Theses, Dissertations, and other Required Graduate Degree Essays

There is a great interest in developing new high-performance piezo-/ferroelectric materials that are lead-reduced or lead-free. This work focuses on using bismuth as a lead alternative, and studies solid solutions based on the end-member Bi(Zn2/3Nb1/3)O3 (BZN). First, ceramics of the (1-x)PbTiO3-xBi(Zn2/3Nb1/3)O3 [(1-x)PT-xBZN] solid solution were synthesized. The tetragonality (c/a ratio) and A-site displacement increase with increasing BZN content, as revealed by X-ray diffraction analysis. Dielectric measurements show that the Curie temperature TC increases with increasing BZN up to a maximum of 520 °C for the composition of x = 0.20. These results indicate the structural origin of the enhanced tetragonality and properties that arise from the increased anisotropy in the Bi-bonding environment with the increased substitution of Bi3+, with its 6s2 stereochemically active lone electron pair. Synchrotron X-ray pair distribution functions (PDFs) reveal that the tetragonal distortions are preserved down to the local scale, suggesting that studies of the average structure provide reasonable insight into the structure-property relationships in this system. These results provide guidance for designing new materials with high TC. Single crystals of (1-x)PT-xBZN were then successfully grown using the high-temperature solution growth (HTSG) method. The dielectric measurements indicate the ferroelectric-paraelectric phase transition at an average TC of 436 °C. Polarized light microscopy reveals the domain structure of tetragonal symmetry, with domain walls oriented along the <100>cub directions, and birefringence measurements as a function of temperature confirmed the first order phase transition. HTSG allows for a higher BZN content to be incorporated into the crystals in comparison to their ceramic counterpart. Moving toward lead-free materials, ceramics of a novel solid solution, (1−x)BaTiO3 xBi(Zn2/3Nb1/3)O3 (BT-BZN) were synthesized. With increasing BZN content, the materials show a decrease in tetragonality and undergo a transition to pseudocubic symmetry, which is accompanied by a crossover from normal ferroelectric to relaxor behaviour. This crossover is explained by increased cationic disorder that disrupts the ferroelectric order. Synchrotron X-ray PDF analysis reveals that all the compositions show local tetragonal distortions that decrease at larger scales to reach the average structure, demonstrating the striking difference between the local and long-range structures.

Cancer is a leading cause of death worldwide. Efforts to improve the longevity and quality of life of cancer patients are hindered by delays in diagnosis of tumours and treatment deficiency, as well as inaccurate prognosis that leads to unnecessary or inefficient treatments. More accurate biomarkers may address these issues and could facilitate the selection of effective treatment courses and development of new therapeutic regimens. Circulating tumour cells (CTCs), which are cancer cells that are shed from tumours and enter the vasculature, hold such a promise. Therefore, there is much interest in the isolation of CTCs from the blood. However, this is not a trivial task given the extreme scarcity of CTCs in the circulation. In this thesis, the development of a microfluidic immunomagnetic approach for isolation of CTCs is presented. First, the design, microfabrication, and experimental evaluation of a novel integrated microfluidic magnetic chip for sensitive and selective isolation of immunomagnetically labelled cancer cells from blood samples is reported. In general, to ensure the efficient immunomagnetic labelling of target cancer cells in a blood sample, an excessive number of magnetic beads should be added to the sample. When an immunomagnetically labelled sample is processed through the chip, not only cancer cells but also free magnetic beads that are not bonded to any target cells would be captured. The accumulation of these beads could disrupt the capture and visual detection of target cells. This is an inherent drawback associated with immunomagnetic cell separation systems and has rarely been addressed in the past. Therefore, the design, microfabrication, and characterization of a microfluidic filter for continuous size-based removal of free magnetic beads from immunomagnetically labelled blood samples is presented next. Connected in tandem, the two chips developed in this work form a microfluidic platform for size-based enrichment and immunomagnetic isolation of CTCs. Preclinical studies showed that the proposed approach can capture up to 75% of blood-borne prostate cancer cells at clinically-relevant low concentrations (as low as 5 cells/mL) at an acceptable throughput (200 μL/min). The retrieval and successful propagation of captured prostate cancer cells is also investigated and discussed in this thesis.

