Quartz Crystal Microbalance Device Research Articles

Real-Time Monitoring of a Nucleic Acid Amplification Reaction Using a Mass Sensor Based on a Quartz-Crystal Microbalance.

Nucleic acid amplification reactions such as polymerase chain reaction (PCR), which uses a DNA polymerase to amplify individual double-stranded DNA fragments, are a useful technique for visualizing the presence of specific genomes. Although the fluorescent labeling method is mainly used with DNA amplification, other detection methods should be considered for further improvements, such as miniaturization and cost reduction, of reaction-monitoring devices. In this study, the quartz-crystal microbalance (QCM) method, which can measure nanogram-order masses, was applied for the real-time detection of DNA fragments in a solution with nucleic acids. This was combined with an isothermal nucleic acid amplification reaction based on the recombinase polymerase amplification (RPA) method, which allowed DNA amplification at a constant temperature. When the DNA amplification reaction was initiated on a QCM sensor plate with an immobilized primer DNA strand, a significant increase in mass was observed compared to when the primer DNA was not immobilized. QCM was shown to be sufficiently sensitive for the in situ detection of amplified DNA fragments. Combining a portable QCM device and RPA offers a sensitive point-of-care method for detecting nucleic acids.

Acetone Detection and Classification as Biomarker of Diabetes Mellitus Using a Quartz Crystal Microbalance Gas Sensor Array.

A gas sensor array was developed and evaluated using four high-frequency quartz crystal microbalance devices (with a 30 MHz resonant frequency in fundamental mode). The QCM devices were coated with ethyl cellulose (EC), polymethylmethacrylate (PMMA), Apiezon L (ApL), and Apiezon T (ApT) sensing films, and deposited by the ultrasonic atomization method. The objective of this research was to propose a non-invasive technique for acetone biomarker detection, which is associated with diabetes mellitus disease. The gas sensor array was exposed to methanol, ethanol, isopropanol, and acetone biomarkers in four different concentrations, corresponding to 1, 5, 10, and 15 µL, at temperature of 22 °C and relative humidity of 20%. These samples were used because human breath contains them and they are used for disease detection. Moreover, the gas sensor responses were analyzed using principal component analysis and discriminant analysis, achieving the classification of the acetone biomarker with a 100% membership percentage when its concentration varies from 327 to 4908 ppm, and its identification from methanol, ethanol, and isopropanol.

Strong Interface Interaction of ZnO Nanosheets and MnSx Nanoparticles Triggered by Light over Wide Ranges of Wavelength to Enhance Their Removal of VOCs

The characteristics of the surface and interface of nanocomposites are important for exerting multi-functional properties and widening interdisciplinary applications. These properties are mainly depending on the electronic structures of materials. Some key factors, such as the surface, interface, grain boundaries, and defects take vital roles in the contribution of desired properties. Due to the excellent sensitivity of the QCM (quartz crystal microbalance) device, the surface and interface features of the nanocomposite were studied with the aid of the gas-response of the sensors (Sensor’s Gas-Sensitivity) in this work. To make full use of the visible light and part of NIR, a ZnO/MnSx nanocomposite was constructed using hydrothermal synthesis for narrowing the bandgap width of wide bandgap materials. The results indicated that the absorbance of the resulting nanocomposite was extended to part of the NIR range due to the introduction of impurity level or defect level, although ZnO and MnS belonged to wide bandgap semiconductor materials. To explore the physical mechanism of light activities, the photoconductive responses to weak visible light (650 nm, etc.) and NIR (near-infrared) (808 nm, 980 nm, and 1064 nm, etc.) were studied based on interdigital electrodes of Au on flexible PET (polyethylene terephthalate) film substrate with the casting method. The results showed that the on/off ratio of ZnO/MnSx nanocomposite to weak visible light and part of NIR light were changed by about one to five orders of magnitude, with changes varying with the amount of MnSx nanoparticle loading due to defect-assisted photoconductive behavior. It illustrated that the ZnO/MnSx nanocomposite easily produced photo-induced free charges, effectively avoiding the recombination of electrons/holes because of the formation of strong built-in electrical fields. To examine the surface and interface properties of nanocomposites, chemical prototype sensor arrays were constructed based on ZnO, ZnO/MnSx nanocomposite, and QCM arrays. The adsorption response behaviors of the sensor arrays to some typical volatile compounds were examined under a similar micro-environment. The results exhibited that in comparison to ZnO nanosheets, the ZnO nanosheets/MnSx nanocomposite increased adsorption properties to some typical organic volatile compounds significantly. It would have good potential applications in photo-catalysts, self-cleaning films, multi-functional coatings, and organic pollutants treatment (VOCs) of environmental fields for sustainable development. It provided some reference value to explore the physical mechanism of materials physics and photophysics for photo-active functional nanocomposites.

