Nanoscale sensors as medical diagnostics

Nanoscale sensors are under development in the Kelley laboratories that report on the
presence of disease-related biomolecules. The ultimate goal of this project is to provide new
technologies that will enable the early diagnosis of cancer and other diseases where early
intervention is critical.

Nanoscale sensors for the detection of cancer biomarkers. Advances in genomic and
proteomic methods now allow classification of disease based on molecular profiling. The
detection of a molecular analytes and use of this type of information for disease diagnosis
requires methods with superior sensitivity and specificity, along with high-throughput.
We are developing new analytical methods with these properties that will permit the
direct readout of nucleic acid sequences and protein biomarkers. Novel technologies for
ultrasensitive DNA and RNA sensing have been developed in our laboratories that use
electrochemical methods for readout. Nanomaterials play an important role in this effort,
as detection sensitivity is greatly enhanced when measurements are performed at the
nanoscale. Our aim is to generate sensors applicable to the diagnosis of cancer and other
disease states. Members of this project team fabricate devices, develop reporter assays
and work with biological and clinical samples to validate new technologies. Substantial
collaboration with engineers and clinical researchers is an important part of this project.

Nucleic acids biosensor based on gold nanowires

Representative publications

"Direct Electrocatalytic mRNA Detection Using PNA-Nanowire Sensors." Anal. Chem.,

2008, in press.

"Ultrasensitive Detection of Enzymatic Activity with Nanowire Electrodes." M.A.

Roberts, S.O. Kelley, J. Am. Chem. Soc. 2007, 129, 11356.
 "An Intercalator Film as a DNA-Electrode Interface." B.J. Taft, M.A. Lapierre-Devlin,
B.J. Taft, S.O. Kelley, Chem. Comm., 2006, 9, 962.

"Amplified Electrocatalysis at DNA-Modified Nanowires." M.A. Lapierre-Devlin, C.

Asher, B.J. Taft, R. Gasparac, M.W. Roberts, S.O. Kelley, Nano Letters, 2005, 5, 1051.

"Ultrasensitive Electrocatalytic DNA Detection at 2D and 3D Nanoelectrodes." R.

Gasparac, B.J. Taft, M. Lapierre-Devlin, A.D. Lazareck, J.M. Xu, S.O. Kelley, J. Am.
Chem. Soc., 2004, 126, 12270.

"Electrocatalytic Detection of Pathogenic DNA Sequences and Antibiotic Resistance

Markers." M.A. Lapierre, M.M. O'Keefe, B.J. Taft, S.O. Kelley, Analytical Chemistry,
2003, 75, 6327.

Using Bacteria to Carry Nanoparticles Into Cells

Bacteria ferry nanoparticles into cells for early diagnosis, treatment

Researchers at Purdue University have shown that common bacteria can deliver a
valuable cargo of “smart nanoparticles” into a cell to precisely position sensors, drugs or
DNA for the early diagnosis and treatment of various diseases. The approach represents a
potential way to overcome hurdles in delivering cargo to the interiors of cells, where they
could be used as an alterative technology for gene therapy, said Rashid Bashir, a
researcher at Purdue’s Birck Nanotechnology Center.
The researchers attached nanoparticles to the outside of bacteria and linked DNA to the
nanoparticles. Then the nanoparticle-laden bacteria transported the DNA to the nuclei of
cells, causing the cells to produce a fluorescent protein that glowed green. The same
method could be used to deliver drugs, genes or other cargo into cells.

“The released cargo is designed to be transported to different locations in the cells to

carry out disease detection and treatment simultaneously,” said Bashir, a professor in the
Weldon School of Biomedical Engineering and the School of Electrical and Computer
Engineering. “Because the bacteria and nanoparticle material can be selected from many
choices, this is a delivery system that can be tailored to the characteristics of the receiving
cells. It can deliver diagnostic or therapeutic cargo effectively for a wide range of needs.”

Harmless strains of bacteria could be used as vehicles, harnessing bacteria’s natural

ability to penetrate cells and their nuclei, Bashir said. “For gene therapy, a big obstacle
has been finding ways to transport the therapeutic DNA molecule through the nuclear
membrane and into the nucleus,” he said. “Only when it is in the nucleus can the DNA
produce proteins that perform specific functions and correct genetic disease conditions.”

When the cargo-carrying bacteria attach to the recipient cell they are engulfed by its outer
membrane, forming “vesicles,” or tiny spheres that are drawn into the cell’s interior.
Once inside the cell, the bacteria dissolve the vesicle membrane and release the cargo.
The method might be used to take images of diseased tissues by inserting a cargo of
fluorescent molecules into tumors that are ordinarily too small to be detected, said Demir
Akin, a research assistant professor of biomedical engineering who specializes in
nanomedicine.

