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Nickel-63 microirradiators and applications

Dissertation
Author: Jennifer L. Steeb
Abstract:
In this thesis, manufacturing of microirradiators, electrodeposition of radioactive elements such as Ni-63, and applications of these radioactive sources are discussed. Ni- 63 has a half life of 100 years and an average low energy beta electron of 17 keV, ideal for low dose low linear energy transfer (LET) research. The main focus of the research is on the novel Ni-63 microirradiator. It contains a small amount of total activity of radiation but a large flux, allowing the user to safely handle the microirradiator without extensive shielding. This thesis is divided into nine chapters. Properties of microirradiators and various competing radioactive sources are compared in the introduction (chapter 1). Detailed description of manufacturing Ni-63 microirradiator using the microelectrode as the starting point is outlined in chapter 2. The microelectrode is a 25 μm in diameter Pt disk sealed in a pulled 1 mm diameter borosilicate capillary tube, as a protruding wire or recessed disk microelectrode. The electrochemically active surface area of each is verified by cyclic voltammetry. Electrodeposition of nickel with a detailed description of formulation of the electrochemical bath in a cold "non-radioactive setting" was optimized by using parameters as defined by pourbaix diagrams, radioactive electroplating of Ni-63, and incorporation of safety regulations into electrodeposition. Calibration and characterization of the Ni-63 microirradiators as protruding wire and recessed disk microirradiators is presented in chapter 3. Diagrams of the estimated flux and calibration curves comparing the amount of Ni-63 deposited versus activity in disintegrations per minute are found here. Estimations of the dose that irradiated objects can receive from the microirradiator in air, water, and tissue are calculated using the calculations shown in this chapter. In chapters 4 through 6, applications of the Ni-63 microirradiators and wire sources are presented. Chapter 4 provides a radiobiological application of the recessed disk microirradiator and a modified flush microirradiator with osteosarcoma cancer cells. Cells were irradiated with two sources, with activities of 1 and 2000 Bq. Real time observations of DNA double strand breaks were observed. A novel benchtop detection system for the microirradiators is presented in chapter 5. Ni-63 is most commonly measured by liquid scintillation counters, which are expensive and not easily accessible within a benchtop setting. A developed solid state plastic scintillation device allows the microirradiators to be measured within a manufactured cavity of the plastic scintillation crystal. Precise measurements of the activity of the tip of the microirradiator were observed and compared against liquid scintillation. Results show liquid scintillation measurements overestimates the amount of radiation coming from the recessed disk. A novel 10 μCi Ni-63 electrochemically deposited wire acting as an ambient chemical ionization source for pharmaceutical tablets in mass spectrometry is in chapter 6. Typically, larger radioactive sources (15 mCi) of Ni-63 have been used in an ambient ionization scenario. However, custom electrochemically depositing Ni-63 onto a copper wire lowers the total activity by three orders of magnitude, allowing safe handling of the radioactive source. Additionally, this is the first application of using Ni-63 to ionize in atmosphere pharmaceutical tablets, leading to a possible field portable device. In the last chapters, chapters 7 through 8, previous microirradiator experiments and future work are summarized. Chapter 7 illustrates the prototype of the electrochemically deposited microirradiator, the Te-125 microirradiator. In conjunction with Oak Ridge National Laboratory, Te-125m is a low dose x-ray emitting element determined to be the best first prototype of an electrochemically deposited microirradiator. Manufacturing, characterization, and experiments that were not successful leading to the development of the Ni-63 microirradiator are discussed. In chapter 8, future work is entailed in continuing on with this thesis project. The work presented in the thesis is concluded in chapter 9. Overall, this thesis has developed a new type of radiation research involving small total activity sources that deliver a large flux. It demonstrates a novel opportunity for using radioactive sources and provides valuable information regarding their implementation to future radioactive sources using electrochemically deposited radioisotopes on microirradiators or other shaped sources. Safety is always a priority in dealing with radioactive materials, and in some instances has hindered research expanding this field.

