Multiplexed Electrochemical Immunosensors for Clinical Biomarkers
Abstract
:1. Introduction
2. Multiplexed Electrochemical Immunosensors Involving Electrode Arrays
3. Multiplexed Electrochemical Immunosensors Using Barcode Configurations
4. Microfluidic Devices
5. General Conclusions and Future Prospects
Acknowledgments
Conflicts of Interest
References
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Electrodes | Label | Analyte | Immunoassay | Technique | Linear Range | LOD | Sample | Ref. |
---|---|---|---|---|---|---|---|---|
Cancer biomarkers | ||||||||
GA/Chit/SPAuEs (2WEs) | Strept/AuNPs/CNHs | AFP CEA | Sandwich-type; Ag deposition | LSASV | 0.1–1000 pg·mL−1 | 0.024 pg·mL−1 AFP 0.032 pg·mL−1 CEA | serum | [7] |
SPAuEs (4WEs) | AuNRs-HRP | phospho-p53392 phospho-p5315 phospho-p5346 total p53 | Sandwich-type; detection of H2O2/THI | SWV | 0.01–20 nM p53392 0.05–20 nM p5315 0.1–50 nM p5346 0.05–20 nM total p53 | 5 pM p53392 20 pM p5315 30 pM p5346 10 pM total p53 | plasma | [8] |
carboxylated-SPCEs (16WEs) | HRP-MWCNTs | PSA IL-8 | Sandwich-type; detection of TMB | amperometry | 5–4000 pg·mL−1 PSA 8–1000 pg·mL−1 IL-8 | 5 pg·mL−1 PSA 8 pg·mL−1 IL-8 | serum | [18] |
AuNPs film/PDMS (8 × 8 WEs) | HRP/AuNRs | PSA; PSMA; IL-6 | Sandwich-type; detection of H2O2 | amperometry | 0.1–10 ng·mL−1 PSA 0.005–1 ng·mL−1 IL-6 0.8–400 PSMA | 0.1 ng·mL−1 PSA 0.005 ng·mL−1 IL-6 0.8 ng·mL−1 PSMA | serum | [19] |
G/SPCEs (3WEs) | M-PtNPs | CA125, CA153, CEA | Sandwich-type; detection of H2O2 | DPV | 0.05–20 U·mL−1 CA125; 0.008–24 U·mL−1 CA153; 0.02–20 24 U·mL−1 CEA | 0.002 U·mL−1; 0.001 U·mL−1; 7.0 pg·mL−1 | serum | [20] |
Chit/SPCEs (2WEs) | AuNPs | CEA AFP | Sandwich-type; Ag deposition | LSASV | 0.005–5.0 ng·mL−1 | 3.5 pg·mL−1 CEA 3.9 pg·mL−1 AFP | serum | [21] |
Chit/SPCEs | Strept/AgNPs/MWCNTs | CEA AFP | Sandwich-type; Ag deposition | LSASV | 0.1–5000 pg·mL−1 | 0.093 pg·mL−1 CEA 0.061 pg·mL−1AFP | serum | [22] |
AuNPs/G/SPCEs (3WEs) | AP-AuCs/G | CA153, CA125, CEA | Sandwich-type; addition of 3-IP and Ag deposition | LSASV | 0.005–50 U·mL−1 CA 153 0.001–100 U·mL−1 CA 125 0.004–200 U·mL−1 CEA | 0.0015 U·mL−1 CA 153 0.00034 U·mL−1 CA 125 0.0012 U·mL−1 CEA | serum | [23] |
SPCEs (2WEs) | Strept-HRP | ERα PR | Sandwich-type magnetoimmuno-sensor; detection of H2O2/HQ | amperometry | 73–1500 pg·mL−1 (PR) | 22 pg·mL−1 (PR) | cell lysates | [24] |
Cardiac biomarkers | ||||||||
CNF microE chip (3 × 3) | - | CRP, cTNI, Mb | Direct; detection of Fe(CN)64− | DPV | - | - | serum | [25] |
HOOC-MBs/SPCEs (2WEs) | HRP | NT-proBNP CRP | Competitive ( NT-pro BNP); sandwich-type (CRP); detection of H2O2 in presence of TMB | amperometry | 2.5–504 ng·mL−1 NT-proBNP 2–100 ng·mL−1 CRP | 0.47 ng·mL−1 | serum | [26] |
