Modulation Detection Method Research Articles

Fine-Tuning Enhancer Models to Predict Transcriptional Targets across Multiple Genomes

Networks of regulatory relations between transcription factors (TF) and their target genes (TG)- implemented through TF binding sites (TFBS)- are key features of biology. An idealized approach to solving such networks consists of starting from a consensus TFBS or a position weight matrix (PWM) to generate a high accuracy list of candidate TGs for biological validation. Developing and evaluating such approaches remains a formidable challenge in regulatory bioinformatics. We perform a benchmark study on 34 Drosophila TFs to assess existing TFBS and cis-regulatory module (CRM) detection methods, with a strong focus on the use of multiple genomes. Particularly, for CRM-modelling we investigate the addition of orthologous sites to a known PWM to construct phyloPWMs and we assess the added value of phylogenentic footprinting to predict contextual motifs around known TFBSs. For CRM-prediction, we compare motif conservation with network-level conservation approaches across multiple genomes. Choosing the optimal training and scoring strategies strongly enhances the performance of TG prediction for more than half of the tested TFs. Finally, we analyse a 35th TF, namely Eyeless, and find a significant overlap between predicted TGs and candidate TGs identified by microarray expression studies. In summary we identify several ways to optimize TF-specific TG predictions, some of which can be applied to all TFs, and others that can be applied only to particular TFs. The ability to model known TF-TG relations, together with the use of multiple genomes, results in a significant step forward in solving the architecture of gene regulatory networks.

Dynamic force spectroscopy using cantilever higher flexural modes

By means of force spectroscopy measurements performed with the cantilever first and second flexural modes under the frequency modulation detection method, the authors corroborate the validity of the relation between tip-surface interaction force and frequency shift for force spectroscopy acquisition using higher cantilever eigenmodes. They estimate a cantilever effective stiffness for the second eigenmode 73 times larger than the static stiffness. This large effective stiffness enables them to perform force spectroscopy with a cantilever oscillation amplitude (A0) as small as 3.6Å. The authors provide experimental evidence that, at such small A0 values, normalized frequency shift curves deviate from a A03∕2 scaling and the signal-to-noise ratio is considerably enhanced.

Multi-Probe Atomic Force Microscopy with Optical Beam Deflection Method

We developed a multi-probe atomic force microscope (AFM) having two AFM cantilevers independently controlled using the optical beam deflection method. We succeeded in simultaneously obtaining images with two independent probes by frequency modulation (FM) detection method. To evaluate the distance between the AFM tips of the cantilevers, we used a new the address-patterned sample, which was also developed for this study. The images obtained show that the distance between the probes was 2 µm. The development of the multi-probe AFM opens a wide variety of applications in the present nanoscience and engineering field.

Noncontact-mode scanning capacitance force microscopy towards quantitative two-dimensional carrier profiling on semiconductor devices

Scanning capacitance force microscopy (SCFM) is a promising tool for investigation of two-dimensional carrier density distribution on semiconducting devices. Its sensitivity is strongly dependent on the Q factor of the mechanical resonance mode of the cantilever. Therefore, measurement in vacuum is more appropriate for increasing the sensitivity. In this letter, the authors describe noncontact-mode (NC) SCFM which is combined with the frequency modulation detection method and its signal characteristics. The authors derived a quasiquantitative calibration curve which correlates to the amplitude signal in NC-SCFM to the dopant density. Using the calibration curve, the authors obtained a quasiquantitative two-dimensional dopant density distribution map on a cross-sectional transistor device.

Investigations of Organic Materials by Kelvin Probe Force Microscopy using Frequency Modulation Method

Kelvin probe force microscopy (KFM), which has been a common method for studying electrical properties of nanometer-scale structures, is a dynamic-mode atomic force microscopy (AFM) technique combined with a traditional Kelvin probe method used for measuring macroscopic contact potential differences. It allows us to map electron affinity or work function on a nanometer scale. In this article KFM using a frequency modulation detection method (FM-KFM) is first explained briefly. The frequency modulation method plays an essential role in high-sensitive interaction force detection. We also describe applications of FM-KFM to the nanometer-scale surface potential investigations of organic materials including phase-separated self-assembled monolayer films (PS-SAM films) and single polymer crystal surfaces. Furthermore, recent results on the local surface potential study of carbon nanotube field effect transistors using FM-KFM is presented.

