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.

Generation of 63-nJ pulses from a fiber oscillator modelocked by nanotubes

We mode-lock a fiber oscillator with cavity length of ~1500m using nanotubes, achieving 1.55ps pulses with pulse energy up to 63nJ at 134 KHz repetition rate. © 2010 Optical Society of America.

Phase noise analysis of a mechanical autonomous impact oscillator with a MEMS resonator

In this paper, phase noise analysis of a mechanical autonomous impact oscillator with a MEMS resonator is performed. Since the circuit considered belongs to the class of hybrid systems, methods based on the variational model for the evaluation of either phase noise or steady state solutions cannot be directly applied. As a matter of fact, the monodromy matrix is not defined at impact events in these systems. By introducing saltation matrices, this limit is overcome and the aforementioned methods are extended. In particular, the unified theory developed by Demir is used to analyze the phase noise after evaluating the asymptotically stable periodic solution of the system by resorting to the shooting method. Numerical results are presented to show how noise sources affect the phase noise performances. © 2011 IEEE.

Modelling non-linearities in a MEMS square wave oscillator

The modelling of the non-linear behaviour of MEMS oscillators is of interest to understand the effects of non-linearities on start-up, limit cycle behaviour and performance metrics such as output frequency and phase noise. This paper proposes an approach to integrate the non-linear modelling of the resonator, transducer and sustaining amplifier in a single numerical modelling environment so that their combined effects may be investigated simultaneously. The paper validates the proposed electrical model of the resonator through open-loop frequency response measurements on an electrically addressed flexural silicon MEMS resonator driven to large motional amplitudes. A square wave oscillator is constructed by embedding the same resonator as the primary frequency determining element. Measurements of output power and output frequency of the square wave oscillator as a function of resonator bias and driving voltage are consistent with model predictions ensuring that the model captures the essential non-linear behaviour of the resonator and the sustaining amplifier in a single mathematical equation. © 2012 IEEE.

Matching an oscillator model to a phase response curve

The Phase Response Curve (PRC) has proven a useful tool for the reduction of complex oscillator models. It is also an information often experimentally available to the biologist. This paper introduces a numerical tool based on the sensitivity analysis of the PRC to adapt initial model parameters in order to match a particular PRC shape. We illustrate the approach on a simple biochemical model of circadian oscillator. © 2011 IEEE.

Controlling the phase of an oscillator: A phase response curve approach

The paper discusses elementary control strategies to control the phase of an oscillator. Both feedforward and feedback (P and PI) control laws are designed based on the phase response curve (PRC) calculated from the linearized model. The performance is evaluated on a popular model of circadian oscillations. ©2009 IEEE.