BIEN 470: Bioengineering Design Projects 2023-2024

2023-2024 projects are posted below

Please note that the deadline for students choosing projects is September 16th, and the deadline for Faculty submitting proposals is September 5th.

 

 

Project 1 Title: Development of a Parallelized Light-Induced Protein Micropatterning Technique for High-throughput Patterned-Based Contractility Screening (PaCs) Applications

Supervisor: Prof Ehrlicher allen.ehrlicher [at] mcgill.ca,

PhD candidate Clayton Molter clayton.molter [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

Cells in our body’s tissue exchange mechanical forces with their external environment which consists of their extracellular matrices or other cells. Aberrant changes in these mechanics can have profound consequences on our health and can even lead to diseases such as cancer. In cancer metastasis, for example, changes in cell-substrate forces may induce cells change their migration behaviour, leading to tissue invasion. These changes may be related to other biological processes, such as changes in protein expression and localization. Thus, there is a need to develop methods to quantify and elucidate how changes in cell contractility correlate with protein localization. However, techniques enabling these analyses are non-trivial and involve the combination of biophysical and biological assays which have historically been distinct. To date, relating contractile forces to endogenous expression and localization of protein with single-cell resolution remains to be a challenge. This is because localization studies of endogenous protein activity typically require immunofluorescence assays, which require the immobilization of cells. This practice is at odds with conventional methodologies used to quantify cell contractility, such as traction force microscopy (TFM) which require a cell-free reference image.

 

The Ehrlicher lab has recently developed a method for the high throughput, reference-free quantification of single cell contractile work based on the cell-induced deformations of adhesive protein micropatterns, called Pattern-based Contractility Screening (PACS). Because no cell-free image is required, this technique has the potential to be used in combination with immunofluorescent assays, potential facilitating paired contractility/localization analyses. However, the existing platform used to prepare PaCs micropatterns requires time- and reagent-intensive laser photo-etching of individual patterns in microscopic areas, hence providing a barrier to scaling this technique up for larger samples. The Ehrlicher Lab aims to develop a separate method which employs photomasks and a single non-laser light source to enable simultaneous parallel printing of patterns across a large surface.

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The student design team will be responsible for developing and optimizing the parallel micropatterning protocol to enable a unified PaCs/immunofluorescence experiment protocol and analysis pipeline to enable the quantitative correlation of protein localization and cell contractility.

Description of Design Component: The design components are below.

 

  1. Develop a photomask-based parallel printing method using widefield UV illumination to micropattern adhesive protein patterns on soft silicone substrates of various stiffnesses.

 

  1. Optimize a high-throughput, parallelized PACs-workflow with a reliable method for re-identification of immobilized single cells after initial PACs image acquisition during immunofluorescence imaging.

 

  1. Develop an analysis scheme capable of identifying and pairing separately acquired PACs and immunofluorescent single cell images in a high throughput manner.

 

Given that all instruments, reagents, and fundamental protocols are available, it is expected that all components (a), (b), and (c) will be completed by the end of the project.

Skills to have or develop: Experience in microfabrication and microscopy will be an asset for the project. Programming and image analysis will be an asset for developing the data analysis scheme.

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Project 2 Title: Development of an Electromagnetic Tweezer Apparatus for Cell Mechanics Studies

Supervisor: Prof Ehrlicher allen.ehrlicher [at] mcgill.ca,

PhD candidate Clayton Molter clayton.molter [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

The Ehrlicher Group is developing a magnetic tweezer apparatus to probe the mechanical properties of the cell cytoplasm. Magnetic tweezers facilitate the measurement of cytoplasmic mechanical properties, such as their stiffness and viscoelasticity, by actuating engulfed magnetic beads by varying the attractive magnetic force acting on the beads. By measuring the distance the bead moves in response to a known force within the cell, we obtain force-displacement curves to which we can apply known mechanical models to characterize the cytoplasmic mechanical properties. A condition of these mechanical models is that it is necessary to apply extremely precise force patterns, which in turn requires precise control over the magnetic tweezers force generation.

 

Although we are already equipped with an electromagnetic tweezer set-up consisting of a solenoid with a mu-metal core and a programmable micromanipulator for actuation, a longstanding obstacle of our group has been the remnant magnetization following several subsequent on/off cycles. This remnant magnetization results in a remnant force field, preventing us to perform repeatable, predictable force regimes on the beads. Recent developments have led to the acquisition of a instruments capable of demagnetizing, but this must be optimized and validated. As such, the goal of this capstone project will be to develop an integrated demagnetization scheme such that users of the magnetic tweezers can manipulate magnetic beads within the cell with a known force regime.

 

Additionally, the force experienced by the bead increases as a function of radius to the magnetic tweezer needle tip. In order to reliably predict the mechanical properties of the cell in a repeatable manner, fine control of the tweezer tip location or current must be achieved to maintain a repeatable uniform force profile. At the current time, placement of the tip relative to the cell and bead of interest is a manual process, and we aim to develop a new routine whereby we can separately or jointly define the placement of the tip and solenoid current in real-time relative to the cell so a known force regime can be implemented. This will involve live particle tracking during image acquisition and for use in the control scheme.