vii TABLE OF CONTENTS Page ACKNOWLEDGEMENTS iv LIST OF TABLES xi LIST OF FIGURES xii SUMMARY xv CHAPTER

1 Introduction 1 1.1 Scope of the Thesis 1 1.2 Sealed vs. Open Radiation Source 1 1.3 Alpha, Beta, Gamma Radiation 2 1.4 Microbeams vs. Microirradiatiors 4 1.5 Nickel-63 Source 5 1.6 Tritium Microirradiator 6 2 Experimental 7 2.1 General 7 2.2 Fabrication of Microelectrodes 7 2.2.1 Recessed Disk Microelectrode 11 2.2.2 Protruding Wire Microelectrode 14 2.3 Electroplating 16 2.3.1 Watt’s Bath 16 2.3.2 Pourbaix Diagram 16 2.3.3 Development of Plating Procedure for Ni-63 18 2.3.4 Plating Ni-63 on Microelectrodes 20

viii 2.4 Assessment of Radioactivity on Ni-63 Plated Microelectrodes 21 2.5 Safety 23 3 Fabrication and Characterization of Ni-63 Microirradiators 24 3.1 Introduction 24 3.2 Results 27 3.2.1 Electrodeposition of Nickel 27 3.2.2 Liquid Scintillation 29 3.2.3 Analysis of the Ni-63 Flux 33 3.2.4 Estimation of the Self-Absorption Factor for Particle Flux 35 3.2.5 Dose Calculations 36 3.3 Conclusions 39 4 Ni-63 Microirradiation System for Observation of DNA Double Strand Break Response 40 4.1 Introduction 40 4.2 Materials and Methods 42 4.2.1 Microirradiator 42 4.2.2 Reporter Plasmid 42 4.2.3 Cells and Electroporation Conditions 43 4.2.4 Conventional γ-Irradiation and Cell Imaging 44 4.2.5 Ni-63 Microirradiator β-Irradiation 44 4.3 Results 45 4.3.1 Microscope Stage-mounted Irradiation System 45 4.3.2 Calibration of Biological Reporter System 48 4.3.3 Real-time Observation of Microirradiator Induced Foci Formation 48 4.3.4 Dynamic Behavior of Individual Foci 52 4.4 Discussion 54

ix 4.5 Previous Experiments 57 5 Portable Solid State Scintillation Calibrator 63 5.1 Introduction 63 5.2 Experimental 64 5.2.1 Safety Considerations 64 5.2.2 Chemicals 64 5.2.3 Calibrator Set-up 64 5.2.4 Characterization of Microirradiators 66 5.2.5 Data Aquisitioning and Processing 67 5.3 Results 69 5.3.1 Timed Calibrations 69 5.3.2 Liquid Scintillation 75 5.3.3 Cell Culture Medium 76 5.3.4 Comparison to LSC 77 5.3.5 Histogram 79 5.4 Conclusions 80 6 Beta Assisted Chemical Desorption Ionization 82 6.1 Introduction 82 6.2 Experimental 83 6.3 Results 86 6.3.1 Pharmaceutical Tablets 87 6.3.2 Limit of Detection 90 6.4 Conclusions 91

x 7 Te-125 Microirradiator 92 7.1 Introduction 92 7.2 Experimental 93 7.3 Conclusions 100 8 Future Work 102 8.1 Table of Radioisotopes 102 8.2 Brachytherapy 104 8.3 Bystander Effect 105 8.4 Ni-63 Batteries 108 9 Conclusions 110 APPENDIX A: Supplemental Information for Chapter 4 112 APPENDIX B: Incomplete Work: Miniature Ni-63 Electron Capture Detector 126 APPENDIX C: Incomplete Work: Polyaniline Reversible Radiation Sensor 131 REFERENCES 138 VITA 145

