Overview on the Design of Magnetically Assisted Electrochemical Biosensors

Abstract

Electrochemical biosensors generally require the immobilization of recognition elements or capture probes on the electrode surface. This may limit their practical applications due to the complex operation procedure and low repeatability and stability. Magnetically assisted biosensors show remarkable advantages in separation and pre-concentration of targets from complex biological samples. More importantly, magnetically assisted sensing systems show high throughput since the magnetic materials can be produced and preserved on a large scale. In this work, we summarized the design of electrochemical biosensors involving magnetic materials as the platforms for recognition reaction and target conversion. The recognition reactions usually include antigen-antibody, DNA hybridization, and aptamer-target interactions. By conjugating an electroactive probe to biomolecules attached to magnetic materials, the complexes can be accumulated near to an electrode surface with the aid of external magnet field, producing an easily measurable redox current. The redox current can be further enhanced by enzymes, nanomaterials, DNA assemblies, and thermal-cycle or isothermal amplification. In magnetically assisted assays, the magnetic substrates are removed by a magnet after the target conversion, and the signal can be monitored through stimuli-response release of signal reporters, enzymatic production of electroactive species, or target-induced generation of messenger DNA.

Keywords: DNA biosensor; aptasensor; electrochemical biosensor; homogeneous assay; immunosensor; magnetic particle.

Figure 1

(A) Schematic illustration of the HaloTag fusion protein modified MB-based immunosensing platform for the amperometric detection of p53-specific autoantibodies. Reproduced with permission [57]. Copyright 2016, American Chemical Society. (B) Schematic illustration of a magneto-controlled HRP-based multiplexed immunoassay for the detection of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP). Reproduced with permission [65]. Copyright 2011, American Chemical Society. (C) Schematic illustration of the bacterial capture and electrochemical detection based on antibody-modified MNPs and ALP. Reproduced with permission [67]. Copyright 2019, American Chemical Society. (D) Schematic illustration of the bacterial capture and electrochemical detection based on antibody-modified MNPs and ALP. Reproduced with permission [68]. Copyright 2020, Elsevier.

Figure 3

(A) Schematic illustration of circulating tumor cell (CTC) measurement in whole blood based on MNP isolation and rolling circle amplification signal amplification. Reproduced with permission [81]. Copyright 2019, American Chemical Society. (B) Schematic illustration of the immuno-hybridization chain reaction assay for human IgG detection. Reproduced with permission [82]. Copyright 2012, American Chemical Society.

Figure 4

(A) Schematic illustration of the p19-based amperometricmagnetosensor designed for the determination of miR-21. Reproduced with permission [91]. Copyright 2014, Wiley. (B) Schematic illustration of the magnetic-controllable electrochemical RNA biosensor. Reproduced with permission [94]. Copyright 2013, Elsevier.

Figure 5

(A) Schematic illustration of the proximity ligation assay with three-way junction-induced rolling circle amplification (RCA) for electrochemical detection of concanavalin A (Con A). Reproduced with permission [98]. Copyright 2014, American Chemical Society. (B) Schematic illustration of the biosensor for the detection of miRNA-21 based on DSN-assisted target recycling. Reproduced with permission [100]. Copyright 2016, Elsevier. (C) Schematic illustration of the label-free and immobilization-free electrochemical magnetobiosensor for 5-hmC assay. Reproduced with permission [101]. Copyright 2019, American Chemical Society. (D) Schematic illustration of a CRISPR/Cas12a-mediated dual-mode electrochemical magnetobiosensor for the determination of genetically modified soybean. Reproduced with permission [102]. Copyright 2021, American Chemical Society.

Figure 7

(A) Schematic illustrations for the electrochemical thrombin detection method that was based on a target-induced, proximity-binding-induced strand displacement reaction for hybridization chain reaction (HCR) formation of the MNPs/DNA polymers for efficient separation and signal amplification. Reproduced with permission [105]. Copyright 2021, Elsevier. (B) Schematic illustration of the amperometric miRNA biosensor designed using MBs as immobilized biomolecule carriers, a sandwich type hybridization assay, HCR amplification, and amperometric detection at disposable electrodes using the HRP/H₂O₂/HQ system. Reproduced with permission [106]. Copyright 2012, American Chemical Society. (C) Schematic illustrations for (part a) the dual 3D DNA nanomachine (DDNM) consisting of DNM-A and DNM-B, (part b) DDNM-mediated catalytic hairpin assembly (DDNM-CHA), and (part c) construction of an immobilization-free electrochemical biosensor for the detection of miRNA-21. Reproduced with permission [117]. Copyright 2021, American Chemical Society.

