Table 1. Recent Advances in GQDs along with Method of Preparation and Conjugation Chemistry for the Detection of Circulating Cell-Free Nucleic Acids Using Different Analytical Methodsa.
| Sample No. | GQDs used | Source and synthesis | Conjugation chemistry | Biomolecule (analyte) | Study | Inference | Analytical method | Ref |
|---|---|---|---|---|---|---|---|---|
| 1. | Ag/GQDs | - | - | Methylated DNA | Plasma | Ag/GQDs nano ink with strong electrical conductivity was employed to make a novel DNA nanosensor that precisely detects methylated DNA. | DNA genosensor | (135) |
| 2. | GQD/GO/AuNPs | - | - | miRNA-21, miRNA-155, miRNA-210 | Serum | GQD/GO/AuNPs biosensor designed for detection of miRNA-21, miRNA-155, and miRNA-210 with LODs of 0.04, 0.33, and 0.28 fM, respectively. | Electrochemical biosensor | (136) |
| 3. | GQDs | Solvothermal method | Carbodiimide coupling | miRNA-21 | MCF-7 cell line and serum | GQDs were synthesized using a solvothermal technique and coupled with carbodiimide chemistry to detect miRNA-21 at a LOD of 0.5 pM in breast cancer patients. | Ratiometric Fluorescent biosensor (FRET assay) | (137) |
| 4. | Ag/Au core–shell nanoparticles electrodeposited GQDs | Citric acid by Bottom-up approach (Pyrolysis) | - | miRNA-21 | Plasma | Ag/Au core–shell GQDs are fabricated using the pyrolysis method and are used for the early detection of cancer by detecting miRNA-21. | Electrochemical biosensor | (138) |
| 5. | GQDs | Graphene sheet | π–π stacking | miRNA-29a | - | The adsorption mechanism of miRNA on GQDs in solution is revealed using molecular dynamics simulations. The GQD model shows the speedy adsorption of miR-29a onto its surface for detection. | Molecular Dynamics Simulation | (139) |
| 6. | r-GQD@HTAB | - | - | Cell free Fetal DNA | Blood | Fluorescence GQDs are designed to detect the target DNA selectively with a detection limit of 0.082 nM. | Fluorescence biosensor | (140) |
| 7. | GCQDs | Carbon fibers + H2SO4 + HNO3 by Ultrasonication | π–π stacking | miRNA-21 | Plasma | Ultrasensitive electrochemiluminescence GCQD synthesized by ultrasonication technique and π–π interaction coupling for specific detection of miRNA-21. | Electrochemiluminescence biosensor | (91) |
| 8. | GQDs | By oxidized Graphene sheets + conc. Sulfuric acid + Nitric acid | π–π stacking | Methylated DNA | - | In this study, it was found that the interaction of GQDs could bind to DNA fragments and lead to different fluorescence patterns. Due to their differing interaction mechanisms, a comparison of these two effects may enable us to discriminate between DNA that has been methylated and unmethylated. | Fluorescence biosensor | (104) |
| 9. | GOQDs | Graphene oxide | - | miRNA-21 | Serum | CL detection technology using GOQDs constructed to achieve highly sensitive and selective detection of microRNA-21. It shows the detection limit is 1.7 fM. | Chemiluminescence biosensor | (141) |
| 10. | GQDs | Citric acid By Pyrolysis | EDC-NHS | DNA | Serum | ECLGQDs are prepared by the pyrolysis method, designed for target DNA detection by a cycling amplification strategy with a detection limit of 0.1 pM. | Electrochemiluminescence biosensor | (92) |
| 11. | GQDs | - | - | miRNA-141 | - | A universal donor/acceptor-induced ratiometric PEC paper analytical device with HDHC is suggested for the biosensing of miRNA-141 using an integrated photoanode (GQD) and photocathode. | Photoelectrochemical (PEC) technique | (142) |
