[DIYbio] Fwd: [tt] Three-dimensional printers are opening up new worlds to research.

Date: Thu, Jul 5, 2012 at 8:35 AM
Subject: [tt] Three-dimensional printers are opening up new worlds to research.
To: tt@postbiota.org

http://www.nature.com/news/science-in-three-dimensions-the-print-revolution-1.10939

Science in three dimensions: The print revolution

Three-dimensional printers are opening up new worlds to research.

Nicola Jones

04 July 2012

Research labs use many types of 3D printers to construct everything from
fossil replicas to tissues of beating heart cells. Arthur Olson's team at the
Scripps Research Institute in La Jolla, California, produces models of
molecules; some are shown here partway through the printing process.

Adam Gardner, Molecular Graphics Lab at TSRI

Christoph Zollikofer witnessed the first birth of a Neanderthal in the modern
age. In his anthropology lab at the University of Zurich, Switzerland, in
2007, the skull of a baby Homo neanderthalensis emerged from a
photocopier-sized machine after a 20-hour noisy but painless delivery of
whirring motors and spitting plastic. This modern miracle had endured a
lengthy gestation: it took years for Zollikofer's collaborators to find
suitable bones from a Neanderthal neonate, analyse them with a
computed-tomography (CT) scanner and digitally stitch them together on the
computer screen. The labour, however, was simple: Zollikofer just pressed
'print' on his lab's US$50,000 three-dimensional (3D) printer.

A pioneer in the use of 3D printing for research, Zollikofer started 20 years
ago with a prototype that was even more expensive and required toxic
materials and solvents — limitations that put off most scientists. But now
newer, cheaper technology is catching on. Just as an inkjet printer sprays
ink onto a page line by line, many modern 3D devices spray material — usually
plastic — layer by layer onto a surface, building up a shape. Others fuse
solid layers out of a vat of liquid or powdered plastic, often using
ultraviolet or infrared light. Any complex shape can be printed, sometimes
with the help of temporary scaffolding that is later dissolved or chipped
away. These days, personal kits go for as little as $500, says Terry Wohlers,
a consultant and market analyst based in Fort Collins, Colorado — although
industrial systems cost an average of $73,000. Last year, he says, nearly
30,000 printers were sold worldwide, with academic institutions buying
one-third of those in the $15,000–30,000 price range.  Related stories

    Homegrown labware made with 3D printer

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    How to print out a blood vessel

More related stories

Early adopters are using the technology to investigate complex molecules,
fashion custom lab tools, share rare artefacts and even print cardiac tissue
that beats like a heart. At palaeontology and anthropology conferences, more
and more people are carrying printouts of their favourite fossils or bones.
"Anyone who thinks of themselves as an anthropologist needs the right
computer graphics and a 3D printer. Otherwise it's like being a geneticist
without a sequencer," says Zollikofer.

The printouts are yielding insights that are not possible with more
conventional methods. Neanderthal neonate fossils, for example, are extremely
rare, so Zollikofer did not want to risk copying his fragile specimen with
the usual plaster-casting methods. With the printout, however, Zollikofer
could explore the logistics of Neanderthal births. Along with the neonate
skull, he printed out an adult, female Neanderthal pelvis and literally
re-enacted a delivery. Some researchers had speculated that Neanderthals'
wide hips made labour easier than it is for modern humans, but Zollikofer's
experiment showed that the bigger skulls of Neanderthal neonates counteracted
that advantage (M. S. Ponce de León et al. Proc. Natl Acad. Sci. USA 105,
13764–13768; 2008). Like humans today, Neanderthals had the biggest heads —
and brains — possible at birth, giving them a jump-start on development.

In his work, Zollikofer swaps back and forth between printed models and
virtual ones. The computer models are good for calculating volumes or piecing
together bone fragments — researchers can position them in space without
gravity causing them to fall. But with the virtual models, he says, "you lose
the sensation of touch, and even a notion of the size of the fossils". The
physical models are far better for seeing how pieces should fit together in
the first place, he adds.

Molecular playground

Chemists and molecular biologists have long used models to get a feel for
molecular structures and make sense of X-ray and crystallography data. Just
look at James Watson and Francis Crick, who in 1953 made their seminal
discovery of DNA's structure with the help of a rickety construction of balls
and sticks.

Printouts of Neanderthal skulls from a child (left) and a neonate.

M. PONCE DELEÓN/C. ZOLLIKOFER/UNIV. ZURICH

These days, 3D printing is being used to mock up far more complex systems,
says Arthur Olson, who founded the molecular graphics lab at the Scripps
Research Institute in La Jolla, California, 30 years ago. These include
molecular environments made up of thousands of interacting proteins, which
would be onerous-to-impossible to make any other way. With 3D printers, Olson
says, "anybody can make a custom model". But not everybody does: many
researchers lack easy access to a printer, aren't aware of the option or
can't afford the printouts (which can cost $100 or more).

