QCM/HCC as a platform for detecting the binding of warfarin to an immobilized film of human serum albumin

Quartz crystal microbalance/heat conduction calorimetry (QCM/HCC) is a new measurement technology that has been used to monitor simultaneously the mass and motional resistance of a thin film in conjunction with the heat flow produced by a chemical change in the film initiated by reaction with a gas. In this work we examine the applicability of the QCM/HCC in detecting chemical changes at the solution/thin film interface. Human serum albumin (HSA) was bound to the gold electrode of a 5 MHz AT-cut quartz resonator using three types of linkers and then exposed to buffered solutions of the anticoagulant drug warfarin. Changes in resonator frequency and motional resistance as well as changes in heat flow produced by warfarin binding to HSA were monitored as a function of the warfarin concentration. Differences in frequency and motional resistance changes depend upon the linker and vary both in magnitude and sign, whereas the integrated heat signal is proportional to the concentration of warfarin and independent of the linker chemistry. Quartz crystal microbalance/heat conduction calorimetry can thus be a useful tool for studying protein-ligand interactions at the solution-surface interface, even though the quartz resonator does not behave as a microbalance.     

Determining the effects of vapor sorption in polymers with the quartz crystal microbalance/heat conduction calorimeter

The quartz crystal microbalance/heat conduction calorimeter (QCM/HCC) is a versatile instrument coupling both gravimetric and calorimetric techniques. The QCM/HCC is used to probe vapor sorption in thin films. Three parameters are measured simultaneously as a thin film undergoes vapor sorption, namely: mass changes in the film (±10 ng), corresponding thermal effects upon vapor sorption (±100 nW), and motional resistance (±0.5Ω) changes within the film. A range of film thicknesses (0.75 to 8.5 μm) of the polymer, Tecoflex? are cast on QCMs and the interaction of each film with ethanol and water is determined. From the direct calorimetric measurements, sorption enthalpies (Δ_sorptionH kJ/mol) are determined for the film–vapor interactions. Sorption isotherms are then analyzed for each film. The isotherms shown here generally display a linear Henry's Law dissolution relationship between the vapor pressure and the amount of vapor sorbed into the film. Motional resistance data provides a window to view viscoelastic effects of the polymer films upon vapor sorption. Motional resistance data are compared for ethanol sorption in a relatively thin (0.75 μm) and thicker (8.5 μm) Tecoflex? film. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3893–3906, 2004     

The effect of heat treatment on water sorption in polylactide and polylactide composites via changes in glass‐transition temperature and crystallization kinetics

Water sorption into polylactide (PLA) and polylactide‐montmorillonite (PLLA‐MONT) composites containing 5 wt % of montmorillonite (MONT) under different heat treatment conditions was studied using the quartz crystal microbalance/heat conduction calorimetry (QCM/HCC) technique. Results showed that water sorption in neat polymer films and composite films increased with heat treatment temperature up to 120 °C. Differential scanning calorimetry was used to measure the glass‐transition temperature and isothermal crystallization kinetics of all samples. The mobility of the amorphous domain in all samples increased with heat treatment temperature, indicated by the decrease in glass‐transition temperature. PLA composites crystallized at a much faster rate than neat PLA did because MONT acted as a nucleating agent. Under the same heat treatment condition, water sorption in PLLA‐MONT composites was always higher than that in neat PLA due to the presence of the hydrophilic hydroxyl groups on the surface of MONT particles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

Quartz Microbalance Microcalorimetry: A new method for studying polymer-solvent thermodynamics

We have developed a sensitive method of determining enthalpy changes for gas-surface interactions: quartz microbalance microcalorimetry. We mount in an isoperibol environment both sample and reference combinations of a quartz crystal microbalance (QCM) in intimate thermal contact with a heat flow sensor. We coat the sample QCM with a thin (1 µm) polymer film. By exposing the film to ethanol vapor, we measure simultaneously the change in mass per unit area (to ±0.25 ng cm^–2) and the resulting heat flows (to ±50 nW) when the polymer adsorbs or desorbs ethanol. The molar enthalpies of sorption of ethanol vapor in Tecoflex, an aliphatic polyurethane elastomer, are _adsorptionH= –53±8 kJ mol^–1 and _desorptionH=52±3 kJ mol^–1.This revised version was published online in November 2005 with corrections to the Cover Date.     

