Automated in Vivo Nanosensing of Breath-Borne Protein Biomarkers

Toxicology
and bedside medical condition monitoring is often desired
to be both ultrasensitive and noninvasive. However, current biomarker
analyses for these purposes are mostly offline and fail to detect
low marker quantities. Here, we report a system called dLABer (detection
of living animal’s exhaled breath biomarker) that integrates
living rats, breath sampling, microfluidics, and biosensors for the
automated tracking of breath-borne biomarkers. Our data show that
dLABer could selectively detect (online) and report differences (of
up to 103-fold) in the levels of inflammation agent interleukin-6
(IL-6) exhaled by rats injected with different ambient particulate
matter (PM). The dLABer system was further shown to have an up to
104 higher signal-to-noise ratio than that of the enzyme-linked
immunosorbent assay (ELISA) when analyzing the same breath samples.
In addition, both blood-borne IL-6 levels analyzed via ELISA in rats
injected with different PM extracts and PM toxicity determined by
a dithiothreitol (DTT) assay agreed well with those determined by
the dLABer system. Video recordings further verified that rats exposed
to PM with higher toxicity (according to a DTT assay and as revealed
by dLABer) appeared to be less physically active. All the data presented
here suggest that the dLABer system is capable of real-time, noninvasive
monitoring of breath-borne biomarkers with ultrasensitivity. The dLABer
system is expected to revolutionize pollutant health effect studies
and bedside disease diagnosis as well as physiological condition monitoring
at the single-protein level.