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

Supplementary information files for article: 'Simple and ultrafast resonance frequency and dissipation shift measurements using a fixed frequency drive'

Supplementary information files for article: '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

Direct detection of small molecules using a nano-molecular imprinted polymer receptor and a quartz crystal resonator driven at a fixed frequency and amplitude

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 µM) 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.</p