Rapid Detection of Broad-Spectrum Pathogenic Bacteria Based on Highly Sensitive Proton Response of the Nucleic Acid Amplification SPQC Platform.

Pathogenic bacteria significantly contribute to elevated morbidity and mortality rates, highlighting the urgent need for early and precise detection. Currently, there is a paucity of effective broad-spectrum methods for detecting pathogenic bacteria. We have developed an innovative proton-responsive series piezoelectric quartz crystal (PR-SPQC) platform for the broad-spectrum identification of pathogenic bacteria. This was achieved by retrieving and aligning sequences from the NCBI GenBank database to identify and validate 16S rRNA oligonucleotide sequences that are signatures of pathogenic bacteria but absent in humans or fungi. The hyperbranched rolling circle amplification, activated exclusively by the screened target, exponentially generates protons that are detected by SPQC through a 2D polyaniline (PANI) film. The PR-SPQC platform demonstrates broad-spectrum capabilities in detecting pathogenic bacteria, with a detection limit of 2 CFU/mL within 90 min. Clinical testing of blood samples yielded satisfactory results. With its advantages in miniaturization, cost efficiency, and suitability for point-of-care testing, PR-SPQC has the potential to be extensively used for the rapid identification of diverse pathogenic bacteria within clinical practice and public health sectors.

A New SPQC Biosensor for the Detection of a New Target of Escherichia/Shigella Genera Based on a Novel Method of Synthesizing Long-Range DNA.

The rapid and sensitive detection of Escherichia/Shigella genera is crucial for human disease and health. This study introduces a novel series of piezoelectric quartz crystal (SPQC) sensors for detecting Escherichia/Shigella genera. In this innovative biosensor, we propose a new target and novel method for synthesizing long-range DNA. The method relies on the amplification of two DNA probes, referred to as H and P amplification (HPA), resulting in the products of long-range DNA named Sn. The new target was screened from the 16S rRNA gene and utilized as a biomarker. The SPQC sensor operates as follows: the Capture probe is modified on the electrodes. In the presence of a Displace probe and target, the Capture can form a complex with the Displace probe. The resulting complex hybridizes with Sn, bridging the gap between the electrodes. Finally, silver wires are deposited between the electrodes using Sn as a template. This process results in a sensitive response from the SPQC. The detection limit of the SPQC sensor is 1 CFU/mL, and the detection time is within 2 h. This sensor would be of great benefit for food safety monitoring and clinical diagnosis.

Tepuazines A-E: Phenazine Glycosides from a Venezuelan Quartz-Rich (Tepui) Cave Soil-Derived Streptomyces virginiae CMB-CA091.

Investigation of the secondary metabolites of Streptomyces virginiae CMB-CA091 isolated from the quartz-rich (tepui) soil of a cave in Venezuela yielded two new dimeric phenazine glycosides, tepuazines A and B (1 and 2); three new monomeric phenazine glycosides, tepuazines C-E (3-5); and a series of known analogues, baraphenazine G (6), phenazinolin D (7), izumiphenazine C (8), 4-methylaminobenzoyl-l-rhamnopyranoside (9), and 2-acetamidophenol (10). Structures were assigned to 1-10 on the basis of detailed spectroscopic analysis and biosynthetic considerations, with 1 and 2 featuring a rare 2-oxabicyclo[3.3.1]nonane-like ring C/D bridge shared with only a handful of known Streptomyces natural products. We propose a plausible convergent biosynthetic relationship linking all known members of this structure class that provides a rationale for the observed ring C/D configuration.

Anti-IgG Doped Melanin Nanoparticles Functionalized Quartz Tuning Fork Immunosensors for Immunoglobulin G Detection: In Vitro and In Silico Study.

The quartz tuning fork (QTF) is a promising instrument for biosensor applications due to its advanced properties such as high sensitivity to physical quantities, cost-effectiveness, frequency stability, and high-quality factor. Nevertheless, the fork's small size and difficulty in modifying the prongs' surfaces limit its wide use in experimental research. Our study presents the development of a QTF immunosensor composed of three active layers: biocompatible natural melanin nanoparticles (MNPs), glutaraldehyde (GLU), and anti-IgG layers, for the detection of immunoglobulin G (IgG). Frequency shifts of QTFs after MNP functionalization, GLU activation, and anti-IgG immobilization were measured with an Asensis QTF F-master device. Using QTF immunosensors that had been modified under optimum conditions, the performance of QTF immunosensors for IgG detection was evaluated. Accordingly, a finite element method (FEM)-based model was produced using the COMSOL Multiphysics software program (COMSOL License No. 2102058) to simulate the effect of deposited layers on the QTF resonance frequency. The experimental results, which demonstrated shifts in frequency with each layer during QTF surface functionalization, corroborated the simulation model predictions. A modelling error of 0.05% was observed for the MNP-functionalized QTF biosensor compared to experimental findings. This study validated a simulation model that demonstrates the advantages of a simulation-based approach to optimize QTF biosensors, thereby reducing the need for extensive laboratory work.

