Clinical
applications for early-stage detection will become possible once validated on
humans
Researchers at the Indian Institute of Technology (IIT) Bombay have set the
stage to possibly sniff out in about a minute early-stage lung cancer from
exhaled breath. A two-member team led by Chandramouli Subramaniam from the
institute’s Department of Chemistry has developed a platform that detects
volatile organic compounds such as benzene, acetone, benzaldehyde and ethanol
in a gas phase at single molecular levels. These organic compounds in exhaled
breath are clinically established biomarkers for early stage lung cancer. The
same platform can also be used to monitor air-pollution levels or detect
explosives like TNT (trinitrotoluene).
The volatile
compounds have been detected using lab samples and clinical applications for
detecting early-stage lung cancer will become possible once validated on human
subjects. The results were published in the journal ACS Sustainable
Chemistry and Engineering.
Raman scattering
Since Raman
scattering is an inherently weak phenomenon, the researchers turned to
surface-enhanced Raman scattering to dramatically increase the sensitivity of
the platform such that it detects molecules at extremely low concentrations
using a small amount of sample. “In our studies, we were able to reliably
achieve sensitivities to the level of tens of molecules,” he says.
“We put the
molecule of interest on a gold or silver nanoparticle and then record the Raman
spectrum. When we shine light [laser] on the sample [molecule plus the
nanoparticle], the Raman spectrum of the molecule gets enhanced,” says Prof.
Subramaniam. “The intensity enhancement of Raman spectrum happens predominantly
through the interaction of localised electromagnetic field on the nanoparticles
surface with the vibrational modes of the molecule.”
The Raman
spectrum intensity increases tremendously — 10,000 million times — and this
allows the detection of molecules at very low concentration.
Scientists
across the world have so far been unsuccessful in applying surface-enhanced
Raman scattering to reliably detect molecules in gas or vapour phase.
In the case of
molecules present in liquid phase, the addition of the liquid to nanoparticles
allows the molecules to get adsorbed on the nanoparticle. Once adsorbed, the
Raman spectrum gets enhanced. But capturing the molecule and adsorbing it on
the nanoparticle has proven to be difficult when the molecule is in a gas
phase.
“This is what we
have solved using out technique,” he says. The challenge was overcome by
designing nanoparticles that behave as a cage to capture the molecule from the
gas phase.
When liquid
containing the nanoparticles is subjected to a thermal gradient (one end is
kept hot while the other is cold) the nanoparticles tend to migrate from the
hot end to the cold one. As a result, the concentration of nanoparticles at the
cold end increases. When the concentration of nanoparticles at the cold end
increases they self-assemble to form the cage. The cage then traps the
molecule, whether it is in a liquid or gas state. “Once the molecule gets
trapped, the Raman spectrum gets enhanced as the cage is made of
nanoparticles,” explains Prof. Subramaniam.
“Since we don’t
use any chemical or lithography to bring the nanoparticles together, there is
minimal interference to the signal. So we were able to detect the analyte
[chemical substance of interest] even when only few molecules of it were
present,” says Maku Moronshing from IIT Bombay and first author of the paper.
Validation of
platform
Since testing
the technique on human subjects for early-stage lung cancer detection is
riddled with ethical and clinical challenges, the researchers looked at
low-hanging fruit. This platform is particularly suited for the detection of
plastic explosives such as TNT and RDX.
To detect the
presence of explosives, air sample containing the molecules is forced into
water that contains nanoparticle cages; the molecules get trapped in the cages.
The presence of molecules is detected by shining laser and measuring the Raman
spectrum. The entire process of sample collection and signal acquisitions takes
about 2-3 minutes.
“As each
molecule has a characteristic signature, the presence of the molecule in the
sample tested can be ascertained by looking for specific signatures,” Prof.
Subramaniam. “Unlike in the case of early-stage lung cancer, validation for
explosives and air-quality monitoring will be easy as no ethical clearances are
required.”
The researchers
are now looking at incorporating data analytics into the platform to make the
system to read the signatures automatically. And they are also trying to reduce
the size of the platform to make it portable. “We are talking to companies to
build miniaturised Raman spectrometers so that this detection technique can be
truly portable and field-deployable,” he says
Source: THE HINDU- 17th September,2018
