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Electrochemical biosensors for measurement of colorectal cancer biomarkers

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Abstract

Colorectal cancer (CRC) is associated with one of the highest rates of mortality among cancers worldwide. The early detection and management of CRC is imperative. Biomarkers play an important role in CRC screening tests, CRC treatment, and prognosis and clinical management; thus rapid and sensitive detection of biomarkers is helpful for early detection of CRC. In recent years, electrochemical biosensors for detecting CRC biomarkers have been widely investigated. In this review, different electrochemical detection methods for CRC biomarkers including immunosensors, aptasensors, and genosensors are summarized. Further, representative examples are provided that demonstrate the advantages of electrochemical sensors modified by various nanomaterials. Finally, the limitations and prospects of biomarkers and electrochemical sensors in detection are also discussed.

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Abbreviations

CRC:

Colorectal cancer

EIS:

Electrochemical impedance spectroscopy

CV:

Cyclic voltammetry

SWV:

Square wave voltammetry

DPV:

Differential pulse voltammetry

LSV:

Linear sweep voltammetry

CEA:

Carcinoembryonic antigen

AuNPs:

Gold nanoparticles

MWCNTs:

Multi-walled carbon nanotubes

RSD:

Relative standard deviation

Ab1 :

Primary antibody

Ab2 :

Secondary antibody

PSA:

Prostate-specific antigen

HIgG:

Human immunoglobulin G

AFP:

Alpha fetoprotein

rGO:

Reduced graphene oxide

PDA:

Polydopamine

AgNPs:

Silver nanoparticles

GO:

Graphene oxide

Fc:

Ferrocene

LR:

Linear range

LOD:

Limit of detection

Rf:

References

GCE:

Glassy carbon electrode

Fc-g-PLL:

Ferrocene-grafted-polylysine

CS-H:

Carbon spheres-Hemin

HRP:

Horseradish peroxidase

Au:

TNPs Au triangular nanoprisms

YNCs:

Yolk-shell nanocubes

CS-N-GR:

Chitosan-nitrogen-graphene

T-GO:

Thiolated graphene oxide

SA:

Streptavidin

B-mAb:

Biotin monoclonal antibody

IC:

Immediate current

SPCE:

Screen-printed carbon electrode

GNP:

Graphene nanoplatelets

CSHs:

Copper silicate hollow spheres

BSA:

Bovine serum albumin

PEDOT:

Poly(3,4-ethylenedioxythiophene)

CA199:

Carbohydrate antigen 199

THi:

Thionine

CS:

Chitosan

GOD:

Glucose oxidase

mSiO2 :

Mesoporous silica

3DOM:

Three-dimensional ordered macroporous

GA:

Glutaraldehyde

TEPA:

Tetraethylene pentamine

SA-Pt:

Sodium alginate platinum nanoparticle

MB:

Methylene blue

CCSP@GOx:

Calcium carbonate nanoparticles with glucose oxidase

FeOx@mC:

Ferric oxide nanoparticles@mesoporous carbon matrix

MA:

Melamine

MUC1:

Mucin1

Apt:

Aptamer

FTO:

Fluorine tin oxide

TMB:

Tetramethylbenzidine

ZrHF@mFe3O4@mC:

Zirconium hexacyanoferrate@Fe3O4@carbon mesoporous nanomaterial

cDNA:

Complementary DNA

IL-6:

Interleukin-6

SWCNTs:

Single walled carbon nanotubes

HCPE:

Heated carbon electrode

PPC:

Phosphorylcholine

GSPE:

Graphite-screen printed electrodes

PPCE:

Polypyrrole polymer containing epoxy

P-Cys:

Poly L-cysteine

StarPGMA :

Star-shaped poly(glycidyl methacrylate)

GQDs:

Graphene quantum dots

PEA:

Phenylethylamine

ALP:

Alkaline phosphatase

P-N3 :

Azide modified hairpin capture probe

P-DBCO:

Dibenzocyclooctyne modified signal probe

LNA:

Locked nucleic acid

ssDNA:

Single-stranded DNA

S1 :

Strand 1

Exo III:

Exonuclease III

EGFR:

Epidermal growth factor receptor

CPE:

Carbon paste electrode

MIS:

Molecularly imprinted siloxane

ns@gold:

Gold nanostructure

3-APTES:

3-Aminopropyl triethoxysilane

MIP:

Molecularly imprinted polymers

PT:

Polythiophene

TMC:

N-Trimethyl chitosan

p-COF:

Porphyrin-covalent organic framework

CMK-3:

Order mesoporous carbon

Poly(AC-co-MDHLA):

Poly-acrylamide-co-methacrylate of dihydrolipoic acid

AMS:

Amino-functionalized mesoporous silica

miRNA:

microRNA

den:

Dendritic

UiO-66:

Pd@metal organic frameworks

H1:

Hairpin DNA 1

GONRs:

Graphene oxide nanoribbons

TDN:

Tetrahedron DNA nanostructure

References

  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–91. https://doi.org/10.1136/gutjnl-2015-310912.

    Article  PubMed  Google Scholar 

  2. Favoriti P, Carbone G, Greco M, Pirozzi F, Pirozzi REM, Corcione F. Worldwide burden of colorectal cancer: a review. Updat Surg. 2016;68:7–11. https://doi.org/10.1007/s13304-016-0359-y.

    Article  Google Scholar 

  3. Simon K. Colorectal cancer development and advances in screening. Clin Interv Aging. 2016;11:967–76. https://doi.org/10.2147/CIA.S109285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hazewinkel Y, Dekker E. Colonoscopy: Basic principles and novel techniques. Nat Rev Gastroenterol Hepatol. 2011;8:554–64. https://doi.org/10.1038/nrgastro.2011.141.

    Article  PubMed  Google Scholar 

  5. Kuipers EJ, Rösch T, Bretthauer M. Colorectal cancer screening - optimizing current strategies and new directions. Nat Rev Clin Oncol. 2013;10:130–42. https://doi.org/10.1038/nrclinonc.2013.12.

    Article  CAS  PubMed  Google Scholar 

  6. Swaroop VS, Larson MV. Colonoscopy as a screening test for colorectal cancer in average-risk individuals. Mayo Clin Proc. 2002;77:951–6. https://doi.org/10.4065/77.9.951.

    Article  PubMed  Google Scholar 

  7. Hoshino N, Sakamoto T, Hida K, Sakai Y. Diagnostic accuracy of computed tomography colonography for tumor depth in colorectal cancer: a systematic review and meta-analysis. Surg Oncol. 2019;30:126–30. https://doi.org/10.1016/j.suronc.2019.08.003.

    Article  PubMed  Google Scholar 

  8. Oono Y, Iriguchi Y, Doi Y, Tomino Y, Kishi D, Oda J, et al. A retrospective study of immunochemical fecal occult blood testing for colorectal cancer detection. Clin Chim Acta. 2010;411:802–5. https://doi.org/10.1016/j.cca.2010.02.057.

    Article  CAS  PubMed  Google Scholar 

  9. Issaka RB, Avila P, Whitaker E, Bent S, Somsouk M. Population health interventions to improve colorectal cancer screening by fecal immunochemical tests: a systematic review. Prev Med (Baltim). 2019;118:113–21. https://doi.org/10.1016/j.ypmed.2018.10.021.

    Article  Google Scholar 

  10. Tarney CM, Wang G, Bateman NW, Conrads KA, Zhou M, Hood BL, et al. Biomarker panel for early detection of endometrial cancer in the prostate, lung, colorectal, and ovarian cancer screening trial. Gynecol Oncol. 2019;154:42–3. https://doi.org/10.1016/j.ygyno.2019.04.102.

    Article  Google Scholar 

  11. Geneve N, Kairys D, Bean B, Provost T, Mathew R, Taheri N. Colorectal Cancer screening. Prim Care - Clin Off Pract. 2019;46:135–48. https://doi.org/10.1016/j.pop.2018.11.001.

    Article  Google Scholar 

  12. Rex DK. The case for high-quality colonoscopy remaining a premier colorectal Cancer screening strategy in the United States. Gastrointest Endosc Clin N Am. 2020;30:527–40. https://doi.org/10.1016/j.giec.2020.02.006.

    Article  PubMed  Google Scholar 

  13. Whitlock EP, Lin JS, Liles E, Beil TL, Fu R. Clinical guidelines annals of internal medicine screening for colorectal Cancer : a targeted, updated systematic. Ann Intern Med. 2008;149:638–58.

    Article  Google Scholar 

  14. Chung SW, Hakim S, Siddiqui S, Cash BD. Update on flexible sigmoidoscopy, computed tomographic Colonography, and capsule colonoscopy. Gastrointest Endosc Clin N Am. 2020;30:569–83. https://doi.org/10.1016/j.giec.2020.02.009.

