Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Biointerface design for vertical nanoprobes

Nature Reviews Materials volume 7, pages 953–973 (2022)Cite this article

Subjects

Abstract

Biointerfaces mediate safe and efficient cell manipulation, which is essential for biomedical innovations in advanced therapies and diagnostics. The biointerface established by vertical nanoprobes — arrays of vertical high-aspect-ratio nanostructures — has emerged as a simple, controllable and powerful tool for interrogating and manipulating cells. Vertical nanoprobes have substantially improved our ability to control and characterize the intracellular environment, guide biophysical stimuli with nanoscale precision to defined cell compartments, stimulate and record the electrical activity of cells, and transport hard-to-deliver drugs. These capabilities are enabling substantial advances in bioelectronics, spatiotemporally resolved molecular diagnostics, and cell and gene therapy — all underpinned by the design versatility of the nanoprobe biointerface. This Review discusses how the design of a vertical nanoprobe biointerface determines its ability to interrogate and control a cell.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Modes of cell–nanoprobe interaction.
Fig. 2: Biointerface design parameters for vertical nanoprobes.
Fig. 3: Nanoprobe-induced biophysical stimulation at or beyond the plasma membrane.
Fig. 4: Nanoprobe-enabled intracellular recordings.
Fig. 5: Nanoprobes for biosensing.
Fig. 6: Intracellular delivery with nanoprobes.

Similar content being viewed by others

References

  1. Lane, S. W., Williams, D. A. & Watt, F. M. Modulating the stem cell niche for tissue regeneration. Nat. Biotechnol. 32, 795–803 (2014).

    Article  CAS  Google Scholar 

  2. Wang, N., Tytell, J. D. & Ingber, D. E. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10, 75–82 (2009).

    Article  CAS  Google Scholar 

  3. Hulshof, F. F. et al. NanoTopoChip: high-throughput nanotopographical cell instruction. Acta Biomater. 62, 188–198 (2017).

    Article  CAS  Google Scholar 

  4. Patel, N. et al. Spatially controlled cell engineering on biodegradable polymer surfaces. FASEB J. 12, 1447–1454 (1998).

    Article  CAS  Google Scholar 

  5. Downing, T. L. et al. Biophysical regulation of epigenetic state and cell reprogramming. Nat. Mater. 12, 1154–1162 (2013).

    Article  CAS  Google Scholar 

  6. Raab, M. et al. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science 352, 359–362 (2016).

    Article  CAS  Google Scholar 

  7. Yu, Y. & Yoshimura, S. H. Investigating the morphological dynamics of the plasma membrane by high-speed atomic force microscopy. J. Cell Sci. 134, jcs243584 (2021).

    Article  CAS  Google Scholar 

  8. Paulitschke, P. et al. Ultraflexible nanowire array for label- and distortion-free cellular force tracking. Nano Lett. 19, 2207–2214 (2019).

    Article  CAS  Google Scholar 

  9. O’Brien, J. A. & Lummis, S. C. Biolistic transfection of neuronal cultures using a hand-held gene gun. Nat. Protoc. 1, 977 (2006).

    Article  Google Scholar 

  10. McMurray, R. J. et al. Nanoscale surfaces for the long-term maintenance of mesenchymal stem cell phenotype and multipotency. Nat. Mater. 10, 637–644 (2011).

    Article  CAS  Google Scholar 

  11. Venslauskas, M. S. & Šatkauskas, S. Mechanisms of transfer of bioactive molecules through the cell membrane by electroporation. Eur. Biophys. J. 44, 277–289 (2015).

    Article  Google Scholar 

  12. Nath, A. R., Chen, R. H. & Stanley, E. F. Cryoloading: introducing large molecules into live synaptosomes. Front. Cell. Neurosci. 8, 4 (2014).

    Article  Google Scholar 

  13. Antkowiak, M. et al. Fast targeted gene transfection and optogenetic modification of single neurons using femtosecond laser irradiation. Sci. Rep. 3, 3281 (2013).

    Article  Google Scholar 

  14. Ramesan, S. et al. Acoustically-mediated intracellular delivery. Nanoscale 10, 13165–13178 (2018).

    Article  CAS  Google Scholar 

  15. Lichtenberg, D., Ahyayauch, H. & Goñi, F. M. The mechanism of detergent solubilization of lipid bilayers. Biophys. J. 105, 289–299 (2013).

    Article  CAS  Google Scholar 

  16. Korzh, V. & Strähle, U. Marshall Barber and the century of microinjection: from cloning of bacteria to cloning of everything. Differentiation 70, 221–226 (2002).

    Article  Google Scholar 

  17. Sakmann, B. & Neher, E. Patch clamp techniques for studying ionic channels in excitable membranes. Annu. Rev. Physiol. 46, 455–472 (1984).

    Article  CAS  Google Scholar 

  18. Lee, S. E. et al. Remote optical switch for localized and selective control of gene interference. Nano Lett. 9, 562–570 (2009).

    Article  CAS  Google Scholar 

  19. Shin, H. et al. 3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics. Nat. Commun. 12, 492 (2021).

    Article  CAS  Google Scholar 

  20. Cai, P. et al. Combinatorial nano–bio interfaces. ACS Nano 12, 5078–5084 (2018).

    Article  CAS  Google Scholar 

  21. Nadeem, D. et al. Embossing of micropatterned ceramics and their cellular response. J. Biomed. Mater. Res. Part A 101, 3247–3255 (2013).

    Google Scholar 

  22. Hondrich, T. J. et al. MEA recordings and cell–substrate investigations with plasmonic and transparent, tunable holey gold. ACS Appl. Mater. Interfaces 11, 46451–46461 (2019).

    Article  CAS  Google Scholar 

  23. Elnathan, R. et al. The start-ups taking nanoneedles into the clinic. Nat. Nanotechnol. https://doi.org/10.1038/s41565-022-01158-5 (2022).

  24. Li, X. et al. Vertical nanowire array-based biosensors: device design strategies and biomedical applications. J. Mater. Chem. B 8, 7609–7632 (2020).

    Article  CAS  Google Scholar 

  25. Lin, Z. C. et al. Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials. Nat. Commun. 5, 3206 (2014).

    Article  Google Scholar 

  26. Shiu, J.-Y. et al. Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction. Nat. Cell Biol. 20, 262–271 (2018).

    Article  CAS  Google Scholar 

  27. Cao, Y. et al. Nondestructive nanostraw intracellular sampling for longitudinal cell monitoring. Proc. Natl Acad. Sci. USA 114, E1866–E1874 (2017).

    Article  CAS  Google Scholar 

  28. Chiappini, C. et al. Biodegradable nanoneedles for localized delivery of nanoparticles in vivo: exploring the biointerface. ACS Nano 9, 5500–5509 (2015).

    Article  CAS  Google Scholar 

  29. Hansel, C. S. et al. Nanoneedle-mediated stimulation of cell mechanotransduction machinery. ACS Nano 13, 2913–2926 (2019).

