Linking mass measured by the quartz crystal microbalance to the SI.

Despite ubiquitous implementation of the quartz crystal microbalance (QCM) for measuring thin film thickness throughout industry and academia, a direct link to the SI (International System of Units) does not exist. Confidence in QCM measurements relies on over a half-a-century of academic and industrial research used to understand the resonant frequency change due to loading mass onto a quartz crystal. Here, we use before and after gravimetric mass measurements, linked directly to the SI, to measure mass change. A custom vacuum metal deposition system is used to deposit gold films of various masses onto a series of quartz crystals while the mass dependent frequency change is monitored in real time. The gravimetric (known) mass changes are compared to three analytical methods (frequency, time and energy) used to convert resonant frequency shifts to mass changes, none of which rely on the material properties of the deposited material. Additionally, we evaluate the reversible and irreversible contributions to mass change from the loading into, and removal from, the vacuum environment. We find the "energy-based" method for frequency to mass conversion has the best accuracy over the longest range, at 0.36 % to > 1 mg. Only for mass changes below 100 µg are deviations > 2 % observed. A complete uncertainty budget is provided.

Work fluctuations in a nonlinear micromechanical oscillator driven far from thermal equilibrium.

We explore fluctuation relations in a periodically driven micromechanical torsional oscillator. In the linear regime where the modulation is weak, we verify that the ratio of the work variance to the mean work is constant, consistent with conventional fluctuation theorems. We then increase the amplitude of the periodic drive so that the response becomes nonlinear and two nonequilibrium oscillation states coexist. Due to interstate transitions, the work variance exhibits a peak at the driving frequency at which the occupation of the two states is equal. Moreover, the work fluctuations depend exponentially on the inverse noise intensity. Our data are consistent with recent theories on systems driven into bistability that predict generic behaviors different from conventional fluctuation theorems.

Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT).

Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.

Switching-path distribution in multidimensional systems.

We explore the distribution of paths followed in fluctuation-induced switching between coexisting stable states. We introduce a quantitative characteristic of the path distribution in phase space that does not require a priori knowledge of system dynamics. The theory of the distribution is developed and its direct measurement is performed in a micromechanical oscillator driven into parametric resonance. The experimental and theoretical results on the shape and position of the distribution are in excellent agreement, with no adjustable parameters. In addition, the experiment provides the first demonstration of the lack of time-reversal symmetry in switching of systems far from thermal equilibrium. The results open the possibility of efficient control of the switching probability based on the measured narrow path distribution.

Paths of fluctuation induced switching.

We demonstrate that the paths followed by a system in fluctuation-activated switching form a narrow tube in phase space. A theory of the path distribution is developed and its direct measurement is performed in a micromechanical oscillator. The experimental and theoretical results are in excellent agreement, with no adjustable parameters. We also demonstrate the lack of time-reversal symmetry in switching of systems far from thermal equilibrium.

Activation barrier scaling and crossover for noise-induced switching in micromechanical parametric oscillators.

We explore fluctuation-induced switching in parametrically driven micromechanical torsional oscillators. The oscillators possess one, two, or three stable attractors depending on the modulation frequency. Noise induces transitions between the coexisting attractors. Near the bifurcation points, the activation barriers are found to have a power law dependence on frequency detuning with critical exponents that are in agreement with predicted universal scaling relationships. At large detuning, we observe a crossover to a different power law dependence with an exponent that is device specific.

Supernarrow spectral peaks near a kinetic phase transition in a driven nonlinear micromechanical oscillator.

We measure the spectral densities of fluctuations of an underdamped nonlinear micromechanical oscillator. By applying a sufficiently large periodic excitation, two stable dynamical states are obtained within a particular range of driving frequency. White noise is injected into the excitation, allowing the system to overcome the activation barrier and switch between the two states. While the oscillator predominately resides in one of the two states for most frequencies, a narrow range of frequencies exist where the occupations of the two states are approximately equal. At these frequencies, the oscillator undergoes a kinetic phase transition that resembles the phase transition of thermal equilibrium systems. We observe a supernarrow peak in the spectral densities of fluctuations of the oscillator. This peak is centered at the excitation frequency and arises as a result of noise-induced transitions between the two dynamical states.

Real-time prediction of hand trajectory by ensembles of cortical neurons in primates.

Signals derived from the rat motor cortex can be used for controlling one-dimensional movements of a robot arm. It remains unknown, however, whether real-time processing of cortical signals can be employed to reproduce, in a robotic device, the kind of complex arm movements used by primates to reach objects in space. Here we recorded the simultaneous activity of large populations of neurons, distributed in the premotor, primary motor and posterior parietal cortical areas, as non-human primates performed two distinct motor tasks. Accurate real-time predictions of one- and three-dimensional arm movement trajectories were obtained by applying both linear and nonlinear algorithms to cortical neuronal ensemble activity recorded from each animal. In addition, cortically derived signals were successfully used for real-time control of robotic devices, both locally and through the Internet. These results suggest that long-term control of complex prosthetic robot arm movements can be achieved by simple real-time transformations of neuronal population signals derived from multiple cortical areas in primates.

Encoding of tactile stimulus location by somatosensory thalamocortical ensembles.

The exquisite modular anatomy of the rat somatosensory system makes it an excellent model to test the potential coding strategies used to discriminate the location of a tactile stimulus. Here, we investigated how ensembles of simultaneously recorded single neurons in layer V of primary somatosensory (SI) cortex and in the ventral posterior medial (VPM) nucleus of the thalamus of the anesthetized rat may encode the location of a single whisker stimulus on a single trial basis. An artificial neural network based on a learning vector quantization algorithm, was used to identify putative coding mechanisms. Our data suggest that these neural ensembles may rely on a distributed coding scheme to represent the location of single whisker stimuli. Within this scheme, the temporal modulation of neural ensemble firing rate, as well as the temporal interactions between neurons, contributed significantly to the representation of stimulus location. The relative contribution of these temporal codes increased with the number of whiskers that the ensembles must discriminate among. Our results also indicated that the SI cortex and the VPM nucleus may function as a single entity to encode stimulus location. Overall, our data suggest that the representation of somatosensory features in the rat trigeminal system may arise from the interactions of neurons within and between the SI cortex and VPM nucleus. Furthermore, multiple coding strategies may be used simultaneously to represent the location of tactile stimuli.

Simultaneous encoding of tactile information by three primate cortical areas.

We used simultaneous multi-site neural ensemble recordings to investigate the representation of tactile information in three areas of the primate somatosensory cortex (areas 3b, SII and 2). Small neural ensembles (30-40 neurons) of broadly tuned somatosensory neurons were able to identify correctly the location of a single tactile stimulus on a single trial, almost simultaneously. Furthermore, each of these cortical areas could use different combinations of encoding strategies, such as mean firing rate (areas 3b and 2) or temporal patterns of ensemble firing (area SII), to represent the location of a tactile stimulus. Based on these results, we propose that ensembles of broadly tuned neurons, located in three distinct areas of the primate somatosensory cortex, obtain information about the location of a tactile stimulus almost concurrently.