“These bacteria can potentially deliver specific molecules into a variety of cells,” said
Akin, the first author of a research paper appearing online this week in the journal Nature
Nanotechnology. Experiments were carried out in cultures of human cancer cells,
including intestinal, oral, liver, ovarian and breast cancer cells. The researchers also
tested their method on live mice and showed how the technique could be used to deliver
specific genes to various organs, including the liver and kidneys.

“The cells in the organs receiving the bacteria with nanoparticles made the intended
therapeutic proteins and emitted a light similar to a firefly’s glow,” Akin said. Certain
bacteria are naturally programmed to dissolve vesicle membranes, a critical step to
delivering the cargo. The nanoparticles are referred to as “smart” because they release
their cargo at precisely the right moment after entering the cell.

“At the same time that the bacteria are breaking up this vesicle membrane, the cargo
dislodges from the bacteria, which are both crucial steps in delivering this cargo,” Akin
said. The nanoparticles, which range in size from 40 to 200 nanometers - or billionths of
a meter - are attached to the bacteria with “linker molecules.”

“The use of commercially available polystyrene nanoparticles makes this delivery system
much simpler to implement than previous alternatives,” Bashir said. This new delivery
system also is more efficient than other experimental techniques using viruses and
bacteria.
“With other techniques, you can usually incorporate only one copy of your gene cargo to
each bacterium or virus particle,” Akin said. In the new approach, bacteria can carry
hundreds of nanoparticles, each of which can in turn carry hundreds of drug molecules,
depending on the size of the nanoparticles.

The approach also could make it possible to insert relatively large structures, such as
sensors and hollow filaments called carbon nanotubes, into the interiors of cells.

The sensors could make it possible to monitor activities inside a single cell for the early
detection of cancer and other diseases and to monitor the progress of disease and
response to drug therapy. The carbon nanotubes could be delivered into diseased cells
and then exposed to light, causing them to heat up and kill only those diseased cells, Akin
said.

The multidisciplinary research has been supported with funding from the Weldon School
of Biomedical Engineering. Research has been conducted by engineers and scientists at
the Birck Nanotechnology Center, the Bindley Bioscience Center and the Oncological
Sciences Center, all at Purdue’s Discovery Park, and the School of Veterinary Medicine
and Department of Food Science.

The Nature Nanotechnology paper was authored by Akin; Jennifer Sturgis and Kathy
Ragheb, both on the research staff at the Bindley Bioscience Center; Debby Sherman,
director of the Life Science Microscopy Facility; Kristin Burkholder, a doctoral student
in the Department of Food Science; J. Paul Robinson, a professor in the Weldon School
of Biomedical Engineering and the School of Veterinary Medicine; Arun K. Bhunia, a
professor of food microbiology in the Department of Food Science; Sulma Mohammed,
an assistant professor of cancer biology in the School of Veterinary Medicine; and
Bashir. A print version will appear in July.

by curiouscat Tags: Engineering, Health Care, Life Science, Nanotechnology, Students,

Universities
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Nanotechnology Breakthroughs for Computer Chips

Photo: Actual scanning

tunneling microscopy
images of the
naphthalocyanine molecule
in the “on” and the “off”
state. More images
IBM Unveils Two Major Nanotechnology Breakthroughs as Building Blocks for Atomic
Structures and Devices

IBM scientists have made major progress in probing a property called magnetic
anisotropy in individual atoms. This fundamental measurement has important
technological consequences because it determines an atom’s ability to store information.
Previously, nobody had been able to measure the magnetic anisotropy of a single atom.

With further work it may be possible to build structures consisting of small clusters of
atoms, or even individual atoms, that could reliably store magnetic information. Such a
storage capability would enable nearly 30,000 feature length movies or the entire
contents of YouTube – millions of videos estimated to be more than 1,000 trillion bits of
data – to fit in a device the size of an iPod. Perhaps more importantly, the breakthrough
could lead to new kinds of structures and devices that are so small they could be applied
to entire new fields and disciplines beyond traditional computing.

In the second report, IBM researchers unveiled the first single-molecule switch that can
operate flawlessly without disrupting the molecule’s outer frame — a significant step
toward building computing elements at the molecular scale that are vastly smaller, faster
and use less energy than today’s computer chips and memory devices.

In addition to switching within a single molecule, the researchers also demonstrated that
atoms inside one molecule can be used to switch atoms in an adjacent molecule,
representing a rudimentary logic element. This is made possible partly because the
molecular framework is not disturbed.

