Table 2.
Analytical parameters of clinical sensors and biosensors recently used for cancer and cardiac biomarkers
| Analyte detected (matrix) | Sensor type | Linear range | LODa | Sensitivity (slope) | Additional information | References | 
|---|---|---|---|---|---|---|
| CANCER BIOMARKERS | ||||||
| PSA (serum samples) | Electrochemical immunosensor based on CdS quantum dot-functionalized graphene sheets | 0.005–10 ng mL−1 | 0.003 ng mL−1 | RSD = 7.9%; n = 5 | [55] | |
| PSA (serum samples) | Electrochemical immunosensor based on graphene–Co hexacyanoferrate nanocomposites (GCE) | 0.02–2 ng mL−1 | 0.01 ng mL−1 (S/N = 3) | RSD = 6.7%; n = 5 | [56] | |
| PSA (serum samples) | Electrochemical immunosensor based on antibody-modified paramagnetic microparticles (screen-printed 8-sensor arrays based on 8 graphite working electrodes) | 0–20 ng mL−1 | 1.4 ng mL−1 (3y0+s) | 0.05 µA ng−1 mL−2 | RSD = 8%; n = 5 r2 = 0.995 | [57] | 
| PSA (serum samples) | Electrochemical immunosensor based on MCWNT (SPCE) | 0.005–4 ng mL−1 | 0.005 ng mL−1 | 0.077 µA pg−1 mL−2 | r2 = 0.97 | [58] | 
| PSA (serum samples) | Electrochemical immunosensor based on Au nanoparticles–MWCNT–cross-linked starch nanocomposites (GCE) | 0.01–0.5 ng mL−1 | 0.007 ng mL−1 (S/N = 3) | 63.94 µA ng−1 mL−2 | RSD = 4.1%; n = 6 r2 = 0.9936 Recovery = 91.0–106.3% | [59] | 
| PSA (serum samples) | Electrochemical immunosensor based on graphene and Ag-hybridized mesoporous silica nanoparticles (GCE) | 0.01–10 ng mL−1 | 0.002 ng mL−1 | 3.6807 µA ng−1 mL−2 | RSD = 6.4%; n = 5 r2 = 0.9963 Recovery = 97.0–102.5% | [60] | 
| IL-8 (serum samples) | Electrochemical immunosensor based on MCWNT (SPCE) | 8–1000 pg mL−1 | 8 pg mL−1 | [58] | ||
| IL-8 (serum samples) | Electrochemical immunosensor based on superparamagnetic particles and Au nanoparticles | 0–2000 pg mL−1 | 0.001 pg mL−1 | 0.0543 nA pg−1 mL−2 | r = 0.9782 | [61] | 
| IL-6 (serum samples) | Electrochemical immunosensor | 0.01–1.3 pg mL−1 | 0.01 pg mL−1 | r = 0.9914 | [62] | |
| IL-6 (serum samples) | Electrochemiluminescence immunosensor based on graphene oxide nanosheet/polyaniline nanowire/CdSe quantum dot nanocomposites (GCE) | 0.5–10,000 pg mL−1 | 0.17 pg mL−1 | RSD = 5.9%; n = 3 | [63] | |
| IL-6 (serum, urine, and saliva samples) | Electrochemical magnetoimmunosensor based on carboxyl-functionalized magnetic microparticles (SPCEs) | 1.75–500 pg mL−1 | 0.39 pg mL−1 (3y0+s) | 336 nA pg−1 mL−2 | RSD = 6.9–8.1%; n = 8 r = 0.999 Recovery = 98–103% | [64] | 
| IL-6 (serum samples) | Electrochemical immunosensor based on Au–Pd–Ag nanoparticles (electrically heated carbon electrode) | 0.1–100,000 pg mL−1 | 0.059 pg mL−1 (S/N = 3) | RSD = 6.3% | [65] | |
| IL-6 (serum samples) | Electrochemical immunosensor based on Au nanoparticle–graphene–silica sol–gel (ITO) | 1–40 pg mL−1 | 0.3 pg mL−1 (S/N = 3) | 20.4 nA pg−1 mL−2 | RSD = 7.2%; n = 3 r = 0.9919 | [66] | 
