Parametric Amplifiers Based on Quantum Dots.

Josephson parametric amplifiers (JPAs) approaching quantum-limited noise performance have been instrumental in enabling high fidelity readout of superconducting qubits and, recently, semiconductor quantum dots (QDs). We propose that the quantum capacitance arising in electronic two-level systems (the dual of Josephson inductance) can provide an alternative dissipationless nonlinear element for parametric amplification. We experimentally demonstrate phase-sensitive parametric amplification using a QD-reservoir electron transition in a CMOS nanowire split-gate transistor embedded in a 1.8 GHz superconducting lumped-element microwave cavity, achieving parametric gains of -3 to +3 dB, limited by Sisyphus dissipation. Using a semiclassical model, we find an optimized design within current technological capabilities could achieve gains and bandwidths comparable to JPAs, while providing complementary specifications with respect to integration in semiconductor platforms or operation at higher magnetic fields.

Towards Portable MEMS Oscillators for Sensing Nanoparticles.

This paper reports on the design, and implementation of piezoelectric-on-silicon MEMS resonators installed within a portable experimental setup for sensing nanoparticles in a laboratory environment. MEMS oscillators with a center frequency of approximately 5.999 MHz are employed for sensing 50 nm size-selected silver nanoparticles generated in the laboratory. The same experimental setup is then assembled to sense indoor particles that are present in the laboratory environment. The challenges associated with particle deposition as a result of assembling the portable experimental setup is highlighted. Furthermore, the MEMS oscillators demonstrate that the total mass of silver nanoparticles deposited onto the MEMS resonator surface using the inertial impaction technique-based experimental setup is approximately 7.993 nanograms. The total indoor particle mass accumulated on the MEMS resonator surface is estimated to be approximately 1.732 nanograms and 26.9 picograms for two different runs. The frequency resolution of the MEMS oscillator is estimated to be approximately 32 ppb and, consequently, the minimum detectable particle mass is approximately 60 femtograms for a 9.2 s integration time.

Weakly Coupled Piezoelectric MEMS Resonators for Aerosol Sensing.

This paper successfully demonstrates the potential of weakly coupled piezoelectric MEMS (Micro-Electro-Mechanical Systems) gravimetric sensors for the detection of ultra-fine particulates. As a proof-of-principle, the detection of diesel soot particles of 100 nanometres or less is demonstrated. A practical monitoring context also exists for diesel soot particles originating from combustion engines, as they are of serious health concern. The MEMS sensors employed in this work operate on the principle of vibration mode-localisation employing an amplitude ratio shift output metric for readout. Notably, gains are observed while comparing parametric sensitivities and the input referred stability for amplitude ratio and resonant frequency variations, demonstrating that the amplitude ratio output metric is particularly suitable for long-term measurements. The soot particle mass directly estimated using coupled MEMS resonators can be correlated to the mass, indirectly estimated using the condensation particle counter used as the reference instrument.

Measuring Aerosol Phase Changes and Hygroscopicity with a Microresonator Mass Sensor.

The interaction between atmospheric aerosol particles and water vapor influences aerosol size, phase, and composition, parameters which critically influence their impacts in the atmosphere. Methods to accurately measure aerosol water uptake for a wide range of particle types are therefore merited. We present here a new method for characterizing aerosol hygroscopicity, an impaction stage containing a microelectromechanical systems (MEMS) microresonator. We find that deliquescence and efflorescence relative humidities (RHs) of sodium chloride and ammonium sulfate are easily diagnosed via changes in resonant frequency and peak sharpness. These agree well with literature values and thermodynamic models. Furthermore, we demonstrate that, unlike other resonator-based techniques, full hygroscopic growth curves can be derived, including for an inorganic-organic mixture (sodium chloride and malonic acid) which remains liquid at all RHs. The response of the microresonator frequency to temperature and particle mechanical properties and the resulting limitations when measuring hygroscopicity are discussed. MEMS resonators show great potential as miniaturized ambient aerosol mass monitors, and future work will consider the applicability of our approach to complex ambient samples. The technique also offers an alternative to established methods for accurate thermodynamic measurements in the laboratory.

Dynamic monitoring of single cell lysis in an impedance-based microfluidic device.

