Originally Published MPMN June 2009

SPECIAL FEATURE: MICROMANUFACFTURING

Manufacturing from the Bottom Up

When it comes to nanotechnology, it seems as though the sky’s the limit in terms of potential applications. Limitations do exist, however, in terms of actualizing these innovative concepts. In fact, nanomanufacturing presents a whole new set of unique challenges for medical device development. To discuss these issues, MPMN caught up with Tihamer Toth-Fejel, who is a senior research engineer at General Dynamics Advanced Information Systems, Michigan Research and Development Center; vice-chair of the Society of Manufacturing Engineers' Nanomanufacturing Technical Group; and an advisory board member of The Nanoethics Group.

Q: What is nanomanufacturing?
A: It depends who you ask and how they define nanotechnology. Technically, it’s defined as any manufacturing in which a pertinent length scale is between 1 and 100 nm.
There are really three ways to perform nanomanufacturing. First, there is the top-down approach, such as chip manufacturing. This approach is deterministic, so it gives control over the process. But the problem is that as smaller and smaller structures are built, it gets exponentially expensive—as exemplified by the $2-billion price tag for semiconductor fabs.
Second, there is the bottom-up approach, which involves the production of complex engineered macromolecules such as dendrimers, silsesquioxanes, carbon nanotubes, and block copolymers. With this approach, you can make large amounts of a product, but you’re at the mercy of thermodynamics. And when you try
to build increasingly complex nanostructures,
it, too, gets more difficult and expensive.
The third approach is something new and completely different: productive nanosystems that make nanoscale products. There are only a few technologies today that take this approach. Some, like DNA origami and its RNA, GNA, and PNA variants, and bis-peptide synthesis are advanced bottom-up approaches that use the informational aspect of nucleic or bis-amino acid sequences to deterministically control local position and orientation for structures up to about 100 nm. Others are derived from top-down approaches, like patterned atomic layer epitaxy and diamondoid mechanosynthesis, which are scanning probe systems that will need to bootstrap to build significant amounts of atomically precise product.

Q: What are some of the emerging nanomanufacturing techniques?
A: Currently, the bottom-up techniques are really glorified chemistry, and the top-down techniques are glorified machine shops. A hybrid of both, productive nanosystems will resemble biology in many ways, especially with respect to the genotype-ribotype-phenotype (GRP) paradigm so common in all life forms and in numerically controlled (NC) machine tools. With the GRP paradigm, you have a machine—like a ribosome, 3-D printer, or NC milling machine—that can make a variety of products, like proteins, plastic prototypes, or metal parts, just by changing the input instructions. Productive nanosystems will be programmable and deterministic like top-down systems, but since they’ll be small and operating in parallel, they will be able to produce large quantities of product just like bottom-up processes.
In terms of near-term deliverable product, I think nanoimprint and dip-pen lithography are the closest to a commercial breakthrough in terms of continuing to push Moore’s law.

Q: How could nanomanufacturing impact the development of medical devices?
A: Again, it depends on your definition, but even primitive nanotechnology will have a significant impact on medicine, from tissue engineering and nanoformulated pharmaceuticals to web-enabled sensor implants and anticancer nanoparticles. The manufacture of atomically precise medical products in bulk quantities by productive nanosystems will blur the line between drugs and devices while giving us powerful tools for fighting disease and aging. The caveat is that first we need to gain the scientific knowledge so that we understand the nanostructures we need to build—though nanotechnology will provide tools with which to gain that scientific knowledge.
One big problem will be FDA’s approval process, however. The agency is terrified of nanotechnology causing another thalidomide or asbestos scenario, and understandably so, since there are still many unknowns. Unfortunately, the cost of not taking risks is also measured in lives, but there is no political or social mechanism for taking that into account, especially in a litigious, risk-adverse environment such as ours. I suspect there will be a significant amount of offshore testing to get around FDA.

Q: What needs to be accomplished to enable widespread adoption of nanomanufacturing?
A: Technically, nanomanufacturing is here now. Tons of engineered nanoparticles are produced around the world today using bottom-up chemistry. And top-down techniques are producing billions of dollars of nanostructures, mostly based on silicon. The more-capable productive nanosystems won’t be built for another 8 to 10 years.
Nanomanufacturing needs to create real wealth so that manufacturers that use it to build products can invest in the next round of improvements. Once the bottom-up techniques can build nanostructures that are complex enough to do error correction, or the top-down techniques can bootstrap themselves into exponential manufacturing, then we will have productive nanosystems, and our only constraints will be human knowledge and the laws of physics.
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