Table 3.
Summary of particle-based optical assays for the detection of biomarkers.
| nanoparticles (NPs) | target length/biomarker | procedure | limit of detection [Ref.] |
| absorbance/enzyme-free | |||
| AuNPs (13 nm) | 30 nt/— | hybridization assay | 10 fmol [60] |
| AuNPs (13 nm) | 24 nt/— | colloidal stability of NPS in the presence of ssDNA or dsDNA | 100 fmol [63] |
| AuNPs (13 nm) | 24 nt/— | hybridization assay | 10 pmol [61] |
| AuNPs (13 nm) | 14 nt/— | salt-induced aggregation of unmodified AuNPs | 0.25 µM [65] |
| AuNPs (18 nm) | 20 nt/EGFR | salt-induced aggregation of unmodified AuNPs | 80 µM [66] |
| AuNPs (13 nm) | 41 nt/JAK2 | salt-induced aggregation of unmodified AuNPs | 0.2 µM [67] |
| AuNPs (13 nm) | 22 nt/— | a logic gate using two distinct target DNA molecules as input to discriminate SNPs using unmodified gold nanoparticles as indicators | 100 pmol [68] |
| AuNPs (10 nm) | 34 nt/— | the product of the catalytic strand displacement cascade disassembly AuNPs | 0.1 µM [69] |
| AuNPs (13 nm) | 14 nt/— | hybridization assay based on Au@LNA/DNA chimeras | 0.1 µM [70] |
| AuNPs (15 nm) | 15 nt/— | noncross-linking hybridization assay | 0.5 µM [62] |
| AuNPs (14 nm) | 395 nt/M. tuberculosis | noncross-linking aggregation of Au@DNA within rpoB locus | 30 µg/mL [71] |
| AuNPs (14 nm) | 16 nt/— | aggregation of unmodified AuNPs induced by CHA | 0.1 pM [72] |
| AuNPs (40 nm), microbeads (MBs, 2.8 μm) | 101 nt/KRAS | MBs@streptavidine hybridizes with the biotinylated target that is complementary to Au@DNA | 20 pM [73] |
| AuNPs (13 nm) | 22 nt/— | hybridization of peptide nucleic acid (PNA) and DNA prevents aggregation of nanoparticles | 1 µM [74] |
| AuNPs (13 nm) | 24 nt/CFTR | hybridization assay using a miniaturized optical monitoring system | 10 nM [75] |
| AuNPs (15 nm) | 22 nt/— | sequential hybridization to the target by allele-specific surface-immobilized capture probes and gene-specific Au@DNA | 500 ng genomic DNA [76] |
| AuNPs (15 nm) | 24 nt/— | hairpin-based amplification assay combined with lateral flow test | 10 pM [77] |
| AuNPs (13, 20, 40 nm) | 24 nt/— | aggregation of AuNPs by target-induced DNA circuits | 200 pM (HCR), 14 pM (CHA) [78] |
| AuNPs (30 nm), MBs (2–3 μm) | 27 nt/— | MBs@DNA, Au@DNA and target hybridization followed by magnetic separation and scanometric detection based on silver reduction for signal amplification | 500 zM (10 copies) [79] |
| AuNPs (13 nm) | 27 nt/— | sandwich assay between target, Au@DNA and a flatbed scanner; signal amplification by Ag reduction | 50 fM [80] |
| AuNPs (20 nm) | 84 nt/EGFR | hairpin assembly produces short DNA catalyst, which induces aggregation of unmodified AuNPs | 7.7 fM [81] |
| AuNRs | 24 nt/— | combination of HCR and unmodified gold nanorods for signal transduction | 1.47 nM [82] |
| AuNPs (13 nm) | 19 nt/BRCA1 | DNA-fueled molecular machine modulates the kinetics of Au@DNA aggregation | 0.26 nM [83] |
| AuNPs (15 nm) | 38 nt/— | target DNA hybridizes with Au@DNA, triggering a HCR that inhibits aggregation of AuNPs | 0.5 nM [84] |
| AuNPs (43 nm) | 22 nt/— | oriented aggregation of nanoparticles on Y-shaped DNA duplex | 10 pM [85] |
| AuNPs (40 nm), MBs (1.5 μm) | 30 nt/— | MBs@DNA, Au@DNA, target hybridization followed by magnetic separation and scanometric detection based on silver reduction for signal amplification | 100 amol [86] |
| AuNPs (15 nm) | 265 nt/hepatitis C | release and adsorption of free primers on the nanoparticle ensuring stability | 50 copies [87] |