A novel quartz crystal microbalance gas sensor based on porous film coatings. A high sensitivity porous poly(methylmethacrylate) water vapor sensor

We describe a novel and generally applicable approach for creating voids in films deposited on the surface of solid substrates. Such films are advantageous when a quartz crystal microbalance (QCM) is the basis of a sensor. We show that films with large void volumes produce more sensitive sensors than with the original film. Poly(methylmethacrylate) (PMMA) was used as the polymer layer deposited on a quartz crystal microbalance (QCM) to demonstrate our technique for the model system of water vapor analysis in flowing nitrogen gas. A film of pure PMMA on a QCM is a sensor for water vapor in a gas phase. A more sensitive sensor was created by dip coating QCM crystals into solutions containing mixtures of PMMA and poly(d,l-lactide) (PDLL) and then evaporating the solution films on the QCM crystals to form mixed polymer films of varying PDLL content. The PDLL was then removed from the mixed polymer films by exposure to a NaOH solution to form pure PMMA films having various void volumes. A leached PMMA film that originally contained 50% by weight PDLL had a 3.7 times larger QCM sensitivity for water vapor than a pure PMMA film.     

Molecular imprinted polymer coated QCM for the detection of nandrolone

An acoustic wave sensor coated with an artificial biomimetic recognition element has been developed to selectively screen for nandrolone in the liquid phase. A highly specific covalently imprinted polymer (MIP) was spin coated onto one electrode of a quartz crystal microbalance (QCM) as a thin permeable film. Selective rebinding of the nandrolone was observed as a frequency shift in the QCM for concentrations up to 0.2 ppm with the sensor binding shown to favour nandrolone over analogous compounds.     

Detecting cells on the surface of a silver electrode quartz crystal microbalance using plasma treatment and graft polymerization

This paper utilizes a silver electrode quartz crystal microbalance (QCM) mass sensor to detect the physiology of cells. This study also investigates the plasma surface modification of silver electrode QCMs through deposition of hexamethyldisilazane (HMDSZ) films as a protection film. To improve the cell growth, this paper also performs post-treatments by surface-grafting acrylic acid (AAc), acrylamide (AAm), and oxygen plasma treatment onto the QCM electrodes. Experimental results indicate that plasma deposition is a useful technique to protect the surface of silver electrodes. This technique extends the unpeeling time of silver electrodes from 1 to 7 days. The hydrophilic silver electrode QCM surface modified by AAm exhibited a better storage time effect than other post-treatments.     

Pathogen detection in complex samples by quartz crystal microbalance sensor coupled to aptamer functionalized core–shell type magnetic separation

A quartz crystal microbalance sensor (QCM) was developed for sensitive and specific detection of Salmonella enterica serovar typhimurium cells in food samples by integrating a magnetic bead purification system. Although many sensor formats based on bioaffinity agents have been developed for sensitive and specific detection of bacterial cells, the development of robust sensor applications for food samples remained a challenging issue. A viable strategy would be to integrate QCM to a pre-purification system. Here, we report a novel and sensitive high throughput strategy which combines an aptamer-based magnetic separation system for rapid enrichment of target pathogens and a QCM analysis for specific and real-time monitoring. As a proof-of-concept study, the integration of Salmonella binding aptamer immobilized magnetic beads to the aptamer-based QCM system was reported in order to develop a method for selective detection of Salmonella. Since our magnetic separation system can efficiently capture cells in a relatively short processing time (less than 10 min), feeding captured bacteria to a QCM flow cell system showed specific detection of Salmonella cells at 100 CFU mL⁻¹ from model food sample (i.e., milk). Subsequent treatment of the QCM crystal surface with NaOH solution regenerated the aptamer-sensor allowing each crystal to be used several times.     

