CoChat
Sign Up
Cited by 361Electrochemical sensors and biosensorsAdvanced biosensing and bioanalysis techniquesElectrochemical Analysis and Applications

Ultrasensitive Electrochemical Immunosensor for Oral Cancer Biomarker IL-6 Using Carbon Nanotube Forest Electrodes and Multilabel Amplification

Open access
Malhotra, Ruchika, Patel, Vyomesh, Vaqué, Jose Pedro, Gutkind, J. Silvio, Rusling, James F.·2010·Analytical Chemistry
DOI 10.1021/ac902802bPMC PMC2854872
Open this paper in CoChat — free account

Abstract

Squamous cell carcinomas of head and neck (HNSCC) are associated with immune, inflammatory, and angiogenic responses involving interleukin-6 (IL-6). This article reports an ultrasensitive electrochemical immunosensor for human IL-6 and proof-of-concept studies of IL-6 detection in HNSCC cells. Single wall carbon nanotube (SWNT) forests with attached capture antibodies (Ab(1)) for IL-6 were used in an electrochemical sandwich immunoassay protocol using enzyme label horseradish peroxidase (HRP) to measure very low (<or=30 pg mL(-1)) and elevated levels of IL-6. Two levels of multienzyme labeling were used to measure a broad concentration range of IL-6 in a representative panel of HNSCC cells. Secondary antibodies (Ab(2)) attached to carboxylated multiwall carbon nanotubes with 106 HRP labels per 100 nm gave the highest sensitivity of 19.3 nA mL (pg IL-6)(-1) cm(-2) and the best detection limit (DL) of 0.5 pg mL(-1) (25 fM) for IL-6 in 10 microL of calf serum. For more concentrated samples, biotinylated Ab(2) bound to streptavidin-HRP to provide 14-16 labels per antigen was used. These immunosensors accurately measured secreted IL-6 in a wide range of HNSCC cells demonstrated by excellent correlations with standard enzyme-linked immunosorbent assays (ELISA), suggesting that SWNT immunosensors combined with multilabel detection have excellent promise for detecting IL-6 in research and clinical applications.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1021/ac902802b

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The recovered fluorescence intensity exhibits a logarithmic linear relationship with miR-21 concentration over the range of 10 aM to 1 pM.

    “The recovered fluorescence intensity exhibits a logarithmic linear relationship with miR-21 concentration over the range of 10 aM to 1 pM.”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [92]

    The Results section (Immunosensor Calibration; page unavailable) reports sensor current measured against IL-6 concentration, not recovered fluorescence intensity against miR-21. It gives a 0.5–30 pg mL−1 range and describes the calibration as nonlinear, rather than reporting a logarithmic linear relationship from 10 aM to 1 pM. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • The miR-21 sensing approach has been applied to salivary samples from 20 oral cancer patients, achieving a diagnostic sensitivity of 90% and a specificity of 85%.

    “This sensing approach has been successfully applied to salivary samples from 20 oral cancer patients, achieving a diagnostic sensitivity of 90% and a specificity of 85%.”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [92]

    The Results section describes testing conditioned media from ten cell lines for IL-6, not salivary samples from 20 oral cancer patients for miR-21. The Discussion reports an IL-6 detection limit and comparison with ELISA, not diagnostic sensitivity of 90% or specificity of 85%. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • PDA films adsorb FAM-labeled probes complementary to miR-21, resulting in a fluorescence quenching efficiency of 96%.

    “PDA films are first used to adsorb FAM-labeled probes complementary to miR-21, resulting in a fluorescence quenching efficiency of 96%.”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [92]

    The Introduction and Discussion describe carbon-nanotube immunosensors for detecting IL-6, not PDA films or miR-21 probes. Searches for FAM-labeled probes, polydopamine, miR-21, and 96% fluorescence quenching found no passage addressing the claim; page numbers were unavailable in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • In vitro tumor cell studies and selected animal tumor models support NIR-mediated photothermal therapy, drug loading, controlled release, and chemo-photothermal synergistic effects for PDA-based oral tumor therapy.

    “In vitro tumor cell studies and selected animal tumor models support NIR-mediated photothermal therapy, drug loading, controlled release, and chemo-photothermal synergistic effects.”

    From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [92]

    The Introduction (page not available) describes an electrochemical immunosensor for detecting IL-6 in oral cancer cells, not a tumor therapy. Searches for NIR photothermal therapy, drug loading, controlled release, polydopamine/PDA, and animal tumor models found no passage addressing the claimed effects. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 31

