DEVELOPMENT OF A NUCLEAR MICROPROBE AND ITS APPLICATION TO NEUROBIOLOGY av Staffan Tapper Civilingenjör, Helsingkrona Nation Akademisk avhandling för avläggande av teknisk doktorsexamen vid tekniska fakulteten vid I' Lunds Tekniska och Naturvetenskapliga Högskola, kommer att offentligen försvaras i fysiska institutionens föreläsningssal B, fredagen 19 maj 1989, kl 14.00. Development of a Nuclear Microprobe and its Application to Neurobiology Staffan Tapper Department of Nuclear Physics, Lund, 1989 Contents Abstract Development of a Nuclear Microprobe and its application to neurobiology 5 Summary of the papers 12 I Achromatic ion-beam focusing using a low aberration 17 quadrupole with symmetric focusing properties II A computer-controlled magnetic post-lens scanning system for the Lund proton microprobe 33 III Enhanced beam quality for proton microprobes using ultrathin stripper foils in tandem accelerators 43 IV Characterization of the response function from a Si(Li)-detector using an absorber technique 49 V Calibration of a proton microprobe set-up 65 VI Accumulation of calcium in substantia nigra lesions induced by status epilepticus - A microprobe analysis 69 VII Elemental regional distribution in human brain tumours; PDCE analysis of biopsy and autopsy samples 83 V VIII Trace elements in astrocytomas and surrounding brain; Correlation to malignancy and survival 89 Acknowledgements 107 ,. Organization Document name LUND UNIVERSITY DOCTORAL DISSERTATION Department of Nuclear Physics Date of issue Sölvegatan 14 April 2S, 19RQ S-223 62 LUND, Sweden CODEN: LUTFD2/(TFKF-101?)/1-106/(19891 Authors) Sponsoring organization Staffan Tapper Titte and subtitle Development of a Nuclear Microprobe and its Application to Neurobiology Abstract A Nuclear Microprobe has been developed at the Pelletron accelerator in Lund. The design of the achromatic beam focusing system as well as of the beam scanning system is described. The focusing system consists of three magnetic- and three electrostatic quadrupole lenses together forming an achromatic quadnipole triplet with symmetric focusing properties. The beam quality from the accelerator has been improved by use of ultrathin stripper foils. The Nuclear Microprobe set-up has been applied to investigations of brain tissue specimens. The elemental disorder following epileptic seizures has been studied by micro-PIXE analysis. A combination of macro- and micro-PIXE analysis have been utilized in an investigation of elemental differences between normal human brain and human brain tumours. In the context of the quantification procedure in micro-PIXE analysis, calibration and X-ray detector i response function are discussed. i- 31 eyw Nuclear Microprobe, beam focusing, achromatic focusing, beam scanning, beam quality, micro-PIXE analysis, macro-PIXE analysis, quantitative analysis, hram tissue, brain tumour Classification system and/or index terms (if any) Supplementary bibliographical information Language F.n p 1 i Q\\ ISSN and key title ISBN Recipient's notes Number of pages Price v^^ 106 Security classification Distribution by (name and address) Department of Nuclear Physics Sölvegatan 14 I, the undersigned, being the copyrighröwnw oi me^iwrac^ÖTTn? above-mentioned dissertation, hereby grant to all reference sources permission to publish and d'swmiiute the abstract of the above-mentioned dissertation. Signature *•' '-— \ Date April 25, 1989 Development of a Nuclear Microprobe and its Application to Neurobiology 1. Introduction During the last decades, several micro analytical techniques. The micro- analytical methods have been developed beam set-up is often referred to as a based upon the high energy ion-beams Nuclear Microprobe (NM). from electrostatic accelerators. When a The principles of the NM are similar heavy-ion beam of a few MeV/u irradiates to that o^ the electron microscope (EM) a target, atomic and nuclear reactions are which has made important contributions to induced and the emitted radiation from the modern science mainly by its excellent reactions can be detected by different types capabilities to imaging small structures in of detectors. By measuring the the energies samples. The electron microscope can also of the emitted photons or particles, be used for elemental analysis by detecting information about the constituents in the the characteristic X-rays produced in the target can be obtained. If the ion-beam is target atoms by the electron beam. The compressed to micrometre dimensions, detection limits reached by this analysing these analytical methods can be used on method are of the order of mg/g. The rea- the micro-scale at the target. son for the high detection limit is that the The problem of obtaining the small- incident electrons produce an intense con- est