Iron-containing metal-organic framework thin film as a drug delivery system.

Selective bulk metal-organic frameworks (MOFs) have exhibited great potential in biomedical applications. However, topical treatments and drug elution coatings will require uniform films as drug delivery systems. This work studies the use of surface supportive MOF thin films for drug loading and releasing. More specifically, we focus on an iron-containing MOF, MIL-88B(Fe), on a COOH-terminated self-assembled monolayer (SAM) modified Au surface for encapsulating ibuprofen as a model drug. A combined experimental and computational approach was employed to study the fabrication of MIL-88B(Fe) film on functionalized Au surfaces. We used several surface characterization techniques, including infrared spectroscopy and scanning electron microscopy, to confirm the chemical composition and morphological changes of the surface after each modification step. The resulting MIL-88B(Fe) thin film was found capable of loading 8.7 wt% of ibuprofen using quartz crystal microbalance analysis. Moreover, we applied cluster simulations to study the binding mechanisms of MIL-88B(Fe) and its interactions with ibuprofen based on the density functional theory (DFT). The unsaturated Fe site was confirmed kinetically more favorable to bind to the COOH-end group on the SAM. Hydrogen bonding and π-CH interactions between ibuprofen and MIL-88B(Fe) promote ibuprofen being retained inside of the cages of MIL-88B(Fe).

Comparing of Frequency Shift and Impedance Analysis Method Based on QCM Sensor for Measuring the Blood Viscosity.

Blood viscosity measurements are crucial for the diagnosis of cardiovascular and hematological diseases. Traditional blood viscosity measurements have obvious limitations because of their expensive equipment usage and large sample consumption. In this study, blood viscosity was measured by the oscillating circuit method and impedance analysis method based on single QCM. In addition, the effectiveness of two methods with high precision and less sample is proved by the experiments. Moreover, compared to the result from a standard rotational viscometer, the maximum relative errors of the proposed oscillating circuit method and impedance analysis method are ±5.2% and ±1.8%, respectively. A reliability test is performed by repeated measurement (N = 5), and the result shows that the standard deviation about 0.9% of impedance analysis is smaller than that of oscillating circuit method. Therefore, the impedance analysis method is superior. Further, the repeatability of impedance analysis method was evaluated by regression analysis method, and the correlation coefficient R2 > 0.965 demonstrated that it had excellent reproducibility.

Advances in the Mass Sensitivity Distribution of Quartz Crystal Microbalances: A Review.

A quartz crystal microbalance (QCM) is a typical acoustic transducer that undergoes a frequency shift due to changes in the mass of its surface. Its high sensitivity, robustness, small size design, and digital output have led to its widespread development for application in the fields of chemistry, physics, biology, medicine, and surface science. Mass sensitivity is one of the vital parameters and forms the basis for quantitative analysis using QCMs. This review firstly introduces the importance, definition, calculation, and measuring method of the mass sensitivity and then focuses on reviewing the influence of electrode parameters (including electrode shape, electrode diameter, electrode thickness, electrode material, etc.) on the mass sensitivity distribution of QCMs. Finally, the effect of the operating frequency on the mass sensitivity of QCMs is also analyzed.

Precision Temperature Control System with Low EMI for Applications in Analyzing Thermal Properties of Highly Sensitive Piezoelectric Sensors.

A low electromagnetic interference (EMI), precision temperature control system for sensitive piezoelectric sensors stabilization and their thermal characteristics research was proposed. Quartz crystal microbalance (QCM) was chosen as the device to be tested. Recently, QCMs found use in many fields of study such as biology, chemistry, and aerospace. They often operate in harsh environments and are exposed to many external factors including temperature fluctuations, to which QCMs are highly susceptible. Such disturbances can cause undesirable resonant frequency shifts resulting in measurement errors that are difficult to eliminate. The proposed solution enables measurements of QCMs thermal characteristics, effectiveness evaluation of temperature compensation methods, and testing of the frequency stability. As a part of the developed solution, two independent temperature regulators were used: first to maintain the QCM crystal at desired temperature, and second to keep the QCM oscillator circuit at fixed temperature. The single regulator consists of a thermoelectric module (TEC) used for both heating and cooling. Two considered TEC driving methods were compared in terms of EMI and their impact on the QCM signal quality. The proposed system was examined for its temperature stabilization capability showing high stability of 11 mKp-p for one hour and the setpoint accuracy of ±15 mK in the full temperature range.

