Quartz Crystal Microbalance Crystal Research Articles

Development of a dry powder insufflation device with application in in vitro cell-based assays in the context of respiratory delivery

Research on pharmaceutical dry powders has been increasing worldwide, along with increased therapeutic strategies for an application through the pulmonary or the nasal routes. In vitro methodologies and tests that mimic the respiratory environment and the process of inhalation itself are, thus, essential. The literature frequently reports cell-based in vitro assays that involve testing the dry powders in suspension. This experimental setting is not adequate, as both the lung and the nasal cavity are devoid of abundant liquid. However, devices that permit powder insufflation over cells in culture are either scarce or technically complex and expensive, which is not feasible in early stages of research. In this context, this work proposes the development of a device that allows the delivery of dry powders onto cell surfaces, thus simulating inhalation more appropriately. Subsequently, a quartz crystal microbalance (QCM) was used to establish a technique enabling the determination of dry powder deposition profiles. Additionally, the determination of the viability of respiratory cells (A549) after the insufflation of a dry powder using the developed device was performed. In all, a prototype for dry powder insufflation was designed and developed, using 3D printing methods for its production. It allowed the homogenous dispersion of the insufflated powders over a petri dish and a QCM crystal, and a more detailed study on how dry powders disperse over the supports. The device, already protected by a patent, still requires further improvement, especially regarding the method for powder weighing and the efficiency of the insufflation process, which is being addressed. The impact of insufflation of air and of locust bean gum (LBG)-based microparticles revealed absence of cytotoxic effect, as cell viability roughly above 70 % was always determined.

Design, Fabrication and Performance Analysis of a Portable, Antenna Analyzer Based, Quartz Crystal Microbalance Measuring System with Energy Dissipation

Impedance measurements play a critical role in analyzing the electrical behavior of piezoelectric biosensors in general. Antenna analyzers are engineered to measure the specific case of input impedance for antenna systems. In this study small form factor antenna analyzer is repurposed to work as driving circuit for a Quartz Crystal Microbalance (QCM) biosensor in combination with a single board computer as an indication of how small and portable an impedance measuring system can be made, while allowing monitoring of important parameters of series and parallel resonance frequencies together with dissipation factor. A QCM crystal with a 10 MHz fundamental resonance frequency is employed to determine the limit of detection of the system in Bovine Serum Albumin (BSA) and glycerol solutions. Dissipation factor and phase angle were monitored during the experiments. Limit of detection is 20 µg/ml BSA in phosphate buffer saline (PBS) and 250 µl of glycerol in 100 ml of deionized water.

Quartz crystal microbalance-based biosensing of proteins using molecularly imprinted polydopamine sensing films: Interplay between protein characteristics and molecular imprinting effect

Biomimetic sensing films based on molecularly imprinted polydopamine (MIPDA) offer a simple, biocompatible, and versatile approach to functionalise quartz crystal microbalance (QCM)-based biosensors for the recognition of target proteins. This study aims to investigate the chemical, morphological, and recognition properties of MIPDA sensing films polymerised on the QCM crystal surface, and to elucidate the impacts of various parameters on the liquid-phase biosensing behaviour. Pepsin, bovine serum albumin, human serum albumin, and lysozyme were used as model proteins to study the effect of molecular imprinting and the influence of protein characteristics on the recognition behaviour of MIPDA-functionalised QCM crystals. Analysis of the protein adsorption patterns revealed that the MIPDA film contained heterogeneous binding sites with a dissociation constant in the µM range, showing that the binding affinity of the synthetic sensing film for the target protein was comparable to that of commonly used bioreceptors. In a case study using a pepsin-imprinted MIPDA film, the specific conformation and surface chemistry of the recognition cavities were discovered to promote the binding of pepsin (imprinting factor = 5.78) while simultaneously reducing the nonspecific binding of incompatible proteins on the QCM crystal surface. Protein recognition on MIPDA-functionalised QCM crystals was found to be governed by a combination of nonspecific interactions (e.g., electrostatic and polar interactions) between the proteins and the MIPDA sensing film. The findings indicate that increasing the density of selective recognition cavities in the MIPDA film and optimising the sample pH are key strategies to improve the selectivity and sensitivity for protein biosensing.

Biased quartz crystal microbalance method for studies of chemical vapor deposition surface chemistry induced by plasma electrons.