| 12. | GQDs | Citric acid By One-step Hydrothermal method | EDC-NHS | miRNA-541 | Plasma | Using the hydrothermal method GQDs were prepared. This label-free DNA assay was developed to detect microRNA-541. The results were analyzed using differential pulse voltammetry. | Electrochemical genosensor | (143) |
| 13. | GQDs | Citric acid By Pyrolysis | EDC-NHS | Mutant DNA | Serum | For the detection of mutant DNA, ultrasensitive enzyme-free signal amplification is used with a detection limit of 0.8 pM. | Resonance light scattering method | (144) |
| 14. | PEHA and Histidine functionalized GQDs | Citric acid by pyrolysis | Carbodiimide coupling | miRNA-141 | Serum | The PEHA-GQD-His was used for the fabrication of fluorescence. Its fluorescence linearly reduces with increasing microRNA-141 concentration, with the detection limit of 4.3 × 10–19 M. | Fluorescence biosensor | (145) |
| 15. | AuNF-GQDs | l-Glutamic acid by Bottom-up method | EDC-NHS | miRNA-34a | H9C2 cell line | The designed AuNF-GQDs biosensor detects miRNA-34a in vitro and in vivo. FRET occurred due to spectral overlap between the emission band of GQDs-ssDNA and the absorption band of AuNF-ssDNA | FRET | (146) |
| 16. | Amino-functionalized GQDs | Direct pyrolysis of Citric acid | - | miRNA-25 | Plasma | The electrochemical genosensor is fabricated for microRNA-25 detection based on the electrochemical response of PBP as an electroactive label. | Electrochemical genosensor | (147) |
| 17. | GQDs | Calcined petroleum coke + Concentrated sulfuric acid + Nitric acid | π–π stacking | DNA | - | Coke-derived GQDs were developed for DNA detection. GQDs functioned as fluorescence resonance energy transfer (FRET) acceptors for DNA detection down to 0.004 nM. | Fluorescence biosensor | (105) |
| 18. | B-GQDs | Electrolytic exfoliation of Boron-doped graphene rods | EDC-NHS | miRNA-20a | Boron-doped GQDss (B-GQDs) with an atomic percentage of boron of 0.67–2.26% were synthesized by electrolytic exfoliation of B-doped graphene rods to detect target miRNA-20a. The detection limit reached is 0.1 pM. | Electrochemiluminescence | (148) | |
| 19. | GQD-PEG-P | Graphite oxide | Carbodiimide coupling | miRNA-155 | MCF-7 cell line | The proposed GQD-PEG-P was efficient in differentiating cancer cells from other cells by the use of blue fluorescence GQDs for the detection of miRNAs. | Fluorescence biosensor | (149) |
| 20. | GQDs | Graphite by Hydrothermal method | π–π stacking | miRNA | - | A sensor for the detection of specific miRNA sequences was developed, which was based on GQDs and UCNP@SiO2-ssDNA. By relative emission measurements compared to a reference, it was possible to determine the presence of complementary miRNA target sequences. | Fluorescence sensor | (150) |
| 21. | Graphene aerogel/gold nanostar | Graphite | - | Circulating cell-free DNA | Serum | For the detection of circulating DNA, a GQDs electrochemical biosensor was devised from graphite with a detection limit of 3.9 × 10–22 g mL. | Electrochemical biosensor | (151) |
| 22. | Graphene oxide | Graphite Powder | EDC-NHS | miRNA-155 | - | The electrochemical sensor was developed using conformational changes in biomolecular receptors for miR-155 detection with detection limits of 5.2 pM. | Electrochemical biosensor | (93) |
| 23. | Graphene oxide | - | - | miRNA-155 | Plasma | For the detection of circulating miR-155. With a detection limit of 0.6 fM, indicating that the nano biosensor had great selectivity. | Electrochemical nanobiosensor | (152) |