MG-Pe: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine.

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.

Recognition of 1-phenylethylamine enantiomers by thin solid films of inherently chiral calix[4]arene.

The enantiodiscrimination properties of stereomerically pure inherently chiral calix[4]arene acetic acids, as well as their esters and amides in relation to 1-phenylethylamine stereoisomers in liquid and gaseous phases were studied by means of proton magnetic resonance spectroscopy (1 H NMR) and quartz crystal microbalance (QCM) techniques. Series of QCM sensors with thin films of inherently chiral calix[4]arenes, immobilized on the quartz resonator surfaces by spin-coating and spreading drop methods have been fabricated. It was shown that sensors based on calix[4]arene acetic acids are able to recognize R- and S-forms of 1-phenylethylamine in gaseous phase under concentration level of 10-400 ppm.

Controllable preparation of ultrathin MXene nanosheets and their excellent QCM humidity sensing properties enhanced by fluoride doping.

A 2D ultrathin MXene nanosheet was prepared under controlled conditions and employed as a sensitive film to construct a QCM (quartz crystal microbalance) humidity sensor by a dip coating method. The MXene nanosheets were obtained by dislodging the element A from the MAX phase by a facile liquid phase etching method. The morphology and composition of the MXene nanosheets were characterized by means of a number of advanced instruments. It was found that the sample is an ultrathin graphene-like nanosheet. The sensing test results showed that the sensor has a 12.8 Hz/% RH sensitivity, 6 s and 2 s (@ 90%) response/recovery time, maximum humidity hysteresis of 1.16% RH, good stability, and selectivity. Finally, the enhanced humidity response mechanism of the MXene nanosheets was explored by density-functional theory (DFT) calculation and experimental verification. The DFT simulation together with comparison of fluoride-free sample revealed that F elements on the surface of the MXene nanosheets play a more important role in improving humidity responses than OH groups. The results present a new strategy to enhance humidity sensing performance of sensing materials by F- doping or decoration. Thus, the sensor has bright potential for humidity sensing.

Development of QCM based biosensor for the selective and sensitive detection of paraoxon.

In this study, a quartz crystal microbalance (QCM) based sensor was developed that selectively recognizes and binds the paraoxon molecule. For this purpose, poly (styrene-maleic anhydride) (PSMA) polymer was synthesized to obtain nanofiber. A 30% (wt/wt) PSMA/DMSO solution was prepared for use in the electrospinning process, with operating conditions of 5 kV potential and 1 mL/h flow rate. After obtaining the nanofibers, AChE enzyme was immobilized to nanofiber. The QCM gold electrode surface was coated with AChE immobilized nanofiber. For this purpose, the QCM electrode was first functionalized with 4-aminothiophenol. The quartz electrode coated with the recognition layer was sequentially studied with aqueous solutions containing 50% (v/v) methanol, ranging from 0.1 ppm to 10 ppm of paraoxon. When the electrode interacts with paraoxon, the frequency value decreases. The obtained data were converted to graphs and a calibration graph was obtained. The LOD value was found to be 4.57 × 10-8 and the LOQ value was found to be 1.52 × 10-7 M. These results show us that the developed method can analyze very small quantities of paraoxon samples. The Langmuir adsorption equation was used to study the interaction of the bond between the electrode surface and the paraoxon. For the calculation of the coupling constant Ka, Δm/C (g/M) versus Δm (g) was plotted on the graph. The Ka binding constant of the obtained graphic was found to be 5 × 107 M-1.

Assessing the Mass Sensitivity for Different Electrode Materials Commonly Used in Quartz Crystal Microbalances (QCMs).

