Nanoprobes come in all shapes and sizes. In the latest advance in probe engineering, chemists, physicists and engineers at the University of California, Los Angeles, are pooling their resources to perfect a method for mass-producing novel fluorescent microparticles. The nature of these particles can be so precisely controlled that researchers have been experimenting by creating entire alphabets that can be manipulated with optical tweezers, raising the intriguing possibility of playing nano-scrabble.

Under the spell: nano-alphabet. Credit: J. N. WILKING/T. G. MASON/UCLA

These so-called LithoParticles are sculpted by electron-beam lithography, directed by the same computer-aided design (CAD) software used by architects. “E-beam writing is a serial process,” says Thomas Mason, who leads the group. “Each letter is written one at a time, so it's not very good for mass production. However, once the mask is made, it can be used over and over again in a special optical-projection printer. We use a mask made by E-beam lithography to expose resist-coated wafers to patterned ultraviolet light. A different projection-printing device — an optical lithography system known as a stepper — is used to mass-produce many particles in parallel.” The Ultratech XLS stepper has a lens weighing over 90 kilograms and its own heating and air-conditioning systems to control thermal expansion. The same technology could be used to mass-produce particles with feature sizes as small as 30 nm.

The potential implications for cell biology are huge. Such accuracy of design, coupled with high fidelity on a mass scale, means researchers could soon be supplied with solutions of probes tailored to their specific needs, as neatly demonstrated by Mason's 'alphabet soup'.

Nanoprobes are being increasingly used in the emerging field of bio-microrheology, which examines transport processes within living cells, and in investigating the mechanical properties of cellular components. Nanoparticles introduced by ballistic injection have revealed how the cytoplasm of human umbilical vein endothelial cells undergoes elastic changes in response to growth factors. But the approach could be expanded to investigate the cell's response to all manner of different shapes. “Tracking how differently shaped particles move and rotate inside cells may provide a wealth of information about life cycles and internal cytoplasmic transport in different cell types,” says Mason. “You could also use these probes to study how cells respond to various external stimuli. For instance, particles that have many long 'arms' may behave very differently to the compact spheres and quantum dots that are currently available.”

UCLA is currently applying to patent their technology and are involved in discussions with commercial partners. Mason is already speculating about building functional nanomachines — including motors, pumps and entire engines — which could be sent to probe even further into the workings of the cell.

H.M.B.