| AuNPs (75 nm) | 22 nt/— | hybridization assay | 3 nM [88] |
| AuNPs (5, 10, 12, 20 nm) | 60 nt/KRAS | target-stabilized nanoparticles interacting with matching or mismatching probe lines in a microfluidic channel | 5 fmol [89] |
| AuNPs (13 nm), growth (40 nm) | 20 nt/— | DNA hybridization-mediated autocatalytic overgrowth of gold nanoparticles | 60 nM [90] |
| AgNPs (13 nm) | 22 nt/— | PNAs induce aggregation of citrate-stabilized AuNPs, which is prevented by DNA targets that complex selectively to PNA | 1 µM [91] |
| AuNPs (18 nm) | 12, 21, 42 nt/c-KIT | selective aggregation of PNA-stabilized AuNPs by target DNA and positively charged AuNPs through electrostatic interactions | 0.1 µM [92] |
| AuNPs (15 nm) | 30 nt/hepatitis A | combination of “click chemical” ligation chain reactions on gold nanoparticles and a magnetic separation to detect DNA and RNA | 50 zM [93] |
| AuNPs (13, 46, 63 nm) | 19 nt/BRCA1 | colorimetric detection based on sandwich assay | 10.85 fmol [94] |
| AuNPs (63 nm) | 70, 140 nt/EGFR | colorimetric detection based on sandwich assay combined with a preincubation step | 100 pM [95] |
| AuNPs (25, 53 nm) | 70, 140 nt/EGFR | chemical modifications of capture probes for a selective aggregation of nanoparticles | 5 nM [96] |
| SiO2 microparticles (MPs) and AuNPs | 22 nt/miR-21 | DNA I located on SiO2MPs captures miRNA, DNA II labeled with EDTA·2Na chelates Au3+ ions and regulates the growth of AuNPs | 8.9 fM [97] |
| absorbance/enzyme-aided | |||
| AuNPs (56, 13 nm) | 30 nt/— | modulation of the enzyme activity of thrombin on the surface of AuNPs relative to fibrinogen | 12 pM [98] |
| AuNPs (13 nm) | 112, 230, 316 nt/BRCA1 | allele‐specific PCR with thiol-labeled primers for the specific stabilization of unmodified AuNPs | 20 ng genomic DNA [99] |
| AuNPs (13 nm) | 40 nt/KRAS | selective ligation of two adjacent Au@DNA probes in the presence of a mutation | 74 pM [100] |
| AuNPs (14 nm) | 36, 48, 80 nt/— | nanoparticle amplification assisted by nicking endonuclease (NEase) for the detection of target DNA | 10 pM [101] |
| AuNPs (15 nm) | 24 nt/keratin 10 | isothermal strand displacement polymerase reaction to produce biotin–digoxin-labeled dsDNA in combination with a lateral flow strip | 0.08 pM [102] |
| AuNPs (20 nm) | 40 nt/— | aggregation of Au@DNA in the presence of single-strand-specific nuclease | 100 nM [103] |
| AuNPs (13 nm) | 22 nt/miR-122 | miRNA–probe heteroduplex as substrate of double strand nuclease, releasing a probe to aggregate the nanoparticles | 16 pM [104] |
| AuNPs (13 nm) | 43 nt/EGFR | coupling of invasive reactions with NEase-assisted nanoparticle amplification to produce linkers that prevent aggregation | 1 pM [105] |
| AuNPs (12 nm) | 33 nt/— | exonuclease III (Exo III)-induced cleavage of dangling ends on Au@dsDNA causing specific aggregation | 2 nM [106] |
| AuNPs (13 nm) | 23 nt/— | coupling of polymerase and NEase through an isothermal exponential amplification reaction to selectively detach DNA from Au@DNA | 46 fM [107] |
| AuNPs (13 nm) | 30 nt/KRAS | cyclic enzymatic cleavage based on Exo III in the presence of the target and a linker to induce aggregation of Au@DNA | 15 pM [108] |
| AuNPs (15 nm), MBs (1 μm) | 46 nt/BRCA1 | Au@DNA complexed with magnetic beads using horseradish peroxidase (HRP, enzymatic catalysis) and bovine serum albumin (BSA, nonspecific blocker) | 25 pM [109] |
