Engineers from the University of California, Los Angeles (UCLA) in the United States have developed a biophotonic laser-assisted surgery tool that delivers nanoparticles, enzymes, antiobodies and bacteria into cells at the rate of 100,000 cells per minute. The device, described in Nature Methods earlier in April, is significantly faster than current methods, which could lead to scientific research that was previously not possible.
Currently, the only way to deliver so-called large cargo − particles up to one micrometre in size − into cells is by using micropipettes, syringe-like tools common in laboratories. This technique is much slower, working at a rate of around one cell per minute. Other approaches for injecting materials into cells − such as using viruses as delivery vehicles or chemical methods − are only useful for small molecules, which are typically several nanometres in length.
The new device, called a biophotonic laser-assisted surgery tool, or BLAST, is a silicon chip with an array of micrometre-wide holes, each surrounded by an asymmetric, semicircular coating of titanium. Underneath the holes is a well of liquid that includes the particles to be delivered.
Researchers use a laser pulse to heat the titanium coating, which instantly boils the water layer adjacent to parts of the cell. That creates a bubble that explodes near the cell membrane, resulting in a large fissure − a reaction that takes only about one millionth of a second. The fissure allows the particle-filled liquid underneath the cells to be jammed into them before the membrane reseals. A laser can scan the entire silicon chip in about 10 seconds.
According to Eric Pei-Yu Chiou, who led the research, the key to the technique’s success is the instantaneous and precise incision of the cell membrane. ‘The faster you cut, the fewer perturbations you have on the cell membrane,' Chiou said, who is also an associate professor at the Henry Samueli School of Engineering and Applied Science.
Inserting large cargo into cells could open up new applications for research. For example, the ability to deliver mitochondria, could alter cells’ metabolism and help researchers study diseases caused by mutant mitochondrial DNA. It also could help scientists dissect the function of genes involved in the lifecycle of pathogens that invade the cell and understand the cell’s defence mechanisms against them.
‘The new information learned from these types of studies could assist in identifying pathogen targets for drug development, or provide fundamental insight on how the pathogen–host interaction enables a productive infection or effective cellular response to occur,’ explained Dr Michael Teitell, chief of the division of paediatric and developmental pathology, and a co-author of the paper.
Because the device can deliver cargo to 100,000 cells at once, a single chip can provide enough data for a statistical analysis of how the cells respond in an experiment.