An atomic force microscope nanoscalpel for nanolithography and biological applications

Abstract

We present the fabrication of specialized nanotools, termed nanoscalpels, and their application for nanolithography and nanomechanical manipulation of biological objects. Fabricated nanoscalpels have the shape of a thin blade with the controlled thickness of 20-30 nm and width of 100-200 nm. They were fabricated using electron beam induced deposition at the apex of atomic force microscope probes and are hard enough for a single cut to penetrate a approximately 45 nm thick gold layer; and thus can be used for making narrow electrode gaps required for fabrication of nanoelectronic devices. As an atomic force microscope-based technique the nanoscalpel provides simultaneous control of the applied cutting force and the depth of the cut. Using mammalian cells as an example, we demonstrated their ability to make narrow incisions and measurements of local elastic and inelastic characteristics of a cell, making nanoscalpels also useful as a nanosurgical tool in cell biology. Therefore, we believe that the nanoscalpel could serve as an important tool for nanofabrication and nanosurgery on biological objects.

Focused Electron Beam-Based 3D Nanoprinting for Scanning Probe Microscopy: A Review

“…Using a similar approach, the work group around Gordeev has used 3D-FEBID for the fabrication of nano-scalpels on top of standard AFM tips, as representatively shown in Figure 14a,b. In a series of publications, they not only demonstrated the controlled scalpel fabrication but also the tuning of their mechanical properties [29,141,142]. The experiments included lithographic applications for the formation of sub-25 nm gaps in Au electrodes and the controlled and precise incision in fixed rat aortic smooth muscle cells with constant cut widths of 50 nm, both shown in Figure 14c,d, respectively.…”

Cellular level robotic surgery: Nanodissection of intermediate filaments in live keratinocytes

“…There have been reports of nanodissection on fixed rat aortic smooth muscle cells (14) and mouse endothelial cells (13); in both cases, a ‘scar’ was created successfully on top of the cell surface. The dissection of live cells proves to be more complicated than fixed cells.…”

“…Studies have shown the capability of AFM nanosurgery on fixed cell membranes by making incisions with a resolution of 100 nm or less (13, 14). Isolated gap junctions were dissected to resolve their detailed structures(12).…”

Probe microscopy methods and applications in imaging of biological materials

“…In addition, other imaging modalities can be combined with AFM to provide more comprehensive information about cellular processes: Gold-and silver-coated AFM tips are known to strongly enhance Raman signals, and nucleic acids [24], proteins [25], bacterial [26,27] and eukaryotic cell surfaces [28], and sectioned erythrocytes [29] have been investigated using a combination of AFM and Raman spectroscopy using TERS-compatible tips, even allowing the nucleotide-level detection in DNA strands [30]. Similarly, AFM can be performed alongside other scanning probe techniques such as scanning near-field optical microscopy (SNOM) [31], and AFM tip-based nanoneedles and nanoscalpels have also been fabricated for performing highly precise measurements in living cells [32][33][34].…”