    Article  PubMed  Google Scholar 

  15. Gonzalez-Pons M, Cruz-Correa M. Colorectal Cancer biomarkers: where are we now? Biomed Res Int. 2015, 2015. https://doi.org/10.1155/2015/149014.

  16. Valori R, Rey JF, Atkin WS, Bretthauer M, Senore C, Hoff G, et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition Quality assurance in endoscopy in colorectal cancer screening and diagnosis. Endoscopy. 2012;44:88–105. https://doi.org/10.1055/s-0032-1309795.

    Article  Google Scholar 

  17. Robertson DJ, Lee JK, Boland CR, Dominitz JA, Giardiello FM, Johnson DA, et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US multi-society task force on colorectal Cancer. Gastroenterology. 2017;152:1217–1237.e3. https://doi.org/10.1053/j.gastro.2016.08.053.

    Article  PubMed  Google Scholar 

  18. Duffy MJ, Van Rossum LGM, Van Turenhout ST, Malminiemi O, Sturgeon C, Lamerz R, Nicolini A, Haglund C, Holubec L, Fraser CG, Halloran SP (2011) Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper. Int J Cancer 128:3–11. https://doi.org/10.1002/ijc.25654.

  19. Arya SK, Estrela P. Recent advances in enhancement strategies for electrochemical ELISA-based immunoassays for cancer biomarker detection. Sensors (Switzerland). 2018:18. https://doi.org/10.3390/s18072010.

  20. Robinson KJ, Hazon N, Lonergan M, Pomeroy PP. Validation of an enzyme-linked immunoassay (ELISA) for plasma oxytocin in a novel mammal species reveals potential errors induced by sampling procedure. J Neurosci Methods. 2014;226:73–9. https://doi.org/10.1016/j.jneumeth.2014.01.019.

    Article  CAS  PubMed  Google Scholar 

  21. Howat WJ, Lewis A, Jones P, Kampf C, Pontén F, van der Loos CM, Gray N, Womack C, Warford A (2014) Antibody validation of immunohistochemistry for biomarker discovery: recommendations of a consortium of academic and pharmaceutical based histopathology researchers. Methods 70:34–38. https://doi.org/10.1016/j.ymeth.2014.01.018.

  22. Rizk EM, Gartrell RD, Barker LW, Esancy CL, Finkel GG, Bordbar DD, et al. Prognostic and predictive immunohistochemistry-based biomarkers in Cancer and immunotherapy. Hematol Oncol Clin North Am. 2019;33:291–9. https://doi.org/10.1016/j.hoc.2018.12.005.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Fourkala EO, Blyuss O, Field H, Gunu R, Ryan A, Barth J, et al. Sex hormone measurements using mass spectrometry and sensitive extraction radioimmunoassay and risk of estrogen receptor negative and positive breast cancer: case control study in UK collaborative Cancer trial of ovarian Cancer screening (UKCTOCS). Steroids. 2016;110:62–9. https://doi.org/10.1016/j.steroids.2016.04.003.

    Article  CAS  PubMed  Google Scholar 

  24. Buono A, Lidbury JA, Wood C, Wilson-Robles H, Dangott LJ, Allenspach K, et al. Development, analytical validation, and initial clinical evaluation of a radioimmunoassay for the measurement of soluble CD25 concentrations in canine serum. Vet Immunol Immunopathol. 2019;215:109904. https://doi.org/10.1016/j.vetimm.2019.109904.

    Article  CAS  PubMed  Google Scholar 

  25. Tian J, Zhou L, Zhao Y, Wang Y, Peng Y, Zhao S. Multiplexed detection of tumor markers with multicolor quantum dots based on fluorescence polarization immunoassay. Talanta. 2012;92:72–7. https://doi.org/10.1016/j.talanta.2012.01.051.

    Article  CAS  PubMed  Google Scholar 

  26. Xie Q, Weng X, Lu L, Lin Z, Xu X, Fu C. A sensitive fluorescent sensor for quantification of alpha-fetoprotein based on immunosorbent assay and click chemistry. Biosens Bioelectron. 2016;77:46–50. https://doi.org/10.1016/j.bios.2015.09.015.

    Article  CAS  PubMed  Google Scholar 

  27. Yang X, Zhao Y, Sun L, Qi H, Gao Q, Zhang C. Electrogenerated chemiluminescence biosensor array for the detection of multiple AMI biomarkers. Sensors Actuators B Chem. 2018;257:60–7. https://doi.org/10.1016/j.snb.2017.10.108.

    Article  CAS  Google Scholar 

  28. Liu J, Zhao J, Li S, Zhang L, Huang Y, Zhao S. A novel microchip electrophoresis-based chemiluminescence immunoassay for the detection of alpha-fetoprotein in human serum. Talanta. 2017;165:107–11. https://doi.org/10.1016/j.talanta.2016.12.038.

    Article  CAS  PubMed  Google Scholar 

  29. Grandjean M, Dieu M, Raes M, Feron O. A new method combining sequential immunoaffinity depletion and differential in gel electrophoresis to identify autoantibodies as cancer biomarkers. J Immunol Methods. 2013;396:23–32. https://doi.org/10.1016/j.jim.2013.07.006.

    Article  CAS  PubMed  Google Scholar 

  30. Issaq HJ, Veenstra TD. Two-dimensional difference in gel electrophoresis for biomarker discovery. 2nd ed: Elsevier Inc.; 2019.

  31. Mehta PK, Raj A, Singh NP, Khuller GK. Detection of potential microbial antigens by immuno-PCR (PCR-amplified immunoassay). J Med Microbiol. 2014;63:627–41. https://doi.org/10.1099/jmm.0.070318-0.

    Article  CAS  PubMed  Google Scholar 

  32. Metkar SK, Girigoswami K. Diagnostic biosensors in medicine – a review. Biocatal Agric Biotechnol. 2019;17:271–83. https://doi.org/10.1016/j.bcab.2018.11.029.

    Article  Google Scholar 

  33. Thévenot DR, Toth K, Durst RA, Wilson GS. Electrochemical biosensors: recommended definitions and classification. Anal Lett. 2001;34:635–59. https://doi.org/10.1081/AL-100103209.

    Article  Google Scholar 

  34. Wang J. Nanomaterial-based electrochemical biosensors. Analyst. 2005;130:421–6. https://doi.org/10.1039/b414248a.

    Article  CAS  PubMed  Google Scholar 

  35. Filik H, Avan AA. Nanostructures for nonlabeled and labeled electrochemical immunosensors: simultaneous electrochemical detection of cancer markers: a review. Talanta. 2019;205:120153. https://doi.org/10.1016/j.talanta.2019.120153.

    Article  CAS  PubMed  Google Scholar 

  36. Ganepola GA. Use of blood-based biomarkers for early diagnosis and surveillance of colorectal cancer. World J Gastrointest Oncol. 2014;6:83. https://doi.org/10.4251/wjgo.v6.i4.83.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Patel JN, Fong MK, Jagosky M. Colorectal cancer biomarkers in the era of personalized medicine. J Pers Med. 2019;9:1–20. https://doi.org/10.3390/jpm9010003.

    Article  Google Scholar 

  38. Hammond JL, Formisano N, Estrela P, Carrara S, Tkac J. Electrochemical biosensors and nanobiosensors. Essays Biochem. 2016;60:69–80. https://doi.org/10.1042/EBC20150008.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ronkainen NJ, Halsall HB, Heineman WR. Electrochemical biosensors. Chem Soc Rev. 2010;39:1747–63. https://doi.org/10.1039/b714449k.

    Article  CAS  PubMed  Google Scholar 

  40. Rezaei B, Irannejad N. Electrochemical detection techniques in biosensor applications: Elsevier Inc.; 2019.

  41. Davis G. Electrochemical techniques for the development of amperometric biosensors. Biosensors. 1985;1:161–78. https://doi.org/10.1016/0265-928X(85)80002-X.

    Article  CAS  Google Scholar 

  42. Ensafi AA, Khoddami E, Rezaei B. Aptamer@au-o-phenylenediamine modified pencil graphite electrode: a new selective electrochemical impedance biosensor for the determination of insulin. Colloids Surfaces B Biointerfaces. 2017;159:47–53. https://doi.org/10.1016/j.colsurfb.2017.07.076.

    Article  CAS  PubMed  Google Scholar 

  43. Ensafi AA, Khoddami E, Rezaei B. Development of a cleanup and electrochemical determination of flutamide using silica thin film pencil graphite electrode functionalized with thiol groups. J Iran Chem Soc. 2016;13:1683–90. https://doi.org/10.1007/s13738-016-0885-z.

