Mechatronics Systems Engineering - Theses, Dissertations, and other Required Graduate Degree Essays

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Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Development of a microfluidic platform for size-based enrichment and immunomagnetic isolation of circulating tumour cells

Date created: 
2017-08-16
Abstract: 

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.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Edward J. Park
Dr. Timothy V. Beischlag
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.

Analysis of 2:1 Internal Resonance in MEMS Applications

Author: 
Date created: 
2018-01-12
Abstract: 

Micromachined resonators are typically used within their linear range of operation. Recently, there has been an increasing interest in understanding nonlinearities and potentially employing them to improve the performance of resonance-based devices. The focus of this thesis is to study the nonlinear mode coupling at 2:1 internal resonance both experimentally and analytically. It is shown that quadratic nonlinearities can couple two vibrational modes of a micro-resonator with a 2:1 ratio between two of its mode frequencies. This nonlinear coupling of modes can lead to the transfer of energy between these two modes through internal resonance. To study the phenomenon, a modified T-beam structure is proposed, and a simplified mathematical model of operation including the nonlinearities is developed for this system. Perturbation solutions of the mathematical model, along with finite element and reduced-order method analysis are used to describe the nonlinear behaviour of the system. Experiments are performed on a modified micro T-beam structure with 2:1 ratio between its resonance frequencies. Nonlinear modal interactions between vibrational modes, jump and saturation phenomena, and bandwidth enhancement are also observed both in experiments and numerical simulations. The effect of damping on the behaviour of the system is also studied. Some of the potential applications of internal resonance in sensing are also proposed and discussed throughout the thesis.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Behraad Bahreyni
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) M.A.Sc.

Design and fabrication of high-performance capacitive micro accelerometers

Author: 
Date created: 
2018-02-22
Abstract: 

This thesis presents the development of capacitive high-performance accelerometers for sonar wave detection. Two different designs of in-plane and out-of-plane accelerometers are developed, micro-fabricated, and experimentally tested.The out-of-plane accelerometer is designed based on a continuous membrane suspension element. In comparison to beam-type suspension elements, the new design provides uniform displacement of the proof mass, lower cross-axis sensitivity, and lower stress concentration in suspension elements which could result in higher yield in the fabrication process. The out-of-plane accelerometer is fabricated using a novel microfabrication method which facilitates developing continuous membrane type suspension elements and full wafer thick proof mass for accelerometers. The designed accelerometer is fabricated on a silicon-on-insulator wafer with an 8 µm device layer, 1.5 µm buried-oxide layer, and 500 µm handle wafer. The developed accelerometer is proven to have resonance frequency of 5.2 kHz, sensitivity of ~0.9 pF/g, mechanical noise equivalent acceleration of less than 450 ng/√Hz, and an open loop dynamic range of higher than 130 dB while operating at atmospheric pressure.The in-plane single-axis accelerometer is designed based on a proposed mode-tuned modified structure. In this modified structure, the proof mass is substituted with a moving frame which also provides the area for increasing the number of sensing electrodes. This substitution contributes to widening the bandwidth of the accelerometer by locating the anchors and elastic elements both inside and outside of the moving frame. The designed accelerometer is fabricated on a silicon-on-insulator wafer with a 100µm device layer and high aspect ratio capacitive gaps of ~2 µm. The sensitivity of the accelerometer is measured as ~0.7 pF/g with the total noise equivalent acceleration of less than 500 ng/√Hz in the flat band region of the bandwidth. The resonance frequency of the devices is 4.2 kHz while maintaining a linearity of better than 0.7%. The open loop dynamic range of the accelerometer, while operating at atmospheric pressure, is higher than 135 dB, and the cross-axis sensitivity is less than -30 dB.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Behraad Bahreyni
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) Ph.D.