Molecular Medicine Israel

Inspired by Nature

Researchers are borrowing designs from the natural world to advance biomedicine.

When biomedical engineer Jeff Karp has questions, he looks to animals for answers. In 2009, Karp gathered his team at the Brigham and Women’s Hospital in Boston to brainstorm novel ways to capture circulating tumor cells (CTCs) in the bloodstream. They mulled over the latest microfluidic devices. Then the conversation turned to the New England Aquarium, and to jellyfish.

Scientists have tried to grab cancer cells from blood ever since they discovered that tumors shed malignant cells that migrate throughout the vasculature a process known as metastasis. “If you pluck out these cells, you have a direct indicator of what the cancer looks like,” says Karp. “Then you can screen drugs to get those that will have the greatest impact.” Doctors might also be able to detect such cells during the earliest stages of metastatic cancer, when it’s more readily treatable.

The problem is, CTCs make up a tiny fraction of cells in the bloodstream of a person with cancer, meaning an effective diagnostic must process relatively large volumes of blood. However, an existing test, which uses magnetic particles to isolate CTCs, processes just 7.5 milliliters of blood, only a fraction of one percent of the 5 liters of blood in an adult human. Dialysis-like microfluidic devices promise to handle larger volumes and improve efficiency, but the best current prototypes still feature extremely narrow microchannels to ensure CTCs pass within reach of CTC-binding antibodies along the perimeter. “Channel height is extremely low in a lot of the proposed devices, meaning you can barely flow any blood through,” says Karp. (See “Capturing Cancer Cells on the Move,” The Scientist, April 2014.)

Karp wanted to change that. “We asked ourselves, ‘What creatures can capture things at a distance?’” he recalls. One of his graduate students suggested jellyfish, whose long, sticky tentacles grab prey and other food particles from water. Within a year, Karp and his colleagues had designed a microfluidic chip on which 800-micron-wide microchannels are lined with long, tentacle-like strands of DNA that bind a protein on the surface of leukemia cells as they pass through the channels. (See illustration below.) In 2012, Karp showed that the jellyfish-inspired device could process 10 times more blood than existing chips in the same amount of time and trap an average of 50 percent of circulating leukemia cells.1 Karp estimates that a device the size of the standard microscope slide could collect hundreds or thousands of tumor cells in minutes. Encouraged by such results, Karp’s team is now improving the platform, designing chips that can catch any CTC of interest.

The jellyfish is far from the only intriguing organism to have served as a blueprint for scientists in the field of bioinspired medicine. Researchers have taken cues from the adhesive chemistry perfected by mussels and marine worms to create tissue glues that stick in wet and turbulent conditions; from red blood cell membranes to help drug-carrying nanoparticles avoid immune attack; and from the slippery slides that help carnivorous pitcher plants catch prey to produce novel antibacterial surfaces. (See “Bioinspired Antibacterial Surfaces.”) Nature, it seems, provides a compendium of biomedical solutions.

“Nature has used the power of evolution by natural selection to develop the most efficient ways to solve all kinds of problems,” says Donald Ingber, founding director of the Wyss Institute for Biologically Inspired Engineering in Boston. “We’ve uncovered so much about how nature works, builds, controls, and manufactures from the nanoscale up. Now we’re starting to leverage those biological principles.”…….

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