A Magnetic Microrobotic System with Raman Spectroscopy and Confocal Fluorescence Microscopy for Molecular Diagnostics and Cell Biology

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Magnetically controlled microrobots represent a promising platform technology for manipulation and characterization of cells and biomolecules. Current magnetic microrobotic systems typically involve brightfield/fluorescence microscopy or ultrasound imaging as visual feedback, which cannot retrieve any biochemical information of the bio-sample under manipulation. This application aims to establish the first magnetic microrobotic system seamlessly integrating both Raman spectroscopy and confocal fluorescence microscopy, for simultaneous manipulation of intracellular organelles/biomolecules and characterization their biophysical and biochemical properties. The unique combination of the Raman and confocal fluorescence imaging modalities provides the microrobotic system with both biophysical and biochemical feedback and allows novel applications in molecular diagnostics and cell biology. The proposed microrobotic system includes: (1) a Raman imaging system based on an inverted microscope for biochemical characterization of bio-samples; (2) a custom-made, coil-based electromagnetic control module for positioning of magnetic bead-based microrobots with sub-micrometer resolution; and (3) a laser scanning confocal fluorescence imaging module, which can be readily integrated onto the inverted microscope of the Raman imaging system, for 3D imaging of the magnetic bead-based microrobot and the bio-sample. With CFI and NSERC Discovery Grant support, the applicants have purchased a Raman imaging system with an inverted microscope, and developed a custom-made electromagnetic control module. This RTI application is to request the laser scanning confocal fluorescence module for integration with the Raman imaging system. Using this unique system, we will pursue the following research projects: (1) microrobotic capture, enrichment, and amplification-free detection of the novel coronavirus (severe acute respiratory syndrome coronavirus 2 SARS-CoV-2); (2) microfluidic characterization of nucleus mechanics and associated molecular mechanisms of brain cancer cells; and (3) label-free detection and spatial profiling of signaling molecules during microfluidic cell co-culture. The requested confocal fluorescence imaging module will be used for: (1) vertical scanning of fluorecence signals from a magnetic bead for amplification-free detection of SARS-CoV-2; (2) 3D imaging of a magnetic bead-based microrobot inside a brain cancer cell and the cell's nuclear deformation during magentic bead indentation; and (3) fluorecence imaging of bone cells (osteocytes) and bone resorption cells (osteoclasts) co-cultured on a microfluidic device. This system be used for training 15 HQPs from 8 research labs, and will serve as a powerful multifunctional facility to enable new collaborations at the interface of robotics, diagnostics and cell research.