Description of the Design Component:

 

The design components are below.

 

(a) Remnant magnetization and associated force fields are to be reduced to zero such that (b) a step force from 0 to some value may be applied to the beads. This demagnetization scheme must be rapid such that the users of the tweezers can conduct several bead manipulations during live-cell experiments.

 

1) Design a method to demagnetize the electromagnetic tweezers. This will involve (i) circuit design and critical analysis thereof which can interface into the existing magnetic tweezer apparatus. Identification of electrical parameters required for the operation of this scheme is required.

 

2) Design a method to place allow fine control the tip at a known distance from the bead whether by control of the tip location, or field modulation. A feedback control scheme whereby the tip location - that is, the predicted origin of the force field - is known relative to the bead. This may require integration of live microscope imaging with micromanipulator actuator control.

 

Given that all instruments are readily available, a prototype of the complete system will be expected.

Skills to have or develop: A strong knowledge of electricity, magnetism, circuit design, and control systems would be an asset. Programming will be an asset for developing control schemes.

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Project 3 Title: Miniscope for Cardiomyocyte Screening

Supervisor: Prof Ehrlicher allen.ehrlicher [at] mcgill.ca,

PhD candidate Pouria Tirgar pouria.tirgarbahnamiri [at] mail.mcgill.ca

Preferred Team size: 4

Background and Objectives:

All chemicals entering human body (e.g. drugs, hormones, etc.) have to be safe to all non-target organs. One such organ is the heart, with an extremely sensitive electro-mechanical machinery that can be disrupted by a wide range of interferences. This has made cardiotoxicity the leading cause of drug failure and recalls. The need to evaluate the effect of different perturbations on cardiac cells have resulted in development of a myriad of techniques to measure the 1) force and 2) the electrical signal (electrophysiology) of cardiac muscle cells in the lab. However, most, if not all, of these techniques require sophisticated imaging systems and scientific microsocpes to visualize and quantify the response of the cells, which both reduces the throughput of such evaluations and requires capital for the initial investment in the imaging system.

 

In this project, we use a miniaturized microscope system called "miniscope" to assemble a lab-on-a-chip setup for imaging and evaluation of traction force and electrophysiology of cardiac muscle cells in vitro. The miniscope was initially designed and widely used to image calcium signal in the brain of living mice, but with some modifications students will adapt it for in vitro imaging comparable with that of scientific microscopes for <500$.

Description of the Design Component:

Selected team/candidate will be involved in design and fabrication of the lab-on-a-chip setup, optical setup of the miniscope, culture and maintenance of heart cells and imaging and quantification of the data collected with miniscope and a scientific microscope.

Given that all instruments are readily available, a prototype of the complete system will be expected.

Skills to have or develop: A strong knowledge of cell culture, microscopy, and microfabrication.

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Project 4 Title: Using deep learning to identify high-risk tumor subregions in soft-tissue sarcoma

Supervisor: Prof Tsui james.tsui [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

Extremity soft-tissue sarcoma is a cancer of the soft tissues and carries a poor prognosis. Even when optimally treated, approximately half of the patients will develop metastatic disease, and most will die as a result. Patients with their tumor completely sterilized with radiation therapy (RT) prior to surgery have better overall survival. However, this is not always achievable. A higher dose of pre-operative RT to the entire tumor may kill off all tumor cells, but this can lead to higher toxicity. Escalating RT dose to the sub-regions most at risk of residual may translate to better outcomes while mitigating toxicity. This project aims to use artificial intelligence to identify these tumor sub-region targets for high-dose RT.

Description of the Design Component:

The main objective of this project is to identify tumor sub-regions on diagnostic imaging at risk of containing viable tumor cells after pre-operative radiotherapy to potentially serve as a target for dose painting with the aim to improve pathological completer response in patients with extremity soft tissue sarcoma.

 

The project will aim to design and implement different convolutional neural networks (CNNs) on a public dataset to predict the risk of lung metastasis, but more importantly the sub-regions in the tumor that drive model decision.

Skills to have or develop: Strong proficiency in Python and experience in deep learning and Github.

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Project 5 Title: A temperature-controlled fragmentation chamber for studying disease transmission

Supervisor: Prof Wagner caroline.wagner [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

For successful onward transmission, respiratory viruses that are enclosed in emitted mucosalivary droplets during events such as talking, coughing, or sneezing must remain viable until being taken up by a new susceptible host. In sneezing and coughing, the size distribution of droplets is critically related to important disease processes. First, the size distribution impacts where droplets deposit in the lung. Large droplets are believed to quickly settle out of the air, favoring direct or fomite-based transmission, while small droplets are believed to remain suspended in the air, and preferentially land in smaller airways in the deep lungs. The distribution of droplet sizes also governs the timescale of their evaporation under ambient air conditions set by the local temperature and humidity. Indeed, the transmission of many respiratory viruses is known to be seasonal, but controlled experiments assessing biophysical mechanisms that may drive this are largely absent from the literature. The goal of this project is to develop a climate-controlled chamber for studying virus survival in droplets and the fragmentation of mucosalivary fluids. The team is also expected to conduct preliminary measurements demonstrating the validity of the chamber for generating experimental data.