    Article  CAS  Google Scholar 

  44. Bansod BK, Kumar T, Thakur R, Rana S, Singh I. A review on various electrochemical techniques for heavy metal ions detection with different sensing platforms. Biosens Bioelectron. 2017;94:443–55. https://doi.org/10.1016/j.bios.2017.03.031.

    Article  CAS  PubMed  Google Scholar 

  45. Campuzano S, Barderas R, Pedrero M, Yáñez-Sedeño P, Pingarrón JM. Electrochemical biosensing to move forward in cancer epigenetics and metastasis: a review. Anal Chim Acta. 2020;1109:169–90. https://doi.org/10.1016/j.aca.2020.01.047.

    Article  CAS  PubMed  Google Scholar 

  46. Justino CIL, Freitas AC, Pereira R, Duarte AC, Rocha Santos TAP. Recent developments in recognition elements for chemical sensors and biosensors. TrAC - Trends Anal Chem. 2015;68:2–17. https://doi.org/10.1016/j.trac.2015.03.006.

    Article  CAS  Google Scholar 

  47. Khanmohammadi A, Aghaie A, Vahedi E, Qazvini A, Ghanei M, Afkhami A, et al. Electrochemical biosensors for the detection of lung cancer biomarkers: a review. Talanta. 2020;206:120251. https://doi.org/10.1016/j.talanta.2019.120251.

    Article  CAS  PubMed  Google Scholar 

  48. Farbod F, Mazloum-Ardakani M. Typically used nanomaterials-based noncarbon materials in the fabrication of biosensors: Elsevier Inc.; 2019.

  49. Heydari-Bafrooei E, Ensafi AA. Typically used carbon-based nanomaterials in the fabrication of biosensors: Elsevier Inc.; 2019.

  50. Maduraiveeran G, Sasidharan M, Ganesan V. Electrochemical sensor and biosensor platforms based on advanced nanomaterials for biological and biomedical applications. Biosens Bioelectron. 2018;103:113–29. https://doi.org/10.1016/j.bios.2017.12.031.

    Article  CAS  PubMed  Google Scholar 

  51. Luo X, Morrin A, Killard AJ, Smyth MR. Application of nanoparticles in electrochemical sensors and biosensors. Electroanalysis. 2006;18:319–26. https://doi.org/10.1002/elan.200503415.

    Article  CAS  Google Scholar 

  52. Gold P, Freedman SO. Demonstration of tumor-specific antigens in human colonic Carcinomata by immunological tolerance and absorption techniques. J Exp Med. 1965;121:439–62. https://doi.org/10.1084/jem.121.3.439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Han J, Li Y, Feng J, Li M, Wang P, Chen Z, et al. A novel sandwich-type immunosensor for detection of carcino-embryonic antigen using silver hybrid multiwalled carbon nanotubes/manganese dioxide. J Electroanal Chem. 2017;786:112–9. https://doi.org/10.1016/j.jelechem.2017.01.021.

    Article  CAS  Google Scholar 

  54. Yang KM, Park IJ, Kim CW, Roh SA, Cho DH, Kim JC. The prognostic significance and treatment modality for elevated pre- and postoperative serum CEA in colorectal cancer patients. Ann Surg Treat Res. 2016;91:165–71. https://doi.org/10.4174/astr.2016.91.4.165.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Paimard G, Shahlaei M, Moradipour P, Akbari H, Jafari M, Arkan E. An Impedimetric Immunosensor modified with electrospun core-shell nanofibers for determination of the carcinoma embryonic antigen. Sensors Actuators B Chem. 2020;311:127928. https://doi.org/10.1016/j.snb.2020.127928.

    Article  CAS  Google Scholar 

  56. Jia Y, Li Y, Zhang S, Wang P, Liu Q, Dong Y. Mulberry-like au@PtPd porous nanorods composites as signal amplifiers for sensitive detection of CEA. Biosens Bioelectron. 2020;149:111842. https://doi.org/10.1016/j.bios.2019.111842.

    Article  CAS  PubMed  Google Scholar 

  57. Yang Y, Jiang M, Cao K, Wu M, Zhao C, Li H, et al. An electrochemical immunosensor for CEA detection based on au-ag/rGO@PDA nanocomposites as integrated double signal amplification strategy. Microchem J. 2019;151:104223. https://doi.org/10.1016/j.microc.2019.104223.

    Article  CAS  Google Scholar 

  58. Feng T, Qiao X, Wang H, Sun Z, Hong C. A sandwich-type electrochemical immunosensor for carcinoembryonic antigen based on signal amplification strategy of optimized ferrocene functionalized Fe3O4@SiO2 as labels. Biosens Bioelectron. 2016;79:48–54. https://doi.org/10.1016/j.bios.2015.11.001.

    Article  CAS  PubMed  Google Scholar 

  59. Chen Y, Wang AJ, Yuan PX, Luo X, Xue Y, Feng JJ. Three dimensional sea-urchin-like PdAuCu nanocrystals/ferrocene-grafted-polylysine as an efficient probe to amplify the electrochemical signals for ultrasensitive immunoassay of carcinoembryonic antigen. Biosens Bioelectron. 2019;132:294–301. https://doi.org/10.1016/j.bios.2019.02.057.

    Article  CAS  PubMed  Google Scholar 

  60. Zhang C, Zhang S, Jia Y, Li Y, Wang P, Liu Q, et al. Sandwich-type electrochemical immunosensor for sensitive detection of CEA based on the enhanced effects of ag NPs@CS spaced hemin/rGO. Biosens Bioelectron. 2019;126:785–91. https://doi.org/10.1016/j.bios.2018.11.039.

    Article  CAS  PubMed  Google Scholar 

  61. Su S, Sun Q, Wan L, Gu X, Zhu D, Zhou Y, et al. Ultrasensitive analysis of carcinoembryonic antigen based on MoS2-based electrochemical immunosensor with triple signal amplification. Biosens Bioelectron. 2019;140:111353. https://doi.org/10.1016/j.bios.2019.111353.

    Article  CAS  PubMed  Google Scholar 

  62. Ma E, Wang P, Yang Q, Yu H, Pei F, Li Y, et al. Electrochemical immunosensor based on MoS2 NFs/au@AgPt YNCs as signal amplification label for sensitive detection of CEA. Biosens Bioelectron. 2019;142:111580. https://doi.org/10.1016/j.bios.2019.111580.

    Article  CAS  PubMed  Google Scholar 

  63. Chen P, Hua X, Liu J, Liu H, Xia F, Tian D, et al. A dual amplification electrochemical immunosensor based on HRP-au@ag NPs for carcinoembryonic antigen detection. Anal Biochem. 2019;574:23–30. https://doi.org/10.1016/j.ab.2019.03.003.

    Article  CAS  PubMed  Google Scholar 

  64. Akbari Nakhjavani S, Afsharan H, Khalilzadeh B, Ghahremani MH, Carrara S, Omidi Y. Gold and silver bio/nano-hybrids-based electrochemical immunosensor for ultrasensitive detection of carcinoembryonic antigen. 2019;141:111439–Biosens Bioelectron. https://doi.org/10.1016/j.bios.2019.111439.

  65. Ma C, Zhao C, Li W, Song Y, Hong C, Qiao X. Sandwich-type electrochemical immunosensor constructed using three-dimensional lamellar stacked CoS2@C hollow nanotubes prepared by template-free method to detect carcinoembryonic antigen. Anal Chim Acta. 2019;1088:54–62. https://doi.org/10.1016/j.aca.2019.09.007.

    Article  CAS  PubMed  Google Scholar 

  66. Butmee P, Tumcharern G, Thouand G, Kalcher K, Samphao A. An ultrasensitive immunosensor based on manganese dioxide-graphene nanoplatelets and core shell Fe3O4@au nanoparticles for label-free detection of carcinoembryonic antigen. Bioelectrochemistry. 2020;132:107452. https://doi.org/10.1016/j.bioelechem.2019.107452.

    Article  CAS  PubMed  Google Scholar 

  67. Song Y, Cao K, Li W, Ma C, Qiao X, Li H, et al. Optimal film thickness of rGO/MoS2 @ polyaniline nanosheets of 3D arrays for carcinoembryonic antigen high sensitivity detection. Microchem J. 2020;155:104694. https://doi.org/10.1016/j.microc.2020.104694.

    Article  CAS  Google Scholar 

  68. Song Y, Li W, Ma C, Sun Y, Qiao J, Li H, et al. First use of inorganic copper silicate-transduced enzyme-free electrochemical immunosensor for carcinoembryonic antigen detection. Sens Actuators B Chem. 2020:128311. https://doi.org/10.1016/j.snb.2020.128311.

  69. Li W, Qiao X, Hong C, Ma C, Song Y. A sandwich-type electrochemical immunosensor for detecting CEA based on CeO2-MoS2 absorbed Pb2+. Anal Biochem. 2020;592. https://doi.org/10.1016/j.ab.2019.113566.

