Nanoneedle Platforms: The Many Ways to Pierce the Cell Membrane

Establishing techniques to efficiently and nondestructively access the intracellular milieu is essential for many biomedical and scientific applications, ranging from drug delivery, to electrical recording, to biochemical detection. Cell penetration using nanoneedle arrays is currently a research focus area because it not only meets the increasing therapeutic demands of cell modifications and genome editing, but also provides an ideal platform for tracking long-term intracellular information. Although the precise mechanism driving membrane penetration by nanoneedle arrays is still unclear, the low cytotoxicity, wide range of delivered materials, diverse cell type targets, and simple material structures of nanoneedle arrays make these splendid platforms for cell access. Here, the recent progress in this field is reviewed by examining device architectures and discussing mechanisms for nanoneedle penetration, and the major studies demonstrating the most general applicability of nanoneedle arrays, typical methodologies to access the intracellular environment using nanoneedles with spontaneous or assisted penetration modes, as well as biosafety aspects are presented. This review should be valuable for deeply understanding the materials fabrication principles, device designs, cell penetration methodologies, biosafety aspects, and application strategies of nanoneedle array-based systems that are of crucial importance for the development of future practical biomedical platforms.