Description of the Design Component:

The design of the chamber is the primary design component for this project. The requirements of the chamber are as follows:

1) The chamber should be able to achieve temperature control in the approximate range of 10C-28C and relative humidity control in the approximate range of 30%-90%.

2) The sides of the chamber should be transparent to be compatible with high speed imaging

3) The chamber should be compatible with the introduction of tracing / stain paper in order to record the deposition pattern of droplets

4) The chamber should be fully airtight in order to comply with Occupational Health and Safety protocols related to the atomization of materials containing virions or model virion systems

5) The chamber should have a fully mechanically actuated inlet for atomizing the fluid of interest

Skills to have or develop: Development of skills in design, iteration, and prototyping.

Development of skills in the areas of decision-making and strategy development with multidisciplinary considerations.

Knowledge accumulation in the areas of fluid fragmentation and routes of disease transmission.

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Project 6 Title: Design and fabrication of instrumentation for studying interfacial and extensional rheological properties of biological fluids

Supervisor: Prof Wagner caroline.wagner [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

For successful onward transmission, respiratory viruses that are enclosed in emitted mucosalivary droplets during events such as talking, coughing, or sneezing must remain viable until being taken up by a new susceptible host. In sneezing and coughing, the size distribution of droplets is critically related to important disease processes. First, the size distribution impacts where droplets deposit in the lung. Large droplets are believed to quickly settle out of the air, favoring direct or fomite-based transmission, while small droplets are believed to remain suspended in the air, and preferentially land in smaller airways in the deep lungs. The distribution of droplet sizes also governs the timescale of their evaporation under ambient air conditions set by the local temperature and humidity. Indeed, the transmission of many respiratory viruses is known to be seasonal, but controlled experiments assessing biophysical mechanisms that may drive this are largely absent from the literature.

 

The breakup process of biological fluids is strongly set by the extensional rheological and interfacial properties of the fluid in question. For biopolymer fluids, the introduction of small charged particles such as viruses can cause important structural rearrangements to the polymer network, resulting in changes to these mechanical properties. The rapid dynamics of surface formation inherent to fragmentation along with the frequently weakly viscoelastic nature of biological fluids and small available sample volumes necessitates the design and use of specialized equipment for measuring these properties. The goal of this capstone project is to design and build two devices for fluid characterization: the first will measure the extensional rheology of weakly viscoelastic fluids, and the second will measure dynamical surface tension. The team is also expected to conduct preliminary measurements demonstrating the ability of the instruments to measure reference properties for known fluids.

Description of the Design Component:

The design of two pieces of equipment, the extensional rheometer and the bubble tensiometer (for measuring dynamic surface tension), are the primary design components of this project. The requirements for both devices are as follows:

1) Require at most 50uL of sample volume per measurement

2) Ideally require only a smart phone for imaging, however a high speed camera may be obtained if necessary

3) Develop a standard protocol to read out and interpret data

Skills to have or develop: Development of skills in design, iteration, and prototyping.

Development of skills in the areas of decision-making and strategy development with multidisciplinary considerations.

Knowledge accumulation in the areas of fluid fragmentation and routes of disease transmission.

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Project 7 Title: Interactive 3D models for teaching and learning embryology

Supervisor: Prof Funnell robert.funnell [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

Goal: Embryological development is difficult to learn and difficult to teach. It involves the appearance and disappearance of structures, and dramatic changes of topology. Numerous groups have proposed interactive multimedia for teaching embryology but the results have been limited: 2D only, simple artistic renderings, restricted interaction, etc. We wish to generate image-based 3D models that change in both shape and topology. The goal is to have an interactive timeline as well as the usual 3D interactions (rotation, zoom, etc.). At least for now, this is a problem of visualization, not of simulating the actual biological growth processes.

 

Deliverables: The key challenge is to design a user-controllable mechanism for defining morphings from one image-based 3D model to another, to implement a prototype, and to test it on some embryological images.

Description of the Design Component:

The project involves designing a software application for a particular task involving computer graphics and a user interface.

Skills to have or develop: Team should have prior knowledge of software development tools and computer graphics. Prior knowledge of embryology is not required.

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Project 8 Title: Engineering catalytic efficiency and product specificity of taxadiene synthase involved in taxol biosynthesis

Supervisor: Prof Ignea, Prof Xia codruta.ignea [at] mcgill.ca; brandon.xia [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

Paclitaxel (trademark Taxol) derived from the stem bark of the Pacific yew tree, Taxus brevifolia, is a widely used chemotherapeutic agent possessing significant anticancer activity. Recently, the development of synthetic biology has allowed for the biomanufacturing of several plant-based terpenoids in the Saccharomyces cerevisiae, with the most recent breakthrough achieved by production of the anticancer drug vinblastine. In this project, a multi-disciplinary approach spanning computational structural biology, enzymology and synthetic biology, will be applied to optimize the catalytic activity and product specificity of the first committed enzyme (taxadiene synthase; TS) involved in early steps of taxol biosynthesis for efficient reconstruction of these steps in yeast. The following objective will be pursued: 1. Machine learning-assisted directed evolution of TS. 2. Homology modelling or molecular docking for rational and semi-rational mutagenesis to identify stabilized candidate variants. 3. Engineering TS variants and evaluated their activity in a yeast available platform.