    Article  CAS  Google Scholar 

  30. Chiappini, C. et al. Mapping local cytosolic enzymatic activity in human esophageal mucosa with porous silicon nanoneedles. Adv. Mater. 27, 5147–5152 (2015).

    Article  CAS  Google Scholar 

  31. Na, Y.-R. et al. Probing enzymatic activity inside living cells using a nanowire–cell ‘sandwich’ assay. Nano Lett. 13, 153–158 (2013).

    Article  CAS  Google Scholar 

  32. Krivitsky, V. et al. Si nanowires forest-based on-chip biomolecular filtering, separation and preconcentration devices: nanowires do it all. Nano Lett. 12, 4748–4756 (2012).

    Article  CAS  Google Scholar 

  33. Zhao, Y. et al. Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording. Nat. Nanotechnol. 14, 783–790 (2019).

    Article  CAS  Google Scholar 

  34. Robinson, J. T. et al. Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits. Nat. Nanotechnol. 7, 180–184 (2012).

    Article  CAS  Google Scholar 

  35. Chiappini, C. et al. Tutorial: using nanoneedles for intracellular delivery. Nat. Protoc. 16, 4539–4563 (2021).

    Article  CAS  Google Scholar 

  36. Xie, X. et al. Nanostraw–electroporation system for highly efficient intracellular delivery and transfection. ACS Nano 7, 4351–4358 (2013).

    Article  CAS  Google Scholar 

  37. Chiappini, C. et al. Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. Nat. Mater. 14, 532–539 (2015).

    Article  CAS  Google Scholar 

  38. Lestrell, E. et al. Engineered nano-bio interfaces for intracellular delivery and sampling: applications, agency and artefacts. Mater. Today 33, 87–104 (2020).

    Article  CAS  Google Scholar 

  39. Chen, Y. et al. Emerging roles of 1D vertical nanostructures in orchestrating immune cell functions. Adv. Mater. 32, 2001668 (2020).

    Article  CAS  Google Scholar 

  40. Buch-Månson, N. et al. Mapping cell behavior across a wide range of vertical silicon nanocolumn densities. Nanoscale 9, 5517–5527 (2017).

    Article  Google Scholar 

  41. Kim, W. et al. Interfacing silicon nanowires with mammalian cells. J. Am. Chem. Soc. 129, 7228–7229 (2007).

    Article  CAS  Google Scholar 

  42. Buch-Månson, N. et al. Towards a better prediction of cell settling on nanostructure arrays — simple means to complicated ends. Adv. Funct. Mater. 25, 3246–3255 (2015).

    Article  Google Scholar 

  43. Xie, X. et al. Mechanical model of vertical nanowire cell penetration. Nano Lett. 13, 6002–6008 (2013).

    Article  CAS  Google Scholar 

  44. Xie, X. et al. Determining the time window for dynamic nanowire cell penetration processes. Acs Nano 9, 11667–11677 (2015).

    Article  CAS  Google Scholar 

  45. Li, C. et al. Large-scale, robust mushroom-shaped nanochannel array membrane for ultrahigh osmotic energy conversion. Sci. Adv. 7, eabg2183 (2021).

    Article  CAS  Google Scholar 

  46. Wen, R. et al. Intracellular delivery and sensing system based on electroplated conductive nanostraw arrays. ACS Appl. Mater. Interfaces 11, 43936–43948 (2019).

    Article  CAS  Google Scholar 

  47. Persson, H. et al. Fibroblasts cultured on nanowires exhibit low motility, impaired cell division, and DNA damage. Small 9, 4006–4016 (2013).

    Article  CAS  Google Scholar 

  48. Persson, H. et al. From immobilized cells to motile cells on a bed-of-nails: effects of vertical nanowire array density on cell behaviour. Sci. Rep. 5, 18535 (2015).

    Article  CAS  Google Scholar 

  49. Matsumoto, D. et al. Oscillating high-aspect-ratio monolithic silicon nanoneedle array enables efficient delivery of functional bio-macromolecules into living cells. Sci. Rep. 5, 15325 (2015).

    Article  CAS  Google Scholar 

  50. Obataya, I. et al. Nanoscale operation of a living cell using an atomic force microscope with a nanoneedle. Nano Lett. 5, 27–30 (2005).

    Article  CAS  Google Scholar 

  51. Kim, H. et al. Flexible elastomer patch with vertical silicon nanoneedles for intracellular and intratissue nanoinjection of biomolecules. Sci. Adv. 4, eaau6972 (2018).

    Article  CAS  Google Scholar 

  52. Buch-Månson, N. et al. Rapid prototyping of polymeric nanopillars by 3D direct laser writing for controlling cell behavior. Sci. Rep. 7, 15325 (2017).

    Article  Google Scholar 

  53. Yoh, H. Z. et al. Polymeric nanoneedle arrays mediate stiffness-independent intracellular delivery. Adv. Funct. Mater. 32, 2104828 (2022).

    Article  CAS  Google Scholar 

  54. He, G. et al. Multifunctional branched nanostraw-electroporation platform for intracellular regulation and monitoring of circulating tumor cells. Nano Lett. 19, 7201–7209 (2019).

    Article  CAS  Google Scholar 

  55. Elnathan, R. et al. Optically transparent vertical silicon nanowire arrays for live-cell imaging. J. Nanobiotechnol. 19, 51 (2021).

    Article  CAS  Google Scholar 

  56. Kim, S. et al. 3D super-resolved imaging in live cells using sub-diffractive plasmonic localization of hybrid nanopillar arrays. Nanophotonics 9, 2847–2859 (2020).

    Article  CAS  Google Scholar 

  57. Frederiksen, R. S. et al. Nanowire-aperture probe: local enhanced fluorescence detection for the investigation of live cells at the nanoscale. ACS Photonics 3, 1208–1216 (2016).

    Article  CAS  Google Scholar 

  58. Wang, Y. et al. Poking cells for efficient vector-free intracellular delivery. Nat. Commun. 5, 4466 (2014).

    Article  CAS  Google Scholar 

  59. Dipalo, M. et al. Cells adhering to 3D vertical nanostructures: cell membrane reshaping without stable internalization. Nano Lett. 18, 6100–6105 (2018).

    Article  CAS  Google Scholar 

  60. Amin, H. et al. Biofunctionalized 3D nanopillar arrays fostering cell guidance and promoting synapse stability and neuronal activity in networks. ACS Appl. Mater. Interfaces 10, 15207–15215 (2018).

    Article  CAS  Google Scholar 

  61. Santoro, F. et al. On chip guidance and recording of cardiomyocytes with 3D mushroom-shaped electrodes. Nano Lett. 13, 5379–5384 (2013).

    Article  CAS  Google Scholar 

  62. Hai, A. et al. Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices. J. R. Soc. Interface 6, 1153–1165 (2009).

    Article  CAS  Google Scholar 

  63. Wang, H. et al. in Non-Viral Gene Delivery Vectors (ed. Candiani, G.) 279–287 (Springer, 2016).

  64. Sridar, S. et al. Peptide modification of polyimide-insulated microwires: towards improved biocompatibility through reduced glial scarring. Acta Biomater. 60, 154–166 (2017).