SiNW array | - | cTnT, CK-MM, CK-MB | Direct assay | Resistance changes caused by specific binding | 1 pg·mL−1–10 ng·mL−1 | 1 pg·mL−1 (2 μL blood 45 min) | blood | [27] |
Other clinical biomarkers | ||||||||
HOOC-Phe-DWCNTs/SPCEs (2WEs) | poly-HRP-Strept | IL-1β TNF-α | Sandwich-type; detection of H2O2 in the presence of HQ | amperometry | 0.5–100 pg·mL−1 IL-1β 1–200 pg·mL−1 TNF-α | 0.38 pg·mL−1 IL-1β 0.85 pg·mL−1 TNF-α | serum saliva | [28] |
Au microE chip (8WEs) | - | IL-1β, IL-10, IL-6 | Direct; detection of Fe(CN)63−/4− | EIS | 1–15 pg·mL−1 | - | - | [29] |
rGO/SPCEs (2WEs) | Strept-AP | GHRL PYY | Sandwich-type; addition of 1-NPP | DPV | 10−3–100 ng·mL−1 GHRL 10−4–10 ng·mL−1 PYY | 1.0 pg·mL−1 GHRL 0.02 pg·mL−1 PYY | serum saliva | [30] |
SPCEs (2WEs) | Strept-AP | cortisol ACTH | Sandwich-type; addition of 1-NPP | DPV | 0.1–500 ng·mL−1 cortisol 5.0 × 10−5–0.1 ng·mL−1 ACTH | 37 pg·mL−1 cortisol 0.04 pg·mL−1 ACTH | serum | [31] |
AuNPs/MWCNTs/SPCEs (2WEs) | AP | IgA and IgG type AGA anti-tTG | Sandwich-type; addition of 3-IP and Ag deposition | cyclic-ASV | up to 100 U mL−1 | 2.45 U·mL−1 tTG IgA 2.95 U·mL−1 tTG IgG | serum | [32] |
Electrode | Label | Analyte | Immunoassay | Technique | Linear Range | LOD | Sample | Ref. |
---|---|---|---|---|---|---|---|---|
Cancer biomarkers | ||||||||
G/Au/GCE | THI (or Co or Fc or AQ)-Strept-Biotin-dsDNA/Strept-Biotin-Ab2/AuNPs/SiO2/Fe3O4 | CEA, CA125, PSA, AFP | Sandwich-type; direct detection after conjugation | DPV | 0.2–600 pg·mL−1 CEA; 0.2–1000 pg·mL−1 CA125; 0.2–800 pg·mL−1 PSA; 0.2–800 pg·mL−1 AFP | 48 fg·mL−1 CEA; 77 fg·mL−1 CA125; 60 fg·mL−1 PSA; 62 fg·mL−1AFP | - | [6] |
AuNPs/GCE | PVP/GS/PtPdNPs/HRP/AQ PVP/GS/PtPdNPs/HRP/THI | AFP, APT; DCP, AFP-L3, γ-GT, AFU | Sandwich-type; addition of H2O2 | DPV | 0.025–5.0 ng·mL−1 AFP; 0.024–9.6 ng·mL−1 APT; 0.032–3.2 UL−1 DCP; 0.024–2.4 ng·mL−1 AFP-L3; 1.0–9.5UL−1 γ-GT; 1.2–9.0 UL−1 AFU | 0.008 ng·mL−1 AFP; 0.0082 ng·mL−1 APT; 0.01UL−1 DCP; 0.008 ng·mL−1 AFP-L3; 0.33 UL−1 γ-GT; 0.4 UL−1 AFU | serum | [12] |
GCE (Hg) | PAMAM-CdS (or ZnS, or PbS) | CA125 CA15-3 CA19-9 | Sandwich-type; direct detection of Cd, Zn and Ag | SWASV | 0.01–50 U·mL−1 | 0.005 U·mL−1 | serum | [13] |
IL/rGO/GCE | PtNPs-Cu2+ PtNPs-Cd2+ | AFP CEA | Sandwich-type; reduction of metal ions | DPV | 0.05–200 ng·mL−1 | 0.05 ng·mL−1 AFP 0.002 ng·mL−1 CEA | serum | [14] |
AuNPs/Chit/GCE | CGS-PB; CGS-TB | CEA; AFP | Sandwich-type; direct detection | DPV | 0.5–60 ng·mL−1 | 0.1 ng·mL−1 (CEA) 0.05 ng·mL−1 (AFP) | serum | [33] |
AuNPs/Chit/GCE | Chit/AuNPs/PB; Chit/AuNPs/Fc | CEA; AFP | Sandwich-type; direct detection | DPV | 0.05–100 ng·mL−1 | 0.02 ng·mL−1 (CEA) 0.03 ng·mL−1 (AFP) | serum | [34] |
