Scientists Put a Tiny Elephant Inside a Living Cell

Here’s what you’ll learn when you read this story:

Scientists were able to 3D-print different microstructures inside live cells, including a delightfully tiny micro-elephant.
The team also printed barcodes and tiny lasers that could both be used to label cells for observation.
While the technology still needs some improvement, it could one day revolutionize how we study cells and their insides.

Ever since the popularity of 3D-printing skyrocketed in the mid-aughts, people have manufactured everything from chocolate to rocket fuel—and that list now includes a microscopic elephant inside of a living cell (which you can see here). Technology has really leveled up since 2005.

As new biological opportunities for 3D printing keep emerging, a team of researchers—from the J. Stefan Institute, University of Ljubljana, and CENN Nanocenter in Slovenia—have found a way to pull the process off within a cell’s cytoplasm. They were successfully able to print not only an elephant, but several other impossibly small structures using a liqiud polymer and a hyperfocused petawatt laser.

What makes this more incredible is how, despite most of these polymers (known as photoresists) being toxic, there were cells that actually survived. Some even divided and took the embedded objects with them.

“Intracellular 3D printing offers an unprecedented degree of control over the cellular interior, allowing the integration of synthetic structures with native biological functions,” the team said in a study recently posted to the preprint server arXiv. “This platform could allow for reconfiguration of cellular architecture, embed logic or mechanical components within the cytoplasm, and design cells with enhanced or entirely new properties.”

For this experiment, the team used a negative photoresist (a material that changes when exposed to certain wavelengths of energy), which became insoluble when exposed to light. It was also the most biocompatible formula possible. After a droplet of photoresist was injected into the cell, an object was printed using a process called two-photon photolithography, which involves targeting an area inside the droplet with a laserto create a microstructure. Anything zapped with two photons from the laser hardens, while any remaining photoresist that has not been lasered into a structure dissolves.

Along with the ironically tiny 10-micrometer elephant, the research team printed other microstructures, like barcodes and a sphere that acted as a micro-laser. The former could eventually allow scientists to track what is going on inside individual cells, and give experts much more detailed insight into cellular function than is currently possible. The latter could be produced in various sizes that all emit light slightly differently, labeling cells with specific light signatures.

Surviving cells continued to go on as if nothing had happened. When a few of them divided, the microstructure inside was passed down to one of the daughter cells. Viability was still an issue, however—even the biocompatible photoresist was still somewhat toxic, and injecting liquid polymer damaged the cell membrane and sometimes caused cell death. How likely cells were to survive depended on the type of cell, and in total, about half of the cells that had microstructures printed in them made it through the experiment.

The 3D-printed microstructures were amazingly precise, but there is an issue with structures which exceed the size of a photoresist droplet. The researchers think one solution to this problem could be using a water-soluble, hydrogel-based photoresist that spreads throughout the cell and provides more space. Being able to print anywhere inside a cell will make it possible to create a compartment isolating a particular part of that cell for observation.

“There are many possible applications of structures printed inside the cells, well beyond what has been shown here,” the team said. “Especially interesting is the prospect of printing functional structures, which would change the properties of cells beyond what has been possible till now.”

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