Description of the Design Component:

The project involves designing a software application for a particular task involving computer graphics and a user interface. In this project, the students will rationally design a mutagenesis strategy to improve product specificity of taxadiene synthase (TS). This strategy include design of: (1) Machine learning-assisted directed evolution; (2) Alanine Scanning to examine the effect of residues at specific sites on protein function, (3) Rational mutagenesis of TS by identifying residuals that are in proximity to or in the active site of TS, (4) Semi-rational mutagenesis to engineer stable variants.

Skills to have or develop: Biochemistry and Molecular biology knowledge (requested), Know-how laboratory techniques (requested), Enzyme function, kinetics and regulation - to be developed, Protein Sequence-based design strategies - to be developed, Enzyme engineering - to be developed.

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Project 9 Title: Engineering substrate selectivity and catalytic activity of taxadiene 5α-hydroxylase involved in early steps of taxol biosynthesis

Supervisor: Prof Ignea, Prof Xia codruta.ignea [at] mcgill.ca; brandon.xia [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

Paclitaxel (trademark Taxol) derived from the stem bark of the Pacific yew tree, Taxus brevifolia, is a widely used chemotherapeutic agent possessing significant anticancer activity. Recently, the development of synthetic biology has allowed for the biomanufacturing of several plant-based terpenoids in the Saccharomyces cerevisiae, with the most recent breakthrough achieved by production of the anticancer drug vinblastine. In this project, a multi-disciplinary approach spanning computational structural biology, enzymology and synthetic biology, will be applied to optimize the substrate selectivity and catalytic activity of the first cytochrome P450 enzyme, taxadiene 5α-hydroxylase (T5αH), involved in early steps of taxol biosynthesis for efficient reconstruction of these steps in yeast. The following objective will be pursued: 1. Machine learning-assisted directed evolution of T5αH. 2. Homology modelling or molecular docking for rational and semi-rational mutagenesis to identify stabilized candidate variants. 3. Engineering T5αH variants and evaluated their activity in a yeast available platform.

Description of the Design Component:

In this project, the students will rationally design a mutagenesis strategy to improve substrate selectivity of taxadiene 5α- hydroxylase (T5αH). This strategy include design of: (1) Machine learning-assisted directed evolution; (2) Alanine Scanning to examine the effect of residues at specific sites on protein function, (3) Rational mutagenesis of T5αH by identifying residuals that are in proximity to or in the active site of TS, (4) Semi-rational mutagenesis to engineer stable variants.

Skills to have or develop: Biochemistry and Molecular biology knowledge (requested), Know-how laboratory techniques (requested), Enzyme function, kinetics and regulation - to be developed, Protein Sequence-based design strategies - to be developed, Enzyme engineering - to be developed.

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Project 10 Title: Unraveling taccalonolide biosynthesis through a transcriptomic approach

Supervisor: Prof Ignea codruta.ignea [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

Plant natural products (PNP) hold promise to expand the currently limited pharmacological depth of anticancer drug portfolios. As the richest source of structurally and functionally diverse compounds, they are currently serving as a hotspot for novel drug discovery. This is well-exemplified by taccalonolide, the first plant-derived product found with microtubule stabilizing activity since paclitaxel. These pentacyclic steroids are a new class of microtube-stabilizing agents isolated from rhizomes of Tacca plants with demonstrated effectiveness against drug-resistant tumors in vitro and in vivo. However, the biosynthetic pathway of taccalonolides is currently unknown, preventing production of these high-value compounds in large amounts in heterologous hosts, such as yeast, and consequently further studies to facilitate designing of new taccalonolide-inspired chemical entities with potent and selective anti-cancer activities. The following objective will be pursued: 1. RNA extraction from rhizomes of different plants to establish a highly efficient protocol. 2. RNA extraction from Tacca rhizomes. 3. Transcriptome data analysis.

Description of the Design Component:

In this project, the students will rationally design a transcriptome analysis strategy to elucidate the biosynthetic steps of taccalonolies in the genus of Tacca. This strategy include design of: (1) RNA extraction from rhizomes; (2) RNA sequencing strategy; (3) Bioinformatic tools; (4) Transcriptome data analysis.

Skills to have or develop: Biochemistry and Molecular biology knowledge (requested), Know-how laboratory techniques (requested), Bioinformatic skills – expected/to be developed, Enzyme function, kinetics and regulation - to be developed, Transcriptome analysis strategies - to be developed.