Relaxor-based piezo-/ferroelectric materials of complex perovskite structure, represented by (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT), have demonstrated excellent piezoelectric performance. However, they also exhibit some inherent drawbacks, such as a low Curie temperature, an even lower de-poling temperature due to the presence of a morphotropic phase boundary (MPB) region, a weak coercive field and a high content of lead, which make them unsuitable for high-temperature and high-field (power) applications and raise environmental concerns. Bismuth-based complex perovskites, such as Bi(Zn1/2Ti1/2)O3 (BZT) seem to be an interesting candidate for the replacement of lead-based compounds because, like Pb2+ ion, Bi3+ also contains the 6s2 lone electron pair which is considered to be essential for the high piezo-/ferroelectric performance in lead-based perovskite. In addition, the solid solution between BZT and PT indeed exhibits larger structural distortion resulting in a higher Curie temperature than PT. However, its coercive field is too large for the material to be poled in order to make its potentially high piezo-/ferroelectric properties useful. Faced with those issues and challenges, outcomes of this thesis are two-fold: Firstly, addition of a non-stereochemically active ion and related complex compound, namely La(Zn1/2Ti1/2)O3 (LZT), as an end-member "softens" the structures, chemical bonding and electric properties of "hard" ferroelectric materials, to achieve improved electric properties, such as giant dielectric constant, smaller coercive field and switching polarization and excellent piezoelectricity and ferroelectricity.Secondly, addition of BZT as the third component "hardens" the structures, chemical bonding and electric properties of PMN-PT binary system in order to increase its coercive field and to improve its piezo-/ferroelectricity. In particular, special efforts have been made to grow the single crystals of the PMN-PT-BZT ternary system. The studies of the single crystals provide invaluable information on the phase symmetry, domain structures, phase transitions and electric properties and allow to gain a better understanding of the relationship between crystal formation, chemical composition, phase symmetry and macroscopic properties.

There is a great interest in developing new high-performance piezo-/ferroelectric materials that are lead-reduced or lead-free. This work focuses on using bismuth as a lead alternative, and studies solid solutions based on the end-member Bi(Zn2/3Nb1/3)O3 (BZN). First, ceramics of the (1-x)PbTiO3-xBi(Zn2/3Nb1/3)O3 [(1-x)PT-xBZN] solid solution were synthesized. The tetragonality (c/a ratio) and A-site displacement increase with increasing BZN content, as revealed by X-ray diffraction analysis. Dielectric measurements show that the Curie temperature TC increases with increasing BZN up to a maximum of 520 °C for the composition of x = 0.20. These results indicate the structural origin of the enhanced tetragonality and properties that arise from the increased anisotropy in the Bi-bonding environment with the increased substitution of Bi3+, with its 6s2 stereochemically active lone electron pair. Synchrotron X-ray pair distribution functions (PDFs) reveal that the tetragonal distortions are preserved down to the local scale, suggesting that studies of the average structure provide reasonable insight into the structure-property relationships in this system. These results provide guidance for designing new materials with high TC. Single crystals of (1-x)PT-xBZN were then successfully grown using the high-temperature solution growth (HTSG) method. The dielectric measurements indicate the ferroelectric-paraelectric phase transition at an average TC of 436 °C. Polarized light microscopy reveals the domain structure of tetragonal symmetry, with domain walls oriented along the <100>cub directions, and birefringence measurements as a function of temperature confirmed the first order phase transition. HTSG allows for a higher BZN content to be incorporated into the crystals in comparison to their ceramic counterpart. Moving toward lead-free materials, ceramics of a novel solid solution, (1−x)BaTiO3 xBi(Zn2/3Nb1/3)O3 (BT-BZN) were synthesized. With increasing BZN content, the materials show a decrease in tetragonality and undergo a transition to pseudocubic symmetry, which is accompanied by a crossover from normal ferroelectric to relaxor behaviour. This crossover is explained by increased cationic disorder that disrupts the ferroelectric order. Synchrotron X-ray PDF analysis reveals that all the compositions show local tetragonal distortions that decrease at larger scales to reach the average structure, demonstrating the striking difference between the local and long-range structures.