  70. Li X, Liu L, Xu Z, Wang W, Shi J, Liu L, et al. Gamma irradiation and microemulsion assisted synthesis of monodisperse flower-like platinum-gold nanoparticles/reduced graphene oxide nanocomposites for ultrasensitive detection of carcinoembryonic antigen. Sensors Actuators B Chem. 2019;287:267–77. https://doi.org/10.1016/j.snb.2019.02.026.

    Article  CAS  Google Scholar 

  71. Zhang X, Yu Y, Shen J, Qi W, Wang H. Design of organic/inorganic nanocomposites for ultrasensitive electrochemical detection of a cancer biomarker protein. Talanta. 2020;212:120794. https://doi.org/10.1016/j.talanta.2020.120794.

    Article  CAS  PubMed  Google Scholar 

  72. Koprowski H, Herlyn M, Steplewski Z, Sears HF. Specific antigen in serum of patients with colon carcinoma. Science (80-). 1981;212:53–5. https://doi.org/10.1126/science.6163212.

    Article  CAS  Google Scholar 

  73. Nakayama T, Watanabe M, Teramoto T, Kitajima M. CA19-9 as a predictor of recurrence in patients with colorectal cancer. J Surg Oncol. 1997;66:238–43. https://doi.org/10.1002/(SICI)1096-9098(199712)66:4<238::AID-JSO3>3.0.CO;2-C.

    Article  CAS  PubMed  Google Scholar 

  74. Xu X, Niu M, Zhang B, Chang J, Su F, Wang K. Clinical value of CEA and CA19-9 in colorectal cancer by Kaplan-Meier survival curve. 2019;12:13305–10.

  75. Wang R, Feng JJ, Liu WD, Jiang LY, Wang AJ. A novel label-free electrochemical immunosensor based on the enhanced catalytic currents of oxygen reduction by AuAg hollow nanocrystals for detecting carbohydrate antigen 199. Biosens Bioelectron. 2017;96:152–8. https://doi.org/10.1016/j.bios.2017.05.007.

    Article  CAS  PubMed  Google Scholar 

  76. Wang L, Shan J, Feng F, Ma Z. Novel redox species polyaniline derivative-au/Pt as sensing platform for label-free electrochemical immunoassay of carbohydrate antigen 199. Anal Chim Acta. 2016;911:108–13. https://doi.org/10.1016/j.aca.2016.01.016.

    Article  CAS  PubMed  Google Scholar 

  77. Yang F, Yang Z, Zhuo Y, Chai Y, Yuan R. Ultrasensitive electrochemical immunosensor for carbohydrate antigen 19-9 using au/porous graphene nanocomposites as platform and au@Pd core/shell bimetallic functionalized graphene nanocomposites as signal enhancers. Biosens Bioelectron. 2015;66:356–62. https://doi.org/10.1016/j.bios.2014.10.066.

    Article  CAS  PubMed  Google Scholar 

  78. Hu F, Chen S, Yuan R. Application of magnetic core-shell microspheres on reagentless immunosensor based on direct electrochemistry of glucose oxidase for detection of carbohydrate antigen 19-9. Sens Actuators, B Chem. 2013;176:713–22. https://doi.org/10.1016/j.snb.2012.08.072.

    Article  CAS  Google Scholar 

  79. Zhang Q, Chen X, Tang Y, Ge L, Guo B, Yao C. Amperometric carbohydrate antigen 19-9 immunosensor based on three dimensional ordered macroporous magnetic au film coupling direct electrochemistry of horseradish peroxidase. Anal Chim Acta. 2014;815:42–50. https://doi.org/10.1016/j.aca.2014.01.033.

    Article  CAS  PubMed  Google Scholar 

  80. Jiang Z, Zhao C, Lin L, Weng S, Liu Q, Lin X. A label-free electrochemical immunosensor based on poly(thionine)-SDS nanocomposites for CA19-9 detection. Anal Methods. 2015;7:4508–13. https://doi.org/10.1039/c5ay00576k.

    Article  CAS  Google Scholar 

  81. Guo A, Li Y, Cao W, Meng X, Wu D, Wei Q, et al. An electrochemical immunosensor for ultrasensitive detection of carbohydrate antigen 199 based on Au@CuxOS yolk-shell nanostructures with porous shells as labels. Biosens Bioelectron. 2015;63:39–46. https://doi.org/10.1016/j.bios.2014.07.017.

    Article  CAS  PubMed  Google Scholar 

  82. Sun AL, Qi QA. Silver-functionalized g-C3N4 nanohybrids as signal-transduction tags for electrochemical immunoassay of human carbohydrate antigen 19-9. Analyst. 2016;141:4366–72. https://doi.org/10.1039/c6an00696e.

    Article  CAS  PubMed  Google Scholar 

  83. Huang Z, Jiang Z, Zhao C, Han W, Lin L, Liu A, et al. Simple and effective label-free electrochemical immunoassay for carbohydrate antigen 19-9 based on polythionine-au composites as enhanced sensing signals for detecting different clinical samples. Int J Nanomedicine. 2017;12:3049–58. https://doi.org/10.2147/IJN.S131805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Weng X, Liu Y, Xue Y, Wang AJ, Wu L, Feng JJ. L-proline bio-inspired synthesis of AuPt nanocalliandras as sensing platform for label-free electrochemical immunoassay of carbohydrate antigen 19-9. Sensors Actuators B Chem. 2017;250:61–8. https://doi.org/10.1016/j.snb.2017.04.156.

    Article  CAS  Google Scholar 

  85. Li W, Shu D, Zhang D, Ma Z. Multi-amplification of the signal of voltammetric immunosensors: highly sensitive detection of tumor marker. Sensors Actuators B Chem. 2018;262:50–6. https://doi.org/10.1016/j.snb.2018.01.208.

    Article  CAS  Google Scholar 

  86. Wang M, Hu M, Hu B, Guo C, Song Y, Jia Q, et al. Bimetallic cerium and ferric oxides nanoparticles embedded within mesoporous carbon matrix: electrochemical immunosensor for sensitive detection of carbohydrate antigen 19-9. Biosens Bioelectron. 2019;135:22–9. https://doi.org/10.1016/j.bios.2019.04.018.

    Article  CAS  PubMed  Google Scholar 

  87. Zhang N, Zhang D, Chu C, Ma Z. Label-assisted chemical adsorption triggered conversion of electroactivity of sensing interface to achieve the ag/AgCl process for ultrasensitive detection of CA 19-9. Anal Chim Acta. 2020;1093:43–51. https://doi.org/10.1016/j.aca.2019.09.061.

    Article  CAS  PubMed  Google Scholar 

  88. McAuley JL, Linden SK, Chin WP, King RM, Pennington HL, Gendler SJ, et al. MUC1 cell surface mucin is a critical element of the mucosal barrier to infection. J Clin Invest. 2007;117:2313–24. https://doi.org/10.1172/JCI26705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hasanzadeh M, Shadjou N, de la Guardia M. Early stage screening of breast cancer using electrochemical biomarker detection. TrAC - Trends Anal Chem. 2017;91:67–76. https://doi.org/10.1016/j.trac.2017.04.006.

    Article  CAS  Google Scholar 

  90. Ahmad R, Alam M, Hasegawa M, Uchida Y, Al-Obaid O, Kharbanda S, et al. Targeting MUC1-C inhibits the AKT-S6K1-elF4A pathway regulating TIGAR translation in colorectal cancer. Mol Cancer. 2017;16:1–9. https://doi.org/10.1186/s12943-017-0608-9.

    Article  CAS  Google Scholar 

  91. Niv Y, Rokkas T. Mucin expression in colorectal Cancer (CRC): systematic review and meta-analysis. J Clin Gastroenterol. 2019;53:434–40. https://doi.org/10.1097/MCG.0000000000001050.

    Article  CAS  PubMed  Google Scholar 

  92. Bharti A, Rana S, Dahiya D, Agnihotri N, Prabhakar N. An electrochemical aptasensor for analysis of MUC1 using gold platinum bimetallic nanoparticles deposited carboxylated graphene oxide. Anal Chim Acta. 2020;1097:186–95. https://doi.org/10.1016/j.aca.2019.11.005.

    Article  CAS  PubMed  Google Scholar 

  93. Zhao RN, Feng Z, Zhao YN, Jia LP, Ma RN, Zhang W, et al. A sensitive electrochemical aptasensor for mucin 1 detection based on catalytic hairpin assembly coupled with PtPdNPs peroxidase-like activity. Talanta. 2019;200:503–10. https://doi.org/10.1016/j.talanta.2019.03.012.