Related: Self-assembling Nanotechnology in Chip Manufacturing - More Microchip

Breakthroughs - Nanotechnology posts

by curiouscat Tags: Engineering, Nanotechnology, Products, Research, Students

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Nanoengineers Use Tiny Diamonds for Drug Delivery

Nanoengineers Mine Tiny Diamonds for Drug Delivery

Northwestern University researchers have shown that nanodiamonds — much like the
carbon structure as that of a sparkling 14 karat diamond but on a much smaller scale —
are very effective at delivering chemotherapy drugs to cells without the negative effects
associated with current drug delivery agents.
…
To make the material effective, Ho and his colleagues manipulated single nanodiamonds,
each only two nanometers in diameter, to form aggregated clusters of nanodiamonds,
ranging from 50 to 100 nanometers in diameter. The drug, loaded onto the surface of the
individual diamonds, is not active when the nanodiamonds are aggregated; it only
becomes active when the cluster reaches its target, breaks apart and slowly releases the
drug. (With a diameter of two to eight nanometers, hundreds of thousands of diamonds
could fit onto the head of a pin.)

“The nanodiamond cluster provides a powerful release in a localized place — an

effective but less toxic delivery method,” said co-author Eric Pierstorff, a molecular
biologist and post-doctoral fellow in Ho’s research group. Because of the large amount of
available surface area, the clusters can carry a large amount of drug, nearly five times the
amount of drug carried by conventional materials.

Nanotube-producing Bacteria Show Manufacturing Promise

Nanotubes may have high-tech applications, study involving UCR engineers reports
(December 7, 2007)

Print Quality Image: Right click image and select "Save Target As."

Genus Shewanella. The nanotube filaments produced by

biological means could point toward semiconductor manufacturing processes with a
smaller energy and environmental footprint. Image credit: Hor-Gil Hur, GIST
RIVERSIDE, Calif. — Two engineers at the University of California, Riverside are part
of a binational team that has found semiconducting nanotubes produced by living bacteria
— a discovery that could help in the creation of a new generation of nanoelectronic
devices.

The research team believes this is the first time nanotubes have been shown to be
produced by biological rather than chemical means. It opens the door to the possibility of
cheaper and more environmentally friendly manufacture of electronic materials.

Study results appear in today’s issue of the early edition of the Proceedings of the
National Academy of Sciences.

The team, including Nosang V. Myung, associate professor of chemical and

environmental engineering in the Bourns College of Engineering, and his postdoctoral
researcher Bongyoung Yoo, found the bacterium Shewanella facilitates the formation of
arsenic-sulfide nanotubes that have unique physical and chemical properties not produced
by chemical agents.

“We have shown that a jar with a bug in it can create potentially useful nanostructures,”
Myung said. “Nanotubes are of particular interest in materials science because the useful
properties of a substance can be finely tuned according to the diameter and the thickness
of the tubes.”
The whole realm of electronic devices which power our world, from computers to solar
cells, today depend on chemical manufacturing processes which use tremendous energy,
and leave behind toxic metals and chemicals. Myung said a growing movement in
science and engineering is looking for ways to produce semiconductors in more
ecologically friendly ways.

Two members of the research team, Hor-Gil Hur and Ji-Hoon Lee from Gwangju
Institute of Science and Technology (GIST), Korea, first discovered something
unexpected happening when they attempted to remediate arsenic contamination using the
metal-reducing bacterium Shewanella. Myung, who specializes in electro-chemical
material synthesis and device fabrication, was able to characterize the resulting nano-
material.

The photoactive arsenic-sulfide nanotubes produced by the bacteria behave as metals

with electrical and photoconductive properties. The researchers report that these
properties may also provide novel functionality for the next generation of semiconductors
in nano- and opto-electronic devices.

In a process that is not yet fully understood, the Shewanella bacterium secretes
polysacarides that seem to produce the template for the arsenic sulfide nanotubes, Myung
explained. The practical significance of this technique would be much greater if a
bacterial species were identified that could produce nanotubes of cadmium sulfide or
other superior semiconductor materials, he added.

“This is just a first step that points the way to future investigation,” he said. “Each species
of Shewanella might have individual implications for manufacturing properties.”

Myung, Yoo, Hur and Lee were joined in the research by Min-Gyu Kim, Pohang
Accelerator Laboratory, Pohang, Korea; Jongsun Maeng and Takhee Lee, GIST; Alice C.
Dohnalkova and James K. Fredrickson, Pacific Northwest National Laboratory, Richland,
Wash.; and Michael J. Sadowsky, University of Minnesota.

The Center for Nanoscale Innovation for Defense provided funding for Myung’s
contribution to the study.

Self-assembling Nanofibers Heal Spinal Cords in Mice

Self-assembling Nanofibers Heal Spinal Cords by Prachi Patel-Predd

An engineered material that can be injected into damaged spinal cords could help prevent
scars and encourage damaged nerve fibers to grow. The liquid material, developed by
Northwestern University materials science professor Samuel Stupp, contains molecules
that self-assemble into nanofibers, which act as a scaffold on which nerve fibers grow.

