(Invited) Detection of Hydrophobic Analytes on a Nanomolar Scale Via Cyclodextrin Mediated Surfaces
Authors: Halpern Jeffrey Mark , Panahi Zahra , Merrill Mckenna , Marnoto Sabrina , Li Li , Ziino Emily 
Published: February 2020

Hydrophobic analytes can be difficult to detect electrochemically in a complex solution, especially in aqueous and biofluid solutions. In aqueous solutions, hydrophobic molecules are in small concentrations and often complexed, meaning they have a co-surfactant or co-solubilizing agent to dissolve the hydrophobic molecule. Also, hydrophobic metabolites are not typically electrochemically active (e.g., cholesterol and cortisol) or are only weakly electrochemically active (e.g., carotenoids and some acylcarnitines). Molecular recognition sensor surfaces that are designed for hydrophobic molecules can improve sensitivity by recruiting hydrophobic bioanalytes to the sensor surface [1]. An increase in sensitivity (25-100 fold) has been observed in measuring lipids and other hydrophobic molecules with chemically modified electrodes, such as cyclodextrin based sensors [2].

Cyclodextrin (CD) is a supramolecule that has a hydrophilic exterior and a hydrophobic pocket, and CD is capable of associating with hydrophobic molecules in a predictable behavior. However, previously developed of CD-sensors were for single-use applications and were evaluated in simple solutions without competing complexing agents [3]. Analysis of repeatability (i.e., reusability) of the sensor is rarely tested because it is difficult to remove the analyte from the CD pocket after a complex forms [4].

Two different CD style sensor paradigms will be included which will indicate sensitivity of nanomolar concentrations or lower of all analytes. The initial paradigm is CD directly grafted onto the surface, where the direct binding of the analyte is monitored [5]. This initial paradigm is a single-use sensor. The second paradigm contains a self-assembled monolayer complexed with cyclodextrin; in the presence of an analyte, the cyclodextrin unbinding from the surface will be monitored. This second paradigm has the capability of being reusable through reloading cyclodextrin on the surface.

Herein, we will present our progress towards a reusable and reproducible CD-sensors. We investigated hydrophobic metabolites including cortisol, beta-carotene, resveratrol, and others. We will use electrochemical impedance spectroscopy to monitor the host-guest complex of analyte-CD. We will report the detected sensitivity, reproducibility, and reusability. Further, we characterize the surfaces with AFM, XPS, and other surface analytical techniques.

This work is supported in part NSF (CBET 1638896) and NIH (P20 GM113131) Center for Integrated Biomedical and Bioengineering Research.

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