Nanometric Volumes Research Articles

Pressure-assisted tip-enhanced Raman imaging at a resolution of a few nanometres

Scanning probe microscopy methods1,2 can image samples with extremely high resolutions, opening up a wide range of applications in physics3, chemistry4 and biology5. However, these passive techniques, which trace the sample surface softly, give indirect topographic information. Here, we show an active imaging technique that has the potential to achieve optically a molecular resolution by directly interacting and perturbing the sample molecules. This technique makes use of an external pressure, applied selectively on a nanometric volume of the sample through the apex of a sharp nanotip, to obtain a local distortion of only those molecules that are pressurized. The vibrational frequencies of these molecules are distinctly different from those of unpressurized molecules. By sensing this difference, our active microscopic technique can achieve extremely high resolution. Using an isolated single-walled carbon nanotube and a two-dimensional adenine nanocrystal, we demonstrate a spatial resolution of 4 nm. Applying external pressure to a sample molecule via the apex of a sharp nanotip allows tip-enhanced Raman imaging of molecules with a spatial resolution of 4 nm.

Fluorescence fluctuations analysis in nanoapertures: physical concepts and biological applications

During the past years, nanophotonics has provided new approaches to study the biological processes below the optical diffraction limit. How single molecules diffuse, bind and assemble can be studied now at the nanometric level, not only in solutions but also in complex and crowded environments such as in live cells. In this context fluorescence fluctuations spectroscopy is a unique tool since it has proven to be easy to use in combination with nanostructures, which are able to confine light in nanometric volumes. We review here recent advances in fluorescence fluctuations' analysis below the optical diffraction limit with a special focus on nanoapertures milled in metallic films. We discuss applications in the field of single-molecule detection, DNA sequencing and membrane organization, and underscore some potential perspectives of this new emerging technology.

Low-energy electron interactions with liquid water and energy depositions in nanometric volumes

Interactions of low-energy electrons with liquid water and DNA were investigated. Elastic and inelastic interaction cross sections were calculated using appropriate models for the response of atomic nuclei, valence band and inner shells. These models included an extended Drude dielectric model for valence-band excitations, a sum-rule-constrained binary-encounter model for inner-shell ionizations, and a phase-shift analysis model for elastic interactions. Applying calculated cross sections, an event-by-event Monte Carlo (MC) program was developed to simulate electron transport in liquid water and energy depositions in nanometric volumes. This simulation provided an estimate of strand breaks of DNA due to direct and indirect actions by low-energy electrons in a simplified DNA model. This model consisted of two parallel cylinders of 0.5nm in diameter, 16nm in height and 1nm in separation. Any energy deposition greater than 17.6eV in the cylinder was assumed to cause a single strand break (ssb) by direct action. An energy deposition of 12.6eV or greater in liquid water within 0.5nm of the cylinder surface was assumed to induce an OH radical which had a probability of 0.13 to produce a ssb by indirect action. When two ssbs occurred on opposite strands separated by 10 or fewer base pairs, a double strand break (dsb) was assumed. The number of deposition events for ssbs or dsbs per electron emission was calculated and analyzed for different electron energies and electron emission positions. The simplified model provided useful information on the energy depositions for DNA strand breaks and on the effectiveness of low-energy electrons in various geometric and irradiation conditions.

A 2D nanosphere array for atomic spectroscopy

We are interested in the spectroscopic behaviour of a gas confined in a micrometric or even nanometric volume. Such a situation could be encountered by the filling-up of a porous medium, such as a photonic crystal, with an atomic gas. Here, we discuss the first step of this program, with the generation and characterization of a self-organized 2D film of nanospheres of silica. We show that an optical characterization by laser light diffraction permits to extract some information on the array structure and represents an interesting complement to electron microscopy.

Bayesian reconstruction of nanodosimetric cluster distributions at 100% detection efficiency

Ionisation spectra in nanometric volumes at a given distance from a charged particle track are obtained by using electron (or ion) gas detectors, having non-uniformly distributed detection efficiency. Therefore, such spectra should be properly processed in order to reconstruct the frequency distribution of clusters really produced in the detector gas. A Bayesian unfolding has been applied to ionisation distributions due to 5.4 MeV alpha particles in a 20-nm site obtained by Monte Carlo simulations, taking into account different detection efficiency conditions. It will be shown that Bayesian analysis provides a valid tool for reconstructing the true ionisation distributions, well beyond the maximum measured cluster size.

