Nanodisk lasers for internalisation by live cells

IntroductionBiomedical imaging has driven research into intracellular light sources which can complement the functionality of presently used molecular dyes. These nanophotonic objects, such as quantum dots, are governed by... [ view full abstract ]

Introduction

Biomedical imaging has driven research into intracellular light sources which can complement the functionality of presently used molecular dyes. These nanophotonic objects, such as quantum dots, are governed by spontaneous processes and as a result exhibit broad spectral features and limited signal to noise ratios. Intercellular laser emitters both overcome these limitations and present opportunities for spectral multiplexing and sensing, as illustrated in recent proof-of-concept studies [1,2]. However, these initial experiments were limited by the large laser sizes and thresholds [3]. Here, we report on design, high-throughput fabrication and application of semiconductor nanodisk lasers for this purpose. By exploiting the large optical gain and high refractive index of GaInP/AlGaInP quantum wells, we obtain lasers with volumes 1000-fold smaller than the eukaryotic nucleus (Vlaser<0.1 µm3), lasing thresholds 500-fold below the pulse energies typically used in two-photon microscopy (Eth≈0.13 pJ), and excellent spectral stability (<50 pm wavelength shift).
Methods
Nanodisks were produced from an epitaxially grown quantum well structure. A resist was patterned using electron beam lithography and a two-step wet etch to deposit the nanolasers into petri-dishes ready for characterisation and cell culturing.
Results and Discussion
A range of different cell types readily internalized nanodisk lasers via natural phagocytosis. Importantly, internalisation was also observed for T-cells and neurons which are too small to engulf the previously reported cell lasers and/or not specialised for phagocytosis, illustrating the importance of using sub-µm sized lasers for cell internalisation. Additionally, due to the small size of our new lasers, each cell can internalise multiple nanodisk lasers without adding a heavy payload. The multiplexed emission spectrum from these lasers provides a highly characteristic optical barcode, thus allowing to uniquely label large numbers of cells. Furthermore, we demonstrate that the lasers do not encumber the cells and so can be used to track migration of cells through micro-pores, thus providing a powerful tool to study processes like cancer invasion.
References
1. Gather, M. C. & Yun, S. H. Nature Photonics 5, 406-410 (2011).
2. Schubert, M. et al. Nano Letters 15, 5647-5652 (2015).
3. Hill, M. T. & Gather, M. C. Nature Photonics 8, 908-918 (2014).