Microfabrication using focused ion beams

“Soon all semiconductor devices could be made this way” is a claim often made for focussed ion beam technology. As the Osaka University team relate in this overview, numerous labs around the world have used FIB to dope, deposit, etch and define semiconductor, and other, films to microfabricate circuits and devices. FIB has yet to become a routine method but the techniques under this banner hold much promise for the production of next generation devices.     

A beam model for focused proton pencil beams

IntroductionWe present a beam model for Monte Carlo simulations of the IBA pencil beam scanning dedicated nozzle installed at the Skandion Clinic. Within the nozzle, apart from entrance and exit windows and the two ion chambers, the beam traverses vacuum, allowing for a beam that is convergent downstream of the nozzle exit.Materials and methodsWe model the angular, spatial and energy distributions of the beam phase space at the nozzle exit with single Gaussians, controlled by seven energy dependent parameters. The parameters were determined from measured profiles and depth dose distributions. Verification of the beam model was done by comparing measured and GATE acquired relative dose distributions, using plan specific log files from the machine to specify beam spot positions and energy.ResultsGATE-based simulations with the acquired beam model could accurately reproduce the measured data. The gamma index analysis comparing simulated and measured dose distributions resulted in >95% global gamma index pass rates (3%/2 mm) for all depths.ConclusionThe developed beam model was found to be sufficiently accurate for use with GATE e.g. for applications in quality assurance (QA) or patient motion studies with the IBA pencil beam scanning dedicated nozzles.     

Longitudinal ion source with the current self-compensation of the focused ion beam

Utilization of ballistic focusing in the longitudinal Hall-type ion source is described. It allows transformation of the ion beam shape from an “ellipsoidal” one to a linear one, as well as increasing the ion beam current density per the operating surface. Both the influence of transverse magnetic field and edge effects on the beam shape are investigated. The ion beam is charge compensated by a plasma neutralizer designed on the basis of a supplementary semi-self-maintained magnetron-type discharge and hollow cathode effect.     

A streamlined workflow for automated cryo focused ion beam milling

Cryo-electron tomography (cryo-ET) is an emerging technique to study the cellular architecture and the structure of proteins at high resolution in situ. Most biological specimens are too thick to be directly investigated and are therefore thinned by milling with a focused ion beam under cryogenic conditions (cryo-FIB). This procedure is prone to contaminations, which makes it a tedious process, often leading to suboptimal results. Here, we present new hardware that overcomes the current limitations. We developed a new glove box and a high vacuum cryo transfer system and installed a stage heater, a cryo-shield and a cryo-shutter in the FIB milling microscope. This reduces the ice contamination during the transfer and milling process and simplifies the handling of the sample. In addition, we tested a new software application that automates the key milling steps. Together, these improvements allow for high-quality, high-throughput cryo-FIB milling. This paves the way for new types of experiments, which have been previously considered infeasible.     

Visualization of air and metal inhomogeneities in phantoms irradiated by carbon ion beams using prompt secondary ions

PurposeNon-invasive methods for monitoring of the therapeutic ion beam extension in the patient are desired in order to handle deteriorations of the dose distribution related to changes of the patient geometry. In carbon ion radiotherapy, secondary light ions represent one of potential sources of information about the dose distribution in the irradiated target. The capability to detect range-changing inhomogeneities inside of an otherwise homogeneous phantom, based on single track measurements, is addressed in this paper.MethodsAir and stainless steel inhomogeneities, with PMMA equivalent thickness of 10 mm and 4.8 mm respectively, were inserted into a PMMA-phantom at different positions in depth. Irradiations of the phantom with therapeutic carbon ion pencil beams were performed at the Heidelberg Ion Beam Therapy Center. Tracks of single secondary ions escaping the phantom under irradiation were detected with a pixelized semiconductor detector Timepix. The statistical relevance of the found differences between the track distributions with and without inhomogeneities was evaluated.ResultsMeasured shifts of the distal edge and changes in the fragmentation probability make the presence of inhomogeneities inserted into the traversed medium detectable for both, 10 mm air cavities and 1 mm thick stainless steel. Moreover, the method was shown to be sensitive also on their position in the observed body, even when localized behind the Bragg-peak.ConclusionsThe presented results demonstrate experimentally, that the method using distributions of single secondary ion tracks is sensitive to the changes of homogeneity of the traversed material for the studied geometries of the target.     

Imaging three-dimensional tissue architectures by focused ion beam scanning electron microscopy

In this protocol, we describe a 3D imaging technique known as 'volume electron microscopy' or 'focused ion beam scanning electron microscopy (FIB/SEM)' applied to biological tissues. A scanning electron microscope equipped with a focused gallium ion beam, used to sequentially mill away the sample surface, and a backscattered electron (BSE) detector, used to image the milled surfaces, generates a large series of images that can be combined into a 3D rendered image of stained and embedded biological tissue. Structural information over volumes of tens of thousands of cubic micrometers is possible, revealing complex microanatomy with subcellular resolution. Methods are presented for tissue processing, for the enhancement of contrast with osmium tetroxide/potassium ferricyanide, for BSE imaging, for the preparation and platinum deposition over a selected site in the embedded tissue block, and for sequential data collection with ion beam milling; all this takes approximately 90 h. The imaging conditions, procedures for alternate milling and data acquisition and techniques for processing and partitioning the 3D data set are also described; these processes take approxiamtely 30 h. The protocol is illustrated by application to developing chick cornea, in which cells organize collagen fibril bundles into complex, multilamellar structures essential for transparency in the mature connective tissue matrix. The techniques described could have wide application in a range of fields, including pathology, developmental biology, microstructural anatomy and regenerative medicine.     

