Microfluidic Sample Handling for the Spectroscopic Integration (SPIN) Program

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Long Term Vision To develop a microfluidic platform to integrate distinct single cell spectroscopic technologies for the study of heterogeneous cell populations with single cell granularity across an unprecedented spectral range. The Full SPectrum INterrogation Project (Full SPIN) is an initiative to incorporate multiple spectral modalities in order to gain a complete picture of dynamics within heterogeneous cell populations with single cell granularity. Full SPIN take disaggregated cell samples, image the cells, and then characterize single cell transmission spectra using four complementary technologies: Radio Frequency spectroscopy, Terahertz spectroscopy, Raman spectroscopy, and (cavity-reflection-enhanced) Visible spectroscopy. This system will allow for the cell-indexed correlation of the spectra at a single cell level so that their contribution to the bulk response can be inferred and the heterogeneous nature of the population can be better understood. The proposed work spans the fabrication of microfluidic modules with optimized materials for each spectroscopic technology, the cell handling needed to index a library of cells so that the spectra can be correlated at the single cell level across all the interrogation wavelengths, and the demonstration of the platform's utility by studying the cell population's response to stimulus. The work supported in this proposal will involve 2 PhD, 1 MASc and 2 undergraduate students per year for the duration of the funding. The HQP will be focused on the development and demonstration of the various modules that make up the Full SPIN platform. Human samples will not be used in the work proposed, which will focus on technology development and use standard cell lines to demonstrate the functionality and utility of the platform. The modular platform consists of several components: an indexing chip to generate a library of single cells stored in a water-in-oil emulsion, an index cartridge that will store the library and maintain cell viability, and a set of interrogation chips customized to each of the spectral interrogation methods. The library of cells will be transferred in the index cartridge to each interrogation chip in turn and a second index cartridge will collect the library again at the output of the interrogation chip and then transfer the library to the next interrogation module in turn. The final milestone for the proposed work is processing an indexed cell library of >1000 cells, imaging the cells, and acquiring correlated spectra in all of the spectral windows, both before and after a stimulus event. The resulting data will then be used to enable the statistical modelling of the individual cellular contribution population's response to the stimuli. The applications of this technology platform are broad, answering basic questions about heterogeneous cellular response.