Stupp and his colleagues described in a recent paper in the Journal of Neuroscience that
treatment with the material restores function to the hind legs of paralyzed mice.
…
The new work is the first test for the material to heal spinal cord injuries in animals. And
Kessler says that it worked better than the researchers expected. The researchers
stimulated a spinal cord injury in mice and injected the material 24 hours later. They
found that the material reduced the size of scars and stimulated the growth of the nerve
fibers through the scars. It promoted the growth of both types of nerve fibers that make
up the spinal cord: motor fibers that carry signals from the brain to the limbs, and sensory
fibers that carry sense signals to the brain. What is more, the material encouraged the
nerve stem cells to mature into cells that create myelin–an insulating layer around nerve
fibers that helps them to conduct signals more effectively.

Micro-robots to ’swim’ Through Veins

Micro-robots take off

Photo: Transmission Electron Microscopy
photograph of an Escherichia coli bacterium with
flagella. The micro-robots are being developed to
mimic the swimming behaviour of E.coli.

Micro-robots that can ’swim’ through the

vascular and digestive systems of the human body
to perform medical tasks via remote control and,
in many cases, avoid invasive major surgery, are being developed at Monash University
following today’s announcement that the project has been funded through the Australian
Research Council’s Discovery Projects scheme.

Microbots Designed to Swim Like

Bacteria

By Bill Christensen

posted: 11 December 2006 11:00 am ET

 Transmission Electron Microscopy photograph of an Escherichia coli bacterium
with flagella. Micro-robots are being developed to mimic the swimming
behaviour of E.coli. Credit: Monash University

Tiny microrobots are under development at Monash University in Australia. A

remarkable micromotor will allow them to swim like an E. coli bacterium, which uses its
flagella to move around.

A flagellum is a long, structure composed of microtubules; bacteria use them in a whip-

like motion to move around.

James Friend's goal is to build a device no wider than 250 microns—that's the width of
two human hairs—that would be capable of swimming through the human body.

He and his team have already built a linear motor the size of a salt crystal. With a
$300,000 grant from the Australian Research Council, Friend believes that his team will
be able to reduce the motor to the necessary size within three years.

According to Friend, the main difference between the microrobot motor and a
conventional electromagnetic type is that the latter spins much faster but has much less
twisting force. In an email interview with Technovelgy.com, he remarked:

"The swimming robot idea in and of itself has indeed been around a long time—since at
least the 1950's anyway, and our motor is of a scale and has the performance
characteristics needed to actually make this sort of thing possible.

We're using ultrasonic motor technology here, which offer higher torques at lower
speeds."

Friend said, "We've operating larger mm-sized prototypes of the motor, and have a fairly
good handle on the analysis, which turns out to be quite complicated for twisted-beam
structures." (See a design for the prototype microrobot.)

The micromotor that Friend and his team have designed for their propulsion system
should be smaller overall than a similar microrobot propulsion system described in
November by Moshe Shoham (see Propulsion System for 'Fantastic Voyage' Robot).
Friend points out that his team has a "motor suitable for his [Shoham's] or our propulsion
system that is far smaller than the technology he's [Shoham's] wanting to use."

Ultimately, tiny microrobots would give surgeons the ability to avoid traumatic and risky
procedures in some cases. A remotely-controlled microrobot would extend a physician's
ability to diagnose and treat patients in a minimally invasive way.

Researchers at UCLA have gone in a different direction for a power source for a
microrobot; click on Musclebot: Microrobot with a Heart for an alternative to
micromotors. If you can't quite picture cell repair by medical nanorobots, click here for a
graphic view.
Other sources for this story include this article and this Monash University press release.

(This Science Fiction in the News story used with permission from Technovelgy.com —
where science meets fiction.)

Nanomachines:

Nanotechnology's Big Promise in a Small Package

By BRENT SILBY
Department of Philosophy
University of Canterbury

www.def-logic.com/articles

Introduction

Nanomachines are devices built from individual atoms. Some researchers believe that
nanomachines will one day be able to enter living cells to fight disease. They also hope to
one day build nanomachines that will be able to rearrange atoms in order to construct
new objects. If they succeed, nanomachines could be used to literally turn dirt into food
and perhaps eliminate poverty.

In this article I will outline some of the possible uses of nanomachines. I will then assess
some of the problems involved in producing such machines. One of the problems I will
look at is that of producing self-replicating machines. Will these machines be
controllable? Or will their reproduction escalate exponentially, thus putting our whole
planet in danger.