Preparation and Photodegradation of TiO2 Thin Films on the Inner Wall of Quartz Tubes.

Titanium dioxide thin films on the inner wall of quartz tubes were prepared in situ by the sol-gel method. Meanwhile, copper and cerium were loaded onto the surface of the titanium dioxide thin films to enhance photocatalytic activity and broaden the range of light absorption. X-ray diffractometer, X-ray photoelectron spectroscopy, scanning electron microscopy, energy dispersive X-ray spectrum, N2 gas adsorption, UV diffuse reflectance spectroscopy, electron paramagnetic resonance, photoluminescene spectroscopy, and so on were used to characterize the structure, morphology, chemical composition, and optical properties of the prepared photocatalyst. Methylene blue (MB) was used as a simulated organic pollutant to study the photocatalytic performance of the photocatalyst, which was a translucent, structurally stable, and reusable high-efficiency photocatalytic catalyst. Under UV lamp irradiation, the MB photodegradation efficiency was 94.5%, which reached 91.2% after multiple cycles.

Mass-Fabrication Scheme of Highly Sensitive Wireless Electrodeless MEMS QCM Biosensor with Antennas on Inner Walls of Microchannel.

Quartz-crystal-microbalance (QCM) biosensor is a typical label-free biosensor, and its sensitivity can be greatly improved by removing electrodes and wires that would be otherwise attached to the surfaces of the quartz resonator. The wireless-electrodeless QCM biosensor was then developed using a microelectro-mechanical systems (MEMS) process, although challenges remain in the sensitivity, the coupling efficiency, and the miniaturization (or mass production). In this study, we establish a MEMS process to obtain a large number of identical ultrasensitive and highly efficient sensor chips with dimensions of 6 mm square. The fundamental shear resonance frequency of the thinned AT-cut quartz resonator packaged in the microchannel exceeds 160 MHz, which is excited by antennas deposited on inner walls of the microchannel, significantly improving the electro-mechanical coupling efficiency in the wireless operation. The high sensitivity of the developed MEMS QCM biosensors is confirmed by the immunoglobulin G (IgG) detection using protein A and ZZ-tag displaying a bionanocapsule (ZZ-BNC), where we find that the ZZ-BNC can provide more effective binding sites and higher affinity to the target molecules, indicating a further enhancement in the sensitivity of the MEMS QCM biosensor. We then perform the label-free C-reactive protein (CRP) detection using the ZZ-BNC-functionalized MEMS QCM biosensor, which achieves a detection limit of 1 ng mL-1 or less even with direct detection.

Noninvasive Skin Respiration (CO2) Measurement Based on Quartz-Enhanced Photoacoustic Spectroscopy.

A noninvasive method for disease diagnosis that does not require complex specialized laboratory facilities and chemical reagents is particularly attractive in the current medical environment. Here, we develop a noninvasive skin respiration sensor based on quartz-enhanced photoacoustic spectroscopy (QEPAS) that can monitor the skin elimination rate of carbon dioxide (CO2). A 3.8 mW distributed feedback laser emitting at 2.0 µm is used as an excitation source, and a three-dimensional (3D)-printed acoustic detection module is designed to apply to the skin as a sensor head. The performance of the noninvasive skin respiration sensor is assessed in terms of detection sensitivity, linearity, long-term stability, and water effect. A minimum detection limit of 35 ppb is achieved at the optimal integration time of 670 s. The skin respiration measurements from eight healthy volunteers are recorded, and the real-time results are analyzed.

Nearly free surface silanols are the critical molecular moieties that initiate the toxicity of silica particles.

