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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 55, Issue 3


Development of a rapid and quantitative lateral flow assay for the simultaneous measurement of serum κ and λ immunoglobulin free light chains (FLC): inception of a new near-patient FLC screening tool

John P. Campbell / Jennifer L.J. Heaney / Meena Shemar / Dene Baldwin / Ann E. Griffin / Emma Oldridge / Margaret Goodall / Zaheer Afzal / Tim Plant / Mark Cobbold
  • Clinical Immunology, University of Birmingham, Birmingham, UK
  • Harvard University Medical School, Massachusetts General Hospital, Boston, MA, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Roy Jefferis / Joannes F.M. Jacobs
  • Department of Laboratory Medicine, Laboratory Medical Immunology, Radboud University Medical Center, Nijmegen, The Netherlands
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Christopher Hand / Mark T. Drayson
Published Online: 2016-08-09 | DOI: https://doi.org/10.1515/cclm-2016-0194



Serum free light chains (FLC) are sensitive biomarkers used for the diagnosis and management of plasma cell dyscrasias, such as multiple myeloma (MM), and are central to clinical screening algorithms and therapy response criteria. We have developed a portable, near-patient, lateral-flow test (Seralite®) that quantitates serum FLC in 10 min, and is designed to eliminate sample processing delays and accelerate decision-making in the clinic.


Assay interference, imprecision, lot-to-lot variability, linearity, and the utility of a competitive-inhibition design for the elimination of antigen-excess (‘hook effect’) were assessed. Reference ranges were calculated from 91 healthy donor sera. Preliminary clinical validation was conducted by retrospective analysis of sera from 329 patients. Quantitative and diagnostic results were compared to Freelite®.


Seralite® gave a broad competitive-inhibition calibration curve from below 2.5 mg/L to above 200 mg/L, provided good assay linearity (between 1.6 and 208.7 mg/L for κ FLC and between 3.5 and 249.7 mg/L for λ FLC) and sensitivity (1.4 mg/L for κ FLC and 1.7 mg/L for λ FLC), and eliminated anomalous results from antigen-excess. Seralite® gave good diagnostic concordance with Freelite® (Roche Hitachi Cobas C501) identifying an abnormal FLC ratio and FLC difference in 209 patients with newly diagnosed MM and differentiating these patients from normal healthy donors with polyclonal FLC.


Seralite® sensitively quantitates FLC and rapidly identifies clinical conditions where FLC are abnormal, including MM.

This article offers supplementary material which is provided at the end of the article.

Keywords: free light chains; multiple myeloma; near-patient testing


  • 1.

    Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361:489–91.Google Scholar

  • 2.

    Drayson M, Tang LX, Drew R, Mead GP, Carr-Smith H, Bradwell AR. Serum free light-chain measurements for identifying and monitoring patients with nonsecretory multiple myeloma. Blood 2001;97:2900–2.Google Scholar

  • 3.

    Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol 2003;122:78–84.Google Scholar

  • 4.

    Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ, 3rd, Colby CL, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet 2010;375:1721–8.Google Scholar

  • 5.

    Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48:1437–44.Google Scholar

  • 6.

    Mead GP, Carr-Smith HD, Drayson MT, Morgan GJ, Child JA, Bradwell AR. Serum free light chains for monitoring multiple myeloma. Br J Haematol 2004;126:348–54.Google Scholar

  • 7.

    Bradwell AR, Carr-Smith HD, Mead GP, Tang LX, Showell PJ, Drayson MT, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001;47:673–80.Google Scholar

  • 8.

    Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–48.Google Scholar

  • 9.

    Lyratzopoulos G, Neal RD, Barbiere JM, Rubin GP, Abel GA. Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England. Lancet Oncol 2012;13:353–65.Google Scholar

  • 10.

    Elliss-Brookes L, McPhail S, Ives A, Greenslade M, Shelton J, Hiom S, et al. Routes to diagnosis for cancer – determining the patient journey using multiple routine data sets. Br J Cancer 2012;107:1220–6.Google Scholar

  • 11.