| AuNPs (13 nm) | 34 nt/— | combination of padlock probe for rolling-circle amplification and NEase-assisted nanoparticle amplification | 1 pM [110] |
| AuNPs (42 nm) | 1130 nt/ chlamydia trachomatis | isothermal target and probe amplification for the hybridization of target amplicons and Au@DNA followed by RNA cleavage | 102 copies [111] |
| AuNPs (15 nm) | 16, 32 nt/ cytochromes P450 | single‐base primer extension in combination with noncrosslinking assay | 1 μM [112] |
| AuNPs (13 nm) | 16–80 nt/rtM204V | selective stabilization of unmodified AuNPs with nucleoside monophosphates after nuclease cleavage | 5 nM [113] |
| AuNPs (20 nm) | —/hepatitis B | ligation chain reaction to induce aggregation of Au@DNA | 20 aM [114] |
| fluorescence/enzyme-free | |||
| AuNPs (13 nm) | 26 nt/— | combination of AuNP fluorescence anisotropy and toehold-mediated strand-displacement reaction | 0.95 nM [115] |
| PS NPs (40 nm) | 57 nt/PKD1 | fluorescence-enhancement from nanoparticle-hybridized DNA complexes by nanostructured photonic crystals due to phase matching of excitation and emission | 50 aM [116] |
| Ag nanoclusters | 22 nt/miR-141 | target-triggered CHA and fluorescence enhancement of DNA–silver nanoclusters to detect miRNA | 0.3 nM [117] |
| AuNPs (5 nm) | 24 nt/— | distance-dependent modulation of electrochemiluminescence from CdS:Mn nanocrystals by gold nanoparticles. | 2.9 fM [118] |
| quantum dots (QDs, 10 nm) | 19 nt/miR-21 | p19-QDs with multiplex antenna capture miRNA-21/antimiRNA-21-Cy3 duplex to form a Förster resonance energy transfer (FRET) detection system between QDs and Cy3 | 0.6 fM [119] |
| MBs (1 μm) | 21 nt/miR-27a | dual toehold-mediated circular strand displacement amplification-based DNA circuit as fluorescent strategy for the detection of miRNA-27a | 0.8 pM [120] |
| fluorescence/enzyme-aided | |||
| AuNPs (5 nm) | 25 nt/— | enhancement of the electrochemiluminescence of a CdS film by a combination of an isothermal circular amplification reaction of polymerase, NEase and Au@DNA | 5 aM [121] |
| QDs (15 nm) | 21 nt/miR-196a2T | miRNA detection by coupling rolling circle amplification and NEase with streptavidin-coated QDs | 51 aM [122] |
| carbon dots (CDs, 8 nm) | 52 nt/H7N9 virus | carbon nanodot‐based fluorescent sensing strategy for H7N9 utilizing isothermal strand displacement amplification | 3.4 fM [123] |
| graphene QDs (5 nm) | 22 nt/miR-141 | pentaethylenehexamine- and histidine-functionalized graphene QD for a microRNA fluorescence biosensing nanoplatform coupled with molecular beacon double-cycle amplification | 0.43 aM [124] |
| QDs (5 nm) | —/miR-148, miR-21 | QD-assisted FRET signal generation | 42 fM [125] |
| optical microscopy | |||
| AuNPs (5 nm) | 22 nt/LET7 | differential interference contrast microscopy with a microarray platform comprising hairpins as capture probes and Au@DNA as signaling probe | 10 fM [126] |
| AuNPs (40 nm) | 45 nt/p53 | aggregation of oligonucleotide-modified organic nanospheres coded with fluorescent dyes (red/green/blue) | 200 fmol [127] |
| AuNPs (15 nm) | 15 nt/— | surface plasmon resonance imaging of Au@DNA in a PDMS–gold–glass hybrid microchip | 32 nM [128] |
| AuNPs (50 nm) | 28, 60, 90 nt/— | dark-field microscopy for the detection of head-to-tail Au@DNA hybridization | 4 pM (28 nt)/40 pM (60 nt) [129] |
| AuNPs (50 nm) | 46 nt/HeLa cells | dark-field microscopy combined with Rayleigh scattering spectrophotometry for single-particle detection | 10 HeLa cells [130] |