Diagonal control design for atomic force microscope piezoelectric tube nanopositioners.

Atomic Force Microscopes (AFM) are used for generating surface topography of samples at micro to atomic resolutions. Many commercial AFMs use piezoelectric tube nanopositioners for scanning. Scanning rates of these microscopes are hampered by the presence of low frequency resonant modes. When inadvertently excited, these modes lead to high amplitude mechanical vibrations causing the loss of accuracy, while scanning, and eventually to break down of the tube. Feedback control has been used to damp these resonant modes. Thereby, enabling higher scanning rates. Here, a multivariable controller is designed to damp the first resonant mode along both the x and y axis. Exploiting the inherent symmetry in the piezoelectric tube, the multivariable control design problem is recast as independent single-input single-output (SISO) designs. This in conjunction with integral resonant control is used for damping the first resonant mode.

Invited review article: high-speed flexure-guided nanopositioning: mechanical design and control issues.

Recent interest in high-speed scanning probe microscopy for high-throughput applications including video-rate atomic force microscopy and probe-based nanofabrication has sparked attention on the development of high-bandwidth flexure-guided nanopositioning systems (nanopositioners). Such nanopositioners are designed to move samples with sub-nanometer resolution with positioning bandwidth in the kilohertz range. State-of-the-art designs incorporate uniquely designed flexure mechanisms driven by compact and stiff piezoelectric actuators. This paper surveys key advances in mechanical design and control of dynamic effects and nonlinearities, in the context of high-speed nanopositioning. Future challenges and research topics are also discussed.

High-speed cycloid-scan atomic force microscopy.

A key hurdle in achieving high scan speeds in atomic force microscopes is that the probe is required to be scanned over the sample in a zig-zag raster pattern. The fast axis of the AFM scanner must track a signal that contains frequencies beyond its mechanical bandwidth. Consequently, fast raster scans generate distortions in the resulting image. We propose a smooth cycloid-like scan pattern that allows us to achieve scan speeds much higher than a raster scan. We illustrate how the proposed method can be implemented on a commercial AFM with minimal modifications.

Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis.

OBJECTIVES: A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia. METHODS: Peripheral blood mononuclear cells were collected at weeks 0, 6, 12, 24 and 48 of ART from five patients experiencing IRD [two with cryptococcal and three with Mycobacterium tuberculosis (Mtb) disease], eight non-IRD controls who had begun ART with CD4 T-cell counts of <100 cells/microL and 17 healthy controls. Leukocytes producing interferon-gamma (IFNgamma) were quantified by enzyme-linked immunospot assay after stimulation with purified protein derivative (PPD), early secretory antigenic target-6 (ESAT-6), Cryptococcus neoformans or Cytomegalovirus antigens. Plasma immunoglobulin (IgG) antibodies reactive with these antigens were assessed by enzyme-linked immunosorbent assay. Proportions of activated (HLA-DR(hi)) and regulatory (CD25 CD127(lo) and CTLA-4(+)) CD4 T-cells were quantified by flow cytometry. RESULTS: Plasma HIV RNA declined and CD4 T-cell counts rose within 8-27 weeks on ART. Mtb IRD patients displayed elevated IFNgamma responses and/or plasma IgG to PPD, but none responded to ESAT-6. Cryptococcal IRD occurred in patients with low baseline CD4 T-cell counts and involved clear IFNgamma and antibody responses to cryptococcal antigen. Proportions of activated and regulatory CD4 T-cells declined on ART, but remained higher in patients than in healthy controls. At the time of IRD, proportions of activated CD4 T-cells and regulatory CD4 T-cells were generally elevated relative to other patients. CONCLUSIONS: Cryptococcal and Mtb IRD generally coincide with peaks in the proportion of activated T-cells, pathogen-specific IFNgamma responses and reactive plasma IgG. IRD does not reflect a paucity of regulatory CD4 T-cells.

Rapid detection and serotyping of dengue virus by multiplex RT-PCR and real-time SYBR green RT-PCR.

INTRODUCTION: Dengue fever and dengue haemorrhagic fever currently rank highly among the newly-emerging infectious diseases, and are considered to be the most important arboviral disease worldwide. The definitive diagnosis is culture analysis, but practical considerations limit its use. Also, the period for viral detection is limited. Within a day or two after fever subsides, rising levels of antibodies interfere with viral cultures. An alternative to this quandary is the use of viral RNA detection assays. In our laboratory, a reverse transcriptase polymerase chain reaction (RT-PCR) assay was developed using a set of degenerate primers. METHODS: This multiplex RT-PCR assay was evaluated with 280 samples collected during the year 2003. These groups include prototype dengue virus (serotypes 1-4), acute serum from which the dengue virus was isolated, seronegative acute samples (culture negative) but whose convalescent samples seroconverted, and sera positive for other microbial diseases. This assay was then modified into a real-time SYBR Green RT-PCR assay. Sensitivity and specificity of both assays were compared. RESULTS: The multiplex RT-PCR assay was able to detect 134 samples whereas SYBR Green RT-PCR assay was able to detect 178 out of 306 samples. Both assays were 100 percent specific. Further analysis of 53 samples showed that the virus could be amplified at IgM positive/negative values of up to 4.2, and up to six days after onset of fever. The viral detection rate was inversely proportional to the day of fever onset as well as IgM values. CONCLUSION: The sensitivity and specificity of the conventional multiplex RT-PCR assay are 98.18 percent and 100 percent, respectively, and for the real-time SYBR Green assay, 99.09 percent and 100 percent, respectively. The melting curve analysis allows all four dengue serotypes to be discriminated based on distinct melting temperature value. The accuracy and speed of this multiplex RTPCR assay makes it a suitable test for the diagnosis of dengue and for epidemiological surveillance.

