Micro and nanoscale probes for spatiotemporal cell analysis and manipulation

Understanding dynamic cellular processes requires technologies capable of probing living cells with high spatial and temporal precision while preserving viability. Conventional approaches, including bulk omics, microinjection, and electroporation, often provide only static snapshots or induce significant cellular perturbation. Recent advances in micro- and nanoscale probes are enabling minimally invasive intracellular delivery, sampling, sensing, and manipulation with unprecedented precision. This review examines the current state of the art in micro and nanoscale probe technologies, including fluidic force microscopy (FluidFM), nanopipettes, open-space microfluidic probes, and nanoneedle arrays. We discuss how these complementary platforms enable controlled delivery of biomolecules, longitudinal molecular sampling, intracellular electrophysiology, electrochemical sensing, and spatiotemporally resolved analyses from single cells to living tissues. We placed particular emphasis on their ability to overcome the limitations of destructive endpoint assays by facilitating repeated interrogation of the same cell, quantitative molecular delivery, and multimodal measurements with subcellular resolution. Finally, we discuss the remaining engineering challenges, including improving throughput, integrating complementary sensing modalities, and advancing these promising technologies into robust platforms for laboratory studies of cultured cells and tissues.