    Article  CAS  Google Scholar 

  65. Duan, X. et al. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor. Nat. Nanotechnol. 7, 174–179 (2012).

    Article  CAS  Google Scholar 

  66. Almquist, B. D. & Melosh, N. A. Fusion of biomimetic stealth probes into lipid bilayer cores. Proc. Natl Acad. Sci. USA 107, 5815–5820 (2010).

    Article  CAS  Google Scholar 

  67. Almquist, B. D. & Melosh, N. A. Molecular structure influences the stability of membrane penetrating biointerfaces. Nano Lett. 11, 2066–2070 (2011).

    Article  CAS  Google Scholar 

  68. Vutti, S. et al. Click chemistry mediated functionalization of vertical nanowires for biological applications. Chem. Eur. J. 22, 496–500 (2016).

    Article  CAS  Google Scholar 

  69. Kihara, T. et al. Nanoneedle surface modification with 2-methacryloyloxyethyl phosphorylcholine polymer to reduce nonspecific protein adsorption in a living cell. NanoBiotechnology 3, 127–134 (2007).

    Article  CAS  Google Scholar 

  70. Qu, Y. et al. A universal platform for high-efficiency ‘engineering’ living cells: integration of cell capture, intracellular delivery of biomolecules, and cell harvesting functions. Adv. Funct. Mater. 30, 1906362 (2020).

    Article  CAS  Google Scholar 

  71. Sahoo, P. K. et al. Nanowire arrays as cell force sensors to investigate adhesin-enhanced holdfast of single cell bacteria and biofilm stability. Nano Lett. 16, 4656–4664 (2016).

    Article  CAS  Google Scholar 

  72. Leriche, G., Chisholm, L. & Wagner, A. Cleavable linkers in chemical biology. Bioorg. Med. Chem. 20, 571–582 (2012).

    Article  CAS  Google Scholar 

  73. Shalek, A. K. et al. Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells. Proc. Natl Acad. Sci. USA 107, 1870–1875 (2010).

    Article  CAS  Google Scholar 

  74. Elnathan, R. et al. Maximizing transfection efficiency of vertically aligned silicon nanowire arrays. Adv. Funct. Mater. 25, 7215–7225 (2015).

    Article  CAS  Google Scholar 

  75. Higgins, S. G. et al. High-aspect-ratio nanostructured surfaces as biological metamaterials. Adv. Mater. 32, 1903862 (2020).

    Article  CAS  Google Scholar 

  76. He, G. et al. Nanoneedle platforms: the many ways to pierce the cell membrane. Adv. Funct. Mater. 30, 1909890 (2020).

    Article  CAS  Google Scholar 

  77. Kawamura, R. et al. A new cell separation method based on antibody-immobilized nanoneedle arrays for the detection of intracellular markers. Nano Lett. 17, 7117–7124 (2017).

    Article  CAS  Google Scholar 

  78. Fang, J. et al. Accurate and efficient intracellular delivery biosensing system by nanostrawed electroporation array. Biosens. Bioelectron. 194, 113583 (2021).

    Article  CAS  Google Scholar 

  79. Messina, G. C. et al. Spatially, temporally, and quantitatively controlled delivery of broad range of molecules into selected cells through plasmonic nanotubes. Adv. Mater. 27, 7145–7149 (2015).

    Article  CAS  Google Scholar 

  80. Dipalo, M. et al. 3D plasmonic nanoantennas integrated with MEA biosensors. Nanoscale 7, 3703–3711 (2015).

    Article  CAS  Google Scholar 

  81. Zhao, W. et al. Nanoscale manipulation of membrane curvature for probing endocytosis in live cells. Nat. Nanotechnol. 12, 750–756 (2017).

    Article  CAS  Google Scholar 

  82. Hanson, L. et al. Vertical nanopillars for in situ probing of nuclear mechanics in adherent cells. Nat. Nanotechnol. 10, 554–562 (2015).

    Article  CAS  Google Scholar 

  83. Wei, Y. et al. Directing stem cell differentiation via electrochemical reversible switching between nanotubes and nanotips of polypyrrole array. ACS Nano 11, 5915–5924 (2017).

    Article  CAS  Google Scholar 

  84. Beckwith, K. S. et al. Influence of nanopillar arrays on fibroblast motility, adhesion, and migration mechanisms. Small 15, 1902514 (2019).

    Article  CAS  Google Scholar 

  85. Dai, J. et al. Cellular architecture response to aspect ratio tunable nanoarrays. Nanoscale 12, 12395–12404 (2020).

    Article  CAS  Google Scholar 

  86. Park, J. et al. Nanosize and vitality: TiO2 nanotube diameter directs cell fate. Nano Lett. 7, 1686–1691 (2007).

    Article  CAS  Google Scholar 

  87. VanDersarl, J. J., Xu, A. M. & Melosh, N. A. Nanostraws for direct fluidic intracellular access. Nano Lett. 12, 3881–3886 (2012).

    Article  CAS  Google Scholar 

  88. Hanson, L. et al. Characterization of the cell–nanopillar interface by transmission electron microscopy. Nano Lett. 12, 5815–5820 (2012).

    Article  CAS  Google Scholar 

  89. Santoro, F. et al. Revealing the cell–material interface with nanometer resolution by focused ion beam/scanning electron microscopy. ACS Nano 11, 8320–8328 (2017).

    Article  CAS  Google Scholar 

  90. von Erlach, T. C. et al. Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate. Nat. Mater. 17, 237–242 (2018).

    Article  Google Scholar 

  91. Berthing, T. et al. Cell membrane conformation at vertical nanowire array interface revealed by fluorescence imaging. Nanotechnology 23, 415102 (2012).

    Article  Google Scholar 

  92. Wang, Z. et al. Interrogation of cellular innate immunity by diamond-nanoneedle-assisted intracellular molecular fishing. Nano Lett. 15, 7058–7063 (2015).

    Article  Google Scholar 

  93. He, G. et al. Hollow nanoneedle-electroporation system to extract intracellular protein repetitively and nondestructively. ACS Sens. 3, 1675–1682 (2018).

    Article  CAS  Google Scholar 

  94. Dipalo, M. et al. Membrane poration mechanisms at the cell–nanostructure interface. Adv. Biosyst. 3, 1900148 (2019).

    Article  Google Scholar 

  95. Arnold, M. et al. Activation of integrin function by nanopatterned adhesive interfaces. ChemPhysChem 5, 383–388 (2004).

    Article  CAS  Google Scholar 

  96. Li, S. et al. Effects of nanoscale spatial arrangement of arginine–glycine–aspartate peptides on dedifferentiation of chondrocytes. Nano Lett. 15, 7755–7765 (2015).

    Article  CAS  Google Scholar 

  97. Maheshwari, G. et al. Cell adhesion and motility depend on nanoscale RGD clustering. J. Cell Sci. 113, 1677–1686 (2000).

