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Analytical and Bioanalytical Chemistry

, Volume 411, Issue 29, pp 7607–7621 | Cite as

Recent advances in immunodiagnostics based on biosensor technologies—from central laboratory to the point of care

  • Andreas Poschenrieder
  • Markus Thaler
  • Ralf Junker
  • Peter B. LuppaEmail author
Review
Part of the following topical collections:
  1. New Developments in Biosensors

Abstract

Immunological methods are widely applied in medical diagnostics for the detection and quantification of a plethora of analytes. Associated analytical challenges usually require these assays to be performed in a central laboratory. During the last several years, however, the clinical demand for rapid immunodiagnostics to be performed in the immediate proximity of the patient has been constantly increasing. Biosensors constitute one of the key technologies enabling the necessary, yet challenging transition of immunodiagnostic tests from the central laboratory to the point of care. This review is intended to provide insights into the current state of this transition process with a focus on the role of biosensor-based systems. To begin with, an overview on standard immunodiagnostic tests presently employed in the central laboratory and at the point of care is given. The review then moves on to demonstrate how biosensor technologies are reshaping this landscape. Single analyte as well as multiplexed immunosensors applicable to point of care scenarios are presented. A section on the areas of clinical application then creates the bridge to day-to-day diagnostic practice. Finally, the depicted developments are critically weighed and future perspectives discussed in order to give the reader a firm idea on the forthcoming trends to be expected in this diagnostic field.

Keywords

Biosensor techniques Immunoassays Immunosensors In vitro diagnostics Near-patient testing Multiplexed detection Nanomaterials Point-of-care testing POCT 

Abbreviations

Ab

Antibody

AFP

Alpha-fetoprotein

AKI

Acute kidney injury

ALP

Alkaline phosphatase

BPE

Bipolar electrode

BNP

B-type natriuretic peptides

CA199

Cancer antigen 19-9

CBP

Calcium-binding protein

CDx

Companion diagnostics

CEA

Carcinoembryonic antigen

CK-MBmass

Creatinine kinase MB

CLIA

Clinical Laboratory Improvement Amendments

ECL

Electrochemiluminescence

FRET

Förster resonance energy transfer

GMR

Giant magnetoresistance

HRP

Horseradish peroxidase

IGFBP-7

Insulin-like growth factor-binding protein 7

ICT

Immunochromatographic test

IFN-γ

Interferon-γ

IL-n

Interleukin n

ISF

Interstitial fluid

IVD

In vitro diagnostics

KIM-1

Kidney injury molecule-1

LFA

Lateral flow immunoassays

LFD

Lateral flow device

LLOD

Lower limits of detection

MW

Molecular weight

NGAL

Neutrophil gelatinase-associated lipocalin

NWA

Nanowell array

PMMA

Poly(methyl methacrylate)

