Quartz Crystal Microbalance Platform Research Articles

Development of poly(safranine-co-phenosafranine)/GNPs/MWCNTs nanocomposites for quartz crystal microbalance sensor detection of arsenic (III) ions

Contamination of drinking water by heavy metals is extremely dangerous to human health. The formation of a quartz crystal microbalance (QCM) sensor for the rapid and portable detection of harmful heavy metals such as arsenic (As) ions in water samples is detailed in this work. Equimolar ratios of safranine (SF) and phenosafranine (Ph) copolymers (PSF-Ph) were synthesized via a chemical oxidative polymerization approach. The copolymer was modified with multi-wall carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) at different percentages (1, 3, 5, and 10%) to form nanocomposites of PSF-Ph/MWCNTs/GNPs. Thermal analysis of the nanocomposites revealed that the final polymer decomposition temperature (PDTfinal) values fell between 619 and 630 °C, and the nanocomposite with 10% loading exhibited the highest decomposition temperatures for T10, T30, and T50. The nanohybrid QCM sensor detected As(III) down to parts-per-billion levels based on the change in the oscillation frequency. The sensor was tested on water samples spiked with different concentrations of As(III) (0–20 ppb). A strong linear correlation (R2 ≈ 0.99) between the frequency shift and concentration with a low detection limit (0.1 ppb) validated the quantitative detection capability of the sensor. This QCM platform with an optimal recognition ligand is a promising field-deployable tool for on-site arsenic analysis in water.

FACILE FABRICATION OF ANILINE SENSOR BY USING COMMERCIAL CALCIUM SILICATE HYDRATE NANOSHEETS AS SENSING MATERIAL

Various aniline sensing materials have excellent properties based on quartz crystal microbalance (QCM) transducer, but their synthesis processes are complex. Herein, commercial calcium silicate hydrate nanosheets (CSH-S) was utilized for facile fabrication of aniline sensor based on QCM platform. This sensor was capable of detecting 0.1 ppm aniline, and the response time (14 s) and recovery time (16 s) were short. Besides, the devices could restore sensitivity after 30 days, demonstrating excellent stability. In addition, variable temperature experiment combined with simulation calculation methods were carried out to study the adsorption of aniline on CSH-S surfaces, then the sensing mechanism was revealed. This work opens up a rapid and convenient method for detecting gaseous aniline.

New Application of Quartz Crystal Microbalance: A Minimalist Strategy to Extract Adsorption Enthalpy.

The capture and separation of CO2 is an important means to solve the problem of global warming. MOFs (metal-organic frameworks) are considered ideal candidates for capturing CO2, where the adsorption enthalpy is a crucial indicator for the screening of materials. For this purpose, we propose a new minimalist solution using QCM (quartz crystal microbalance) to extract the CO2 adsorption enthalpy on MOFs. Three kinds of MOFs with different properties, sizes and morphologies were employed to study the adsorption enthalpy of CO2 using a QCM platform and a commercial gas sorption analyzer. A Gaussian simulation calculation and previously data reported were used for comparison. It was found that the measuring errors were between 5.4% and 6.8%, proving the reliability and versatility of our new method. This low-cost, easy-to-use, and high-accuracy method will provide a rapid screening solution for CO2 adsorption materials, and it has potential in the evaluation of the adsorption of other gases.

