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.

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.

Novel nonlinear sliding mode observers for state and parameter estimation

Author: 
Date created: 
2018-04-16
Abstract: 

Interest in the area of state and parameter estimation in nonlinear systems has grown significantly in recent years. The use of sliding mode observers promises superior robustness characteristics that make them very attractive for noisy uncertain systems. In this thesis, a novel Time-Averaged Lypunov functional (TAL) is proposed that examines the effect of Gaussian noise on the stability of a sliding mode observer. The TAL averages the Lyapunov analysis over a small finite time interval, allowing for intuitive analysis of noises and disturbances affecting the system. Initially, a sliding mode observer for a linear system is analysed using the proposed functional. Later, the results are extended to various classes of nonlinear systems. The necessary and sufficient conditions for the existence of the observer are presented in the form of Linear Matrix Inequality (LMI), which can be explicitly solved offline using commercial LMI solvers. The types of nonlinearity examined are fairly general and embodies Lipschitz, bounded Jacobian, Sector bounded and Dissipative nonlinearities. All the system models considered are highly nonlinear and consist of system disturbances and sensor noise. The proposed sliding mode observer provides less conservative conditions to verify the existence and stability of the observer. The observer can also be effectively used for unknown parameter estimation as outlined in the final chapter of this report. Various examples are provided throughout the premise to support the proposed observer design and demonstrate its effectiveness.

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

Differentiating Common Workplace Postures through Plantar Pressure: Laying the Groundwork for a Low-Cost Instrumented Insole

Author: 
Date created: 
2017-12-05
Abstract: 

Prolonged weight bearing (WBR) at work is a suspected risk factor for the development of musculoskeletal disorders that commonly occur in the feet. No objective measure to quantify time spent in different WBR postures currently exists, creating a barrier in investigating the connection between WBR and foot pain. This study aimed to develop a prototype design for a low-cost instrumented insole system capable of differentiating workplace postures (sitting, standing and walking). Three objectives were defined: 1) quantify and differentiate the pedobarographic characteristics associated with each posture, 2) classify the postures from plantar pressure characteristics and 3) develop an insole system with off-the-shelf sensors capable of classifying workplace postures. Pressure measures near the hindfoot and central/lateral forefoot were found to simultaneously differentiate the postures, and machine learning algorithms accurately classified the postures using plantar pressure metrics. This foundational work facilitates the deployment of a low-cost instrumented insole for workplace studies where it will provide the objective evidence needed to resolve the link between WBR and foot pain.

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

Multi-Modality Breast Cancer Assessment Tools Using Diffuse Optical and Electrical Impedance Spectroscopy

Author: 
Date created: 
2016-11-23
Abstract: 

Diffuse optical spectroscopy (DOS) and electrical impedance spectroscopy (EIS) are promising non-invasive and non-ionizing techniques for breast anomaly detection. This research aims at development of low-cost and novel hand-held devices that are able to differentiate between malignant and benign lesions in human subjects. Three probes have been designed and developed in this research, including a diffuse optical spectroscopy probe for measuring the optical properties of breast tissue, a combined diffuse optical spectroscopy probe with electrical impedance spectroscopy probe for measuring the optical and electrical properties of the breast tissue simultaneously, and a diffuse optical breast-scanning (DOB-Scan) probe for creating cross-sectional optical images of the breast.In addition to a detailed description of the developed instruments, two studies are presented: a phantom study detecting inhomogeneity in the homogeneous phantom using DOS and DOB-Scan probe, and a clinical study to diagnosis malignant lesions in the patients who have breast cancer.The DOS-EIS probe was successfully used in an initial clinical study on cancer patients, and the results conclusively demonstrated its ability to differentiate between cancerous breast tissue and healthy tissue using diffuse optical spectroscopy combined with electrical impedance spectroscopy. The results of DOB-Scan imaging probe in the clinical study reflect that the probe can capture malignant tissues underneath of the probe. These studies demonstrate that diffuse optical spectroscopy and electrical impedance spectroscopy are valuable modalities that can play an important role in breast tumor detection and monitoring.

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

An extremum seeking control system for control of RF cavity resonators

Author: 
Date created: 
2016-09-15
Abstract: 

RF cavity resonators are one of the key structures in particle accelerators. They provide accelerating field for a beam of charged particles passing through them. An RF source transmits required power for acceleration to cavity through waveguides. Due to impedance mismatch, some amount of available power generated by the RF source reflects back from the cavity. To save power and provide the maximum accelerating field, it is desirable to minimize this reflected power by equalizing the frequencies of the cavity and source. A mechanical tuner mounted on top of the cavity moves a tuner plate in or out of the cavity, thereby changing cavity’s resonance frequency. In this thesis, first a mathematical dynamic model of the cavity in terms of its transient and steady state signals is provided. Then based on the dynamic model, an extremum seeking (ES) algorithm is developed to automatically reach the minimum value of the reflected power and maintain this condition by keeping the resonance frequency of the cavity equal to the source frequency. The ES algorithm is derived through a Lyapunov-based analysis and uses only reflected power as feedback signal. A gradient estimation is performed to determine the direction of movement. The proposed ES controller is further compared with classical perturbation-based ES methods. Simulation and experimental results are presented to evaluate stability and the response behavior of the algorithms in reaching the minimum condition. While both algorithms successfully minimize reflected power in finite time, the results obtained from the Lyapunov-based algorithm are faster and smoother. However, if the cavity is not perfectly coupled and the minimum reflected power is greater than zero, the performance of the proposed controller degrades due to appearance of steady state oscillation. This problem can be solved by adding an initialization phase to the controller, to track the minimum value of reflected power and update the control law with the new value of the minimum.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Mehrdad Moallem
Ken Fong
Department: 
Applied Sciences: School of Mechatronic Systems Engineering
Thesis type: 
(Thesis) M.A.Sc.