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Validation of the analytical performance of the NOVEOS™ System, a system which improves upon the third-generation in vitro allergy testing technology

Daniel Bauersachs , Ekaterina Potapova , Harald Renz , Stephanie Hagner Benes , Paolo Maria Matricardi and Chrysanthi Skevaki EMAIL logo



Detection of allergen-specific immunoglobulin E (sIgE) is important for the diagnosis of allergy. IgE sensitization is commonly demonstrated in vivo by skin prick testing (SPT), or in vitro utilizing automated systems. Recently, HYCOR® Biomedical launched its new system for allergen sIgE testing called the NOVEOS™ Immunoanalyzer. This study aims to evaluate the analytical performance of the NOVEOS system in a bi-center study at Philipps-University Marburg (Site-1) and Charité Medical University Berlin (Site-2), respectively.


The analytical performance was evaluated based on the guidelines I/LA20-A3, EP5-A3, EP17-A2, EP6-A, EP7-A3, and EP9-A3 of the Clinical and Laboratory Standards Institute (CLSI).


The conducted repeatability and within-laboratory precision tests provided acceptable performance with 3.0%–11.9% coefficient of variation across both sites. The limit of blank (LoB) and limit of detection (LoD) were <0.1 kU/L at both centers. A within-parameter linearity for all tested allergens was reported at both sites. Of note, no significant interference was observed for high levels of biotin, methylprednisolone, diphenhydramine, omalizumab, or ranitidine. Method comparison between the NOVEOS calibration and the latest World Health Organization (WHO) reference standard showed good agreement at both sites.


The results from the analytical performance of the NOVEOS allergen sIgE assay and instrument testing at both sites were comparable. Overall, a good precision and linearity as well as a detection limit <0.1 kU/L were observed, with minimal impact of common interfering substances on patient recoveries. The NOVEOS is calibrated to the latest WHO reference standard and adds benefits like a small sample size and para-magnetic microparticles that improve upon third-generation allergen sIgE assays’ design and performance.

  1. Author contributions: HYCOR Biomedical, CS, and PM conceived the study and interpreted the data. Daniel Bauersachs and Ekaterina Potapova were involved in sample analysis and data collection. Daniel Bauersachs wrote the first draft of the manuscript. All authors edited, reviewed, and approved the final manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  2. Research funding: CS and HR are supported by Universities Giessen and Marburg Lung Center (UGMLC), the German Center for Lung Research (DZL; 82DZL00502/A2 to HR), University Hospital Gießen and Marburg (UKGM) research funding according to article 2, section 3 cooperation agreement (to CS and HR), the Deutsche Forschungsgemeinschaft (DFG) (Funder Id: – funded – SFB 1021 (C04, to HR and CS), KFO309 (P10 to CS), and SK 317/1-1 (Project Nr 428518790) (to CS). PM is funded by the Deutsche Forschungsgemeinschaft (DFG; grant number MA 4740/2-1).

  3. Competing interests: For CS: Consultancy and research funding, Hycor Biomedical, Bencard Allergie, and Thermo Fisher Scientific; Research Funding, Mead Johnson Nutrition (MJN). The research of HR is supported by Mead Johnson Nutritional and Beckman Coulter. He receives speaker’s honorarium from Allergopharma, Novartis, Thermo Fisher, Danone, Mead Johnson Nutritional, and Bencard. Further, HR is consulting Bencard, and Secarna Pharmaceuticals (co-founder). PM is consultant for HYCOR Biomedical, Euroimmun, and Thermo Fisher Scientific, has received research funding from HYCOR Biomedical, Euroimmun, reagents for research from Thermo Fisher and HYCOR Biomedical, and speaker’s fees from Euroimmun, Thermo Fisher Scientific, Stallergenes-Greer, and HAL Allergy. The rest of the authors declare that they have no relevant conflict of interest. All other authors reported no conflicts of interest.

  4. Employment or leadership: None declared.

  5. Honorarium: None declared.

  6. Ethical approval: All samples, courtesy of HYCOR Biomedical, were collected under Institutional Review Board (IRB)-approved protocols. The study was conducted following the ethical principles identified in the Declaration of Helsinki.


1. Meyer R, Fox AT, Chebar Lozinsky A, Michaelis LJ, Shah N. Non-IgE-mediated gastrointestinal allergies – do they have a place in a new model of the Allergic March. Pediatr Allergy Immunol 2019;30:149–58.10.1111/pai.13000Search in Google Scholar

2. Platts-Mills TA. The allergy epidemics: 1870–2010. J Allergy Clin Immunol 2015;136:3–13.10.1016/j.jaci.2015.03.048Search in Google Scholar

3. Matricardi PM, Kleine-Tebbe J, Hoffmann HJ, Valenta R, Hilger C, Hofmaier S, et al. EAACI Molecular Allergology User’s Guide. Pediatr Allergy Immunol 2016;27 Suppl 23:1–250.10.1111/pai.12563Search in Google Scholar

4. Descotes J, Choquet-Kastylevsky G. Gell and Coombs’s classification: is it still valid? Toxicology 2001;158:43–9.10.1016/S0300-483X(00)00400-5Search in Google Scholar

