Welcome to deMello Group to perform your student projects. There are constantly open projects for bachelor and master students. You can either follow an ongoing research project or define a new project in discussion with a mentor in deMello Group. Here we list some of the currently available student projects (topics). For more possibilities, you can ask by email or visiting our lab.
Development of Microfluidic Chip for Coronary Microvascular Disease
Coronary microvasculature is subjected to a plethora of diseases that are poorly understood and diagnosed. The systematic integration of microfluidics in the analysis of coronary microvascular disease (CMVD) is essential for a better understanding of the hemodynamic alteration and the consequent endothelial dysfunction leading to the pathological cardiac impairment.
Starting from the latest experimental set-up and chips microfabricated in our group, we herein propose to optimize the microvascular perfusion model through in-silico and/or in-vitro modelling, with the final goal of replicating with high-fidelity the pathological condition observed in-vivo through qualitative positron emission tomography images.
To achieve this goal, we will need to:
Optimize the perfusing system for a controlled hemodynamic stimulation;
Characterize the biomechanical and biocompatibility properties of the developed platform.
Prior knowledge of computational fluid dynamics and/or microfabrication is preferential.
Dr. Monika Colombo
Optimizing Fluid Transport and Saturation Kinetics in Lateral Flow Assays
Paper-based lateral flow assays (LFA) are widely employed as diagnostic tools within a broad range of fields, including biomedical research, healthcare, and environmental science. Due to their simplicity and affordability, LFAs are especially useful for Point-of-care (POC) diagnosis. Paper-based LFAs are attractive as tools to evaluate biological markers in bodily fluids (saliva, urine, etc), and are perhaps most well known for their role in affordable disease diagnostics. Paper-based devices are especially simple because of the power-free fluid transport by capillary action. The flow characteristics of these assays determine the diagnostic performance (i.e. sensitivity and specificity) of the tests, so improving our fundamental understanding of flow in paper-based LFAs is of paramount importance. Several questions remain regarding how fluid flow impacts target binding and signal generation in these assays, and we believe recent advances in computational simulation can help us to find the necessary answers.
Herein we propose to develop an in-silico model to reproduce with high-fidelity real-life LFA test performance. This model, once calibrated and validated with real LFA tests, will be used to answer important questions regarding how LFAs operate. We will subsequently use the knowledge we have gained to improve the performance of this important class of diagnostic tool.
To achieve this goal, we will need to:
Derive the parameters to define the computational model;
Verify the simulated binding and transport phenomena with the experimental data – through real-time image acquisition;
Optimize the real materials (with possibility of introducing novel components) to improve efficacious transport and binding in the LFA.
Prior knowledge of computational fluid dynamics and/or pharmaco-kinetics simulations is preferential.
This project is co-supervised by Dr. Monika Colombo, Leonard Bezinge and Dr. Daniel Richards.
Dr. Monika Colombo
Smart Hydrogel for Monitoring Extracellular Vesicles Biogenesis at the Single Cell Level
Human cells communicate within tissue and more generally within the organism using diffusible factors to adapt and synchronize biological processes. Many proteins secreted by cells, such as hormones, cytokines, and growth factors, have already been involved in these processes.
Interestingly, cells also communicate by secreting "information packets" in the form of extracellular vesicles (EV) containing proteins and nucleic acids cargos. However, characterizing the nature and function of these vesicles remains challenging because of their size (40-1000nm), and our current lack of knowledge about the processes ruling their secretion. Hence, dissecting the fundamental mechanisms associated with their biogenesis could teach us a lot about cellular communication and the biology of certain viruses that are known to exploit similar mechanisms. We can also use this knowledge to develop innovative diagnostic or therapeutic tools based on the encapsulation of bioactive molecules in these vesicles.
This project aims to combine advanced chemistry and biology approaches to develop novel assays allowing monitoring of EV secretion at the single-cell level. To achieve this goal, we are currently creating hydrogel materials that become fluorescent in the presence of EVs. By encapsulating cells into these "smart" hydrogels using microfluidics approaches, we can then study single-cell EV production over time using microscopy and flow cytometry. Our long-term objectives are to exploit these new tools to study the dynamics of extracellular vesicle secretions and perform CRISPR genetic screens to identify which proteins are involved in these processes.
Alessandra Stürchler, Dr. Bogdan Mateescu
Spatial Mapping of Tissue Sections
In this work, we propose using a microfluidic probe (MFP) to quantify heterogeneity in tissue sections by periodic sampling and spatial mapping of the tissue section.
