posted on 2021-08-25, 17:45authored byFarah C. Alimagham, Dan Hutter, Núria Marco-García, Emma Gould, Victoria H. Highland, Anna Huefner, Susan Giorgi-Coll, Monica J. Killen, Agnieszka P. Zakrzewska, Stephen R. Elliott, Keri L. H. Carpenter, Peter J. Hutchinson, Tanya Hutter
The brains of patients
suffering from traumatic brain-injury (TBI)
undergo dynamic chemical changes in the days following the initial
trauma. Accurate and timely monitoring of these changes is of paramount
importance for improved patient outcome. Conventional brain-chemistry
monitoring is performed off-line by collecting and manually transferring
microdialysis samples to an enzymatic colorimetric bedside analyzer
every hour, which detects and quantifies the molecules of interest.
However, off-line, hourly monitoring means that any subhourly neurochemical
changes, which may be detrimental to patients, go unseen and thus
untreated. Mid-infrared (mid-IR) spectroscopy allows rapid, reagent-free,
molecular fingerprinting of liquid samples, and can be easily integrated
with microfluidics. We used mid-IR transmission spectroscopy to analyze
glucose, lactate, and pyruvate, three relevant brain metabolites,
in the extracellular brain fluid of two TBI patients, sampled via
microdialysis. Detection limits of 0.5, 0.2, and 0.1 mM were achieved
for pure glucose, lactate, and pyruvate, respectively, in perfusion
fluid using an external cavity-quantum cascade laser (EC-QCL) system
with an integrated transmission flow-cell. Microdialysates were collected
hourly, then pooled (3–4 h), and measured consecutively using
the standard ISCUSflex analyzer and the EC-QCL system. There was a
strong correlation between the compound concentrations obtained using
the conventional bedside analyzer and the acquired mid-IR absorbance
spectra, where a partial-least-squares regression model was implemented
to compute concentrations. This study demonstrates the potential utility
of mid-IR spectroscopy for continuous, automated, reagent-free, and
online monitoring of the dynamic chemical changes in TBI patients,
allowing a more timely response to adverse brain metabolism and consequently
improving patient outcomes.