BARIUM STRONTIUM ZIRCONATE TITANATE (BSZT) THIN FILMS FOR OPTICAL WAVEGUIDE APPLICATIONS

ABSTRACT Barium strontium zirconate titanate [(Ba1-xSrx)(ZrxTi1-x)O3, BSZT-100x], thin films with x = 0.025 and 0.05 (BSZT-2.5 and BSZT-5) were grown on MgO (100) substrates by pulsed laser deposition. X-ray diffraction measurements revealed that the BSZT films had grown epitaxially on the MgO (100) substrates. The refractive index and thickness of the BSZT-2.5 and BSZT-5 films were determined using a prism coupler. The electro-optic (E-O) properties were measured at 632.8 nm wavelength using a phase modulation detection method. The BSZT films exhibited a predominantly quadratic E-O behavior and the E-O coefficient of BSZT-2.5 and BSZT-5 were found to be 1.52 × 10−18 m2/V2 and 2.04 × 10−18 m2/V2, respectively.

Capacitive resonant mass sensor with frequency demodulation detection based on resonant circuit

In this letter, capacitive mass sensing with a 250-nm-thick single-crystalline silicon cantilever is investigated. The mass sensor employs the frequency modulation detection method using an electrical LC oscillator, in which the capacitance of the sensor serves as the component of the oscillator. The displacement noise of the demonstrated capacitive detection is 0.05nm∕(Hz)0.5, which is equivalent to the capacitance change of 2.4×10−21F. It is experimentally shown that the capacitive detection is less affected to temperature fluctuation noise than optical detection. The detectable minimum mass of 1×10−14g is achieved using capacitive detection in ambient atmosphere.

Scanning probe microscopy with quartz crystal cantilever

This paper reports a quartz crystal cantilever for piezoelectric vibration sensing in scanning probe microscopy (SPM). SPM imaging by a frequency modulation detection method is demonstrated in ambient atmosphere using a 22.5-μm-thick cantilevered AT-cut quartz crystal with metal electrodes on both sides. The spring constant of the cantilever is calculated to be 10N∕m. Despite the low electromechanical coupling between the piezoelectric effect and the flexural vibration, a high sensitivity of 0.07nm∕(Hz)0.5 to vibration is achieved in the second flexural mode. The cantilever self-oscillates on the basis of piezoelectric detection, and offers short-term stability of within approximately 0.5Hz in ambient atmosphere at room temperature. The force curve of the self-oscillating cantilever shows that the self-oscillation can be sustained even when in contact with a sample.

Pulsed Laser Deposition of Ba0.6Sr0.4TiO3 Thin Films and Their Optical Properties

ABSTRACTBarium strontium titanate [Ba0.6Sr0.4TiO3 or BST (60/40)] thin films were deposited on MgO (100) substrates using pulsed laser deposition. X-ray diffraction (XRD) measurements revealed that the BST thin films had epitaxially grown on the MgO (100) substrates. The surface morphology of the thin films was observed using an atomic force microscope and the grain size was found to be about 100–150 nm. The surface roughness was around 4.9 nm for a 250 nm thick film. The optical transmittance of the BST thin film was measured using a transmission mode ellipsometer. The BST/MgO configuration was highly transparent in the visible region. The optical band gap energy of the BST film, calculated by applying the Tauc relation, was 3.56 eV. Optical waveguide characteristics of the BST (60/40) thin film were determined using a prism coupler. The electro-optic (E-O) properties were measured at 632.8 nm wavelength using a phase modulation detection method. The BST film exhibited a predominately quadratic E-O behavior and the quadratic E-O coefficient was found to be 0.58 × 10− 17 m2/V2.