POCT

Point-of-care testing

PSA

Prostate-specific antigen

PTFE

Polytetrafluoroethylene

SAW

Surface acoustic wave

SPCE

Screen-printed carbon electrode

SPE

Screen-printed electrode

SPR

Surface plasmon resonance

SWNT

Single-wall carbon nanotube

TDM

Therapeutic drug monitoring

TNF

Tumor necrosis factor

TPA

Tripropylamine

TSH

Thyroid-stimulating hormone

TIMP-2

Tissue inhibitor of metalloproteinases-2

Notes

Funding information

This work was supported in part by the European Commission (NANODEM, #318372) and the Bundesministerium für Bildung und Forschung (Q-Flow, #13N13867 and KAREL, #13GW0154D).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    von Lode P. Point-of-care immunotesting: approaching the analytical performance of central laboratory methods. Clin Biochem. 2005;38(7):591–606.  https://doi.org/10.1016/j.clinbiochem.2005.03.008.CrossRefGoogle Scholar
  2. 2.
    Luppa PB, Sokoll LJ, Chan DW. Immunosensors - principles and applications to clinical chemistry. Clin Chim Acta. 2001;314(1–2):1–26.CrossRefGoogle Scholar
  3. 3.
    Luppa PB, Junker R. Point-of-care testing. Principles and clinical applications, vol 1. 1 edn. Berlin: Springer. 2018.  https://doi.org/10.1007/978-3-662-54497-6.Google Scholar
  4. 4.
    Luppa PB, Bietenbeck A, Beaudoin C, Giannetti A. Clinically relevant analytical techniques, organizational concepts for application and future perspectives of point-of-care testing. Biotechnol Adv. 2016;34(3):139–60.  https://doi.org/10.1016/j.biotechadv.2016.01.003.CrossRefPubMedGoogle Scholar
  5. 5.
    Vashist SK, Luppa PB, Yeo LY, Ozcan A, Luong JHT. Emerging technologies for next-generation point-of-care testing. Trends Biotechnol. 2015;33(11):692–705.  https://doi.org/10.1016/j.tibtech.2015.09.001.CrossRefPubMedGoogle Scholar
  6. 6.
    Vashist SK. Point-of-care diagnostics: recent advances and trends. Biosensors. 2017;7(4).  https://doi.org/10.3390/bios7040062.CrossRefGoogle Scholar
  7. 7.
    Bietenbeck A, Junker R, Luppa PB. Central laboratory service and point-of-care testing in Germany. From conflicting notions to complementary understandings. Point of Care. 2015;14(1):1–11.  https://doi.org/10.1097/poc.0000000000000043.CrossRefGoogle Scholar
  8. 8.
    Wang P, Kricka LJ. Current and emerging trends in point-of-care technology and strategies for clinical validation and implementation. Clin Chem. 2018;64(10):1439–52.  https://doi.org/10.1373/clinchem.2018.287052.CrossRefPubMedGoogle Scholar
  9. 9.
    Sakamoto S, Omagari K, Kita Y, Mochizuki Y, Naito Y, Kawata S, et al. Magnetically promoted rapid immunoreactions using functionalized fluorescent magnetic beads: a proof of principle. Clin Chem. 2014;60(4):610–20.  https://doi.org/10.1373/clinchem.2013.211433.CrossRefPubMedGoogle Scholar
  10. 10.
    Felix FS, Angnes L. Electrochemical immunosensors - a powerful tool for analytical applications. Biosens Bioelectron. 2018;102:470–8.  https://doi.org/10.1016/j.bios.2017.11.029.CrossRefPubMedGoogle Scholar
  11. 11.
    Ko Ferrigno P. Non-antibody protein-based biosensors. Essays Biochem. 2016;60(1):19–25.  https://doi.org/10.1042/EBC20150003.CrossRefPubMedGoogle Scholar
  12. 12.
    Li Z, Chen G-Y. Current conjugation methods for immunosensors. Nanomaterials (Basel). 2018;8(5).  https://doi.org/10.3390/nano8050278.CrossRefGoogle Scholar
  13. 13.
    Mao SY. Biotinylation of antibodies. Methods Mol Biol. 2010;588:49–52.  https://doi.org/10.1007/978-1-59745-324-0_7.CrossRefPubMedGoogle Scholar
  14. 14.
    Omi K, Ando T, Sakyu T, Shirakawa T, Uchida Y, Oka A, et al. Noncompetitive immunoassay detection system for haptens on the basis of antimetatype antibodies. Clin Chem. 2015;61(4):627–35.  https://doi.org/10.1373/clinchem.2014.232728.CrossRefPubMedGoogle Scholar
  15. 15.
    Bradbury A, Plückthun A. Reproducibility: standardize antibodies used in research. Nature. 2015;518(7537):27–9.  https://doi.org/10.1038/518027a.CrossRefPubMedGoogle Scholar
