A team led
by scientists at the California Institute of Technology (Caltech) have made the
first-ever mechanical device that can measure the mass of individual molecules
one at a time.
This new
technology, the researchers say, will eventually help doctors diagnose
diseases, enable biologists to study viruses and probe the molecular machinery
of cells, and even allow scientists to better measure nanoparticles and air
pollution.
The device, which
is only a couple millionths of a meter in size, consists of a tiny, vibrating
bridge-like structure. When a particle or molecule lands on the bridge, its
mass changes the oscillating frequency in a way that reveals how much the
particle weighs.
The new
instrument is based on a technique Roukes and his colleagues developed over the
last 12 years. In work published in 2009, they showed that a bridge-like nanoelectromechanical
device could indeed measure the masses of individual particles, which were
sprayed onto the apparatus. The difficulty, however, was that the measured
shifts in frequencies depended not only on the particle's actual mass, but also
on where the particle landed. Without knowing the particle's landing site, the
researchers had to analyze measurements of about 500 identical particles in
order to pinpoint its mass.
But with the
new and improved technique, the scientists need only one particle to make a
measurement. To do so, the researchers analyzed how a particle shifts the
bridge's vibrating frequency. All oscillatory motion is composed of so-called
vibrational modes. If the bridge just shook in the first mode, it would sway
side to side, with the center of the structure moving the most. The second
vibrational mode is at a higher frequency, in which half of the bridge moves
sideways in one direction as the other half goes in the opposite direction,
forming an oscillating S-shaped wave that spans the length of the bridge. There
is a third mode, a fourth mode, and so on. Whenever the bridge oscillates, its
motion can be described as a mixture of these vibrational modes.
The team
found that by looking at how the first two modes change frequencies when a
particle lands, they could determine the particle's mass and position. Traditionally,
molecules are weighed using a method called mass spectroscopy, in which tens of
millions of molecules are ionized -- so that they attain an electrical charge
-- and then interact with an electromagnetic field. By analyzing this
interaction, scientists can deduce the mass of the molecules.
The problem
with this method is that it does not work well for more massive particles which
have a harder time gaining an electrical charge. As a result, their
interactions with electromagnetic fields are too weak for the instrument to
make sufficiently accurate measurements.
The new
device, on the other hand, does work well for large particles. In fact, the
researchers say, it can be integrated with existing commercial instruments to
expand their capabilities, allowing them to measure a wider range of masses.
The
researchers demonstrated how their new tool works by weighing a molecule called
immunoglobulin, an antibody produced by immune cells in the blood. By weighing
each molecule, which can take on different structures with different masses in
the body, the researchers were able to count and identify the various types of immunoglobulin.
Not only was this the first time a biological molecule was weighed using a
nanomechanical device, but the demonstration also served as a direct step
toward biomedical applications. Future instruments could be used to monitor a
patient's immune system or even diagnose immunological diseases.
In the more
distant future, the new instrument could give biologists a view into the
molecular machinery of a cell. Proteins drive nearly all of a cell's functions,
and their specific tasks depend on what sort of molecular structures attach to
them -- thereby adding more heft to the protein -- during a process called
posttranslational modification. By weighing each protein in a cell at various
times, biologists would now be able to get a detailed snapshot of what each
protein is doing at that particular moment in time.
Another
advantage of the new device is that it is made using standard, semiconductor
fabrication techniques, making it easy to mass-produce. That's crucial, since
instruments that are efficient enough for doctors or biologists to use will
need arrays of hundreds to tens of thousands of these bridges working in
parallel.