  1. [1]Kishimoto T Annu. Rev. Immunol 2005 23 1 21 15771564
  2. [2]Jemal A Murray T Ward E CA Cancer J. Clin 2005 55 10 30 15661684
  3. [3]Thomas GR Nadiminti H Regalado J Int. J. Exp. Pathol 2005 86 347 363 16309541 PMC2517451
  4. [4]Riedel F Zaiss I Herzog D Götte K Naim R Hörmann K Anticancer Res 2005 25 2761 2765 16080523
  5. [5]Hong DS Angelo LS Kurzrock R Cancer 2007 110 1911 1928 17849470
  6. [6]Lilja H Ulmert D Vickers AJ Nat. Rev. Cancer 2008 8 268 278 18337732
  7. [7]Xiao Z Prieto D Conrads TP Veenstra TD Issaq HJ Mol. Cell Endocrinol 2005 230 95 106 15664456
  8. [8]Weston AD Hood L J. Proteome Res 2004 3 179 196 15113093
  9. [9]Wagner PD Verma M Srivastava S Ann. NY Acad. Sci 2004 1022 9 16 15251933
  10. [10]Hanash SM Pitteri SJ Faca VM Nature 2008 452 571 579 18385731
  11. [11]Stevens EV Liotta LA Kohn EC Int. J. Gynecol. Cancer 2003 13 133 139 14656269
  12. [12]Williams TI Toups KL Saggese DA Kalli KR Cliby WA Muddiman DC J. Proteome Res 2007 6 2936 2962 17583933
  13. [13]Kingsmore SF Nat. Rev. Drug Discov 2006 5 310 320 16582876 PMC1780251
  14. [14]Ward MA Catto JWF Hamdy FC Ann. Clin. Biochem 2001 38 633 651 11732646
  15. [15]Hendricks HA Kortlandt W Verweij WM Clin. Chem 2000 46 105 111 10620578
  16. [16]Aebersold R Mann M Nature 2003 422 198 207 12634793
  17. [17]Yurkovetsky ZR Kirkwood JM Edington HD Marrangoni AM Velikokhatnaya L Winans MT Gorelik E Lokshin AE Clin. Cancer Res 2007 13 2422 2428 17438101
  18. [18]Ferrari M Nat. Rev. Cancer 2005 5 161 171 15738981
  19. [19]Debad JB Glenzer EN Wholstadter J Sigal GB Leland JK Bard AJ “Electrogenerated Chemiluminescence”, Chapter 8 2004 NY Marcel Dekker
  20. [20]Lee HJ Wark A Corn RM Analyst 2008 133 975 983 18645635 PMC2738748
  21. [22]Kim SN Rusling JF Papadimitrakopoulos F Adv. Mater 2007 19 3214 3228 18846263 PMC2564812
  22. [23](a) Patolsky F Zheng G Lieber CM Anal. Chem 2006 78 4260 4269 16856252 (b) Zhang H Zhao Q Li XF Le XC Analyst 2007 132 724 737 17646870
  23. [24]Yu X Munge B Patel V Jensen G Bhirde A Gong JD Kim SN Gillespie J Gutkind JS Papadimitrakopoulos F Rusling JF J. Am. Chem. Soc 2006 128 11199 11205 16925438 PMC2482602
  24. [25]Chikkaveeraiah BV Bhirde A Malhotra R Patel V Gutkind JS Rusling JF Anal. Chem 2009 81 9129 9134 19775154 PMC2901508
  25. [26]Munge BS Krause CE Malhotra R Patel V Gutkind JS Rusling JF Electrochem. Comm 2009 11 1009 1012 PMC2735272 20046945
  26. [27]Sriuranpong V Park JI Amornphimoltham P Patel V Nelkin BD Gutkind JS Cancer Res 2003 63 2948 2956 12782602
  27. [28]Jeon GA Lee JS Patel V Gutkind JS Thorgeirsson SS Kim EC Chu IS Amornphimoltham P Park MH Int. J. Cancer 2004 112 249 258 15352037
  28. [29]Yu X Kim SN Papadimitrakopoulos F Rusling JF Mol. BioSyst 2005 1 70 78 16880966
  29. [32]Gallati H J. Clin. Chem. Clin. Biochem 1979 17 1 7 33227
  30. [33]Jensen GC Yu X Gong JD Munge B Bhirde A Kim SN Papadimitrakopoulos F Rusling JF J. Nanosci. Nanotechnol 2009 9 249 255 19441303 PMC2735079
  31. [34]Lu B Elias PM Feingold KR “Skin Barrier”, Chapter 19 2006 Taylor and Francis Group

Cited by

Sorted by citations

Authors
Malhotra, R., Patel, V., Vaqué, J. P., Gutkind, J. S., & Rusling, J. F.
Affiliations
  • National Institutes of Health (US)
  • Department of Chemistry and Institute of Materials Science, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06032, and National University of Ireland at Galway, Ireland
Corresponding author
Rusling, James F.
ORCID
Venue
Analytical Chemistry
Publisher
American Chemical Society (ACS)
Published
2010-03-01
Volume
82
Issue
8
Pages
3118-3123
ISSN
  • 0003-2700 (ISSN-L)
  • 1520-6882
DOI
10.1021/ac902802b
PMC
PMC2854872
OpenAlex
W2038089067
Cited by
361
References
1
Citations by year
2026: 3 · 2025: 8 · 2024: 18 · 2023: 14 · 2022: 13 · 2021: 22 · 2020: 24 · 2019: 17 · 2018: 18 · 2017: 25 · 2016: 27 · 2015: 22 · 2014: 25 · 2013: 36 · 2012: 33
FWCI
31.27
Type
journal article
Language
en
Open access
Locations
  • Analytical Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (acceptedVersion, cc-by-nc-nd)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion)
  • ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc-nd)
  • ARAN (University of Galway Research Repository) (Ollscoil na Gaillimhe – University of Galway) (submittedVersion, cc-by-nc)
  • Research Repository UCD (University College Dublin) (cc-by-nc)
Funders
  • National Institutes of Health
  • National Institute of Environmental Health Sciences (ES013557, R01ES013557)
Topics
  • Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
  • Physical Sciences › Chemistry › Electrochemistry › Electrochemical Analysis and Applications
Keywords
electrochemical immunosensor, interleukin-6, head and neck squamous cell carcinoma, oral cancer biomarkers, sandwich immunoassay, horseradish peroxidase, multi-walled carbon nanotubes, ultrasensitive detection, tumor inflammation
MeSH terms
Carcinoma, Squamous Cell, Electrodes, Enzyme-Linked Immunosorbent Assay, Head and Neck Neoplasms, Humans, Immunoenzyme Techniques, Staining and Labeling, Biomarkers, Tumor, Biosensing Techniques, Interleukin-6, Nanotubes, Carbon, Cell Line, Tumor

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review