CoChat
Sign Up
Cited by 35Nanoparticles: synthesis and applicationsAnimal testing and alternativesCarcinogens and Genotoxicity Assessment

Cause-and-effect analysis as a tool to improve the reproducibility of nanobioassays: four case studies

Open access
Petersen, Elijah J., Hirsch, Cordula, Elliott, John T., Krug, Harald F., Aengenheister, Leonie, Arif, Ali Talib, Bogni, Alessia, Kinsner-Ovaskainen, Agnieszka +4 more·2020·Chemical Research in Toxicology
DOI 10.1021/acs.chemrestox.9b00165
Open this paper in CoChat — free accountOpen PDF

Abstract

One of the challenges in using in vitro data to understand the potential risks of engineered nanomaterials (ENMs) is that results often differ or are even contradictory among studies. While it is recognized that numerous factors can influence results produced by nanobioassays, there has not yet been a consistently used conceptual framework to identify key sources of variability in these assays. In this paper, we use cause-and-effect analysis to systematically describe sources of variability in four key in vitro nanobioassays: the 2′,7′-dichlorofluorescein assay, an enzyme-linked immunosorbent assay for measuring interleukin-8, a flow cytometry assay (Annexin V/propidium iodide), and the Comet assay. These assays measure end points that can occur in cells impacted by ENMs through oxidative stress, a principle mechanism for ENM toxicity. The results from this analysis identify control measurements to test for potential artifacts or biases that could occur during conduct of these assays with ENMs. Cause-and-effect analysis also reveals additional measurements that could be performed either in preliminary experiments or each time the assay is run to increase confidence in the assay results and their reproducibility within and among laboratories. The approach applied here with these four assays can be used to support the development of a broad range of nanobioassays.

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/acs.chemrestox.9b00165

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?

  • Petersen and colleagues discussed sources of variability in four distinct nano-bioassays.

    “Recently, Petersen and colleagues very specifically discussed sources of variability in four distinct nano-bioassays (Petersen et al., 2019).”

    From In Vitro research Reproducibility: Keeping up High Standards (2019) · cites this paper as Petersen et al., 2019