Pocketable Biosensor Based on Quartz-Crystal Microbalance and Its Application to DNA Detection

Quartz-crystal microbalance (QCM) is a technique that can measure nanogram-order masses. When a receptor is immobilized on the sensor surface of a QCM device, the device can detect chemical molecules captured by the mass change. Although QCM devices have been applied to biosensors that detect biomolecules without labels for biomolecular interaction analysis, most highly sensitive QCM devices are benchtop devices. We considered the fabrication of an IC card-sized QCM device that is both portable and battery-powered. Its miniaturization was achieved by repurposing electronic components and film batteries from smartphones and wearable devices. To demonstrate the applicability of the card-sized QCM device as a biosensor, DNA-detection experiments were performed. The card-sized QCM device could detect specific 10-mer DNA chains while discerning single-base differences with a sensitivity similar to that of a conventional benchtop device. The card-sized QCM device can be used in laboratories and in various other fields as a mass sensor.

Coating-Based Quartz Crystal Microbalance Detection Methods of Environmentally Relevant Volatile Organic Compounds

Volatile organic compounds (VOCs) that evaporate under standard atmospheric conditions are of growing concern. This is because it is well established that VOCs represent major contamination risks since release of these compounds into the atmosphere can contribute to global warming, and thus, can also be detrimental to the overall health of worldwide populations including plants, animals, and humans. Consequently, the detection, discrimination, and quantification of VOCs have become highly relevant areas of research over the past few decades. One method that has been and continues to be creatively developed for analyses of VOCs is the Quartz Crystal Microbalance (QCM). In this review, we summarize and analyze applications of QCM devices for the development of sensor arrays aimed at the detection of environmentally relevant VOCs. Herein, we also summarize applications of a variety of coatings, e.g., polymers, macrocycles, and ionic liquids that have been used and reported in the literature for surface modification in order to enhance sensing and selective detection of VOCs using quartz crystal resonators (QCRs) and thus QCM. In this review, we also summarize novel electronic systems that have been developed for improved QCM measurements.

Novel analysis of a micropillar coupled acoustic wave sensor

Acoustic wave sensors are being developed for many emerging applications such as in semiconductor fabrication, biological diagnostics and polymer characterization. Traditional acoustic wave sensing devices such as quartz crystal microbalance (QCM) rely on polymer thin films coated on quartz plates to detect chemical and biological agents. It has been found that significant sensitivity enhancement of QCM devices can be achieved by simply attaching a polymer micropillar film onto the QCM substrate (QCM-P) to enable a unique coupled resonance between the micropillars and quartz substrate. In the present work, an equivalent circuit model integrating mechanical vibration of micropillars and electrical load impedance of piezoelectric substrate was developed to predict the frequency shift and Q-factor of the QCM-P devices when operating in air and liquid environments. In the model, the vibration of micropillars was solved simultaneously with the liquid loading on the pillar surface. The resultant hydraulic force was integrated into the circuit model to predict the load impedance on the sensor surface. The developed model was validated by experimental results for QCM-P devices operating in air and water with different micropillar heights. It will serve as a powerful tool to predict the performance of the QCM-P devices for different applications.