My conclusion will be that nanomachines offer humanity hope for the future, so the
research should be pursued. However, I will also suggest that the dangers involved in
producing self-replicating machines out weigh the potential gains and for this reason,
self-replicating machines should not be built.

What are Nanomachines?

As the terminology implies, nanomachines are extremely small devices. Their size is
measured in nanometers (a nanometer is about 1 billionth of a meter) and they are built
from individual atoms. During the 1980's and 1990's, futurist and visionary K. Eric
Drexler popularized the potential of nanomachines. For Drexler, the ultimate goal of
nanomachine technology is the production of the 'assembler'. The assembler is a
nanomachine designed to manipulate matter at the atomic level. It will be built with
extremely small 'pincers' (as small as a chain of atoms) which will be used to move atoms
from existing molecules into new structures. The idea is that the assembler will be able to
rearrange atoms from raw material in order to produce useful items. In theory, one could
shovel dirt into a vat and wait patiently for a team of nanomachine assemblers to convert
the dirt into an apple, a chair, or even a computer. The machines in the vat would have a
molecular schematic of the object to be built encoded in their 'memory'. They would then
systematically rearrange the atoms contained in the dirt to produce the desired item.

This is a representation of a nanomachine. The colored balls represent the individual

atoms that comprise the machine. (Picture from Twibell (2000), see references.)

Another goal of nanotechnology is to design nanomachines that can make copies of

themselves. The thought is that if a machine can rearrange atoms in order to build new
materials, it should also be able to build copies of itself. If this goal is achieved, products
produced by nanomachines will be extremely inexpensive. This is because the technology
(once perfected) will be self-replicating and will not require specific materials, which
might be rare and therefore cost money. Arthur C. Clarke has predicted that
nanotechnology will herald an end to conventional monetary systems.

If scientists manage to build nanomachines that can rearrange atoms, a world of exciting
possibilities will open up. Purpose designed nanomachines could be used to provide
breakthrough treatments for many diseases. Medical nanomachines programmed to
recognize and disassemble cancerous cells could be injected into the bloodstream of
cancer suffers, thus providing a quick and effective treatment for all types of cancer.
Nanomachines could be used to repair damaged tissue and bones. They could even be
used to strengthen bones and muscle tissue by building molecular support structures by
reassembling nearby tissue. With the ability to manipulate human cells at the atomic
level, medical science will rapidly devise treatments for most human illnesses. And since
nanomachines will be designed to make copies of themselves, these treatments will be
inexpensive and available to the entire population.

Food shortages and starvation will be a thing of the past if nanotechnology is perfected.
Nanomachines will be able to turn any material into food, and this food could be used to
feed millions of people world wide. Again, since the technology is self replicating, food
produced by nanomachines will be low cost and available to all.
As well as food, nanomachines will be able to build other items to satisfy the demands of
our growing population of consumers. Clothing, houses, cars, televisions, and computers
will be readily available at virtually no cost. Furthermore, there will be no concern about
the garbage produced by the new consumerist society because nanomachines will convert
it all back into new consumable goods.

Environmental problems such as ozone depletion and global warming could be solved
with nanotechnology. Swarms of nanomachines could be released into the upper
atmosphere. Once there, they could systematically destroy the ozone depleting
chlorofluorocarbons (CFCs) and build new ozone molecules out of water (H2O) and
carbon dioxide (CO2). Ozone (O3) is built out of 3 oxygen atoms, and since water and
carbondioxide both contain oxygen, the atmosphere contains a plentiful supply of oxygen
atoms. While the ozone construction teams are at work in the upper atmosphere, teams of
specialized nanomachines could be employed to destroy the excess CO2 in the lower
atmosphere. CO2 is a heat trapping gas, which has been identified as one of the major
contributors to global warming. Removing excess CO2 could help halt global warming
and bring the planet's ecosystem back into balance. This will benefit all species on Earth.

The perfection of nanotechnology and the production of nanomachines could herald a

new age for humanity. Starvation, illness, and environmental problems could quickly
come to an end. But how realistic are the goals of nanotechnology? Will it ever be
possible to produce machines the size of atoms? And if so, how feasible is it to build
nanomachines that can build objects from the atom up? Is it possible for nanomachines to
build copies of themselves? Before we get carried away with the promises of
nanotechnology, we should take a look at some of the problems that are yet to be solved.

Challenges to overcome

An important challenge to overcome is one of engineering. How can we physically build

machines out of atoms? Rearranging atoms into new shapes is essentially building new
molecules (nanomachines are sometimes called 'molecular machines') and this is no easy
task. Using contemporary technology to rearrange atoms has been said to be analogous to
assembling LEGO blocks while wearing boxing gloves. It is virtually impossible to snap
individual atoms together. All we can do is crudely push large piles of them together and
hope for the best. Scientists hope that once this initial challenge is overcome,
nanomachines will usher in a new age of molecular engineering and previous problems
will be a thing of the past. The new nanomachines will allow scientists to take off the
boxing gloves and accurately snap together individual atoms to build virtually any
molecule (within the laws of physics, of course).

