Scott Manalis - Faster, smaller, more informative
Device can measure the distribution of tiny particles as they flow through a microfluidic channel.
Anne Trafton | MIT News Office
May 12, 2015
new technique invented at MIT can measure the relative positions of
tiny particles as they flow through a fluidic channel, potentially
offering an easy way to monitor the assembly of nanoparticles, or to
study how mass is distributed within a cell.
With further advancements, this technology has the potential to
resolve the shape of objects in flow as small as viruses, the
The new technique, described in the May 12 issue of Nature Communications,
uses a device first developed by MIT’s Scott Manalis and colleagues in
2007. That device, known as a suspended microchannel resonator (SMR),
measures particles’ masses as they flow through a narrow channel.
The original mass sensor consists of a fluid-filled microchannel
etched in a tiny silicon cantilever that vibrates inside a vacuum
cavity. As cells or particles flow through the channel, one at a time,
their mass slightly alters the cantilever’s vibration frequency. The
masses of the particles can be calculated from that change in frequency.
In this study, the researchers wanted to see if they could gain more
information about a collection of particles, such as their individual
sizes and relative positions.
“With the previous system, when a single particle flows through we
can measure its buoyant mass, but we don’t get any information about
whether it’s a very small, dense particle, or maybe a large,
not-so-dense particle. It could be a long filament, or spherical,” says
grad student Nathan Cermak, one of the paper’s lead authors.
Postdoc Selim Olcum is also a lead author of the paper; Manalis, the
Andrew and Erna Viterbi Professor in MIT’s departments of Biological
Engineering and Mechanical Engineering, and a member of MIT’s Koch
Institute for Integrative Cancer Research, is the paper’s senior author.
To obtain information about the mass distribution, the researchers
took advantage of the fact that each cantilever, much like a violin
string, has many resonant frequencies at which it can vibrate. These
frequencies are known as modes.
The MIT team came up with a way to vibrate the cantilever in many
different modes simultaneously, and to measure how each particle affects
the vibration frequency of each mode at each point along the resonator.
The cumulative sum of these effects allows the researchers to determine
not only the mass, but also the position of each particle.
“All these different modes react differently to the distribution of
mass, so we can extract the changes in mode frequencies and use it to
calculate where the mass is concentrated within the channel,” Olcum
The particles flow along the entire cantilever in about 100
milliseconds, so a key advance that allowed the researchers to take
rapid measurements at each point along the channel was the incorporation
of a control system known as a phase-locked loop (PLL). This has an
internal oscillator that adjusts its own frequency to correspond to the
frequency of a resonator mode, which changes as particles flow through.
Each vibration mode has its own PLL, which responds to any changes in
the frequency. This allows the researchers to rapidly measure any
changes caused by particles flowing through the channel.
In this paper, the researchers tracked two particles as they flowed
through a channel together, and showed they could distinguish the masses
and positions of each particle as it flowed. Using four vibrational
modes, the device can attain a resolution of about 150 nanometers. The
researchers also calculated that if they could incorporate eight modes,
they could improve the resolution to about 4 nanometers.
High-resolution mass imaging
This advance could help spur the development of a technique known as
inertial imaging, which makes use of several vibration modes to image an
object as it sits on a nanomechanical resonator.
Inertial imaging could allow scientists to visualize very small
particles, such as viruses or single molecules. “Multimode mass sensing
has previously been limited to air or vacuum environments, where objects
must be attached to the resonator. The ability to achieve this
dynamically in flow opens up exciting possibilities,” Manalis says.
The new MIT technology could enable very high-speed inertial imaging as cells flow through a channel.
“The suspended nanochannel technology pioneered by the Manalis group
is remarkable,” says Michael Roukes, a professor of physics, applied
physics, and bioengineering at Caltech, who is pioneering the
development of inertial imaging but was not part of this study.
“Their application of our approach for simultaneous monitoring
position and mass of the fluidic analytes opens up many new
possibilities,” Roukes says. “Extension of their efforts to fully employ
our recently developed method of inertial imaging will also permit
characterizing the shape of analytes, in addition to their mass and
position, as they flow through the nanochannels.”
Manalis’ lab is also using the new technique to study how cells’
densities change as they pass through constrictions. This could help
them to better understand how cancer cells behave mechanically as they
metastasize, which requires squeezing through small spaces. They are
also using the PLL approach to increase throughput by operating many
cantilevers on a single chip.
The research was funded by the U.S. Army Research Office, the Center
for Integration of Medicine and Innovative Technology, and the National