Development of an open-source thermally stabilized quartz crystal microbalance instrument for biomolecule-substrate binding assays on gold and graphene

The interaction of biomolecules, such as proteins, with biomaterial surfaces is key to disease diagnostic and therapeutic development applications. There is a significant need for rapid, low-cost, field-serviceable instruments to monitor such interactions, where open-source tools can help to improve the accessibility to disease screening instruments especially in low- and middle-income countries. We have developed and evaluated a low-cost integrated quartz crystal microbalance (QCM) instrument for biomolecular analysis based on an open-source QCM device. The custom QCM instrument was equipped with a custom-made electronically controlled isothermal chamber with a closed-loop control routine. A thermal coefficient of 5.6 ppm/°C was obtained from a series of evaluations of the implemented control. Additionally, a custom-designed data acquisition system and a mathematical processing and analysis tool is implemented. The quartz crystal detection chips used here incorporate gold and reduced graphene oxide (rGO) coated surfaces. We demonstrate the system capability to monitor and record the biomolecular interaction between a typical protein bovine serum albumin (BSA) and these two substrates. This instrument was compared to a commercial QCM, demonstrating good correspondence between the computed mass adsorption density responses using the Sauerbrey model. For both Au and rGO surfaces, the custom QCM significantly outperforms the commercial system in limit of detection, sensitivity and linear range. The instrument presented here has the potential to serve as a ubiquitous bioelectronic tool for point-of-care disease screening and rapid therapeutics development.

Target-Triggered Polymerization of Branched DNA Enables Enzyme-free and Fast Discrimination of Single-Base Changes.

SummarySingle-base changes lead to important biological and biomedical implications; however, the discrimination of single-base changes from normal DNA always remains a grand challenge. Herein we developed a DNA recognition and amplification system based on artificial branched DNA, namely, target-triggered polymerization (TTP), to realize enzyme-free and fast discrimination of single-base changes. Branched DNA as monomers rapidly polymerized into DNA nanospheres only with the trigger of specific DNA. Our TTP system worked reliably over a wide range of conditions. Remarkably, our TTP system was capable of discriminating base-changing DNA from normal DNA, including distinguishing 1–4 nucleotide changes and positions of single base, which was attributed to the significant amplification of small differences in hybridization thermodynamics and kinetics. We further proposed a theoretical method for calculating the hybridization probability of nucleic acids, which performed highly consistent with experimental results.

An ultrasensitive acoustic wave resonator device enabled by gluing a replaceable micropillar film

Traditional acoustic wave based sensing devices such as quartz crystal microbalance (QCM) rely on the thin films coated on the piezoelectric substrates as the sensing films for chemical and biological detection. This study demonstrates that significant sensitivity enhancement over traditional film based QCM (QCM-F) devices can be achieved by simply attaching a poly(methylmethacrylate) (PMMA) micropillar film onto a QCM substrate (QCM-P) by using a UV-curable glue. Humidity absorption measurements shows that the unique resonance occurred between the micropillars and the piezoelectric substrate improved the mass sensitivity of the QCM sensor by more than eight-fold. In addition, the newly developed QCM-P sensor and traditional QCM-F were utilized to detect bovine serum albumin (BSA) protein immobilization on PMMA surfaces. It was found that the glued QCM-P was capable of measuring BSA at a much lower concentration (200 nM) in comparison to QCM-F (1500 nM). The glue-based micropillar QCM device showed great potential for improving the sensitivity, simplifying the fabrication process, and reducing the cost of QCM sensors for various biosensing and chemical usages.

Homogeneous thin coatings of zeolitic imidazolate frameworks prepared on quartz crystal sensors for CO2 adsorption

Thin films of four zeolitic-imidazolate frameworks (ZIF-8, ZIF-67, ZIF-7, and ZIF-93) have been fabricated by a dip-coating method on glass and quartz crystal microbalance (QCM) substrates. Homogeneous coatings with sizes of crystals of 65 ± 20, 285 ± 96, 61 ± 20 and 72 ± 21 nm for ZIF-8, ZIF-67, ZIF-7, and ZIF-93, respectively, were obtained. Upon characterization of the ZIFs and coatings by XRD, TGA, SEM, FTIR, contact angle measurement and N2 adsorption, the coatings were exposed to vapors of dichloromethane for activation. The CO2 adsorption of the coatings was then studied using a QCM device.

Label-Free Bioanalyte Detection from Nanometer to Micrometer Dimensions-Molecular Imprinting and QCMs †.