| MMP-2 (serum samples) | Electrochemical immunosensor based on Au nanoparticles and nitrogen-doped graphene composites (GCE) | 0.5–50,000 pg mL−1 | 0.11 pg mL−1 (S/N = 3) | 4.20 µA ng−1 mL−2 | RSD = 5.7% r = 0.997 | [67] | 
| MMP-2 (serum samples) | Optical biosensor based on graphene oxide | 10,000–150,000 pg mL−1 | 2500 pg mL−1 | RSD = 0.53–4.56% Recovery = 93.6–98.8% | [68] | |
| MMP-3 | Electrochemical immunosensor based on graphene oxide/polypyrrole ionic liquid nanocomposite (ITO) | 1–1000 pg mL−1 | 1 pg mL−1 | [69] | ||
| α-fetoprotein (serum samples) | Electrochemical magnetoimmunosensor based on Fe3O4/ZrO2/nano-Au composite (GCE) | 0.05–10 ng mL−1 | 0.01 ng mL−1 (S/N = 3) | 0.2906 µA ng−1 mL−2 | RSD = 2.5% r = 0.9905 | [70] | 
| α-fetoprotein (serum samples) | Photoelectrochemical immunosensor based on CdTe quantum dot–glucose oxidase bioconjugate (ITO) | 0.0005—10,000 ng mL−1 | 0.00013 ng mL−1 | 4.60 µA ng−1 mL−2 | RSD = 0.8–1.5%; n = 5 r = 0.9997 | [71] | 
| α-fetoprotein (serum samples) | Electrochemical sensor based on MWCNT and Au nanoparticles | 0.0005–100 ng mL−1 | 0.00015 ng mL−1 (S/N = 3) | RSD = 2.7–5.1% r = 0.9969 | [72] | |
| α-fetoprotein (serum samples) | Electrochemical immunosensor based on Au and Ag nanoparticles (SPCE) | 0.005–5.0 ng mL−1 | 0.0039 ng mL−1 (S/N = 3) | CV = 5.3–7.9%; n = 5 r = 0.9954 | [73] | |
| α-fetoprotein (serum samples) | Electrochemical immunosensor based on mesoporous silica nanoparticles with Fe3O4 nanoparticles (GCE) | 0.01–25 ng mL−1 | 0.004 ng mL−1 (S/N = 3) | RSD = 1.8–3.5%; n = 5 | [74] | |
| CEA (serum samples) | Electrochemical immunosensor based on CNT/Au nanoclusters (GCE) | 0.1–2.0 ng mL−1 | 0.06 ng mL−1 (S/N = 3) | 4.69 µA ng−1 mL−2 | CV = 5.6%; n = 5 r = 0.992 | [75] | 
| CEA (serum samples) | Electrochemical immunosensor based on chitosan–ferrocene and nano-TiO2 film and Au nanoparticle–graphene nanohybrid | 0.01–80 ng mL−1 | 0.0034 ng mL−1 (S/N = 3) | 0.5289 µA ng−1 mL−2 | RSD = 2.5%; n = 5 r = 0.9991 | [76] | 
| CEA (serum samples) | Electrochemical immunosensor based on Au nanoparticle–thionine–reduced graphene oxide nanocomposite film (GCE) | 0.01–0.5 ng mL−1 | 0.004 ng mL−1 (S/N = 3) | 4.2 µA ng−1 mL−2 | RSD = 4.6%; n = 5 r = 0.9978 Recovery = 92.5–113.0% | [77] | 
| CEA (serum samples) | Electrochemical sensor based on MWCNT and Au nanoparticles | 0.0005–100 ng mL−1 | 0.00002 ng mL−1 (S/N = 3) | RSD = 1.9–5.8% r = 0.9954 | [72] | |
| CEA (serum samples) | Electrochemical immunosensor based on MWCNT (µPAD) | 0.05–50 ng mL−1 | 0.01 ng mL−1 | 2.587 µA ng−1 mL−2 | RSD = 4.2%; n = 10 r = 0.9964 | [78] | 
| CEA (serum samples) | Electrochemical immunosensor based on Au and Ag nanoparticles (SPCE) | 0.005–5.0 ng mL−1 | 0.0035 ng mL−1 (S/N = 3) | CV = 4.7–5.9%; n = 5 r = 0.9975 | [73] | |
| CEA (serum samples) | Electrochemical immunosensor based on Nafion membrane–SiO2 nanoparticles (GCE) | 0.000001–0.1 ng mL−1 | 0.000001 ng mL−1 (S/N = 3) | 0.10016 µA fg−1 mL−2 | RSD = 3.5%; n = 3 r2 = 0.9944 | [79] | 