Mass sensitivity is vital for quartz crystal microbalance (QCM)-based data analysis. The mass sensitivity distribution of QCMs may differ greatly depending on the shapes, thicknesses, sizes, and materials of the metal electrodes. This is not considered by the Sauerbrey equation, and has a large potential to cause errors in QCM-based data analysis. Many previous works have studied the effects of shape, thickness, and size of metal electrodes on mass sensitivity. However, it is necessary to continue to clarify the relationship between the mass sensitivity and the electrode material of the QCM. In this paper, the results of both theoretical calculation and experimental analysis showed that the mass sensitivity of QCMs with gold electrodes is higher than that of the QCMs with silver electrodes, which in turn indicated that the mass sensitivity of QCMs varies with the electrode material. Meanwhile, the results of this study showed that the mass sensitivity of QCMs with different electrode materials is not proportional to the density of the electrode materials. This result suggests that, in order to obtain more accurate results in the practical applications of QCMs, the influence of electrode material on the mass sensitivity of the QCMs must be considered.

Investigation on Mass Sensitivity of N-M Type Electrode Quartz Crystal Microbalance.

Mass sensitivity plays a crucial role in the practical application of quartz crystal microbalances (QCMs)-based quantitative analysis. n-m type QCMs have many applications, so it is necessary to clarify the relationship between the mass sensitivity and the electrode of the n-m type QCM. The performance of gold-plated films with different electrodes was studied by theoretical calculation and experiment. The results show that the mass sensitivity on the surface of the n electrode and the surface of the m electrode are essentially the same. Meanwhile, the mass sensitivity of n-m type QCMs varies with the diameter of the n and m electrodes. When the diameter of the n electrode is close to half the diameter of the m electrode, mass sensitivity is at maximum value. These results are important for the further designs and applications of n-m type QCMs.

An Overview of High Frequency Acoustic Sensors-QCMs, SAWs and FBARs-Chemical and Biochemical Applications.

Acoustic devices have found wide applications in chemical and biosensing fields owing to their high sensitivity, ruggedness, miniaturized design and integration ability with on-field electronic systems. One of the potential advantages of using these devices are their label-free detection mechanism since mass is the fundamental property of any target analyte which is monitored by these devices. Herein, we provide a concise overview of high frequency acoustic transducers such as quartz crystal microbalance (QCM), surface acoustic wave (SAW) and film bulk acoustic resonators (FBARs) to compare their working principles, resonance frequencies, selection of piezoelectric materials for their fabrication, temperature-frequency dependency and operation in the liquid phase. The selected sensor applications of these high frequency acoustic transducers are discussed primarily focusing on the two main sensing domains, i.e., biosensing for working in liquids and gas/vapor phase sensing. Furthermore, the sensor performance of high frequency acoustic transducers in selected cases is compared with well-established analytical tools such as liquid chromatography mass spectrometry (LC-MS), gas chromatographic (GC) analysis and enzyme-linked immunosorbent assay (ELISA) methods. Finally, a general comparison of these acoustic devices is conducted to discuss their strengths, limitations, and commercial adaptability thus, to select the most suitable transducer for a particular chemical/biochemical sensing domain.

Preparation of a molecularly imprinted sensor based on quartz crystal microbalance for specific recognition of sialic acid in human urine.

A novel molecularly imprinted quartz crystal microbalance (QCM) sensor was successfully prepared for selective determination of sialic acid (SA) in human urine samples. To obtain the QCM sensor, we first modified the gold surface of the QCM chip by self-assembling of allylmercaptane to introduce polymerizable double bonds on the chip surface. Then, SA molecularly imprinted polymer (MIP) nanofilm was attached to the modified QCM chip surface. For comparison, we have also characterized the nonmodified and improved surfaces of the QCM sensor by using atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy. We then tested the selectivity and detection limit of the imprinted QCM sensor via a series of adsorption experiments. The results show a linear response in the range of 0.025-0.50 µmol L-1 for sialic acid. Moreover, the limit of detection (LOD) of the prepared imprinted QCM sensor was found to be 1.0 nmol L-1 for sialic acid, and high recovery values range from 87.6 to 108.5% with RSD < 8.7 (n = 5) for the spiked urine sample obtained. Overall, this work presents how a novel QCM sensor was developed and used to detect sialic acid in human urine samples. Graphical abstract Specific recognition of sialic acid by the MIP-QCM sensor system.

HCl Gas Sensor Coating Based on Poly(N-isopropylacrylamide) Nanoparticles Prepared from Water-Methanol Binary Solvent.