A microfluidic device that is capable of trapping and sensing dynamic variations in the electrical properties of individual cells is demonstrated. The device is applied to the real-time recording of impedance measurements of mouse embryonic stem cells (mESCs) during the process of membrane lysis, with the resulting changes in the electrical properties of cells during this process being quantitatively tracked over time. It is observed that the impedance magnitude decreases dramatically after cell membrane lysis. A significant shift in the phase spectrum is also observed during the time course of this process. By fitting experimental data to physical models, the electrical parameters of cells can be extracted and parameter variations quantified during the process. In the cell lysis experiments, the equivalent conductivity of the cell membrane is found to increase significantly due to pore formation in the membrane during lysis. An increase in the specific capacitance of the membrane is also observed. On the other hand, the conductivity of the cytoplasm is observed to decrease, which may be explained the fact that excess water enters the cell through the gradual permeabilization of the membrane during lysis. Cells can be trapped in the device for periods up to several days, and their electrical response can be monitored by real-time impedance measurements in a label-free and non-invasive manner. Furthermore, due to the highly efficient single cell trapping capacity of the device, a number of cells can be trapped and held in separate wells for concurrent parallel experiments, allowing for the possibility of stepped parametric experiments and studying cell heterogeneity by combining measurements across the array.

Comparison of the specificity and affinity of surface immobilised Affimer binders using the quartz crystal microbalance.

To enable multiplexed protein analysis through the use of microarrays, reliable molecules capable of specifically binding to a protein of interest with high affinity are required. Further, this specificity and affinity must be retained upon immobilization to the microarray surface. This study investigates the performance of surface bound Affimer proteins, comparing the affinity and specificity of different binders for closely related immunoglobulin molecules using the quartz crystal microbalance with dissipation monitoring (QCM-D). It is demonstrated that the surface bound Affimer proteins are highly specific, differentiating between their target IgG and other closely related IgG subclasses. The binding affinities of the protein aptamers for their target IgG molecules are determined to be in the nanomolar range, comparable to typical antibody-antigen binding affinities. While measurements herein are done using QCM-D, the high specificity and binding affinities of the surface bound Affimer proteins opens applications in a range of microarray biosensors.

A microfluidic platform for trapping, releasing and super-resolution imaging of single cells.

A multi-layer device, combining hydrodynamic trapping with microfluidic valving techniques, has been developed for on-chip manipulation and imaging of single cells and particles. Such a device contains a flow layer with trapping channels to capture single particles or cells and a control layer with valve channels to selectively control the trap and release processes. Particles and cells have been successfully trapped and released using the proposed device. The device enables the trapping of single particles with a trapping efficiency of greater than 95%, and allows for single particles and cells to be trapped, released and manipulated by simply controlling corresponding valves. Moreover, the trap and release processes are found to be compatible with biological samples like cells. Our device allows stable immobilisation of large numbers of single cells in a few minutes, significantly easing the experiment setup for single-cell characterisation and offering a stable platform for both single-molecule and super-resolution imaging. Proof-of-concept super- resolution imaging experiments with mouse embryonic stem cells (mESCs) have been conducted by exploiting super-resolution photoactivated localisation microscopy (PALM). Cells and nuclei were stably trapped and imaged. Centromeres of ∼200 nm size could be identified with a localisation precision of <15 nm.

Observation of locked phase dynamics and enhanced frequency stability in synchronized micromechanical oscillators.

Even though synchronization in autonomous systems has been observed for over three centuries, reports of systematic experimental studies on synchronized oscillators are limited. Here, we report on observations of internal synchronization in coupled silicon micromechanical oscillators associated with a reduction in the relative phase random walk that is modulated by the magnitude of the reactive coupling force between the oscillators. Additionally, for the first time, a significant improvement in the frequency stability of synchronized micromechanical oscillators is reported. The concept presented here is scalable and could be suitably engineered to establish the basis for a new class of highly precise miniaturized clocks and frequency references.

Electrical actuation and readout in a nanoelectromechanical resonator based on a laterally suspended zinc oxide nanowire.

