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Nano World Printing At Its Ultimate Limit

Photo by Bill Arsenault for Northwestern magazine
New York NY (UPI) Sept 24, 2004
The invention of printing about a thousand years ago transformed history, much as nanotechnology - science and engineering at the molecular scale - is expected to trigger a second Industrial Revolution. Now, nanotechnology and printing are converging in a technique growing in popularity worldwide that brings printing to its fundamental limit of detail only nanometers or billionths of a meter wide.

The devices that promise to unfurl from this convergence over the next five years are called nanoarrays - labs-on-a-chip that will be able to run billions of experiments simultaneously.

One day, you could take a few microliters of blood or saliva or urine, and analyze it for every possible thing with these arrays - every type of infectious disease - and get information out rapidly and with minimal invasiveness, Chad Mirkin, a chemist at Northwestern University in Chicago, told United Press International.

Mirkin and colleagues recently demonstrated a nanoarray that can detect the human immunodeficiency virus with more than 1,000 times more sensitivity than available with conventional tests - the first example of a clinical application of a nanoarray in detecting germs using real patient samples.

HIV-1 is the predominant strain of the virus responsible for the AIDS pandemic, co-researcher Steven Wolinsky, a physician at Northwestern University, told UPI. The results appear in the journal Nano Letters, released online Sept. 9.

Mirkin and his lab invented a technique to create nanoarrays in 1999 using infinitesimally small pen tips dipped into wells of ink made of virtually any solution - for instance, antibodies. Known as dip-pen lithography, it's the evolution of printing tools all the way to their theoretical limit, Mirkin said.

It's in use today in 18 different countries and 60 different labs. The number of groups using it has more than doubled every year of its existence.

A variety of techniques already exists to draw nano-scale features, but dip-pen lithography offers the unique ability to use multiple inks.

Others have to etch away at a surface and then backfill the scratches with one kind of ink, Mirkin explained. He founded NanoInk in Chicago, which has exclusive rights to commercialize Northwestern's dip-pen lithography technology.

This capacity for multiple inks grants dip-pen lithography enormous potential. Imagine printing 10 billion or so dots onto a chip, each dot made of a different ink that sticks to a specific molecule found in one or many diseases, anything from an infection to cancer or Alzheimer's disease.

Instead of engaging an entire medical laboratory to run battery upon battery of tests on a patient, requiring loads of equipment and lots of blood samples, such a nanoarray could run the entire gamut of exams at once using droplets of blood.

In biology, samples are precious. For instance, if you wanted a diagnostic tool for Alzheimer's, you want to look at cerebro-spinal fluid, and you can't take much more than milliliters of fluid, Mirkin said. So you want to be able to run as many tests with as small amounts of fluid as possible.

Along the same lines, nanoarrays could help decode a person's genome, or identify biowarfare agents, or test which potential drugs work best on a germ.

This is a very powerful technology with great potential in terms of biodefense applications or clinical applications, Wolinsky said.

I think the most exciting thing about the technique is that you can use it to put pretty much anything on any surface, as long as you can figure out the right surface chemistry, Albena Ivanisevic, a biomedical scientist at Purdue University in West Lafayette, Ind., told UPI.

She is using dip-pen lithography to print biological molecules, not onto a hard, inorganic surface, but onto actual living tissues. Her idea is to place chemicals onto retinas that can help them grow, perhaps allowing transplanted retinal tissue to correct vision diseases.

One complaint about dip-pen lithography, when it first emerged, was it was too slow. A single pen, naturally, would take quite a while to draw thousands of dots. The remedy became having lots of pens working at once.

Right now we have 1.3-million-pen arrays, and a 10-million-pen prototype, Mirkin said. You can stamp out a whole gene chip, a whole protein array, in one pass.

In their latest published work, Mirkin, Wolinsky and colleagues created 100-spot arrays, with antibodies that stick to HIV-1 on the spots, each of which is 60 nanometers across. The scientists tested plasma samples from eight HIV-1 infected men and 10 uninfected men using both the nanoarrays and conventional techniques. The nanoarrays scored correctly each time.

Only a microliter of plasma was needed to detect the virus - a thousand-fold less than with conventional AIDS tests. The small-volume requirement would be critical, for example, in testing whether newborns are infected by HIV-1 from their mothers, because removing large samples of blood from infants is undesirable.

To read the HIV nanoarray, the researchers used an atomic force microscope, which scans a surface by running a probe over it to detect bumps and grooves, much like running a needle over an old record.

They also added gold nanoparticles to HIV-1. Because HIV-1 sticks to antibodies on the nanoarrays, adding the particles made the resulting bumps even higher off the surface, allowing the AFM to read the results more easily.

The microscope represents a current limitation of nanoarrays, however, because using it requires dragging a probe to read thousands or more bumps - a time-consuming process. Mirkin said the hope is to employ other reading techniques that are electronically or optically based.

For instance, Wolinsky said the gold nanoparticles used in the HIV nanoarray are highly electrically conductive, so one can imagine reading it quickly using an electric current or voltage instead of the AFM.

In the future, Mirkin imagines nanoarrays that can be used to capture single cells or viruses for use in novel experiments.

You can begin to ask all sorts of interesting questions, he said. How does an individual virus particle interact with cells? Does an individual virus particle infect, or does it take more than one?

Are all virus particles created equal? Once in a cell, how do they move? We can literally study the interactions on a one-on-one basis instead of working at the large scales we do know and taking statistical averages.

Ivanisevic said she expects the first nanoarrays to find use in labs in at most the next five years, but really probably sooner.

All rights reserved. Copyright 2004 by United Press International. Sections of the information displayed on this page (dispatches, photographs, logos) are protected by intellectual property rights owned by United Press International. As a consequence, you may not copy, reproduce, modify, transmit, publish, display or in any way commercially exploit any of the content of this section without the prior written consent of by United Press International.

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