Cancer is a leading cause of death worldwide. Efforts to improve the longevity and quality of life of cancer patients are hindered by delays in diagnosis of tumours and treatment deficiency, as well as inaccurate prognosis that leads to unnecessary or inefficient treatments. More accurate biomarkers may address these issues and could facilitate the selection of effective treatment courses and development of new therapeutic regimens. Circulating tumour cells (CTCs), which are cancer cells that are shed from tumours and enter the vasculature, hold such a promise. Therefore, there is much interest in the isolation of CTCs from the blood. However, this is not a trivial task given the extreme scarcity of CTCs in the circulation. In this thesis, the development of a microfluidic immunomagnetic approach for isolation of CTCs is presented. First, the design, microfabrication, and experimental evaluation of a novel integrated microfluidic magnetic chip for sensitive and selective isolation of immunomagnetically labelled cancer cells from blood samples is reported. In general, to ensure the efficient immunomagnetic labelling of target cancer cells in a blood sample, an excessive number of magnetic beads should be added to the sample. When an immunomagnetically labelled sample is processed through the chip, not only cancer cells but also free magnetic beads that are not bonded to any target cells would be captured. The accumulation of these beads could disrupt the capture and visual detection of target cells. This is an inherent drawback associated with immunomagnetic cell separation systems and has rarely been addressed in the past. Therefore, the design, microfabrication, and characterization of a microfluidic filter for continuous size-based removal of free magnetic beads from immunomagnetically labelled blood samples is presented next. Connected in tandem, the two chips developed in this work form a microfluidic platform for size-based enrichment and immunomagnetic isolation of CTCs. Preclinical studies showed that the proposed approach can capture up to 75% of blood-borne prostate cancer cells at clinically-relevant low concentrations (as low as 5 cells/mL) at an acceptable throughput (200 μL/min). The retrieval and successful propagation of captured prostate cancer cells is also investigated and discussed in this thesis.

Relaxor-based piezo-/ferroelectric materials of complex perovskite structure, represented by (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT), have demonstrated excellent piezoelectric performance. However, they also exhibit some inherent drawbacks, such as a low Curie temperature, an even lower de-poling temperature due to the presence of a morphotropic phase boundary (MPB) region, a weak coercive field and a high content of lead, which make them unsuitable for high-temperature and high-field (power) applications and raise environmental concerns. Bismuth-based complex perovskites, such as Bi(Zn1/2Ti1/2)O3 (BZT) seem to be an interesting candidate for the replacement of lead-based compounds because, like Pb2+ ion, Bi3+ also contains the 6s2 lone electron pair which is considered to be essential for the high piezo-/ferroelectric performance in lead-based perovskite. In addition, the solid solution between BZT and PT indeed exhibits larger structural distortion resulting in a higher Curie temperature than PT. However, its coercive field is too large for the material to be poled in order to make its potentially high piezo-/ferroelectric properties useful. Faced with those issues and challenges, outcomes of this thesis are two-fold: Firstly, addition of a non-stereochemically active ion and related complex compound, namely La(Zn1/2Ti1/2)O3 (LZT), as an end-member "softens" the structures, chemical bonding and electric properties of "hard" ferroelectric materials, to achieve improved electric properties, such as giant dielectric constant, smaller coercive field and switching polarization and excellent piezoelectricity and ferroelectricity.Secondly, addition of BZT as the third component "hardens" the structures, chemical bonding and electric properties of PMN-PT binary system in order to increase its coercive field and to improve its piezo-/ferroelectricity. In particular, special efforts have been made to grow the single crystals of the PMN-PT-BZT ternary system. The studies of the single crystals provide invaluable information on the phase symmetry, domain structures, phase transitions and electric properties and allow to gain a better understanding of the relationship between crystal formation, chemical composition, phase symmetry and macroscopic properties.

