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Molecular-scale devices could be precisely oriented on chips

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Engineers from California Institute of Technology have placed molecule-scale devices in precise orientation, in a demonstration of a technique which paves the way for the integration of molecules with computer chips.

The technique allowed them to place microscopic devices formed from folded DNA not just in a specific location but also with a precise orientation.

In their proof-of-concept experiment, they arranged more than 3,000 of these glowing, moon-shaped devices into a flower-shaped instrument for indicating the polarisation of light. Each of these pointed in a different direction, forming 12 petals around the centre of the flower. Because each device only glows when struck by polarised light matching its orientation, the flower’s petals are illuminated in sequence as the polarisation of incident light is rotated.

The flower spans a distance smaller than the width of a human hair, demonstrating than thousands of molecules can be reliably orientated on the surface of a chip.

Flower made from DNA origami devices

Ashwin Gopinath/Caltech

Image credit: Ashwin Gopinath/Caltech

The demonstration builds on more than 15 years of work by Professor Paul Rothemund and his colleagues. In 2006, he demonstrated that DNA can be directed to fold into precise shapes (“DNA origami”), and he later described a technique for positioning these objects precisely using a process in which they were bound to a surface at the location of “sticky” patches matching their shape.

They later extended and refined the technique such that molecular devices constructed from DNA origami can be integrated into optical devices, demonstrating the high precision possible by reproducing a 65,000-pixel image of Vincent van Gogh’s Starry night using triangular DNA origami carrying fluorescent molecules. However, the technique had a serious limitation.

“Because the triangles were equilateral and were free to rotate and flip upside-down, they could stick flat onto the triangular sticky patch on the surface in any one of six ways. This meant we couldn’t use the devices that required a particular orientation to function. We were stuck with devices that would work equally well when pointed up, down, or in any direction” said MIT’s Professor Ashwin Gopinath, who previously worked with Rothemund. This limitation prevented the engineers using molecular devices intended for DNA sequencing or measuring proteins, which must be oriented correctly.

In order to make the DNA origami land with the correct side facing upwards, they coated them with flexible DNA strands on one side, which enabled more than 95 per cent to land face up. Rothemund and Gopinath worked with collaborators from other universities to identify a shape which would only be stuck in the intended (rotational) orientation, no matter how it landed. They settled on a moon-like disc with a small, off-centre hole; unlike a triangle, this shape smoothly rotates into the optimal alignment without becoming stuck. Over 98 per cent of these shapes found the correct orientation.

The engineers then added fluorescent molecules that wedge themselves snugly into the DNA helix of the shape (perpendicular to the axis); this ensured that all the molecules within each DNA origami device were oriented in the same direction and would glow most brightly when stimulated.

“It’s as if every molecule carries a little antenna, which can accept energy from light most efficiently only when the polarisation of light matches the orientation of the antenna,” said Gopinath. This technique made it possible to create the polarisation-sensitive flower shape.

These methods for controlling the position and orientation of DNA-based devices open up the possibility to integrate a range of molecular devices into computer chips, for applications such as DNA sequencing or measuring the concentrations of thousands of proteins at once. Rothemund and Gopinath have since founded a company, Palamedrix, to commercialise the technology for building chips which enable simultaneous study of all the proteins relevant to human health.

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