    Article  CAS  Google Scholar 

  98. Sun, Z., Guo, S. S. & Fässler, R. Integrin-mediated mechanotransduction. J. Cell Biol. 215, 445–456 (2016).

    Article  CAS  Google Scholar 

  99. Yurugi, H. et al. A subset of flavaglines inhibits KRAS nanoclustering and activation. J. Cell Sci. 133, jcs244111 (2020).

    Article  CAS  Google Scholar 

  100. Liang, H. et al. Membrane curvature sensing of the lipid-anchored K-Ras small GTPase. Life Sci. Alliance 2, e201900343 (2019).

    Article  Google Scholar 

  101. Mu, H. W. et al. Patterning of oncogenic Ras clustering in live cells using vertically aligned nanostructure arrays. Nano Lett. 22, 1007–1016 (2022).

    Article  CAS  Google Scholar 

  102. Galic, M. et al. Dynamic recruitment of the curvature-sensitive protein ArhGAP44 to nanoscale membrane deformations limits exploratory filopodia initiation in neurons. eLife 3, e03116 (2014).

    Article  Google Scholar 

  103. McMahon, H. T. & Boucrot, E. Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 12, 517–533 (2011).

    Article  CAS  Google Scholar 

  104. Gopal, S. et al. Porous silicon nanoneedles modulate endocytosis to deliver biological payloads. Adv. Mater. 31, 1806788 (2019).

    Article  Google Scholar 

  105. Aslanoglou, S. et al. Efficient transmission electron microscopy characterization of cell–nanostructure interfacial interactions. J. Am. Chem. Soc. 142, 15649–15653 (2020).

    Article  CAS  Google Scholar 

  106. Chen, Y. et al. Silicon-nanotube-mediated intracellular delivery enables ex vivo gene editing. Adv. Mater. 32, 2000036 (2020).

    Article  CAS  Google Scholar 

  107. Chen, Y. et al. Cellular deformations induced by conical silicon nanowire arrays facilitate gene delivery. Small 15, 1904819 (2019).

    Article  CAS  Google Scholar 

  108. Peter, B. J. et al. BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303, 495–499 (2004).

    Article  CAS  Google Scholar 

  109. Galic, M. et al. External push and internal pull forces recruit curvature-sensing N-BAR domain proteins to the plasma membrane. Nat. Cell Biol. 14, 874–881 (2012).

    Article  CAS  Google Scholar 

  110. Su, M. et al. Comparative study of curvature sensing mediated by F-BAR and an intrinsically disordered region of FBP17. iScience 23, 101712 (2020).

    Article  CAS  Google Scholar 

  111. Lou, H.-Y. et al. Membrane curvature underlies actin reorganization in response to nanoscale surface topography. Proc. Natl Acad. Sci. USA 116, 23143–23151 (2019).

    Article  CAS  Google Scholar 

  112. Li, L.-L. et al. Nanobar array assay revealed complementary roles of BIN1 splice isoforms in cardiac T-tubule morphogenesis. Nano Lett. 20, 6387–6395 (2020).

    Article  CAS  Google Scholar 

  113. Li, X. et al. Nanoscale surface topography reduces focal adhesions and cell stiffness by enhancing integrin endocytosis. Nano Lett. 21, 8518–8526 (2021).

    Article  CAS  Google Scholar 

  114. Beckwith, K. S. et al. Tunable high aspect ratio polymer nanostructures for cell interfaces. Nanoscale 7, 8438–8450 (2015).

    Article  CAS  Google Scholar 

  115. De Martino, S. et al. Dynamic manipulation of cell membrane curvature by light-driven reshaping of azopolymer. Nano Lett. 20, 577–584 (2019).

    Article  Google Scholar 

  116. Qi, S. et al. Cell adhesion and spreading behavior on vertically aligned silicon nanowire arrays. ACS Appl. Mater. Interfaces 1, 30–34 (2009).

    Article  CAS  Google Scholar 

  117. Liu, H. et al. TiO2 nanorod arrays with mesoscopic micro–nano interfaces for in situ regulation of cell morphology and nucleus deformation. ACS Appl. Mater. Interfaces 10, 66–74 (2018).

    Article  CAS  Google Scholar 

  118. Aalipour, A. et al. Plasma membrane and actin cytoskeleton as synergistic barriers to nanowire cell penetration. Langmuir 30, 12362–12367 (2014).

    Article  CAS  Google Scholar 

  119. Seong, H. et al. Size-tunable nanoneedle arrays for influencing stem cell morphology, gene expression, and nuclear membrane curvature. ACS Nano 14, 5371–5381 (2020).

    Article  CAS  Google Scholar 

  120. Carthew, J. et al. Precision surface microtopography regulates cell fate via changes to actomyosin contractility and nuclear architecture. Adv. Sci. 8, 2003186 (2021).

    Article  CAS  Google Scholar 

  121. Seo, J. et al. Neuro-taxis: neuronal movement in gradients of chemical and physical environments. Dev. Neurobiol. 80, 361–377 (2020).

    Article  Google Scholar 

  122. Dong, Y. et al. Nanotechnology shaping stem cell therapy: recent advances, application, challenges, and future outlook. Biomed. Pharmacother. 137, 111236 (2021).

    Article  CAS  Google Scholar 

  123. Yang, J. et al. Nanotopographical induction of osteogenesis through adhesion, bone morphogenic protein cosignaling, and regulation of microRNAs. ACS Nano 8, 9941–9953 (2014).

    Article  CAS  Google Scholar 

  124. Qiu, J. et al. TiO2 nanorod array constructed nanotopography for regulation of mesenchymal stem cells fate and the realization of location-committed stem cell differentiation. Small 12, 1770–1778 (2016).

    Article  CAS  Google Scholar 

  125. Kim, H. et al. Neuron-like differentiation of mesenchymal stem cells on silicon nanowires. Nanoscale 7, 17131–17138 (2015).

    Article  CAS  Google Scholar 

  126. Lin, H.-I. et al. SiNWs biophysically regulate the fates of human mesenchymal stem cells. Sci. Rep. 8, 12913 (2018).

    Article  Google Scholar 

  127. Kuo, S.-W. et al. Regulation of the fate of human mesenchymal stem cells by mechanical and stereo-topographical cues provided by silicon nanowires. Biomaterials 33, 5013–5022 (2012).

    Article  CAS  Google Scholar 

  128. Kim, Y. J. et al. Association between cell microenvironment altered by gold nanowire array and regulation of partial epithelial-mesenchymal transition. Adv. Funct. Mater. 31, 2008758 (2021).

    Article  CAS  Google Scholar 

  129. Rasmussen, C. H. et al. Enhanced differentiation of human embryonic stem cells toward definitive endoderm on ultrahigh aspect ratio nanopillars. Adv. Funct. Mater. 26, 815–823 (2016).

    Article  CAS  Google Scholar 

  130. Harberts, J. et al. Interfacing human induced pluripotent stem cell-derived neurons with designed nanowire arrays as a future platform for medical applications. Biomater. Sci. 8, 2434–2446 (2020).

