Studying adsorbent dynamics on a quartz crystal resonator using its nonlinear electrical response

The quartz crystal resonator has been traditionally employed in studying surface-confined physisorbed films and particles by measuring dissipation and frequency shifts. However, theoretical interpretation of the experimental observations is often challenged due to limited understanding of physical interaction mechanisms at the interfaces involved. Here we model a physisorbed interaction between particles and gold electrode surface of a quartz crystal and demonstrate how the nonlinear modulation of the electric response of the crystal due to the nonlinear interaction forces may be used to study the dynamics of the particles. In particular, we show that the graphs of the deviation in the third Fourier harmonic response versus oscillation amplitude provide important information about the onset, progress and nature of sliding of the particles. The graphs also present a signature of the surface-particle interaction and could be used to estimate the interaction energy profile. Interestingly, the insights gained from the model help to explain some of the experimental observations with physisorbed streptavidin-coated polystyrene microbeads on quartz resonators. © 2012 Elsevier B.V. All rights reserved

Anharmonic acoustic effects during DNA hybridization on an electrochemical quartz crystal resonator

The paper describes a sensor for single-stranded DNA (ssDNA) biomarker based on anharmonic acoustic signals arising during hybridization with complementary thiolated ssDNA functionalised on the gold electrode of an electrochemical quartz crystal resonator. The steps of sensor preparation and hybridization are carried out in an electrochemical microfluidic flowcell. While the electrochemical impedance spectroscopy does not allow a definitive interpretation, the changes in resonance frequency and third Fourier harmonic current of the resonator on actuation at the fundamental mode indicate formation of a flexibly bound layer. The functionalization and hybridization steps monitored by the anharmonic detection technique (ADT) are described with a simple model based on Duffing nonlinear equation

Probing biomolecular interaction forces using an anharmonic acoustic technique for selective detection of bacterial spores

Receptor-based detection of pathogens often suffers from non-specific interactions, and as most detection techniques cannot distinguish between affinities of interactions, false positive responses remain a plaguing reality. Here, we report an anharmonic acoustic based method of detection that addresses the inherent weakness of current ligand dependant assays. Spores of Bacillus subtilis (Bacillus anthracis simulant) were immobilized on a thickness-shear mode AT-cut quartz crystal functionalized with anti-spore antibody and the sensor was driven by a pure sinusoidal oscillation at increasing amplitude. Biomolecular interaction forces between the coupled spores and the accelerating surface caused a nonlinear modulation of the acoustic response of the crystal. In particular, the deviation in the third harmonic of the transduced electrical response versus oscillation amplitude of the sensor (signal) was found to be significant. Signals from the specifically-bound spores were clearly distinguishable in shape from those of the physisorbed streptavidin-coated polystyrene microbeads. The analytical model presented here enables estimation of the biomolecular interaction forces from the measured response. Thus, probing biomolecular interaction forces using the described technique can quantitatively detect pathogens and distinguish specific from non-specific interactions, with potential applicability to rapid point-of-care detection. This also serves as a potential tool for rapid force-spectroscopy, affinity-based biomolecular screening and mapping of molecular interaction networks. © 2011 Elsevier B.V

Simple and ultrafast resonance frequency and dissipation shift measurements using a fixed frequency drive

A new method for determination of resonance frequency and dissipation of a mechanical oscillator is presented. Analytical expressions derived using the Butterworth-Van Dyke equivalent electrical circuit allow the determination of resonance frequency and dissipation directly from each impedance datapoint acquired at a fixed amplitude and frequency of drive, with no need for numerical fitting or measurement dead time unlike the conventional impedance or ring-down analysis methods. This enables an ultrahigh time resolution and superior noise performance with relatively simple instrumentation. Quantitative validations were carried out successfully against the impedance analysis method for inertial and viscous loading experiments on a 14.3 MHz quartz crystal resonator (QCR). Resonance frequency shifts associated with the transient processes of quick needle touches on a thiol self-assembled-monolayer functionalised QCR in liquid were measured with a time resolution of 112 μs, which is nearly two orders of magnitude better than the fastest reported quartz crystal microbalance. This simple and fast fixed frequency drive (FFD) based method for determination of resonance frequency and dissipation is potentially more easily multiplexable and implementable on a single silicon chip delivering economies of scale

Characterisation of particle-surface interactions via anharmonic acoustic transduction

Most transduction methods for measuring particle-surface interactions are unable to differentiate the strength of interaction and largely reliant on extensive washing to reduce the ubiquitous non-specific background. Label-based methods, in particular, are limited in wide applicability due to their inherent operational complexity. On the other hand, label-free force-spectroscopic methods that can differentiate particle-surface interaction strength are skill-demanding and time-consuming. Here, we present a label-free anharmonic (nonlinear) acoustic transduction method employing the quartz crystal resonator that reads out ligand-receptor binding based on the interaction strength. We show that while stronger specific interactions are transduced more strongly, and in linear proportionality to the ligand concentration on microparticles, non-specific interactions are significantly attenuated. This allows ligand quantification with high specificity and sensitivity in realtime under flow without separate washing steps. Constructing an analytical model of a quartz resonator, we can relate the number and type (specific vs. non-specific) of ligand-receptor interactions with the change in characteristic nonlinearity coefficient of the resonator. The entirely-electronic and microfluidic-integrable transduction method could potentially allow a simple, fast and reliable way for characterising particle-surface interactions with economy of scale