Modern diagnostic tools and immunoassay protocols urges direct analyte recognition based on its intrinsic behavior without using any labeling indicator. This not only improves the detection reliability, but also reduces sample preparation time and complexity involved during labeling step. Label-free biosensor devices are capable of monitoring analyte physiochemical properties such as binding sensitivity and selectivity, affinity constants and other dynamics of molecular recognition. The interface of a typical biosensor could range from natural antibodies to synthetic receptors for example molecular imprinted polymers (MIPs). The foremost advantages of using MIPs are their high binding selectivity comparable to natural antibodies, straightforward synthesis in short time, high thermal/chemical stability and compatibility with different transducers. Quartz crystal microbalance (QCM) resonators are leading acoustic devices that are extensively used for mass-sensitive measurements. Highlight features of QCM devices include low cost fabrication, room temperature operation, and most importantly ability to monitor extremely low mass shifts, thus potentially a universal transducer. The combination of MIPs with quartz QCM has turned out as a prominent sensing system for label-free recognition of diverse bioanalytes. In this article, we shall encompass the potential applications of MIP-QCM sensors exclusively label-free recognition of bacteria and virus species as representative micro and nanosized bioanalytes.

Electric Charge Detection of Sparse Organic Acid Molecules Using an Organic Field-Effect Transistor (OFET)-Based Sensor

Abstract Detection and measurement of organic acids, such as small carboxylic acids, are useful for quality control of processed food and drinks and in the healthcare sector. Previously, chromatographic and electrophoresis methods requiring a bench-top device were used for their detection. In this article, we report an organic field-effect transistor (OFET)-based sensor capable of sensing electrical changes, which was applied to the detection of citric acid, chosen as a small organic acid model. When citric acid was injected into the OFET-sensor equipped with a nickel-nitrilotriacetic acid-immobilized gold-electrode (Ni-NTA-immobilized Au-electrode), the shifts of the OFET transfer characteristic curves were observed to depend on the citric acid concentration, in the range from 0 to 1000 µM. On the other hand, there was no response after citric acid addition in the case of a quartz-crystal microbalance (QCM)-sensor, which is a mass-sensitive device, under similar low-salt conditions because the mass change on the sensor surface was below the detection limit of the QCM device owing to inter-anion repulsions. OFET-sensors have advantages in the detection of small organic molecules with an electro-charged group as well as the possibility to be incorporated into portable devices in the future.

Solid-Phase Isothermal DNA Amplification and Detection on Quartz Crystal Microbalance Using Liposomes and Dissipation Monitoring

In our sensing configuration, the quartz crystal microbalance device is employed for the first time for the solid phase amplification via the recombinase polymerase amplification method and simultaneous detection of DNA amplicons on the device surface. For amplicon detection, a novel methodology is described, where the formation of surface-bound DNA amplicons is detected by using liposomes as an amplification probe and by selectively monitoring the dissipation change during liposome binding. The presented methodology possesses several advantages over existing methods, i.e., it is fast, achieving the detection of DNA produced after only 5 min of amplification, and simple, since it does not require any post-amplification DNA extraction step.

An ultrasensitive micropillar-based quartz crystal microbalance device for real-time measurement of protein immobilization and protein-protein interaction

A new sensing device was developed to achieve ultrahigh sensitivity, by coupling polymer micropillars with a quartz crystal microbalance (QCM) substrate to form a two-degree- of-freedom resonance system (QCM-P). The sensitivity of these QCM-P devices was evaluated by measuring mass changes for both deposited gold film and adsorption of bovine serum albumin (BSA), respectively, on poly(methyl methacrylate) (PMMA) micropillar surfaces, as well as assessing ligand-analyte binding interactions between anti-human immunoglobulin G (anti-hIgG) and human immunoglobulin G (hIgG). The anti-hIgG and hIgG binding results show QCM-P achieved an eightfold improvement in sensitivity relative to conventional QCM sensors. In addition, the binding affinity obtained from the QCM-P device for anti-hIgG and hIgG proteins was found in good agreement with that measured by surface plasmon resonance (SPR) for the same binding reaction.