Yet Olson says that these models can bring important insights. When he
printed out one protein for a colleague, they found a curvy 'tunnel' of empty
space running right through it. The conduit couldn't be seen clearly on the
computer screen, but a puff of air blown into one side of the model emerged
from the other. Determining the length of such tunnels can help researchers
to work out whether, and how, those channels transport molecules. Doing that
on the computer would have required some new code; with a model, a bit of
string did the trick.

Software that lets researchers twist and turn such structures on a computer
screen is extremely useful, says Olson, but inadequate. Even the most
advanced software will let two atoms occupy the same space. And tinkering
with molecules inside a computer is a grind — it takes time for the computer
to re-render an object after every turn, and interpreting the pictures
requires mental effort. Fiddling with a physical model, on the other hand, is
more like play. "I don't have to think about it; I just do it," says Olson.

Olson is now trying to meld the tactile advantages of 3D printing with
computer power: he has tagged printed models with small paper labels that can
be recognized by a webcam, to create an 'augmented reality' view. In this
way, a user can play with a physical model, while at the same time using the
computer to explore aspects such as the potential energy of a given molecular
arrangement. Olson is also looking forward to using printers that can more
easily swap between rigid and bendable materials, so as to better replicate
molecular behaviour such as protein folding.  The cellular matrix

Printer 'inks' aren't limited to plastic. Biologists have been experimenting
with printing human cells — either individually or in multi-cell blobs — that
fuse together naturally. These techniques have successfully produced blood
vessels and beating heart tissue. The ultimate dream of printing out working
organs is still a long way off — if it proves possible at all. But in the
short term, researchers see potential for printing out 3D cell structures far
more life-like than the typical flat ones that grow in a Petri dish.

For example, Organovo, a company based in San Diego, California, has
developed a printer to build 3D tissue structures that could be used to test
pharmaceuticals. The most advanced model it has created so far is for
fibrosis: an excess of hard fibrous tissue and scarring that arises from
interactions between an organ's internal cells and its outer layer. The
company's next step will be to test drugs on this system. "It might be the
case that 3D printing isn't the only way to do this, but it's a good way,"
says Keith Murphy, a chemical engineer and chief executive of Organovo.

Other groups are using 3D printing of plastic or collagen to construct
scaffolds on which cells can grow. Carl Simon, a biologist with the
biomaterials group at the US National Institute of Standards and Technology
in Gaithersburg, Maryland, says that the intricacies of scaffold shape can
help to determine how cells grow, or how stem cells differentiate into
different cell types. With 3D printing, researchers have a very controlled
way to play with different scaffold configurations to see which work best.
One problem, however, is that most 3D printers can produce details on the
scale of only tens to hundreds of micrometres, whereas cells sense
differences at the single-micrometre level. Top-quality printers can
currently achieve 100-nanometre resolutions by using very short laser bursts
to cure plastics, says Neil Hopkinson, an engineer who works with 3D printing
at the University of Sheffield, UK, but this is "still very much in the lab".

Custom tools

In the meantime, basic plastic 3D printers are starting to allow researchers
to knock out customized tools. Leroy Cronin, a chemist at the University of
Glasgow, UK, grabbed headlines this year with his invention of 'reactionware'
— printed plastic vessels for small-scale chemistry (M. D. Symes et al.
Nature Chem. 4, 349–354; 2012). Cronin replaced the 'inks' in a $2,000
commercially available printer with silicone-based shower sealant, a catalyst
and reactants, so that entire reaction set-ups could be printed out. The
point, he says, is to make customizable chemistry widely accessible. His
paper showed how reactionware might be harnessed to produce new chemicals or
to make tiny amounts of specific pharmaceuticals on demand. For now, other
chemists see the idea as a clever gimmick, and are waiting to see what
applications will follow.

Researchers in other fields have found a more immediate use for the
technology. Philippe Baveye, an environmental engineer at Rensselaer
Polytechnic Institute in Troy, New York, uses 3D printing to make custom
parts for a permeameter — a device used to measure the flow of water through
soils. Although commercially available devices are fine for routine work, he
has often had to design his own for more precise research — a task that
previously required many hours on a lathe. Printing, he says, is much easier.

Perhaps more importantly, Baveye can share his product just by publishing the
design file. "The idea of being able to reproduce experiments described in
the literature is taking on a new meaning," he says.

Others agree that the real power of 3D printing lies in its ability to put
science into the hands of the many. Cronin wants to enable anyone — whether
in the far corners of Africa or in outer space — to print their own tiny drug
factory. Museums can already distribute exact copies of rare or delicate
fossils as widely as they wish. And students can print out whatever molecule
they're trying to come to grips with. "Through 3D printing,' says Olson, "the
ability to make physical models has become democratized."

    Nature 487, 22–23 (05 July 2012) doi:10.1038/487022a
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