A recently presented chemical vapor deposition (CVD) method involves using plasma electrons as reducing agents for deposition of metals. The plasma electrons are attracted to the substrate surface by a positive substrate bias. Here, we present how a standard quartz crystal microbalance (QCM) system can be modified to allow applying a DC bias to the QCM sensor to attract plasma electrons to it and thereby also enable in situ growth monitoring during the electron-assisted CVD method. We show initial results from mass gain evolution over time during deposition of iron films using the biased QCM and how the biased QCM can be used for process development and provide insight into the surface chemistry by time-resolving the CVD method. Post-deposition analyses of the QCM crystals by cross-section electron microscopy and high-resolution x-ray photoelectron spectroscopy show that the QCM crystals are coated by an iron-containing film and thus function as substrates in the CVD process. A comparison of the areal mass density given by the QCM crystal and the areal mass density from elastic recoil detection analysis and Rutherford backscattering spectrometry was done to verify the function of the QCM setup. Time-resolved CVD experiments show that this biased QCM method holds great promise as one of the tools for understanding the surface chemistry of the newly developed CVD method.

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.

Thiol-Based Probe Linker with Antifouling Properties for Aptasensor Development

Surfaces with antifouling properties are critical for optimizing biosensors to improve the selectivity and specificity of analyte detection in complex biological samples. This work describes the four-step synthesis of 3-dithiothreitol propanoic acid (DTTCOOH), a new antifouling thiol linker that (a) significantly reduces fouling of raw human serum samples and (b) binds amino receptors via its terminal carboxylic acid group. DTTCOOH was successfully functionalized on quartz crystal microbalance (QCM) discs and used to anchor penicillin-binding aptamers. Relative to bare and coated (11-mercaptoundecanoic acid (MUA) and 1-undecanethiol (UDT)) QCM crystals, DTTCOOH’s antifouling improved by approximately 75–86%. Following aptamer/ethanolamine extension, the modified DTTCOOH layer reduced serum fouling by approximately 95–97% compared to bare and coated (MUA, UDT) crystals. QCM with dissipation (QCM-D) monitoring, contact goniometry, and cyclic voltammetry techniques were used to compare the DTTCOOH surfaces with quartz crystals functionalized with hydrophobic and hydrophilic molecules.

Simulation analysis and experimental verification for sensitivity of IDE-QCM humidity sensors

• A facile and effective approach to improve the sensitivity of piezoelectric quartz crystal humidity sensors was presented. • Both IDE and QCM are used as sensitive components to improve humidity sensitivity. • The superposition relationship of the frequency change in IDE-PQC and QCM was proved using equivalent circuit method. • The sensitivity of the IDE-QCM humidity sensor reaches 262.21 Hz/%RH in the humidity range of 11.3–97.3 % RH. This paper proposes a new, simple, and effective approach that uses both an interdigital electrode (IDE) and a quartz crystal microbalance (QCM) as sensitive components to improve humidity sensitivity. First, a simulation analysis of the equivalent electronic circuit was used to verify that the frequency response of the IDE-QCM humidity sensor is the sum of that of the QCM and interdigital electrode-piezoelectric quartz crystal (IDE-PQC) sensors. Then, cellulose nanocrystals (CNCs) were used as humidity-sensitive materials deposited on IDE and QCMs, respectively, to fabricate several PQC sensors. The humidity-sensing performances of all sensors were tested at room temperature, including the dynamic response, sensitivity, response/recovery time, repeatability, and long-term stability. The experimental results prove the superposition relationship and can be used to enhance the humidity sensitivity. The maximum sensitivity of the IDE-QCM sensor reaches 262.21 Hz/%RH in the humidity range of 11.3 %–97.3 %, which is higher than that of all frequency-modulated piezoelectric quartz crystal humidity sensors. Moreover, the humidity hysteresis (∼ 8.1 %RH) and response/recovery time (68/4 s) did not significantly increase compared with the IDE-PQC and QCM sensors. All the sensors exhibited good repeatability and long-term stability. Finally, the humidity-sensing mechanism of the CNC-based IDE-QCM sensor is discussed in detail. This work demonstrates that using both IDE and QCM as sensitive elements is a simple and effective method to improve the humidity sensitivity of frequency-modulated piezoelectric quartz crystal sensors. This superposition relationship of capacitance-inductance frequency modulation to enhance sensitivity also provides an excellent reference for the design of other high-performance sensors.