Inhalation of silica particles can induce inflammatory lung reactions that lead to silicosis and/or lung cancer when the particles are biopersistent. This toxic activity of silica dusts is extremely variable depending on their source and preparation methods. The exact molecular moiety that explains and predicts this variable toxicity of silica remains elusive. Here, we have identified a unique subfamily of silanols as the major determinant of silica particle toxicity. This population of "nearly free silanols" (NFS) appears on the surface of quartz particles upon fracture and can be modulated by thermal treatments. Density functional theory calculations indicates that NFS locate at an intersilanol distance of 4.00 to 6.00 Å and form weak mutual interactions. Thus, NFS could act as an energetically favorable moiety at the surface of silica for establishing interactions with cell membrane components to initiate toxicity. With ad hoc prepared model quartz particles enriched or depleted in NFS, we demonstrate that NFS drive toxicity, including membranolysis, in vitro proinflammatory activity, and lung inflammation. The toxic activity of NFS is confirmed with pyrogenic and vitreous amorphous silica particles, and industrial quartz samples with noncontrolled surfaces. Our results identify the missing key molecular moieties of the silica surface that initiate interactions with cell membranes, leading to pathological outcomes. NFS may explain other important interfacial processes involving silica particles.

Surface Roughness Effects on the Vibration Characteristics of AT-Cut Quartz Crystal Plate.

With the miniaturization and high-frequency requirements of quartz crystal sensors, microscopic issues affecting operating performance, e.g., the surface roughness, are receiving more and more attention. In this study, the activity dip caused by surface roughness is revealed, with the physical mechanism clearly demonstrated. Firstly, the surface roughness is considered as a Gaussian distribution, and the mode coupling properties of an AT-cut quartz crystal plate are systematically investigated under different temperature environments with the aid of two-dimensional thermal field equations. The resonant frequency, frequency-temperature curves, and mode shapes of the quartz crystal plate are obtained through the partial differential equation (PDE) module of COMSOL Multiphysics software for free vibration analysis. For forced vibration analysis, the admittance response and phase response curves of quartz crystal plate are calculated via the piezoelectric module. The results from both free and forced vibration analyses demonstrate that surface roughness reduces the resonant frequency of quartz crystal plate. Additionally, mode coupling is more likely to occur in a crystal plate with a surface roughness, leading to activity dip when temperature varies, which decreases the stability of quartz crystal sensors and should be avoided in device fabrication.

Effects of Oscillation Amplitude Variations on QCM Response to Microspheres of Different Sizes.

Suspended particulate matter (PMx) is one of the most important environmental pollutants. Miniaturized sensors capable of measuring and analyzing PMx are crucial in environmental research fields. The quartz crystal microbalance (QCM) is one of the most well-known sensors that could be used to monitor PMx. In general, in environmental pollution science, PMx is divided into two main categories correlated to particle diameter (e.g., PM < 2.5 µm and PM < 10 µm). QCM-based systems are capable of measuring this range of particles, but there is an important issue that limits the application. In fact, if particles with different diameters are collected on QCM electrodes, the response will be a result of the total mass of particles; there are no simple methods to discriminate the mass of the two categories without the use of a filter or manipulation during sampling. The QCM response depends on particle dimensions, fundamental resonant frequency, the amplitude of oscillation, and system dissipation properties. In this paper, we study the effects of oscillation amplitude variations and fundamental frequency (10, 5, and 2.5 MHz) values on the response, when particle matter with different sizes (2 µm and 10 µm) is deposited on the electrodes. The results showed that the 10 MHz QCM was not capable of detecting the 10 µm particles, and its response was not influenced by oscillation amplitude. On the other hand, the 2.5 MHz QCM detected the diameters of both particles, but only if a low amplitude value was used.

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.

Clamp-type quartz tuning fork enhanced photoacoustic spectroscopy.

In this Letter, clamp-type quartz tuning fork enhanced photoacoustic spectroscopy (Clamp-type QEPAS) is proposed and realized through the design, realization, and testing of clamp-type quartz tuning forks (QTFs) for photoacoustic gas sensing. The clamp-type QTF provides a wavefront-shaped aperture with a diameter up to 1 mm, while keeping Q factors > 104. This novel, to the best of our knowledge, design results in a more than ten times increase in the area available for laser beam focusing for the QEPAS technique with respect to a standard QTF. The wavefront-shaped clamp-type prongs effectively improve the acoustic wave coupling efficiency. The possibility to implement a micro-resonator system for clamp-type QTF is also investigated. A signal-to-noise enhancement of ∼30 times has been obtained with a single-tube acoustic micro resonator length of 8 mm, ∼20% shorter than the dual-tube micro-resonator employed in a conventional QEPAS system.

Compact GC-QEPAS for On-Site Analysis of Chemical Threats.

