On-chip magnetic separation and encapsulation of cells in droplets

Abstract

The demand for high-throughput single cell assays is gaining importance because of the heterogeneity of many cell suspensions, even after significant initial sorting. These suspensions may display cell-to-cell variability at the gene expression level that could impact single cell functional genomics, cancer, stem-cell research and drug screening. The on-chip monitoring of individual cells in an isolated environment would prevent cross-contamination, provide high recovery yield, and enable study of biological traits at a single cell level. These advantages of on-chip biological experiments is a significant improvement for myriad of cell analyses over conventional methods, which require bulk samples providing only averaged information on cell metabolism. We report on a device that integrates mobile magnetic trap array with microfluidic technology to provide, combined functionality of separation of immunomagnetically labeled cells or magnetic beads and their encapsulation with reagents into pico-liter droplets. This scheme of simultaneous reagent delivery and compartmentalization of the cells immediately after sorting, all performed seamlessly within the same chip, offers unique advantages such as the ability to capture cell traits as originated from its native environment, reduced chance of contamination, minimal use and freshness of the reagent solution that reacts only with separated objects, and tunable encapsulation characteristics independent of the input flow. In addition to the demonstrated preliminary cell viability assay, the device can potentially be integrated with other up- or downstream on-chip modules to become a powerful single-cell analysis tool.

The 2017 Magnetism Roadmap

“…In particular, the versatility of magnetic shuttle technology has great potential in the logical manipulation of a specific cell selection, capture, transport and encapsulation with the support of superparamagnetic iron oxide nanoparticle (SPION) carriers within the magnetophoretic platform [186,187], as depicted in figure 24. Here, the shuttling performance relies on both magnetic energy and force tunability on the periphery of the micro-and nano-patterned magnetic structures, fabricated by successive procedures of photolithography and magnetron sputtering deposition, and their logical manipulation is accomplished by the remote control of an external magnetic field [186,[188][189][190].…”

Dynamic trajectory analysis of superparamagnetic beads driven by on-chip micromagnets

“…This approach has been studied previously in colloidal suspensions interacting with arrays of optical traps, 16,17 or in periodic magnetization patterns exposed to a time-varying magnetic field. [10][11][12]14,[18][19][20][21][22] Magnetic separation, in particular, has notable advantages including its biocompatibility, absence of magnetic shielding from the environment, the wide selection of commercially available magnetic beads, and finally its ability to apply strong forces remotely to colloidal particles without significant heating or other deleterious effects.…”

Micromagnet arrays for on-chip focusing, switching, and separation of superparamagnetic beads and single cells

“…The combination of MMA and rotating fields has been used for on-chip cell manipulation. [22][23][24] Using engineered microstructures, the controlled transport, assembly, and isolation of both labelled and non-labelled cells have been recently demonstrated.…”