  16. 16.
    Bradbury ARM, Trinklein ND, Thie H, Wilkinson IC, Tandon AK, Anderson S, et al. When monoclonal antibodies are not monospecific: hybridomas frequently express additional functional variable regions. MAbs. 2018;10(4):539–46.  https://doi.org/10.1080/19420862.2018.1445456.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Knappik A, Ge L, Honegger A, Pack P, Fischer M, Wellnhofer G, et al. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J Mol Biol. 2000;296(1):57–86.CrossRefGoogle Scholar
  18. 18.
    Frenzel A, Hust M, Schirrmann T. Expression of recombinant antibodies. Front Immunol. 2013;4.  https://doi.org/10.3389/fimmu.2013.0021710.
  19. 19.
    Aydin S. A short history, principles, and types of ELISA, and our laboratory experience with peptide/protein analyses using ELISA. Peptides. 2015;72:4–15.  https://doi.org/10.1016/j.peptides.2015.04.012.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Gao Y, Huang X, Zhu Y, Lv Z. A brief review of monoclonal antibody technology and its representative applications in immunoassays. J Immunoass Immunochem. 2018;39(4):351–64.  https://doi.org/10.1080/15321819.2018.1515775.CrossRefGoogle Scholar
  21. 21.
    Glahn-Martinez B, Benito-Pena E, Salis F, Descalzo AB, Orellana G, Moreno-Bondi MC. Sensitive rapid fluorescence polarization immunoassay for free mycophenolic acid determination in human serum and plasma. Anal Chem. 2018;90(8):5459–65.  https://doi.org/10.1021/acs.analchem.8b00780.CrossRefPubMedGoogle Scholar
  22. 22.
    Baibich MN, Broto JM, Fert A, Vandau FN, Petroff F, Eitenne P, et al. Giant magnetoresistance of (001)Fe/(001) Cr magnetic superlattices. Phys Rev Lett. 1988;61:2472–5.CrossRefGoogle Scholar
  23. 23.
    Binasch G, Grunberg P, Saurenbach F, Zinn W. Enhanced magnetoresistance in layered magnetic-structures with antiferromagnetic interlayer exchange. Phys Rev B. 1989;39:4828–30.CrossRefGoogle Scholar
  24. 24.
    Ismail AA. Identifying and reducing potentially wrong immunoassay results even when plausible and “not-unreasonable”. Adv Clin Chem. 2014;66:241–94.CrossRefGoogle Scholar
  25. 25.
    Clerico A, Belloni L, Carrozza C, Correale M, Dittadi R, Dotti C, et al. A black swan in clinical laboratory practice: the analytical error due to interferences in immunoassay methods. Clin Chem Lab Med. 2018;56(3):397–402.CrossRefGoogle Scholar
  26. 26.
    Thomas L. Labor und Diagnose. 8 edn. New York: TH-Books, Frankfurt/Main. 2012.Google Scholar
  27. 27.
    Klewitz T. Entwicklung eines quantitativen Lateral-Flow-Immunoassays zum Nachweis von Analyten in geringsten Konzentrationen. Inauguraldissertation. Hannover: Universität Hannover. 2005.Google Scholar
  28. 28.
    Inverness m, BioStar OIA GC (2006) An enhanced optical immunoassay for the rapid detection of Neisseria gonorrhoeae from female endocervical swabs and male urine specimens. Product insert. Inverness Medical Innovations, vol Rev 02. Waltham, MA, USA.Google Scholar
  29. 29.
    Miocevic O, Cole CR, Laughlin MJ, Buck RL, Slowey PD, Shirtcliff EA. Quantitative lateral flow assays for salivary biomarker assessment: a review. Front Public Health. 2017;5:133.  https://doi.org/10.3389/fpubh.2017.00133.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Burbelo PD, Gunti S, Keller JM, Morse CG, Deeks SG, Lionakis MS, et al. Ultrarapid measurement of diagnostic antibodies by magnetic capture of immune complexes. Sci Rep. 2017;7(1):3818.  https://doi.org/10.1038/s41598-017-03786-7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kozel TR, Burnham-Marusich AR. Point-of-care testing for infectious diseases: past, present, and future. J Clin Microbiol. 2017;55(8):2313–20.  https://doi.org/10.1128/JCM.00476-17.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Luppa PB, Müller C, Schlichtiger A, Schlebusch H. Point-of-care testing (POCT): current techniques and future perspectives. Trends Anal Chem. 2011;30(6):887–98.  https://doi.org/10.1016/j.trac.2011.01.019.CrossRefGoogle Scholar
