Microfluidic Probe for Multiphysics Enabled Single Cell Manipulation

In this work, we develop microfluidic probes (MFPs) by utilizing high resolution 3D printing, and demonstrate applications in targeted drug delivery with a single cell resolution. In addition, the MFP's features are extended to include heating elements in order to facilitate its application as a single cell micro-thermo-fluidic tweezer - a heat assisted microfluidic single cell tweezer. With the high resolution 2-photon photolithography 3D printing technique (Nanoscribe), we achieve microfluidic injection apertures of 30 μm diameter which corresponds to the average span of single cells in adherent culture. Flow characterization demonstrates the devices' capability of rapidly adjusting its localized target area from about 100 cells (32,000 μm ² ) to single cell resolutions (320 μm ² ). Results show that these resolutions can be maintained in the scanning mode to achieve high resolution drug delivery in cultured adherent cells. Furthermore, as an advancement to the conventional MFP, pin shape electrodes were introduced at the tip to incorporate localized heating features for optimal cell dissociation conditions. Characterization of the heat generated by the pin electrodes is reported and an application of the microthermo-fluidic tweezer to selectively detach and collect single adherent cells is demonstrated.