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Analytical Chemistry

Tiny Silicon Claws Capture Single Cells

Bioanalytical Devices: Grippers could capture cells in the bloodstream for analysis

by Neil Savage
June 27, 2014

Get A Grip
Micrographs of silicon cell grippers in open and closed states.
Credit: Nano Lett.
Cross-shaped grippers remain open while attached to a silicon substrate with blood cells floating above them (left). Once released from the substrate, the arms close, capturing the cells (right). The scale bar on the left represents 35 µm, and the one on the right represents 10 µm.

Using techniques developed by computer chip manufacturers, scientists have created tiny silicon claws that can grasp and hold individual living cells to isolate and analyze them (Nano Lett. 2014, DOI: 10.1021/nl500136a).

The researchers, from Johns Hopkins University and the U.S. Army Research Laboratory, created a variety of grippers out of thin layers of silicon oxide, using electron-beam lithography to fashion devices with three or four gripping arms, ranging from 10 to 70 µm in length. The arms extend from a square base, where a cell would sit. At the base of each arm, the team built a hinge, consisting of two thin layers of silicon oxide and silicon dioxide. Stress between the two layers causes the hinges to bend, drawing the arms closed.

To make a lab device to capture and analyze many cells at once, the team built the bases of the grippers directly on a silicon chip. Then they added a dissolvable layer of copper and deposited the arms and hinges on top of that. The researchers pipetted a liquid cell culture containing cancer cells from mice on their chip, and as the water in the culture dissolved away the copper, the arms closed around the cells. Gaps between the arms allowed nutrients and metabolites to flow in and out, keeping the cells alive. The thin silicon was transparent, so the team could image the captured cells.

But the grippers could also be free-floating and used to capture cells in the bloodstream, says David H. Gracias, a biomolecular engineer at Johns Hopkins, who led the team. In that case, the grippers would be coated with a rigid polymer holding the arms open. After injection into the bloodstream, a trigger, such as body heat or a change in pH, would cause the polymer to soften, allowing the grippers to close around cells. Researchers could then collect the devices to analyze the cells. Gracias’s team has already used larger grippers to biopsy cells from a pig colon (Gastroenterology 2013, DOI: 10.1053/j.gastro.2013.01.066), but the hope is these tiny claws will allow them to do it inside veins.

Gracias hopes to add other functions to the claws, such as attaching antibodies to the arms to target specific cells.



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