Opening transient pores in the membranes of living cells is highly desirable in many fields of biology to enable the transfer of DNA, RNA, and proteins for cell engineering. The delivery of non-biologics is also important for intracellular sensing and probing by patch clamp, quantum dots, and surface-enhanced Raman scattering (SERS) particles. However, it is difficult to achieve controlled, patterned cutting on mammalian cell membranes because the membrane is elastic, mechanically fragile, and reseals rapidly [1
]. Conventional microinjection uses a sharp glass microcapillary pipette to mechanically penetrate the membrane and enter the cell interior. The extent of cell deformation and trauma from this procedure severely limits the delivery pipette tip diameter to smaller than 0.5 µm in order to maintain cell viability [3
]. Alternate delivery technologies include electroporation [5
] and sonoporation [6
] which induce transient circular pores in the cell membrane, but the pore size and spatial distribution are probabilistic and difficult to control. Optoporation [7
] ablates a single hole in the cell membrane at the focal point of a tightly focused pulsed laser beam. Two dimensional patterned membrane poration can also be achieved by rapidly scanning the laser focus within a field of view [9
] or by using beam-shaping optics [10
Metallic nanoparticles such as gold nanospheres or nanorods randomly adhered to cell surfaces have been shown to transiently porate the cell membrane for small molecule delivery or to cause membrane rupture and cell death under pulsed laser irradiation [11
]. Compared to particle-free direct laser surgery methods, metallic nanoparticles allow the generation of nanoscale bubbles with a non-focused laser beam for large area operation at a lower cost with a more accessible nanosecond pulse laser. The nanoparticles exhibit large optical absorption cross-sections due to their surface plasmon resonance, with tuning of the absorption peak by engineering the metallic nanostructure material and configuration [17
]. Absorbed energy is converted to lattice heat in picoseconds [17
] and heats up the particle along with a thin layer of adjacent liquid medium through thermal conduction. When the laser energy density exceeds the threshold to superheat the liquid layer beyond the critical temperature [19
], explosive vapor bubbles are created, which exert transient shear stress that punctures an adjacent cell membrane.
The aim of the current study is to provide a photothermal nanoblade mechanism that utilizes metallic nanostructures to harvest optical pulse energy and trigger spatially patterned, temporally synchronized cavitation bubbles. These controllable cavitation bubbles generate high-speed fluidic flows that enable patterned cutting of an adjacent cell membrane. Our photothermal nanoblade can be readily integrated with other delivery vehicles, such as a microcapillary pipette. In this configuration, active and pressure-driven cargo delivery into cells can be achieved via a large bore pipette without inducing severe damage to the cell since the pipette does not enter the cell.