Long-Term Measurement of PM2.5 Mass Concentration Using an Electrostatic Particle Concentrator-Based Quartz Crystal Microbalance Integrated With Carbon Dioxide Aerosol Jets for PM Sensing in Remote Areas

Fine particulate matter (PM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2.5</sub> ) is a major environmental health risk. Several instruments based on the quartz crystal microbalance (QCM) have been developed for PM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2.5</sub> measurement because of their accurate, sensitive, real-time, and low-cost mass measurements. However, prolonged or non-uniform deposition on the quartz crystal can cause nonlinear responses between frequency shifts and mass deposition, and its frequent manual cleaning with wet sponges is required. These disable long-term measurements of the instruments, thus limiting their applications in remote areas. Herein, we present a new PM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2.5</sub> instrument called qEPC-Snow. This instrument consists of a QCM crystal embedded in an electrostatic particle concentrator (EPC) for collection and sensing of PM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2.5</sub> and a carbon dioxide aerosol (snow) jet unit for residue-free, rapid, effective, and non-destructive cleaning of the crystal. Laboratory tests were conducted with aerosolized 100-nm and 2- μm polystyrene latex microspheres as PM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2.5</sub> representatives to evaluate (i) frequency responses and (ii) mass sensitiveness of qEPC-Snow, (iii) particle removal efficiencies, and (iv) reuse of the used crystals. Experimental results demonstrated high removal efficiencies (approximately 99.9% for both particle sizes) and statistical similarity between the initial and cleaned QCM crystals in the frequency shift-mass deposition relationship, thereby enabling measurement for more than one month without demounting the crystals. The mass sensitivity was 57.34 (Hz/ μg) with R <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> = 0.9904, corresponding to 0.05667 [(Hz/min)/( μg/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> )] in mass concentration sensitivity for the PM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2.5</sub> representatives. The influence of particle sizes on qEPC-Snow's frequency behaviors will also be discussed in detail.

Probing fibronectin adsorption on chemically defined surfaces by means of single molecule force microscopy

Atomic force microscope (AFM) based single molecule force spectroscopy (SMFS) and a quartz crystal microbalance (QCM) were respectively employed to probe interfacial characteristics of fibronectin fragment FNIII8–14 and full-length fibronectin (FN) on CH3–, OH–, COOH–, and NH2-terminated alkane-thiol self-assembled monolayers (SAMs). Force-distance curves acquired between hexahistidine-tagged FNIII8–14 immobilised on trisNTA-Ni2+ functionalized AFM cantilevers and the OH and COOH SAM surfaces were predominantly ‘loop-like’ (76% and 94% respectively), suggesting domain unfolding and preference for ‘end-on’ oriented binding, while those generated with NH2 and CH3 SAMs were largely ‘mixed type’ (81% and 86%, respectively) commensurate with unravelling and desorption, and ‘side-on’ binding. Time-dependent binding of FN to SAM-coated QCM crystals occurred in at least two phases: initial rapid coverage over the first 5 min; and variably diminishing adsorption thereafter (5–70 min). Loading profiles and the final hydrated surface concentrations reached (~ 950, ~ 1200, ~ 1400, ~ 1500 ng cm−2 for CH3, OH, COOH and NH2 SAMs) were consistent with: space-filling ‘side-on’ orientation and unfolding on CH3 SAM; greater numbers of FN molecules arranged ‘end-on’ on OH and especially COOH SAMs; and initial ‘side-on’ contact, followed by either (1) gradual tilting to a space-saving ‘end-on’ configuration, or (2) bi-/multi-layer adsorption on NH2 SAM.

Production of low-energy fragment-ion beams from hexamethyldisiloxane and the irradiation of SiO+ ion beam to substrates with supplemental oxygen gas for SiO2 film formation

In this work, low-energy fragment-ion beams were produced from hexamethyldisiloxane (HMDSO) used as a source material and substrates were irradiated by these beams with supplemental oxygen gas for the formation of silicon dioxide (SiO2) film. During this process, SiO+ ions having an energy of 50 eV were mass-selected from various fragments derived from the decomposition of HMDSO. These ions were subsequently transferred to a Si substrate at room temperature in conjunction with a supplemental oxygen flow. The resulting film was assessed by Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy to confirm SiO2 deposition. The bonding of incident SiO+ ions with a quartz crystal microbalance (QCM) was assessed at ion energies of 50, 100 and 200 eV, and the sticking probability of incident SiO+ ions to the QCM crystal substrate was found to decrease monotonically with increasing energy.

