Nature's ability to shape a petal has inspired a new tool that uses photolithography and printing techniques to manufacture 3-D shapes easily and inexpensively. The technique, half-tone gel lithography for photopatterning polymer gel sheets, could advance robotics, tunable micro-optics and biomedicine. Developed by Ryan C. Hayward, Christian D. Santangelo and their colleagues at the University of Massachusetts Amherst, the method may someday enable direct cells cultured in laboratories to be grown into the correct shape to form a blood vessel or a particular organ, they say. “We wanted to develop a strategy that would allow us to pattern growth with some of the same flexibility that nature does,” Hayward said. Controlling growth in a polymer system at the microscale with a technique akin to halftone printing, the polymer swells like a sponge when exposed to water. Printing “resist dots” in the polymer substrate creates points that will not swell. When the dot size changes, buckling occurs from the mismatch in growth from one area to another. With a proper halftone pattern of resist dots, almost any 3-D shape can be achieved. Courtesy of Zina Deretsky, NSF. Curves, tubes and other shapes are created in many plants by the variability of growth in adjacent areas. Although some leaf or petal cells expand, others nearby do not, and this contrast causes buckling into a variety of shapes, including curly edges and cones. For example, a lily petal's curve comes from patterned areas of elongation that define a specific 3-D shape. Using this concept, the scientists created a method that exposes ultraviolet-sensitive thin polymer sheets to patterns of light. The amount of light absorbed at each position on the sheets programs how much that region expands when put in water, thus mimicking nature's ability to direct certain cells to grow while suppressing the growth of others. The technique involves spreading a 10-µm-thick layer of polymer onto a substrate before exposure. Areas of the gel exposed to light became cross-linked, restricting their ability to expand. Nearby unexposed areas, on the other hand, swelled like a sponge as they absorbed water. This patterned growth, as in nature, caused the gel to buckle into the desired shape. However, in contrast to nature, these materials can be repeatedly flattened and reshaped if dried and rehydrated. The researchers have made shapes including cones, spheres and saddles, as well as more complex ones such as minimal surfaces. To create the latter, fundamental challenges that demonstrated the basic principles of the method were represented, Hayward said. He explained that, as happens when photographic film is exposed to patterns of light, a chemical pattern is encoded within the film. Later, when various solvents etch the exposed and unexposed regions of the film, images are produced on the photographic negative. To pattern growth in gel sheets, a similar process must be completed. The team employed a photolithography technique to simplify the complicated patterns needed for the gels. As in printing, photolithography using various color shades can be costly because each shade requires different inks. Most high-volume printing relies on a technique called “halftoning,” which uses only a few ink colors to print various size dots; smaller dots take up less space and allow more white light to reflect from the paper, thus appearing lighter than larger dots. Importantly, the halftoning concept applies equally well to patterning the growth of the gel sheets, the researchers discovered. Instead of trying to make smooth patterns with many levels of growth, they printed dots of highly restricted growth and varied the dot sizes to program a patterned shape. “By directly transferring the image onto the soft gel with halftones of light, we direct its growth,” Santangelo said. “We aren't sure yet how many shapes we can make this way, but for now, it's exciting to explore, and we're focused on understanding the process better. “For biomedicine or bioengineering, one of the questions has been how to create tissues that could help to grow you a new blood vessel or a new organ. We now know a little more about how to go from a flat sheet of cells to a complex organism.” The method was described in Science (doi: 10.1126/science.1215309).