Detection of Folic Acid Binding Protein in Human Serum using Folic Acid Modified Reduced Graphene Oxide Matrix

Lijie He, Institute Of Chemistry,faculty Of Mathematics and Natural Science, The Hebrew University Of Jerusalem, Jerusalem, Israel
Qian Wang, Institute of Electronics, Microelectronics and Nanotechnology (iemn), Université Lille 1
Daniel Mandler, Institute of Chemistry,faculty of Mathematics and Natural Science, The Hebrew University of Jerusalem, Jerusalem, Israel
Musen Li, Key Laboratory for Liquid-solid Structural Evolution and Processing of Materials, Shandong University, Jinan, China
Rabah Boukherroub, Microelectronics and Nanotechnology (iemn), Institute Of Electronics, Lille, Université Lille 1
Sabine Szunerits, Microelectronics and Nanotechnology (iemn), Institute of Electronics, Lille, Université Lille 1

The use of biosensors for the early diagnosis of diseases has become widely accepted. These sensors are based on the detection of disease markers (e.g. proteins over expressed in blood and serum) and provide a point-of-care diagnosis that is rapid and cheap with appropriate specificity and sensitivity. However, to obtain clinically relevant results, it is essential to perform the tests in human serum sample. The main difficulty of using serum as the analysis media is the high non-specific interaction between the sensors surface and the serum proteins. Moreover, biomarkers are present at very low concentrations in the early stage of cancer and necessitate the use of design devices with extremely high sensitivity. One way to overcome some of the current limitations of biomarker sensors is through the use of nanostructures, which can be integrated into sensing platforms. Next to particles, graphene-based sensors have shown promise for the sensitive and selective detection of key biomarker proteins.

We have developed in this work novel electrochemical sensing matrixes which allow the selective and sensitive detection of folic acid protein (FAP) (Figure 1). The study describes for the first time the use of electrophoretically deposited reduced graphene oxide electrodes, functionalized with folic acid as receptors for FP, as well as dopamine/bovine serum albumin (BSA) for limiting non-specific FP-interactions. Reduced graphene oxide provides a simple mean for integrating folic acid ligands via non-covalent interactions onto the transducer interface. Electrochemical readout through the peak current change in differential pulse voltammetry using [Ru(NH₃)₆]^3+/2+ as redox probe allows reaching a detection limit of 1 pM for FP. The possibility to use this sensor interface in human serum spiked with FP shows clearly that this system is suitable for biomedical analysis conditions. It is thus expected that this strategy holds promise for quantitative clinical analysis.