On the accuracy of Mindlin plate predictions for the frequency-temperature behavior of resonant modes in AT- and SC-cut quartz plates.

The frequency spectra of resonant modes in AT- and SC-cut quartz plates and their frequency-temperature behavior were studied using Mindlin first- and third-order plate equations. Both straight-crested wave solutions and two-dimensional plate solutions were studied. The first-order Mindlin plate theory with shear correction factors was previously found to yield inaccurate frequency spectra of the modes in the vicinity of the fundamental thickness-shear frequency. The third-order Mindlin plate equations without correction factors, on the other hand, predict well the frequency spectrum in the same vicinity. In general, the frequency-temperature curves of the fundamental thickness-shear obtained from the first-order Mindlin plate theory are sufficiently different from those of the third-order Mindlin plate theory that they raise concerns. The least accurately predicted mode of vibration is the flexure mode, which results in discrepancies in its frequency-temperature behavior. The accuracy of other modes of vibrations depends on the degree of couplings with the flexure mode. Mindlin first-order plate theory with only the shear correction factors is not sufficiently accurate for high frequency crystal vibrations at the fundamental thickness-shear frequency. Comparison with measured resonant frequencies and frequency-temperature results on an AT-cut quartz plate shows that the third-order plate theory is more accurate than the first-order plate theory; this is especially true for the technically important fundamental thickness shear mode in the AT-cut quartz plate.

Numerical algorithms and results for SC-cut quartz plates vibrating at the third harmonic overtone of thickness shear.

Finite element matrix equations, derived from two-dimensional piezoelectric high frequency plate theory are solved to study the vibrational behavior of the third overtone of thickness shear in square and circular SC-cut quartz resonators. The mass-loading and electric effects of electrodes are included. A perturbation method which reduces the memory requirements and computational time significantly is employed to calculate the piezoelectric resonant frequencies. A new storage scheme is introduced which reduces memory requirements for mass matrix by about 90% over that of the envelope storage scheme. Substructure techniques are used in eigenvalue calculation to save storage. Resonant frequency and the mode shapes of the harmonic third overtone thickness shear vibrations for square and circular plates are calculated. A predominant third overtone thickness shear displacement, coupled with the third overtone of thickness stretch and thickness twist, is observed. Weak coupling between the third order thickness shear displacement and the zeroth-, first-, and second-order displacements is noted. The magnitudes of the lower order displacements are found to be about two orders smaller than that of the third overtone thickness shear displacement.

A perturbation method for finite element modeling of piezoelectric vibrations in quartz plate resonators.

When the piezoelectric stiffening matrix is added to the mechanical stiffness matrix of a finite element model, its sparse matrix structure is destroyed. A direct consequence of this loss in sparseness is a significant rise in memory and computational time requirements for the model. For weakly coupled piezoelectric materials, the matrix sparseness can be retained by a perturbation method which separates the mechanical eigenvalue solution from its piezoelectric effects. Using this approach, a perturbation and finite element scheme for weakly coupled piezoelectric vibrations in quartz plate resonators has been developed. Finite-element matrix equations were derived specifically for third-overtone thickness-shear, SC-cut quartz plate resonators with electrode platings. High-frequency piezoelectric plate equations were employed in the formulation of the finite element matrix equation. Results from the perturbation method compared well with the direct solution of the piezoelectric finite element equations. This method will result in significant savings in the computer memory and computational time. Resonance and antiresonance frequencies of a certain mode could be calculated easily by using the same eigenpair from the purely mechanical stiffness matrix. Numerical results for straight crested waves in a third overtone SC-cut quartz strip with and without electrodes are presented. The steady-state response to an electrical excitation is calculated.

Thickness-shear mode shapes and mass-frequency influence surface of a circular and electroded AT-cut quartz resonator.