This is nice in principle, but the question of how to build the first nanomachines remains.
Nanotechnologists think that it will be impossible to build the first nanomachines by
using large scale equipment (Chen C. 2000). Although progress is being made in the
miniaturization of integrated circuits and in the ultra-fine finishing of high quality optical
components, the large scale technology being used doesn't let us take off the boxing
gloves. There is a limit to how far down these machines can go. Super smooth lens
polishing is one thing, but moving individual atoms is something else all together.
Nanotechnologists need to get the boxing gloves off before they can build the first
nanomachines.

One way to work without boxing gloves is to patiently experiment with chemical
synthesis. The idea is to build molecules of increasing complexity by allowing atoms to
assemble or rearrange in natural ways. When molecules are mixed, they naturally form
new molecules. Through extensive experimentation, more control can be gained over
how molecules are formed. In time, it is conceivable that chemists will be able to position
individual atoms by using a range of techniques developed in chemical synthesis.

One of these techniques might involve the removal and relocation of hydrogen atoms.
This technique could be developed with knowledge of how hydrogen atoms interact with
other atoms. For example, it is known that the propynyl radical C3H3 (its made out of 3
carbon atoms and 3 hydrogen atoms) is 'attracted' to hydrogen. It is also known that this
radical has two ends. At one end there is a highly reactive radical, while at the other end
there is stable carbon. This feature means that chemists may be able to synthesize a larger
molecule with the propynyl radical at one end (the rest of the molecule would be built
from the stable carbon end). If this larger molecule was held on a positioning device, it
could be used to extract hydrogen from a range of different molecules by passing them by
the reactive radical (Merkle R.C. 1993).

Chemical synthesis is promising. In computer simulations, molecularly stable gears and

cogs have been formed through chemical synthesis.

A representation of nanogears made from graphitetubes billionths of a meter wide.

(Picture from the NanoGallery, see references)

If chemists and engineers succeed in building nanomachines the hope is that these
machines will be able to build a whole range of new molecules from the atom up. If all
goes well, scientists will never have to move atoms round while wearing boxing gloves
and the lengthy experimental process of chemical synthesis will no longer be required.
But will it be that easy?
In order to make new molecules, a nanomachine has to somehow 'grab' individual atoms
with its pincers and move them into new positions or attach them to other molecules. This
seems to be quite simple, but as George M. Whitesides (2001) points out, there are
serious problems that need to be overcome. Consider, for example, the fact that a
nanomachine's pincers will be made out of several atoms and will therefore be larger than
the individual atoms that it needs to move around. This means that the intricacy and
accuracy of the nanomachine's movement will be severely limited. It will be clumsy.
Assembling atoms would be like trying to piece together a mechanical wristwatch with
your fingers rather than small tweezers.

Another problem arises from the fact that individual atoms are compelled to 'attach' to
other atoms. Some atomic bonds can be extremely strong (especially with carbon atoms)
so pulling them apart will require large amounts of energy. Furthermore, since carbon
atoms attach to just about anything it seems likely that they will bond to the
nanomachine's pincers after they've been pried away from their original molecules
(Whitesides 2001). The only way to remove them could be to move them to molecules
that they are more strongly attracted to. But then there is the possibility that the entire
nanomachine will stick to the molecule. The situation is analogous to trying to build a
wristwatch with magnetized tweezers and screwdrivers. It can't be done because the
individual components stick to the tools.

Drexler et al (2001) brush aside these problems. They suggest that such concerns arise
from a misunderstanding of how nanomachines work. For example, the idea that
nanomachines use 'pincers' to move objects around is nothing more than a poor metaphor.
In reality, nanomachines might contain an active tip (like the hydrogen extractor
described above), which is no larger than the atom it is designed to manipulate. So
Whitesides' concerns about the size of a nanomachine's pincers are easily answered.
However, his concerns about the bonding of carbon atoms to nanomachines seem more
difficult to answer. Drexler attempts to bury the problem by citing theoretical work done
with the hydrogen extraction tool and by referring to experimental work done with
hydrogen atoms. He doesn't directly address concerns about manipulating carbon atoms.
This is important, because carbon is one of the most common atoms found on Earth and
will no doubt be involved if nanomachines are used to build new molecules. Progress
made with hydrogen might not translate easily to future work on carbon atoms.

