Antifouling (Bio)materials for Electrochemical (Bio)sensing

Abstract

(Bio)fouling processes arising from nonspecific adsorption of biological materials (mainly proteins but also cells and oligonucleotides), reaction products of neurotransmitters oxidation, and precipitation/polymerization of phenolic compounds, have detrimental effects on reliable electrochemical (bio)sensing of relevant analytes and markers either directly or after prolonged incubation in rich-proteins samples or at extreme pH values. Therefore, the design of antifouling (bio)sensing interfaces capable to minimize these undesired processes is a substantial outstanding challenge in electrochemical biosensing. For this purpose, efficient antifouling strategies involving the use of carbon materials, metallic nanoparticles, catalytic redox couples, nanoporous electrodes, electrochemical activation, and (bio)materials have been proposed so far. In this article, biomaterial-based strategies involving polymers, hydrogels, peptides, and thiolated self-assembled monolayers are reviewed and critically discussed. The reported strategies have been shown to be successful to overcome (bio)fouling in a diverse range of relevant practical applications. We highlight recent examples for the reliable sensing of particularly fouling analytes and direct/continuous operation in complex biofluids or harsh environments. Opportunities, unmet challenges, and future prospects in this field are also pointed out.

Keywords: (Bio)fouling; (bio)materials; complex biofluids; electrodes; hydrogels; peptides; polymers; thiolated self-assembled monolayers.

Figure 1

Steps involved in the preparation of an electrochemical nucleic-acid biosensor for BRCA1 determination fabricated onto a PEGylated polyaniline glassy carbon electrode (PANI/PEG/GCE). (a) Deposition of PANI nanofibers on the GCE; (b) PEG modification onto PANI nanofibers; (c) monoethanolamine (MEA) modification; (d) immobilization of DNA capture probe (C1) onto PANI/PEG/GCE; (e) MB interaction with C1; and (f) hybridization with target DNA (T2). Reproduced from [3] with permission.

Figure 2

Preparation of an immunosensor for B-IFN-γ using poly (3,4-ethylenedioxythiophene) poly (ethylene glycol) (PEDOT/PEG)-conductive hydrogels. (Step 1) Fabrication of the PEDOT/PEG nanocomposite hydrogel forming the PEG gel film on the electrode surface and electropolymerizing the PEDOT on the PEG gel. (Step 2) incorporation of specific monoclonal antibodies into the gel via PEDOT-COOH groups. (Step 3) selective immunorecognition of the target B-IFN-γ. (Step 4) Comparison of the PEDOT reduction peak current measured by CV before (blue) and after (red) B-IFN-γ binding. Reproduced from [34] with permission.

Figure 3

Electrochemical DNA sensor for BRCA1 determination involving the use of a zwitterionic peptide anchored to the conducting polymer PEDOT. Reproduced from [41] with permission.

Figure 4

Schematic illustration of antifouling aptasensing interfaces developed through self-assembly of zwitterionic peptides and the specific aptamers for (a) alpha-fetoprotein (AFP) determination onto a gold electrode and (b) IgE onto a macroporous Au substrate electrochemically fabricated on a GCE. Reprinted from (a) [6] and (b) [5] with permission.

Figure 5

Schematic illustration of three different antifouling thiolated monolayers: (a) thioaromatic DNA monolayer prepared by covalent immobilization of amino-functionalized capture probes onto p-mercaptobenzoic acid (p-MBA) monolayers; (b) ternary DNA monolayer composed of a SHCP, 1,6-hexanedithiol (HDT) and MCH; and (c) thiolated DNA tetrahedral nanostructures.

Figure 6

Fundamentals of the peptide-based electrochemical platforms functioning. (a) The target protease catalyzes the cleavage of the immobilized redox-labeled peptide (1), releasing the redox-containing fragment into solution (2) leading to a decrease of the SWV electrochemical signal. (b) Chemical structures of the different PEG spacer lengths evaluated in the redox-labeled peptide probe (number of EG units are denoted by PEG-x). Reproduced from (a) [72] and (b) [58] with permission.

Figure 7

Aptasensors prepared for PSA determinations using (a) conventional binary self-assembled monolayers (SAMs) composed of a thiolated specific aptamer and mercaptohexanol (MCH) and (b) a SAM prepared by covalent immobilization on the amine terminated aptamer onto 11-mercaptoundecanoic acid and thiolated sulfobetaine (structure displayed in (c)). Reproduced from [95] with permission.