Laser-induced breakdown of an optically trapped gold nanoparticle for single cell transfection

Abstract

The cell selective introduction of therapeutic agents remains a challenging problem. Here we demonstrate spatially controlled cavitation instigated by laser-induced breakdown of an optically trapped single gold nanoparticle of diameter 100 nm. The energy breakdown threshold of the gold nanoparticle with a single nanosecond laser pulse at 532 nm is three orders of magnitude lower than water, which leads to nanocavitation allowing single cell transfection. We quantify the shear stress to cells from the expanding bubble and optimize the pressure to be in the range of 1-10 kPa for transfection. The transfection of genes and injection of therapeutic agents into individual mammalian cells are among the most important research tools in modern molecular biology [1]. The use of acoustic bubbles in the proximity of cells oscillated by ultrasonic irradiation (insonation) can lead to enhanced membrane permeabilization of cells, and is known as sonoporation. Acoustic streaming, shock waves, and liquid microjets associated with the dynamics of cavitation bubble are implicated in gene and drug delivery into cells [2]. This approach, however, often leads to nonuniform and sporadic molecular uptake that lacks cell selectivity and suffers from a significant loss of cell viability. Recently a suite of optical methods in the domain of cavitation-based therapies has provided the potential of sterility, reconfigurability, and single cell selectivity [3]. Laser-induced breakdown (LIB) of a liquid medium containing cells, has demonstrated cell lysis, necrosis or membrane permeabilization, with the outcome dependent upon the hydrodynamic shear stress to cells caused by the expanding bubble [4]. However, the relatively high energy deposition required for this process resulted in a much larger cavitation bubble (typically >200 μm in diameter) compared to the typical cell size that effectively reduces cell viability and has been detrimental to allow its wider usage.More spatially controlled cavitation may be achieved by optically trapping particles for subsequent LIB instead of the surrounding liquid [5]. Optical tweezers allow the positioning of individual nanoparticles or microparticles at a desired location within the buffer medium. Therefore, using this tool for LIB offers additional degrees of freedom-the particle material, its size, and the LIB position relative to cells or tissues. We have shown that the LIB of trapped polystyrene nanoparticles significantly reduced the energy required for cavitation [6,7]. This leads to the permeabilization of cell membranes and transfection of cells in a targeted area in the absence of a lysis zone of cells.Gold nanoparticle clusters have played a key role in this field, through antibody binding and sequestration with subsequent irradiation by nanosecond or femtosecond laser pulses [8][9][10]. A unique interaction of gold nanoparticles with light, known as surface plasmon resonance, can lead to strong absorption of light for heat generation. However, the introduction of gold nanoparticles in the c...

Dynamic imaging of a single gold nanoparticle in liquid irradiated by off-resonance femtosecond laser

“…Plasmonic bubble (PB) detection and more importantly PB insitu monitoring allows for understanding the cell nanosurgery mechanism as well as for processing optimization. Therefore, due to their crucial role in cell nanosurgery, PB generation around pulsed laser excited plasmonic NPs is receiving growing interest by several research groups [13][14][15][16][17] . Due to their transient and confined nature, PB studies demand the development of detection methods with nanoscale temporal and spatial resolution.…”

Laser Trapping of Colloidal Metal Nanoparticles

“…Both the molecular spectroscopy and laser heating opportunities are probably best taken advantage of in combination with applications that require confined spaces or have limited physical access, such as in bioassays based on microfluidics or in single cell experiments. 130 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 …”

Invited Article: Optical trapping of ultrasmooth gold nanoparticles in liquid and air

“…We modeled the amount of energy absorbed by a gold NP positioned at the focus of the beam and the dissipation of the heat through conduction into air using the COMSOL Multiphysics software (RF module in scattering formulation). 10 The model calculates the absorption and scattering cross sections of a single airborne gold NP and estimates its temperature rise ∆T at a given incident power, which is 0.57 KmW −1 and 3.2 KmW −1 for particle diameters of 50 nm and 100 nm, respectively [see blue and green lines in Fig. 4(b)].…”

“…4 Moreover, laser-induced breakdown of gold NPs can be used for cell poration. 10 In virtually all investigations, gold NPs have been sourced commercially and an inherent aspect of their response has been due to their morphology. For example, in a key study in 2005, gold NPs were seen to exhibit unexpected trapping characteristics, as particles as large as 254 nm could be stably trapped in three-dimensional potential well by a single beam.…”