xi LIST OF TABLES Page Table 1: Calculated Dose Rates at Different Distances for Both Microirradiators 38 Table 2: Averaged Measured Activity Values in Bq 71 Table 3: Averaged Measured Activity Values in Bq continued 72 Table 4: Limit of Detection of Different API’s using BADCI 91 Table 5: Radioisotopes of General Interest to Health Physicists 103

xii LIST OF FIGURES Page Figure 1: Decay Scheme of Ni-63 5 Figure 2: Diagram of three electrode cell 9 Figure 3: Top view micrograph of recessed disk microelectrode 12 Figure 4: Voltammetric responses of recessed disk microelectrode 13 Figure 5: Top view micrograph of protruding wire microelectrode. 14 Figure 6: Voltammetric responses of protruding wire microelectrode 15 Figure 7: Porbaix diagram of the different forms of Ni depositions 17 Figure 8: Linear Sweep Voltammetry of cold Ni pseudo Watt’s bath solution 18 Figure 9: Picture of radioelectrochemical cell 19 Figure 10: Diagram of projected radiation field from recessed disk and protruding wire microirradiator. 25 Figure 11: Anodic stripping analysis of Ni from protruding wire and recessed disk microirradiators 27 Figure 12: Bar graph of current efficiencies of seven recessed disk microelectrodes 28 Figure 13: Experimental, theoretical, and self absorption corrected activity versus nickel deposited. 31 Figure 14: Calibration of 100 µCi source vs. 6 µCi source. 32 Figure 15: Various views of microirradiation system. 46 Figure 16: Calibration of reporter system. 47 Figure 17: Real time imaging of microirradiator induced 53-BP1 foci. 50 Figure 18: Real time observation of foci in absence of microirradiator. 51 Figure 19: A, Tracking of individual foci. B, Quantification of image intensity. 53 Figure 20: Experimental setup with straight recessed microirradiator. 58

xiii Figure 21: Optical micrographs of the nucleus of one osteosarcoma cell undergoing irradiation. 59 Figure 22: Graph in time of foci observed from 2 Bq irradiator vs. control. 60 Figure 23: Time lapsed image of osteocarcoma nucleus undergoing irradiation by 10 µCi Ni-63 source. 61 Figure 24: A, Schematic of Calibrator. B, Picture of calibrator setup. 65 Figure 25: Scheme of data acquisition. 68 Figure 26: Graph of counts versus time of one individual trial of microirradiator 1 within the calibrator. 69 Figure 27: Graph of counts versus time of one individual trial of a Ni-63 electroplated wire source. 70 Figure 28: Comparison of short, long, liquid scintillation and cell culture medium measurements for the solid state scintillation calibrator. 76 Figure 29: Comparison of the microirradiators’ liquid scintillation measured activities versus solid state scintillation activities. 78 Figure 30: Energy spectrum of Ni-63 (3766 Bq) plated source. 80 Figure 31: A, Schematic of the BADCI ion source. B, Mass spectrum showing typical reactant ion background. 85 Figure 32: Analysis of various pharmaceutical tablets. 88 Figure 33: Mass spectra of multi-component pharmaceutical tablet in positive and negative ionization mode. 89 Figure 34: Decay Scheme of Te-125m. 93 Figure 35: Bar graph of 3 Te-125 microirradiators tested. 95 Figure 36: Superimposed graph of the stripped and stripped solution from Figure 34. 96 Figure 37: Linear stripping voltammetry of Te from microelectrode. 97 Figure 38: Linear stripping voltammetry of Te from microelectrode without removal of electrode from solution. 98 Figure 39: Linear Stripping Voltammetry of Te , tapped after electrodeposition. 99 Figure 40: MCNP dose profile of 25 micron Te-125 deposit onto Pt. 100

xiv Figure 41: Illustration of the bystander effect from ionizing radiation. 106 Figure 42: Image of Japanese medaka fish. 107 Figure 43: Diagram of ECD housing with Ni-63 source. 128 Figure 44: Scheme of ECD 129 Figure 45: Structure of polyaniline in redox states 131 Figure 46: CV of polyaniline cycled before and after irradiation. 133 Figure 47: UVvis spectrum of polyaniline with chloranil with irradiation. 134 Figure 48: Polyaniline no additives after irradiation 135