  33. 33.
    Justino CI, Duarte AC, Rocha-Santos TA. Immunosensors in clinical laboratory diagnostics. Adv Clin Chem. 2016;73:65–108.  https://doi.org/10.1016/bs.acc.2015.10.004.CrossRefPubMedGoogle Scholar
  34. 34.
    Kokkinos C, Economou A, Prodromidis MI. Electrochemical immunosensors: critical survey of different architectures and transduction strategies. Trends Anal Chem. 2016;79:88–105.  https://doi.org/10.1016/j.trac.2015.11.020.CrossRefGoogle Scholar
  35. 35.
    Cho IH, Lee J, Kim J, Kang MS, Paik JK, Ku S, et al. Current technologies of electrochemical immunosensors: perspective on signal amplification. Sensors (Basel). 2018;18(1).  https://doi.org/10.3390/s18010207.CrossRefGoogle Scholar
  36. 36.
    Contreras-Naranjo JE, Aguilar O. Suppressing non-specific binding of proteins onto electrode surfaces in the development of electrochemical immunosensors. Biosensors. 2019;9(1).  https://doi.org/10.3390/bios9010015.CrossRefGoogle Scholar
  37. 37.
    Damborsky P, Svitel J, Katrlik J. Optical biosensors. Essays Biochem. 2016;60(1):91–100.  https://doi.org/10.1042/EBC20150010.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Wang Z, Zong S, Wu L, Zhu D, Cui Y. SERS-activated platforms for immunoassay: probes, encoding methods, and applications. Chem Rev. 2017;117(12):7910–63.  https://doi.org/10.1021/acs.chemrev.7b00027.CrossRefPubMedGoogle Scholar
  39. 39.
    Geissler D, Hildebrandt N. Recent developments in Förster resonance energy transfer (FRET) diagnostics using quantum dots. Anal Bioanal Chem. 2016;408(17):4475–83.  https://doi.org/10.1007/s00216-016-9434-y.CrossRefPubMedGoogle Scholar
  40. 40.
    Chen Y, Xianyu Y, Wu J, Dong M, Zheng W, Sun J, et al. Double-enzymes-mediated bioluminescent sensor for quantitative and ultrasensitive point-of-care testing. Anal Chem. 2017;89(10):5422–7.  https://doi.org/10.1021/acs.analchem.7b00239.CrossRefPubMedGoogle Scholar
  41. 41.
    Wolfbeis OS. Fiber-optic chemical sensors and biosensors. Anal Chem. 2000;72(12):81R–9R.CrossRefGoogle Scholar
  42. 42.
    Becker H, Gärtner C. Microfluidics-enabled diagnostic systems: markets, challenges, and examples. Methods Mol Biol. 2017;1547:3–21.  https://doi.org/10.1007/978-1-4939-6734-6_1.CrossRefPubMedGoogle Scholar
  43. 43.
    Nasseri B, Soleimani N, Rabiee N, Kalbasi A, Karimi M, Hamblin MR. Point-of-care microfluidic devices for pathogen detection. Biosens Bioelectron. 2018;117:112–28.  https://doi.org/10.1016/j.bios.2018.05.050.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Dincer C, Bruch R, Kling A, Dittrich PS, Urban GA. Multiplexed point-of-care testing - xPOCT. Trends Biotechnol. 2017;35(8):728–42.  https://doi.org/10.1016/j.tibtech.2017.03.013.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Munge BS, Stracensky T, Gamez K, DiBiase D, Rusling JF. Multiplex immunosensor arrays for electrochemical detection of cancer biomarker proteins. Electroanalysis. 2016;28(11):2644–58.  https://doi.org/10.1002/elan.201600183.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Tang J, Tang D, Niessner R, Chen G, Knopp D. Magneto-controlled graphene immunosensing platform for simultaneous multiplexed electrochemical immunoassay using distinguishable signal tags. Anal Chem. 2011;83(13):5407–14.  https://doi.org/10.1021/ac200969w.CrossRefPubMedGoogle Scholar
  47. 47.
    Wan Y, Deng W, Su Y, Zhu X, Peng C, Hu H, et al. Carbon nanotube-based ultrasensitive multiplexing electrochemical immunosensor for cancer biomarkers. Biosens Bioelectron. 2011;30(1):93–9.  https://doi.org/10.1016/j.bios.2011.08.033.CrossRefPubMedGoogle Scholar
  48. 48.
    Feng X, Gan N, Zhou J, Li T, Cao Y, Hu F, et al. A novel dual-template molecularly imprinted electrochemiluminescence immunosensor array using Ru (bpy)32+−silica@poly-L-lysine-Au composite nanoparticles as labels for near-simultaneous detection of tumor markers. Electrochim Acta. 2014;139:127–36.  https://doi.org/10.1016/j.electacta.2014.07.008.CrossRefGoogle Scholar