Tumors, as all biological organisms, provide a wide range of variability in their structure and expression. This variability manifests itself in the macro scale – the morphology itself, and also in the micro-scale – the difference in molecular expression. These molecular variations are expressed as inter-tumor and intra-tumor heterogeneities. Traditional gold standard technique of tumor analysis – immunohistochemistry (IHC) provided an elegant staining method but is limited by being an end-point assay and is used to provide one data point for the whole tissue. Averaging out all heterogeneity information in the entire tissue section leads to loss of important diagnostic information. A recently developed workflow, called GeneScape (Voithenberg et. al., Small, 2021), allows localized analysis while preserving spatial information.
We propose to extend the workflow to parallelize sample collection and subsequent analysis. Adapting sample collection techniques to existing workflows will further allow easy acceptance and adoption of the proposed technique in general practice. The application of spatial information in tumor heterogeneity will be in basic research and clinical use to adapt tumor therapy based on molecular heterogeneity.
New CRISPR/Cas13 Tool for Context-dependent Manipulation of Cells
CRISPR, and specifically Cas9, is truly an exceptional genome engineering tool and winner of the Nobel prize in Chemistry 2020. It is easy to use, functional in most species, and has many applications in research and clinical studies. The focus of this project is to develop a new CRISPR tool based on Cas13 enzyme, which has the ability to bind target RNA instead of DNA, enabling transcriptome manipulation without direct and permanent genome modification. The cherry on the top of this new tool will be to combine CRISPR/Cas13 with the endogenous RNA silencing machinery in order to control the cell transcriptome in a context-dependent manner, allowing modifications only in specific cell types and/or stages. Aspects of the project will be:
Molecular cloning (generation of guide RNA constructs with different conformations)
Cell culture (cell lines generation, tool optimization)
Flow cytometry and data analysis
On-chip Three-dimensional Cell Imaging
Three-dimensional (3D) imaging of cells can reflect important morphological information, which is crucial for understanding complex biological processes. However, current 3D cell imaging techniques typically suffer from inherently low throughput (few cells per second) which is not suitable for the vast majority of biological applications. To this end, we will develop a high-throughput microfluidic platform for multiparametric 3D cell imaging. We envision our platform can be a powerful tool for high content cell analyses.
CLOUD-ON-A-CHIP: When Does Ice Nucleate?
It is a collaboration between the Atmospheric Physics (Lohmann, D-USYS) and Microfluidics (deMello, D-CHAB) groups. The project is to improve our ability to predict the formation of ice and clouds (cold and mixed-phase) in the atmosphere by quantifying the ice nucleation activity of particles (mineral, biological, and/or anthropogenic). More details can be seen here.
A Well-defined Double Emulsion System for High-throughput Biological Screening Experiments
Water-in-oil-in-water emulsions or double emulsions (DB) could be the next research focus of droplet-based microfluidics. The semi-permeable interface of the DB and the aqueous surrounding environment provide new opportunities for performing high-throughput biological screening experiments. In this project, you will define a DB system and optimize its workflow for the usage in a specific biological task. You will have a lot of fun to play with these lovely DBs. This project is suitable for creative master students.
Dr. Yun Ding
A High-Throughput Optofluidics for Rare Cells Enrichment
Rare cells sorting is important for single cell analysis and disease diagnosis. However, these cells, like circulating tumor cells (CTCs), usually present at very low levels (around 1~10 CTCs per milliliter), which challenges the current benchtop fluorescence-activated cell sorting systems. For this project, a high throughput microfluidic flow cytometer for CTCs enrichment will be developed, the goal of which is to provide a pre-sorting strategy which can enrich the CTCs concentration to a large extent in quite a short time with high accuracy before downstream analysis.
Microfluidic System for Extracellular Vesicles Fractionation
Extracellular vesicles (EVs), including apoptotic bodies, microvesicles and exosomes, is a kind of lipid-based vector which contains nucleic acids and proteins for intracellular communication, demonstrating great potential for early disease detection and therapeutic drug delivery systems. Traditional separation methods, e.g. differential centrifugation and ultrafiltration, are time-consuming and labor-intensive, and suffer from low sample purity or low sample yield. Towards this end, a novel and simple microfluidic system for isolation of EVs based on their size will be developed. Downstream analysis, e.g. western blot and sequencing, will be employed, hopefully providing an easy-operating way for early detection of cancer.
Yingchao Meng, Mohammad Asghari