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: 66

  1. Pavlidou, S.; Papaspyrides, C. D., A review on polymer-layered silicate nanocomposites. Prog. 552 Polymer Sci. 2008, 33 (12), 1119-1198. 553
  2. Petersen, E. J.; Lam, T.; Gorham, J. M.; Scott, K. C.; Long, C. J.; Stanley, D.; Sharma, R.; Liddle, J. 557 A.; Pellegrin, B.; Nguyen, T., Methods to assess the impact of UV irradiation on the surface chemistry 558 and structure of multiwall carbon nanotube epoxy nanocomposites. Carbon 2014, 69, 194-205. 559
  3. Potts, J. R.; Dreyer, D. R.; Bielawski, C. W.; Ruoff, R. S., Graphene-based polymer 560 nanocomposites. Polymer 2011, 52 (1), 5-25. 561
  4. Zou, H.; Wu, S. S.; Shen, J., Polymer/silica nanocomposites: Preparation, characterization, 562 properties, and applications. Chem. Rev. 2008, 108 (9), 3893-3957. 563
  5. Froggett, S. J.; Clancy, S. F.; Boverhof, D. R.; Canady, R. A., A review and perspective of existing 564 research on the release of nanomaterials from solid nanocomposites. Part. Fibre Toxicol. 2014, 11. 565
  6. Kuhlbusch, T. A. J.; Wijnhoven, S. W. P.; Haase, A., Nanomaterial exposures for worker, 568 consumer and the general public. Nanoimpact 2018, 10, 11-25. 569
  7. Mitrano, D. M.; Motellier, S.; Clavaguera, S.; Nowack, B., Review of nanomaterial aging and 570 transformations through the life cycle of nano-enhanced products. Environ. Intl. 2015, 77, 132-147. 571
  8. Nowack, B.; David, R. M.; Fissan, H.; Morris, H.; Shatkin, J. A.; Stintz, M.; Zepp, R.; Brouwer, D., 572 Potential release scenarios for carbon nanotubes used in composites. Environ. Intl. 2013, 59, 1-11. 573
  9. G. C. Waissi-Leinonen, E. J. Petersen, K. Pakarinen, J. Akkanen, M. T. Leppanen and J. V. K. 574 Kukkonen, Toxicity of fullerene (C60) to sediment-dwelling invertebrate Chironomus riparius larvae, 575 Environ. Toxicol. Chem., 2012, 31, 2108-2116. 576
  10. Kukkonen, J. V. K., A screening study on the fate of fullerenes (nC60) and their toxic implications in 578 natural freshwaters. Environ. Toxicol. Chem. 2013, 32 (6), 1224-1232. 579
  11. B. C. Nelson, E. J. Petersen, B. J. Marquis, D. H. Atha, J. T. Elliott, D. Cleveland, S. S. Watson, I. H. 580 Tseng, A. Dillon, M. Theodore and J. Jackman, NIST gold nanoparticle reference materials do not induce 581 oxidative DNA damage, Nanotoxicology, 2013, 7, 21-29. 582
  12. Roesslein, M.; Hirsch, C.; Kaiser, J. P.; Krug, H. F.; Wick, P., Comparability of in Vitro Tests for 583 Bioactive Nanoparticles: A Common Assay to Detect Reactive Oxygen Species as an Example. Inter. J. 584 Mol. Sci. 2013, 14 (12), 24320-24337. 585
  13. Rösslein, M.; Elliott, J. T.; Salit, M.; Petersen, E. J.; Hirsch, C.; Krug, H. F.; Wick, P., Use of Cause- 586 and-Effect Analysis to Design a High-Quality Nanocytotoxicology Assay. Chem. Res. Toxicol. 2015, 28 (1), 587 21-30. 588
  14. Rowland, J.; Stone, V.; Doak, S. H., Aligning nanotoxicology with the 3Rs: What is needed to realise the 590 short, medium and long-term opportunities? Regul. Toxicol. and Pharmacol. 2017, 91, 257-266. 591
  15. Haase, A.; Lynch, I., Quality in nanosafety -Towards reliable nanomaterial safety assessment. 595 Nanoimpact 2018, 11, 67-68. 596
  16. Hackley, V.; Xing, B.; White, J. C., Identification and Avoidance of Potential Artifacts and 601 Misinterpretations in Nanomaterial Ecotoxicity Measurements. Environ. Sci. Technol. 2014, 48 (8), 4226- 602 4246. 603
  17. Petersen, E. J.; Reipa, V.; Watson, S. S.; Stanley, D. L.; Rabb, S. A.; Nelson, B. C., DNA Damaging 604 Potential of Photoactivated P25 Titanium Dioxide Nanoparticles. Chem. Res. Toxicol. 2014, 27 (10), 1877- 605 1884. 606
  18. Riebeling, C.; Piret, J.-P.; Trouiller, B.; Nelissen, I.; Saout, C.; Toussaint, O.; Haase, A., A guide to 607 nanosafety testing: Considerations on cytotoxicity testing in different cell models. Nanoimpact 2018, 10, 608 1-10. 609