Cancer is a leading cause of death worldwide. Efforts to improve the longevity and quality of life of cancer patients are hindered by delays in diagnosis of tumours and treatment deficiency, as well as inaccurate prognosis that leads to unnecessary or inefficient treatments. More accurate biomarkers may address these issues and could facilitate the selection of effective treatment courses and development of new therapeutic regimens. Circulating tumour cells (CTCs), which are cancer cells that are shed from tumours and enter the vasculature, hold such a promise. Therefore, there is much interest in the isolation of CTCs from the blood. However, this is not a trivial task given the extreme scarcity of CTCs in the circulation. In this thesis, the development of a microfluidic immunomagnetic approach for isolation of CTCs is presented. First, the design, microfabrication, and experimental evaluation of a novel integrated microfluidic magnetic chip for sensitive and selective isolation of immunomagnetically labelled cancer cells from blood samples is reported. In general, to ensure the efficient immunomagnetic labelling of target cancer cells in a blood sample, an excessive number of magnetic beads should be added to the sample. When an immunomagnetically labelled sample is processed through the chip, not only cancer cells but also free magnetic beads that are not bonded to any target cells would be captured. The accumulation of these beads could disrupt the capture and visual detection of target cells. This is an inherent drawback associated with immunomagnetic cell separation systems and has rarely been addressed in the past. Therefore, the design, microfabrication, and characterization of a microfluidic filter for continuous size-based removal of free magnetic beads from immunomagnetically labelled blood samples is presented next. Connected in tandem, the two chips developed in this work form a microfluidic platform for size-based enrichment and immunomagnetic isolation of CTCs. Preclinical studies showed that the proposed approach can capture up to 75% of blood-borne prostate cancer cells at clinically-relevant low concentrations (as low as 5 cells/mL) at an acceptable throughput (200 μL/min). The retrieval and successful propagation of captured prostate cancer cells is also investigated and discussed in this thesis.

Relaxor-based piezo-/ferroelectric materials of complex perovskite structure, represented by (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT), have demonstrated excellent piezoelectric performance. However, they also exhibit some inherent drawbacks, such as a low Curie temperature, an even lower de-poling temperature due to the presence of a morphotropic phase boundary (MPB) region, a weak coercive field and a high content of lead, which make them unsuitable for high-temperature and high-field (power) applications and raise environmental concerns. Bismuth-based complex perovskites, such as Bi(Zn1/2Ti1/2)O3 (BZT) seem to be an interesting candidate for the replacement of lead-based compounds because, like Pb2+ ion, Bi3+ also contains the 6s2 lone electron pair which is considered to be essential for the high piezo-/ferroelectric performance in lead-based perovskite. In addition, the solid solution between BZT and PT indeed exhibits larger structural distortion resulting in a higher Curie temperature than PT. However, its coercive field is too large for the material to be poled in order to make its potentially high piezo-/ferroelectric properties useful. Faced with those issues and challenges, outcomes of this thesis are two-fold: Firstly, addition of a non-stereochemically active ion and related complex compound, namely La(Zn1/2Ti1/2)O3 (LZT), as an end-member "softens" the structures, chemical bonding and electric properties of "hard" ferroelectric materials, to achieve improved electric properties, such as giant dielectric constant, smaller coercive field and switching polarization and excellent piezoelectricity and ferroelectricity.Secondly, addition of BZT as the third component "hardens" the structures, chemical bonding and electric properties of PMN-PT binary system in order to increase its coercive field and to improve its piezo-/ferroelectricity. In particular, special efforts have been made to grow the single crystals of the PMN-PT-BZT ternary system. The studies of the single crystals provide invaluable information on the phase symmetry, domain structures, phase transitions and electric properties and allow to gain a better understanding of the relationship between crystal formation, chemical composition, phase symmetry and macroscopic properties.

