Last winter, researchers at MIT demonstrated a way to generate bar-coded microparticles by the millions. The technique, based on a novel microfluidic device, could provide a way to create millions of labeled tags for medical diagnostics. (See "New Bedside-Diagnostics Tool.")

Now the researchers have converted the microfluidic fab to turn out particles with precisely structured internal parts. MIT materials scientist Ned Thomas, who co-led the team with MIT chemical engineer Patrick Doyle, says that the new system could increase the sensitivity of the mass-produced diagnostic probes by 10,000-fold. The research is described in the chemistry journal Angewandte Chemie.

In the two-dimensional system invented last year by Doyle, unique biosensor particles are produced by flowing two solutions containing the molecular building blocks for a plastic down a channel one-fifth of a millimeter wide etched into a silicone-polymer block. A pulse of ultraviolet light projected through a stencil stimulates the plastic precursors to solidify into a single particle that's 50 micrometers across. To turn the particles into biosensors, Doyle's team doped the plastic solution with a DNA biotag; a series of dots added to the stencil labeled the particles with a pattern visible with a low-magnification microscope.

Subsequently, Thomas and Doyle's research teams realized that they could use the lithography technique recently developed at the University of Illinois, called phase-mask lithography, to build internal structure into Doyle's solid particles. Unlike a stencil, which casts a shadow to create a two-dimensional pattern, a phase mask produces a three-dimensional interference pattern. The researchers saw that the transparent block forming the base of Doyle's microfluidic device could easily double as a phase mask by cutting an undulating pattern into the bottom face of the base. The ultraviolet light needed to activate the polymer precursor is projected up from below and emerges in the microfluidic fab's flow channel as a blend of beams whose waves are out of phase with one another. Constructive and destructive interference between the beams creates a three-dimensional image within the channel. When the liquid polymer precursor flowing through is exposed to that 3-D image, it solidifies to form a corresponding 3-D plastic structure.

In the work published in Angewandte Chemie, Thomas and Doyle's team reports producing particles of acrylic plastic 60 micrometers across at a rate of 10,000 per hour. The particles are composed of one-micrometer-wide plastic rods in a square lattice with openings that are roughly two micrometers square. Thomas says that a tighter patterning of the phase mask could narrow the scaffold's elements to as thin as 200 nanometers, while a smaller stencil could shrink the particles down to 10 micrometers or less.