Importance of trimethylaluminum diffusion in three-step ABC molecular layer deposition using trimethylaluminum, ethanolamine, and maleic anhydride

Hybrid organic-inorganic films were grown by molecular layer deposition (MLD) with a three-step ABC reaction sequence using (A) trimethylaluminum (TMA), (B) ethanolamine (EA), and (C) maleic anhydride (MA) at 90 °C. Very large steady state mass gains of 1854-4220 ng/(cm(2) cycle) were measured depending on reaction conditions. These mass gains are much larger than typical mass gains for surface reactions. The quartz crystal microbalance (QCM) mass profiles during the TMA reaction were consistent with TMA diffusion into and out of the ABC films. The ABC mass gains per cycle also displayed a strong dependence on the TMA dose and purge times that was consistent with the effects of TMA diffusion. Multiple dose experiments conducted at 130 °C revealed that the ABC reactions were self-limiting for thin ABC films. For thicker ABC films, increased TMA diffusion into the ABC film led to non-self-limiting behavior. Numerical modeling assuming Fickian diffusion for TMA diffusing into and out of the ABC film could fit the QCM mass profiles. The results all indicate that TMA diffusion into the ABC MLD film plays a key role in the thin film growth. In addition, X-ray reflectivity (XRR) measurements revealed that the ABC films were exceptionally smooth.     

Characterization of N-cyclohexylmethacrylamide LB thin films for room temperature vapor sensor application

This study reports the synthesis, characterization and gas sensing applications of N-cyclohexylmethacrylamide (NCMA) monomer material using FT-IR, ¹H and ¹³C NMR, UV-visible spectroscopy, Quartz Crystal Microbalance (QCM) and Langmuir-Blodgett (LB) thin film deposition techniques. The thin film deposition conditions of NCMA monomer material, which are prepared by LB film technique, are characterized by UV-visible spectroscopy and QCM system. The sensing behaviors of the LB film with respect to volatile organic compounds (VOCs) at room temperature are investigated. Surface pressure change as a function of surface area of NCMA molecule at the water surface shows a well-organized and stable monolayer at 18 mN m^?1 surface pressure value for LB film deposition. Transfer ratio values are found to be ≥ 0.94 for quartz glass and ≥ 0.93 for quartz crystal substrate. The typical frequency shift per layer is obtained 20.10 Hz/layer and the deposited mass onto a quartz crystal is calculated as 824.62 ng/layer. The sensing responses of the LB films against chloroform, dichloromethane, acetone, toluene, benzene and ethanol are measured by QCM system. The sensitivities of the NCMA LB film sensor are determined between 0.085 and 0.029 Hz ppm^?1. Sensitivities with detection limits are between 35.29 and 100.33 ppm against organic vapors. These results can be concluded that the monomer LB film sample is found to be significantly more sensitive to chloroform and dichloromethane vapors than others organic vapors used in this work. This material may find potential applications in the development of room temperature organic vapor sensing.     

Investigation by QCM of the Specific and Nonspecific Avidin Interaction onto a Biotinylated Polypyrrole Film

We have studied by gravimetric measurements using a quartz crystal microbalance (QCM), the adsorption of avidin onto a polypyrrole film. From QCM results, it appears that both the thickness and the redox state of polypyrrole strongly influence the avidin adsorption. This nonspecific interaction is larger for a thick film than for a thin one and, also for when the polymer is in its reduced state. We have also investigated by QCM the specific and nonspecific interaction of avidin onto biotinylated polypyrrole films having either a hydrophilic or hydrophobic character. It is shown that the amount of avidin immobilized by specific recognition is almost the same whatever the nature of the polymer matrix.     

Organic vapor sensing properties and characterization of α-naphthylmethacrylate LB thin films

Determination of organic vapor sensing properties of α-Naphthylmethacrylate (α-NMA) monomer based Langmuir-Blodgett (LB) thin films was aimed in this study. LB thin film fabrication was performed on quartz glass and quartz crystal substrates in order to investigate the characterization and organic vapor properties of α-NMA materials by using UV-Visible, Atomic Force Microscopy (AFM) and Quartz Crystal Microbalance (QCM) techniques. π-A isotherm graph was taken and a suitable surface pressure value were primarily determined as 13?mN m^?1 for successful α-NMA LB thin film fabrication. Transfer ratio value was found to be ≥ 0.93 for quartz glass and quartz crystal substrates. The typical frequency shift per layer was obtained as 16.93?Hz/layer and the deposited mass onto a quartz crystal was calculated as 271.30?ng/layer (1.02?ng mm^?2). The sensing responses of α-NMA LB films against dichloromethane, chloroform, toluene and m-xylene were measured by QCM system. Dichloromethane created the maximum shift in the resonance frequency than other organic vapors used in this study. Results exhibited that α-NMA LB thin films were potential candidates for organic vapor sensing applications, especially high sensitive detection of dichloromethane at room temperature.     

