(700h) Nanostructured Polymeric Membranes for Overcoming Obstacles Associated with the Use of Exhaled Breath Acetone As a Non-Invasive Biomarker for Diabetes

The detection of volatile organic compounds (VOCs) in human breath as a portable, non-invasive diagnostic technique for human disease has been a long sought after goal. In particular, acetone breath concentrations have been correlated with blood glucose concentrations in diabetics to monitor the patientâ??s condition allowing for better control of their symptoms compared to blood glucose measurements and could potentially lead to better glucose monitoring compliance.

Unfortunately, practical implementation of acetone breath monitoring utilizing various portable instrumentation methods has been hampered by the interference of water. Accurate VOC detection in the absence of water has been achieved utilizing nanomaterials whose resistance to electrical current is altered by the adsorption of acetone as well as colorimetric approaches wherein acetone reacts chemically with a chromophore. The presence of water vapor can provide false positives by reacting with the detection media thus lowering the selectivity of the sensor, deactivating the catalyst used in the process, or reducing the sensitivity of response in the sensor, which greatly decreases the accuracy and precision necessary to be utilized in a medical device.

A less well-known phenomenon is responsible inconsistent findings in the literature is the significant change in breath acetone concentration that occurs during the brief period of patient exhalation (typically less than 1 minute). VOC content in human breath is governed by a material balance involving exhalation and transpiration from blood vessels lining the lungs. Transpiration, in turn, depends on both the thermodynamic partitioning of the acetone concentration (between the blood, vessel wall, and vapor phases) and dynamic convection through the vessel wall. Both thermodynamic and kinetic processes are governed by the physical make-up of the vessel wall. Consequently, real-time analysis (response times on the order of seconds) are essential to obtain accurate correlations between acetone and blood glucose and approaches based on long-term sample collection are susceptible to error.

We here demonstrate this phenomenon using real-time chemical sensing data obtained from patients utilizing a unique colorimetric approach that mitigates water interference. The method involves the use of nanostructured polymeric membranes that serve as both scaffolds and catalysts to drive highly sensitive and selective colorimetric responses to acetone in humid environments. The fundamental mechanism involves protection of acid catalyst sites within the membranes from de-protonation by altering their local pKa through the incorporation of specific organic acids. Successful clinical trials for the approach for diabetes management and assessment of vascular degeneration will be discussed.