A Point-of-Care Quartz Biosensor Chip for Detection of PF4/Heparin Complexes

BACKGROUNDOur recent studies indicate that circulating PF4/heparin complexes activate complement and contribute to a subsequent immune response seen in heparin-induced thrombocytopenia (HIT) (Khandelwal, Blood 2016). We undertook studies to develop a sensitive assay for measuring circulating PF4/heparin. To do so, we utilize a quartz crystal microbalance (QCM) device, which is a piezoelectric acoustic resonator that detects decreases in the resonance frequency of the quartz crystal due to the increased mass caused by molecules binding to the electrode surface. We hypothesize that a novel label-free QCM biosensor functionalized with PF4/heparin capture antibodies can provide for robust quantitative antigen detection and physical characterization of antigen-antibody interactions. METHODSWe formed a mixed self-assembled monolayer by using thiol-functionalized polyethylene glycols (PEGs) with -OH and biotin terminated head-groups on gold electrodes of quartz biosensor (Nelson; Langmuir 2001). PEG-backfilling of this surface provided protein non-fouling effects (1% BSA adsorbed only 10 ng/cm2), while biotin end-groups enabled close to full surface coverage of streptavidin (180 ng/cm2). This surface became our platform to immobilize biotinylated KKO (anti-PF4/heparin IgG2Κb monoclonal antibody, developed in Arepally Lab) and TRA (isotype IgG2Κb control antibody; developed in Arepally Lab).To characterize the sensor's detection ability, we flowed recombinant PF4 (provided by M. Poncz, Children's Hospital of Philadelphia) with a range of heparin (Elkins-Sinn, NJ) concentrations. The solutions are introduced to the biosensors 10 minutes after mixing the heparin and flowed through the system until the frequency readout stabilized. We determined the amount of captured PF4/heparin complexes and the layer thickness by monitoring the sensor's resonance frequency shifts and acoustic dissipation.The surface distribution of PF4/heparin complexes on KKO-functionalized surfaces was imaged by tapping-mode atomic force microscopy (AFM). The imaging results are used to verify layer thickness calculated by acoustic modeling of the QCM signal. RESULTSIn initial experiments, KKO showed no changes in the presence of buffer or PF4 alone. However, when PF4 (10 μg/ml) was infused with increasing amounts of heparin (0.2, 1 or 10 U/ml) significant binding was detected starting at 0.2 U/ml heparin (Figure A). The acoustic modeling of the KKO-bound PF4 complexes with 0.2 U/ml heparin suggested that the macromolecular complexes were nearly 25 nm high. These results are consistent with the neutralization model for the role of PF4 in heparin-induced thrombocytopenia, in which the amount of PF4/ heparin complexes peaks at a specific molar ratio of PF4:heparin (Kowalska; Thrombosis Research 2010). Comparatively, almost no binding occurred when the quartz crystal was functionalized with TRA. This result not only demonstrates the protein non-fouling capacity of the PEG backfilling of the surface, but also shows the specificity of the surface-immobilized assay.To gauge the sensitivity of the QCM biosensor to lower concentrations of PF4 and heparin that may be found in vivo, we tested 1µg/mL PF4 with lower heparin concentrations (0.02-0.05 U/ml). As shown in Figure B, a nearly linear KKO binding response was observed in this range capable of distinguishing heparin concentrations that differed by as little as 0.01 U/ml. The highest adsorption was observed at heparin concentration of 0.02 U/ml with associated atomic force microscopy (AFM) images again showing spherical particles with 25 nm diameter on the KKO immobilized surface. CONCLUSIONSHighly specific binding to PF4 complexes demonstrates the sensitivity of the QCM platform and its ability to distinguish differences between heparin concentrations of even 0.01 U/ml. Since QCM is a mass-sensing biosensor, it has a unique sensitivity advantage while sensing high molecular weight macromolecular complexes. This, combined with possible miniaturization of the sensor and integration with lab-on-a-chip systems, creates the potential for point-of-care bed-side detection of PF4/heparin. [Display omitted] DisclosuresArepally:Biokit: Patents & Royalties.

Superhydrophobic Hierarchical Porous Divinylbenzene Polymer for BTEX Sensing and Toluene/Water Selective Detection

As shown in the Fig.1, this work reports a superhydrophobic divinylbenzene polymer with hierarchical porous structure as sensing material to modify the quartz crystal microbalance (QCM) to detect benzene, toluene, ethylbenzene, and xylene (BTEX) vapor. Notably, sensing results toward toluene vapor in different relative humidities indicates that this superhydrophobic polymer has favorable toluene/water selective detection performance. Besides, the limit of detection toward toluene is lower than 1 ppm.IntroductionAs typical hazardous chemicals, benzene series, especially BTEX, are easily dispersed in the air because of their extremely easy volatile nature. BTEX can paralyze the central nervous system of humans, causing neurasthenia, liver disease, and even cancer. Therefore, using gas sensor for real-time detection of BTEX is necessary.Compared with other sensors, QCM sensor has the advantages of low cost and working at room temperature. By modifying sensitive materials on the surface of QCM, the target gas can be adsorbed and the surface quality of QCM changes. This change can be further transformed into frequency shift by Sauerbrey equation, and recorded by computer. Based on QCM platform, some benzene sensors have been reported. For example, Kumar et al. used tetra-tert-butyl copper phthalocyanine to realize the sensing of BTEX. The response to 500 ppm of toluene can reach 60 Hz. But none of these reports discussed the effect of humidity on the sensor response. Our research group detected the BTEX vapor via using superhydrophobic polyoctadecylsiloxane (PODS) based on QCM. Besides, PODS can stably detect toluene vapor under different relative humidities. However, when the concentration of toluene is 20 ppm, the response value is only about 7 Hz. It is indicating that the detection limit of PODS to toluene cannot be less than 20 ppm. Figure 1

Reaction-Based Amine and Alcohol Gases Detection with Triazine Ionic Liquid Materials.

