Aaron Wheeler

MY RESEARCH OVERVIEW (GO TO SCIENTIFIC OVERVIEW)

Microfluidics for Chemistry, Biology, and Medicine

I have to think small to think big. My research focuses on creating “labs-on-a-chip” (LOCs)—miniaturized, automated devices that are capable of conducting several laboratory experiments at once. LOCs use tiny amounts of reagents (a material that can start a chemical reaction) and other materials, which results in less environmental waste, reduced lab costs and overall increased efficiency.

In developing LOCs, we take advantage of a wide range of tools, including microfabrication, fluorescence microscopy, chemical separations, mass spectrometry, and in vitro cell culture and analysis. A key technology that we use is called digital microfluidics (DMF). In DMF, discrete liquid droplets are manipulated on the surface of an insulated array of electrodes. DMF facilitates an unparalleled level of control over microchemical reactions, and we are exploring the unique capabilities of DMF for applications ranging from chemical synthesis to clinical sample preparation to tissue engineering. We are fortunate to be surrounded by top-notch biologists from the Donnelly Centre, who have more interesting problems than we can possibly ever solve!

This environment is perfect for my research. If you take a quick stroll through the building, you are liable to run into a geneticist, chemist, molecular biologist, chemical engineer, and computer scientist. Members of the Donnelly Centre were pre-selected for their willingness to participate in unconventional collaborations and our physical proximity allows scientists from different worlds to bump into each other and dream up new research projects.

SCIENTIFIC RESEARCH OVERVIEW

Our research group is engaged in a diverse range of projects using microfluidics to solve problems in chemistry, biology, and medicine. Vignettes describing four current projects are described below.

(A) The Wheeler-group partnered with the U.S. Centers for Disease Control and Prevention (CDC), the United Nations (UN), and the Kenyan Ministry of Health to implement the world’s first field trial for a digital microfluidics-powered instrument operated outside of the laboratory. In 2016, a team from the lab accompanied the CDC on a trip to Kakuma Refugee camp in northwest Kenya (accessible only by charter flight operated by the UN) to conduct a digital microfluidic serological survey for measles and rubella among residents of the camp. A paper describing the work was recently published [Science Trans. Med. 2018, 10, eaar6076], and a five-minute movie about the trip can be seen here: https://www.youtube.com/watch?v=Bvs2J1K_WTE. The group recently completed a second field trial with CDC and the Institut National de la Recherche Biomédicale in Democratic Republic of Congo [not yet published].

(B) The Wheeler-group was the first to use digital microfluidics for applications involving mammalian cells [Lab Chip 2008, 8, 519-526], and has continued to set the curve in an area of intense interest by researchers around the world. Most recently the group reported the world's first system that allows for sub-classification of invading cells into hydrogel matrices as a function of their transcriptomes [Science Adv. 2020, 6, eaba9589], as well as the first platform to connect single-cell genome, transcriptome, and proteome sequencing results to immunofluorescence-based phenotypes [Nature Comm. 2020, 11, 5632].

(C) The Wheeler-group was the first to propose digital microfluidics as an alternative to microchannels for miniaturized organic synthesis, describing a device designed to handle solid and liquid reagents with diverse properties for up to thirty reaction steps in parallel [Angew. Chem. 2010, 49, 8625 –8629]. The group's recent work in this area has focused on micro-coil NMR spectroscopy, with a recent report of a system that allows for conditions to be screened to either characterize a known reaction in detail or search for novel reactions and unexpected products while using only tiny amounts of reagents [Angew. Chem. 2019, 58, 15372-15376].

(D) The Wheeler-group has developed innovative optical techniques to control the positions and behaviour of cells and particles. Recent work in this area includes a "micro-robot" that can be programmed to carry out sophisticated, multiaxis operations, which was demonstrated to be useful for single-cell isolation, clonal expansion, RNA sequencing, manipulation within enclosed systems, controlling cell–cell interactions, and isolating precious microtissues from heterogeneous mixtures. [Proc. National Acad. Sci. 2019, 116, 14823-14828], and a rapid prototyping technique for forming opto-topographical patterns and labels [Advanced Opt. Mater. 2019, 7, 1900669].

SELECT PUBLICATIONS

• Digital Microfluidic Isolation of Single Cells for -Omics. Lamanna, J.; Scott, E.Y.; Edwards, H.S.; Chamberlain, M.D.; Dryden, M.D.M.; Peng, J.; Mair, B.; Lee, A.; Chan, C.; Sklavounos, A.A.; Heffernan, A.; Abbas, F.; Lam, C.; Olson, M.E.; Moffat, J.; Wheeler, A.R. Nature Comm., 2020, 11, 5632. 
• Cell Invasion in Digital Microfluidic Microgel Systems. Li, B.B.; Scott, E.Y.; Chamberlain, M.D.; Duong, B.T.V.; Zhang, S.; Done, S.J.; Wheeler, A.R. Science Advances. 2020, 6, eaba9589.
• A Digital Microfluidic System for Serological Immunoassays in Remote Settings. Ng, A.H.C.; Fobel, R.; Fobel, C.; Lamanna, J.; Rackus, D.G.; Summers, A.; Dixon, C.; Dryden, M.D.M.; Lam, C.; Ho, M.; Mufti, N.S.; Lee, V.; Asri, M.A.M.; Sykes, E.A.; Chamberlain, D.; Joseph, R.; Ope, M.; Scobie, H.M.; Knipes, A.; Rota, P.A.; Marano, N.; Chege, P.M.; Njuguna, M.; Nzunza, R.; Kisangau, N.; Kiogora, J.; Karuingi, M.; Burton, J.W.; Borus, P.; Lam, E.; Wheeler, A.R. Sci. Trans. Med. 2018, 10, eaar6076.