HAG/PANI/rGO/GCE | AuNPs/rGO/PB; AuNPs/rGO/PDDA/THI | CEA; AFP | Sandwich-type; direct detection | DPV | 0.6–80 ng·mL−1 | 0.12 ng·mL−1 (CEA) 0.08 ng·mL−1 (AFP) | serum | [35] |
AuNPs/GCE | Fc/HRP THI/HRP | CEA AFP | Direct assay after addition of H2O2 | DPV | 0.01–50 ng·mL−1 | 0.01 ng·mL−1 | serum | [36] |
AuNPs/G/GCE | THI-HRP-NPG-MnO2 Fc-HRP-NPG-MnO2 | CA-15-3 CA-125 | Sandwich-type; addition of H2O2 | SWV | 0.01–50 U·mL−1 | 3.5 mU·mL−1 (CA-153) 4.1 mU·mL−1(CA-125) | serum | [37] |
PDPMT-Cl-Chit/GCE | THI-Fe3O4NPs Fca-Fe3O4NPs | SCC-Ag CEA | Sandwich; direct detection | DPV | 0.01–10 ng·mL−1 | 4 pg·mL−1 (SCC-Ag) 5 pg·mL−1 (CEA) | serum | [38] |
CD/G/GCE | CD/Fc/G CD/THI/G | CEA AFP | Sandwich-type with HRP-Ab2 and H2O2 detection | DPV | 0.003–40 ng·mL−1 CEA 0.001–60 ng mL−1 AFP | 0.8 pg·mL−1 CEA 0.5 pg·mL−1 AFP | serum | [39] |
rGO/THI (or PB)/AuNPs/ITO | - | CEA AFP | Direct detection of of THI or PB | SWV | 0.01–300 ng·mL−1 | 0.650 pg·mL−1 CEA 0.885 pg·mL−1 AFP | serum | [40] |
TB (orPB)/AuNPs/TCCRMSs/FTO | - | CEA NSE | Direct; detection of TB or PB | SWV | 2–25 ng·mL−1 | 0.11 ng·mL−1 CEA 0.08 ng·mL−1 NSE | serum | [41] |
HOOC-MBs/SPCE | ACTP/AuNPs ATLP/AuNPs | p5315, p53392 | Sandwich-type; detection of metals | SWV | 1–20 ng·mL−1 (p5315) 0.5–20 ng·mL−1 (p53392) | 0.5 ng·mL−1 (p5315) 0.2 ng·mL−1 (p53392) | serum | [42] |
GCE (Bi) | G/AuNPs-r-Apo-Cd G/AuNPs-r-Apo-Pb | AFP CEA | Sandwich-type; detection of metals | SWASV | 0.001–5 ng·mL−1 | 0.3 pg·mL−1 AFP; 0.35 pg·mL−1 CEA | serum | [43] |
rGO | CdSeTe@CdS Ag NCs | Bcl-2 Bax | Sandwich-type; direct detection of Cd and Ag | SWASV | 1–250 ng·mL−1 | 0.5 fmol | leukemiaK562 cells | [44] |
Chit/MWCNTs/GCE | OMC-Zn OMC-Cd | AFP HER-2 | Sandwich-type; oxidation of metal ions | DPV | 0.001–150 ng·mL−1 | 0.6 pg·mL−1 AFP 0.35 pg·mL−1 HER-2 | serum | [45] |
GCE | EnvisionTM-CdS (or PbS or AuNPs) | AFP CEA CA19-9 | Sandwich-type; detection of metals | DPASV DPCSV | 0.001–50 ng·mL−1 AFP; CEA; 0.005–100 ng·mL−1 CA19-9 | 0.02 pg·mL−1 AFP; 0.05 pg·mL−1 CEA; 0.3 pg·mL−1 CA19-9 | serum | [46] |
Glu/Chit/AuNPs/AuE | BSA/AuNPs-Pb2+ BSA/AuNPs-Cd2+ | CEA AFP | Sandwich-type; reduction of metal ions | DPV | 0.01–50 ng·mL−1 | 4.6 pg·mL−1 CEA 3.0 pg·mL−1 AFP | serum | [47] |
AuNPs/AuE | AuNPs@MWCNTs-Pb2+ AuNPs@MWCNTs-Cd2+ | CEA AFP | Sandwich-type; reduction of metal ions | SWV | 0.01–60 ng·mL−1 | 3.0 pg·mL−1 CEA 4.5 pg·mL−1 AFP | serum | [48] |
AuNPs/rGO/Chit | AgNPs/THI/CNSs AgNPs/CNSs | CEA AFP | Sandwich-type; direct detection | DPV | 0.01–80 ng·mL−1 | 2.8 pg·mL−1 CEA 3.5 pg·mL−1 AFP | serum | [49] |