We demonstrated in this work the use of affinity ionic liquids, AIL 1 and AIL 2, for chemoselective detection of amine and alcohol gases on a quartz crystal microbalance (QCM). These detections of gaseous amines and alcohols were achieved by nucleophilic aromatic substitution reactions with the electrophilic 1,3,5-triazine-based AIL 1 thin-coated on quartz chips. Starting with inexpensive reagents, bicyclic imidazolium ionic liquids AIL 1 and AIL 2 were readily synthesized in six and four synthetic steps with high isolated yields: 51% and 63%, respectively. The QCM platform developed in this work is readily applicable and highly sensitive to low molecular weight amine gases: for isobutylamine gas (a bacterial volatile) at 10 Hz decrease in resonance frequency (i.e., ΔF = −10 Hz), the detectability using AIL 1 was 6.3 ppb. Our preliminary investigation on detection of the much less nucleophilic alcohol gas by AIL 1 was also promising. To our knowledge, no example to date of reports based on nucleophilic aromatic substitution reactions demonstrating sensitive gas detection in these triazine ionic liquids on a QCM has been reported.

Use of a quartz crystal microbalance platform to study protein adsorption on aluminum hydroxide vaccine adjuvants: Focus on phosphate-hydroxide ligand exchanges.

Aluminum hydroxide (AH) salts are widely used as vaccine adjuvants and controlling antigen-AH interactions is a key challenge in vaccine formulation. In a previous work, we have developed a quartz crystal microbalance (QCM) platform, based on stable AH-coated sensors, to explore the mechanisms of model antigen adsorption. The QCM study of bovine serum albumin (BSA) adsorption at different pH and ionic strength (I) values showed that protein adsorption on AH adjuvant at physiological pH cannot be explained mainly by electrostatic interactions, in contrast with previous reports. Here, we exploit further the developed QCM platform to investigate the role of phosphate-hydroxyl ligand exchanges in the adsorption mechanism of BSA, human serum albumin (HSA) and ovalbumin (OVA) on two commercial AH adjuvants. BSA adsorption decreased on immobilized AH particles previously treated with KH2PO4, highlighting the role of exchangeable sites on AH particles in the adsorption process. BSA and OVA were dephosphorylated by treatment with an acid phosphatase to decrease their phosphate content by about 80% and 25%, respectively. Compared to native BSA, adsorption of dephosphorylated BSA decreased significantly on one AH adjuvant at pH 7. Adsorption of dephosphorylated OVA was comparable to the one of native OVA. Further QCM assays showed that phospho-amino acids (PO4-serine and PO4-threonine) displaced previously adsorbed BSA and OVA from AH particles in conditions that were depending on the protein and the AH. Taken together, these observations suggest that phosphate-hydroxyl ligand exchange is an important adsorption mechanism of proteins on AH. These results moreover confirm that the developed AH-coated QCM sensors offer a new platform for the study of antigen adsorption, to the benefit of vaccine formulation.

QCM immunosensor for the determination of Staphylococcus aureus antigen

Staphylococcus aureus is a causative agent of infectious diseases and a producer of a group of highly toxic proteins called Staphylococcal enterotoxins. Currently, the presence of S. aureus in a sample can be determined by a wide spectrum of genetic, immunochemical and microbiological techniques. Despite availability of standard methods and devices, they are not fully suitable for a simple, label-free mode of use by an unskilled worker. In this paper, a biosensor based on quartz crystal microbalance (QCM) sensor is performed as a tool for a simple and reliable determination of S. aureus. The biosensor contained an antibody specific to S. aureus immobilized through protein A on 10 MHz QCM sensors and the interdigitated layer was stabilized by iron nanoparticles. The assay was performed as label free and sample was applied without any pretreatment. Limit of detection 145 µg/ml (5.18 × 108 CFU/ml) was achieved. When considered standard size of a sample 50 μl, the limit of detection was equal to 7.25 μg (2.59 × 107 CFU). The biosensors kept more than 90% sensitivity to the analyte after storage in laboratory conditions for 90 days. Good correlation to standard enzyme-linked immunosorbent assay was also proved. The biosensor appears as a simple but reliable tool for S. aureus assay and the QCM platform would provide further applications in microbial analyses.