xv SUMMARY

In this thesis, manufacturing of microirradiators, electrodeposition of radioactive elements such as Ni-63, and applications of these radioactive sources are discussed. Ni- 63 has a half life of 100 years and an average low energy beta electron of 17 keV, ideal for low dose low linear energy transfer (LET) research. The main focus of the research is on the novel Ni-63 microirradiator. It contains a small amount of total activity of radiation but a large flux, allowing the user to safely handle the microirradiator without extensive shielding. This thesis is divided into nine chapters. Properties of microirradiators and various competing radioactive sources are compared in the introduction (chapter 1). Detailed description of manufacturing Ni-63 microirradiator using the microelectrode as the starting point is outlined in chapter 2. The microelectrode is a 25 µm in diameter Pt disk sealed in a pulled 1 mm diameter borosilicate capillary tube, as a protruding wire or recessed disk microelectrode. The electrochemically active surface area of each is verified by cyclic voltammetry. Electrodeposition of nickel with a detailed description of formulation of the electrochemical bath in a cold “non-radioactive setting” was optimized by using parameters as defined by pourbaix diagrams, radioactive electroplating of Ni-63, and incorporation of safety regulations into electrodeposition. Calibration and characterization of the Ni-63 microirradiators as protruding wire and recessed disk microirradiators is presented in chapter 3. Diagrams of the estimated flux and calibration curves comparing the amount of Ni-63 deposited versus activity in disintegrations per minute are found here. Estimations of the dose that irradiated objects

xvi can receive from the microirradiator in air, water, and tissue are calculated using the calculations shown in this chapter. In chapters 4 through 6, applications of the Ni-63 microirradiators and wire sources are presented. Chapter 4 provides a radiobiological application of the recessed disk microirradiator and a modified flush microirradiator with osteosarcoma cancer cells. Cells were irradiated with two sources, with activies of 1 and 2000 Bq. Real time observations of DNA double strand breaks were observed. A novel benchtop detection system for the microirradiators is presented in chapter 5. Ni-63 is most commonly measured by liquid scintillation counters, which are expensive and not easily accessible within a benchtop setting. A developed solid state plastic scintillation device allows the microirradiators to be measured within a manufactured cavity of the plastic scintillation crystal. Precise measurements of the activity of the tip of the microirradiator were observed and compared against liquid scintillation. Results show liquid scintillation measurements overestimates the amount of radiation coming from the recessed disk. A novel 10 µCi Ni-63 electrochemically deposited wire acting as an ambient chemical ionization source for pharmaceutical tablets in mass spectrometry is in chapter 6. Typically, larger radioactive sources (15 mCi) of Ni-63 have been used in an ambient ionization scenario. However, custom electrochemically depositing Ni-63 onto a copper wire lowers the total activity by three orders of magnitude, allowing safe handling of the radioactive source. Additionally, this is the first application of using Ni-63 to ionize in atmosphere pharmaceutical tablets, leading to a possible field portable device. In the last chapters, chapters 7 through 8, previous microirradiator experiments and future work are summarized. Chapter 7 illustrates the prototype of the

xvii electrochemically deposited microirradiator, the Te-125 microirradiator. In conjunction with Oak Ridge National Laboratory, Te-125m is a low dose x-ray emitting element determined to be the best first prototype of an electrochemically deposited microirradiator. Manufacturing, characterization, and experiments that were not successful leading to the development of the Ni-63 microirradiator are discussed. In chapter 8, future work is entailed in continuing on with this thesis project. The work presented in the thesis is concluded in chapter 9. Overall, this thesis has developed a new type of radiation research involving small total activity sources that deliver a large flux. It demonstrates a novel opportunity for using radioactive sources and provides valuable information regarding their implementation to future radioactive sources using electrochemically deposited radioisotopes on microirradiators or other shaped sources. Safety is always a priority in dealing with radioactive materials, and in some instances has hindered research expanding this field.