    Article  CAS  Google Scholar 

  131. Kwon, J. et al. Vertical nanowire electrode array for enhanced neurogenesis of human neural stem cells via intracellular electrical stimulation. Nano Lett. 21, 6343–6351 (2021).

    Article  CAS  Google Scholar 

  132. Gautam, V. et al. Engineering highly interconnected neuronal networks on nanowire scaffolds. Nano Lett. 17, 3369–3375 (2017).

    Article  CAS  Google Scholar 

  133. Prinz, C. et al. Axonal guidance on patterned free-standing nanowire surfaces. Nanotechnology 19, 345101 (2008).

    Article  Google Scholar 

  134. Bhingardive, V. et al. Nanowire based mechanostimulating platform for tunable activation of natural killer cells. Adv. Funct. Mater. 31, 2103063 (2021).

    Article  CAS  Google Scholar 

  135. McWhorter, F. Y. et al. Modulation of macrophage phenotype by cell shape. Proc. Natl Acad. Sci. USA 110, 17253–17258 (2013).

    Article  CAS  Google Scholar 

  136. Bhingardive, V. et al. Antibody-functionalized nanowires: a tuner for the activation of T cells. Nano Lett. 21, 4241–4248 (2021).

    Article  CAS  Google Scholar 

  137. Wang, J. et al. Physical activation of innate immunity by spiky particles. Nat. Nanotechnol. 13, 1078–1086 (2018).

    Article  CAS  Google Scholar 

  138. Le Saux, G. et al. Nanoscale mechanosensing of natural killer cells is revealed by antigen-functionalized nanowires. Adv. Mater. 31, 1805954 (2019).

    Article  Google Scholar 

  139. Arias, S. L. et al. Bacterial envelope damage inflicted by bioinspired nanostructures grown in a hydrogel. ACS Appl. Bio Mater. 3, 7974–7988 (2020).

    Article  CAS  Google Scholar 

  140. Bhadra, C. M. et al. Antibacterial titanium nano-patterned arrays inspired by dragonfly wings. Sci. Rep. 5, 16817 (2015).

    Article  CAS  Google Scholar 

  141. Hasan, J. et al. Multi-scale surface topography to minimize adherence and viability of nosocomial drug-resistant bacteria. Mater. Des. 140, 332–344 (2018).

    Article  CAS  Google Scholar 

  142. Jenkins, J. et al. Antibacterial effects of nanopillar surfaces are mediated by cell impedance, penetration and induction of oxidative stress. Nat. Commun. 11, 1626 (2020).

    Article  CAS  Google Scholar 

  143. Michalska, M. et al. Tuning antimicrobial properties of biomimetic nanopatterned surfaces. Nanoscale 10, 6639–6650 (2018).

    Article  CAS  Google Scholar 

  144. Velic, A. et al. Effects of nanopillar size and spacing on mechanical perturbation and bactericidal killing efficiency. Nanomaterials 11, 2472 (2021).

    Article  CAS  Google Scholar 

  145. Zhang, A., Lee, J.-H. & Lieber, C. M. Nanowire-enabled bioelectronics. Nano Today 38, 101135 (2021).

    Article  CAS  Google Scholar 

  146. Spira, M. E. & Hai, A. Multi-electrode array technologies for neuroscience and cardiology. Nat. Nanotechnol. 8, 83–94 (2013).

    Article  CAS  Google Scholar 

  147. Mariano, A. et al. Advances in cell-conductive polymer biointerfaces and role of the plasma membrane. Chem. Rev. 122, 4552–4580 (2022).

    Article  CAS  Google Scholar 

  148. Hai, A., Shappir, J. & Spira, M. E. Long-term, multisite, parallel, in-cell recording and stimulation by an array of extracellular microelectrodes. J. Neurophysiol. 104, 559–568 (2010).

    Article  CAS  Google Scholar 

  149. Hai, A., Shappir, J. & Spira, M. E. In-cell recordings by extracellular microelectrodes. Nat. Methods 7, 200–202 (2010).

    Article  CAS  Google Scholar 

  150. Shmoel, N. et al. Multisite electrophysiological recordings by self-assembled loose-patch-like junctions between cultured hippocampal neurons and mushroom-shaped microelectrodes. Sci. Rep. 6, 27110 (2016).

    Article  CAS  Google Scholar 

  151. Chen, R., Canales, A. & Anikeeva, P. Neural recording and modulation technologies. Nat. Rev. Mater. 2, 16093 (2017).

    Article  CAS  Google Scholar 

  152. McGuire, A. F., Santoro, F. & Cui, B. Interfacing cells with vertical nanoscale devices: applications and characterization. Annu. Rev. Anal. Chem. 11, 101–126 (2018).

    Article  Google Scholar 

  153. Abbott, J. et al. Optimizing nanoelectrode arrays for scalable intracellular electrophysiology. Acc. Chem. Res. 51, 600–608 (2018).

    Article  CAS  Google Scholar 

  154. Tian, B. et al. Three-dimensional, flexible nanoscale field-effect transistors as localized bioprobes. Science 329, 830–834 (2010).

    Article  CAS  Google Scholar 

  155. Fu, T.-M. et al. Sub-10-nm intracellular bioelectronic probes from nanowire–nanotube heterostructures. Proc. Natl Acad. Sci. USA 111, 1259–1264 (2014).

    Article  CAS  Google Scholar 

  156. Qing, Q. et al. Free-standing kinked nanowire transistor probes for targeted intracellular recording in three dimensions. Nat. Nanotechnol. 9, 142–147 (2014).

    Article  CAS  Google Scholar 

  157. Yoo, J. et al. Long-term intracellular recording of optogenetically-induced electrical activities using vertical nanowire multi electrode array. Sci. Rep. 10, 4279 (2020).

    Article  Google Scholar 

  158. Liu, R. et al. High density individually addressable nanowire arrays record intracellular activity from primary rodent and human stem cell derived neurons. Nano Lett. 17, 2757–2764 (2017).

    Article  CAS  Google Scholar 

  159. Staufer, O. et al. Adhesion stabilized en masse intracellular electrical recordings from multicellular assemblies. Nano Lett. 19, 3244–3255 (2019).

    Article  CAS  Google Scholar 

  160. Verma, P. & Melosh, N. A. Gigaohm resistance membrane seals with stealth probe electrodes. Appl. Phys. Lett. 97, 033704 (2010).

    Article  Google Scholar 

  161. Keefer, E. W. et al. Carbon nanotube coating improves neuronal recordings. Nat. Nanotechnol. 3, 434–439 (2008).

    Article  CAS  Google Scholar 

  162. Hong, G. et al. Mesh electronics: a new paradigm for tissue-like brain probes. Curr. Opin. Neurobiol. 50, 33–41 (2018).

    Article  CAS  Google Scholar 

  163. Hong, G. & Lieber, C. M. Novel electrode technologies for neural recordings. Nat. Rev. Neurosci. 20, 330–345 (2019).