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Project 11 Title: Patient Mobile App for Emergency Department Visits

Supervisor: Prof Robert antony.robert [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

Patient experience is an important outcome of healthcare quality, and patient-reported experiences are key to improving the quality of care. Evaluating patient experience in the Emergency Department (ED) can help policy makers, healthcare managers and physicians to identify areas of patient care that should be prioritized for quality improvement. During ED visits, patients waiting have a lot of idle time in between various physician and nursing evaluations or interactions.

 

During idle time, patients:

May experience changes in symptoms (worsening or improvement);

Seek information about what they are waiting for (a treatment, a specialty consultation, the results of investigations (labs or imaging) or simply waiting for a clinician to re-evaluate them); and/or

Want more information about their symptoms, potential diagnosis, or a confirmed diagnosis.

 

 

After their visit, patients:

May want to have a summary of their visit (what was done, what was the diagnosis);

May want to know what to expect or observe in the coming days (including reasons to return to the ED); and/or

May want to give feedback to clinicians about their visit.

May want more information about their results

 

The MUHC ED and the Hematology departments have shown interest in acquiring a mobile app that could improve patient experience. Our target population is hematology patients who present with critical pain in the ED that needs urgent and high-quality care. We believe that a patient app can improve patient experience in the Emergency Department and provide data driven feedback to improve the quality of healthcare and patient satisfaction. However, this concept can be expanded to all patients coming to the ED. This mobile app needs to be compliant with Canadian and Quebec patient confidentiality and privacy requirements.

Description of the Design Component:

Given that the ministry approves the use of cloud-based projects for healthcare projects, we need to:

 

Design a privacy and security compliant cloud-based app architecture

Design and implement an android and IOS patient mobile app to map a patient's journey in the Emergency Department and allow them to complete dynamic surveys, questionnaires, and forms. This data entry needs to be seamless and user friendly and follow current standards of app development.

Furthermore, this app should enable extraction of data for reporting purposes

Any data stored on cloud environment needs to follow current data and interoperability standards including FHIR and HL7.

Skills to have or develop: A passion for solving problems that will help people

A strong background in software engineering or computer science

Previous experience in any of these fields is an asset: 1) App development in React Native (or languages similar to React Native). 2) Cloud database and web service (AWS, Microsoft Azure) Project Conditions. 3) Machine learning + Chat-GPT

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Project 12 Title: Development of methods for designing 3D-printed holders for optimal MRI of the brain

Supervisor: Prof Amir Shmuel amir.shmuel [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

Structural MRI is a non-invasive imaging method commonly used to image the brain in health and disease. Many MRI scanners in clinical facilities are used for imaging patients with neurological and psychiatric conditions. Ex-vivo structural MRI of brain tissue is commonly used for investigating the structure of the brain at high resolution and the mechanisms underlying MRI signals.
The project aims to develop methods for optimizing the positioning of a subject’s head or brain tissue in an MRI scanner, acquiring MRI data, aligning and resampling the different data sets, and creating digital templates of brain MRI volumes.

Description of the Design Component:

The students will review material to learn the basics of MRI and quantitative MRI. They will receive data, and learn how to write analysis pipelines using available scripts from software packages. They will create an analysis package for quantitative MRI of the brain. They will document the methods and the results. They will write a detailed report that we intend to submit for publication in a journal.

Skills to have or develop: The students will gain knowledge and experience in the basics of MRI, Computer-Aided Design And Manufacturing, 3D printing, preparing analysis pipelines based on existing software packages, and writing a journal paper.

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Project 13 Title: Development of a pipeline for analyzing quantitative MRI data of the brain

Supervisor: Prof Amir Shmuel amir.shmuel [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

Structural MRI is a non-invasive imaging method commonly used to image the brain in health and disease. Many MRI scanners in clinical facilities are used for imaging patients with neurological and psychiatric conditions. Structural MRI measures, such as T1 (longitudinal relaxation) and T2 (transverse relaxation) intensities vary across the cerebral cortex. Analysis of such MRI features has made it possible to detect variations in the thickness of the cortical manifold as well as variations in measures hypothesized to co-vary with relative myelin content. Both the cortical thickness and the myelin content are bio-markers of neurological disease.
A recently developed method of neuroimaging is quantitative MRI. Using this technique, multiple scans are performed and brain- and tissue-specific parameters are extracted by fitting models to the acquired data. It is expected that quantitative MRI will yield more accurate bio-markers of neurological diseases.

The project aims to develop scripts for analyzing quantitative MRI data of the brain.

Description of the Design Component:

The students will learn the basics of MRI. They will learn how to write analysis pipelines using available scripts from software packages for the analysis of structural MRI data. They will modify custom-made software already written in the lab for creating 3D-printed models to hold a subject’s head or tissue in the scanner. The modification will make it possible to optimize the position during the MRI, based on signal-to-noise ratio and homogeneity of the MRI image. They will align and resample the acquired data sets in a common 3D space to create MRI templates. They will document the methods, the data sets they acquired, and the templates they created. They will write a detailed report that we intend to submit for publication in a journal.

Skills to have or develop: The students will gain knowledge and experience in the basics of MRI, preparing analysis pipelines based on existing software packages, neuroimaging, and how to write a journal paper.