Using gamification and flipped classroom for remote/virtual labs for engineering students

Providing students with a virtual and remotely accessible version of in-person labs as well as virtual and interactive tutoring is a continuous challenge during the pandemic. The paper outlines the design, development, and implementation of 6 virtual experiments for mechanical engineering students, which combines gamification principles and flipped classroom. The virtual labs allow the students to measure the data from the experiment as they would in reality. Instead of having a lecturer showing how to calculate the results based on an example, the students are guided through the theory like a computer game. The game has a step-by-step process which allows the student to find the correct solution themselves. The more they progress through the game the fewer guides and hints they receive. While at the beginning the students answer simple multiple-choice questions, later the students’ progress to “minigames” where they place building blocks into the correct position to build an equation or a Freebody/kinetic diagram. The paper evaluates the feedback received from the students as well as compares this with the in-person version of the lab. The paper explores the option to adapt existing software to create a low-cost gamification and flipped classroom experience

Comparison of in-person and virtual labs/tutorials for engineering students using blended learning principles

The paper compares the effectiveness of in-person and virtual engineering laboratory sessions. The in-person and virtual laboratory sessions reported here comprise six experiments combined with short tutorials. The virtual lab combined enquiry-based learning and gamification principles. The integration of the virtual labs with in-person teaching created a blended learning environment. The effectiveness of this approach was assessed based on (i) the student feedback (i.e., a questionnaire with open-ended questions and Likert scale feedback), (ii) the students’ engagement with the virtual lab, and (iii) the impact on the academic performance (i.e., class test results). The students reported greater confidence in the understanding of theory in the virtual lab than the in-person lab. This is interesting given that the instruction for the virtual lab and the in-person lab of one experiment is identical (i.e., same instructor, same enquiry-based learning techniques, and same explanations). The students also appreciated the ability to complete the virtual lab anytime, anywhere, for as long as they needed, and highlighted the benefits of the interactivity. The median class test scores of the students who completed some or all the virtual lab experiments was higher than those who did not (83–89% vs. 67%)

Anharmonic surface interactions for biomolecular screening and characterization

The acoustic response of conventional mechanical oscillators, such as a piezoelectric crystal, is predominantly harmonic at modest amplitudes. However, here, we observe from the electrical response that significant motional anharmonicity is introduced in the presence of attached analyte. Experiments were conducted with streptavidin-coated polystyrene microbeads of various sizes attached to a quartz crystal resonator via specific and nonspecific molecular tethers in liquid. Quantitative analysis reveals that the deviation of odd Fourier harmonics of the response caused by introduction of microbeads as a function of oscillation amplitude presents a unique signature of the molecular tether. Hence, the described anharmonic detection technique (ADT) based on this function allows screening of biomolecules and provides an additional level of selectivity in receptor-based detection that is often associated with nonspecific interactions. We also propose methods to extract mechanical force-extension characteristics of the molecular tether and activation energy using this technique. © 2010 American Chemical Society

Anharmonic interaction signals for acoustic detection of analyte

The challenges with frequency-based acoustic detection systems in sensitive, selective, and reliable quantitative estimation of surface-bound analyte are well-known. These systems are traditionally used in their linear incarnations; i.e., the measurement frequency is the same as the driving frequency. However, it was found in this work that interactions of adsorbents with sensor surface show significant anharmonicity even at low drive amplitudes. In particular, using streptavidin-coated polystyrene microbeads on an oscillating quartz surface in air, it has been demonstrated through modeling and experiments that the anharmonic signal from microparticle to surface interaction is significantly higher relative to that from bare quartz and orders of magnitude higher than relative shifts in resonant frequency. The signal is proportional to the number of microparticles and holds a well-defined functional relationship with the amplitude of oscillation, distinct to the nature of interaction with the surface for a given analyte. This approach, thus, can be used for ultrasensitive and quantitative detection of surface adsorbents and characterization of different kinds of surface interactions, distinguishing specific from nonspecific adsorbents. The modeling also reveals a direct functional relationship between the measured anharmonic signal and the interaction potential of the adsorbent with the surface. © 2010 American Chemical Society

Simpler and faster quartz crystal microbalance for macromolecule detection using fixed frequency drive

Despite advancements in analytical technologies, their complexity and cost have largely restricted their application in scalable online or multiplexed measurements. Here we report a quartz crystal resonator (QCR)-based method for detection of macromolecules that allows immensely simpler and faster measurements by employing for the first time a fixed frequency drive (FFD) and analytical expressions of acoustic parameters. Using human immunoglobulin E (hIgE) as an exemplar macromolecule and an anti-hIgE aptamer functionalised on a QCR, quantitative accuracy was benchmarked against the traditional impedance analysis method. The ability of FFD to capture data over longer observation periods at significantly higher acquisition rates at a fixed amplitude showed improvement in the QCR’s sensitivity and specificity of transduction. The foundations for low-cost and low-power online integration and large-scale multiplexability are also discussed