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The Biomimicry Column

Can nature unlock the potential of additive manufacturing?

Recent developments in chemistry may have taken us closer to the Holy Grail of finding a universal kit of parts with which to "print" our world.

If the ultimate prize in additive manufacturing is finding a universal kit of parts, then recent nature-inspired developments in small molecule chemistry may have brought us closer to this world of the future.

Suppose you went home tonight and found out that the float arm in your toilet tank was broken, you were having several unexpected guests for dinner, your mother-in-law needed new eyeglasses and Junior had to make a scale model of a California Mission building by tomorrow.

In the future world of additive manufacturing you would hardly raise a sweat, because you would be able to turn to your home 3-D printer and make everything you needed: strong metal parts; clear acrylics; food; and, of course, all those tiny Spanish roof tiles.

This really isn’t that far-fetched, is it? As a matter of fact, all these things can be made today (albeit slowly), from engine parts to dentures to designer dinner entrees. Most current AM methods take a chemical mix of molecules and zap it with something such as UV light or heat in order to catalyze it into a different molecular structure, often a phase change; from a liquid to a solid.

This is done within the context of building this material up in newly fused layers. Typically, however, different products require different materials and types of machines. What might be done best by stereolithography, for example, may not work so well with fused deposition modeling. What we are missing is the ability to make a wide variety of things without changing the feedstock or the type of machine.

Minimum parts for maximum diversity

Nature, of course, is a past master at all of this. Modularity is her middle name, and the mini/max model is always in operation at Bio Central. Minimum parts for maximum diversity, that is, because it is often how a small number of components are arranged up through linear scales, rather than the number of components, that determines behavior and performance.

There are, nonetheless, significant differences between nature and technology. One big difference is the base scale at which natural materials are created; another is the continual information flow needed to keep the manufacturing going.

Recent research developments may have brought us closer to the natural model on the first count, scale. A team at the University of Illinois at Urbana-Champaign has devised a single automated process to synthesize 14 distinct classes of small molecules from a common set of building blocks.

Small molecules such as O2, N2 and CO2 have very important uses in medicine, biological research and technology. Most drugs can be classified as small molecules, for instance.

As their formulas suggest, these molecules have just a few or a couple of atoms linked together. In nature they are joined together again and again into complex arrays and these are used for different tasks according to those arrays.

The proteins in your body, for example, perform many jobs according to their array, from enzymes to transporters. The University of Illinois team studied thousands of chemical structures in order to discern basic patterns.

If they could synthesize them in a more efficient way based on these patterns, then countless hours of customized chemistry could be eliminated and many non-specialist researchers could explore new types of drugs.

"Nature makes most small molecules the same way,” reported team leader Martin Burke to Burke is a professor of chemistry, an M.D. and an early career scientist of the Howard Hughes Medical Institute. “There are a small number of building blocks that are coupled together over and over again, using the same kind of chemistry in an iterative fashion. (These) building blocks appear over and over again, and we've been able to dissect out the building blocks that are most common."

Props for a B-movie?

To produce these basic formulations they have built a machine that looks like a prop for a science fiction B-movie: vials and tubes abound with an almost scary retro mechanical look. The device modulates a process of building molecules by isolating and sequencing the steps needed. At each station the required ingredients are added, a chemical reaction is induced and its byproducts washed away and the product kept for the next step.

Apparently, the most difficult challenge for the researchers was figuring out how to consistently wash out the byproducts and retain the desired molecules. This is truly “bottom up” construction, much as nature does, with the researchers able to link together their basic parts to make more complex arrays.

The team reported their findings in the March 13 issue of the journal Science, and have demonstrated the ability to produce thousands of chemicals, most within a matter of hours.

Burke hopes that this development will open up a whole new world of exploration, much like macro-scale 3-D printing is doing now: "The vision is that anybody could go to a website, pick the building blocks they want, instruct their assembly through the Web, and the small molecules would get synthesized and shipped. We're not there yet, but we now have an actionable roadmap toward on-demand small-molecule synthesis for non-specialists."

Burke has established a privately held company, Revolution Medicines, with $45 million in Series A financing from Third Rock Ventures to commercialize this technology.

Infomatics and automation

They are developing two methodologies that are the outgrowth of the University of Illinois research and under special license arrangement: The informatics platform used to discern the basic construction patterns or scaffolds, and the automation process used in the company’s prototype device.

The Redwood City, Calif., company will use the new technology to quickly make candidate compounds for the pharmaceutical market. Their first objective is to make new formulations that can improve a well-tested antifungal medicine, amphotericin B.

While this naturally occurring compound has been used clinically for 50 years with no significant drug resistance, it does have a dose-limiting side effect: too much can damage the kidneys. Already Burke’s team has proven that the antifungal mechanism can be separated from the kidney cell damaging mechanism. The team is developing novel compounds for an improved version that kills fungi without damaging human cells.

By tracking through and analyzing patterns in nature, then streamlining these processes for a bottom-up approach to manufacturing that will scale up current long and laborious custom chemistry, this development appears to represent a distinct milestone in the field of medicine.

I also think that it could offer a model for a wider application and may represents a closer step to the kind of universal feedstock and process needed in that truly marvelous 3-D printer in your home of the future.

As we become more adept at mimicking nature at the scale of atoms and molecules, we will see more things in our daily lives done that way.

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