1 CHAPTER 1 INTRODUCTION

1.1 General The main objective of this thesis is the microirradiator, which is a microelectrode with a radioactive element deposited onto the end. A microelectrode is an electrochemical tool using a 25 µm and under 1 micron diameter conducting wire (Pt, Au, C) encapsulated in glass. Instead of using this as an electroanalytical device, the microirradiator’s main purpose is to deliver high flux density of ionizing radiation while allowing the user to encounter only a minimal amount of radiation. It is transformed into a radiation delivery tool by depositing a radioisotope onto its electroactive surface area (4.9 x 10 -6 cm 2 ). 1 This allows for a small amount of total activity but for a high flux density (electrons (β)/cm 2 ) due to the small surface area. This allows the microirradiator to be used in various experiments by introducing a low activity from an open source that can be handled safely in the laboratory.

1.2 Sealed vs. Open Source A sealed source is defined as a radioactive source that has been sealed within an outer container and tested to ensure that the active materials cannot escape the container. Various types of sealed sources are used for calibration and research, anywhere from a button source to irradiators used in large facilities. 2 Specific categories are held for each sealed source, ranging from sources that can deliver a lethal dose with close exposure in minutes (industrial irradiators) to sealed sources that are unlikely to cause harm (x-ray

2 fluorescence generators). Especially in the case of irradiators and electron beams, mostly used in research type applications are one of the most dangerous kind (Category 5). These irradiators need to be housed in separate buildings with extensive shielding, controlled access and other safety procedures. Electron beams also require high vacuum to prevent scattering of the electrons in air and have mica windows underneath specimens to be irradiated to ensure delivery of radiation. 3

The advantage of our microirradiator is that it is an open source. An open source in contrast to a sealed source is not in an external container, allowing the source to interact with the adjacent areas where it is located. These types of sources are extensively used in biology and medical applications, where radiation is commonly used as radiolabeled tracers and/or radiation delivered therapy (prostate seeds). 4 An important issue when dealing with open sources is contamination with radioactivity. In contrast, the microirradiator has a low activity for an open source. This advantage has opened the door for using low activity sources in various bench applications in-situ. 1, 5

1.3 Alpha, Beta, Gamma Radiation Within open and sealed sources different types of radiation can be housed. The three main types of radiation are alpha, beta, and gamma rays. Alpha particles are a He nucleus ejected from the atom. In general the equation for alpha decay is

(1) Where X is the parent nuclide and Y is the daughter nuclide. Heavy and proton rich nuclei are the most common alpha emitters, where the elements typically above Polonium (Z=84) are almost exclusively alpha emitters. 4 Concerning alpha particle

3 interaction with humans, alphas are the most dangerous particle internally, and the least harmful externally. This is due to the fact that alphas are high linear energy transfer (LET) radiation. LET is defined as the amount of energy deposited within a material per unit distance. An alpha particle release all of its energy within 50-70 microns of dead skin layer, rendering the particle harmless transdermally. However, internally there is no protective dead skin cell layer, and alpha particles wreak havoc on the living cells because of this. Gamma decay is a high energy photon emission (150 keV-GeV) from a nucleus transition from the excited state to the ground state. Gamma rays are also most commonly accompanying other modes of radioactive decay such as in transition to other elements. Gamma photons are not as dangerous externally because of their low LET, however in high enough doses they are dangerous externally. Beta particles are the ejection of an electron (or positron) from the nucleus of an atom. In general the equation for beta emission is

(2) Where X is the parent nuclei, Y is the daughter nuclei, and is the antineutrino. Beta particles are unique because they do not emit monoenergetic energies such as alpha and gamma emitters. 4 Because of the ejection of the antineutrino in following Fermi’s golden rule, a spectrum of energy levels is released dependent upon how much interaction the electron and antineutrino had before passing the outer electron shell boundaries. This leads to a broad energy spectrum with an E max representing the endpoint of the distribution. Beta is a low LET emitter. Beta particles are not as dangerous as alpha internally, and not as dangerous as gamma externally. Because of this, Beta particles are

4 not as heavily studied in radiation studies because of the lack of pure beta emitting materials and the need for an electron gun or large scale irradiators for research if electron studies are required.