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Project 14 Title: Design and fabrication of skin-interfaced microfluidics for biosensing

Supervisor: Prof Sara Mahshid sara.mahshid [at] mcgill.ca

Preferred Team size: 2

Background and Objectives:

Skin derived biofluids is a rick bank of biomarkers that are indicative of person’s health status. These biomarkers range from small molecules to proteins to nucleic acids. However, tapping into this biomarker information requires performing complex bioassays on-the-body. Microfluidics interfaced with the skin is a great tool for sample collection and handling on-skin. Microfluidic interface enables incorporation of unit operations like mixing, and valving on small amounts of fluid. Downstream, the sample delivered to a nanostructured transducer that enables detection of the target of interest. The facile integration of skin-interfaced microfluidics with high-performing sensing modules paves way for personalized medicine. To this end the project aims to explore novel mechanisms of fluid handling in skin-interfaced microfluidics for biosensing.

Description of the Design Component:

The design components of the project are, (i) developing and fabricating microfluidic circuits (with unit operations) for skin-derived fluids, (ii) computational simulations for fluidic and mechanical characterisation, (iii) testing of microfluidic integration with a sensing platform.

Skills to have or develop: Experience with microfabrication and 3D printing is desired. The team will develop skills on microfluidic design and nanomaterials.

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Project 15 Title: Establishment of a machine learning analysis pipeline for rapid antibiotic susceptibility testing via discrimination of colorimetric images

Supervisor: Prof Sara Mahshid sara.mahshid [at] mcgill.ca

Preferred Team size: 1

Background and Objectives:

The need for contactless and point-of-care diagnostic devices has burst with the recent COVID-19 pandemic. The point-of-care detection of pathogens, such as viruses should be quantifiable, rapid, accurate, easy to operate, and inexpensive. This project involved working with a library of colorimetric images collected from our custom-designed microfluidic device equipped with a plasmonic colorimetry platform. The highly sensitive and quantifiable colorimetry results are owed to the novel modulation of a plasmonic chamber that sensitively monitors the color change of the assay fluid. The COVID-19-positive sample's color change can be detected at 15 min using a manual analysis and at 10 min using a Support Vector Machine (SVM) algorithm.

Description of the Design Component:

The goal is to modify, implement, validate, and optimize an effective analysis pipeline for our point-of-need COVID-19 colorimetry diagnosis device by modifying a code/machine learning algorithm for the automated detection of color change from microscopy images (image libraries available).

Skills to have or develop: Required background includes prior experience with machine learning and coding. An asset would be prior experience with analyzing the colorimetric readout of sensors.

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Project 16 Title: Development of data processing algorithm based on machine learning for classification of Surface Enhanced Raman Spectroscopy spectra of cancerous biomarkers

Supervisor: Prof Sara Mahshid sara.mahshid [at] mcgill.ca

Preferred Team size: 1

Background and Objectives:

A liquid biopsy is a non-invasive approach aiming to diagnose or monitor patients’ diseases by studying biomarkers, such as extracellular vesicles (EVs). EVs are nanosized vesicles recently appointed as cancer biomarkers that are shed from cells into biofluids like blood, carrying within representative material of their cells of origin. Cancerous cells-derived EVs contain information that can be used to elucidate the molecular differences with healthy EVs. A challenge in the EVs study is their heterogeneity and intrinsic complexity. Machine learning algorithms overcome the complexity of biological data and successfully classify large datasets like spectra of heterogeneous biological samples generated by surface-enhanced Raman spectroscopy (SERS). We developed a SERS-assisted nanostructured microchip, MoSERS, to collect the SERS fingerprints of cancerous EVs to study the biomarker status. We generated databases of single-EV spectra derived from glioblastoma multiforme and medulloblastoma cancers, including cell lines, patient samples, and healthy controls. This project involves the development of a custom-design data processing to be integrated with our current data analysis algorithm (convolutional neural network) to analyze the SERS spectra libraries and generate a prediction on the biomarker status.

Description of the Design Component:

The project goal is to design, implement, validate, and optimize add-on strategies (like feature recognition and data augmentation) to machine learning algorithms for effective data processing of our available spectra library (collected via our liquid biopsy device) to be integrated into the automated analysis pipeline.

Skills to have or develop: Prior experience with machine learning analysis and coding (required). Integration of the code into a friendly readout system (to be developed).

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Project 17 Title: Fabrication of a microfluidic device for extracellular vesicle isolation from plasma

Supervisor: Prof Sara Mahshid sara.mahshid [at] mcgill.ca

Preferred Team size: 2

Background and Objectives:

A liquid biopsy is a non-invasive approach aiming to diagnose or monitor patients’ diseases by studying biomarkers, such as extracellular vesicles (EVs). EVs are nanosized vesicles recently appointed as cancer biomarkers that are shed from cells into biofluids like blood, carrying within representative material of their cells of origin. Cancerous cells-derived EVs contain information that can be used to elucidate the molecular differences with healthy EVs. A challenge in the EVs study is their heterogeneity and intrinsic complexity as well as isolation of them from body fluids on chip. We developed a nanostructured microchip, to collect the fingerprints of cancerous EVs to study the biomarker status. We want to combine this microchip with an EV’s isolation fluidic device for separation from human plasma.