Cancer is a leading cause of death worldwide. Efforts to improve the longevity and quality of life of cancer patients are hindered by delays in diagnosis of tumours and treatment deficiency, as well as inaccurate prognosis that leads to unnecessary or inefficient treatments. More accurate biomarkers may address these issues and could facilitate the selection of effective treatment courses and development of new therapeutic regimens. Circulating tumour cells (CTCs), which are cancer cells that are shed from tumours and enter the vasculature, hold such a promise. Therefore, there is much interest in the isolation of CTCs from the blood. However, this is not a trivial task given the extreme scarcity of CTCs in the circulation. In this thesis, the development of a microfluidic immunomagnetic approach for isolation of CTCs is presented. First, the design, microfabrication, and experimental evaluation of a novel integrated microfluidic magnetic chip for sensitive and selective isolation of immunomagnetically labelled cancer cells from blood samples is reported. In general, to ensure the efficient immunomagnetic labelling of target cancer cells in a blood sample, an excessive number of magnetic beads should be added to the sample. When an immunomagnetically labelled sample is processed through the chip, not only cancer cells but also free magnetic beads that are not bonded to any target cells would be captured. The accumulation of these beads could disrupt the capture and visual detection of target cells. This is an inherent drawback associated with immunomagnetic cell separation systems and has rarely been addressed in the past. Therefore, the design, microfabrication, and characterization of a microfluidic filter for continuous size-based removal of free magnetic beads from immunomagnetically labelled blood samples is presented next. Connected in tandem, the two chips developed in this work form a microfluidic platform for size-based enrichment and immunomagnetic isolation of CTCs. Preclinical studies showed that the proposed approach can capture up to 75% of blood-borne prostate cancer cells at clinically-relevant low concentrations (as low as 5 cells/mL) at an acceptable throughput (200 μL/min). The retrieval and successful propagation of captured prostate cancer cells is also investigated and discussed in this thesis.

Relaxor-based piezo-/ferroelectric materials of complex perovskite structure, represented by (1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 (PMN-PT), have demonstrated excellent piezoelectric performance. However, they also exhibit some inherent drawbacks, such as a low Curie temperature, an even lower de-poling temperature due to the presence of a morphotropic phase boundary (MPB) region, a weak coercive field and a high content of lead, which make them unsuitable for high-temperature and high-field (power) applications and raise environmental concerns. Bismuth-based complex perovskites, such as Bi(Zn1/2Ti1/2)O3 (BZT) seem to be an interesting candidate for the replacement of lead-based compounds because, like Pb2+ ion, Bi3+ also contains the 6s2 lone electron pair which is considered to be essential for the high piezo-/ferroelectric performance in lead-based perovskite. In addition, the solid solution between BZT and PT indeed exhibits larger structural distortion resulting in a higher Curie temperature than PT. However, its coercive field is too large for the material to be poled in order to make its potentially high piezo-/ferroelectric properties useful. Faced with those issues and challenges, outcomes of this thesis are two-fold: Firstly, addition of a non-stereochemically active ion and related complex compound, namely La(Zn1/2Ti1/2)O3 (LZT), as an end-member "softens" the structures, chemical bonding and electric properties of "hard" ferroelectric materials, to achieve improved electric properties, such as giant dielectric constant, smaller coercive field and switching polarization and excellent piezoelectricity and ferroelectricity.Secondly, addition of BZT as the third component "hardens" the structures, chemical bonding and electric properties of PMN-PT binary system in order to increase its coercive field and to improve its piezo-/ferroelectricity. In particular, special efforts have been made to grow the single crystals of the PMN-PT-BZT ternary system. The studies of the single crystals provide invaluable information on the phase symmetry, domain structures, phase transitions and electric properties and allow to gain a better understanding of the relationship between crystal formation, chemical composition, phase symmetry and macroscopic properties.