  49. 49.
    Wu MS, Liu Z, Shi HW, Chen HY, Xu JJ. Visual electrochemiluminescence detection of cancer biomarkers on a closed bipolar electrode array chip. Anal Chem. 2015;87(1):530–7.  https://doi.org/10.1021/ac502989f.CrossRefPubMedGoogle Scholar
  50. 50.
    Sardesai NP, Barron JC, Rusling JF. Carbon nanotube microwell array for sensitive electrochemiluminescent detection of cancer biomarker proteins. Anal Chem. 2011;83(17):6698–703.  https://doi.org/10.1021/ac201292q.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Rissin DM, Kan CW, Campbell TG, Howes SC, Fournier DR, Song L, et al. Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol. 2010;28(6):595–9.  https://doi.org/10.1038/nbt.1641.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Wilson DH, Rissin DM, Kan CW, Fournier DR, Piech T, Campbell TG, et al. The Simoa HD-1 analyzer: a novel fully automated digital immunoassay analyzer with single-molecule sensitivity and multiplexing. J Lab Autom. 2016;21(4):533–47.  https://doi.org/10.1177/2211068215589580.CrossRefPubMedGoogle Scholar
  53. 53.
    Seo Y, Jeong S, Lee J, Choi HS, Kim J, Lee H. Innovations in biomedical nano-engineering: nanowell array biosensor. Nano Converg. 2018;5(1):9.  https://doi.org/10.1186/s40580-018-0141-6.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Graham H, Chandler DJ, Dunbar SA. The genesis and evolution of bead-based multiplexing. Methods. 2019;158:2–11.  https://doi.org/10.1016/j.ymeth.2019.01.007.CrossRefGoogle Scholar
  55. 55.
    Agarwal R, Heinz T. Bedside hemoglobinometry in hemodialysis patients: lessons from point-of-care testing. ASAIO J. 2001;47(3):240–3.CrossRefGoogle Scholar
  56. 56.
    Lehmann CA, Giacini JM. Point-of-care testing in the home and community environment: key ingredients for tomorrow’s community health. In: Price CP, St John A, Kricka LJ, editors. Point-of-care testing. 3rd ed. Washington: AACC Press; 2010.Google Scholar
  57. 57.
    Wurcel V, Perche O, Lesteven D, Williams DA, Schäfer B, Hopley C, et al. The value of companion diagnostics: overcoming access barriers to transform personalised health care into an affordable reality in Europe. Public Health Genomics. 2016;19(3):137–43.CrossRefGoogle Scholar
  58. 58.
    Hafner G, Peetz D, Dati F. Patientennahe Bestimmung der Troponine zur diagnostik akuter koronarsyndrome. Near-patient testing of troponins for the diagnosis of acute coronary syndromes. J Lab Med. 2003;27(7–8):279–87.  https://doi.org/10.1046/j.1439-0477.2003.03048.x.CrossRefGoogle Scholar
  59. 59.
    Collinson P. Detecting cardiac events - state-of-the-art. Ann Clin Biochem. 2015;52(Pt 6):702–4.  https://doi.org/10.1177/0004563215596761.CrossRefPubMedGoogle Scholar
  60. 60.
    Peetz D, Hafner G, Lackner KJ. Patientennahe Bestimmung natriuretischer peptide. Near-patient testing of natriuretic peptides. J Lab Med. 2005;29(4):219–28.  https://doi.org/10.1515/jlm.2005.030.CrossRefGoogle Scholar
  61. 61.
    Banerjee R, Jaiswal A. Recent advances in nanoparticle-based lateral flow immunoassay as a point-of-care diagnostic tool for infectious agents and diseases. Analyst. 2018;143(9):1970–96.  https://doi.org/10.1039/c8an00307f.CrossRefPubMedGoogle Scholar
  62. 62.
    Stürenburg E, Junker R. Point-of-care testing in microbiology: the advantages and disadvantages of immunochromatographic test strips. Dtsch Arztebl Int. 2009;106:48–54.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Reinert RR. Streptokokkenschnelltests. Rapid streptococcal antigen detection tests. J Lab Med. 2007;31(6):280–93.  https://doi.org/10.1515/jlm.2007.046.CrossRefGoogle Scholar
  64. 64.
    Stenken JA, Poschenrieder AJ. Bioanalytical chemistry of cytokines - a review. Anal Chim Acta. 2015;853:95–115.  https://doi.org/10.1016/j.aca.2014.10.009.CrossRefPubMedGoogle Scholar
