• Advanced Photonics
  • Vol. 4, Issue 1, 016001 (2022)
Danran Li1、2, Nina Wang3, Tianyang Zhang3, Guangxing Wu1、2, Yifeng Xiong1、2, Qianqian Du4, Yunfei Tian1、2, Weiwei Zhao3, Jiandong Ye4, Shulin Gu4, Yanqing Lu1、2, Dechen Jiang3、*, and Fei Xu1、2、*
Author Affiliations
  • 1Nanjing University, College of Engineering and Applied Sciences, Nanjing, China
  • 2Nanjing University, National Laboratory of Solid State Microstructures, Collaborative Innovation Center of Advanced Microstructures, Nanjing, China
  • 3Nanjing University, School of Chemistry and Chemical Engineering, Nanjing, China
  • 4Nanjing University, School of Electronic Science and Engineering, Nanjing, China
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    The achievement of functional nanomodules for subcellular label-free measurement has long been pursued in order to fully understand cellular functions. Here, a compact label-free nanosensor based on a fiber taper and zinc oxide nanogratings is designed and applied for the early monitoring of apoptosis in individual living cells. Because of its nanoscale dimensions, mechanical flexibility, and minimal cytotoxicity to cells, the sensing module can be loaded in cells for long term in situ tracking with high sensitivity. A gradual increase in the nuclear refractive index during the apoptosis process is observed, revealing the increase in molecular density and the decrease in cell volume. The strategy used in our study not only contributes to the understanding of internal environmental variations during cellular apoptosis but also provides a new platform for nonfluorescent fiber devices for investigation of cellular events and understanding fundamental cell biochemical engineering.

    1 Introduction

    The intracellular microenvironment involves vital physiological characteristics of various cellular compartments. The fabrication of nanoprobes for subcellular measurement is important to fully characterize cellular function. Single-cell interrogation at the nanoscale is carried out mainly via optical approaches, such as the use of fluorescent dyes,13 quantum dots or nanoparticles,411 nanofiber probes,12,13 single nanowire probes,1419 and planar photonic crystal nanowaveguides;20 mechanical approaches, such as the use of atomic force microscopy probes2123 and nanobeam arrays;24 and electrochemical approaches, such as the utilization of single metal nanowires,25,26 pillars, or tube electrodes.2731 Dyes and quantum-dot-based probes have attracted much attention in biology, attributable to their photoluminescence (PL), and achieved great success in measuring the temperature of cells and their organelles,32,33 as they can be easily phagocytosed by cells due to their ultrasmall dimensions and are quite robust against external disturbances. However, these techniques suffer from some limitations, such as fluorescence bleaching and background fluorescence interruption. Optical nanofibers have become increasingly popular owing to their excellent optical waveguiding property, high flexibility, and ease of integration34 and thus have been applied for the detection of intracellular pH14 and ionic concentrations.15 Notably, the existing fiber probes are passive in nature and serve only as conduits to guide light signals into/from a cell but not as a complete optical functional module for physical or chemical label-free sensing. Accordingly, most nanoprobe techniques still have to modify other nanoparticles, resulting in the low functional integration of structures.