Interrogating and Manipulating Biological Material at Small Scales

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Advances in the development of novel biophysical analytical capabilities provide access to new insight into the biological condition of living systems. Our ability to manipulate fluids at the micro- and the nano-scales is allowing us to conceive of new analytical devices that utilize remarkable small-scale phenomena in mitigating some of the issues found in conventional sensing platforms. In the last decade, nanopore sensors have emerged as one of the most promising next-generation analytical tools given their ability to analyze biological samples with single-molecule sensitivity. Solid-state nanopores are synthetic analogs to the biological pores found in cell membranes. These nanopores are nanofluidic channels that allow the translocation of single biomolecules, such as DNA, RNA and proteins, from one side of a membrane to the other. When used as sensors, we can monitor the ionic current through such nanopores in order to gain a wealth of physical and chemical information about the translocating molecule. In addition to its use in DNA sequencing, this concept exhibits great promise in other applications including disease diagnostics and the study of single-cell signaling. Recently, we discovered an approach to integrating such nanopore sensors within microfluidic networks. This has opened the door to the development of portable lab-on-a-chip analytical platforms that can accommodate real-world samples, by offering on-chip sample processing capabilities (filtering, mixing, pre-concentrating, etc.) upstream of the nanopore sensor. Intriguingly, nanopore performance is altered when confined within microchannels. In this Discovery program, we will investigate the mass transport phenomena that occur near the nanopores when integrated within microchannels, and use these results to tune sensor performance. Also, we will use our ability to trap picolitre-scale samples near the nanopore to enable the accurate quantification of biomolecular concentration, and this platform will enable the study of cell signaling at the single cell level. These discoveries will lead to the development of new analytical platforms that will greatly broaden disease diagnostic capabilities by enabling the analysis of ultra-low concentration biomarkers, while also providing insight into the biology of single cells. The knowledge acquired and the technologies developed over this DG cycle could potentially secure a global competitive edge for the Canadian biomedical sector. Our work provides a path towards the development of point-of-care diagnostics platforms that could greatly enhance our ability to track disease. Moreover, the associated interdisciplinary training will undoubtedly provide students (HQP) with a broad skillset in science and engineering while focusing on single-molecule techniques, which are in growing demand in Canada's high-tech industry.