optical interference. The consistent and reproducible nanomechanical detection of cholera toxin in nanomolar range concentrations is demonstrated. The results validated with such a model system suggest that the combination of a microcantilever platform with receptor nanodiscs is a promising approach for monitoring invasive pathogens and other types of biomolecular detection relevant to drug discovery.     

Fabrication of SiO2 Microcantilever Using Isotropic Etching With ICP

This paper reports a new design and microfabrication process for high sensing guard-armed silicon dioxide (SiO₂ ) microcantilever sensor, which can be widely used in chemical, environmental and biomedical applications. One sensor platform consists of two SiO₂ cantilever beams as the sensing and reference elements, two connecting wings, and three guard arms. The guard arms prevent damage to the cantilever beam from collision. To efficiently release the SiO₂ cantilevers from the silicon substrate, an isotropic etch method using inductively coupled plasma (ICP) was developed. The isotropic etching with ICP system provides an advantage in good profile control and high etching rate than wet isotropic etching or conventional RIE (reactive ion etching); however, it has not been gained many attentions. In this work, the effects of chamber pressure, plasma source power, substrate power, SF₆ flow rate relating with Si etching rate, undercutting rate, and isotropic ratio were investigated and discussed. The optimum isotropic etching process achieved a 9.1 mum/min etch rate, 70% isotropic ratio, and 92% etching uniformity. The SiO₂ cantilever sensor was fabricated and the cantilever beam was successfully released using a patterned photoresist layer as an etching mask. This plasma isotropic etching release processing can be also applied to release other SiO₂ or metal suspended MEMS structures, such as bridges and membranes, with a fast etch rate and reasonable isotropic ratio.     

Vibration energy harvester with sustainable power based on a single-crystal piezoelectric cantilever array

We designed and fabricated a bimorph cantilever array for sustainable power with an integrated Cu proof mass to obtain additional power and current. We fabricated a cantilever system using single-crystal piezoelectric material and compared the calculations for single and arrayed cantilevers to those obtained experimentally. The vibration energy harvester had resonant frequencies of 60.4 and 63.2 Hz for short and open circuits, respectively. The damping ratio and quality factor of the cantilever device were 0.012 and 41.66, respectively. The resonant frequency at maximum average power was 60.8 Hz. The current and highest average power of the harvester array were found to be 0.728 mA and 1.61 mW, respectively. The sustainable maximum power was obtained after slightly shifting the short-circuit frequency. In order to improve the current and power using an array of cantilevers, we also performed energy conversion experiments.     

Quantitative and label-free technique for measuring protease activity and inhibition using a microfluidic cantilever array

We report the use of a SiN x based gold coated microcantilever array to quantitatively measure the activity and inhibition of a model protease immobilized on its surface. Trypsin was covalently bound to the gold surface of the microcantilever using a synthetic spacer, and the remaining exposed silicon nitride surface was passivated with silanated polyethylene glycol. The nanoscale cantilever motions induced by trypsin during substrate turnover were quantitatively measured using an optical laser-deflection technique. These microcantilever deflections directly correlated with the degree of protease turnover of excess synthetic fibronectin substrate ( K M = 0.58 x 10 (-6) M). Inhibition of surface-immobilized trypsin by soybean trypsin inhibitor (SBTI) was also observed using this system.     

Dynamic microcantilever sensors for discerning biomolecular interactions

Response of a conductive micromechanical cantilever placed in close proximity to a surface undergoing electrical excitation near the resonance frequency of the cantilever is influenced by the presence of microscopic dielectrics in the gap between the cantilever and the sample surface. The variations of the resonance response of unmodified cantilevers at gap distances below a few hundred nanometers are used to discern biomolecular differences of oligomeric nucleic acids in an array format without the use of extrinsic labels. The resonance response variation paves the way for the development of high throughput detection of biomolecular reactions, such as DNA hybridization reactions or antibody-antigen interactions without the use of external labels, in which the need is only to see the presence or absence of interaction. This dynamic method is simple, does not require immobilizing individual elements on a cantilever array, and is compatible with current generation DNA chips in which DNA spots are deposited in micro- and nanoarray format.     

Glucose biosensor based on the microcantilever

Diagnosis and management of diabetes require quantitative and selective detection of blood glucose levels. We report a technique for micromechanical detection of biologically relevant glucose concentrations by immobilization of glucose oxidase (GOx) onto a microcantilever surface. Microfabricated cantilevers have traditionally found utility in atomic force microscope imaging. During the past decade, however, microcantilevers have been increasingly used as transducers in chemical-sensing systems. This paper describes the combination of this technology with enzyme specificity to construct a highly selective glucose biosensor. The enzyme-functionalized microcantilever undergoes bending due to a change in surface stress induced by the reaction between glucose in solution and the GOx immobilized on the cantilever surface. Experiments were carried out under flow conditions. The common interferences for glucose detection in other detection schemes have been tested and have shown to have no effect on the measurement of blood glucose level by this technique.