A myriad of different therapeutic, diagnostic, and research-oriented nano-scale devices and molecules have been developed to work inside living cells. While many of these particles are very effective at what they do, it is often the difficulty of delivering them that is the real challenge in using them for practical purposes. Typically, either some sort of vessels are used to carry these particles into cells or the cell membrane is broken to let the invaders in. As such, these techniques either injure cells or are not very good at consistently delivering their cargo, and they can be hard to automate. Now, a team of collaborators from Korea University and Okinawa Institute of Science and Technology Graduate University in Japan have developed an entirely novel way of getting particles and chemical compounds, including proteins, DNA, and drugs, into the interior of cells without causing much damage. The new technique relies on creating spiral vortexes around cells that temporarily deform cellular membranes long enough to let things in. The membranes seem to immediately restore themselves to their original state once the vortex stimulation ceases. All this is performed in one step and doesn’t require any complex biochemistry, nano delivery vehicles, or permanent damage to the cells involved. The device built for the task, called a spiral hydroporator, can deliver gold nanoparticles, functional mesoporous silica nanoparticles, dextran, and mRNA into different types of cells within a minute at an efficiency of up to 96% and a cellular survival of up to 94%. All this at an incredible rate of about one million cells per minute and from a device that is cheap to produce and simple to operate. “Current methods suffer from numerous limitations, including issues with scalability, cost, low efficiency and cytotoxicity,” said Professor Aram Chung from the School of Biomedical Engineering at Korea University, the study lead. “Our aim was to use microfluidics, where we exploited the behavior of tiny currents of water, to develop a powerful new solution for intracellular delivery… You just pump a fluid containing the cells and nanomaterials in two ends, and the cells – now containing the nanomaterial – flow out of the other two ends. The entire process takes only one minute.” The interior of the microfluidic device has cross junctions and T junctions through which cells and the nanoparticles flow. The junction configurations create the necessary vortexes that lead to the penetration of cell membranes and the nanoparticles naturally enter when the opportunity arises. Here’s a simulation of a spiral vortex which causes cell deformation at the cross-junction and T-junction: When two opposing streams of water meet at a cross-junction at low flow rates (left), the streams part and continue flowing symmetrically, which causes cells to elongate when in the center. When the flow rate is increased to a moderate flow (right), small instabilities in the flow are compounded. This results in the formation of a swirling spiral vortex, which deforms cells in the center of the cross-junction. Source