Galvanic replacement of colloidal monolayer crystal on a QCM device for selective detection of mercury vapor

Bimetallic nanostructures formed through galvanic replacement (GR) reaction have extraordinary activity in various applications such as catalysis, optics, electronics and bio/chemical sensing, just to name a few. However, the homogenous decoration of metal nanoparticles on less noble metal thin-film substrates to produce long range ordered surfaces for sensing applications using this simple, one step reaction has proved to be a challenge. Here, we demonstrate the formation of polystyrene-based (PS-based) monodispersed nanosphere monolayer (PS-MNM), homogeneously decorated with bi-metallic Pd–Au nanostructures through GR reaction. Furthermore, the size of the Au nanoparticles decorated on the Pd-MNM colloids was controlled for gas sensing applications during GR reaction. Upon transferring the developed materials onto a sensor transducer, namely the quartz crystal microbalance (QCM), it was found that the 1mM Au GR solution produced the best performing sensitive layer for elemental mercury (Hg0) vapor sensing application. The sensor had more than 26 times higher response magnitude at 30°C as well as enhanced sensitivity and selectivity over the control Pd-MNM counterpart at 75°C. The homogeneous decoration concept developed here can be transferred to other bimetallic systems.

Microfluidic quartz-crystal-microbalance (QCM) sensors with specialized immunoassays for extended measurement range and improved reusability

Quartz crystal microbalances (QCM) are well known mass sensitive devices. By combining them with specialized antibodies, sensitive biosensors with detection limits down to some nanogram of substance can be obtained. While the antibody coating determines which substances will be detected, the QCM's limit of detection is determined by the required minimal mass change. Therefore, measurements of biological samples containing small target molecules at low concentrations remain challenging. Here, we present the fabrication of disposable but also regenerative QCM devices with microfluidic housing and an approach to improve the detection limit of a QCM by employing an additional, heavier molecule to increase the total added apparent mass, leading to a larger drop of the QCMs resonant frequency per amount of measured substance. As any signal amplification bears the risk to lose its benefit by amplification of unspecific binding too, we further developed an in vitro designed antibody sandwich pair, offering more specific target molecule (CRP) detection and only temporary binding which renders the device reusable within minutes. No additional chemicals or regeneration protocols between measurements are necessary, sole purging with buffer solution is sufficient. To achieve signal amplification, streptavidin was attached via biotin to the second antibody. The resulting frequency drop was up to five times higher compared to the original antibody sandwich. In the absence of CRP, no resonant frequency change rising above signal noise could be observed in presence of the second antibody and streptavidin. The presented concept is broadly expandable. The use of even heavier molecules or nanoparticles for mass amplification should allow higher frequency shifts per amount of target substance and promises to extend the measurement range of QCMs into the sub-nanogramm region.

Molecular Imprinting Technology in Quartz Crystal Microbalance (QCM) Sensors.

Molecularly imprinted polymers (MIPs) as artificial antibodies have received considerable scientific attention in the past years in the field of (bio)sensors since they have unique features that distinguish them from natural antibodies such as robustness, multiple binding sites, low cost, facile preparation and high stability under extreme operation conditions (higher pH and temperature values, etc.). On the other hand, the Quartz Crystal Microbalance (QCM) is an analytical tool based on the measurement of small mass changes on the sensor surface. QCM sensors are practical and convenient monitoring tools because of their specificity, sensitivity, high accuracy, stability and reproducibility. QCM devices are highly suitable for converting the recognition process achieved using MIP-based memories into a sensor signal. Therefore, the combination of a QCM and MIPs as synthetic receptors enhances the sensitivity through MIP process-based multiplexed binding sites using size, 3D-shape and chemical function having molecular memories of the prepared sensor system toward the target compound to be detected. This review aims to highlight and summarize the recent progress and studies in the field of (bio)sensor systems based on QCMs combined with molecular imprinting technology.