Finite-element solutions for the fundamental thickness shear mode and the second-anharmonic overtone of a circular, 1.87-MHz AT-cut quartz plate with no electrodes are presented and compared with previously obtained results for a rectangular plate of similar properties. The edge flexural mode in circular plates, a vibration mode not seen in the rectangular plate is also presented. A 5-MHz circular and electroded AT-cut quartz plate is studied. A portion of the frequency spectrum is constructed in the neighborhood of the fundamental thickness-shear mode. A convergence study is also presented for the electroded 5-MHz plate. A new two-dimensional (2-D) technique for visualizing the vibration mode solutions is presented. This method departs substantially from the three-dimensional (3-D) ;wire-frame' plots presented in the previous analysis. The 2-D images can be manipulated to produce nodal line diagrams and can be color coded to illustrate mode shapes and energy trapping phenomenon. A contour plot of the mass-frequency influence surface for the plated 5-MHz resonator is presented. The mass-frequency influence surface is defined as a surface giving the frequency change due to a small localized mass applied to the resonator surface.

Mass-frequency influence surface, mode shapes, and frequency spectrum of a rectangular AT-cut quartz plate.

The mass-frequency influence surface and frequency spectrum of a rectangular AT-cut quartz plate are studied. The mass-frequency influence surface is defined as a surface giving the frequency change due to a small localized mass applied on the plate surface. Finite-element solutions of R.D. Mindlin's (1963) two-dimensional plate equations for thickness-shear, thickness-twist, and flexural vibrations are given. Spectrum splicing, and an efficient eigenvalue solver using the C. Lanczos (1950) algorithm are incorporated into the finite-element program. A convergence study of the fundamental thickness-shear mode and its first symmetric, anharmonic overtone is performed for finite-element meshes of increasing fineness. As a general rule, more than two elements must span any half-wave in the plate or spurious mode shapes will be obtained. Two-dimensional (2D) mode shapes and frequency spectrum of a rectangular AT-cut plate in the region of the fundamental thickness-shear frequency are presented. The mass-frequency influence surface for a 5-MHz rectangular, AT-cut plate with patch electrodes is obtained by calculating the frequency change due to a small mass layer moving over the plate surface. The frequency change is proportional to the ratio of mass loading to mass of plate per unit area and is confined mostly within the electrode area, where the magnitude is on the order 10(8) Hz/g.

Modeling resonator frequency fluctuations induced by adsorbing and desorbing surface molecules.

Resonator frequency fluctuations due to adsorption and desorption of molecules on plate electrodes are studied using the principle of mass-loading effects of adsorbed molecules. The study is based on a 525 MHz, AT-cut quartz resonator enclosed in a small crystal holder. Equations relating the surface adsorption rates of the crystal holder to pressure were derived and found to be quadratic polynomial functions of the adsorption rates. Calculations based on these equations show that a contaminant gas with a higher desorption energy creates larger changes in pressure when the temperature is varied. The function describing the frequency fluctuations due to any one contaminant site is a continuous-time Markov chain. Kolmogorov equations and an autocorrelation function for the Markov chain are derived. The autocorrelation and spectral density function of resonator frequency fluctuations are derived. The spectral density of frequency fluctuations at 1 Hz is studied as a function of pressure, temperature, and desorption energy of molecules. The noise levels for a contaminant gas with one type of molecules are found to be lower for lower desorption energies, and higher at lower pressures.

Resonator surface contamination-a cause of frequency fluctuations?

The mass loading effects of adsorbing and desorbing contaminant molecules on the magnitude and characteristics of frequency fluctuations in a thickness-shear resonator are studied. The study is motivated by the observation that the frequency of a thickness-shear resonator is determined predominantly by such mechanical parameters as the thickness of the resonator, elastic stiffnesses, mass loading of the electrodes, and energy trapping. An equation was derived relating the spectral density of frequency fluctuations to: (1) rates of adsorption and desorption of one species of contaminant molecules; (2) mass per unit area of a monolayer of molecules: (3) frequency constant; (4) thickness of resonator; and (5) number of molecular sites on one resonator surface. The induced phase noises were found to be significant in very-high-frequency resonators and are not simple functions of the percentage of area contaminated. The spectral density of frequency fluctuations was inversely proportional to the fourth power of the thickness if other parameters were held constant.

Characteristics of a Lagrangian, high-frequency plate element for the static temperature behavior of low-frequency quartz resonators.

Finite-element matrix equations based on the Lagrangian, first-order, incremental plate equations of motion superposed on homogeneous thermal strains were formulated using virtual work principles. A program for an isoparametric, four-node quadrilateral element was written and applied to the study of the frequency-temperature (FT) behavior of flexure-mode quartz resonators. The lumped-mass and consistent-mass matrices were found to yield practically the same FT curves. For simple prismatic resonators, two schemes, reduced/selective integration and incompatible modes, produced relatively similar FT curves. The incompatible modes scheme yielded better results for resonators of more complex shapes, such as the tuning fork. It is concluded that the six-degree-of-freedom per node element is needed for the analysis of the FT behavior of a fully anisotropic flexure-mode resonator.