Nanodosimetry, the metrological tool for connecting radiation physics with radiation biology

It is generally accepted that the early damage to genes or cells by ionising radiation starts with the early damage to segments of the DNA, at least, to the greater part. This damage is the result of the spatial distribution of inelastic interactions of single ionising particles within the DNA or in its neighbourhood and is, in consequence, determined by the stochastics of particle interactions in volumes a few nanometre in size. Due to the latter fact radiation damage strongly depends on radiation quality and cannot be described satisfactorily in detail by macroscopic quantities like absorbed dose or linear energy transfer (LET). It can, however, be described approximately by the probability distribution of ionisation cluster-size formation in nanometric target volumes of liquid water (nanodosimetry). One aim of nanodosimetry is, therefore, to measure the radiation induced frequency distribution of ionisation cluster-size formation in liquid water, as a substitute for sub-cellular material, in volumes which are comparable in size with those of the most probable radio-sensitive volumes of biological systems. After a short description of the main aspects of cluster-size formation by ionising particles, an overview is given about the measuring principles applied in present-day nanodosimetric measurements. Afterwards, physical principles are discussed which can be used to convert ionisation cluster-size distributions measured in gases into those caused by ionising radiation in liquid water. In a final section, the probability distribution of ionisation cluster-size formation in liquid water is discussed from the point of view of damage formation to segments of the DNA.

Ionisation cluster-size formation by electrons: from macroscopic to nanometric target sizes

An indispensable prerequisite for a deeper understanding of specified physical, chemical or biological changes initiated in matter when being exposed to ionising radiation is a detailed knowledge of particle track structure. Here, the structure of electron tracks is of particular interest since electrons are set in motion in large numbers as secondary particles during the slow down of any kind of ionising radiation in matter. From the point of view of radiation induced early damage to genes and cells, which starts with the early damage to segments of the DNA molecule, the most effective secondary electrons are those at energies of a few hundred eV since the yield of double-strand breaks induced by such electrons in the DNA shows a maximum. This can be explained by the fact that in water cylinders, 2 nm in diameter and height (as a substitute to small segments of the DNA), the probability of the electron-induced formation of ionisation cluster sizes greater than or equal to two is highest also at initial electron energies of a few hundred eV. In view of this promising feature of ionisation cluster-size distributions formed by low-energy electrons in nanometric targets of liquid water for explaining particular radio-biological endpoints, it is the aim of the present work to investigate the properties of cluster-size formation by electrons as a function of target size. Here, main emphasis is laid on the behaviour of cluster-size distributions if the target size is reduced from macroscopic to nanometric volumes.

Simulation of the measured ionisation-cluster distributions of alpha-particles in nanometric volumes of propane

In the last years, the probability of the formation of ionisation clusters by primary alpha particles at 5.4 MeV in nanometric volumes of propane (20.6 and 24.0 nm in a material of density 1.0 g cm(-3)) was studied experimentally and by Monte Carlo simulation. Calculations were performed taking into account the single electron detection efficiency of the track-nanodosimetric counter, which was estimated on the base of Monte Carlo calculations of electron transport inside the detector. Now a new evaluation of the efficiency has been performed, pointing out a value lower than previously estimated. Besides, the efficiency of the counter in resolving temporally the collected electrons has been calculated, together with its effect on the measured distribution. On the base of these evaluations, a new comparison has been performed between measurements and calculations, pointing out a better agreement than previously reported.

Effective Mode Volume of Nanoscale Plasmon Cavities

The controlled squeezing of electromagnetic energy into nanometric volumes via surface plasmon-polariton excitations in plasmonic nanoresonators is analyzed using the concept of an effective electromagnetic mode volume Veff, while taking careful account of the plasmon-polariton dispersion and the electromagnetic energy stored in the metal. Together with the quality factor Q of the cavity resonance, this enables a comparison with dielectric optical cavities, where Veff is limited by diffraction. For a Fabry–Perot type planar metallic cavity, a one-dimensional analytic model as well as a three-dimensional finite-difference time-domain simulation reveal that Veff is not bounded by diffraction, and that Q/Veff increases for decreasing cavity size. In this picture, matter–plasmon interactions can be quantified in terms of Q and Veff, and a resonant cavity model for the enhancement of spontaneous Raman scattering is presented.

