Research Progress in Small-Molecule Detection Using Aptamer-Based SERS Techniques

Abstract

Nucleic acid aptamers are single-stranded oligonucleotides that are selected through exponential enrichment (SELEX) technology from synthetic DNA/RNA libraries. These aptamers can specifically recognize and bind to target molecules, serving as specific recognition elements. Surface-enhanced Raman scattering (SERS) spectroscopy is an ultra-sensitive, non-destructive analytical technique that can rapidly acquire the "fingerprint information" of the measured molecules. It has been widely applied in qualitative and trace analysis across various fields, including food safety, environmental monitoring, and biomedical applications. Small molecules, such as toxins, antibiotics, and pesticides, have significant biological effects and are harmful to both human health and the environment. In this paper, we mainly introduced the application and the research progress of SERS detection with aptamers (aptamer-based SERS techniques) in the field of small-molecule detection, particularly in the analysis of pesticide (animal) residues, antibiotics, and toxins. And the progress and prospect of combining the two methods in detection were reviewed.

Keywords: SERS; aptamer; sensors; small molecule.

Figure 1

(A) Schematic diagram of the principle of SELEX [13]. (B) Schematic diagram of DNA origami nanotechnology [14]. (C) Schematic diagram of the DNA nanorobot based on DNA origami technology [15]. (D) The principle of the smart drug delivery system [15].

Figure 2

The annual distribution of aptamer selection studies (DNA, RNA, and MNA) [17].

Figure 3

Schematic representation of classic MBs-SELEX technology [28].

Figure 4

(A) The procedure of DNA Capture-SELEX [34]. (B) The procedure of RNA Capture-SELEX [34].

Figure 5

(A) Operational diagram of the microfluidic SELEX prototype device [37]. (B) Schematic illustration of the steps involved in the GO-SELEX procedure of aptamer identification [36].

Figure 6

Schematic representation of the principle of CE-SELEX [38].

Figure 7

(A) Principle of split aptamers regulated CRISPR-SERS LFA for 17β-estradiol detection. T line and C line represent the test line and control line of the strip, respectively [40]. (B) Graphic expression for label-free, enzyme-free, and signal-on analysis of profenofos based on target-switched HCR and the specific intercalation of NMM in G-quadruplex DNA [40].

Figure 8

Schematic representation of SERS and its enhancement mechanisms [45]. (A) SERS. (B) Electromagnetic enhancement mechanism. (C) Chemical enhancement mechanism.

Figure 9

Ultraviolet absorption spectrum of gold nanostars (Au NS) [50] (A) and TEM images (B,C). (D) Silver-shell gold-core nanoparticles (Au@Ag NPs) [51].

Figure 10

Overview of the general composition, structure, and design of SERS-tags, together with the function of each component [55].

Figure 11

(A) Scheme for the homogeneous DNA machine based on Exo III-assisted RCA cascade amplification for the intelligent detection of HIV/HCV DNA [61]. (B) Schematic representation of the principle for the analysis of atrazine based on the SERS aptasensor [47].

Figure 12

(A) Schematic diagram of LIBS combined with the DNN model [62]. (B) Schematic diagram of cascaded deep convolutional neural networks (CNNs) [63]. (C) Schematic diagram of the dynamic online acquisition device of Yali pears [64].

Figure 13

(A) Schematic diagrams of SERS aptasensor for different pesticide detections [79]. (B) SERS aptasensor technology for CPF detection based on bimetallic nanolabels and magnetic substrates [80]. (C) SERS aptasensor technology for simultaneous detection of ACE and CBZ mixed pesticides using Raman silent spectral window labeling molecules [81].

Figure 14

(A) Schematic diagram for the detection of levamisole using SERS-SELEX technology [89]. (B) Schematic diagram of SERS-active Au@Ag nanostars for CAP detection [87].

Figure 15

(A) Schematic diagram of a SERS sensor for tetracycline detection based on aptamer-gated HP-UiO-66-NH₂ with target-responsive release [94]. (B) Schematic diagram of a SERS aptasensor for tetracycline detection based on aptamer recognition and cascade DNA network amplification [95]. (C) Schematic diagram of a SERS-based nanobiosensor for the detection of tetracycline [96].

Figure 16

(A) Schematic diagram of the SERS sensor for the detection of OTA [101]. (B) Schematic diagram of the Fe₃O₄@Au magnetic nanoparticles (MGNPs) and Au-DTNB@Ag NPs [102]. (C) Typical Raman signal curves of OTA detection using the SERS-based aptasensor [102]. (D) Dose–response curve of OTA detection [102]. (E) Schematic illustration of the developed SERS/fluorescence dual mode nanosensor based on AuNFs for AFB1 detection. (F) The Raman and (G) fluorescence spectra of the nanosensor after incubation with different concentrations of AFB1. AuNFs/aptamer/DNA2 with different concentrations of DNA2. The corresponding calibration curve according to the SERS intensity at 1366 cm⁻¹ and fluorescence intensity at 670 nm [103].

Figure 17

(A) Schematic diagram of qualitative to semiquantitative trace detection via SERS-ICA [104]. (B) Schematic diagram of multipesticide aptamer sensor detection principle [105].