Poly(N-isopropylacrylamide) (PNIPAM) nanoparticles formed in water-methanol binary solvent were successfully deposited on a resonator surface at room temperature by exploiting the cononsolvency effect on the phase transition of PNIPAM aqueous solutions. Scanning electron microscopic observation revealed that the nanoparticles were secondary and made up of agglomerated primary spherical particles of about 10-nm diameter, buried in the film. The magnitude of the sensor response toward HCl gas was larger than that of the nanoparticle sensor prepared from pure water solvent, and the sensitivity to 1 ppm of HCl of sensor-coated nanoparticles based on the present method was 3.3 Hz/ppm. The recovery of the sensors was less than 90% at first cycle measurement, but had improved to almost 100% at the third cycle.

Quartz crystal microbalance as an assay to detect anti-drug antibodies for the immunogenicity assessment of therapeutic biologics.

Because of their biological origins, therapeutic biologics can trigger an unwanted deleterious immune response with some patients. The immunogenicity of therapeutic biologics can affect drug efficacy and patient safety by the production of circulating anti-drug antibodies (ADA). In this study, quartz crystal microbalance (QCM) was developed as an assay to detect ADA. Etanercept (Enbrel®) was covalently grafted to dextran-modified QCM surfaces. Rabbits were immunized with etanercept to generate ADA. Results showed the QCM assay could detect purified ADA from rabbits at concentrations as low as 50 ng/mL, within the sensitivity range of ELISA. The QCM assay could also assess the ADA isotype. It was shown that the ADA were composed of the IgG isotype, but not IgM, as expected. Furthermore, it was shown that QCM surfaces that had been used to detect ADA could be regenerated in glycine-HCl solution and reused. The QCM assay was also demonstrated to detect ADA in crude serum samples. Serum was collected from the rabbits and analyzed before and after etanercept immunization. ADA were clearly detected in serum from rabbits after immunization, but not in serum before immunization. Serum from patients administered with etanercept for rheumatoid arthritis (RA) treatment was also analyzed and compared to serum from healthy donors. Sera from 10 RA patients were analyzed. Results showed one of the RA patient serum samples may have ADA present. In conclusion, QCM appears to be a viable assay to detect ADA for the immunogenicity assessment of therapeutic biologics.

A Practical Model of Quartz Crystal Microbalance in Actual Applications.

A practical model of quartz crystal microbalance (QCM) is presented, which considers both the Gaussian distribution characteristic of mass sensitivity and the influence of electrodes on the mass sensitivity. The equivalent mass sensitivity of 5 MHz and 10 MHz AT-cut QCMs with different sized electrodes were calculated according to this practical model. The equivalent mass sensitivity of this practical model is different from the Sauerbrey's mass sensitivity, and the error between them increases sharply as the electrode radius decreases. A series of experiments which plate rigid gold film onto QCMs were carried out and the experimental results proved this practical model is more valid and correct rather than the classical Sauerbrey equation. The practical model based on the equivalent mass sensitivity is convenient and accurate in actual measurements.

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.

The Resistance-Amplitude-Frequency Effect of In-Liquid Quartz Crystal Microbalance.

Due to the influence of liquid load, the equivalent resistance of in-liquid quartz crystal microbalance (QCM) increases sharply, and the quality factor and resonant frequency decreases. We found that the change in the resonant frequency of in-liquid QCM consisted of two parts: besides the frequency changes due to the mass and viscous load (which could be equivalent to motional inductance), the second part of frequency change was caused by the increase of motional resistance. The theoretical calculation and simulation proved that the increases of QCM motional resistance may indeed cause the decreases of resonant frequency, and revealed that the existence of static capacitance was the root cause of this frequency change. The second part of frequency change (due to the increases of motional resistance) was difficult to measure accurately, and may cause great error for in-liquid QCM applications. A technical method to reduce the interference caused by this effect is presented. The study contributes to the accurate determination of the frequency and amplitude change of in-liquid QCM caused by liquid load, which is significant for the QCM applications in the liquid phase.

Influence of the protein context on the polyglutamine length-dependent elongation of amyloid fibrils.