1.4 Microbeams vs. Microirradiators Irradiators and microbeams have long been used in the field of radiobiology for the study of the “bystander effect” and the study of the mechanism of double strand DNA (dsDNA) breaks. Commonly, these experiments are run in sequences such as by using a microbeam, running experiments, fixing cells, and then recording the observations. These irradiators and microbeams typically involve a large collimated radioactive source (such as Cs-137) with shielding to form a microbeam. Alternatively, x-ray and electron beams are used, where monoenergetic electron beams are under vacuum. Samples must then be placed under a sheath of mica to form the boundary layer between atmosphere and vacuum when they are irradiated. The drawback of using microbeams and macroirradiators are that real short-time experiments are not possible to conduct due to the physical space separation of the beam and biological facilities. In other words, large amounts of radiation are not allowed in standard biological laboratories for safety reasons. In contrast, the microirradiator enables to use a microscope and to observe the experiment in situ, while irradiation experiments are taking place. Furthermore, many research experiments cannot be done because of the health and safety concerns with working with large amounts of radiation. Microbeams have been available since the 90’s, but the field of radiobiology much is to be gained with real time observations and data collection whilst radiation is being applied. 3, 6, 7

5

1.5 Ni-63 Ni-63 was chosen as the element to be used in the microirradiator throughout this thesis due to its low energy beta emission with a maximum energy of 67 keV, average 18 keV. Ni-63 decays to stable Cu-63 by pure beta emission with a 100 year half life, as shown below in the equation.

Figure 1. Decay Scheme of Ni-63

Ni-63 is most commonly used in electron capture detectors, where halogenated organics, nitro and amine groups are particularly suitable for this mode of detection. 8 In these instances, Ni-63 comes in a foil, with an activity from 10-15 mCi. This radioisotope is only available as a NiCl 2 salt, where nickel forms a strong and stable electrochemical deposit, with formal potential E= -.259 V vs. the standard hydrogen electrode potential (SHE). 9 Because of these reasons, Ni-63 was the element of choice for all of the microirradiators manufactured in this project. E max

6

1.6 Tritium Microirradiator Previously, our research group had developed a tritium irradiator incorporating tritiated sodium propionate within a polyaniline (PANI) film on a microelectrode. Tritium has the unique capability of being incorporated into any compound with hydrogens. Therefore, a microirradiator can be made from a molecule with radiolabeled hydrogen instead of an electrochemically deposited metal. However, from this prototype, we learned that the use of tritiated ions presented serious handling and regulatory problems. Moreover, the PANI film was not stable enough for repetitive use. We also learned that an electrochemical metallic deposition would be easier and more reliable for deposition strength and stability. 10

7 CHAPTER 2 EXPERIMENTAL

2.1 General This chapter is dedicated to the detailed description of manufacturing and electrodepositing onto microirradiators. To start, a microirradiator is a microelectrode with a radioactive metal electrodeposited onto its electroactive surface. Specific microelectrodes, including the recessed disk microelectrode and the microcylinder electrodes are outlined below. Since the microirradiator uses a microelectrode as the tool for radiation delivery, specific microelectrodes are manufactured to optimize the flux delivered to the source at hand. In electrochemistry in general, the most popular microelectrode used is the radial disk microelectrode, in which a micron sized electroactive surface is flush to the glass. The microirradiator differs from general electrochemistry tools due to the shape of the microelectrode enhancing the delivery of radiation by shielding or projecting radiation to the sample. In this chapter a detailed description of the fabrication of microelectrodes, specific microelectrodes used, and electrodeposition techniques of Ni-63 will be discussed.