Design of a multi-channel quartz crystal microbalance data acquisition system

In this study a multi-channel data acquisition system has been designed, by which mass changes in small quantities can be monitored and recorded by means of a quartz crystal microbalance (QCM) technique. The whole system is controlled by an Arduino Atmega 2560 microcontroller and can be run independently or via a personal computer. A PIC16F628A microcontroller is used for each channel of the prototype device designed for the system, and frequency measurements of the QCM crystals to be used for sensor investigations have been performed by this microcontroller. The temperatures of sensor environments and ambient humidity can be measured at the same time as the frequency measurements. The frequency response performance of QCM crystal has been tested by experiment. The system is able to measure and monitor QCM frequencies in the 1–50 MHz range, at 1 ppm accuracy and 1 Hz precision. The front surface of a QCM crystal was coated with NiO by a physical vapor deposition technique, and the mass of the film layer grown on the QCM crystal surface was precisely calculated to be 26.53 µg with an error rate of less than 1%. The mass value obtained in this way is in reasonably good agreement with the values obtained by oscilloscope and frequency meter methods.

Photodegradation of Secondary Organic Aerosol Material Quantified with a Quartz Crystal Microbalance

We used a quartz crystal microbalance (QCM) to quantify the mass loss resulting from exposure of secondary organic aerosol (SOA) particles deposited on the QCM crystal to 254, 305, and 365 nm radiation. We coupled the QCM setup to a proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS) to chemically resolve the photoproduced volatile organic compounds (VOCs) responsible for the mass loss. The photoproduced VOCs detected by the PTR-ToF-MS accounted for ∼50% of the mass loss rates measured with the QCM. Weakly absorbing SOA produced by ozonolysis of α-pinene or d-limonene exhibited a much larger mass loss rate in both the QCM and the PTR-ToF-MS data compared to that of strongly absorbing SOA produced by photooxidation of guaiacol. We predict that the fractional mass loss rate of α-pinene ozonolysis SOA should be as high as ∼1%/h on the summer solstice in Los Angeles in the lower troposphere and ∼4%/h in the stratosphere. The mass loss rates for SOA particles crossing a typical 254 nm oxidat...

PEALD of SiO2 and Al2O3 Thin Films on Polypropylene: Investigations of the Film Growth at the Interface, Stress, and Gas Barrier Properties of Dyads.

A study on the plasma-enhanced atomic layer deposition of amorphous inorganic oxides SiO2 and Al2O3 on polypropylene (PP) was carried out with respect to growth taking place at the interface of the polymer substrate and the thin film employing in situ quartz-crystal microbalance (QCM) experiments. A model layer of spin-coated PP (scPP) was deposited on QCM crystals prior to depositions to allow a transfer of findings from QCM studies to industrially applied PP foil. The influence of precursor choice (trimethylaluminum (TMA) vs [3-(dimethylamino)propyl]-dimethyl aluminum (DMAD)) and of plasma pretreatment on the monitored QCM response was investigated. Furthermore, dyads of SiO2/Al2O3, using different Al precursors for the Al2O3 thin-film deposition, were investigated regarding their barrier performance. Although the growth of SiO2 and Al2O3 from TMA on scPP is significantly hindered if no oxygen plasma pretreatment is applied to the scPP prior to depositions, the DMAD process was found to yield comparable Al2O3 growth directly on scPP similar to that found on a bare QCM crystal. From this, the interface formed between the Al2O3 and the PP substrate is suggested to be different for the two precursors TMA and DMAD due to different growth modes. Furthermore, the residual stress of the thin films influences the barrier properties of SiO2/Al2O3 dyads. Dyads composed of 5 nm Al2O3 (DMAD) + 5 nm SiO2 exhibit an oxygen transmission rate (OTR) of 57.4 cm3 m-2 day-1, which correlates with a barrier improvement factor of 24 against 5 when Al2O3 from TMA is applied.

