Highly Sensitive Biosensors Based on Biomolecules and Functional Nanomaterials Depending on the Types of Nanomaterials: A Perspective Review

Abstract

Biosensors are very important for detecting target molecules with high accuracy, selectivity, and signal-to-noise ratio. Biosensors developed using biomolecules such as enzymes or nucleic acids which were used as the probes for detecting the target molecules were studied widely due to their advantages. For example, enzymes can react with certain molecules rapidly and selectively, and nucleic acids can bind to their complementary sequences delicately in nanoscale. In addition, biomolecules can be immobilized and conjugated with other materials by surface modification through the recombination or introduction of chemical linkers. However, these biosensors have some essential limitations because of instability and low signal strength derived from the detector biomolecules. Functional nanomaterials offer a solution to overcome these limitations of biomolecules by hybridization with or replacing the biomolecules. Functional nanomaterials can give advantages for developing biosensors including the increment of electrochemical signals, retention of activity of biomolecules for a long-term period, and extension of investigating tools by using its unique plasmonic and optical properties. Up to now, various nanomaterials were synthesized and reported, from widely used gold nanoparticles to novel nanomaterials that are either carbon-based or transition-metal dichalcogenide (TMD)-based. These nanomaterials were utilized either by themselves or by hybridization with other nanomaterials to develop highly sensitive biosensors. In this review, highly sensitive biosensors developed from excellent novel nanomaterials are discussed through a selective overview of recently reported researches. We also suggest creative breakthroughs for the development of next-generation biosensors using the novel nanomaterials for detecting harmful target molecules with high sensitivity.

Keywords: biosensors; graphene; hybrid nanomaterials; nanoparticles; novel nanomaterials; transition-metal dichalcogenide (TMD) materials.

Figure 1

Highly sensitive biosensors based on biomolecules and functional nanomaterials.

Figure 2

Biosensors developed based on nanoparticles (NPs). (a) A schematic of a surface-enhanced Raman spectroscopy (SERS)-based biosensor based on Au and magnetic NPs to detect and distinguish two different prostate-specific antigens (PSAs) for the accurate diagnosis of prostate cancer, with TEM analysis of magnetic NPs with antibodies and formation of a sandwich structure, and SERS results for PSA solutions prepared with different ratio of complexed (c)-PSA and free (f)-PSA (reproduced with permission from Reference [47], published by the American Chemical Society, 2017). (b) A highly sensitive optical lateral flow assay (LFA) biosensor based on catalytic Pt NPs for the detection of the human immunodeficiency virus (HIV) p24 biomarker, and detection of colorimetric band formation on the LFA chip before and after addition of hydrogen peroxide to the Pt NPs on the chromogenic substrate (reproduced with permission from Reference [48], published by American Chemical Society (ACS), 2017, (https://doi.org/10.1021/acsnano.7b06229, further permission related to this material should be directed to the ACS)). (c) A schematic of an electrochemical eosinophil cationic protein (ECP) biosensor based on Au-coated magnetic NPs (reproduced with permission from Reference [50], published by Elsevier, 2017).

Figure 3

Biosensors based on carbon nanomaterials. (a) Schematic images of a DNA biosensor composed of carbon nanodots (CNDs) on a screen-printed disposable electrode to detect gene mutations, and differential pulse voltammetry (DPV) analysis of electrochemical detection performance (reproduced with permission from Reference [62], published by Elsevier, 2018). (b) An ultrasensitive electrochemical biosensor based on surface-modified graphene quantum dots (GQDs) to detect metal ions and small molecules, and DPV analysis of Hg(II), Cu(II), and Cd(II) detection (reproduced with permission from Reference [63], published by American Chemical Society, 2018). (c) A schematic of an electrochemical microfluidic DNA biosensor based on multiwalled carbon nanotubes (MWCNTs) (reproduced with permission from Reference [64], published by Elsevier, 2018).

Figure 4

Biosensors developed based on novel nanomaterials. (a) Electrochemical biosensor composed of high-quality 2H-MoS₂ to detect the VP40 matrix protein from the Ebola virus, and I–V characteristics for detecting the antigen–antibody reaction (reproduced with permission from Reference [74], published by John Wiley and Sons, 2019). (b) A schematic of the electrochemical biosensor composed of Ti₃C₂–MXene (few-atom-thick layer of transition metal carbides, nitrides, or carbonitrides) for sensitive and reproducible carcinoembryonic antigen (CEA) detection, and cyclic voltammogram obtained by using fabricated electrochemical biosensor for detection of different concentrations of target molecules (reproduced with permission from Reference [75], published by Elsevier, 2018). (c) A schematic of the LFA biosensor based on highly doped upconverting NPs (UCNPs) to detect PSA and type-A receptor 2 (EphA2) with high sensitivity and selectivity, and photo and fluorescence intensities of testing areas of different concentrations of PSA and EphA2 (reproduced with permission from Reference [77], published by American Chemical Society, 2018).

Figure 5

Biosensors based on hybrid NPs. (a) A dopamine biosensor composed of graphene oxide (GO)-encapsulated sandwich-structured UCNPs, and its sensitive dopamine detection performance obtained by fluorescence spectrophotometer (reproduced with permission from Reference [88], published by John Wiley and Sons, 2019). (b) Cyclic voltammograms of a flexible electrochemical biosensor based on an Au/MoS₂/Au hybrid nanofilm on a polyimide (PI), and its ability for flexibility acquired by using a fatigue tester (reproduced with permission from Reference [32], published by Elsevier, 2019). (c) Schematic images of flexible biosensing platform based on silver nanocubes (NCs) encapsulated by Prussian blue (AgNCs@PB) bio-ink, and the amperometric response following the addition of hydrogen peroxide (reproduced with permission from reference [96], published by John Wiley and Sons, 2016).