(157d) A Capacitive Electronic Tongue Based on Cyclodextrins for Rapid Assessment of Sepsis Biomarkers

Sepsis, a life-threatening medical condition and a major cause of in-hospital deaths, contributes to more than 250,000 deaths in the United States. Early administration of antibiotics and infusion of intravenous fluids is essential to decrease in-hospital mortality rates. Development of a device for early diagnosis of sepsis, monitoring the course of the disease, and monitoring septic patients’ response to the treatment is necessary for full recovery.

In this work, we employed cyclodextrins (CDs) to design an in-situ cross-reactive sepsis biosensor. CDs are oligosaccharides consisting of a hydrophobic cavity and a hydrophilic exterior. CDs are composed of six (αCD), seven (βCD), or eight (γCD) glucose units and they form host-guest inclusion complexes with various hydrophobic guest analytes. The formation and stability of inclusion complexes depend not only on the size of the cyclodextrin and guest analyte, but also the number and placement of hydrogen donors. Therefore, various cyclodextrin surfaces can be integrated to create a cross-reactive sensing array for recognition of a class of hydrophobic molecules.

For the first part of this project we improved the stability and reusability of our previously developed αCD biosensor by replacing gold-thiol bonds with diazonium salt chemistry on glassy carbon (GC) surface. We used polypropylene glycol (PPG) as a support for βCD and used the GC-carboxyphenyl-PPG:βCD surface for detection of a sepsis biomarker, cortisol. Our results showed that when βCD surface is introduced to the solution containing cortisol, βCD molecules leave the PPG surface to interact with cortisol in the solution. After use, the surface could be regenerated by reloading of βCD. We could successfully regenerate the GC-carboxyphenyl-PPG:βCD surface for ten times. Besides, the βCD/PPG-carboxyphenyl-GC surface was shown to be selective toward cortisol as opposed to uric acid, acetaminophen, and resveratrol. However, the selectivity of individual CD surfaces was still limited and development of cross-reactive CD sensor is necessary for clinical application.

In the second part of the project, we created five stable diazonium salt based CD biosensors with αCD, βCD, γCD, hydroxypropyl-βCD, and hydroxypropyl-γCD. We employed the developed CD biosensors for detection of various sepsis biomarkers. Linear discriminant analysis (LDA) and principal component analysis (PCA) were used to simplify the data, reduce variables, separate, and classify the data into different groups. The developed cross-reactive CD biosensor can potentially be used in urinary catheters for diagnosis and prognosis purposes.