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Biointerface design for vertical nanoprobes

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.

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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.

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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).

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

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