  19. Wang, X.; Duch, M. C.; Mansukhani, N.; Ji, Z.; Liao, Y.-P.; Wang, M.; Zhang, H.; Sun, B.; Chang, C. 610 H.; Li, R.; Lin, S.; Meng, H.; Xia, T.; Hersam, M. C.; Nel, A. E., Use of a Pro-Fibrogenic Mechanism-Based 611 Predictive Toxicological Approach for Tiered Testing and Decision Analysis of Carbonaceous 612 Nanomaterials. ACS Nano 2015, 9 (3), 3032-3043. 613
  20. Xia, T.; Hamilton, R. F.; Bonner, J. C.; Crandall, E. D.; Elder, A.; Fazlollahi, F.; Girtsman, T. A.; Kim, 614 K.; Mitra, S.; Ntim, S. A.; Orr, G.; Tagmount, M.; Taylor, A. J.; Telesca, D.; Tolic, A.; Vulpe, C. D.; Walker, A. 615 J.; Wang, X.; Witzmann, F. A.; Wu, N.; Xie, Y.; Zink, J. I.; Nel, A.; Holian, A., Interlaboratory Evaluation of 616 in Vitro Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: The NIEHS Nano GO 617 Consortium. Environ. Health Perspect. 2013, 121 (6), 683-690. 618
  21. Paget, V.; Grall, R.; Delic, J.; Goni-de-Cerio, F.; Suarez-Merino, B.; Fessard, V.; Hogeveen, K. N.; Fjellsbo, L. 621 M.; Pran, E. R.; Brzicova, T.; Topinka, J.; Silva, M. J.; Leite, P. E.; Ribeiro, A. R.; Granjeiro, J. M.; Grafstrom, 622 R.; Prina-Mello, A.; Dusinska, M., High throughput toxicity screening and intracellular detection of 623 nanomaterials. Wiley Interdisc. Rev. Nanomed. Nanobiotechnol. 2017, 9 (1). 624
  22. Milcamps, A.; Huk, A.; Collins, A. R.; Dusinska, M.; Whelan, M., Iron oxide nanoparticle toxicity testing 626 using high-throughput analysis and high-content imaging. Nanotoxicology 2015, 9, 87-94. 627
  23. Pinkerton, K.; Pleus, R. C.; Shatkin, J. A.; Thomas, R.; Tolaymat, T.; Wang, A.; Wong, J., A Multi- 631 Stakeholder Perspective on the Use of Alternative Test Strategies for Nanomaterial Safety Assessment. 632 ACS Nano 2013, 7 (8), 6422-6433. 633
  24. NRC, Toxicity Testing in the 21st Century: A Vision and a Strategy. The National Academies Press: 634 2007. 635
  25. Pleus, R. C.; Sayre, P.; Stone, V.; Sullivan, K. M.; Tentschert, J.; Wallis, P.; Nel, A. E., Nanomaterial 639 Categorization for Assessing Risk Potential To Facilitate Regulatory Decision-Making. ACS Nano 2015, 9 640 (4), 3409-3417. 641
  26. Halappanavar, S.; Hotchkiss, J. A.; Jarabek, A. M.; Maier, M.; Polk, W.; Rothen-Rutishauser, B.; Sayes, C. 643 M.; Sayre, P.; Sharma, M.; Stone, V., Expert consensus on an in vitro approach to assess pulmonary 644 fibrogenic potential of aerosolized nanomaterials. Arch. Toxicol. 2016, 90 (7), 1769-1783. 645
  27. Landsiedel, R.; Kapp, M. D.; Schulz, M.; Wiench, K.; Oesch, F., Genotoxicity investigations on 646 nanomaterials: Methods, preparation and characterization of test material, potential artifacts and 647 limitations-Many questions, some answers. Mut. Res. 2009, 681 (2-3), 241-258. 648
  28. Landsiedel, R.; Sauer, U. G.; Ma-Hock, L.; Schnekenburger, J.; Wiemann, M., Pulmonary toxicity 649 of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation 650 studies. Nanomedicine 2014, 9 (16), 2557-2585. 651
  29. Belyanskaya, L.; Manser, P.; Spohn, P.; Bruinink, A.; Wick, P., The reliability and limits of the MTT 657 reduction assay for carbon nanotubes-cell interaction. Carbon 2007, 45 (13), 2643-2648. 658
  30. Guo, L.; Bussche, A. V.; Buechner, M.; Yan, A. H.; Kane, A. B.; Hurt, R. H., Adsorption of essential 659 micronutrients by carbon nanotubes and the implications for nanotoxicity testing. Small 2008, 4 (6), 660 721-727. 661
  31. Kroll, A.; Pillukat, M. H.; Hahn, D.; Schnekenburger, J., Interference of engineered nanoparticles 662 with in vitro toxicity assays. Arch. Toxicol. 2012, 86 (7), 1123-1136. 663
  32. Worle-Knirsch, J. M.; Pulskamp, K.; Krug, H. F., Oops they did it again! Carbon nanotubes hoax 664 scientists in viability assays. Nano Lett. 2006, 6 (6), 1261-1268. 665