possible ion-beam focus was initiated tinuous bremsstrahlung which obscure by Cookson in 1972 (1) and has since then weak-intensity peaks of characteristic X- attracted increasing interest among scien- rays. The bremsstrahlung decreases with tist working in ion- beam analysis. Micro- increasing mass of the impinging particle, analysis can add information into various which make heavy ions a straightforward fields of science e.g. investigation of way to lower the attainable limits of detec- elemental composition of biological cells tion. with the possibility to reveal trace element Compared to the EM, the proton distributions within single cells. The in- microscope, i.e. NM, does not produce creasing demand for characterization of such high quality images of the sample produced materials in material science is surface, equivalent to these of the EM but another application of microanalysis which the detection limits for X-ray analysis are will become more important. significantly better, typically by two orders The fast progress in this scientific of magnitude. In addition, heavy ions can area has partly been facilitated by the cause nuclear reactions among the target decreasing interest for small accelerators atoms and these nuclear reactions can give from scientists in the field of pure nuclear additional information as to the compo- physics. After years of declining import- nents of the sample. In its ability to detect ance these laboratories now experience a and quantify elements with high sensitivity febrile activity from scientists working on the micro-scale, NM has virtually no with application of science, e.g. competitor. PART I: The Nuclear Microprobe by a second larger collimator which limits Instrument the beam divergence from the object. This beam angle aperture limits aberrations in focusing due to vanishing with angle. The lens system then transfers the object to the 2. The Nuclear Microprobe set-up target plane, demagnified by a factor of 5- 100 depending on the particular lens syst- A schematic drawing of the NM set-up in em used. After the lenses are situated the Lund is shown in Fig 1. beam scanning system, which enables movement of the beam focus relative to the target. Different detectors are situated in the target chamber to detect the radiation produced by the ion beam. Focusing and deflection of the beam in the NM is a considerable problem due to the rigidity of high-energy heavy-ions. For ACCELERATOR focusing, quadrupole lenses have mainly been used. They yield field gradients high enough to bend the beam but their team optical properties are rather compliciited. However, the behaviour of charged pj nic- ies moving in electromagnetic fields is collimators well-known from Maxwell's laws, making it possible to investigate focusing proper- ties by using computer programs to simul- ate the behaviour of the ion-beam. Magne- tic fields are more powerful in bending high energy beams, but electrostatic fields may sometimes be advantageous, e.g. for focusing the reasons discussed in publications no. 1 lenses and 2 in this thesis. With current high-resolution nuclear target microprobes, the spatial resolution attain- chamber able is limited by aberrations in the focus- ing of the object collimator. These are usually divided into two categories intrin- Fig 1. Schematic drawing of the Lund NM sic aberrations and parasitic aberrations. Intrinsic aberrations consist of spherical and chromatic aberrations, whereas parasi- tic aberrations are focusing distortions The NM set-up is placed at an acce- caused by lens misalignment, distorting lerator beam-line after the analysing stray fields, non-perfect lenses etc. While magnet. The beam is collimated by a slit intrinsic aberrations define the ultimate system, the object collimator, with an limits of resolution in NM, in most systems aperture of about 0.02-0.10 mm in both it is the chromatic aberrations which are directions. The function of the accelerator responsible for the dominant contribution. is to accelerate the ions and transfer an It is possible to construct achromatic image of the ion-source to the object colli- lenses and lens systems with non-spherical mator with minimum beam quality degra- focusing properties by using complex dation. The object collimator is followed combinations of magnetic and electrostatic lenses in the former case and by the use of (Nuclear Reaction Analysis). Used to- quadrupole and octupole lenses in the gether, these analytical techniques facili- latter. However, with increasing system tate analysis of essentially the entire complexity, parasitic aberrations producing periodical table simultaneously, making beam distortions larger than the corrected NM a very powerful tool for micro- aberration can be introduced. Corrections