Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles

Nanoneedles are developing into versatile nanoscale tools for cell biology and medical intervention.1 Their fabrication draws from the experience of vertically aligned nanowires, allowing for the development of solid,2 hollow or porous3, 4 structures from silicon,5 carbon,6 and several other semiconductors.7 Nanoneedles are one of the most sophisticated and minimally invasive tools that allow direct access and manipulation of the intracellular environment. They can deliver a vast range of bioactive molecules and nanoparticles to the cytosol,2, 3, 8 as well as probe the electrical and the biochemical environment inside cells. Metallized silicon nanoneedles can interface in parallel to multiple neuronal cells, enabling either intracellular electrical stimulation or recording of the propagation of action potentials across a synapse.9 Arrays of nanoneedle‐based field effect transistors enable the recording of the electrical activity across a network of cardiomyocytes.5 Nanoneedles functionalized with proton sensitive fluorescent probes can sense the lowered intracellular pH of cultured cancer cells,8 whilst functionalization with caspase sensors enables the identification of apoptosis induced in cells.10 Indeed nanoneedles could be a unique tool for large scale mapping of the intracellular environment, inducing minimal perturbation to the target culture or tissue. This capability also enables nanoneedles to compete in the development of medically translatable therapeutic and diagnostic devices that have a low invasive potential.