    Article  CAS  Google Scholar 

  164. Tang, J. et al. Nanowire arrays restore vision in blind mice. Nat. Commun. 9, 786 (2018).

    Article  Google Scholar 

  165. Suyatin, D. B. et al. Nanowire-based electrode for acute in vivo neural recordings in the brain. PLoS ONE 8, e56673 (2013).

    Article  CAS  Google Scholar 

  166. Xie, C. et al. Intracellular recording of action potentials by nanopillar electroporation. Nat. Nanotechnol. 7, 185–190 (2012).

    Article  CAS  Google Scholar 

  167. Abbott, J. et al. A nanoelectrode array for obtaining intracellular recordings from thousands of connected neurons. Nat. Biomed. Eng. 4, 232–241 (2020).

    Article  CAS  Google Scholar 

  168. Abbott, J. et al. CMOS nanoelectrode array for all-electrical intracellular electrophysiological imaging. Nat. Nanotechnol. 12, 460–466 (2017).

    Article  CAS  Google Scholar 

  169. Ham, D. et al. Neuromorphic electronics based on copying and pasting the brain. Nat. Electron. 4, 635–644 (2021).

    Article  Google Scholar 

  170. Shokouhi, A.-R. et al. Vertically configured nanostructure-mediated electroporation: a promising route for intracellular regulations and interrogations. Mater. Horiz. 7, 2810–2831 (2020).

    Article  CAS  Google Scholar 

  171. Dipalo, M. et al. Intracellular and extracellular recording of spontaneous action potentials in mammalian neurons and cardiac cells with 3D plasmonic nanoelectrodes. Nano Lett. 17, 3932–3939 (2017).

    Article  CAS  Google Scholar 

  172. Chen, C. et al. Electrical stimulation as a novel tool for regulating cell behavior in tissue engineering. Biomater. Res. 23, 25 (2019).

    Article  Google Scholar 

  173. Ghezzi, D. et al. A hybrid bioorganic interface for neuronal photoactivation. Nat. Commun. 2, 166 (2011).

    Article  Google Scholar 

  174. Ghezzi, D. et al. A polymer optoelectronic interface restores light sensitivity in blind rat retinas. Nat. Photonics 7, 400–406 (2013).

    Article  CAS  Google Scholar 

  175. Mathieson, K. et al. Photovoltaic retinal prosthesis with high pixel density. Nat. Photonics 6, 391–397 (2012).

    Article  CAS  Google Scholar 

  176. Parameswaran, R. et al. Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix. Proc. Natl Acad. Sci. USA 116, 413–421 (2019).

    Article  CAS  Google Scholar 

  177. Rotenberg, M. Y. et al. Silicon nanowires for intracellular optical interrogation with subcellular resolution. Nano Lett. 20, 1226–1232 (2020).

    Article  CAS  Google Scholar 

  178. Parameswaran, R. et al. Photoelectrochemical modulation of neuronal activity with free-standing coaxial silicon nanowires. Nat. Nanotechnol. 13, 260–266 (2018).

    Article  CAS  Google Scholar 

  179. Han, X. et al. Silicon nanowire-based surface-enhanced Raman spectroscopy endoscope for intracellular pH detection. ACS Appl. Mater. Interfaces 5, 5811–5814 (2013).

    Article  CAS  Google Scholar 

  180. Barrios-Rodiles, M. et al. High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307, 1621–1625 (2005).

    Article  CAS  Google Scholar 

  181. Papalexi, E. & Satija, R. Single-cell RNA sequencing to explore immune cell heterogeneity. Nat. Rev. Immunol. 18, 35–45 (2018).

    Article  CAS  Google Scholar 

  182. Wang, Z. et al. High-throughput intracellular biopsy of microRNAs for dissecting the temporal dynamics of cellular heterogeneity. Sci. Adv. 6, eaba4971 (2020).

    Article  CAS  Google Scholar 

  183. Xie, K. et al. Profiling microRNAs with associated spatial dynamics in acute tissue slices. ACS Nano 15, 4881–4892 (2021).

    Article  CAS  Google Scholar 

  184. Xie, C. et al. Vertical nanopillars for highly localized fluorescence imaging. Proc. Natl Acad. Sci. USA 108, 3894–3899 (2011).

    Article  CAS  Google Scholar 

  185. Adolfsson, K. et al. Ingestion of gallium phosphide nanowires has no adverse effect on Drosophila tissue function. Nanotechnology 24, 285101 (2013).

    Article  Google Scholar 

  186. ten Siethoff, L. et al. Molecular motor propelled filaments reveal light-guiding in nanowire arrays for enhanced biosensing. Nano Lett. 14, 737–742 (2014).

    Article  Google Scholar 

  187. Frederiksen, R. S. et al. Modulation of fluorescence signals from biomolecules along nanowires due to interaction of light with oriented nanostructures. Nano Lett. 15, 176–181 (2015).

    Article  CAS  Google Scholar 

  188. Verardo, D. et al. Nanowires for biosensing: lightguiding of fluorescence as a function of diameter and wavelength. Nano Lett. 18, 4796–4802 (2018).

    Article  CAS  Google Scholar 

  189. Harris, A. K., Wild, P. & Stopak, D. Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208, 177–179 (1980).

    Article  CAS  Google Scholar 

  190. Engler, A. J. et al. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  CAS  Google Scholar 

  191. Munevar, S., Wang, Y.-l & Dembo, M. Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. Biophys. J. 80, 1744–1757 (2001).

    Article  CAS  Google Scholar 

  192. Kraning-Rush, C. M., Califano, J. P. & Reinhart-King, C. A. Cellular traction stresses increase with increasing metastatic potential. PLoS ONE 7, e32572 (2012).

    Article  CAS  Google Scholar 

  193. Koch, T. M. et al. 3D traction forces in cancer cell invasion. PLoS ONE 7, e33476 (2012).

    Article  CAS  Google Scholar 

  194. Dembo, M. et al. Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys. J. 70, 2008–2022 (1996).

    Article  CAS  Google Scholar 

  195. Beningo, K. A., Lo, C.-M. & Wang, Y.-L. Flexible polyacrylamide substrata for the analysis of mechanical interactions at cell-substratum adhesions. Methods Cell Biol. 69, 325–339 (2002).

    Article  CAS  Google Scholar 

  196. Pelham, R. J. Jr & Wang, Y.-l High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. Mol. Biol. Cell 10, 935–945 (1999).

    Article  CAS  Google Scholar 

  197. Tan, J. L. et al. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl Acad. Sci. USA 100, 1484–1489 (2003).

    Article  CAS  Google Scholar 

  198. Rape, A. D., Guo, W.-H. & Wang, Y.-L. The regulation of traction force in relation to cell shape and focal adhesions. Biomaterials 32, 2043–2051 (2011).

    Article  CAS  Google Scholar 

  199. Trichet, L. et al. Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. Proc. Natl Acad. Sci. USA 109, 6933–6938 (2012).