Preparation of functional ordered mesoporous carbons and their application as the QCM sensor with ultra-low humidity

Ordered mesoporous carbon (OMCs) FDU-15 was synthesized through an EISA (Evaporation-Induced Self-Assembly) method, and the oxidized OMCs (FDU-15-COOH) were obtained by subsequent oxidation treatments in liquid phase to introduce functional groups. The samples were characterized by XRD, TEM, FT-IR and nitrogen adsorption-desorption test. The low humidity sensing performances of FDU-15 and FDU-15-COOH thin films were investigated by using a quartz crystal microbalance (QCM) transducer. The responses of FDU-15-COOH is higher than that of the pristine FDU-15 at very low humidity (< 729 ppm_v) with high long-term stability, implying that FDU-15-COOH is a good candidate for low humidity QCM sensor.     

Validation of the mass response of a quartz crystal microbalance coated with Prussian Blue film for ac electrogravimetry

Prussian Blue (PB) films have been considerably studied for many research applications such as electrochromic material development, new material for batteries, etc. Many analytical techniques were employed for examining PB electrochemical behaviour in solution and the quartz crystal microbalance (QCM) used in the alternative regime (ac electrogravimetry) appeared as an attractive in situ mass sensor due to its low cost and its high mass sensitivity. Unfortunately, the validity of the common Sauerbrey equation was questionable with these films or in other terms if the QCM was used as a pure mass sensor. In this work PB film is examined through acoustic measurements and the response can be interpreted as a pure mass change if the thickness is around 0.15 μm. Over this limit, film viscoelastic contributions can affect drastically the mass change estimation: if the thickness is two times larger, the mass error reaches 40%.     

pH sensor based on polyaniline and aniline–anthranilic acid copolymer films using quartz crystal microbalance and electronic absorption spectroscopy

The pH sensitivity based on conducting polyaniline (PANI) and copolymer of aniline and o‐anthranilic acid (AA) films were studied using quartz crystal microbalance (QCM) technique and UV–Vis spectroscopy. The sensor was constructed from these polymer films coated on the electrode of the QCM. The resonant frequency changes as a function of pH in the range of 2–12 were measured. These changes are quantitative indication of the degree of dedoping or redoping of the polymer films upon the subsequent exposure of the electrode to 0.25 M sulfuric acid and different pH solutions. There are two linear regressions between the frequency change and pH with two different and opposite slopes in the regions from 2 to 9 and 9 to 12. The pH sensitivity of the copolymer film was found to be less than using the PANI film. Thin films of PANI and copolymer, which were chemically polymerized in a sulfuric acid solution, were deposited onto the inner walls of the quartz cuvettes. The UV–Vis absorption spectra of these films were measured in different pH solutions. Relations between the maximum absorption and its wavelength versus pH were constructed. The copolymer film shows some advantages over the PANI film. The difference between the PANI and copolymer films as pH sensors using the QCM and electronic absorption extends from the determination of pK_a for both films. Copyright © 2008 John Wiley & Sons, Ltd.     

Moisture absorption and absorption kinetics in polyelectrolyte films: influence of film thickness

Specular X-ray reflectivity (XR) and quartz crystal microbalance (QCM) measurements were used to determine the absorption of water into thin poly(4-ammonium styrenesulfonic acid) films from saturated vapor at 25 degrees C. The effect of film thickness on the absorption kinetics and overall absorption was investigated in the range of thickness from (3 to 200) nm. The equilibrium swelling of all the films irrespective of film thickness was (0.57+/-0.03) volume fraction. Although the equilibrium absorption is independent ofthickness, the absorption rate substantially decreases for film thickness < 100 nm. For the thinnest film (3 nm), there is a 5 orders of magnitude decrease in the diffusion coefficient for water.     

Quartz Crystal Microbalance Study of Q-State PbS Particle Formation in Lead Arachidate Langmuir-BIodgett Films

The formation of Q-state PbS particle in lead arachidate (PbAr) Langmuir-Blodgett films has been monitored using the quartz crystal microbalance (QCM) measurement. The study showed that the mass uptake of PbAr films with different thicknesses on exposure to hydrogen sulfide was consistent with that expected for the quantitative conversion of Pb²⁺ in the films to PbS and the corresponding conversion of PbAr to arachidic acid. Mass uptake measurement on PbAr films extensively exposed to H₂S gas showed the arachidic acid molecules left after Q-state particle formation could be quantitatively converted to PbAr by immersing the film in a stirred aqueous solution containing lead ions. Subsequent reexposure of the film to H₂S increases the mole fraction of PbS in the film.     