Studying the effect of dealloying Cu-Au nanostructures on their mercury sensing performance

In this study we demonstrate that the dealloying of Cu-Au nanostructures electrochemically deposited on the electrodes of a quartz crystal microbalance (QCM) can significantly increase its sensing performance (sensitivity, reversibility) toward low concentrations of elemental mercury (Hg0) vapor. The Cu‐Au alloy nanostructures were electrodeposited on the Au electrodes of the QCM device for periods of 2, 4 and 8min from an electrolyte containing equimolar concentrations of CuSO4 and HAuCl4 salts. When tested with Hg0 vapor concentrations ranging from 24 to 365 ppbv, it was found that the 4min Cu-Au alloy had up to 10.4 times higher response magnitude than a control Au electrode-based QCM sensor. Furthermore, when dealloying experiments were conducted, it was found that electrochemical dealloying periods of 4 and 8min significantly increased the reversibility of the 4min Cu-Au alloy nanostructure based sensor. For instance, the structures made by a 4min–8min alloy-dealloy periods showed up to 5.6 times higher response magnitude toward different concentrations of Hg0 vapor when compared to the control Au thin‐film (Au-ctrl) based sensor. In addition, the same sensors exhibited an average reversibility of 84.4% following Hg0 vapor exposure, which is high when compared to the average reversibility of 63.3 and 44.4% observed from the Au-ctrl and Cu-Au (4min alloy) based sensors, respectively. Surface characterization and analysis indicated that the enhanced sensitivity of the Cu-Au based sensors was not just due to higher surface area but also due to the surface defects that are formed on the surface during electrochemical treatments. Overall, the results indicate that the low concentrations Hg0 vapor sensing performance of a QCM device can be tuned by controlling the alloy and dealloying conditions of the Cu‐Au system directly on the electrode surface. The sensor with optimum alloying and dealloying time (4min–8min) showed good repeatability and selectivity with the sensor showing a coefficient of variance of 5.45% when exposed with the mixture of common industrial interfering gas species such as ammonia, acetaldehyde and ethyl mercaptan. Furthermore, the sensor was also showed a low coefficient of variance of 3% when exposed without and with the presence of water vapor, indicating the sensor’s high repeatability and selectivity even in humid environments.

Simulation of electrical properties of quartz crystal microbalance using multi-resonance thickness-shear mode technique

The use of quartz crystal microbalance (QCM) in chemistry, biophysics, microbiology and electronics has grown tremendously in recent years. In this paper, the properties of a QCM sensor (a system include QCM device and viscoelastic medium) operating in the range of 5 MHz to 35 MHz of Multi-resonance Thickness-Shear Mode (MTSM, n = 1, 3, 5, 7) are described. We calculate the changes both in resonant frequencies and attenuation of the QCM. The penetration depth of the shear waves propagating from quartz into loaded thin film varies in different values due to the harmonics, from which we infer the properties of the loaded thin film. The multi-harmonic operation of QCM was presented to collect the information of the loaded thin film on QCM’s electrode. This enables a “virtual slicing technique” because a harmonic relates to a different penetration depth even with the same material. The theoretical analysis of MTSM has been developed to model and simulate the signature of the sensor responses at harmonic frequencies. The signatures of the evaporation- induced deposition processes were investigated by studying the effect of the thickness and stiffness of the medium.

Charge Behavior of Low-Dimensional V<sub>2</sub>O<sub>5</sub>/Graphene Nanoribbons Oxides Nanocomposites under Irradiation of Visible Light and its Application

Due to its outstanding photo-catalysis properties, low-dimensional V2O5 has many important applications in lithium ion batteries, supercapacitors, electrochromic devices, photocatalysts, sensors, et al. As good photocatalysts for organic pollutants, some key issues of photocatalysts are charge generation, separation, transfer of nanocomposites under irradiation of visible light. To improve their important properties and pave the effective conductive channels for charge transfer and separation, low-dimensional V2O5/graphene nanoribbons nanocomposites were prepared. The emphasis is put on adsorption response to VOC of nanocomposite based on the QCM (quartz crystal microbalance) device. In order to investigate the mechanism of charge-generated by visible light, the photoconductivity response to visible light and 808 nm laser with low-power were studied based on interdigital electrodes of Au on flexible PET (polyethylene terephthalate) film substrate. Some good results were obtained. This illustrates that this nanocomposite can easily produce the charge-generate with visible light and 808 nm laser with low-power, avoiding the recombination of charge-generate by light. It would be good applications in remove the organic pollutants with photocatalysis effects.