    Article  CAS  PubMed  Google Scholar 

  94. Nawaz MAH, Rauf S, Catanante G, Nawaz MH, Nunes G, Marty JL, et al. One step assembly of thin films of carbon nanotubes on screen printed interface for electrochemical aptasensing of breast cancer biomarker. Sensors (Switzerland). 2016;16. https://doi.org/10.3390/s16101651.

  95. Wang M, Hu B, Ji H, Song Y, Liu J, Peng D, et al. Aptasensor based on hierarchical core-shell nanocomposites of zirconium hexacyanoferrate nanoparticles and mesoporous mFe3O4@mC: electrochemical quantitation of epithelial tumor marker mucin-1. ACS Omega. 2017;2:6809–18. https://doi.org/10.1021/acsomega.7b01065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Song J, Zhou Y, Chen B, Lou W, Gu J. Development of electrochemical aptamer biosensor for tumor marker MUC1 determination. Int J Electrochem Sci. 2017;12:5618–27. https://doi.org/10.20964/2017.06.46.

    Article  CAS  Google Scholar 

  97. Gupta P, Bharti A, Kaur N, Singh S, Prabhakar N. An electrochemical aptasensor based on gold nanoparticles and graphene oxide doped poly(3,4-ethylenedioxythiophene) nanocomposite for detection of MUC1. J Electroanal Chem. 2018;813:102–8. https://doi.org/10.1016/j.jelechem.2018.02.014.

    Article  CAS  Google Scholar 

  98. Yang S, Zhang F, Liang Q, Wang Z. A three-dimensional graphene-based ratiometric signal amplification aptasensor for MUC1 detection. Biosens Bioelectron. 2018;120:85–92. https://doi.org/10.1016/j.bios.2018.08.036.

    Article  CAS  PubMed  Google Scholar 

  99. Rauf S, Mishra GK, Azhar J, Mishra RK, Goud KY, Nawaz MAH, et al. Carboxylic group riched graphene oxide based disposable electrochemical immunosensor for cancer biomarker detection. Anal Biochem. 2018;545:13–9. https://doi.org/10.1016/j.ab.2018.01.007.

    Article  CAS  PubMed  Google Scholar 

  100. Wang H, Sun J, Lu L, Yang X, Xia J, Zhang F, et al. Competitive electrochemical aptasensor based on a cDNA-ferrocene/MXene probe for detection of breast cancer marker Mucin1. Anal Chim Acta. 2020;1094:18–25. https://doi.org/10.1016/j.aca.2019.10.003.

    Article  CAS  PubMed  Google Scholar 

  101. Esfandi F, Mohammadzadeh Ghobadloo S, Basati G. Interleukin-6 level in patients with colorectal cancer. Cancer Lett. 2006;244:76–8. https://doi.org/10.1016/j.canlet.2005.12.003.

    Article  CAS  PubMed  Google Scholar 

  102. Knüpfer H, Preiss R. Serum interleukin-6 levels in colorectal cancer patients-a summary of published results. Int J Colorectal Dis. 2010;25:135–40. https://doi.org/10.1007/s00384-009-0818-8.

    Article  PubMed  Google Scholar 

  103. Tertis M, Leva PI, Bogdan D, Suciu M, Graur F, Cristea C. Impedimetric aptasensor for the label-free and selective detection of Interleukin-6 for colorectal cancer screening. Biosens Bioelectron. 2019;137:123–32. https://doi.org/10.1016/j.bios.2019.05.012.

    Article  CAS  PubMed  Google Scholar 

  104. Tertiş M, Ciui B, Suciu M, Săndulescu R, Cristea C. Label-free electrochemical aptasensor based on gold and polypyrrole nanoparticles for interleukin 6 detection. Electrochim Acta. 2017;258:1208–18. https://doi.org/10.1016/j.electacta.2017.11.176.

    Article  CAS  Google Scholar 

  105. Yang T, Wang S, Jin H, Bao W, Huang S, Wang J. An electrochemical impedance sensor for the label-free ultrasensitive detection of interleukin-6 antigen. Sensors Actuators, B Chem. 2013;178:310–5. https://doi.org/10.1016/j.snb.2012.12.107.

    Article  CAS  Google Scholar 

  106. Wang G, He X, Chen L, Zhu Y, Zhang X. Ultrasensitive IL-6 electrochemical immunosensor based on Au nanoparticles-graphene-silica biointerface. Colloids Surfaces B Biointerfaces. 2014;116:714–9. https://doi.org/10.1016/j.colsurfb.2013.11.015.

    Article  CAS  PubMed  Google Scholar 

  107. Lou Y, He T, Jiang F, Shi JJ, Zhu JJ. A competitive electrochemical immunosensor for the detection of human interleukin-6 based on the electrically heated carbon electrode and silver nanoparticles functionalized labels. Talanta. 2014;122:135–9. https://doi.org/10.1016/j.talanta.2014.01.016.

    Article  CAS  PubMed  Google Scholar 

  108. Kumar LSS, Wang X, Hagen J, Naik R, Papautsky I, Heikenfeld J. Label free nano-aptasensor for interleukin-6 in protein-dilute bio fluids such as sweat. Anal Methods. 2016;8:3440–4. https://doi.org/10.1039/c6ay00331a.

    Article  CAS  Google Scholar 

  109. Qi M, Huang J, Wei H, Cao C, Feng S, Guo Q, et al. Graphene oxide thin film with dual function integrated into a nanosandwich device for in vivo monitoring of Interleukin-6. ACS Appl Mater Interfaces. 2017;9:41659–68. https://doi.org/10.1021/acsami.7b10753.

    Article  CAS  PubMed  Google Scholar 

  110. Tertiş M, Melinte G, Ciui B, Şimon I, Ştiufiuc R, Săndulescu R, et al. A Novel Label Free Electrochemical Magnetoimmunosensor for Human Interleukin-6 Quantification in Serum. Electroanalysis. 2019;31:282–92. https://doi.org/10.1002/elan.201800620.

    Article  CAS  Google Scholar 

  111. Russell C, Ward AC, Vezza V, Hoskisson P, Alcorn D, Steenson DP, et al. Development of a needle shaped microelectrode for electrochemical detection of the sepsis biomarker interleukin-6 (IL-6) in real time. Biosens Bioelectron. 2019;126:806–14. https://doi.org/10.1016/j.bios.2018.11.053.

    Article  CAS  PubMed  Google Scholar 

  112. Aydın EB. Highly sensitive impedimetric immunosensor for determination of interleukin 6 as a cancer biomarker by using conjugated polymer containing epoxy side groups modified disposable ITO electrode. Talanta. 2020;215:120909. https://doi.org/10.1016/j.talanta.2020.120909.

    Article  CAS  PubMed  Google Scholar 

  113. Wright M, Beaty JS, Ternent CA. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97:683–701. https://doi.org/10.1016/j.suc.2017.01.014.

    Article  PubMed  Google Scholar 

  114. Attallah AM, Abdel-Aziz MM, El-Sayed AM, Tabll AA. Detection of serum p53 protein in patients with different gastrointestinal cancers. Cancer Detect Prev. 2003;27:127–31. https://doi.org/10.1016/S0361-090X(03)00024-2.

    Article  CAS  PubMed  Google Scholar 

  115. Aydın EB, Aydın M, Sezgintürk MK. Electrochemical immunosensor based on chitosan/conductive carbon black composite modified disposable ITO electrode: An analytical platform for p53 detection. Biosens Bioelectron. 2018;121:80–9. https://doi.org/10.1016/j.bios.2018.09.008.

    Article  CAS  PubMed  Google Scholar 

  116. Giannetto M, Bianchi MV, Mattarozzi M, Careri M. Competitive amperometric immunosensor for determination of p53 protein in urine with carbon nanotubes/gold nanoparticles screen-printed electrodes: A potential rapid and noninvasive screening tool for early diagnosis of urinary tract carcinoma. Anal Chim Acta. 2017;991:133–41. https://doi.org/10.1016/j.aca.2017.09.005.

    Article  CAS  PubMed  Google Scholar 

  117. Ding L, Zhang L, Yang H, Liu H, Ge S, Yu J (2018) Electrochemical biosensor for p53 gene based on HRP-mimicking DNAzyme-catalyzed deposition of polyaniline coupled with hybridization chain reaction. Sensors Actuators, B Chem 268:210–216. https://doi.org/10.1016/j.snb.2018.04.126

  118. Wang X, Gao C, Shu G, Wang Y, Liu X. The enzyme electrocatalytic immunosensor based on functional composite nanofibers for sensitive detection of tumor suppressor protein p53. J Electroanal Chem. 2015;756:101–7. https://doi.org/10.1016/j.jelechem.2015.08.022.