QCM formaldehyde sensing materials: Design and sensing mechanism

Gaseous formaldehyde (HCHO) sensing is indispensable because HCHO is hazardous to health and widely exists in newly decorated house and newly painted furniture. Multitudinous HCHO sensors based on various platforms, such as semiconductor sensor, electrochemical sensor, surface acoustic wave sensor (SAW), fluorescent sensor, have been fabricated over the last few years. Except these sensors, quartz crystal microbalance (QCM) sensors have received increasing attention because of their high sensitivity, convenient operation, low energy consumption, and excellent modifiable property. Recently, based on QCM, many efforts have been made to design chemical sensing materials to detect HCHO gas sensitively and selectively. In this review, we summary the scientific researches of gaseous HCHO detection based on QCM platform, and introduce the related works of sensing HCHO carried out by our group as well as the exploration of sensing mechanism.

Reaction-Based Detection of Chemical Warfare Agent Mimics with Affinity Ionic Liquids.

We are demonstrating here the successful development of an ionic liquid device based on affinity ionic liquids AIL 1-6 tailored for chemoselective detection of gaseous chemical warfare agent (CWA) mimics on a quartz crystal microbalance (QCM) as well as on disposable filter papers. In the QCM platform, the negligible vapor pressure of ionic liquids ensures that AILs do not dry out on quartz chips and are used free of leakage during the measurements. This lack of vapor pressure makes these ionic liquid devices highly attractive for gas analysis. In the present study, chemoselective CWA mimic vapor detection by QCM occurs when gas rapidly diffuses into the AIL thin film and accordingly the nucleophilic substitution reaction emerges under the experimental conditions developed. Our initial results give credence to three important conclusions: (i) AILs could be prepared in short synthetic steps and are remarkable in detecting CWA mimics, (ii) the analysis of gaseous CWA mimics on QCM is label-free and chemoselective, and (iii) the detection of CWA mimic vapor by AILs on filter paper discs is colorimetric and portable, and, once used, the paper disc can be disposed. To the best of our knowledge, this is the first report in the literature based on the CWA mimic vapor detection in ionic liquids on a QCM.

QCM mass underestimation in molecular biotechnology: Proximity ligation assay for norovirus detection as a case study

The development of piezoelectric mass-sensitive devices is based on the shift in resonance frequency that is proportional to the deposited mass. However, this holds true only for small, rigid masses, while it can result in mass underestimation for heavy, non-rigid masses. In this work, we demonstrate this ‘missing mass’ phenomenon by measurement of high molecular weight biomolecules on a Quartz Crystal Microbalance (QCM) platform. For this, we present a model bioassay consisting of a sandwich-type proximity ligation assay for the detection of norovirus-like particles, and its real-time build-up on QCM as an experimental evidence. Upon combination with a localized QCM platform, we explain the pronounced slipping effect in multilayer biological systems resulting in energy dissipation and subsequent mass underestimation. This helps in pointing out the limitations of mega-gravity field sensors for molecular diagnostics where absolute quantification of pathogen load becomes indispensable towards biosensing applications.

Application of Polymethacrylic Acid Imprinted Quartz Crystal Microbalance Sensor for Detection of 3-Carene in Mango

This paper aims to develop a selective molecularly imprinted polymer (MIP) layer combined with quartz crystal microbalance sensor for the detection of 3-Carene, a significant aroma compound of mango. The proposed sensor is prepared from the co-polymer of methacrylic acid and divinylbenzene, and it is imprinted with 3-Carene. The MIP template was synthesized and deposited onto the quartz crystal microbalance platform by proper functionalizing the gold electrode using 2-propene 1- thiol. The developed MIP material is characterized by fourier transform infra-red, scanning electron microscope, and atomic force microscope techniques. The sensor offers very good selectivity and sensitivity (1–1000 ppm) of 0.11 Hz/ppm to 3-Carene from its structural analogies. The limit of detection and the limit of quantitation of the sensor are found to be 0.8 and 1.4 ppm, respectively. The performance of the sensor offers satisfactory reproducibility and repeatability to 3-Carene. Moreover, the response of the sensor has been correlated to the standard gas- chromatography-mass spectrometry data to detect 3-Carene in Langda and Chausa mango.