    Article  CAS  Google Scholar 

  200. Ghassemi, S. et al. Cells test substrate rigidity by local contractions on submicrometer pillars. Proc. Natl Acad. Sci. USA 109, 5328–5333 (2012).

    Article  CAS  Google Scholar 

  201. Miyamoto, S., Akiyama, S. K. & Yamada, K. M. Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science 267, 883–885 (1995).

    Article  CAS  Google Scholar 

  202. Schäfer, C. et al. One step ahead: role of filopodia in adhesion formation during cell migration of keratinocytes. Exp. Cell Res. 315, 1212–1224 (2009).

    Article  Google Scholar 

  203. Kuo, C. W. et al. Polymeric nanopillar arrays for cell traction force measurements. Electrophoresis 31, 3152–3158 (2010).

    Article  CAS  Google Scholar 

  204. Hällström, W. et al. Fifteen-piconewton force detection from neural growth cones using nanowire arrays. Nano Lett. 10, 782–787 (2010).

    Article  Google Scholar 

  205. Li, Z. et al. Quantifying the traction force of a single cell by aligned silicon nanowire array. Nano Lett. 9, 3575–3580 (2009).

    Article  CAS  Google Scholar 

  206. Li, Z. et al. Cellular traction forces: a useful parameter in cancer research. Nanoscale 9, 19039–19044 (2017).

    Article  CAS  Google Scholar 

  207. Zheng, Q. et al. Dynamic real-time imaging of living cell traction force by piezo-phototronic light nano-antenna array. Sci. Adv. 7, eabe7738 (2021).

    Article  CAS  Google Scholar 

  208. Wolfenson, H. et al. Tropomyosin controls sarcomere-like contractions for rigidity sensing and suppressing growth on soft matrices. Nat. Cell Biol. 18, 33–42 (2016).

    Article  CAS  Google Scholar 

  209. da Silva, A. M. et al. Nanowire arrays as force sensors with super-resolved localization position detection: application to optical measurement of bacterial adhesion forces. Small Methods 2, 1700411 (2018).

    Article  Google Scholar 

  210. Kumar, A. R. et al. Materials for improving immune cell transfection. Adv. Mater. 33, 2007421 (2021).

    Article  CAS  Google Scholar 

  211. Lestrell, E., O’Brien, C. M., Elnathan, R. & Voelcker, N. H. Vertically aligned nanostructured topographies for human neural stem cell differentiation and neuronal cell interrogation. Adv. Ther. 4, 2100061 (2021).

    Article  Google Scholar 

  212. Schmiderer, L. et al. Efficient and nontoxic biomolecule delivery to primary human hematopoietic stem cells using nanostraws. Proc. Natl Acad. Sci. USA 117, 21267–21273 (2020).

    Article  CAS  Google Scholar 

  213. Yosef, N. et al. Dynamic regulatory network controlling TH17 cell differentiation. Nature 496, 461–468 (2013).

    Article  CAS  Google Scholar 

  214. Cao, Y. et al. Universal intracellular biomolecule delivery with precise dosage control. Sci. Adv. 4, eaat8131 (2018).

    Article  CAS  Google Scholar 

  215. Dixit, H. G. et al. Massively-parallelized, deterministic mechanoporation for intracellular delivery. Nano Lett. 20, 860–867 (2020).

    Article  CAS  Google Scholar 

  216. Elnathan, R. et al. Engineering vertically aligned semiconductor nanowire arrays for applications in the life sciences. Nano Today 9, 172–196 (2014).

    Article  CAS  Google Scholar 

  217. Tay, A. The benefits of going small: nanostructures for mammalian cell transfection. ACS Nano 14, 7714–7721 (2020).

    Article  CAS  Google Scholar 

  218. Chiappini, C. & Almeida, C. in Semiconducting Silicon Nanowires for Biomedical Applications (ed. Coffer, J. L.) 144–167 (Elsevier, 2014).

  219. Han, S.-W. et al. High-efficiency DNA injection into a single human mesenchymal stem cell using a nanoneedle and atomic force microscopy. Nanomed. Nanotechnol. Biol. Med. 4, 215–225 (2008).

    Article  CAS  Google Scholar 

  220. Leprince, L. et al. Dexamethasone electrically controlled release from polypyrrole-coated nanostructured electrodes. J. Mater. Sci. Mater. Med. 21, 925–930 (2010).

    Article  CAS  Google Scholar 

  221. Chen, X. et al. High-throughput delivery: a diamond nanoneedle array for potential high-throughput intracellular delivery. Adv. Healthc. Mater. 2, 1065–1065 (2013).

    Article  Google Scholar 

  222. Chiappini, C. et al. Biodegradable porous silicon barcode nanowires with defined geometry. Adv. Funct. Mater. 20, 2231–2239 (2010).

    Article  CAS  Google Scholar 

  223. Salonen, J. et al. Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs. J. Control. Release 108, 362–374 (2005).

    Article  CAS  Google Scholar 

  224. Lee, C. H. et al. Biological lipid membranes for on-demand, wireless drug delivery from thin, bioresorbable electronic implants. NPG Asia Mater. 7, e227–e227 (2015).

    Article  CAS  Google Scholar 

  225. Huang, J.-A. et al. On-demand intracellular delivery of single particles in single cells by 3D hollow nanoelectrodes. Nano Lett. 19, 722–731 (2019).

    Article  CAS  Google Scholar 

  226. Xu, A. M. et al. Temporally resolved direct delivery of second messengers into cells using nanostraws. Lab Chip 16, 2434–2439 (2016).

    Article  CAS  Google Scholar 

  227. Lee, K. et al. Physical delivery of macromolecules using high-aspect ratio nanostructured materials. ACS Appl. Mater. Interfaces 7, 23387–23397 (2015).

    Article  CAS  Google Scholar 

  228. Kim, K. & Lee, W. G. Electroporation for nanomedicine: a review. J. Mater. Chem. B 5, 2726–2738 (2017).

    Article  CAS  Google Scholar 

  229. Fajrial, A. K. et al. A review of emerging physical transfection methods for CRISPR/Cas9-mediated gene editing. Theranostics 10, 5532 (2020).

    Article  CAS  Google Scholar 

  230. Saklayen, N. et al. Intracellular delivery using nanosecond-laser excitation of large-area plasmonic substrates. ACS Nano 11, 3671–3680 (2017).

    Article  CAS  Google Scholar 

  231. Wang, Y. et al. High-efficiency cellular reprogramming by nanoscale puncturing. Nano Lett. 20, 5473–5481 (2020).

    Article  CAS  Google Scholar 

  232. Chen, Y. et al. Engineering micro–nanomaterials for biomedical translation. Adv. NanoBiomed Res. 1, 2100002 (2021).

    Article  Google Scholar 

  233. Choi, M. et al. Intracellular delivery of bioactive cargos to hard-to-transfect cells using carbon nanosyringe arrays under an applied centrifugal g-force. Adv. Healthc. Mater. 5, 101–107 (2016).