2.2 Fabrication of Microelectrodes Microelectrodes can be defined as an electrode in which the electroactive area is less than or equal to 25 microns. 11 These are common tools used in the field of electrochemistry to quantify oxidation and reduction potentials, diffusion coefficients, and electron transfer to name a few. To manufacture a microelectrode, typically glass is

8 melted around the electroactive surface to ensure proper sealing and to prevent the outer solution from coming into contact with the inner wires of the microelectrode. There are several methods involving melting the glass around the electrochemical surface, including by hand or by a glass puller. Glass pullers are preferred due to minimizing the glass surrounding the microelectrode surface, in turn minimizing surface imperfections and/or adsorption of undesired compounds by conducting experiments in solution. Types of pullers that can be used are either vertical or horizontal, in which the glass containing the platinum wire is sealed within by melting and pulling simultaneously. The amount of glass and or the amount of pulling done can be controlled by the instrument. Common glass used to make microelectrodes are capillary tubes made of either borosilicate or lead glass. Depending upon the application, 1 mm outer diameter capillary tubes are most commonly used throughout the literature for pulled microelectrodes. For the application of the microirradiator, minimal glass is ideal due to the main use in cells 20 µm in diameter and the minimization of radioactive materials adsorbed onto the glass. The electroactive surface can involve various conducting materials, such as gold, platinum, silver, and carbon fiber. Metals that are unreactive are most desirable for experimentation within solution, and the noble metals with the highest overpotential such as gold and platinum are most commonly used in electrochemical microelectrode research. 11 Once the electroactive surface material has been sealed within glass, a contact, usually involving metallic epoxy is made between the microelectrode and the external contact and is ready for electrochemical experiments. A three electrode cell is a basic electrochemical setup to study oxidation and reduction. Within the scope of this thesis, many methods from the field of

9 electrochemistry are used and will be explained further below. A three electrode electrochemical cell consists of a working, auxillary, and reference electrode. 11, 12

Figure 2. Diagram of three electrode cell. 13

The working electrode is the microelectrode, the auxillary electrode is a Pt wire (1 mm diameter, 3 mm in length) and the reference electrode is a Ag/AgCl reference manufactured in house. Within the electrochemical cell, an electrically conducting solution contacts all three electrodes, forming the complete cell. A potentiostat is used to control the current between the auxillary and working electrode, where the working electrode’s potential is controlled in respect to the reference electrode. In electrochemistry, oxidation and reduction can be monitored using the three electrode cell by cyclic voltammetry, which is a measurement involving a potentiodynamic change in time while monitoring the current. 1 The electrode potential ramps in time, and is defined as the scan rate (V/s). Diffusion to the surface of the

10 working electrode can also be determined from cyclic voltammetry. This is governed by the Cottrell equation, where

(3) i is current in amps, n is electrons transferred in the reaction, F is faraday’s constant, A is area of the electrode in cm 2 , Cj is the initial concentration of solution in mol/cm 3 , D is diffusion coefficient in cm 2 /s, and t is time. 11 According to this equation, the current will decrease as time increases. For a planar electrode, in which diffusion to the electrode is limited by current, a decrease due to mass transport will occur (Fig.4,5). However, in the case of disk microelectrodes used throughout this thesis, the diffusion layer expands spherically in time, leading to the equation modification of

4 (4)

Where 4 is a constant, n is the number of electrons transferred in the reaction, F is Faraday’s constant, A is area of the electrode in cm 2 , c is the initial concentration of solution in mol/cm 3 , D is diffusion coefficient in cm 2 /s, and a is the radius of the disk. 11, 14, 15 These equations allow the determination of the surface area of an electrode using current. This equation more specifically is used for the microirradiators to determine whether the area has changed or has been modified by calculating the amount of current passed. All electrochemical characterizations of microelectrodes before and after etching utilized a Princeton Applied Research Potentiostat/Galvanostat 273 A. The potentiostat was interfaced to a PC computer, and all voltammetric data was acquired through CView and CWare v 2.8d electrochemical software programs (Scribner Associates, Inc).