Description of the Design Component:

The project goal is to assist in the design, implementation, validate, and optimization of a custom-designed microfluidic device equipped with a nanostructured chip for a controlled separation of EVs from human plasma and its components using principles of size exclusion chromatography.

Skills to have or develop: Prior experience with cad design (required). 3D printing of microfluidic to be developed.

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Project 18 Title: Computer controlled gas mixing system for probing neural circuits of respiratory function

Supervisor: Prof. Georgios Mitsis and Prof. Richard Hoge

georgios.mitsis [at] mcgill.ca; rick.hoge@mcgill

Preferred Team size: 4

Background and Objectives:

Background: Changes to blood levels of oxygen and carbon dioxide trigger several neural responses that are essential to homeostatic regulation. These responses can be affected by pharmacological interventions or disease, and are also associated with a person's subjective experience of stimuli such as exercise, changing environmental conditions, or impaired lung function. Much of our understanding of respiratory control mechanisms in health and disease has come from physiological studies (including neuroimaging studies) in which arterial blood gases have been manipulated accordingly.

Objectives: In this context, the main objective of the current project is to design and build a system that will allow computerized control of the amount of O2 and CO2 inspired by human research participants breathing through a face mask. The system will also need to record the concentration of O2 and CO2 in exhaled air, which can be used as an indicator of blood levels of these gases. The system must be designed in a way that ensures "fail safe" operation, meaning that the gas mixture received by human research participants must always be sufficient to support respiration with adequate O2 and maintaining CO2 within a specified limit.

 

Description of the Design Component:

The design component entails three main elements:

1) Hardware and software for controlled mixing of inspired gas concentrations

2) Hardware and software for recording of expired gas concentrations

3) Breathing mask and tubing for delivery of inspired gas and sampling of expired gas

These components must be able to operate in an integrated fashion, during programmed sequences in which the inspired gas mixture is automatically changed under computer control according to a predetermined schedule. Some applications, such as magnetic resonance imaging (MRI) scanning during a gas manipulation, may require the mixing and recording hardware to be kept several meters away from the breathing mask and gas sampling ports. The breathing mask geometry must be compatible with other equipment that may be used during these experiments, such as an MRI head coil.

Certain components of the system, such as voltage controlled gas mixers and transducers for measuring expired blood gases, will be provided in the form of commercially available "off the shelf" modules. The main design work will be related to the computer interfacing, physical packaging, and system integration aspects.

The group will have opportunities to discuss the various design objectives, and consider the relative merits of different "off the shelf" options for system modules. Some fabrication work, such as light machining, 3D printing, and electronics assembly/soldering will be required.

Skills to have or develop: Reuqested:

- some programming experience is essential
- experience with computer-hardware-sensor interfacing, ADC/DAC systems, is an asset
- experience in basic fabrication methods, such as CNC machining and/or 3D printing
- understanding of basic fluid dynamic concepts
- basic understanding of human physiology (respiratory, nervous system) is an asset

To be developed:

- understanding of respiratory physiology, including blood gas transport mechanisms and chemoreceptor systems
- experience with medical gas practices and standards
- system integration skills, related to the various hardware and software components of the system
- experience in the safety and ethical considerations of instrumentation used with human research participants

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Project 19 Title: Development of an integrated 3D-printed microfluidic device for point-of-care and electrochemical antimicrobial susceptibility testing applications

Supervisor: Prof Sara Mahshid sara.mahshid [at] mcgill.ca

Preferred Team size: 4

Background and Objectives:

Microfluidics is a cutting-edge field that deals with manipulating tiny volumes of fluids on a microscale. It has immense potential in developing rapid
and cost-effective point-of-care detection devices. We will harness the power of 3D
printing to create intricate microfluidic structures with precision and ease. You'll learn how
to design and print microfluidic devices tailored for specific applications. Gain practical
experience in designing, 3D printing, and assembling microfluidic devices. You'll work
closely with a team of fellow students and experienced mentors. The devices you create
will be used for point-of-care detection, bringing healthcare closer to the patient. Your
work could contribute to early disease detection, environmental monitoring, and more.
Antimicrobial resistance (AMR) is a major global health threat and among top research priorities. Rapid phenotypic profiling of drug-resistant bacteria for rapid and effective treatment is necessary. While new technologies now allow rapid detection of AMR genes, such technologies are limited to known gene targets and the poor correlation between AMR genotypes and drug susceptibility phenotypes. Therefore, innovating a point-of-care microfluidic base device for simultaneous validated diagnostic and rapid phenotypic antimicrobial susceptibility testing (AST) is essential for healthcare. Mahshid Lab is currently AST testing to make it easier and cheaper to manufacture tests and providing faster results for diagnostics. Furthermore, Mahshid Lab combines bottom-up and top-down fabrication techniques for fabrication of advanced nanostructured platforms and their integration with fluidic devices for optical and electrochemical sensing.