| 24. | GQDs/PTCA-NH2 | By refluxing Graphene Oxide | π–π stacking | miRNA-155 | Cell lines (HeLa and HK-2) | GQDs are produced by refluxing graphene oxide and linked using π–π stacking. With further immobilization of the target miRNA, a noticeable decrease in the ECL signal was observed. | Electrochemiluminescence biosensor | (153) |
| 25. | GQDs | - | EDC-NHS | miRNA-155 | Serum | These GQDs biosensors were modified by HRP and can effectively catalyze the oxidation reaction of 3,3,5,5-tetramethylbenzidine mediated by H2O2. Due to GQDs and enzyme catalysis, the biosensor can sensitively detect miRNA-155 between 1 fM to 100 pM. | Electrochemical biosensor | (133) |
| 26. | GQDs | Citric acid by Bottom-up method (pyrolysis) | π–π stacking | miRNA-155 | Pyrene and fluorescent dye dual labeled MBs were employed to make GQDs via π–π interactions, triggering FRET and generating fluorescent intensity changes as signals for target miRNA detection with a LOD of 0.1 nM to 200 nM. | Fluorescence biosensor | (154) | |
| 27. | Nanoscale graphene oxide | Graphene Oxide By Ultrasonication | - | miRNA-10a/b | Cell lines (4T1 and MCF-7) | To detect miRNA, a fluorescence-based device was developed. The fluorescence of the probe strands labeled with a molecular fluorescent dye is completely quenched by the graphene oxide surface but is regained with target molecules by hybridization. Thus, specific detection of miRNA was performed. | Fluorescence | (155) |
| 28. | Nanoscale graphene Oxide | Graphene Oxide | - | miRNA-21 | Serum | A biosensor designed using GO for the detection of miRNAs. In the presence of the target miRNA, surface-adsorbed fluorophore-labeled nucleic acids can be desorbed from the nGO surface, recovering their fluorescence and enabling the precise identification of circulating oncomiR. | Fluorescence biosensor | (156) |
| miRNA-141 | ||||||||
| 29. | GQDs | Graphite powder + H2S4 + HNO3by Oxidation | π–π interactions | DNA | - | Using rGQDs and GO as fluorescent sensing platforms, a sensitive sensing system for quantitative DNA analysis can be constructed. | Fluorescence biosensor (FRET) | (157) |
| 30. | Reduced Graphene oxide | Graphene oxide By Sonication | EDC-NHS | miRNA-141 miRNA-29b-1 | - | Using reduced graphene oxide, an electrochemical immunosensor for miRNA detection was produced. An electrochemical ELISA-like amplification step was performed after the DNA hybrids were introduced. As a result, with a detection limit in the fM range. | Electrochemical immunosensor | (158) |
| 31. | Graphene nanosheet | Graphene | Streptavidin–Biotin | miRNA-21 | - | An electrochemical biosensor for sensitive detection of miRNA-21 was designed, and the synthesized complex DNA–AuNPs–LNA hybridizes with target miRNA. The electrochemical method was used for detection with a detection limit of 0.06 pM. | Electrochemical biosensor | (86) |
| 32. | GQDs | Graphene | EDC-NHS | lncRNA | Plasma | GQDs are used for the detection of target lncRNAs by sequence-specific biotinylated oligonucleotide probes conjugated to streptavidin-labeled GQDs. | Fluorescence | (159) |
a
Ag/GQD: Silver-graphene quantum dots, AuNPs: Gold Nanoparticles, GCQD: Graphene Carbon Quantum Dot, B-GQDs: Boron doped Graphene Quantum Dots, GOQDs: Graphene Oxide Quantum Dots, GQD-PEG-P: Graphene Quantum Dots - Polyethylene Glycol - Porphyrin, MWCNTs: Multiwalled carbon nanotubes, r-GQD@HTAB: reduced graphene quantum dots modified with hexadecyl trimethylammonium bromide, PBP: p Biphenol, py-MBs: pyrene-functionalized molecular beacon probes.