Quantitative nanopatterning of fg-scale liquids with dip-pen nanolithography

The ability to precisely pattern nanoscale amounts of liquids is essential for biotechnology and high-throughput chemistry, but controlling fluid flow on these scales is very challenging. Scanning probe lithography methods such as dip-pen nanolithography (DPN) provide a mechanism to write fluids at the nanoscale, but this is an open loop process as methods to provide feedback while patterning sub-pg features have yet to be reported. Here, we demonstrate a novel method for programmably nanopatterning liquid features at the fg-scale through a combination of ultrafast atomic force microscopy probes, the use of spherical tips, and inertial mass sensing. We begin by investigating the required probe properties that would provide sufficient mass responsivity to detect fg-scale mass changes and find ultrafast probes to be capable of this resolution. Further, we attach a spherical bead to the tip of an ultrafast probe as we hypothesize that the spherical tip could hold a drop at its apex which both facilitates interpretation of inertial sensing and maintains a consistent fluid environment for reliable patterning. We experimentally find that sphere-tipped ultrafast probes are capable of reliably patterning hundreds of features in a single experiment. Analyzing the changes in the vibrational resonance frequency during the patterning process, we find that drift in the resonance frequency complicates analysis, but that it can be removed through a systematic correction. Subsequently, we quantitatively study patterning using sphere-tipped ultrafast probes as a function of retraction speed and dwell time to find that the mass of fluid transferred can be modulated by greater than an order of magnitude and that liquid features as small as 6 fg can be patterned and resolved. Taken together, this work addresses a persistent concern in DPN by enabling quantitative feedback for nanopatterning of aL-scale features and lays the foundation for programmably nanopatterning fluids.