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Small molecule detection is of wide interest in clinical and industrial applications. However, its accessibility is still limited as miniaturisation and system integration is challenged in reliability, costs and complexity. Here we combined a 14.3 MHz quartz crystal resonator (QCR), actuated and analysed using a fixed frequency drive (FFD) method, with a nanomolecular imprinted polymer for label-free, realtime detection of N-hexanoyl-L-homoserine lactone (199 Da), a gram-negative bacterial infection biomarker. The lowest concentration detected (1 mu M) without any optimisation was comparable with that of a BIAcore SPR system, an expensive laboratory gold standard, with significant enhancement in sensitivity and specificity beyond the state-of-the-art QCR. The analytical formula-based FFD method can potentially allow a multiplexed "QCR-on-chip" technology, bringing a paradigm shift in speed, accessibility and affordability of small molecule detection., QC 20200525

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., QC 20181129

Introduction: Quartz crystal microbalance (QCM) is commonly used to study biomolecular binding by measuring shifts in resonance frequency of a quartz-crystal-oscillator. However, the currently used methods like impedance analysis or QCM-D, which require repeated sweeps or ringing, are limited in time resolution (~1 second) due to the need for averaging. This restricts our ability to study transient biomolecular processes, which occur in sub-millisecond time scale. A novel technique has been reported here that allows quantification of resonance frequency of a quartz-crystal-oscillator with significantly improved time resolution by driving and measuring continuously at a constant frequency within the resonance bandwidth. Method: The reactive component of the experimentally obtained impedance is utilized for the estimation of resonance frequency from the Butterworth Van-dyke (BVD) model of a quartz-crystal-oscillator, assuming that changes in motional inductance and capacitance around resonance are negligible. Triplicate sets of experiments involving the binding of streptavidin with a biotin functionalized 14.3 MHz quartz oscillator surface were performed. Intermittent frequency sweeps and fixed frequency drives, both of 0.1 second duration and around 14.3 MHz, were taken at intervals of 2 minutes under the flow of phosphate-buffer-saline (PBS buffer) before and after injection of streptavidin. Results: The average shift in resonance frequency from the baseline (measurements before streptavidin injection) due to streptavidin-biotin binding, calculated from the fixed frequency drive or FFD (148 Hz) was within 1% of that estimated from the frequency sweep method by fitting the experimentally recorded impedance employing the BVD model (149 Hz). Discussion: The agreement of the FFD with conventional frequency sweep method suggests that protein binding can be quantified with reasonable accuracy from each impedance data point, which with our set-up is recorded at 30 kHz s, QC 20190522