Quartz crystal microbalance monitoring of density changes in mesoporous TiO2 phytate films during redox and ion exchange processes

Nanofilm deposits of TiO₂ nanoparticle phytates are formed on gold electrode surfaces by ‘directed assembly’ methods. Alternate exposure of a 3-mercapto-propionic acid modified gold surface to (i) a TiO₂ sol and (ii) an aqueous phytic acid solution (pH 3) results in layer-by-layer formation of a mesoporous film. Ru(NH₃)₆³⁺ is shown to strongly adsorb/accumulate into the mesoporous structure whilst remaining electrochemically active. Scanning the electrode potential into a sufficiently negative potential range allows the Ru(NH₃)₆³⁺ complex to be reduced to Ru(NH₃)₆²⁺ which undergoes immediate desorption. When applied to a gold coated quartz crystal microbalance (QCM) sensor, electrochemically driven adsorption and desorption processes in the mesoporous structure become directly detectable as a frequency response, which corresponds directly to a mass or density change in the membrane. The frequency response (at least for thin films) is proportional to the thickness of the mass-responsive film, which suggests good mechanical coupling between electrode and film. Based on this observation, a method for the amplified QCM detection of small mass/density changes is proposed by conducting measurements in rigid mesoporous structures.     

Different experimental results for the influence of immersion angle on the resonant frequency of a quartz crystal microbalance in a liquid phase: with a comment

This paper presents different experimental results of the influence of an immersion angle (θ, the angle between the surface of a quartz crystal resonator and the horizon) on the resonant frequency of a quartz crystal microbalance (QCM) sensor exposed one side of its sensing surfaces to liquid. The experimental results show that the immersion angle is an added factor that may influence the frequency of the QCM sensor. This type of influence is caused by variation of the reflection conditions of the longitudinal wave between the QCM sensor and the walls of the detection cell. The frequency shifts, measured by varying θ, are related to the QCM sensor used. When a QCM sensor with a weak longitudinal wave is used, its resonant frequency is nearly independent of θ. But, if a QCM sensor with a strong longitudinal wave is employed, the immersion angle is a potential error source for the measurements performed on the QCM sensor. When the reflection conditions of the longitudinal wave are reduced, the influence of θ on the resonant frequency of the QCM sensor is negligible. The slope of the plot of frequency shifts (ΔF) versus (ρη)^1/2, the square root of the product of solution density (ρ) and viscosity (η), may be influenced by θ in a single experiment for the QCM sensor with a strong longitudinal wave in low viscous liquids, which can however, be effectively weakened by using the averaged values of reduplicated experiments. In solutions with a large (ρη)^1/2 region (0-55 wt% sucrose solution as an example, with ρ value from 1.00 to 1.26 g cm⁻³ and η value from 0.01 to 0.22 g cm⁻¹ s⁻¹, respectively), the slope of the plot of ΔF versus (ρη)^1/2 is independent of θ even for the QCM sensor with a strong longitudinal wave in a single experiment. The influence of θ on the resonant frequency of the QCM sensor should be taken into consideration in its applications in liquid phase.     

QCM studies of gel spreading: Kraton gels on polystyrene surfaces

Contact of a polymer gel made from a styrene/ethylene-butene/styrene triblock copolymer in mineral oil was investigated by bringing the gel into contact with the coated surface of a quartz crystal microbalance (QCM). The experimental apparatus enabled simultaneous measurement of the load, displacement, and contact area, in addition to the resonant frequency and dissipation of the oscillating quartz crystal. The QCM response was determined by the linear viscoelastic properties of the gel at the frequency of oscillation. A geometric correction factor involving the contact area provided a means for quantitatively determining these viscoelastic parameters as the gel spread over the QCM surface. When the gel was removed from the surface, a thin solvent layer was left behind. The thickness of this solvent layer was determined from the QCM response and was compared to predictions from a simple model involving the disjoining pressure of the film and the osmotic pressure of the gel. Qualitative agreement with the model required that tensile, adhesive forces at the perimeter of the gel/QCM contact area were taken into account when calculating the film thickness.