Highly stable integration of graphene Hall sensors on a microfluidic platform for magnetic sensing in whole blood

The detection and analysis of rare cells in complex media such as blood is increasingly important in biomedical research and clinical diagnostics.Micro-Hall detectors(μHD)for magnetic detection in blood have previously demonstrated ultrahigh sensitivity to rare cells.This sensitivity originates from the minimal magnetic background in blood,obviating cumbersome and detrimental sample preparation.However,the translation of this technology to clinical applications has been limited by inherently low throughput(<1 mL/h),susceptibility to clogging,and incompatibility with commercial CMOS foundry processing.To help overcome these challenges,we have developed CMOS-compatible graphene Hall sensors for integration with PDMS microfluidics for magnetic sensing in blood.We demonstrate that these grapheneμHDs can match the performance of the best publishedμHDs,can be passivated for robust use with whole blood,and can be integrated with microfluidics and sensing electronics for in-flow detection of magnetic beads.We show a proof-of-concept validation of our system on a silicon substrate and detect magnetic agarose beads,as a model for cells,demonstrating promise for future integration in clinical applications with a custom CMOS chip.

Pico-washing:simultaneous liquid addition and removal for continuous-flow washing of microdroplets

Droplet microfluidics is based on a toolbox of several established unit operations,including droplet generation,incubation,mixing,pico-injection,and sorting.In the last two decades,the development of droplet microfluidic systems,which incorporate these multiple unit operations into a workflow,has demonstrated unique capabilities in fields ranging from single-cell transcriptomic analyses to materials optimization.One unit operation that is sorely underdeveloped in droplet microfluidics is washing,exchange of the fluid in a droplet with a different fluid.Here,we demonstrate what we name the"pico-washer,"a unit operation capable of simultaneously adding fluid to and removing fluid from droplets in flow while requiring only a small footprint on a microfluidic chip.We describe the fabrication strategy,device architecture,and process parameters required for stable operation of this technology,which is capable of operating with kHz droplet throughput.Furthermore,we provide an image processing workflow to characterize the washing process with microsecond and micrometer resolution.Finally,we demonstrate the potential for integrated droplet workflows by arranging two of these unit operations in series with a droplet generator,describe a design rule for stable operation of the pico-washer when integrated into a system,and validate this design rule experimentally.We anticipate that this technology will contribute to continued development of the droplet microfluidics toolbox and the realization of novel droplet-based,multistep biological and chemical assays.