Superhydrophobic Polymerized n-Octadecylsilane Surface for BTEX Sensing and Stable Toluene/Water Selective Detection Based on QCM Sensor.

The present study reports a facile and low-cost route to produce a superhydrophobic polymerized n-octadecylsilane surface with micronano hierarchical structure on the surface of quartz crystal microbalance (QCM). The surface is used as a novel functional sensing material to detect benzene, toluene, ethylbenzene, and xylene (BTEX) vapor on the basis of QCM platform. The composites were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle measurements. The type of solvent used to dissolve N-octadecyltrichlorosilane has a big impact on the morphology, wettability, and sensing performance of the polymer material. Further systematic studies suggest that surface wettability (contact angle) and molecular polarity of the detected analytes are effective factors in selective detection toward BTEX using resonator-type gas sensors. Gas sensing results toward toluene in different relative humidities show that the new-style sensor has stable toluene/water selective detection performance and that the disturbance of water is negligible. Besides, the limit of detection toward toluene of the sensor is lower than the odor threshold value.

Ultrasensitive Detection of DNA and Ramos Cell Using In Situ Selective Crystallization Based Quartz Crystal Microbalance.

Herein we introduce the first successful assay of biomolecule by in situ selective crystallization based quartz crystal microbalance (QCM). Selective crystallization of CaCO3 on QCM sensor surface was utilized as an efficient mass amplification strategy and enhanced the sensitivity of QCM significantly. High specificity is guaranteed by the cooperation of two functional groups: -N(CH3)3 and -COOH. Passivation of sensor surface is realized by self-assembly of -N(CH3)3, which effectively inhibited the nonspecific crystallization. The DNA target is detected through hybridization of probe DNA labeled with -COOH, which can effectively promot the in situ surface crystallization of CaCO3. The concentration of target DNA is reflected by the frequency shift of QCM which is directly induced by the surface crystallization. The selective crystallization based QCM platform is simple, straightforward, high sensitive, and high specific. We demonstrate the excellent LOD (2 aM DNA) and a linear range of 10aM to 1 nM for DNA. Detection of Ramos cells are also realized with a LOD of five cells and a linear range of 5-6000 cells.

Detection of Gliadin in Foods Using a Quartz Crystal Microbalance Biosensor That Incorporates Gold Nanoparticles

This work develops a label-free gliadin immunosensor that is based on changes in the frequency of a quartz crystal microbalance (QCM) chip. A higher sensitivity was obtained by applying 25 nm gold nanoparticles (AuNPs) to the surface of a bare QCM electrode. Subsequently, chicken anti-gliadin antibodies (IgY) were immobilized directly on the AuNP-modified surface by cross-linking amine groups in IgY with glutaraldehyde. Experimental results revealed that the change in frequency exhibited when 2 ppm gliadin was bound to the AuNP-modified electrode was 35 Hz (48%) greater than that of the bare gold electrode. The linear dynamic range in 60% ethanol was from 1 × 10(1) to 2 × 10(5) ppb gliadin, and the calculated limit of detection (LOD) was 8 ppb. The entire detection process was completed in 40 min and was highly repeatable. Additionally, the AuNP-modified QCM system generated results in the detection of gliadin in 10 commercial food products that were consistent with those obtained using an AOAC-approved gliadin kit. In conclusion, the QCM platform provides a potential alternative means of ensuring that people with wheat allergies and celiac patients have access to gliadin-free food.

Quantification of Cellulase Activity Using the Quartz Crystal Microbalance Technique

The development of more efficient utilization of biomass has received increased attention in recent years. Cellulases play an important role in processing biomass through advanced biotechnological approaches. Both the development and the application of cellulases require an understanding of the activities of these enzymes. A new method to determine the activity of cellulase has been developed using a quartz crystal microbalance (QCM) technique. We compare the results from this technique with those from the IUPAC (International Union of Pure and Applied Chemistry) dinitrosalicylic acid (DNS) standard method and also from biccinchoninic acid and ion chromatography methods. It is shown that the QCM technique provides results closer to those obtained by measuring the actual reducing sugars. The elimination of the use of color development in the standard redox methods makes the QCM platform easier to implement; it also allows more flexibility in terms of the nature of the substrate. Finally, validation of the proposed method was carried out by relating the crystallinity of different substrates to the cellulase activity. Numerical values of cellulase activities measured with the QCM method showed that celluloses with higher crystallinity indices were hydrolyzed slower and to a lower extent than those of lower crystallinity indices for the cellulase mixtures examined.