A QCM Sensor Array-Based Electronic Tongue With the Optimized Oscillator Circuit Using FPGA

In this paper, an electronic tongue (ET) based on a quartz-crystal microbalance (QCM) sensor array was designed and the methods for sensor data analysis were described. In this regard, as chemical sensors, QCM crystals coated with three different phthalocyanines were employed to discriminate toxic chemicals in liquid media. For sensors’ preparation, an automatic coating instrument was developed based on the airbrush technique. The oscillator circuits used in the coating instrument and measurement setup were optimized to minimize the noise and mutual interference of the other oscillator circuits in the sensor array. The designed measurement system, which was responsible for collecting and storing data, communicating with a computer, consisted of a field-programmable gate-array-based control unit. The measurement system collected training data from the sensor array, and then computer application using MATLAB used an artificial neural network to find the composition of toxic chemicals in the sample water. The measurement system was tested for three different toxic chemicals, and the average success rate in predicting them was 4.08%. The desired chemicals can be detectable by preparing the necessary sensor array with the proposed ET.

Using a high-stability quartz-crystal microbalance to measure and model the chemical kinetics for gases in and on metals: Oxygen in gold

This paper describes the use of a high-stability quartz-crystal microbalance (QCM) to measure the mass of a gas absorbed on and in the metal electrode on the quartz oscillator, when the gas pressure is low and the gas can be considered as rigidly attached to the metal, so the viscosity effects are negligible. This provides an absolute measure of the total mass of gas uptake as a function of time, which can be used to model the kinetic processes involved. The technique can measure diffusion parameters of gases in metals close to room temperature at gas pressures much below one atmosphere, as relevant to surface processes such as atomic layer deposition and model studies of heterogeneous catalysis, whereas traditional diffusion measurements require temperatures over 400 °C at gas pressures of at least a few Torr. A strong aspect of the method is the ability to combine the “bulk” measurement of absorbed mass by a QCM with a surface-sensitive technique such as Auger electron spectroscopy in the same vacuum chamber. The method is illustrated using atomic oxygen, formed under O2 gas at 6 × 10−5 Torr in the presence of a hot tungsten filament, interacting with the gold electrode on a QCM crystal held at 52 to 120 °C. Some of the incident oxygen forms a surface oxide which eventually blocks more uptake, and the rest (about 80%) indiffuses. Surprisingly, the rate of oxygen uptake initially increases with the amount of oxygen previously absorbed; therefore, the measured oxygen uptake with time is reproducible only if preadsorption of oxygen conditions the sample. Temperatures above 130 °C are necessary for measurable thermal desorption, but all the oxygen can be removed by CO scavenging at all temperatures of these experiments. Simple kinetic models are developed for fitting the experimental QCM data to extract parameters including those controlling adsorption of oxygen, the CO scavenging probability, and limits on the diffusion jump frequency of dissolved oxygen. The reproducibility of the data and the good model fits to it provide proof-of-principle for the technique.

Water Sorption in Electron-Beam Evaporated SiO2 on QCM Crystals and Its Influence on Polymer Thin Film Hydration Measurements

Spectroscopic ellipsometry (SE) and quartz crystal microbalance (QCM) measurements are two critical characterization techniques routinely employed for hydration studies of polymer thin films. Water uptake by thin polymer films is an important area of study to investigate antifouling surfaces, to probe the swelling of thin water-containing ionomer films, and to conduct fundamental studies of polymer brush hydration and swelling. SiO2-coated QCM crystals, employed as substrates in many of these hydration studies, show porosity in the thin electron-beam (e-beam) evaporated SiO2 layer. The water sorption into this porous SiO2 layer requires correction of the optical and mass characterization of the hydrated polymer due to changes in the SiO2 layer as it sorbs water. This correction is especially important when experiments on SiO2-coated QCM crystals are compared to measurements on Si wafers with dense native SiO2 layers. Water adsorption filling void space during hydration in ∼200-260 nm thick SiO2 layers deposited on a QCM crystal resulted in increased refractive index of the layer during water uptake experiments. The increased refractive index led to artificially higher polymer swelling in the optical modeling of the hydration experiments. The SiO2-coated QCM crystals showed between 6 and 8% void as measured by QCM and SE, accounting for 60%-85% of the measured polymer swelling in the low humidity regime (<20% RH) and 25%-40% of the polymer swelling in the high humidity regime (>70% RH) from optical modeling for 105 and 47 nm thick sulfonated polymer films. Correcting the refractive index of the SiO2 layer for its water content resulted in polymer swelling that successfully resembled swelling measured on a silicon wafer with nonporous native oxide.