Drexler does, however, mention some very promising work by Wilson Ho and Hyojune
Lee. In an experiment, Ho and Lee

"...used an STM tip first to locate two carbon monoxide (CO) molecules and one iron
(Fe) atom adsorbed on a silver surface in vacuum at 13 K. Next, they lowered the tip
over one CO molecule and increased the voltage and current flow of the instrument to
pick up the molecule; then they moved the tip-bound molecule over the surface-bound Fe
atom and reversed the current flow, causing the CO molecule to covalently bond to the
Fe atom, forming an iron carbonyl Fe(CO) molecule on the surface. Finally, the
researchers repeated the procedure, returning to the exact site of the first Fe(CO) and
adding a second CO molecule to the Fe(CO), forming a molecule of Fe(CO)2, which in
subsequent images of the surface appeared as a tiny "rabbit ears" structure, covalently
bound to the silver surface. Ho's group has also demonstrated single-atom hydrogen
abstraction experimentally, using an STM" (Drexler et al. 2001).

This type of work will hopefully lead to more complex manipulation of atoms, and this
could result in the development of tools that successfully 'pick and place' carbon atoms.

As our technological capacities develop, the promise of nanomachine technology

becomes more of a reality. We may one day see the successful creation of nanomachine
assemblers. These machines could end hunger and bring in a new age of advancement for
humanity. Nanotechnology offers us big promises in a small package. However, the
advantages it promises do not come for free. They come with some very big risks.

Big risks come in small packages

Cutting edge technology can take a while to catch on in the commercial world. However,
there is one place in which it catches on very quickly: The Military! During humanity's
history, technological research has moved fastest when there is a potential military
application. The danger is that this trend will continue with nanotechnology. Imagine the
possible uses of nanomachines in warfare. Self replicating nanomachines designed to
target and destroy organic material could be released over enemy territory reducing the
population to dust within a matter of hours. If these machines were designed to destroy
each other after (say) 24 hours, the enemy's country would be left empty and safe to be
invaded by military forces. Biological warfare would be a thing of the past since
nanomachine warfare would be so much safer (well, for the 'good guys' anyway).

The only way to prevent this use of nanomachines would be through international
agreements. Unfortunately, not all countries are willing to sign such agreements. And
those who do sign might be tempted to develop the technology in secret--just incase the
enemy is doing the same thing. Perhaps the most we could hope for would be a stalemate
situation like the one between the United States and the U.S.S.R during the cold war. If
both sides have the technology, they might be too nervous to use it, since they know that
the other side will retaliate.

A more serious danger of nanomachine technology involves the ability to self replicate.
Imagine that a nanomachine has the ability to make a copy of itself by rearranging the
atoms contained in any nearby matter. Since it is producing an exact copy of itself, it is
likely that the 'offspring' machine will be able to replicate. This is, after all, the way in
which nanotechnologists intend to keep the cost of nanomachines down.

So now we have 2 nanomachines that can replicate. One more cycle will produce 2 more,
which leaves a total of 4.

4 becomes 8.

8 becomes 16.
16 becomes 32, and so on.

After only 27 generations we would have over 134 million nanomachines on our hands.
Since they are molecular, this doesn't seem like a big number. But the number could keep
growing. After 39 generations there would be over 549 billion nanomachines on the
planet. The point is obvious. Without a way of controlling the reproduction of
nanomachines, the planet is in danger of being over run. Furthermore, since the
nanomachines are using the planet's resources as raw material with which to replicate, the
danger is that the planet could eventually be transformed into a seething mass of
nanomachines.

George Whitesides (2001) responds to this problem by pointing out that Earth has already
been ravaged by molecular machines--namely, biological cells. This is true. Earth was a
much different place 3.5 billion years ago before the emergence of life. Self replicating
cells have, over 3.5 billion years, completely transformed the planet. They have changed
the planet from a world of inorganic minerals with a CO2 rich atmosphere, to a world
that is perfect for biological life.

But this fact doesn't negate the danger in creating replicating nanomachines. In fact,
Whitesides has reminded us that it is possible for molecular machines to replicate
exponentially and transform the planet. If self replicating nanomachines get out of
control, then they could alter the planet to such an extent that it is no longer suitable for
biological life.

A possible solution to the problem is to limit the replicating abilities of nanomachines.

For example, a mechanism could be developed by which new nanomachines are tagged
with a number. This number could represent their generation. So, a nanomachine labeled
'gen 2' would produce offspring labeled 'gen 3', and their offspring would be labeled 'gen
4'. The replicating algorithm could be designed to only function if the generation number
is less than 4. Also, nanomachines with a generation number higher than 1 could be
encoded with a function that limits the number of reproductive cycles they can execute.
By building in these safeguards, we may be able to control the population of
nanomachines while at the same time allowing the existence of a number necessary to
facilitate some of the advantages mentioned earlier.