This paper reports on a compact, portable, and selective chemical sensor for hazardous vapors at trace levels, which is under development and validation within the EU project H2020 "RISEN". Starting from the prototype developed for a previous EU project, here, we implemented an updated two-stage purge and trap vapor pre-concentration system, a more compact MEMS- based fast gas-chromatographic separation module (Compact-GC), a new miniaturized quartz-enhanced photoacoustic spectroscopy (QEPAS) detector, and a new compact laser source. The system provides two-dimensional selectivity combining GC retention time and QEPAS spectral information and was specifically designed to be rugged, portable, suitable for on-site analysis of a crime scene, with accurate response in few minutes and in the presence of strong chemical background. The main upgrades of the sensor components and functional modules will be presented in detail, and test results with VOCs, simulants of hazardous chemical agents, and drug precursors will be reported and discussed.

A New Analytical Method to Quantify Ammonia in Freshwater with a Bulk Acoustic Wave Sensor.

A new method to analyse ammonia in freshwater, based on a piezoelectric quartz crystal coated with the metalloporphyrin chloro[5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato] manganese(III) is presented. A 9 MHz quartz crystal coated on both faces with an amount of porphyrin produced a frequency decrease of 21.4 kHz, which allowed ammonia in a 10.00 mL sample to be quantified in concentrations between 5 and 70 µg L-1, with a sensitivity of 0.60 Hz L µg-1, over a period of at least eight months. The proposed method has several advantages over the officially recommended indophenol spectrophotometric method: sample volume was reduced by a factor of 2.5, toxic reagents (phenol and sodium nitroprusside) were eliminated, analysing turbid samples presented no difficulty, and there was not only a significant time saving in solution preparation, but also in sample analysis time, which was reduced from 1 h to 2 min. No statistically significant differences (α = 0.05) were found both in the mean and precision of the results obtained for ammonia in water samples collected from domestic wells, analysed by this new method and by the indophenol spectrophotometric method. Furthermore, the proposed method would allow the individual quantification, with similar sensitivity, of amines and ammonia within a single analytical run.

Advanced Impedance Spectroscopy for QCM Sensor in Liquid Medium.

Technological evolution has allowed impedance analysis to become a versatile and efficient method for the precise measurement of the equivalent electrical parameters of the quartz crystal microbalance (QCM). By measuring the dissipation factor, or another equivalent electrical parameter, the QCM sensor provides access to the sample mass per unit area and its physical parameters, thus ensuring a detailed analysis. This paper aims to demonstrate the benefits of advanced impedance spectroscopy concerning the Butterworth-van Dyke (BVD) model for QCM sensors immersed with an electrode in a liquid medium. The support instrument in this study is a fast and accurate software-defined virtual impedance analyzer (VIA) with real-time computing capabilities of the QCM sensor's electric model. Advanced software methods of self-calibration, real-time compensation, innovative post-compensation, and simultaneous calculation by several methods are the experimental resources of the results presented in this paper. The experimental results validate the theoretical concepts and demonstrate both the capabilities of VIA as an instrument and the significant improvements brought by the advanced software methods of impedance spectroscopy analysis related to the BVD model.

Strategies for the Accurate Measurement of the Resonance Frequency in QCM-D Systems via Low-Cost Digital Techniques.

In this paper, an FPGA (Field Programmable Gate Array)-based digital architecture for the measurement of quartz crystal microbalance (QCM) oscillating frequency of transient responses, i.e., in QCM-D (QCM and Dissipation) applications, is presented. The measurement system is conceived for operations in liquid, with short QCM transient responses due to the large mechanical load. The proposed solution allows for avoiding the complex processing systems typically required by the QCM-D techniques and grants frequency resolutions better than 1 ppm. The core of the architecture is a reciprocal digital frequency meter, combined with the preprocessing of the QCM signal through mixing operations, such as a step-down of the input frequency and reducing the measurement error. The measurement error is further reduced through averaging. Different strategies are proposed to implement the proposed measurement solution, comprising an all-digital circuit and mixed analog/digital ones. The performance of the proposed architectures is theoretically derived, compared, and analyzed by means of experimental data obtained considering 10 MHz QCMs and 200 µs long transient responses. A frequency resolution of about 240 ppb, which corresponds to a Sauerbrey mass resolution of 8 ng/cm2, is obtained for the all-digital solution, whereas for the mixed solution the resolution halves to 120 ppb, with a measurement time of about one second over 100 repetitions.

Additively Manufactured Detection Module with Integrated Tuning Fork for Enhanced Photo-Acoustic Spectroscopy.