Polyglutamine (polyQ) diseases, including Huntington's disease, are neurodegenerative disorders associated with the abnormal expansion of a polyQ tract within nine proteins. The polyQ expansion is thought to be a major determinant in the development of neurotoxicity, triggering protein aggregation into amyloid fibrils, although non-polyQ regions play a modulating role. In this work, we investigate the relative importance of the polyQ length, its location within a host protein, and the conformational state of the latter in the amyloid fibril elongation. Model polyQ proteins made of the ß-lactamase BlaP containing up to 79Q inserted at two different positions, and quartz crystal microbalance and atomic force microscopy were used for this purpose. We demonstrate that, independently of the polyQ tract location and the conformational state of the host protein, the relative elongation rate of fibrils increases linearly with the polyQ length. The slope of the linear fit is similar for both sets of chimeras (i.e., the elongation rate increases by ~1.9% for each additional glutamine), and is also similar to that previously observed for polyQ peptides. The elongation rate is, however, strongly influenced by the location of the polyQ tract within BlaP and the conformational state of BlaP. Moreover, comparison of our results with those previously reported for aggregation in solution indicates that these two parameters also modulate the ability of BlaP-polyQ chimeras to form the aggregation nucleus. Altogether our results suggest that non-polyQ regions are valuable targets in order to interfere with the process of amyloid fibril formation associated with polyQ diseases.

Evaluation of the effect of hot-compressed water treatment on enzymatic hydrolysis of lignocellulosic nanofibrils with different lignin content using a quartz crystal microbalance.

Hot-compressed water (HCW) treatment is known to not only improve enzymatic hydrolysis efficiency of lignocellulosic biomass but to also generate insoluble lignin droplets, which retard enzymatic hydrolysis. In this study, the inhibitory effect of the lignin droplets was evaluated by monitoring the initial enzyme adsorption and degradation of lignocellulosic nanofibrils (LCNFs) using a quartz crystal microbalance (QCM). Lignin content was adjusted by the sodium chlorite-acetic acid method and divided into samples with high (24.9 wt%) and low (5.6 wt%) lignin content, which were then subjected to HCW treatment at various temperatures. The changes in lignin content were small with increasing HCW temperature, whereas hemicellulose content decreased, regardless of the initial lignin content. The formation of lignin droplets and pseudo-lignin-like products was confirmed in both LCNFs by atomic force microscopy (AFM) and was predominant in LCNFs with high lignin content treated at 200°C. QCM data showed that the enzyme adsorption amount in both LCNFs after HCW treatment was increased and was greater in LCNFs with low lignin content. Initial enzymatic degradation was substantially slowed in LCNFs with high lignin content, particularly after HCW treatment at temperatures higher than 180°C. These QCM results suggest that the steric hindrance of the deposited lignin is the primary mechanism by which the initial enzymatic hydrolysis is delayed. Biotechnol. Bioeng. 2016;113: 1441-1447. © 2015 Wiley Periodicals, Inc.

Enhanced Dibutyl Phthalate Sensing Performance of a Quartz Crystal Microbalance Coated with Au-Decorated ZnO Porous Microspheres.

Noble metals addition on nanostructured metal oxides is an attractive way to enhance gas sensing properties. Herein, hierarchical zinc oxide (ZnO) porous microspheres decorated with cubic gold particles (Au particles) were synthesized using a facile hydrothermal method. The as-prepared Au-decorated ZnO was then utilized as the sensing film of a gas sensor based on a quartz crystal microbalance (QCM). This fabricated sensor was applied to detect dibutyl phthalate (DBP), which is a widely used plasticizer, and its coating load was optimized. When tested at room temperature, the sensor exhibited a high sensitivity of 38.10 Hz/ppb to DBP in a low concentration range from 2 ppb to 30 ppb and the calculated theoretical detection limit is below 1 ppb. It maintains good repeatability as well as long-term stability. Compared with the undecorated ZnO based QCM, the Au-decorated one achieved a 1.62-time enhancement in sensitivity to DBP, and the selectivity was also improved. According to the experimental results, Au-functionalized ZnO porous microspheres displayed superior sensing performance towards DBP, indicating its potential use in monitoring plasticizers in the gaseous state. Moreover, Au decoration of porous metal oxide nanostructures is proved to be an effective approach for enhancing the gas sensing properties and the corresponding mechanism was investigated.