5. Vuljanić D, Dukić L, Krleža JL, Juroš GF, Pozaić P, Šimundić A-M. Third-party verification of total and specific immunoglobulin E on analyzer Immulite® 2000XPi. Clin Chim Acta 2020;500:28–33.10.1016/j.cca.2019.09.015Search in Google Scholar

6. Hemmer W, Altmann F, Holzweber F, Gruber C, Wantke F, Wöhrl S. ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD) epitopes and can cause false-positive test results in patients with high anti-CCD IgE antibody levels. J Allergy Clin Immunol 2018;141:372–81.e3.10.1016/j.jaci.2017.04.028Search in Google Scholar

7. Hycor Biomedical Inc. NOVEOS-operator’s manual. Hycor Bioemedical Inc 2018:1–268.Search in Google Scholar

8. Li TM, Chuang T, Tse S, Hovanec-Burns D, El Shami AS. Development and validation of a third generation allergen-specific IgE assay on the continuous random access IMMULITE 2000 analyzer. Ann Clin Lab Sci 2004;34:67–74.Search in Google Scholar

9. Johansson SG. ImmunoCAP Specific IgE test: an objective tool for research and routine allergy diagnosis. Expert Rev Mol Diagn 2004;4:273–9.10.1586/14737159.4.3.273Search in Google Scholar

10. Adams J. I/LA20-A3: analytical performance characteristics, quality assurance and clinical utility of immunological assays for human immunoglobulin E (IgE) antibodies of defined allergen specificities; approved guideline, 3rd ed. Vol. 3. Clinical and Laboratory Standards Institute, 2014:1–100.Search in Google Scholar

11. Carey RN. User verification of precision and estimation of bias: approved guideline, 3rd ed. Wayne, Penn.: Clinical and Laboratory Standards Institute, 2014. (Clinical and Laboratory Standards Institute. 34, no. 12).Search in Google Scholar

12. Kleine-Tebbe J, Jakob T. Molecular allergy diagnostics using IgE singleplex determinations: methodological and practical considerations for use in clinical routine. Allergo J Int 2015;24:185–97.10.1007/s40629-015-0067-zSearch in Google Scholar

13. Hamilton RG. Accuracy of US Food and Drug Administration-cleared IgE antibody assays in the presence of anti-IgE (omalizumab). J Allergy Clin Immunol 2006;117:759–66.10.1016/j.jaci.2006.01.012Search in Google Scholar

14. Seagroatt V, Anderson SG. The second international reference preparation for human serum immunoglobulin E and the first British standard for human serum immunoglobulin E. J Biol Stand 1981;9:431–7.10.1016/S0092-1157(81)80034-0Search in Google Scholar

15. NIBSC. Immunoglobulin E (IgE), human serum. Potters Bar, Hertfordshire, United Kingdom: National Institute for Biological Standards and Control, 2013:1–2.Search in Google Scholar

16. Williams PB, Barnes JH, Szeinbach SL, Sullivan TJ. Analytic precision and accuracy of commercial immunoassays for specific IgE: establishing a standard. J Allergy Clin Immunol 2000;105(6 Pt 1): 1221–30.10.1067/mai.2000.105219Search in Google Scholar PubMed

17. Yang J, Lee H, Choi AR, Park KH, Ryu JH, Oh E-J. Comparison of allergen-specific IgE levels between Immulite 2000 and ImmunoCAP systems against six inhalant allergens and ten food allergens. Scand J Clin Lab Invest 2018;78:606–12.10.1080/00365513.2018.1528506Search in Google Scholar PubMed

18. Avery G. Biotin interference in immunoassay: a review for the laboratory scientist. Ann Clin Biochem 2019;56: 424–30.10.1177/0004563219842231Search in Google Scholar PubMed

19. Colon PJ, Greene DN. Biotin interference in clinical immunoassays. J App Lab Med 2018;2:941–51.10.1373/jalm.2017.024257Search in Google Scholar PubMed

20. Kwok JS-S, Chan IH-S, Chan MH-M. Biotin interference on TSH and free thyroid hormone measurement. Pathology 2012;44:278–80.10.1097/PAT.0b013e3283514002Search in Google Scholar PubMed

21. Haslam S, Oakey J, Brown A, Bradshaw S, Myers M. A comparison of biotin interference in routine immunoassays on the Roche Cobas 8000, Beckman Coulter DXi and Siemens Advia Centaur XPT immunoassay platforms. Clin Chem Lab Med 2019;57:e287–90.10.1515/cclm-2019-0078Search in Google Scholar PubMed

22. Li J, Wagar EA, Meng QH. Comprehensive assessment of biotin interference in immunoassays. Clin Chim Acta 2018;487:293–8.10.1016/j.cca.2018.10.013Search in Google Scholar PubMed

23. FDA. The FDA Warns that Biotin May Interfere with Lab Tests; NaN [cited 2020 Mar 17]. in Google Scholar

24. Statement-from-acb-scicom-biotin-oct2018-1 [cited 2020 Mar 17]. in Google Scholar

25. Sinson E, Rodems K, Whitters E. Biotin interference in allergy testing. Hycor Biomedical Inc 2019:1–4.Search in Google Scholar

Received: 2020-04-17
Accepted: 2020-05-13
Published Online: 2020-06-05
Published in Print: 2020-10-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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