Nanoneedles are high aspect ratio nanostructures with a unique biointerface. Thanks to their peculiar yet poorly understood interaction with cells, they very effectively sense intracellular conditions, typically with lower toxicity and perturbation than traditionally available probes. Through long-term, reversible interfacing with cells, nanoneedles can monitor biological functions over the course of several days. Their nanoscale dimension and the assembly into large scale, ordered, dense arrays enable monitoring the functions of large cell populations, to provide functional maps with sub-micron spatial resolution. Intracellularly, they sense electrical activity of complex excitable networks, as well as concentration, function and interaction of biomolecules in situ, while extracellularly they can measure the forces exerted by cells with piconewton detection limits, or efficiently sort rare cells based on their membrane receptors. Nanoneedles can investigate the function of many biological systems, ranging from cells, to biological fluids, to tissues and living organisms. This review examines the devices, strategies and workflows developed to use nanoneedles for sensing in biological systems.
KeywordsNanoneedles, nanowires, biointerface, intracellular sensing, review, biomarkers, label-free, minimally invasive.Nanoneedles are rapidly emerging as a tool to interact with the intracellular environment of large number of cells simultaneously, with limited perturbation of their physiological processes. This interaction provides characteristics advantages for minimally invasive cell and molecular biology investigations, as well as to progress biomedical translation of regenerative and precision medicine approaches. A quick string of several successful proofs of principles have established nanoneedles' potential to efficiently deliver impermeant molecules 1,2 and nanoparticles 3 directly to the cell cytosol, and to sense the intracellular milieu 4-6 across biological systems ranging from cells in culture 7 to living organisms 8 . Nanoneedles can be broadly defined as nanomaterials whose high aspect ratio enables their biological interaction; this definition encompasses a broad range of classically defined nanomaterials, which cater for different biointerfacing needs and applications ( Figure 1).
Figure 1 Overview of the nanoneedle devices and strategies used for sensing in biological systems.Each nanoneedle is a stacked bar of a bar graph. The legend below each nanoneedle is color-coded and connects to the associated bar. The height of each bar represents the fraction of reviewed papers with that characteristic. The number in each bar is the number of reviewed publications with that characteristic. Numbers for each bar do not sum to the same total as publications can contribute to more than one bar in a given stack. *"Fluid" excludes biological fluids, + "in vivo/ex vivo" includes biological fluids. The overview is compiled from all the publications reviewed herein that include sensing work.Nanoneedles belong t...