Nanofountain‐Probe‐Based High‐Resolution Patterning and Single‐Cell Injection of Functionalized Nanodiamonds

Abstract

Nanodiamonds are rapidly emerging as promising carriers for next-generation therapeutics and drug delivery. However, developing future nanoscale devices and arrays that harness these nanoparticles will require unrealized spatial control. Furthermore, single-cell in vitro transfection methods lack an instrument that simultaneously offers the advantages of having nanoscale dimensions and control and continuous delivery via microfluidic components. To address this, two modes of controlled delivery of functionalized diamond nanoparticles are demonstrated using a broadly applicable nanofountain probe, a tool for direct-write nanopatterning with sub-100-nm resolution and direct in vitro single-cell injection. This study demonstrates the versatility of the nanofountain probe as a tool for high-fidelity delivery of functionalized nanodiamonds and other agents in nanomanufacturing and single-cell biological studies. These initial demonstrations of controlled delivery open the door to future studies examining the nanofountain probe's potential in delivering specific doses of DNA, viruses, and other therapeutically relevant biomolecules.

In situ lipid dip‐pen nanolithography under water

“…Although nanofountain pens, which combine concepts of DPN with those of micropipettes (Moldovan et al 2006), have recently been used in parallel and multiplexed to increase scale, and materials have even been delivered to living cells in air (Loh et al 2009), carrying out such experiments under water remains a challenge, as the concepts of DPN are so far limited to air. Microcontact printing of water-insoluble thiols has been carried out under water for some time now, for example, to minimize ink transfer from the stamp through the vapor phase by the use of reactive thiol spreading on a gold surface (Xia and Whitesides 1995).…”

System control-mediated drug delivery towards complex systems via nanodiamond carriers

“…So far, it is known that pH and salts within buffers have a considerable effect on ND aggregation and stability, which ultimately effects cell internalization behavior [36].…”

Micro/nanofabricated environments for synthetic biology

“…Examples of electrochemical strategies that have been developed for controlling biological activity include engineered molecular 'wires' that can amplify catalysis of redox-active enzymes with electron transfer reactions [99], controlled release of different cell signaling molecules at specific locations via electrochemically activated leaving groups [100,101], and the use of electrostatic fields to induce conformational changes and hybridization reactions in charged biopolymers [102][103][104]. These and other strategies are being implemented in the development of a number of new nanofabricated device concepts, such as functionalized nanotube/nanowire sensors [105][106][107][108][109] and nanoprobes [110 ] that can not only sense biomolecules, but also trigger specific biochemical changes in cells and tissue, the integration of nanofluidics-based platforms on scanning probes [111,112], and the fabrication of high-density nanowells sealed with supported lipid bilayers that can release encapsulated molecules on demand [113].…”