Nanodosimetry, from radiation physics to radiation biology

In view of the fact that early damage to genes and cells by ionising radiation starts with the early damage to segments of the DNA, it is a great challenge to radiation research to describe the general behaviour of ionising radiation in nanometric target volumes (nanodosimetry). After summarising basic aspects of nanodosimetry, an overview is given about its present state. As far as experimental procedures are concerned, main emphasis is laid on single-ion counting and single-electron counting methods, which use millimetric target volumes filled with a low-pressure gas to simulate nanometric target volumes at unit density. Afterwards, physical principles are discussed, which can be used to convert experimental ionisation cluster-size distributions into those caused by ionising radiation in liquid water. In the final section, possibilities are analysed of how to relate parameters derived from the probability of cluster-size formation in liquid water to parameters derived from radiobiological experiments.

Microdosimetric Analysis of Various Mammography Spectra: Lineal Energy Distributions and Ionization Cluster Analysis

In view of recent recommendations on the frequency and the starting age of mammography screening in healthy women, it is desirable to quantify the enhanced relative biological effectiveness (RBE) of mammography X rays compared to hard X rays. While there is little doubt that the former are more potent in inducing biological damage than the latter, the magnitude of the effect is still hotly debated in the literature. We used Monte Carlo simulations and track structure analysis in micrometer and nanometer volumes to investigate differences in distributions of lineal energy and ionization clusters for a range of mammography X-ray qualities. Dose-averaged lineal energies, (yD), in breast tissue for various mammography qualities were found to result in quality factors about 40% higher than unity. Among the various mammography qualities studied, the popular molybdenum/molybdenum target/filter combination was found to have the highest (yD) in 1-microm spheres (about 5.0 keV/microm near the entrance surface of breast tissue). In 10-nm radius spheres, the mean ionization cluster order was found to be about 35% higher in mammography X rays compared to 300 keV electrons (roughly representing 60Co or 192Ir photon radiation). In even smaller spheres (2 nm radius), no significant differences were observed for the mean ionization cluster order between mammography X rays and 300 keV electrons. We conclude that the potential of mammography X rays to induce biological damage is probably not much higher than a factor of two compared to hard X rays.

Ionization-cluster distributions of alpha-particles in nanometric volumes of propane: measurement and calculation.

The probability of the formation of ionization clusters by primary alpha-particles at 5.4 MeV in nanometric volumes of propane was studied experimentally and by Monte Carlo simulation, as a function of the distance between the center line of the particle beam and the center of the target volume. The volumes were of cylindrical shape, 3.7 mm in diameter and height. As the investigations were performed at gas pressures of 300 Pa and 350 Pa, the dimensions of the target volume were equivalent to 20.6 nm or 24.0 nm in a material of density 1.0 g/cm(3). The dependence of ionization-cluster formation on distance was studied up to values equivalent to about 70 nm. To validate the measurements, a Monte Carlo model was developed which allows the experimental arrangement and the interactions of alpha-particles and secondary electrons in the counter gas to be properly simulated. This model is supplemented by a mathematical formulation of cluster size formation in nanometric targets. The main results of our study are (i) that the mean ionization-cluster size in the delta-electron cloud of an alpha-particle track segment, decreases as a function of the distance between the center line of the alpha-particle beam and the center of the sensitive target volume to the power of 2.6, and (ii) that the mean cluster size in critical volumes and the relative variance of mean cluster size due to delta-electrons are invariant at distances greater than about 20 nm. We could imagine that the ionization-cluster formation in nanometric volumes might in future provide the physical basis for a redefinition of radiation quality.

On the equivalence of propane-based tissue-equivalent gas and liquid water with respect to the ionisation-yield formation by electrons and alpha-particles.

One encouraging way, at present, to put the investigation of ionisation-yield formation in sub-cellular structures or, at least, in nanometric volumes of liquid water on an experimental basis is the use of highly sophisticated counters filled with gases at low operating pressure to simulate target volumes a few nm in diameter at unit density. To check the validity of such measurements, the ionisation-yield formation by electrons and alpha particles in liquid water was simulated using the Monte Carlo method and compared with that produced in propane-based tissue-equivalent gas (composition by volume: 55% C3H8, 39.6% CO2, 5.4% N2). After a short summary of the most important physical aspects of ionisation cluster formation, new results are presented and discussed from the point of view of radiation physics and radiation biology.

Ion-counting nanodosimetry: a new method for assessing radiation damage to DNA

A novel nanodosimeter is described, based on ion counting. It provides precise model-evaluation of radiation-induced ionization patterns in small condensed-matter volumes of nanometric size. The nanodosimeter consists of a millimetric, low-pressure, wall-less gas cell, serving as an expanded model of a nanometric condensed-matter volume. The method can also be employed for the assessment of radiation damage to advanced nanoelectronics.