  33. Shinohara, N.; Matsumoto, T.; Gamo, M.; Miyauchi, A.; Endo, S.; Yonezawa, Y.; Nakanishi, J., Is 666 Lipid Peroxidation Induced by the Aqueous Suspension of Fullerene C-60 Nanoparticles in the Brains of 667 Cyprinus carpio? Environ. Sci. Technol. 2009, 43 (3), 948-953. 668
  34. DeLoid, G. M.; Cohen, J. M.; Pyrgiotakis, G.; Demokritou, P., Preparation, characterization, and in 669 vitro dosimetry of dispersed, engineered nanomaterials. Nat. Prot. 2017, 12 (2), 355-371. 670
  35. Taurozzi, J. S.; Hackley, V. A.; Wiesner, M. R., Ultrasonic dispersion of nanoparticles for 671 environmental, health and safety assessment -issues and recommendations. Nanotoxicology 2011, 5 672 (4), 711-729. 673
  36. Taurozzi, J. S.; Hackley, V. A.; Wiesner, M. R., A standardised approach for the dispersion of 674 titanium dioxide nanoparticles in biological media. Nanotoxicology 2013, 7 (4), 389-401. 675
  37. Ellison, S. L. R.; Barwick, V. J., Estimating measurement uncertainty: reconciliation using a cause 680 and effect approach. Accredit. Qual. Assur. 1998, 3 (3), 101-105. 681
  38. Salit, M. L.; Petersen, E. J.; Sequeira, F.; Romsos, E. L.; Kim, S. J.; Lee, J.; von Moos, N. R.; Rossi, F.; Hirsch, 685 C.; Krug, H. F.; Suchaoin, W.; Wick, P., Toward Achieving Harmonization in a Nanocytotoxicity Assay 686 Measurement Through an Interlaboratory Comparison Study. Altex-Alt. Anim. Exper. 2017, 34 (2), 201- 687 218. 688
  39. Hellack, B.; Nickel, C.; Albrecht, C.; Kuhlbusch, T. A. J.; Boland, S.; Baeza-Squiban, A.; Wohlleben, 689 W.; Schins, R. P. F., Analytical methods to assess the oxidative potential of nanoparticles: a review. 690 Environ. Sci.: Nano 2017, 4 (10), 1920-1934. 691
  40. Nel, A.; Xia, T.; Madler, L.; Li, N., Toxic potential of materials at the nanolevel. Science 2006, 311 692 (5761), 622-627. 693
  41. Petry, T.; Sauer, U. G.; Warheit, D.; Wiench, K.; Wohlleben, W.; Landsiedel, R., A decision-making 695 framework for the grouping and testing of nanomaterials (DF4nanoGrouping). Regul. Toxicol. 696 Pharmacol. 2015, 71 (2), S1-S27. 697
  42. Petry, T.; Sauer, U. G.; Warheit, D.; Wiench, K.; Wohileben, W.; Landsiedel, R., Case studies putting the 699 decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) into 700 practice. Regul. Toxicol. Pharmacol. 2016, 76, 234-261. 701
  43. Baeza-Squiban, A.; Cho, A.; Duggan, S.; Froines, J., Evaluating the toxicity of airborne particulate matter 704 and nanoparticles by measuring oxidative stress potential -A workshop report and consensus 705 statement. Inhal. Toxicol. 2008, 20 (1), 75-99. 706
  44. Gelein, R.; Finkelstein, J.; Oberdorster, G., Concept of assessing nanoparticle hazards considering 708 nanoparticle dosemetric and chemical/biological response metrics. J. Toxicol. Environ. Health-Part A- 709 Current Issues 2010, 73 (5-6), 445-461. 710
  45. El Yamani, N.; Collins, A. R.; Runden-Pran, E.; Fjellsbo, L. M.; Shaposhnikov, S.; Zienolddiny, S.; 711 Dusinska, M., In vitro genotoxicity testing of four reference metal nanomaterials, titanium dioxide, zinc 712 oxide, cerium oxide and silver: towards reliable hazard assessment. Mutagenesis 2017, 32 (1), 117-126. 713
  46. Hanna, S. K.; Cooksey, G. A.; Dong, S.; Nelson, B. C.; Mao, L.; Elliott, J. T.; Petersen, E. J., 714 Feasibility of using a standardized Caenorhabditis elegans toxicity test to assess nanomaterial toxicity. 715 Environ. Sci.: Nano 2016, 3 (5), 1080-1089. 716
  47. Saunders, M.; Juillerat-Jeanneret, L.; Marcomini, A.; Huk, A.; Dusinska, M.; Fjellsbo, L. M.; Marano, F.; 718
  48. Boland, S., Toxicity screenings of nanomaterials: challenges due to interference with assay processes 719 and components of classic in vitro tests. Nanotoxicology 2015, 9, 13-24. 720
  49. Horst, A. M.; Vukanti, R.; Priester, J. H.; Holden, P. A., An Assessment of Fluorescence-and 721 Absorbance-Based Assays to Study Metal-Oxide Nanoparticle ROS Production and Effects on Bacterial 722 Membranes. Small 2013, 9 (9-10), 1753-1764. 723