| CEA (serum samples) | Electrochemical immunosensor based on nano-Au-functionalized mesoporous carbon foam (GCE) | 0.00005–1 ng mL−1 | 0.000024 ng mL−1 (S/N = 3) | RSD = 7.6%; n = 3 r = 0.9997 | [80] | |
| CEA (serum samples) | Electrochemical immunosensor based on Au–Ag bimetallic nanoparticles (paper working electrode) | 0.001–50 ng mL−1 | 0.0003 ng mL−1 (S/N = 3) | 15.58 µA ng−1 mL−2 | RSD = 5.1%; n = 11 r = 0.9965 | [81] | 
| CA 125 (serum samples) | Electrochemical immunosensor based on MWCNT (µPAD) | 0.001–75.0 U mL−1 | 0.2 U mL−1 | 1.285 µA U−1 mL−2 | r = 0.9968 | [78] | 
| CA 125 (serum samples) | Electrochemical sensor based on MWCNT and Au nanoparticles | 0.0001–100 U mL−1 | 0.000037 U mL−1 (S/N = 3) | RSD = 3.6–5.9% r = 0.9965 | [72] | |
| CARDIAC BIOMARKERS | ||||||
| CRP (serum samples) | Electrochemical immunosensor based on aldehyde-terminated nanocrystalline diamond | 1–1000 nM | 10 nM | [82] | ||
| CRP (serum samples) | Electrochemical immunosensor based Fe3O4–Au magnetic nanoparticles (SPCE) | 1.2–200 ng mL−1 | 0.5 ng mL−1 | [83] | ||
| CRP | Electrochemical immunosensor based on ZnO nanotubes | 10–1000000 ng L−1 | 0.0010 ng mL−1 | 13.17 mV mg−1 L−1 | RSD < 5%; n = 6 r2 = 0.99 | [84] | 
| CRP (serum samples) | Electrochemical magnetoimmunosensor based on carboxylic acid-modified magnetic beads (gold SPE) | 0.07–1000 ng mL−1 | 0.021 ng mL−1 (3s/m) | 0.203 µA ng−1 mL−2 | RSD = 6.5%; n = 9 r = 0.997 | [85] | 
| CRP (serum samples) | Electrochemical immunosensor (polycrystalline Au electrodes) | 60000–6000000 ng L−1 | 19000 ng mL−1 (S/N = 3) | [86] | ||
| CRP (serum samples) | Piezoelectric immunosensor based on Fe3O4–SiO2 magnetic nanoprobes | 0.001–100 ng mL−1 | 0.0003 ng mL−1 | 30.1 Hz pg−1 mL−2 | CV = 2.4%; n = 5 r = 0.9943 Recovery = 86.7–107.0% | [87] | 
| CRP (serum and saliva samples) | Electrochemical immunosensor based on SWCNT | 0.1–100000 ng mL−1 | 0.1 ng mL−1 | CV = 1.0–9.4%; n = 3 r2 = 0.9924 | [88] | |
| CRP (serum samples) | Electrochemical magnetoimmunosensor based on carboxylic acid-modified magnetic beads (SPCE) | 2–100 ng mL−1 | 0.47 ng mL−1 (3s/m) | 0.386 µA ng−1 mL−2 | RSD = 6.3%; n = 10 r = 0.996 | [89] | 
| NT-proBNP | Electrochemical immunosensor with Au and MWCNT composite | 0.02–100 ng mL−1 | 0.006 ng mL−1 (S/N = 3) | 2.023 µA ng−1 mL−2 | RSD = 3.4%; n = 10 r = 0.997 | [90] | 
| NT-proBNP (serum samples) | Electrochemical magnetoimmunosensor based on avidin-functionalized magnetic nanoparticles | 0.04–2.5 ng mL−1 | 0.03 ng mL−1 (S/N = 3) | r = 0.9827 | [91] | |
| NT-proBNP (serum samples) | Electrochemical magnetoimmunosensor based on carboxylic acid-modified magnetic beads (SPE) | 0.12–42.9 ng mL−1 | 0.02 ng mL−1 | RSD = 9.7%; n = 9 | [92] | |
