Reconfigurable multipolar microfluidics
Microfluidics multipoles (MFMs) are open-space microfluidics devices allowing the localized control of fluid on surfaces. Because of their compatibility with planar samples, such as petris, tissue slices, and proteins microarrays, which are extensively used in biology, they can be used for applications where the use of channels-based microfluidic devices is inconvenient.
Our last article on the subject “Microfluidic multipoles theory and applications” (available at https://doi.org/10.1038/s41467-019-09740-7) present an analytical framework to study the general problem of advective-diffusive transport in MFMs. It provides a simple strategy for theory-guided design of open-space microfluidics systems. Furthermore, reconfigurable MFMs are presented. Using the flow rate modulation, these devices can dynamically control fluids and can address multiple surface regions in parallel. The reconfigurable MFMs are then tested for the automatization of immunofluorescent assay.
The next generation of reconfigurable multipolar devices will aim at addressing hundreds of independent areas in parallel. Further automatization of surface processing experiments will be performed.
Radiotherapy on chip
Collaboration with Philip Wong (Centre de recherche du CHUM)
At least 60% of patients with cancer will receive radiotherapy as part of their treatment. Many drugs are developed for use as monotherapy or drug-drug combination, but fewer drugs are evaluated for their beneficial or negative interactions with radiotherapy. In parallel, each year thousands of pharmacological compounds are abandoned because of their weak efficacy in monotherapy. These compounds could have important radio-sensitizing or radio-protective properties. To test the efficacy of drugs 3D cell culture models are emerging, motivated by the need of better preclinical models. Spheroids are a 3D model that recapitulate some important 3D properties of tissues, including a resistance to oxygen and metabolite transport. Building upon our previous work (https://doi.org/10.3390/s17102271), the goal of this project is to optimize microfluidic chips towards high-throughput pre-clinical screening of therapeutic agents with radiotherapy on spheroids. This work leads towards a systematic method to assay synergies of molecular agents with radiotherapy using simple, disposable Lab-on-a-chip systems.
Hyperspectral imaging of spheroids
Collaboration with Frédéric Leblond (Polytechnique Montréal)
In epithelial ovarian cancer, the 5-year survival rate is less than 45%, due to late diagnoses and resistance to chemotherapy, underscoring the need for chemoresistance assays. The growing field of 3D cell culture on-chip provides new tools to cancer biologists to study aspects of chemoresponse neglected by 2D cultures, such as 3D cell-cell interactions and transport limitations. However, there remains significant challenges with respect to obtaining reliable readouts of chemotherapeutic responses. In this project, wide-field hyperspectral imaging (HSI) is used to study the chemoresponse of co-culture tumor spheroids trapped in microfluidic chips. Based on fluorescence spectroscopy rather than microscopy, it enables the quantification of multiple fluorescent markers, allowing analyses of the same spheroid at multiple time-points without digesting it (https://doi.org/10.1093/intbio/zyz012).
By simultaneously combining wide-field imaging and fluorescence quantification, fluorescence spectroscopy imaging provides a unique approach to non-destructive, long-term monitoring of highly multiplexed fluorescent signals on chip. Although this work focuses on spheroid analysis and chemoresistance assays, the technique is directly applicable to other types of assays, such as live-dead assays, and other 3D cell cultures, such as organoids, microdissected tissues, and organs-on-chips.