Medical Design Briefs - November 2021 - 35

However, in clinical trials, intramuscular
DNA vaccines have been limited in their
effectiveness because, unlike RNA or protein,
the DNA must find its way inside the
cell nucleus to work. By delivering the vaccine
into APC-rich skin rather than muscle,
the researchers reasoned that they
could increase the chances that the DNA
would enter the nucleus of an APC.
To make their delivery system, the team
attached DNA sequences encoding either
the SARS-CoV-2 spike protein or nucleocapsid
protein to the surface of nontoxic
nanoparticles.
Inside the nanoparticles
was an adjuvant - a molecule that helps
stimulate an immune response. Then, the
researchers coated a microneedle patch
with the vaccine nanoparticles.
The small rectangular patch contained
100 biodegradable microneedles, each
less than 1
⁄10 the diameter of a bee's
stinger, that could painlessly penetrate
the skin's outer layer. The researchers
tested the system in mice, showing that
the spike-protein-encoding microneedle
patch caused strong antibody and T-cell
responses, with no observable side effects.
Because the vaccine patches can be
stored at room temperature for at least 30
days without losing efficacy, they could be
an important tool for developing COVID19
vaccines with global accessibility, the
researchers say.
The authors acknowledge funding from
the National Natural Science Foundation
of China and the Key Laboratory for
Biomedical Effects of Nanomaterials and
Nanosafety, Chinese Academy of Sciences.
For more information, visit www.acs.org.
JILA Comb Breathalyzer Now More Sensitive to Disease
Biomarkers
The sensitivity of the
decade-old frequency comb
breathalyzer now detects
four additional biomarkers.
NIST
Washington, DC
JILA scientists have boosted the sensitivity
of their decade-old frequency comb
breathalyzer a thousandfold and can
detect additional biomarkers of disease
- four now, with the potential for six
more. When validated and engineered
into a portable design, the comb system
could offer real-time, noninvasive analysis
of human breath to detect and monitor
diseases. JILA is jointly operated by the
National Institute of Standards and
Technology (NIST) and the University of
Colorado Boulder.
The JILA system " fingerprints " chemicals
by measuring the colors and amounts
of light absorbed as a laser frequency
comb passes back and forth through
breath samples loaded into a mirrored
glass tube. Recent upgrades include a
shift in the light spectrum analyzed from
the near-infrared to the mid-infrared
band, where more molecules absorb light,
and advances in optical coatings and several
other technologies to achieve detection
sensitivity up to the parts-per-trillion
level.
As described in Proceedings of the National
Academy of Sciences, NIST/JILA Fellows Jun
Ye and David Nesbitt detected and monitored
four biomarkers - methanol
(CH3OH), methane (CH4), water (H2O),
and a form of heavy water (HDO) - in
the breath of a volunteer. These are indiMedical
Design Briefs, November 2021
Cov
Graduate student Qizhong Liang adjusts JILA's frequency comb breathalyzer, which identifies molecules
associated with disease based on colors and amounts of light absorbed inside the tube (left)
containing breath samples. (Credit: R. Jacobson/NIST)
cators of health conditions such as, in the
case of methane, intestinal problems.1
The researchers say it is feasible to
use the same apparatus to detect six
more chemicals: formaldehyde, ethane,
carbonyl sulfide, ethylene, carbon
disulfide, and ammonia. In addition,
extending the comb lasers further into
the infrared should greatly expand the
detection capability and enable the
identification of many hundreds of
trace breath chemicals.
JILA researchers demonstrated a prototype
comb breathalyzer in 2008 but
did not develop it further at that time.
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ToC
They have now refocused on it, prompted
by the possibility of eventually testing
for COVID-19.
" We are really quite optimistic and
committed to pushing this technology to
real medical applications, " Ye says.
The most widely used analytical technique
in breath research is gas chromatography
combined with mass spectrometry,
which can detect hundreds of
exhaled molecules but works slowly,
requiring tens of minutes. Most optical
breath tests approved by the U.S. Food
and Drug Administration detect only
one chemical. JILA is the only institu35

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Medical Design Briefs - November 2021

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