Capturing living cells in micropyramids

‘Chance find’ in lithography yields new 3D structures

21 November 2012

A whole field of pyramids, but at microscale, each pyramid containing a living cell. 3D micro and nanofabrication technology is yielding surprising new applications. In cell studies, for instance, the pyramids’ open sides enable cell interaction to be studied. Scientists at the University of Twente’s MESA+ and MIRA research institutes will present this new technology and its first applications in the journal Small at the beginning of December.

Many cell studies are carried out in a two-dimensional setting – not a natural situation, as the cells organize themselves differently from in the body, for instance. If you give them free play in a 3D setting, however, this is a better approximation of the natural situation, while you can still keep them within an array. This is how the ‘open-sided pyramids’ fabricated at the MESA+ Institute for Nanotechnology’s NanoLab work.

Material left in the tip

The technology used to achieve this, known as ‘corner lithography’, was in fact discovered by chance. If you bring together a number of planes of, say, silicon at a sharp angle, you can apply a film of another material to those planes. If you then remove that film, not everything is gone; a small amount of material remains in the tip. And that tiny residue of material provides the base for forming a minuscule pyramid, which can then be used as a tip for an atomic force microscope, for instance. The technology also offers the possibility of writing fluids at nanoscale: here the space above the pyramid is filled with material, part of the pyramid is etched away, leaving a ‘pen’ with a hole the same size as the base of the pyramid.

Fabrication of a whole array of open-sided pyramids on a membrane

Capturing cells

In collaboration with the UT’s MIRA Institute for Biomechanical Technology and Technical Medicine the researchers investigated whether the pyramids, attached to a membrane, can act as tiny cages. This was found to work fine with microspheres, so the scientists went on to experiment with chondrocytes, the cells that produce cartilage. Capillary fluid flow causes the cells to drop into the cages of their own accord through a hole in the underside. Compounds and protein-like deposits were soon seen forming between cells in nearby pyramids. Changes in cell phenotype can therefore be studied better than in a flat plane, as this is the right way to grow cells. This yields a promising tool for research into such things as tissue regeneration.

Microspheres captured in the micropyramids

Living cells, chondrocytes captured in micropyramids. They are already starting to form compounds.

The researchers expect there to be a whole range of ways of developing this technology: the ribs of the pyramids could be made hollow, for example, creating a fluid channel, or fluid channels could be fabricated between the pyramids so as to enable the cells to receive nutrition, for example.

3D Nanofabrication of Fluidic Components by Corner Lithography by Erwin Berenschot, Narges Barouni, Bart Schurink, Joost van Honschoten†, Remco Sanders, Roman Truckenmuller, Henri Jansen, Miko Elwenspoek, Aart van Apeldoorn and Niels Tas is to be published in December as an inside cover article in the journal Small. The digital version is already available on request.

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