    Augustson BM, Begum G, Dunn JA, Barth NJ, Davies F, Morgan G, et al. Early mortality after diagnosis of multiple myeloma: analysis of patients entered onto the United kingdom Medical Research Council trials between 1980 and 2002–Medical Research Council Adult Leukaemia Working Party. J Clin Oncol 2005;23:9219–26.Google Scholar

  • 12.

    Kariyawasan CC, Hughes DA, Jayatillake MM, Mehta AB. Multiple myeloma: causes and consequences of delay in diagnosis. Q J Med 2007;100:635–40.Google Scholar

  • 13.

    Hutchison CA, Blade J, Cockwell P, Cook M, Drayson M, Fermand JP, et al. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat Rev Nephrol 2012;8:234–43.Google Scholar

  • 14.

    Hutchison CA, Cockwell P, Stringer S, Bradwell A, Cook M, Gertz MA, et al. Early reduction of serum-free light chains associates with renal recovery in myeloma kidney. J Am Soc Nephrol 2011;22:1129–36.Google Scholar

  • 15.

    Hutchison CA, Batuman V, Behrens J, Bridoux F, Sirac C, Dispenzieri A, et al. The pathogenesis and diagnosis of acute kidney injury in multiple myeloma. Nat Rev Nephrol 2012;8:43–51.Google Scholar

  • 16.

    Friese CR, Abel GA, Magazu LS, Neville BA, Richardson LC, Earle CC. Diagnostic delay and complications for older adults with multiple myeloma. Leuk Lymphoma 2009;50:392–400.Google Scholar

  • 17.

    Brioli A, Giles H, Pawlyn C, Campbell JP, Kaiser MF, Melchor L, et al. Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome. Blood 2014;123:3414–9.Google Scholar

  • 18.

    Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, et al. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215–24.Google Scholar

  • 19.

    Tate J, Bazeley S, Sykes S, Mollee P. Quantitative serum free light chain assay – analytical issues. Clin Biochem Rev 2009;30:131–40.Google Scholar

  • 20.

    Bradwell AR. Serum free light chain analysis (plus Hevylite), 6th ed. Birmingham: Binding Site Group, 2010.Google Scholar

  • 21.

    Campbell JP, Cobbold M, Wang Y, Goodall M, Bonney SL, Chamba A, et al. Development of a highly-sensitive multi-plex assay using monoclonal antibodies for the simultaneous measurement of kappa and lambda immunoglobulin free light chains in serum and urine. J Immunol Methods 2013;391:1–13.Google Scholar

  • 22.

    Nakano T, Nagata A. ELISAs for free light chains of human immunoglobulins using monoclonal antibodies: comparison of their specificity with available polyclonal antibodies. J Immunol Methods 2003;275:9–17.Google Scholar

  • 23.

    Nakano T, Miyazaki S, Takahashi H, Matsumori A, Maruyama T, Komoda T, et al. Immunochemical quantification of free immunoglobulin light chains from an analytical perspective. Clin Chem Lab Med 2006;44:522–32.Google Scholar

  • 24.

    Kim HS, Shin KS, Song W, Kim HJ, Park MJ. Clinical comparisons of two free light chain assays to immunofixation electrophoresis for detecting monoclonal gammopathy. Biomed Res Int 2014;2014:647238.Google Scholar

  • 25.

    Hoedemakers RM, Pruijt JF, Hol S, Teunissen E, Martens H, Stam P, et al. Clinical comparison of new monoclonal antibody-based nephelometric assays for free light chain kappa and lambda to polyclonal antibody-based assays and immunofixation electrophoresis. Clin Chem Lab Med 2012;50:489–95.Google Scholar

  • 26.

    Schneider N, Wynckel A, Kolb B, Sablon E, Gillery P, Maquart FX. [Comparative analysis of immunoglobulin free light chains quantification by Freelite (The Binding Site) and N Latex FLC (Siemens) methods]. Ann Biol Clin (Paris) 2013;71:13–9. Etude comparative du dosage des chaines legeres libres d'immunoglobulines par technique Freelite (The Binding Site) et N Latex FLC (Siemens).Google Scholar

  • 27.

