The use of personalized medicine in the treatment of cancer has garnered significant interest in recent year; however, many challenges arise due to the heterogeneous nature of cancer and high patient to patient variability. In order to overcome this limitation, combinations of multiple therapeutics have been considered, particularly in targeting drug-resistant tumor cells. Such an approach requires new technology capable of high-throughput screening (HTS) coupled with the analysis of individual cellular behavior. Droplet microfluidic devices is an ideal candidate to achieve this; however, they are often limited to a single input and are not capable of assessing multiple drug combinations simultaneously. The goal of this work was to address this issue by designing and fabricating a triple-input microfluidic droplet trapping device to perform high-throughput single cell analysis in samples treated with various concentration of known drugs. The multi-input microfluidic device was designed using AutoCAD to incorporate three flow-focusing junctions followed by a large downstream trapping array. The device inputs include both aqueous and oil (2 w/w % fluorosurfactant) streams from three distinct sources that are capable of generating 70 µm droplets with a 40-50% single cell encapsulation efficiency. The downstream trapping array has a capacity of 4,000 droplets, which are separated from the bulk solution due to the difference in densities between the aqueous and oil phases. This array allows for time-dependent single cell analysis without the need for expensive high-speed cameras. To ensure an equal distribution (both spatially and quantity) of droplets in the trapping array, a mixing-baffle system was included. The devices were fabricated via a two-step and cost-efficient fabrication process incorporating a soft-lithography wafer fabrication process followed by a polydimethylsiloxane (PDMS) replication process. To demonstrate the feasibility of the proposed triple-input microfluidic device, photo luminescent rare earth doped nanoparticles developed in our lab were utilized as an optical method for droplet tracking to follow the droplets generated at the three different inputs. The work described here is a first step towards a fully characterized multi-input microfluidic droplet trapping device capable of performing high-throughput screening of individual cellular behavior under a variety of cancer therapeutics simultaneously in a time and cost-efficient manner.

Design and fabrication of a triple-input microfluidic droplet trapping array towards multiplexed cancer diagnostics

255th National Meeting (2018)

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