Anharmonic Surface Interactions for Biomolecular Screening and Characterization

Abstract

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.

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

“…Although the degree of non-complementarity of the sequences was not investigated as part of this work, and it is possible that the random sequence had some degree of affinity towards the receptor sequence, the specificity using the third harmonic signal is comparatively much better. Improved specificity in transduction using third harmonic shift signal agrees with that observed in our previous work [7,8,22].…”

“…Therefore, although the EQCM offers a direct and rapid platform for measurement, there is a need for an improved method for quantification of flexible adsorbate, such as ssDNA. An anharmonic detection technique, or ADT, has been reported recently to overcome the abovementioned issues and measure flexible adsorbates, such as microparticles, with a strong quantitative correlation and transduction specificity [7][8][9][10]. A QCM is largely linear at modest amplitudes, i.e.…”

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

“…This deviation can be measured in practice to detect the presence of surface-bound particles 10,11 . To be able to understand this nonlinear modulation of the electrical current due to the surface-adsorbent interactions, we have attempted to model the case of a particle physisorbed on a gold electrode of a quartz crystal resonator with a single point of contact (Figure 1a).…”

Characterisation of particle-surface interactions via anharmonic acoustic transduction

“…Quartz crystal resonators have been widely used for label-free quantification of biomolecular binding 5 . Quartz crystals are commonly driven close to their fundamental or higher modes of resonance.…”

“…In our earlier work, the quartz crystal was driven close to its fundamental resonance mode and the electrical current was measured exactly at three times the drive frequency (3f), referred to as the third Fourier harmonic 5,8 . It should be noted that the third Fourier harmonic is a result of nonlinear response of an oscillator and may be present even in an oscillator with a single-mode of resonance, such as a spring-mass oscillatory system.…”