A detector for track-nanodosimetry

In this paper, we describe a gas counter able to measure electron cluster distributions in nanometric sized sites. We designed a system of electrodes that is able to collect electrons from a nanometric wall-less sensitive volume and to transfer them to a counter that detects single electrons. Measurements of electron collection efficiency in propane gas confirm that we successfully collected electrons from a wall-less sensitive volume, of about 20 mm width, with an average efficiency of more than 20%.

Model for Radial Dependence of Frequency Distributions for Energy Imparted in Nanometer Volumes from HZE Particles

This paper develops a deterministic model of frequency distributions for energy imparted (total energy deposition) in small volumes similar to DNA molecules from high-energy ions of interest for space radiation protection and cancer therapy. Frequency distributions for energy imparted are useful for considering radiation quality and for modeling biological damage produced by ionizing radiation. For high-energy ions, secondary electron (delta-ray) tracks originating from a primary ion track make dominant contributions to energy deposition events in small volumes. Our method uses the distribution of electrons produced about an ion's path and incorporates results from Monte Carlo simulation of electron tracks to predict frequency distributions for ions, including their dependence on radial distance. The contribution from primary ion events is treated using an impact parameter formalism of spatially restricted linear energy transfer (LET) and energy-transfer straggling. We validate our model by comparing it directly to results from Monte Carlo simulations for proton and alpha-particle tracks. We show for the first time frequency distributions of energy imparted in DNA structures by several high-energy ions such as cosmic-ray iron ions. Our comparison with results from Monte Carlo simulations at low energies indicates the accuracy of the method.

Nucleation and Growth in Nanometric Volumes

Nucleation and Growth in Nanometric Volumes

Unconventional Laser Chemistry. Measurement of Chemical Reaction Processes with Localized Optical Fields.

A new microprobe of a near field scanning optical microscope has been developed for elucidating chemical reaction processes occurring in nanometer volumes. The probe is composed of a lasing microsphere, that induces the high-intensity localized optical field just outside of the sphere, and of a nanometer-sized particle fixed on the surface. Photon tunneling through the nanoparticle can be observed with high sensitivity due to the intracavity effect. Three-dimensional positioning control of the microprobe is performed by a laser manipulation technique based on radiation pressure.

Charged particle track structure parameters for application in radiation biology and radiation chemistry

Chemical and biological damage, caused by directly or indirectly ionizing radiations, is attributable to the action of the charged particle tracks in the absorbing medium. Attempts to elucidate the biophysical mechanisms involved, and to quantify the damage, are typically made in terms of one or more of the main physical parameters descriptive of the charged particle tracks. To meet a need for a ready reference source of such information, tables of the relevant parameters have been calculated for a liquid water medium. The full tables are obtainable elsewhere. Here, a description is given of the quantities calculated and an extended example is given of their application in elucidating the physical mechanisms of radiation-induced biological damage. A representative selection of data is displayed graphically to illustrate the extent of the information obtained and its value in, e.g., application to fundamental radiation dosimetry. Track structure data is tabulated for instantaneous energies of individual particles and for the fluence and dose-weighted spectra at charged particle equilibrium. Data are listed for incident electrons (50 eV to 30 MeV); characteristic Kα X-rays from carbon to uranium; commonly used radioisotope sources of 241Am, 137Cs, and 60Co and for continuous X-ray spectra (⩽300 kV); Auger electron and beta-emitter radionuclides; heavy charged particles having specific energies of 0.5 keV/μ to 1 GeV/μ for 74 ion types ranging from protons to uranium ions, and for monoenergetic neutrons (0.5 keV to 100 MeV). Quantities listed are kerma factors; fluence of charged particles per unit source concentration; buildup factors; track and dose-average LET and restricted LET; W values; z2/β2;β2; delta-ray yields, energies, and ranges; ion ranges; and the mean free path for primary ionization and the linear primary ionization. For indirectly ionizing radiations, the microdose quantities, frequency, and dose means of lineal energy are tabulated along with typical energy deposition distribution spectra for neutrons and gamma rays in micron and nanometer volumes. © 1994 John Wiley & Sons, Inc.

Calculation of Distributions for Energy Imparted and Ionization by Fast Protons in Nanometer Sites

Results are presented for a Monte Carlo calculation of energy imparted and ionization in nanometer volumes by individual proton tracks. Representative frequency distributions for ionization are presented for 0.25- to 3-MeV protons passing through and near spherical sites of 1- to 200-nm-diameter unit density water in specified geometry. In addition, the radial dependences of the mean energy imparted and of the relative variance of the distributions are obtained as functions of the site diameter and of the ion energy.