Engineers and doctors at the University of California Los Angeles (UCLA) have developed a new biophotonic tool that could enable study of disease development and improve imaging of the inside of cells, among other uses in medical and biological research.
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The biophotonic laser-assisted surgery tool (BLAST) delivers nanoparticles, enzymes, antibodies, bacteria, and other large cargo into mammalian cells at the rate of 100,000 cells per minute—significantly faster than current technology, which works at about one cell per minute. The BLAST device is a silicon chip with an array of micrometer-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 s.
The research was led by Eric Pei-Yu Chiou, associate professor of mechanical and aerospace engineering and of bioengineering at UCLA's Henry Samueli School of Engineering and Applied Science, who says the key to the technique's success is the instantaneous and precise incision of the cell membrane.
Inserting large cargo into cells could lead to scientific research that was previously not possible, including the ability to deliver mitochondria, which 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 defense 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," says Dr. Michael Teitell, chief of the division of pediatric and developmental pathology, and a co-author of the study.
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.
Full details of the work appear in the journal Nature Methods; for more information, please visit http://dx.doi.org/10.1038/nmeth.3357.
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