Investigations of Nanoparticles by Scanning Near-Field Optical Microscopy Combined with Kelvin Probe Force Microscopy Using a Piezoelectric Cantilever

A microfabricated cantilever with a lead zirconate titanate (PZT) piezoelectric thin film used as an integrated deflection sensor was applied to dynamic-mode atomic force microscopy (AFM). This probe can be used for scanning near-field optical microscopy (SNOM) and Kelvin-probe force microscopy (KFM). We adopted a frequency modulation (FM) detection method not only to stabilize imaging conditions in dynamic-mode AFM but also to enhance sensitivity for the detection of electrostatic forces in KFM measurement. We investigated local optical and electrical properties of gold and polystyrene nanoparticles dispersed on an indium tin oxide (ITO) substrate. We successfully identified the species of each particle by different contrasts obtained in SNOM and KFM images.

Optical properties of Ba 0.5Sr 0.5TiO 3 thin films grown on MgO substrates by pulsed laser deposition

Barium strontium titanate (Ba 0.5Sr 0.5TiO 3 or BST (50/50)) thin films were grown on MgO(1 0 0) substrates using pulsed laser deposition (PLD). The surface morphology of the thin films was observed using a scanning probe microscope and the grain size was found to be around 100–150 nm. The surface roughness is below 5 nm for a 250 nm thick film. X-ray diffraction (XRD) results revealed that the BST thin films were epitaxially grown on the MgO(1 0 0) substrates. Optical transmittance and electro-optic (E-O) properties of the BST thin films were measured using a phase modulation detection method. The BST/MgO configuration was highly transparent in the visible region. The BST film exhibited a predominantly quadratic E-O behavior and the quadratic E-O coefficient was found to be 0.42×10 −17 m 2/V 2.

Nanoscale Investigation of Optical and Electrical Properties by Dynamic-Mode Atomic Force Microscopy Using a Piezoelectric Cantilever

We demonstrated a novel application of a microfabricated force-sensing cantilever with a lead zirconate titanate (PZT) thin film as an integrated deflection sensor for a dynamic-mode atomic force microscope (AFM) combined with a scanning near-field optical microscope (SNOM). This experimental setup was also applied to a Kelvin-probe force microscope (KFM) for the investigation of local electrical properties. A frequency modulation (FM) detection method was used for enhancing the detection sensitivity of electrostatic forces between a probe tip and a sample. Local optical properties of a PbTiO3 single crystal were investigated using the conductive PZT cantilever as an AFM/SNOM probe. Furthermore, studies on local optical and electrical properties of ferroelectric copolymer films were also presented.

Two-dimensional dopant profiling by scanning capacitance force microscopy

We developed scanning capacitance force microscopy (SCFM) capable of mapping local differential capacitance (∂ C/∂ V), based on atomic force microscopy (AFM), by detecting an electrostatic force (ESF) between a tip and a sample. While an electric field alternating at an angular frequency ( ω) is applied between the tip and the sample, an induced ESF oscillating at its third harmonic frequency (3 ω), which contain information on ∂ C/∂ V is detected using a lock-in amplifier (LIA). In this paper, we showed some dynamic-mode SCFM results obtained on a Si test sample. Clear dopant contrasts were obtained by dynamic-mode SCFM operated in air. An apparent position of the p–n junction was moved when an applied d.c. bias voltage was changed. A dynamic-mode SCFM image obtained in a vacuum condition utilizing frequency modulation (FM) detection method also showed clear dopant contrast.

Dynamic force microscopy using FM detection in various environments

High resolution imaging of the organic monolayer film in an ambient condition by dynamic force microscopy (DFM) utilizing the frequency modulation (FM) detection method was demonstrated. Although the mechanical Q-factor of the cantilever used was about 1000, we could image molecular rows in the monolayer film whose pitch was about 2 nm. The image was not clear probably due to the adsorbed water layer on the film. Furthermore, we also demonstrated the operation of the FM detection method in liquid with mechanical excitation of the cantilever by using a PLL circuit with a narrow operating range.