  50. Tarpey, M. M.; Wink, D. A.; Grisham, M. B., Methods for detection of reactive metabolites of 724 oxygen and nitrogen: in vitro and in vivo considerations. Amer. J. Physiol.-Regulat. Integrat. Compar. 725 Physiol. 2004, 286 (3), R431-R444. 726
  51. Cedervall, T.; Lynch, I.; Lindman, S.; Berggård, T.; Thulin, E.; Nilsson, H.; Dawson, K. A.; Linse, S., 727 Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities 728 of proteins for nanoparticles. Proceedings of the National Academy of Sciences 2007, 104 (7), 2050- 729 2055. 730
  52. Lundqvist, M.; Stigler, J.; Elia, G.; Lynch, I.; Cedervall, T.; Dawson, K. A., Nanoparticle size and 731 surface properties determine the protein corona with possible implications for biological impacts. Proc. 732 Nat.Acad. Sci.2008, 105 (38), 14265-14270. 733
  53. Bordeaux, J.; Welsh, A. W.; Agarwal, S.; Killiam, E.; Baquero, M. T.; Hanna, J. A.; Anagnostou, V. 734 K.; Rimm, D. L., Antibody validation. BioTechniques 2010, 48 (3), 197-209. 735
  54. Nelissen, I.; Misra, S. K.; Toussaint, O., Pan-European inter-laboratory studies on a panel of in vitro 739 cytotoxicity and pro-inflammation assays for nanoparticles. Arch. Toxicol. 2017, 91 (6), 2315-2330. 740
  55. Wu, D. Y.; Patti-Diaz, L.; Hill, C. G., Development and validation of flow cytometry methods for 745 pharmacodynamic clinical biomarkers. Bioanalysis 2010, 2 (9), 1617-1626. 746
  56. Hande, K. R., Etoposide: Four decades of development of a topoisomerase II inhibitor. Eur. J. 750 Cancer 1998, 34 (10), 1514-1521. 751
  57. Karlsson, H. L.; Di Bucchianico, S.; Collins, A. R.; Dusinska, M., Can the Comet Assay be Used 756 Reliably to Detect Nanoparticle-Induced Genotoxicity? Environ. Mol. Mutag. 2015, 56 (2), 82-96. 757
  58. Rajapakse, K.; Drobne, D.; Kastelec, D.; Marinsek-Logar, R., Experimental evidence of false- 758 positive Comet test results due to TiO2 particle -assay interactions. Nanotoxicology 2013, 7 (5), 1043- 759 1051. 760
  59. Lin, M. H.; Hsu, T. S.; Yang, P. M.; Tsai, M. Y.; Perng, T. P.; Lin, L. Y., Comparison of organic and 761 inorganic germanium compounds in cellular radiosensitivity and preparation of germanium 762 nanoparticles as a radiosensitizer. Inter. J. Rad. Biol. 2009, 85 (3), 214-226. 763
  60. Magdolenova, Z.; Lorenzo, Y.; Collins, A.; Dusinska, M., Can standard genotoxicity tests be 764 applied to nanoparticles? J. Toxicol. Environ. Health-Part A-Current Issues 2012, 75 (13-15), 800-806. 765
  61. Ferraro, D.; Anselmi-Tamburini, U.; Tredici, I. G.; Ricci, V.; Sommi, P., Overestimation of 766 nanoparticles-induced DNA damage determined by the comet assay. Nanotoxicology 2016, 10 (7), 861- 767 870. 768
  62. George, J. M.; Magogotya, M.; Vetten, M. A.; Buys, A. V.; Gulumian, M., An Investigation of the 769 Genotoxicity and Interference of Gold Nanoparticles in Commonly Used In Vitro Mutagenicity and 770 Genotoxicity Assays. Toxicol. Sci. 2017, 156 (1), 149-166. 771
  63. Gerloff, K.; Albrecht, C.; Boots, A. W.; Forster, I.; Schins, R. P. F., Cytotoxicity and oxidative DNA 772 damage by nanoparticles in human intestinal Caco-2 cells. Nanotoxicology 2009, 3 (4), 355-364. 773
  64. Ellison, S. L. R., Uncertainties in qualitative testing and analysis. Accredit. Qual. Assur. 2000, 5, 777 346-348. 778
  65. Ellison, S. L. R.; Gregory, S.; Hardcastle, W. A., Quantifying uncertainty in qualitative analysis. 779 Analyst 1998, 123 (5), 1155-1161. 780
  66. Barosova, H.; Hirsch, C.; Petri-Fink, A.; Rothen-Rutishauser, B.; Wick, P., Single exposure to aerosolized 782 graphene oxide and graphene nanoplatelets did not initiate an acute biological response in a 3D human 783 lung model. Carbon 2018, 137, 125-135. 784 785 786