  65. 65.
    Pawlak M, Schick E, Bopp MA, Schneider MJ, Oroszlan P, Ehrat M. Zeptosens’ protein microarrays: a novel high performance microarray platform for low abundance protein analysis. Proteomics. 2002;2(4):383–93.  https://doi.org/10.1002/1615-9861(200204)2:4<383::AID-PROT383>3.0.CO;2-E.CrossRefPubMedGoogle Scholar
  66. 66.
    Potuckova L, Franko F, Bambouskova M, Draber P. Rapid and sensitive detection of cytokines using functionalized gold nanoparticle-based immuno-PCR, comparison with immuno-PCR and ELISA. J Immunol Methods. 2011;371(1–2):38–47.  https://doi.org/10.1016/j.jim.2011.06.012.CrossRefPubMedGoogle Scholar
  67. 67.
    Duking P, Achtzehn S, Holmberg HC, Sperlich B. Integrated framework of load monitoring by a combination of smartphone applications, wearables and point-of-care testing provides feedback that allows individual responsive adjustments to activities of daily living. Sensors (Basel). 2018;18(5).  https://doi.org/10.3390/s18051632.CrossRefGoogle Scholar
  68. 68.
    Kiang TKL, Ranamukhaarachchi SA, Ensom MHH. Revolutionizing therapeutic drug monitoring with the use of interstitial fluid and microneedles technology. Pharmaceutics. 2017;9(4).  https://doi.org/10.3390/pharmaceutics9040043.CrossRefGoogle Scholar
  69. 69.
    Singh V, Krishnan S. Electrochemical and surface plasmon insulin assays on clinical samples. Analyst. 2018;143(7):1544–55.  https://doi.org/10.1039/c7an01872j.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Wood F, Brookes-Howell L, Hood K, Cooper L, Verheij T, Goossens H, et al. A multi-country qualitative study of clinicians’ and patients’ views on point of care tests for lower respiratory tract infection. Fam Pract. 2011;28(6):661–9.  https://doi.org/10.1093/fampra/cmr031.CrossRefPubMedGoogle Scholar
  71. 71.
    Dunn SG, Visnich MR. Home-based point-of-care testing. In: Kost GJ, editor. Princinples and practice of point-of-care testing. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 376–90.Google Scholar
  72. 72.
    Siebenhofer A, Jeitler K, Horvath K, Habacher W, Schmidt L, Semlitsch T. Self-management of oral anticoagulation. Dtsch Arztebl Int. 2014;111(6):83–91.  https://doi.org/10.3238/arztebl.2014.0083.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Robinson JE, Wakelin M, Ellis JE. Increased pregnancy rate with use of the Clearblue easy fertility monitor. Fertil Steril. 2007;87(2):329–34.  https://doi.org/10.1016/j.fertnstert.2006.05.054.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Friedewald S, Finke E-J, Dobler G. Patientennahe Diagnostik in Krisensituationen. J Lab Med. 2006;30:211–8.Google Scholar
  75. 75.
    Kost GJ, Ferguson WJ, Hoe J, Truong AT, Banpavichit A, Kongpila S. The Ebola spatial care path: accelerating point-of-care diagnosis, decision making, and community resilience in outbreaks. Am J Disaster Med. 2015;10(2):121–43.  https://doi.org/10.5055/ajdm.2015.0196.CrossRefPubMedGoogle Scholar
  76. 76.
    Price CP, St. John A. Innovation in healthcare. The challenge for laboratory medicine. Clin Chim Acta. 2014;427:71–8.CrossRefGoogle Scholar
  77. 77.
    Deutsches Institut für Normung. DIN 58964:2015-09 - quality assurance of POCT results. Assessment criteria for comparison measurement and implementation. Berlin: Beuth Verlag. 2015.Google Scholar
  78. 78.
    Zhang WR, Parikh CR (2019) Biomarkers of acute and chronic kidney disease. Annu Rev Physiol 81:309-333. doi:  https://doi.org/10.1146/annurev-physiol-020518-114605. (Feb 10):309-333.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Andreas Poschenrieder
    • 1
  • Markus Thaler
    • 1
  • Ralf Junker
    • 2
  • Peter B. Luppa
    • 1
    Email author
  1. 1.Klinikum rechts der Isar der TU MünchenInstitut für Klinische Chemie und PathobiochemieMunichGermany
  2. 2.Institut für Klinische ChemieUniversitätsklinikum Schleswig-HolsteinKielGermany

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