    Pretorius CJ, Klingberg S, Tate J, Wilgen U, Ungerer JP. Evaluation of the N Latex FLC free light chain assay on the Siemens BN analyser: precision, agreement, linearity and variation between reagent lots. Ann Clin Biochem 2012;49:450–5.Google Scholar

  • 28.

    Mollee P, Tate J, Pretorius CJ. Evaluation of the N Latex free light chain assay in the diagnosis and monitoring of AL amyloidosis. Clin Chem Lab Med 2013;51:2303–10.Google Scholar

  • 29.

    Lock RJ, Saleem R, Roberts EG, Wallage MJ, Pesce TJ, Rowbottom A, et al. A multicentre study comparing two methods for serum free light chain analysis. Ann Clin Biochem 2013;50:255–61.Google Scholar

  • 30.

    Tate JR, Mollee P, Dimeski G, Carter AC, Gill D. Analytical performance of serum free light-chain assay during monitoring of patients with monoclonal light-chain diseases. Clin Chim Acta 2007;376:30–6.Google Scholar

  • 31.

    Jacobs JF, Hoedemakers RM, Teunissen E, van der Molen RG, te Velthuis H. Effect of sample dilution on two free light chain nephelometric assays. Clin Chim Acta 2012;413:1708–9.Google Scholar

  • 32.

    Levinson SS. Hook effect with lambda free light chain in serum free light chain assay. Clin Chim Acta 2010;411:1834–6.Google Scholar

  • 33.

    Daval S, Tridon A, Mazeron N, Ristori JM, Evrard B. Risk of antigen excess in serum free light chain measurements. Clin Chem 2007;53:1985–6.Google Scholar

  • 34.

    Jacobs JF, van der Molen RG, Bossuyt X, Damoiseaux J. Antigen excess in modern immunoassays: to anticipate on the unexpected. Autoimmun Rev 2015;14:160–7.Google Scholar

  • 35.

    Murata K, Clark RJ, Lockington KS, Tostrud LJ, Greipp PR, Katzmann JA. Sharply increased serum free light-chain concentrations after treatment for multiple myeloma. Clin Chem 2010;56:16–8.Google Scholar

  • 36.

    Graziani MS, Merlini G. Serum free light chain analysis in the diagnosis and management of multiple myeloma and related conditions. Expert Rev Mol Diagn 2014;14:55–66.Google Scholar

  • 37.

    de Kat Angelino CM, Raymakers R, Teunesen MA, Jacobs JF, Klasen IS. Overestimation of serum kappa free light chain concentration by immunonephelometry. Clin Chem 2010;56:1188–90.Google Scholar

  • 38.

    VanDuijn MM, Jacobs JF, Wevers RA, Engelke UF, Joosten I, Luider TM. Quantitative measurement of immunoglobulins and free light chains using mass spectrometry. Anal Chem 2015;87:8268–74.Google Scholar

  • 39.

    Jacobs JF, Tate JR, Merlini G. Is accuracy of serum free light chain measurement achievable? Clin Chem Lab Med 2016;54:1021–30.Google Scholar

  • 40.

    Graziani MS. Measurement of free light chains – pros and cons of current methods. Clin Chem Lab Med 2016;54:1015–20.Google Scholar

  • 41.

    Drayson M, Carr-Smith H. Clinical comparison of new monoclonal antibody-based nephelometric assays for free light chain kappa and lambda to polyclonal antibody-based assays and immunofixation electrophoresis. Clin Chem Lab Med 2012;50:587–8.Google Scholar

About the article

aJohn P. Campbell and Jennifer L.J. Heaney contributed equally to this work.

Received: 2016-03-08

Accepted: 2016-07-07

Published Online: 2016-08-09

Published in Print: 2017-03-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Seralite® development was funded by Abingdon Health Ltd. J.H. receives research funding from Abingdon Health Ltd.

Employment or leadership: M.S., A.G., E.O. and D.B. are, or were, employees of Abingdon Health Ltd. M.D. has, and R.J. has previously had, an advisory role with Abingdon Health Ltd. J.C., M.G., R.J., M.C., T.P., C.H. and M.D. have shares in Abingdon Health Ltd.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in thestudy design; in the collection, analysis, and interpretationof data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 55, Issue 3, Pages 424–434, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2016-0194.

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