Computation of cell survival in heavy ion beams for therapy

A simplified method for the calculation of mammalian cell survival after charged particle irradiation is presented that is based on the track structure model of Scholz and Kraft [1, 2]. Utilizing a modified linear-quadratic relation for the x-ray survival curve, one finds that the model yields linear-quadratic relations also for heavy ion irradiation. If survival is calculated as a function of specific energy, z, in the cell nucleus – thus reducing the stochastic fluctuations of energy deposition – the increase in slope of the survival curve and therefore the coefficient β _z can be estimated with sufficient accuracy from the initial slope, α _z . This permits the tabulation of the coefficients α _z for the particle types and energies of interest, and subsequent fast calculations of survival levels at any point in a mixed particle beam. The complexity of the calculations can thereby be reduced in a wide range of applications, which permits the rapid calculations that are required for treatment planning in heavy ion therapy. The validity of the modified computations is assessed by the comparison with explicit calculations in terms of the original model and with experimental results for track-segment conditions. The model is then used to analyze the influence of beam fragmentation on the biological effect of charged particle beams penetrating to different depths in tissue. In addition, cell-survival rates after neutron irradiation are computed from the slowing-down spectra of secondary charged particles and are compared to experimental observations. Received: 10 August 1996 / Accepted in revised form: 16 December 1996     

Focusing of heavy ion beams by a high-current plasma lens

Results are presented from studies of the focusing of wide-aperture low-energy (100–400 eV) and moderate-energy (5–25 keV) beams of heavy-metal ions by a high-current electrostatic plasma lens. It is found experimentally that, because of the significant electron losses, the efficient focusing of such beams can be achieved only if the external potentials at the plasma-lens electrodes are maintained constant. Static and dynamic characteristics of the lens are studied under these conditions. It is shown that, as the beam current and the electrode voltage increase, the maximum electrostatic field in the lens tends to a certain limiting value because of the increase in the spatial potential near the lens axis. The role of spherical and moment aberrations in the focusing of wide-aperture low-divergence ion beams is revealed. It is shown that, even when spherical aberrations are minimized, unremovable moment aberrations decrease the maximum compression ratio of a low-energy heavy-ion beam because of the charge separation of multiply charged ions in the focal region. At the same time, as the ion energy increases, the role of the moment aberrations decreases and the focusing of high-current heavy-ion beams by a plasma lens becomes more efficient than the focusing of light-ion (hydrogen) beams. This opens up the possibility of using electrostatic plasma lenses to control ion beams in high-dose ion implanters and high-current accelerators of heavy ions.     

Biological effects of ion beams in Nicotiana tabacum L.

The biological effects of ion beams on Nicotiana tabacum L., particularly the induction of chromosome aberrations, were investigated. Dry seeds were exposed to ¹²C⁵⁺, ⁴He²⁺ and ¹H⁺ beams with linear energy transfer (LET) ranging from 1 to 111 keV/μm and irradiated with gamma-rays. Ion beams were more effective in reducing germination and survival of the seeds than gamma-rays. The LD₅₀ for ¹²C⁵⁺ beams, ⁴He²⁺ beams and gamma-rays were 35, 60 and 500 Gy, respectively. The frequencies of mitotic cells with chromosome aberrations, such as chromosome bridges, acentric fragments and lagging chromosomes in the root tip cells of the exposed seeds, increased linearly with increasing doses. Relative biological effectiveness (RBE) values, based on the doses that induced a survival inhibition of 50% and a 10% frequency of aberrant cells, were 14.3–17.5 for the ¹²C⁵⁺ beams, 7.0–8.3 for the ⁴He²⁺ beams and 7.8 for the ¹H⁺ beams. Furthermore, the relative ratios of the chromosome aberration types were significantly different between the ion beam and the gamma-ray regimes: chromosome fragments were more frequent in the former, and chromosome bridges in the latter. Based on these results, we concluded that the repair process of initial lesions induced by ion beams may be different from that induced by low- LET radiation. Received: 29 October 1998 / Accepted in revised form: 25 March 1999     

Quality assurance of carbon ion and proton beams: A feasibility study for using the 2D MatriXX detector

PurposeThe quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements.MethodsMatriXX is a commercial detector composed of 32 × 32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44 MeV proton and a 221.45 MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia – Italy, and the results were analyzed and compared.ResultsThe sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230 μm for carbon ions and less than 100 μm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement.ConclusionsThe results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.     

Impedance characterization of a piezoelectric immunosensor part II: Salmonella typhimurium detection using magnetic enhancement

This study investigated the usefulness and characteristics of a 5-MHz quartz crystal resonator as a sensor of biological pathogens such as Salmonella typhimurium. An impedance analyzer measured the impedance behavior of the oscillating quartz crystal exposed to various concentrations of Salmonella (10(2)-10(8) cells per ml). The Salmonella cells were captured by antibody-coated paramagnetic microspheres, and then these complexes were moved magnetically to the sensing quartz and were captured by antibodies immobilized on the crystal surface. The response of the crystal was expressed in terms of equivalent circuit parameters. The motional inductance and the motional resistance increased as a function of the concentration of Salmonella. The viscous damping was the main contributor to the resistance and the inductance in a liquid environment. The load resistance was the most effective and sensitive circuit parameter. A magnetic force was a useful method to collect the complexes of Salmonella-microspheres on the crystal surface and enhance the response of the sensor. In this system, the detection limit, based on resistance monitoring, was about 10(3) cells per ml.