However, these safeguards may not be enough. The biological world has shown us that
evolution occurs and cannot be stopped. The same may be true of the nano-world.
Consider the idea that each time a nanomachine makes a copy of itself, there is a
possibility that an error could be made during the copying process. Such errors could be
very small--perhaps no larger than a single 'bit' of information. Now imagine what would
happen if an error occurred while a nanomachine was building its offspring's copying
mechanism. To be more specific, imagine that a single 'bit' error occurred when encoding
the function that limits the machine's replicative abilities. So, instead of checking that the
machine's generation number is less than 4, it checks to see that it is less than 40. When
this error is passed on to the machine's offspring, they will reproduce providing their
generation number is less than 40. Since the error will be passed on to each subsequent
generation, there will be a substantial explosion in nanomachine population. A single
error could have the potential to send the nanomachine population out of control. And the
more reproducing nanomachines there are, the greater the chance of another error
occurring in at least one of them.

The only way to avoid the problem of uncontrollable replication is to avoid building self-
replicating nanomachines. It may be true that self-replicating machines are the only way
to ensure a cheap supply of nanomachines, but the potential risks outweigh the benefits.
If nanomachines are built individually in labs, they will still be useful to cure disease and
they will still be potentially useful for rearranging molecules to build new objects such as
food. The only drawback is that none of it will come for free. Someone will still have to
pay for the construction of the machines, and this means that their products will have to
be paid for by consumers. So, poverty will not be eradicated. However, it could be that
producing food with nanomachines is faster and cheaper than conventional means, which
will mean that poverty may be eased a bit. Furthermore, if governments are willing to
invest in the technology, nanomachines may be able to be used to fix some of our
environmental problems by repairing the damage we've done to the atmosphere. So the
research is worth continuing.

Conclusion

Nanomachines offer humanity hope for the future. The idea that we could one day cure
diseases, fix the atmosphere, and reduce poverty in the world is an exciting one. If
scientists can overcome the technical difficulties involved in producing nanomachines
capable of these goals, then the fruits of their efforts will benefit us all. However, we
must be cautious. The temptation to build self-replicating machines is strong, since it will
give us an endless supply of new nanomachines at virutally no cost but self-replicating
machines have the potential to get out of control. The best efforts to limit their replicative
abilities may be insufficient, and our planet could be at risk of being over run by
machines that can consume anything to produce more machines at an astounding rate.

The benefits of building nanomachines that can manipulate matter are real and cannot be
ignored, so the technology should be pursued with vigor. However, the risks in producing
self-replicating machines outweigh the benefits, so I conclude that self-replicating
nanomachine technology should not be pursued. We should focus our efforts on
perfecting machines that can produce the benefits outlined in this article while never
building machines that can make copies of themselves.

© Copyright BRENT SILBY 2002

=ALL RIGHTS RESERVED=

References and further reading

Caudle, Neil (2000). "Gearing up for Nanomachines",

http://research.unc.edu/endeavors/spr2000/nano_side.htm
Chen, Chau-Jeng (Jeremy) (2000). "Nanotechnology--Magic of Century 21",
http://www.gwforecast.gwu.edu/documents/nanotech.doc

Drexler, K. Eric (1992). Nanosystems: Molecular Machinery, Manufacturing, and

Computation (New York: Wiley, 1992).

Drexler, K. Eric (1991). Unbounding the Future : Nanotechnology Revolution (New

York: William Morrow, 1991)

Drexler, K. Eric; Forrest, David; Freitas, Robert A. Jr.; Hall, J. Storrs; Jacobstein, Neil;
McKendree, Tom; Merkle, Ralph; Peterson, Christine (2001). "Many Future
Nanomachines: A Rebuttal to Whiteside's Assertion That Mechanical Molecular
Assemblers Are Not Workable and Not A Concern",
http://www.imm.org/SciAmDebate2/whitesides.html

Johnson, Matt (2001). "On The Brink of Nano Technology",

http://www.ce.org/vision_magazine/editions/2001/marapr/p19.asp

Merkle, Ralph C. (1993). "Molecular Manufacturing: Adding Positional Control to

Chemical Synthesis" in Chemical Design Automation News, Vol 8, Numbers 9 & 10,
September/October 1993. Also available at:
http://www.zyvex.com/nanotech/CDAarticle.html

The NanoGallery: http://nanozine.com/Dr.R.Smalley_Nobel.htm

Twibell, T.S. (2000). "Nano Law The Legal Implications of Self-Replicating

Nanotechnology", http://wwww.nanozine.com/nanolaw.htm

Whitesides, George M. (2001). "The Once and Future Nanomachine",

http://www.sciam.com/2001/0901issue/0901whitesides.html

"What is NanoTechnology?", http://www.nanozine.com/WHATNANO.HTM