Dynamic-mode AFM using the piezoelectric cantilever: investigations of local optical and electrical properties

We demonstrated applications of a microfabricated cantilever with a lead zirconate titanate (PZT) piezoelectric thin film as an integrated deflection sensor to dynamic-mode atomic force microscopy (AFM) and to the related techniques including scanning near-field optical microscopy (SNOM) and Kelvin force microscopy (KFM). In the SNOM measurement, the evanescent light scattered by the tip apex was transmitted through the pyramidal hollow tip of the cantilever and it was detected by a photodetector placed in a confocal arrangement. Furthermore, local surface potential of a ferroelectric film was mapped by KFM using the frequency modulation (FM) detection method. Local poled ferroelectric domains made by the AFM tip were imaged by both SNOM and KFM.

Surface Potential Measurement of Oligothiophene Ultrathin Films by Kelvin Probe Force Microscopy

Surface structures and local surface potential of oligothiophene single molecular films deposited on metal substrates were investigated by Kelvin probe force microscopy using the frequency modulation detection method. Two-dimensional growth of the dimethylquinquethiophene (DM5T) films with the molecular axes perpendicular to the metal substrates was observed. Furthermore, the obtained surface potential of the DM5T film was 170 mV higher than that of Pt substrate and 200 mV lower than that of Ta substrate.

Surface potential measurement on organic ultrathin film by Kelvin probe force microscopy using a piezoelectric cantilever

We measured surface potential (SP) on a π-conju-gated thiophene oligomer monolayer film deposited on a metallic substrate by Kelvin probe force microscopy using a piezoelectric cantilever. Since the cantilever has a relatively large spring constant (calculated as about 150 N/m), the frequency modulation detection method was used for tip–sample distance regulation in order to achieve high-sensitivity SP measurement. A contact potential difference between monolayer regions and the metallic substrate was clearly observed in an SP image. Furthermore, an apparent change in a contrast of the SP image was observed while the sample was irradiated with ultraviolet light.

Comparative Surface Studies at Atomic Resolution with Ultrahigh Vacuum Variable-Temperature Atomic Force and Scanning Tunneling Microscopes.

: With the ultrahigh vacuum variable-temperature scanning tunneling microscope (UHV-VT-STM), atomic-level observation has been achieved. An ultrahigh vacuum atomic force microscope (UHV-AFM) has also been developed, with success in obtaining atom images where observation in noncontact (NC) mode with a frequency modulation (FM) detection method was attempted. Using the FM detection method in the constant oscillation amplitude of the cantilever excitation mode, we have obtained atomic-resolution images of Si(111) 7 x 7 structures and Si(100) 2 x 1 structures and other structures together with STM images in an ultrahigh vacuum environment. Also shown here are contact potential difference (CPD) images using the NC-AFM method.

The atomic resolution imaging of metallic Ag(111) surface by noncontact atomic force microscope

Atomic resolution imaging of the Ag(111) surface is demonstrated with the noncontact atomic force microscope (AFM) using frequency modulation (FM) detection method in an ultrahigh vacuum at room temperature, for the first time. The constant excitation mode is used to suppress the destruction of the tip apex and sample surface, in which the constant amplitude voltage is supplied to piezoelectric scanner for cantilever oscillation. Trigonal pattern can be clearly seen. Measured distance between the protrusions is 2.8±0.1 Å, which is in good agreement with the lattice spacing of Ag(111) surface. The corrugation height is estimated to be 0.1–0.2 Å. These results suggest that the noncontact AFM has potential for imaging pure metal surfaces with atomic resolution.

True atomic resolution imaging of surface structure and surface charge on the GaAs(110)

We demonstrated a novel method to detect the van der Waals and the electrostatic force interactions simultaneously on an atomic scale, which is based on frequency modulation detection method. For the first time, the surface structure and the surface charge at atomic-scale point defects on the GaAs(110) surface have been simultaneously resolved with true atomic resolution under ultra-high vacuum condition. From the bias voltage dependence of the image contrast, we can verify that the sign of the atomically resolved surface charge at the point defect was positive.