| NT-proBNP (serum samples) | Electrochemical magnetoimmunosensor based on carboxylic acid-modified magnetic beads (SPCE) | 2–100 ng mL−1 | 0.47 ng mL−1 (3s/m) | RSD = 9.4%; n = 10 Recovery = 105–111% | [89] | |
| cTnT (serum samples) | Piezoelectric immunosensor based on Au nanoparticles | 0.003–0.5 ng mL−1 | 0.0015 ng mL−1 | 63.82 Hz ng−1 mL−2 | CV = 7%; n = 5 r = 0.989 | [93] | 
| cTnT (serum samples) | Electrochemical immunosensor based on carboxylated CNT | 0.1–10 ng mL−1 | 0.033 ng mL−1 | CV = 3.7%; n = 10 r = 0.9996 | [94] | |
| cTnT (serum samples) | Electrochemical immunosensor based on amine-functionalized CNT (SPE) | 0.0025–0.5 ng mL−1 | 0.0035 ng mL−1 (3s/m) | 3.25 µA ng−1 mL−2 | RSD = 3.8%; n = 7 r = 0.995 | [95] | 
| cTnT (serum samples) | Electrochemical immunosensor based on o-aminobenzoic film | 0.05–5.0 ng mL−1 | 0.016 ng mL−1 (3s/m) | RSD = 6.2%; n = 6 r = 0.992 | [96] | |
| cTnI | Electrochemical immunosensor based on Au nanoparticles (ITO) | 1–100 ng mL−1 | [97] | |||
| cTnI | Electrochemical immunosensor (SPE) | 1–100 ng mL−1 | 5.5 µA ng−1 cm−2 | r = 0.987 | [98] | |
| cTnI | Electrochemical immunosensor based on Pt nanoparticles and graphene composite (GCE) | 0.01–10 ng mL−1 | 0.0042 ng mL−1 (S/N = 3) | RSD = 4–11%; n = 3 r = 0.991 | [99] | |
| cTnI (serum samples) | Optical immunosensor (fluorescence) | 0–50 ng mL−1 | 0.05 ng mL−1 | RSD = 7.5%; n = 6 r2 = 0.9984 | [100] | |
| Myoglobin (plasma samples) | Electrochemical immunosensor based on Au nanoparticles | 10–400 ng mL−1 | 5 ng mL−1 (S/N = 3) | RSD = 15%; n = 3 r = 0.981 | [101] | |
| Myoglobin | Electrochemical immunosensor based on liquid crystal and Au nanoparticles (GCE) | 9.96–72.8 ng mL−1 | 6.29 ng mL−1 (3s/m) | RSD = 4.3%; n = 5 Recovery = 99.7–109.1% | [102] | |
| Myoglobin (serum samples) | Optical immunosensor (SPR) | 100–1000 ng mL−1 | 31.0 ng mL−1 (S/N = 3) | CV = 4.9% r2 = 0.99 | [103] | |
| Myoglobin (serum samples) | Optical immunosensor (fluorescence) | 0–340 ng mL−1 | RSD = 2.3%; n = 6 r2 = 0.979 | [100] | ||
CA 125: cancer antigen 125; CEA: carcinoembryonic antigen; CNT: carbon nanotubes; CRP: C-reactive protein; cTnI: cardiac troponin I; cTnT: cardiac troponin T; CV: coefficient of variation; GCE: glassy carbon electrode; IL-6: interleukin-6; IL-8: interleukin-8; ITO: indium tin oxide electrode; LOD: limit of detection; MMP-2: matrix metalloproteinase-2; MMP-3: matrix mettaloproteinase-3; MWCNT: multiwalled carbon nanotubes; NT-proBNP: amino-terminal pro-brain natriuretic peptide; PSA: prostate-specific antigen; RSD: residual standard deviation; SPCE: screen-printed carbon electrode; SPE: screen-printed electrode; SPR: Surface Plasmon Resonance; SWCNT: single-walled carbon nanotubes; µPAD: microfluidic paper-based analytical device.
Determination of LOD: “S/N = 3”: LOD is three times the signal-to-noise ratio; “3s/m”: LOD is 3 times the standard deviation (s)/slope of calibration plot (m); “3y0+s”: LOD is 3 times the blank response (y0) plus the standard deviation (s).