IL/rGO/PSS/GCE | CGN-THI CGN-DAP CGN-Cd2+ | CEA PSA AFP | Sandwich-type; direct detection | SWV | 0.01–100 ng·mL−1 | 2.7 pg·mL−1 CEA 4.8 pg·mL−1 PSA 3.1 pg·mL−1 AFP | serum | [50] |
AuNPs/AuE | TiO2/Nf- Co(dcbpy)32+ TiO2/Nf- MB | CA15-3 CA19-9 | Sandwich-type; direct detection | DPV | 5–100 U·mL−1 CA15-3 1–100 U·mL−1 CA19-9 | 0.3 UmL−1 CA15-3 1.6 UmL−1 CA19-9 | serum | [51] |
AuNPs/PAPT/GCE | poly(VFc-ATP) AuNPsPOPD/AuNPs | AFP CEA | Sandwich-type; direct detection | DPV | 0.01–100 ng·mL−1 | 0.003 ng·mL−1 AFP 0.006 ng·mL−1 CEA | serum | [52] |
AuNPs/G/GCE | PS-Cd2+ PS-Fc | IL-6 IL-17 | Sandwich-type; direct detection | SWV | 1–1000 pg·mL−1 IL-6 2–1000 pg·mL−1 IL-17 | 0.5 pg·mL−1 1 pg | serum | [53] |
Protein A/Nafion/GCE | GS/AuNPs-THI (or Cobpy)33+ or Fc) | AFP CEA SS2 | Sandwich.type; direct detection | DPV | 0.016–50 ng·mL−1 AFP 0.010–50 ng·mL−1CEA 0.012–50 ng·mL−1 AFP | 5.4 pg·mL−1 AFP 2.8 pg·mL−1 CEA 4.2 pg·mL−1 AFP | - | [54] |
AuNPs/PEI/PTCA/GCE | Au@PBNPs/O-GS-Strept-AP; Au@NiNPs/O-GS-Strept-AP | fPSA PSA | Sandwich-type; AA-P addition | DPV | 0.02–10 ng·mL−1 fPSA 0.01–50 ng·mL−1 PSA | 6.7 pg·mL−1 3.4 pg·mL−1 | serum | [55] |
MWCNTs/GCE | AA liposome UA liposome | NSE ProGRP | Sandwich-type, direct detection | LSV | 50–1000 pg·mL−1 | 5.0 pg·mL−1 NSE 100 pg·mL−1 ProGRP | serum | [56] |
AuNPs/IL/rGO/GCE | Cd (or Pb or Cu) AlgNBs | AFP CEA PSA | Sandwich-type; direct detection | DPV | 0.01–100 ng·mL−1 | 0.01 ng·mL−1AFP 0.0086 ng·mL−1CEA 0.0075 ng·mL−1PSA | serum | [57] |
GCE (Bi) | PLL/AuNPs/Cd-Apo (or Pb-Apo) | AFP CEA | Sandwich-type; direct detection | ASSWV | 0.01–50 ng·mL−1 | 4 pg·mL−1 | serum | [58] |
Chit/AuNPs/GCE | GA/Chit/pAA NSs-Cu2+ (or Cd2+ or Zn2+) | CEA CA19-9 CA125 CA242 | Sandwich-type; direct detection | SWV | 0.1–100 ng·mL−1 CEA 1–150 U·mL−1 CA 19-9, CA125,CA242 | 0.02 ng·mL−1 CEA 0.4 U·mL−1 CA19-9 0.3 U·mL−1 CA125 0.4 U·mL−1 CA242 | serum | [59] |
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Yáñez-Sedeño, P.; Campuzano, S.; Pingarrón, J.M. Multiplexed Electrochemical Immunosensors for Clinical Biomarkers. Sensors 2017, 17, 965. https://doi.org/10.3390/s17050965
Yáñez-Sedeño P, Campuzano S, Pingarrón JM. Multiplexed Electrochemical Immunosensors for Clinical Biomarkers. Sensors. 2017; 17(5):965. https://doi.org/10.3390/s17050965
Chicago/Turabian StyleYáñez-Sedeño, Paloma, Susana Campuzano, and José M. Pingarrón. 2017. "Multiplexed Electrochemical Immunosensors for Clinical Biomarkers" Sensors 17, no. 5: 965. https://doi.org/10.3390/s17050965
APA StyleYáñez-Sedeño, P., Campuzano, S., & Pingarrón, J. M. (2017). Multiplexed Electrochemical Immunosensors for Clinical Biomarkers. Sensors, 17(5), 965. https://doi.org/10.3390/s17050965