Starting from Quartz-Enhanced Photo-Acoustic Spectroscopy (QEPAS), we have explored the potential of a tightly linked method of gas/vapor sensing, from now on referred to as Tuning-Fork-Enhanced Photo-Acoustic Spectroscopy (TFEPAS). TFEPAS utilizes a non-piezoelectric metal or dielectric tuning fork to transduce the photoacoustic excitation and an optical interferometric readout to measure the amplitude of the tuning fork vibration. In particular, we have devised a solution based on Additive Manufacturing (AM) for the Absorption Detection Module (ADM). The novelty of our solution is that the ADM is entirely built monolithically by Micro-Metal Laser Sintering (MMLS) or other AM techniques to achieve easier and more cost-effective customization, extreme miniaturization of internal volumes, automatic alignment of the tuning fork with the acoustic micro-resonators, and operation at high temperature. This paper reports on preliminary experimental results achieved with ammonia at parts-per-million concentration in nitrogen to demonstrate the feasibility of the proposed solution. Prospectively, the proposed TFEPAS solution appears particularly suited for hyphenation to micro-Gas Chromatography and for the analysis of complex solid and liquid traces samples, including compounds with low volatility such as illicit drugs, explosives, and persistent chemical warfare agents.

Effect of Electrode Thickness on Quality Factor of Ring Electrode QCM Sensor.

As a key type of sensor, the quartz crystal microbalance (QCM) has been widely used in many research areas. Recently, the ring electrode QCM sensor (R-QCM) with more uniform mass sensitivity has been reported. However, the quality factor (Q-factor) of the R-QCM has still not been studied, especially regarding the effect of electrode thickness on the Q-factor. Considering that the Q-factor is one of crucial parameter to the QCM and it is closely related to the output frequency stability of the QCM, we study the effect of different electrode thicknesses on the Q-factor of the R-QCM in this paper. On the other hand, we clarify the relationship between the electrode thickness and the Q-factor of the R-QCM. The measurement results show that the average Q-factor increases with increases in the thickness of ring electrodes generally; however, the resonance frequency of the QCM resonator decreases with increases in the thickness. The low half-bandwidth (2Γ < 1630 Hz) of the R-QCM shows that the frequency performance is good. Additionally, the R-QCM has a higher Q-factor (Q > 6000), which indicates that it has a higher frequency stability and can be applied in many research areas.

Design and Analysis of Quartz Crystal Microbalance with a New Ring-Shaped Interdigital Electrode.

In this paper, a new type of ring-shaped interdigital electrode is proposed to improve the accuracy and repeatability of quartz crystal microbalance. The influence of different types of single finger, dot finger, dot double-finger electrodes on mass sensitivity distribution as well as the optimal proportion of finger and gap width are obtained through multi-physical coupling simulation. The results show that the design criteria of interdigital electrodes will not change with the increase in the number of fingers. The gap width should obey the decrease order from central to edge and be about twice the width of finger. The width of the outermost finger and the radius of the middle dot electrode should be maintained at about 0.4 and 0.2 times of the total electrode radius. An experiment was carried out to verify that the quartz wafer with a dot double-finger electrode has high quality factors and less modal coupling, which can satisfy the engineering application well. As a conclusion, this study provides a design idea for the electrode to maintain a uniform distribution of quartz crystal microbalance mass sensitivity.

Top-Down Preparation of Nanoquartz for Toxicological Investigations.

Occupational exposure to quartz dust is associated with fatal diseases. Quartz dusts generated by mechanical fracturing are characterized by a broad range of micrometric to nanometric particles. The contribution of this nanometric fraction to the overall toxicity of quartz is still largely unexplored, primarily because of the strong electrostatic adhesion forces that prevent isolation of the nanofraction. Furthermore, fractured silica dust exhibits special surface features, namely nearly free silanols (NFS), which impart a membranolytic activity to quartz. Nanoquartz can be synthetized via bottom-up methods, but the surface chemistry of such crystals strongly differs from that of nanoparticles resulting from fracturing. Here, we report a top-down milling procedure to obtain a nanometric quartz that shares the key surface properties relevant to toxicity with fractured quartz. The ball milling was optimized by coupling the dry and wet milling steps, using water as a dispersing agent, and varying the milling times and rotational speeds. Nanoquartz with a strong tendency to form submicrometric agglomerates was obtained. The deagglomeration with surfactants or simulated body fluids was negligible. Partial lattice amorphization and a bimodal crystallite domain size were observed. A moderate membranolytic activity, which correlated with the number of NFS, signaled coherence with the previous toxicological data. A membranolytic nanoquartz for toxicological investigations was obtained.