    Article  CAS  Google Scholar 

  234. Pan, J. et al. Stimulation of gene transfection by silicon nanowire arrays modified with polyethylenimine. ACS Appl. Mater. Interfaces 6, 14391–14398 (2014).

    Article  CAS  Google Scholar 

  235. Chan, M. S. & Lo, P. K. Nanoneedle-assisted delivery of site-selective peptide-functionalized DNA nanocages for targeting mitochondria and nuclei. Small 10, 1255–1260 (2014).

    Article  CAS  Google Scholar 

  236. Xu, A. M. et al. Direct intracellular delivery of cell-impermeable probes of protein glycosylation by using nanostraws. ChemBioChem 18, 623–628 (2017).

    Article  CAS  Google Scholar 

  237. Shalek, A. K. et al. Nanowire-mediated delivery enables functional interrogation of primary immune cells: application to the analysis of chronic lymphocytic leukemia. Nano Lett. 12, 6498–6504 (2012).

    Article  CAS  Google Scholar 

  238. Karra, D. & Dahm, R. Transfection techniques for neuronal cells. J. Neurosci. 30, 6171–6177 (2010).

    Article  CAS  Google Scholar 

  239. Kim, H. et al. Bioresorbable, miniaturized porous silicon needles on a flexible water-soluble backing for unobtrusive, sustained delivery of chemotherapy. ACS Nano 14, 7227–7236 (2020).

    Article  CAS  Google Scholar 

  240. Tay, A. & Melosh, N. Mechanical stimulation after centrifuge-free nano-electroporative transfection is efficient and maintains long-term T cell functionalities. Small 17, 2103198 (2021).

    Article  CAS  Google Scholar 

  241. Fox, C. B. et al. Fabrication of sealed nanostraw microdevices for oral drug delivery. ACS Nano 10, 5873–5881 (2016).

    Article  CAS  Google Scholar 

  242. Hebisch, E. et al. Nanostraw-assisted cellular injection of fluorescent nanodiamonds via direct membrane opening. Small 17, 2006421 (2021).

    Article  CAS  Google Scholar 

  243. Piret, G., Perez, M.-T. & Prinz, C. N. Neurite outgrowth and synaptophysin expression of postnatal CNS neurons on GaP nanowire arrays in long-term retinal cell culture. Biomaterials 34, 875–887 (2013).

    Article  CAS  Google Scholar 

  244. Li, Z. et al. Morphology of living cells cultured on nanowire arrays with varying nanowire densities and diameters. Sci. China Life Sci. 61, 427–435 (2018).

    Article  Google Scholar 

  245. Li, Z. et al. Single cell analysis of proliferation and movement of cancer and normal-like cells on nanowire array substrates. J. Mater. Chem. B 6, 7042–7049 (2018).

    Article  CAS  Google Scholar 

  246. Roy, A. R. et al. Exploring cell surface–nanopillar interactions with 3D super-resolution microscopy. ACS Nano 16, 192–210 (2022).

    Article  CAS  Google Scholar 

  247. Lin, Z. C. et al. Accurate nanoelectrode recording of human pluripotent stem cell-derived cardiomyocytes for assaying drugs and modeling disease. Microsyst. Nanoeng. 3, 1–7 (2017).

    Article  Google Scholar 

Download references

Acknowledgements

R.E. thanks the Australian government (ARC DECRA project number: DE170100021), the Melbourne Centre for Nanofabrication (MCN) in the Victorian Node of the Australian National Fabrication Facility (ANFF), the ANFF-Vic Tech Ambassador Program for Deakin University, Deakin’s School of Medicine and Deakin’s Institute of Frontier Materials. X.X. acknowledges financial support from the National Natural Science Foundation of China (grant no. 32171399) and National Key R&D Program of China (grant no. 2021YFF1200700, 2021YFA0911100). P.S. acknowledges support from the Hong Kong Centre for Cerebro-cardiovascular Health Engineering, funded by the Innovation and Technology Commission of Hong Kong. F.S. acknowledges the support of the European Research Council starting grant BRAIN-ACT no. 949478. C.C. acknowledges the support of the European Research Council starting grant ENBION no. 759577. Y.Z. acknowledges the support of the UK Department for Business, Energy, and Industrial Strategy through the National Measurement System (NMS project, Bioelectronics integrated multifunctional physiological measurement platform) and EPSRC Industrial CASE 2020 (20000128). W.Z. acknowledges the support of the Singapore Ministry of Education (MOE) (W.Z., RG112/20, NGF-2021-10-026 and MOET32020-0001), the Singapore National Research Foundation (W.Z., NRF2019-NRF-ISF003-3292), the Human Frontier Science Program (RGY0088/2021) and the NTU start-up grant. N.H.V. thanks the Australian Research Council for support under the Industrial Transformation Training Centre Scheme (IC170100016 and IC190100026).

Author information

Authors and Affiliations

  1. School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia

    Roey Elnathan

  2. Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

    Roey Elnathan & Nicolas H. Voelcker

  3. Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, Victoria, Australia

    Roey Elnathan & Nicolas H. Voelcker

  4. Centre for Craniofacial and Regenerative Biology, King’s College London, London, UK

    Maria Grazia Barbato & Ciro Chiappini

  5. London Centre for Nanotechnology, King’s College London, London, UK

    Maria Grazia Barbato & Ciro Chiappini

  6. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore

    Xiangfu Guo & Wenting Zhao

  7. Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia, Naples, Italy

    Anna Mariano & Francesca Santoro

  8. Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China

    Zixun Wang & Peng Shi

  9. Hong Kong Center for Cerebro-cardiovascular Health Engineering, Science Park, Hong Kong SAR, China

    Zixun Wang & Peng Shi

  10. Faculty of Electrical Engineering and Information Technology, RWTH Aachen, Aachen, Germany

    Francesca Santoro

  11. Institute for Biological Information Processing-Bioelectronics, IBI-3, Forschungszentrum Juelich, Juelich, Germany

    Francesca Santoro

  12. State Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology, Sun Yat-sen University, Guangzhou, China

    Xi Xie

  13. Mechanobiology Institute, National University of Singapore, Singapore, Singapore

    Jennifer L. Young

  14. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

    Jennifer L. Young

  15. Advanced Technology Institute, University of Surrey, Guildford, UK

    Yunlong Zhao

  16. National Physical Laboratory, Teddington, UK

    Yunlong Zhao

Authors
  1. Roey Elnathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Grazia Barbato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiangfu Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Mariano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zixun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Francesca Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peng Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicolas H. Voelcker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xi Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jennifer L. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yunlong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Wenting Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ciro Chiappini
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Roey Elnathan, Francesca Santoro, Peng Shi, Nicolas H. Voelcker, Xi Xie, Jennifer L. Young, Yunlong Zhao, Wenting Zhao or Ciro Chiappini.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Materials thanks Mark Schvartzman and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elnathan, R., Barbato, M.G., Guo, X. et al. Biointerface design for vertical nanoprobes. Nat Rev Mater 7, 953–973 (2022). https://doi.org/10.1038/s41578-022-00464-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41578-022-00464-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research