    Article  CAS  Google Scholar 

  119. Afsharan H, Khalilzadeh B, Tajalli H, Mollabashi M, Navaeipour F, Rashidi MR. A sandwich type immunosensor for ultrasensitive electrochemical quantification of p53 protein based on gold nanoparticles/graphene oxide. Electrochim Acta. 2016;188:153–64. https://doi.org/10.1016/j.electacta.2015.11.133.

    Article  CAS  Google Scholar 

  120. Hasanzadeh M, Baghban HN, Mokhtarzadeh A, Shadjou N, Mahboob S. An innovative immunosensor for detection of tumor suppressor protein p53 in unprocessed human plasma and cancer cell lysates. Int J Biol Macromol. 2017;105:1337–48. https://doi.org/10.1016/j.ijbiomac.2017.07.165.

    Article  CAS  PubMed  Google Scholar 

  121. Aydın M, Aydın EB, Sezgintürk MK. A disposable immunosensor using ITO based electrode modified by a star-shaped polymer for analysis of tumor suppressor protein p53 in human serum. Biosens Bioelectron. 2018;107:1–9. https://doi.org/10.1016/j.bios.2018.02.017.

    Article  CAS  PubMed  Google Scholar 

  122. Hasanzadeh M, Baghban HN, Shadjou N, Mokhtarzadeh A. Ultrasensitive electrochemical immunosensing of tumor suppressor protein p53 in unprocessed human plasma and cell lysates using a novel nanocomposite based on poly-cysteine/graphene quantum dots/gold nanoparticle. Int J Biol Macromol. 2018;107:1348–63. https://doi.org/10.1016/j.ijbiomac.2017.11.006.

    Article  CAS  PubMed  Google Scholar 

  123. Adeniyi OK, Mashazi PN. Stable thin films of human P53 antigen on gold surface for the detection of tumour associated anti-P53 autoantibodies. Electrochim Acta. 2020;331:135272. https://doi.org/10.1016/j.electacta.2019.135272.

    Article  CAS  Google Scholar 

  124. Amor-Gutiérrez O, Costa-Rama E, Arce-Varas N, Martínez-Rodríguez C, Novelli A, Fernández-Sánchez MT, et al. Competitive electrochemical immunosensor for the detection of unfolded p53 protein in blood as biomarker for Alzheimer’s disease. Anal Chim Acta. 2020;1093:28–34. https://doi.org/10.1016/j.aca.2019.09.042.

    Article  CAS  PubMed  Google Scholar 

  125. Bi Q, Gan X, Yuan R, Xiang Y. Copper-free click chemistry-mediated cyclic ligation amplification for highly sensitive and non-label electrochemical detection of gene mutation. J Electrochem Soc. 2020;167:027535. https://doi.org/10.1149/1945-7111/ab6a81.

    Article  CAS  Google Scholar 

  126. Das J, Kelley SO. High-Performance Nucleic Acid Sensors for Liquid Biopsy Applications. Angew Chemie - Int Ed. 2020;59:2554–64. https://doi.org/10.1002/anie.201905005.

    Article  CAS  Google Scholar 

  127. Lin L, Weng S, Zhao C, Liu Q, Liu A, Lin X. Hairpin LNA biosensor with enzyme tagged AuNPs as tracer foramperometric detection of K-ras mutation gene. Electrochim Acta. 2013;108:808–13. https://doi.org/10.1016/j.electacta.2013.07.042.

    Article  CAS  Google Scholar 

  128. Wang X, Shu G, Gao C, Yang Y, Xu Q, Tang M. Electrochemical biosensor based on functional composite nanofibers for detection of K-ras gene via multiple signal amplification strategy. Anal Biochem. 2014;466:51–8. https://doi.org/10.1016/j.ab.2014.08.023.

    Article  CAS  PubMed  Google Scholar 

  129. Zhou X, Liu X, Xia X, Yang X, Xiang H. Sensitive, enzyme-free and label-free electrochemical sensor for K-ras G12D point mutation detection based on double cascade amplification reaction. J Electroanal Chem. 2020;870:114270. https://doi.org/10.1016/j.jelechem.2020.114270.

    Article  CAS  Google Scholar 

  130. Xiao Q, Feng J, Li J, Liu Y, Wang D, Huang S. A ratiometric electrochemical biosensor for ultrasensitive and highly selective detection of the K-ras gene via exonuclease III-assisted target recycling and rolling circle amplification strategies. Anal Methods. 2019;11:4146–56. https://doi.org/10.1039/c9ay01007f.

    Article  CAS  Google Scholar 

  131. Shu Q, Liao F, Hong N, Cheng L, Lin Y, Cui H, et al. A novel DNA sensor of homogeneous electrochemical signal amplification strategy. Microchem J. 2020;156:104777. https://doi.org/10.1016/j.microc.2020.104777.

    Article  CAS  Google Scholar 

  132. Zhao C, Gao F, Weng S, Liu Q, Lin L, Lin X. An electrochemical sensor based on DNA polymerase and HRP-SiO2 nanoparticles for the ultrasensitive detection of K-ras gene point mutation. RSC Adv. 2016;6:8669–76. https://doi.org/10.1039/c5ra24737c.

    Article  CAS  Google Scholar 

  133. Fang X, Bai L, Han X, Wang J, Shi A, Zhang Y. Ultra-sensitive biosensor for K-ras gene detection using enzyme capped gold nanoparticles conjugates for signal amplification. Anal Biochem. 2014;460:47–53. https://doi.org/10.1016/j.ab.2014.05.019.

    Article  CAS  PubMed  Google Scholar 

  134. Rashid JIA, Yusof NA. The strategies of DNA immobilization and hybridization detection mechanism in the construction of electrochemical DNA sensor: A review. Sens Bio-Sensing Res. 2017;16:19–31. https://doi.org/10.1016/j.sbsr.2017.09.001.

    Article  Google Scholar 

  135. Martinelli E, Ciardiello D, Martini G, Troiani T, Cardone C, Vitiello PP, et al. Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives. Ann Oncol. 2020;31:30–40. https://doi.org/10.1016/j.annonc.2019.10.007.

    Article  CAS  PubMed  Google Scholar 

  136. Cohen RB. Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clin Colorectal Cancer. 2003;2:246–51. https://doi.org/10.3816/CCC.2003.n.006.

    Article  CAS  PubMed  Google Scholar 

  137. Vasudev A, Kaushik A, Bhansali S. Electrochemical immunosensor for label free epidermal growth factor receptor (EGFR) detection. Biosens Bioelectron. 2013;39:300–5. https://doi.org/10.1016/j.bios.2012.06.012.

    Article  CAS  PubMed  Google Scholar 

  138. Mousavi MF, Mirsian S, Noori A, Ilkhani H, Sarparast M, Moradi N, et al. BSA-templated Pb Nanocluster as a Biocompatible Signaling Probe for Electrochemical EGFR Immunosensing. Electroanalysis. 2017;29:861–72. https://doi.org/10.1002/elan.201600537.

    Article  CAS  Google Scholar 

  139. Ilkhani H, Sarparast M, Noori A, Bathaie SZ, Mousavi MF. Electrochemical aptamer/antibody based sandwich immunosensor for the detection of EGFR, a cancer biomarker, using gold nanoparticles as a signaling probe. Biosens Bioelectron. 2015;74:491–7. https://doi.org/10.1016/j.bios.2015.06.063.

    Article  CAS  PubMed  Google Scholar 

  140. Shoja Y, Kermanpur A, Karimzadeh F, Ghodsi J, Rafati AA, Adhami S (2019) Electrochemical molecularly bioimprinted siloxane biosensor on the basis of core/shell silver nanoparticles/EGFR exon 21 L858R point mutant gene/siloxane film for ultra-sensing of gemcitabine as a lung cancer chemotherapy medication. Elsevier B.V.

  141. Bakshi S, Mehta S, Kumeria T, Shiddiky MJA, Popat A, Choudhury S, et al. Rapid fabrication of homogeneously distributed hyper-branched gold nanostructured electrode based electrochemical immunosensor for detection of protein biomarkers. Sensors Actuators, B Chem. 2021;326:128803. https://doi.org/10.1016/j.snb.2020.128803.

    Article  CAS  Google Scholar 

  142. Ortega FG, Piguillem SV, Messina GA, Tortella GR, Rubilar O, Jiménez Castillo MI, et al. EGFR detection in extracellular vesicles of breast cancer patients through immunosensor based on silica-chitosan nanoplatform. Talanta. 2019;194:243–52. https://doi.org/10.1016/j.talanta.2018.10.016.

    Article  CAS  PubMed  Google Scholar 

  143. Johari-Ahar M, Karami P, Ghanei M, Afkhami A, Bagheri H. Development of a molecularly imprinted polymer tailored on disposable screen-printed electrodes for dual detection of EGFR and VEGF using nano-liposomal amplification strategy. Biosens Bioelectron. 2018;107:26–33. https://doi.org/10.1016/j.bios.2018.02.005.