Quartz crystal microbalance apparatus for study of viscous liquids at high temperatures.

A design for a Quartz Crystal Microbalance (QCM) setup for use with viscous liquids at temperatures of up to 300 °C is reported. The system response for iron and gold coated QCM crystals to two common lubricant base oils, polyalphaolefin and halocarbon, is reported, yielding results that are consistent with theoretical predictions that incorporate electrode nanoscale surface roughness into their analysis.

Morphology-defined interaction of copper phthalocyanine with O2/H2O

Copper phthalocyanine (CuPc) is an important hole transport layer for organic photovoltaics (OPVs), but interaction with ambient gas/vapor may lead to changes in its electronic properties and limit OPV device lifetimes. CuPc films of thickness 25 and 100 nm were grown by thermal sublimation at 25°C, 150°C, and 250°C in order to vary morphology. We measured electrical resistance and film mass in situ during exposure to controlled pulses of O2 and H2O vapor. CuPc films deposited at 250°C showed a factor of 5 higher uptake of O2 as detected by a quartz crystal microbalance (QCM), possibly due to the formation of β-CuPc at T>200°C which allows higher O2 mobility between stacked molecules. While weight-based measurements stabilize after ∼10 min of gas exposure, resistance response stabilizes over times >1 h, suggesting that mass change occurs by rapid adsorption at active surface sites whereas resistive response is dominated by slow diffusion of adsorbates into the bulk film. The 25 nm films exhibit higher resistive response than 100 nm films after an hour of O2/H2O exposure due to fast analyte diffusion down to the film/electrode interface. We found evidence of decoupling of CuPc from the gold-coated QCM crystal due to preferential adsorption of O2/H2O molecules on gold.

Real-time label-free detection and kinetic analysis of Etanercept—Protein A interactions using quartz crystal microbalance

A quartz crystal microbalance (QCM) was constructed to assess if such a biosensor has value as a complementary real-time label-free analysis platform for the biopharmaceutical industry. This was achieved through modifying QCM crystals with a low-fouling carboxymethyl-dextran layer bearing Protein A, and then injecting solutions containing Etanercept (i.e., Enbrel®) into the QCM chambers. The kinetics of Enbrel® – Protein A interactions was modeled using the Langmuir binding model and Enbrel® concentrations between 0.75–300ngmL−1. The resulting equilibrium dissociation and association constants (KD and KA) were 5.06×10−8M and 1.98×107M−1, respectively. The association and dissociation rate constants (kon and koff) decreased substantially as Enbrel® concentration, [C], increased, despite that the net binding rate, (kon[C]+koff), increased. The decrease in kon and koff was hypothesized to be a consequence of mass transport limitations. To verify this, QCM dissipation measurements were analyzed to provide insight on solution viscosity. As Enbrel® concentration increased, the net change in dissipation, ΔD, became larger. An augmentation of ΔD is associated with a higher solution viscosity, which would result in an increase in mass transport limitations. Therefore, the decrease in kon and koff for increasing Enbrel® concentration can be attributed to mass transport limitations. In conclusion, QCM is a valuable complementary real-time label-free biosensor analysis platform for the biopharmaceutical industry. Unlike the surface plasmon resonance (SPR) platform, QCM allows measuring dissipation, which can provide insight on how mass transport limitations impact interaction kinetics.

Quartz crystal microbalance with microfluidic multi-stream solution control for mineralization kinetic analysis

We present a quartz crystal microbalance (QCM) sensor integrated with microfluidic multi-stream solution control for a variety of analysis applications, including improved studies of mineralization kinetics. The cost-effective assembly of this device and functionality of the QCM crystal in situations of rigid and viscoelastic mass loading are demonstrated. The significant advantage of this system is the control of solution mixing on-chip through the use of laminar parallel-flow which creates a liquid–liquid reaction interface at the QCM sensor. This shows improved sensor response times, due to laminar flow, of 105Hz/min compared to 19Hz/min for turbulent mixing in a bulk solution flow cell. This device adds to the current real-time mass measurements obtained from traditional QCM by allowing for simultaneous optical microscopy. The combination of QCM mass analysis, optical microscopy, and laminar parallel-flow to achieve a liquid–liquid reaction interface provides an analytical system well suited for the study of controlled mineralization. The microfluidic solution flow decreases non-specific mineralization and offers significant experimental control.