In this paper, we present experimental results describing enhanced readout of the vibratory response of a doubly clamped zinc oxide (ZnO) nanowire employing a purely electrical actuation and detection scheme. The measured response suggests that the piezoelectric and semiconducting properties of ZnO effectively enhance the motional current for electromechanical transduction. For a doubly clamped ZnO nanowire resonator with radius ~10 nm and length ~1.91 µm, a resonant frequency around 21.4 MHz is observed with a quality factor (Q) of ~358 in vacuum. A comparison with the Q obtained in air (~242) shows that these nano-scale devices may be operated in fluid as viscous damping is less significant at these length scales. Additionally, the suspended nanowire bridges show field effect transistor (FET) characteristics when the underlying silicon substrate is used as a gate electrode or using a lithographically patterned in-plane gate electrode. Moreover, the Young's modulus of ZnO nanowires is extracted from a static bending test performed on a nanowire cantilever using an AFM and the value is compared to that obtained from resonant frequency measurements of electrically addressed clamped­clamped beam nanowire resonators.

Mode-localized accelerometer in the nonlinear Duffing regime with 75 ng bias instability and 95 ng/√Hz noise floor.

Mode-localized sensors have attracted attention because of their high parametric sensitivity and first-order common-mode rejection to temperature drift. The high-fidelity detection of resonator amplitude is critical to determining the resolution of mode-localized sensors where the measured amplitude ratio in a system of coupled resonators represents the output metric. Operation at specific bifurcation points in a nonlinear regime can potentially improve the amplitude bias stability; however, the amplitude ratio scale factor to the input measurand in a nonlinear regime has not been fully investigated. This paper theoretically and experimentally elucidates the operation of mode-localized sensors with respect to stiffness perturbations (or an external acceleration field) in a nonlinear Duffing regime. The operation of a mode-localized accelerometer is optimized with the benefit of the insights gained from theoretical analysis with operation in the nonlinear regime close to the top critical bifurcation point. The phase portraits of the amplitudes of the two resonators under different drive forces are recorded to support the experimentally observed improvements for velocity random walk. Employing temperature control to suppress the phase and amplitude variations induced by the temperature drift, 1/f noise at the operation frequency is significantly reduced. A prototype accelerometer device demonstrates a noise floor of 95 ng/√Hz and a bias instability of 75 ng, establishing a new benchmark for accelerometers employing vibration mode localization as a sensing paradigm. A mode-localized accelerometer is first employed to record microseismic noise in a university laboratory environment.

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.

On Weakly Coupled Resonant MEMS Transducers Operating in the Modal Overlap Regime.

Miniaturized physical transducers based on weakly coupled resonators have previously demonstrated the twin benefits of high parametric sensitivity and the first-order common-mode rejection of environmental effects. Current approaches to sensing based on coupled resonator transducers employ strong coupling where the modal overlap of the responses is avoided. This strong coupling limits the sensitivity for such mode-localized sensors that utilize an amplitude ratio (AR) output metric as opposed to tracking resonant frequency shifts. In this article, this limitation is broken through by theoretically and experimentally demonstrating the operation of the weakly coupled resonators in the weak-coupling (modal overlap) regime. Especially, a prototype microelectromechanical systems (MEMS) sensor based on this principle is employed to detect shifts in stiffness, with a stiffness bias instability of [Formula: see text]/m (9.5 ppb) and a corresponding noise floor of [Formula: see text]/m/ √ Hz (6.8 ppb/ √ Hz). The linear dynamic range of such AR readout sensors is first explored and found to be defined by the dynamic range of the secondary resonator. The proposed method provides a promising approach for high-performance resonant force and inertial sensors.

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.

Transduction dependent optimization of electromechanical parameters for electrostatically actuated MEMS/NEMS resonators.

This paper demonstrates an accurate model to predict the overall effective mass in micro- and nanomechanical resonators with non-uniform deformation along the transduction area. The model is verified experimentally through parameter extraction on various types of resonators with an error less than 3% well within the bounds dictated by manufacturing tolerances. Based on the model, an optimization of transduction electrode designs is proposed for micro- and nanomechanical resonators vibrating in the fabrication plane.

A vibrating beam MEMS accelerometer for gravity and seismic measurements.

This paper introduces a differential vibrating beam MEMS accelerometer demonstrating excellent long-term stability for applications in gravimetry and seismology. The MEMS gravimeter module demonstrates an output Allan deviation of 9 µGal for a 1000 s integration time, a noise floor of 100 µGal/√Hz, and measurement over the full ±1 g dynamic range (1 g = 9.81 ms-2). The sensitivity of the device is demonstrated through the tracking of Earth tides and recording of ground motion corresponding to a number of teleseismic events over several months. These results demonstrate that vibrating beam MEMS accelerometers can be employed for measurements requiring high levels of stability and resolution with wider implications for precision measurement employing other resonant-output MEMS devices such as gyroscopes and magnetometers.