Figure 8

Schematic illustration of (A) preparation of the Fc-HPNs-pDNA. (B) Design principle of the circulating tumor DNA (ctDNA) biosensor. Reproduced with permission [119]. Copyright 2022, Elsevier.

Figure 9

(A) Schematic illustration of the biosensing mechanism for avian influenza virus that was based on enzyme catalysis in ultra-low ion strength media using a bare interdigitated electrode. Reproduced with permission [133]. Copyright 2014, American Chemical Society. (B) Schematic illustration of the Ag/CdO-NP-engineered magnetic electrochemical aptasensor for prostatic-specific antigen (PSA) detection. Reproduced with permission [135]. Copyright 2019, American Chemical Society. (C) Schematic illustration of the DNA-nanostructure-based magnetic beads for potentiometric aptasensing. Reproduced with permission [137]. Copyright 2019, American Chemical Society.

Figure 10

Schematic illustration of the magnetic MIPs for selective and label-free detection of SMX. Reproduced with permission [141]. Copyright 2016, American Chemical Society.

Figure 11

(A) Schematic illustrations for the preparation process of V₂O₅-NP-encapsulated liposomes (a) and norovirus detection principle (b). Reproduced with permission [147]. Copyright 2020, Elsevier. (B) Schematic illustrations for the magneto-mediated electrochemical sensor for exosomal proteins analysis based on host−guest recognition. Reproduced with permission [148]. Copyright 2020, American Chemical Society.

Figure 12

(A) Schematic illustrations for the one-to-many single-entity electrochemistry biosensing using satellite MN-DNA-Pt NP conjugates. Reproduced with permission [150]. Copyright 2020, American Chemical Society. (B) Schematic illustration of the optical and electrochemical virus detection method using plasmon nanocomposites and QDs. Reproduced with permission [159]. Copyright 2021, American Chemical Society. (C) Schematic illustration of the electrochemical immunosensor for the simultaneous detection of carcinoembryonic antigen (CEA) and α-fetoprotein (AFP) that were based on QDs/DNA nanochains as labels. Reproduced with permission [165]. Copyright 2013, Elsevier.

Figure 14

(A) Schematic illustrations for the DNA walker induced a “signal off” electrochemical sensor for tumor cells detection. Reproduced with permission [178]. Copyright 2022, Elsevier. (B) Schematic illustrations for the BLM assay based on BLM-mediated activation of Zn²⁺-dependent DNAzyme for the release of massive Fc-DNAs and preparation of MOF/GCE and the successive adsorption of Fc-DNAs by MOF/GCE for electrochemical measurement. Reproduced with permission [181]. Copyright 2021, Elsevier. (C) Schematic illustration of the ratiometric immobilization-free electrochemical sensing system for tumor exosome detection. Reproduced with permission [184]. Copyright 2021, American Chemical Society.

Figure 15

(A) Schematic illustration of the dual-bioreceptor immunoassay construction. Reproduced with permission [189]. Copyright 2020, Elsevier. (B) Schematic illustration of an enzyme-free electrochemical platform for miRNA-21 detection that was based on MBs and de novo growth of electroactive polymers. Reproduced with permission [196]. Copyright 2021, American Chemical Society. (C) Schematic illustration of the nanozyme-based assay for direct exosome isolation and detection from cell culture media. Reproduced with permission [197]. Copyright 2021, American Chemical Society. (D) Schematic illustration of the integrated nanochannel-electrode-based separation-detection system for the detection of bacteria. Reproduced with permission [200]. Copyright 2020, American Chemical Society.

Scheme 1

Schematic illustration of the strategies for magnetically assisted electrochemical biosensors involving magnetic materials as the platforms for recognition reaction and target conversion.

Figure 2

Schematic illustrations of the competitive immunoassay for conformationally altered p53 detection using Au@Pt/Au NP tags. Reproduced with permission [76]. Copyright 2020, American Chemical Society.

Figure 6

Schematic illustration of the phagomagnetic separation (A) of the bacteria followed by the double-tagging PCR (B) and the electrochemical magneto-genosensing (C). Reproduced with permission [103]. Copyright 2013, American Chemical Society.

Figure 13

Schematic illustrations for the DNA synergistic enzyme-mediated cascade reaction for homogeneous electrochemical bioassay. Reproduced with permission [172]. Copyright 2019, Elsevier.