    Article  CAS  PubMed  Google Scholar 

  144. Omidfar K, Darzianiazizi M, Ahmadi A, Daneshpour M, Shirazi H. A high sensitive electrochemical nanoimmunosensor based on Fe3O4/TMC/Au nanocomposite and PT-modified electrode for the detection of cancer biomarker epidermal growth factor receptor. Sens Actuators, B Chem. 2015;220:1311–9. https://doi.org/10.1016/j.snb.2015.07.021.

    Article  CAS  Google Scholar 

  145. Yan X, Song Y, Liu J, Zhou N, Zhang C, He L. Biosensors and Bioelectronics Two-dimensional porphyrin-based covalent organic framework : A novel platform for sensitive epidermal growth factor receptor and living cancer cell detection. Biosens Bioelectron. 2019;126:734–42. https://doi.org/10.1016/j.bios.2018.11.047.

    Article  CAS  PubMed  Google Scholar 

  146. Wang Y, Sun S, Luo J, Xiong Y, Ming T, Liu J, et al. Low sample volume origami-paper-based graphene-modified aptasensors for label-free electrochemical detection of cancer biomarker-EGFR. Microsystems Nanoeng. 2020;6. https://doi.org/10.1038/s41378-020-0146-2.

  147. Regiart M, Fernández-baldo MA, Villarroel-rocha J, Germán A, Bertolino FA, Sapag K, et al. AC SC. Anal Chim Acta. 2017. https://doi.org/10.1016/j.aca.2017.01.029.

  148. Maqbool R, Hussain MU. MicroRNAs and human diseases: diagnostic and therapeutic potential. Cell Tissue Res. 2014;358:1–15. https://doi.org/10.1007/s00441-013-1787-3.

    Article  CAS  PubMed  Google Scholar 

  149. Shirafkan N, Mansoori B, Mohammadi A, Shomali N, Ghasbi M, Baradaran B. MicroRNAs as novel biomarkers for colorectal cancer: New outlooks. Biomed Pharmacother. 2018;97:1319–30. https://doi.org/10.1016/j.biopha.2017.11.046.

    Article  CAS  PubMed  Google Scholar 

  150. Ng EKO, Chong WWS, Jin H, Lam EKY, Shin VY, Yu J, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: A potential marker for colorectal cancer screening. Gut. 2009;58:1375–81. https://doi.org/10.1136/gut.2008.167817.

    Article  CAS  PubMed  Google Scholar 

  151. Marcuello M, Vymetalkova V, Neves RPL, Duran-Sanchon S, Vedeld HM, Tham E, et al. Circulating biomarkers for early detection and clinical management of colorectal cancer. Mol Aspects Med. 2019;69:107–22. https://doi.org/10.1016/j.mam.2019.06.002.

    Article  CAS  PubMed  Google Scholar 

  152. Li T, Leong MH, Harms B, Kennedy G, Chen L. MicroRNA-21 as a potential colon and rectal cancer biomarker. World J Gastroenterol. 2013;19:5615–21. https://doi.org/10.3748/wjg.v19.i34.5615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50:298–301. https://doi.org/10.1016/j.ymeth.2010.01.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Jiang L, Wu CL, Wu JZ, Yang X, Lin WH, Li GJ. Microarray-based measurement of microRNA-449c-5p levels in hepatocellular carcinoma and bioinformatic analysis of potential signaling pathways. Pathol Res Pract. 2019;215:68–81. https://doi.org/10.1016/j.prp.2018.10.007.

    Article  CAS  PubMed  Google Scholar 

  155. Lovatt D, Eberwine J. Northern blotting: Elsevier Inc.; 2013.

  156. Kilic T, Erdem A, Ozsoz M, Carrara S. microRNA biosensors: Opportunities and challenges among conventional and commercially available techniques. Biosens Bioelectron. 2018;99:525–46. https://doi.org/10.1016/j.bios.2017.08.007.

    Article  CAS  PubMed  Google Scholar 

  157. Hamidi-Asl E, Palchetti I, Hasheminejad E, Mascini M. A review on the electrochemical biosensors for determination of microRNAs. Talanta. 2013;115:74–83. https://doi.org/10.1016/j.talanta.2013.03.061.

    Article  CAS  PubMed  Google Scholar 

  158. Mohammadi H, Yammouri G, Amine A. Current advances in electrochemical genosensors for detecting microRNA cancer markers. Curr Opin Electrochem. 2019;16:96–105. https://doi.org/10.1016/j.coelec.2019.04.030.

    Article  CAS  Google Scholar 

  159. Mandli J, Mohammadi H, Amine A. Electrochemical DNA sandwich biosensor based on enzyme amplified microRNA-21 detection and gold nanoparticles. Bioelectrochemistry. 2017;116:17–23. https://doi.org/10.1016/j.bioelechem.2017.03.002.

    Article  CAS  PubMed  Google Scholar 

  160. Tian L, Qian K, Qi J, Liu Q, Yao C, Song W, et al. Gold nanoparticles superlattices assembly for electrochemical biosensor detection of microRNA-21. Biosens Bioelectron. 2018;99:564–70. https://doi.org/10.1016/j.bios.2017.08.035.

    Article  CAS  PubMed  Google Scholar 

  161. Xu L, Duan J, Chen J, Ding S, Cheng W. Recent advances in rolling circle amplification-based biosensing strategies-A review. Anal Chim Acta. 2020. https://doi.org/10.1016/j.aca.2020.12.062.

  162. Duan Y, Li Y, Zhang C, Chen J, Sun R, Huang Z, et al. The recent development of hybridization chain reaction strategies in biosensors. ACS Sensors. 2020;5:2977–3000. https://doi.org/10.1021/acssensors.0c01453.

    Article  CAS  PubMed  Google Scholar 

  163. Cui Y, Fan S, Yuan Z, Song M, Hu J, Qian D, et al. Ultrasensitive electrochemical assay for microRNA-21 based on CRISPR/Cas13a-assisted catalytic hairpin assembly. Talanta. 2021;224:121878. https://doi.org/10.1016/j.talanta.2020.121878.

    Article  CAS  PubMed  Google Scholar 

  164. Li Q, Zeng F, Lyu N, Liang J. Highly sensitive and specific electrochemical biosensor for microRNA-21 detection by coupling catalytic hairpin assembly with rolling circle amplification. Analyst. 2018;143:2304–9. https://doi.org/10.1039/c8an00437d.

    Article  CAS  PubMed  Google Scholar 

  165. Liang M, Pan M, Hu J, Wang F, Liu X. Electrochemical Biosensor for MicroRNA Detection Based on Cascade Hybridization Chain Reaction. ChemElectroChem. 2018;5:1380–6. https://doi.org/10.1002/celc.201800255.

    Article  CAS  Google Scholar 

  166. Cheng H, Li W, Duan S, Peng J, Liu J, Ma W, et al. Mesoporous silica containers and programmed catalytic hairpin assembly/hybridization chain reaction based electrochemical sensing platform for MicroRNA ultrasensitive detection with low background. Anal Chem. 2019;91:10672–8. https://doi.org/10.1021/acs.analchem.9b01947.

    Article  CAS  PubMed  Google Scholar 

  167. Sabahi A, Salahandish R, Ghaffarinejad A, Omidinia E. Talanta Electrochemical nano-genosensor for highly sensitive detection of miR-21 biomarker based on SWCNT-grafted dendritic Au nanostructure for early detection of prostate cancer. Talanta. 2020;209:120595. https://doi.org/10.1016/j.talanta.2019.120595.

    Article  CAS  PubMed  Google Scholar 

  168. Meng T, Shang N, Nsabimana A, Ye H, Wang H, Wang C, et al. Analytica Chimica Acta An enzyme-free electrochemical biosensor based on target-catalytic hairpin assembly and Pd @ UiO-66 for the ultrasensitive detection of. Anal Chim Acta. 2020;1138:59–68. https://doi.org/10.1016/j.aca.2020.09.022.

    Article  CAS  PubMed  Google Scholar 

  169. Shin S, Pan Y, Ji D, Li Y, Lu Y, He Y, et al. Sensors and Actuators B : Chemical Smartphone-based portable electrochemical biosensing system for detection of circulating microRNA-21 in saliva as a proof-of-concept. Sens Actuators B Chem. 2020;308:127718. https://doi.org/10.1016/j.snb.2020.127718.

    Article  CAS  Google Scholar 

  170. Cui Y, Fan S, Yuan Z, Song M, Hu J, Qian D, et al. Talanta Ultrasensitive electrochemical assay for microRNA-21 based on CRISPR / Cas13a-assisted catalytic hairpin assembly. Talanta. 2020:121878. https://doi.org/10.1016/j.talanta.2020.121878.