Thermoelastic dissipation in MEMS/NEMS flexural mode resonators.

Understanding the energy dissipation mechanisms in single-crystal silicon MEMS/NEMS resonators are particularly important to maximizing an important figure of merit relevant for miniature sensor and signal processing applications: the Quality factor (Q) of resonance. This paper discusses thermoelastic dissipation (TED) as the dominant internal-friction mechanism in flexural mode MEMS/NEMS resonators. Criteria for optimizing the geometrical design of flexural mode MEMS/NEMS resonators are theoretically established with a view towards minimizing the TED for single-crystal silicon MEMS/NEMS flexural mode resonators.

Closed-Loop Characterization of Noise and Stability in a Mode-Localized Resonant MEMS Sensor.

This paper presents results from the closed-loop characterization of an electrically coupled mode-localized sensor topology including measurements of amplitude ratios over a long duration, stability, noise floor, and the bandwidth of operation. The sensitivity of the prototype sensor is estimated to be -5250 in the linear operation regime. An input-referred stability of 84 ppb with respect to normalized stiffness perturbations is achieved at 500 s. When compared to frequency shift sensing within the same device, amplitude ratio sensing provides higher resolution for long-term measurements due to the intrinsic common-mode rejection properties of a mode-localized system. A theoretical framework is established to quantify noise floor associated with measurements validated through numerical simulations and experimental data. In addition, the operating bandwidth of the sensor is found to be 3.5 Hz for 3-dB flatness.

Dynamic modulation of modal coupling in microelectromechanical gyroscopic ring resonators.

Understanding and controlling modal coupling in micro/nanomechanical devices is integral to the design of high-accuracy timing references and inertial sensors. However, insight into specific physical mechanisms underlying modal coupling, and the ability to tune such interactions is limited. Here, we demonstrate that tuneable mode coupling can be achieved in capacitive microelectromechanical devices with dynamic electrostatic fields enabling strong coupling between otherwise uncoupled modes. A vacuum-sealed microelectromechanical silicon ring resonator is employed in this work, with relevance to the gyroscopic lateral modes of vibration. It is shown that a parametric pumping scheme can be implemented through capacitive electrodes surrounding the device that allows for the mode coupling strength to be dynamically tuned, as well as allowing greater flexibility in the control of the coupling stiffness. Electrostatic pump based sideband coupling is demonstrated, and compared to conventional strain-mediated sideband operations. Electrostatic coupling is shown to be very efficient, enabling strong, tunable dynamical coupling.

Highly specific label-free protein detection from lysed cells using internally referenced microcantilever sensors.

We report the investigation of label-free protein detection directly from lysed cells using microcantilever sensors. The integration of an internally referenced microcantilever sensor combined with peptide aptamer technology enables scalable and label-free detection of proteins from a complex biological environment (e.g. cell lysate). The internally referenced microcantilever sensor was found to be effective in minimizing both the effects of thermal drift and non-specific binding interactions with the backside of the cantilever, thereby allowing protein detection in a complex biological background. Highly specific peptide aptamers are used to modify the cantilever surface to specifically detect less than 80 nM CDK2 protein from yeast cell lysate. This binding of CDK2 on the microcantilever generates a tensile surface stress of average magnitude equal to 70+/-22 mN/m. Similar experiments conducted with quartz crystal microbalance (QCM) technology are consistent with the response observed using microcantilever sensors.

Investigation of biotin-streptavidin binding interactions using microcantilever sensors.

We report the investigation of biotin-streptavidin binding interactions using microcantilever sensors. A symmetric cantilever construction is employed to minimize the effects of thermal drift and the control of surface chemistry on the backside of the cantilever is demonstrated to reduce the effects of non-specific binding interactions on the cantilever. Three structurally different biotin modified cantilever surfaces are used as a model system to study the binding interaction with streptavidin. The cantilever response to the binding of streptavidin on these biotin sensing monolayers is compared. The lowest detection limit of streptavidin using biotin-HPDP is found to be between 1 and 10nM limited by the optical measurement setup. Surface characterization using quartz crystal microbalance (QCM) and high-resolution atomic force microscope (AFM) is used to benchmark the cantilever sensor response. In addition, the QCM and AFM studies reveal that the surface density of bound streptavidin on biotin modified surfaces was low, thereby implying that effects other than steric hindrance are responsible for defining cantilever response.