Description of the Design Component:

The aim of this project is to advance the development of point-of-care (POC) diagnostic devices for multiplexing microfluidic AST platforms with preparation chambers, diagnosis chambers for genotyping and phenotyping plasmonic electrochemical AST chambers for different antibiotic testing. We aim to fabricate a fully functional and fully integrated electrochemical biosensor device via a three-dimensional (3D)- printing approach. Additive manufacturing or 3D printing is a promising technology with numerous applications in the development of novel materials and devices for a wide range of electrochemistry and biosensing. The device will be produced entirely by 3D printing and equipped with three conductive electrodes (working, counter, and reference) printed from a conductive filament and an electrode holder printed from a non-conductive filament. This project will pave the way for the creation of a wide range of designs based on 3D-printing technology in modern on-a-chip devices. As a key part of this project, you will be involved in the design
aspect, contributing to the modification, miniaturization, validation, and optimization of a
custom-designed microfluidic device. This device is equipped with a flowing actuation
mechanism designed for efficient sample mixing, preparation, and purification.

Skills to have or develop: Knowledge of CAD designing (required), Hands-on laboratory experience (required), Additive manufacturing and 3D printing (be developed), Electrochemistry sensing (be developed)

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Project 20 Title: Development of an integrated 3D-printed microfluidic device for point-of-care and electrochemical antimicrobial susceptibility testing applications

Supervisor: Prof David Juncker David.Juncker [at] mcgill.ca

Preferred Team size: Any

Background and Objectives:

A pressure and flow modulating system for promoting aerosol sequestration in ventilated patients. Our lab has designed an aerosol capture device (ACD) currently undergoing adaptation to sampling from intubated ICU patients. Intubated patients often suffer from unmonitored respiratory tract infections which can lead to worse clinical outcomes. The ACD can be inserted into the exhaled tubing to help capture bacteria, viruses and detect lung biomarkers. During tidal breathing the ventilator mechanically assists with patient inhalation, but during exhalation the pressure is patient driven without ventilator assistance. The added flow resistance of the ACD could interfere with the breathing of the patient, and with the flow control of the ventilator. The objective of this project would be to design and fabricate an active air flow controller comprising sensors and a fan to compensate for the resistance of the ACD, i.e. to render the ACD invisible to the ventilator and patient during tidal ventilated breathing.

Description of the Design Component:

The main challenge of this project is the design and integration of a feedback and control system to precisely control the airflow around the ACD. Students will be provided a budget and the ability to choose suitable sensors, fans, circuitry and a control unit capable of negating the resistance of the chip without interfering with the operation of the ventilator. Additionally students will have to consider the limitations of the available fabrication techniques and the specifications of both the aerosol capture device and the available ventilators in the design of the enclosure and air flow interfaces. Students will be able to utilize CAD softwares such as Fusion 360 and simulate their designs using COMSOL prior to fabrication and validation. Final tests will be conducted with an artificial lung model and medical ventilators prior to any patient implementation.

Skills to have or develop: Skills involved in this project: CAD, Fluid dynamics, High resolution 3D printing, Comsol simulation, basic electrical feedback systems and sensors, circuitry and wiring.

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Project 21 Title: Multiplexed colorimetric biosensor on contact-mode CMOS image sensor

Supervisor: Prof Sebastian Wachsmann Hogiu

sebastian.wachsmannhogiu [at] mcgill.ca

Preferred Team size: 5

Background and Objectives:

The students will participate in the ongoing project of developing a multiplexed biosensor with colorimetric assays on a CMOS image sensor. The biosensor will provide quantitative results indicting the concentration of target analytes via optical signals captured by the CMOS image sensor. They will investigate the market and existing literature to identify suitable target analytes and help develop a complete device.
Objectives:
1. Conduct market study and literature search about which (~9 different) analytes to measure in the colorimetric assays to create a test that provides full analytical profile depending on the use case (e.g. electrolyte/cancer/hormonal profile). Look for corresponding biorecognition elements for the analytes of choice.
2. Fabricate a substrate with multiple microwells or microfluidic channels with minimized sample-to-sensor distance based on an existing design.
3. Add biorecognition elements to the substrate.
4. Interface via bluetooth to an electronic device such as cell phone. An app can be developed for interfacing with healthcare providers.
5. Prototype a box where an LED light source and pinhole is placed at the top to provide controlled illumination.

Description of the Design Component:

The students will participate in the design process starting with the definition of the use case, identify constraints and related specifications, design and build components according to specifications, including packaging and user interface, evaluate economic, social, and environmental impact.

Skills to have or develop: Biosensors, analytical methods, market evaluation, prototyping.

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The Capstone Design Project Proposals listed below are available to undergraduate students registered in the Department of Bioengineering. Students interested in a particular project are welcome express their interest by sending an email to the supervisor offering the project. Note that each project has been created for teams of 3 to 4 bioengineering students.

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Please also see the MedTech sponsored projects

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