Full document contains 164 pages
Abstract: In this thesis, manufacturing of microirradiators, electrodeposition of radioactive elements such as Ni-63, and applications of these radioactive sources are discussed. Ni- 63 has a half life of 100 years and an average low energy beta electron of 17 keV, ideal for low dose low linear energy transfer (LET) research. The main focus of the research is on the novel Ni-63 microirradiator. It contains a small amount of total activity of radiation but a large flux, allowing the user to safely handle the microirradiator without extensive shielding. This thesis is divided into nine chapters. Properties of microirradiators and various competing radioactive sources are compared in the introduction (chapter 1). Detailed description of manufacturing Ni-63 microirradiator using the microelectrode as the starting point is outlined in chapter 2. The microelectrode is a 25 μm in diameter Pt disk sealed in a pulled 1 mm diameter borosilicate capillary tube, as a protruding wire or recessed disk microelectrode. The electrochemically active surface area of each is verified by cyclic voltammetry. Electrodeposition of nickel with a detailed description of formulation of the electrochemical bath in a cold "non-radioactive setting" was optimized by using parameters as defined by pourbaix diagrams, radioactive electroplating of Ni-63, and incorporation of safety regulations into electrodeposition. Calibration and characterization of the Ni-63 microirradiators as protruding wire and recessed disk microirradiators is presented in chapter 3. Diagrams of the estimated flux and calibration curves comparing the amount of Ni-63 deposited versus activity in disintegrations per minute are found here. Estimations of the dose that irradiated objects can receive from the microirradiator in air, water, and tissue are calculated using the calculations shown in this chapter. In chapters 4 through 6, applications of the Ni-63 microirradiators and wire sources are presented. Chapter 4 provides a radiobiological application of the recessed disk microirradiator and a modified flush microirradiator with osteosarcoma cancer cells. Cells were irradiated with two sources, with activities of 1 and 2000 Bq. Real time observations of DNA double strand breaks were observed. A novel benchtop detection system for the microirradiators is presented in chapter 5. Ni-63 is most commonly measured by liquid scintillation counters, which are expensive and not easily accessible within a benchtop setting. A developed solid state plastic scintillation device allows the microirradiators to be measured within a manufactured cavity of the plastic scintillation crystal. Precise measurements of the activity of the tip of the microirradiator were observed and compared against liquid scintillation. Results show liquid scintillation measurements overestimates the amount of radiation coming from the recessed disk. A novel 10 μCi Ni-63 electrochemically deposited wire acting as an ambient chemical ionization source for pharmaceutical tablets in mass spectrometry is in chapter 6. Typically, larger radioactive sources (15 mCi) of Ni-63 have been used in an ambient ionization scenario. However, custom electrochemically depositing Ni-63 onto a copper wire lowers the total activity by three orders of magnitude, allowing safe handling of the radioactive source. Additionally, this is the first application of using Ni-63 to ionize in atmosphere pharmaceutical tablets, leading to a possible field portable device. In the last chapters, chapters 7 through 8, previous microirradiator experiments and future work are summarized. Chapter 7 illustrates the prototype of the electrochemically deposited microirradiator, the Te-125 microirradiator. In conjunction with Oak Ridge National Laboratory, Te-125m is a low dose x-ray emitting element determined to be the best first prototype of an electrochemically deposited microirradiator. Manufacturing, characterization, and experiments that were not successful leading to the development of the Ni-63 microirradiator are discussed. In chapter 8, future work is entailed in continuing on with this thesis project. The work presented in the thesis is concluded in chapter 9. Overall, this thesis has developed a new type of radiation research involving small total activity sources that deliver a large flux. It demonstrates a novel opportunity for using radioactive sources and provides valuable information regarding their implementation to future radioactive sources using electrochemically deposited radioisotopes on microirradiators or other shaped sources. Safety is always a priority in dealing with radioactive materials, and in some instances has hindered research expanding this field.