Cited by

Sorted by citations

Authors
Petersen, E. J., Hirsch, C., Elliott, J. T., Krug, H. F., Aengenheister, L., Arif, A. T., Bogni, A., Kinsner-Ovaskainen, A., May, S., Walser, T., Wick, P., & Roesslein, M.
Affiliations
  • National Institute of Standards and Technology (US)
  • Empa (CH)
  • NanoCASE GmbH, St. Gallerstr. 58, 9032 Engelburg, Switzerland
  • University of Freiburg (DE)
  • Joint Research Centre (IT)
  • European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy
  • Vereala GmbH, Eyhof 34, 8047 Zürich, Switzerland
Corresponding author
Petersen, Elijah J.
ORCID
Venue
Chemical Research in Toxicology
Publisher
American Chemical Society (ACS)
Published
2019-09-11
Volume
33
Issue
5
Pages
1039-1054
ISSN
  • 0893-228X (ISSN-L)
  • 1520-5010
DOI
10.1021/acs.chemrestox.9b00165
OpenAlex
W2973209080
Cited by
35
References
1
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2022: 12 · 2021: 7 · 2020: 6 · 2019: 2
FWCI
0.34
Type
journal article
Language
en
Open access
Licence
Locations
  • Chemical Research in Toxicology (publishedVersion)
  • PubMed (publishedVersion)
  • DORA Empa (Swiss Federal Laboratories for Materials Science and Technology (Empa)) (submittedVersion, other-oa)
  • Joint Research Centre (European Commission) (submittedVersion)
Topics
  • Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
  • Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
cause-and-effect analysis, engineered nanomaterials, assay reproducibility, sources of variation, oxidative stress, interleukin-8, comet assay, in vitro toxicity testing, inter-laboratory variability
MeSH terms
Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluoresceins, Fluorescent Dyes, Fluorometry, Humans, Reproducibility of Results, Interleukin-8, Comet Assay, Nanotechnology

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