  171. Liu S, Yang Z, Chang Y, Chai Y, Yuan R. Biosensors and Bioelectronics An enzyme-free electrochemical biosensor combining target recycling with Fe 3 O 4 / CeO 2 @ Au nanocatalysts for microRNA-21 detection. Biosens Bioelectron. 2018;119:170–5. https://doi.org/10.1016/j.bios.2018.08.006.

    Article  CAS  PubMed  Google Scholar 

  172. Wang J, Lu J, Dong S, Zhu N, Gyimah E, Wang K, et al. Biosensors and Bioelectronics An ultrasensitive electrochemical biosensor for detection of microRNA-21 based on redox reaction of ascorbic acid / iodine and duplex-specific nuclease assisted target recycling. Biosens Bioelectron. 2019;130:81–7. https://doi.org/10.1016/j.bios.2019.01.031.

    Article  CAS  PubMed  Google Scholar 

  173. Meng T, Zhao D, Ye H, Feng Y, Wang H, Zhang Y. Journal of Colloid and Interface Science Construction of an ultrasensitive electrochemical sensing platform for microRNA-21 based on interface impedance spectroscopy. J Colloid Interface Sci. 2020;578:164–70. https://doi.org/10.1016/j.jcis.2020.05.118.

    Article  CAS  PubMed  Google Scholar 

  174. Xiao Q, Li J, Jin X, Liu Y, Huang S. Sens Actuators B : Chemical Ultrasensitive electrochemical microRNA-21 biosensor coupling with speci fi c nuclease-assisted target recycling. Sens Actuators B Chem. 2019;297:126740. https://doi.org/10.1016/j.snb.2019.126740.

    Article  CAS  Google Scholar 

  175. Meng T, Jia H, An S, Wang H, Yang X, Zhang Y. Sensors and Actuators B : Chemical Pd nanoparticles-DNA layered nanoreticulation biosensor based on target- catalytic hairpin assembly for ultrasensitive and selective biosensing of. Sens Actuators B Chem. 2020;323:128621. https://doi.org/10.1016/j.snb.2020.128621.

    Article  CAS  Google Scholar 

  176. Xu S, Chang Y, Wu Z, Li Y, Yuan R, Chai Y. Biosensors and Bioelectronics One DNA circle capture probe with multiple target recognition domains for simultaneous electrochemical detection of miRNA-21 and miRNA-155. Biosens Bioelectron. 2020;149:111848. https://doi.org/10.1016/j.bios.2019.111848.

    Article  CAS  PubMed  Google Scholar 

  177. Ordóñez NG. Cadherin 17 is a novel diagnostic marker for adenocarcinomas of the digestive system. Adv Anat Pathol. 2014;21:131–7. https://doi.org/10.1097/PAP.0000000000000008.

    Article  CAS  PubMed  Google Scholar 

  178. Tian X, Han Z, Zhu Q, Tan J, Liu W, Wang Y, et al. Silencing of cadherin-17 enhances apoptosis and inhibits autophagy in colorectal cancer cells. Biomed Pharmacother. 2018;108:331–7. https://doi.org/10.1016/j.biopha.2018.09.020.

    Article  CAS  PubMed  Google Scholar 

  179. Valverde A, Povedano E, Ruiz-Valdepeñas Montiel V, Yáñez-Sedeño P, Garranzo-Asensio M, Rodríguez N, et al. Determination of Cadherin-17 in tumor tissues of different metastatic grade using a single incubation-step Amperometric Immunosensor. Anal Chem. 2018;90:11161–7. https://doi.org/10.1021/acs.analchem.8b03506.

    Article  CAS  PubMed  Google Scholar 

  180. Mahasneh A, Al-Shaheri F, Jamal E. Molecular biomarkers for an early diagnosis, effective treatment and prognosis of colorectal cancer: Current updates. Exp Mol Pathol. 2017;102:475–83. https://doi.org/10.1016/j.yexmp.2017.05.005.

    Article  CAS  PubMed  Google Scholar 

  181. Aghabozorgi AS, Bahreyni A, Soleimani A, Bahrami A, Khazaei M, Ferns GA, et al. Role of adenomatous polyposis coli (APC) gene mutations in the pathogenesis of colorectal cancer; current status and perspectives. Biochimie. 2019;157:64–71. https://doi.org/10.1016/j.biochi.2018.11.003.

    Article  CAS  PubMed  Google Scholar 

  182. Garcia-Melo LF, Álvarez-González I, Madrigal-Bujaidar E, Madrigal-Santillán EO, Morales-González JA, Pineda Cruces RN, et al. Construction of an electrochemical genosensor based on screen-printed gold electrodes (SPGE) for detection of a mutation in the adenomatous polyposis coli gene. J Electroanal Chem. 2019;840:93–100. https://doi.org/10.1016/j.jelechem.2019.03.048.

    Article  CAS  Google Scholar 

  183. Hashkavayi AB, Raoof JB, Ojani R, Kavoosian S. Ultrasensitive electrochemical aptasensor based on sandwich architecture for selective label-free detection of colorectal cancer (CT26) cells. Biosens Bioelectron. 2017;92:630–7. https://doi.org/10.1016/j.bios.2016.10.042.

    Article  CAS  PubMed  Google Scholar 

  184. Liu F, Gao Z, Shen D, Zhao H, Wang C, Ye Y, et al. Significance of SATB2 expression in colon cancer and its differential diagnosis in digestive tract adenocarcinoma and ovarian primary and metastatic carcinoma. Pathol Res Pract. 2019, 215:152430. https://doi.org/10.1016/j.prp.2019.04.022.

  185. Magnusson K, De Wit M, Brennan DJ, Johnson LB, McGee SF, Lundberg E, et al. SATB2 in combination with cytokeratin 20 identifies over 95% of all colorectal carcinomas. Am J Surg Pathol. 2011;35:937–48. https://doi.org/10.1097/PAS.0b013e31821c3dae.

    Article  PubMed  Google Scholar 

  186. Berretta M, Alessandrini L, De Divitiis C, Nasti G, Lleshi A, Di Francia R, et al. Serum and tissue markers in colorectal cancer. State of art. Crit Rev Oncol Hematol. 2017;111:103–16. https://doi.org/10.1016/j.critrevonc.2017.01.007.

    Article  PubMed  Google Scholar 

  187. Rong Q, Feng F, Ma Z. Metal ions doped chitosan-poly(acrylic acid) nanospheres: Synthesis and their application in simultaneously electrochemical detection of four markers of pancreatic cancer. Biosens Bioelectron. 2015;75:148–54. https://doi.org/10.1016/j.bios.2015.08.041.

    Article  CAS  PubMed  Google Scholar 

  188. Valverde A, ben Hassine A, Serafín V, Muñoz-San Martín C, Pedrero M, Garranzo-Asensio M, et al. Dual Amperometric Immunosensor for Improving Cancer Metastasis Detection by the Simultaneous Determination of Extracellular and Soluble Circulating Fraction of Emerging Metastatic Biomarkers. Electroanalysis. 2020;32:706–14. https://doi.org/10.1002/elan.201900506.

    Article  CAS  Google Scholar 

  189. Serafín V, Valverde A, Garranzo-Asensio M, Barderas R, Campuzano S, Yáñez-Sedeño P, et al. Simultaneous amperometric immunosensing of the metastasis-related biomarkers IL-13Rα2 and CDH-17 by using grafted screen-printed electrodes and a composite prepared from quantum dots and carbon nanotubes for signal amplification. Microchim Acta. 2019;186:4–13. https://doi.org/10.1007/s00604-019-3531-5.

    Article  CAS  Google Scholar 

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Acknowledgments

The research is supported by the National Natural Science Fund of China (No. 61901239), Taishan Scholars Program of Shandong Province (No. tsqn201812087), QingChuang science and technology plan of colleges and universities in Shandong Province (No. 2019KJB009), Major Research & Development Program of Shandong Province (No. 2019GGX104044), Shandong Provincial Natural Science Foundation (No. ZR201911150517), 2020 Lu-Yu Science and Technology Cooperation Program (No. 2020LYXZ20), and Undergraduate teaching reform project of higher education of Shandong (No. M2020086).

Funding

Major Research & Development Program of Shandong Province (No. 2019GGX104044), Shandong Provincial Natural Science Foundation (No. ZR201911150517), 2020 Lu-Yu Science and Technology Cooperation Program (No. 2020LYXZ20), Undergraduate teaching reform project of higher education of Shandong (No.M2020086).

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Zhang, W., Xiao, G., Chen, J. et al. Electrochemical biosensors for measurement of colorectal cancer biomarkers. Anal Bioanal Chem 413, 2407–2428 (2021). https://doi.org/10.1007/s00216-021-03197-8

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