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A needle-like optofluidic probe enables targeted intracellular delivery of molecular cargo into single-cells and tissue ex-vivo (Conference Presentation)

Intracellular delivery of molecular cargo is the basis for a plethora of therapeutic applications, including gene therapy and cancer treatment. An efficient method to perform intracellular delivery is the photoactivation of nanomaterials that bear releasable molecular cargo. However, potential in vivo applications of this method are limited by our ability to deliver nanomaterials and light in tissue. 
In this paper, we will present method to perform intracellular delivery of molecular cargo on live cells and tissue by using a reusable, needle-like optofluidic probe capable of penetrating soft tissue. The probe consists of a dual-core glass fiber, enabling simultaneous light and liquid delivery. First, we used the optofluidic probe to confine an intracellular delivery mixture, composed of 100 nm gold nanoparticles (AuNP) and membrane-impermeable calcein, in the vicinity of cancer cells and mouse retinal explants. Secondly, we delivered nanosecond (ns) laser pulses (wavelength: 532 nm; duration: 5 ns; 30-90 mJ/cm2) using the same probe and without introducing a AuNP cells incubation step. 
We found that AuNP photo-activation caused localized and reversible disruption of the cell membrane, enabling calcein delivery into the cytoplasm. We measured 67% intracellular delivery efficacy and showed that the optofluidic probe can be used to treat cells with single-cell precision. 
The method presented here can facilitate in vivo treatments in soft tissue of small animals (e.g. brain, retina), such us nanomaterial-assisted neuro-stimulation, transfection and tumor elimination.