Microscale Redox Titrations for the Quantification of Surface-Captured Analytes: A Strategy for Cancer Biomarker Detection

Electrochemistry offers unparalleled versatility in the design of sensors for the low-cost detection of bioanalytes. In particular, the detection of redox-active analytes attached to electrodes enables the quantification of very minute amounts. Unfortunately, for biomolecules this often involves the construction of highly complex structures to carry out such assays. Often, mediated electron transfer helps circumvent difficulties in activating direct electron transfer from the electrode to the bioanalyte.
In this talk, I will discuss a radically different approach to detect surface-captured biomolecules using reactive redox titrations in a scanning electrochemical microscopy (SECM) configuration. Our approach allows to use 1) a non-electrode based capture medium to impart selectivity to the detection, and 2) a redox mediator-based detection at the microscale based on Surface Interrogation SECM (SI-SECM) to separately provide the quantification step. SI-SECM is a highly sensitive technique with a demonstrated capability of detecting down to 30 attomole of redox equivalents on a surface. In SI-SECM, an electrode-generated reactive redox mediator interacts with the chemistry of interest, generating a current transient from which kinetic and quantitation information is suitably extracted.
In our first application of this reactive titration concept, we will discuss the detection of glycosylated protein biomarkers for identifying early stages of leukemia and other cancers. This includes the development of a selective strategy to detect the presence of certain glycosylations using a low-cost capture agent and their subsequent quantification using the SI-SECM mediated approach. We will discuss the impact of pH, redox mediator, and other factors on the response, and will highlight fundamental differences observed when comparing free analytes to those in solution.