Publications

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Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the outbreak to identify since most outbreaks are only recognized through reportable diseases by health departments and reports of unusual diseases by clinicians. In recent decades, arthropod-borne viruses (arboviruses) have emerged as some of the most significant threats to human health. They emerge, often unexpectedly, from cryptic transmission foci causing localized outbreaks that can rapidly spread to multiple continents due to increased human travel and trade. Currently, diagnosis of acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No diagnostic devices suitable for use at the bedside or in an outbreak setting currently exist. The original goals of this project were to 1) develop two highly sensitive and specific diagnostic assays for detecting RNA from a wide range of arboviruses; one based on an electrochemical approach and the other a fluorescent based assay and 2) develop prototype microfluidic diagnostic platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were developed for DNA-RNA hybridization detection and were implemented in microfluidic diagnostic sensing platforms that were developed in this project.

This report describes X-cut lithium niobates (LiNbO3) utilization for voltage sensing by monitoring the acoustic wave propagation changes through LiNbO3 resulting from applied voltage. Direct current (DC), alternating current (AC) and pulsed voltage signals were applied to the crystal. Voltage induced shift in acoustic wave propagation time scaled quadratically for DC and AC voltages and linearly for pulsed voltages. The measured values ranged from 10 - 273 ps and 189 ps 2 ns for DC and non-DC voltages, respectively. Data suggests LiNbO3 has a frequency sensitive response to voltage. If voltage source error is eliminated through physical modeling from the uncertainty budget, the sensors U95 estimated combined uncertainty could decrease to ~0.025% for DC, AC, and pulsed voltage measurements.

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Recently reported narrow bandwidth, <;2%, aluminum nitride microresonator filters in the 100-500 MHz range offer lower insertion loss, 100x smaller size, and elimination of large external matching networks, when compared to similar surface acoustic wave filters. While the initial results are promising, many microresonators exhibit spurious responses both close and far from the pass band which degrade the out of band rejection and prevent the synthesis of useful filters. This paper identifies the origins of several unwanted modes in overtone width extensional aluminum nitride microresonators and presents techniques for mitigating the spurious responses.

While individual neurons function at relatively low firing rates, naturally-occurring nervous systems not only surpass manmade systems in computing power, but accomplish this feat using relatively little energy. It is asserted that the next major breakthrough in computing power will be achieved through application of neuromorphic approaches that mimic the mechanisms by which neural systems integrate and store massive quantities of data for real-time decision making. The proposed LDRD provides a conceptual foundation for SNL to make unique advances toward exascale computing. First, a team consisting of experts from the HPC, MESA, cognitive and biological sciences and nanotechnology domains will be coordinated to conduct an exercise with the outcome being a concept for applying neuromorphic computing to achieve exascale computing. It is anticipated that this concept will involve innovative extension and integration of SNL capabilities in MicroFab, material sciences, high-performance computing, and modeling and simulation of neural processes/systems.

Elucidating the role of calcium fluctuations at the cellular level is essential to gain insight into more complex signaling and metabolic activity within tissues. Recent developments in optical monitoring of calcium transients suggest that cells integrate and transmit information through large networks. Thus, monitoring calcium transients in these populations is important for identifying normal and pathological states of a variety of systems. Though optical techniques can be used to image calcium fluxes using fluorescent probes, depth penetration limits the information that can be acquired from tissues in vivo. Alternatively, the calcium-sensitive dye arsenazo III is useful for optical techniques that rely on absorption of light rather than fluorescence for image contrast. We report on the use of arsenazo III for detection of calcium using photoacoustics, a deeply penetrating imaging technique in which an ultrasound signal is generated following localized absorption of light. The absorbance properties of the dye in the presence of calcium were measured directly using UV-Vis spectrophotometry. For photoacoustic studies, a phantom was constructed to monitor the change in absorbance of 25 μM arsenazo III at 680 nm in the presence of calcium. Subsequent results demonstrated a linear increase in photoacoustic signal as calcium in the range of 1 - 20 μM complexed with the dye, followed by saturation of the signal as increasing amounts of calcium were added. For delivery of the dye to tissue preparations, a liposomal carrier was fabricated and characterized. This work demonstrates the feasibility of using arsenazo III for photoacoustic monitoring of calcium transients in vivo. © 2010 Copyright SPIE - The International Society for Optical Engineering.

In this paper, we discuss our work in the modeling and characterization of an acousdc-microfluidlc focusing device that uses standing bulk acoustic waves to focus particles under flow. Modeling was done using Comsol Multiphysics® (Comsol, Los Angeles, CA), a multiphysics FEM tool, and the performance of the device was assessed through coefficient of variance (CV) measurements using a confocal microscope. © 2008 IEEE.

The rapid autonomous detection of pathogenic microorganisms and bioagents by field deployable platforms is critical to human health and safety. To achieve a high level of sensitivity for fluidic detection applications, we have developed a 330 MHz Love wave acoustic biosensor on 36{sup o} YX Lithium Tantalate (LTO). Each die has four delay-line detection channels, permitting simultaneous measurement of multiple analytes or for parallel detection of single analyte containing samples. Crucial to our biosensor was the development of a transducer that excites the shear horizontal (SH) mode, through optimization of the transducer, minimizing propagation losses and reducing undesirable modes. Detection was achieved by comparing the reference phase of an input signal to the phase shift from the biosensor using an integrated electronic multi-readout system connected to a laptop computer or PDA. The Love wave acoustic arrays were centered at 330 MHz, shifting to 325-328 MHz after application of the silicon dioxide waveguides. The insertion loss was -6 dB with an out-of-band rejection of 35 dB. The amplitude and phase ripple were 2.5 dB p-p and 2-3{sup o} p-p, respectively. Time-domain gating confirmed propagation of the SH mode while showing suppression of the triple transit. Antigen capture and mass detection experiments demonstrate a sensitivity of 7.19 {+-} 0.74{sup o} mm{sup 2}/ng with a detection limit of 6.7 {+-} 0.40 pg/mm{sup 2} for each channel.

Recently, the generalized method for calculation of the 16-element Green's function for analysis of surface acoustic waves has proven crucial to develop more sophisticated transducers. The generalized Green's function provides a precise relationship between the acoustic stresses and electric displacement on the three mechanical displacements and electric potential. This generalized method is able to account for mass loading effects which is absent in the effective permittivity approach. However, the calculation is numerically intensive and may lead to numerical instabilities when solving for both the eigenvalues and eigenvectors simultaneously. In this work, the general eigenvalue problem was modified to eliminate the numerical instabilities in the solving procedure. An algorithm is also presented to select the proper eigenvalues rapidly to facilitate analysis for all types of acoustic propagation. The 4 x 4 Green's functions and effective permittivities were calculated for materials supporting Rayleigh, leaky, and leaky longitudinal waves as demonstration of the method.

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Flow cytometry is an indispensable tool in clinical diagnostics, for example in cancer, AIDS, infectious disease outbreaks, microbiology, and others. The cost and size of existing cytometers precludes their entry into field clinics, water monitoring, agriculture/veterinary diagnostics, and rapidly deployable biothreat detection. Much of the cost and footprint of conventional cytometers is dictated by the high speed achieved by cells or beads in a hydrodynamically focused stream. This constraint is removed by using ultrasonic focusing in a parallel microfluidic architecture. In this paper, we describe our progress towards a microfabricated flow cytometer that uses bulk and microfabricated planar piezoelectric transducers in glass microfluidic channels. In addition to experimental data, initial modeling data to predict the performance of our transducers are discussed.

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