Доступ предоставлен для: Guest
Портал Begell Электронная Бибилиотека e-Книги Журналы Справочники и Сборники статей Коллекции
Critical Reviews™ in Biomedical Engineering
SJR: 0.26 SNIP: 0.375 CiteScore™: 1.4

ISSN Печать: 0278-940X
ISSN Онлайн: 1943-619X

Том 48, 2020 Том 47, 2019 Том 46, 2018 Том 45, 2017 Том 44, 2016 Том 43, 2015 Том 42, 2014 Том 41, 2013 Том 40, 2012 Том 39, 2011 Том 38, 2010 Том 37, 2009 Том 36, 2008 Том 35, 2007 Том 34, 2006 Том 33, 2005 Том 32, 2004 Том 31, 2003 Том 30, 2002 Том 29, 2001 Том 28, 2000 Том 27, 1999 Том 26, 1998 Том 25, 1997 Том 24, 1996 Том 23, 1995

Critical Reviews™ in Biomedical Engineering

DOI: 10.1615/CritRevBiomedEng.2019026532
pages 169-178

Development Toward a Triple-Marker Biosensor for Diagnosing Cardiovascular Disease

Anna Deng
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona
Daniel Matloff
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona
Chi-En Lin
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona
David Probst
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona
Theresa Broniak
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona
Maryam Alsuwailem
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona
Jeffrey T. La Belle
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona

Краткое описание

Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 30% of all deaths globally. The diagnosis and management of CVD requires monitoring of multiple biomarkers, which comprehensively represents the state of the disease. However, many assays for cardiac biomarkers today are complicated and laborious to perform. Rapid and sensitive biosensors capable of giving accurate measurements of vital cardiac biomarkers without complex procedures are thus in high demand. In the work presented below, rapid, label-free biosensor prototypes for three Food and Drug Administration–approved biomarkers are reported: B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and C-reactive protein (CRP). The sensors were prepared by immobilizing each biomarker's antibody onto gold working electrodes with platinum counter and silver/silver chloride reference electrodes. The sensors were tested using electrochemical impedance spectroscopy (EIS), a femto-molar sensitive technique capable of label-free, multi-marker detection if a biomarker's optimal frequency (OF) can be identified. The OFs of BNP, cTnI, and CRP were found to be 1.74, 37.56, and 253.9 Hz, respectively. The performance of the BNP biosensor was also evaluated in blood and achieved clinically relevant detection limits of 100 pg/mL.


  1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS. , Executive summary: heart disease and stroke statistics— 2013 update. Circulation. 2013;127(1):143–52.

  2. Cardiac risk assessment [Internet]. [cited 2018 May 26]. Available from: https://labtestsonline.org/tests/cardiacrisk- assessment.

  3. Honikel MM, Lin C-E, Probst D, La Belle JT. , Facilitating earlier diagnosis of cardiovascular disease through point-of-care biosensors: a review. Crit Rev Biomed Eng. 2018;46(1):53–82.

  4. Gaggin HK, Januzzi JL. , Biomarkers and diagnostics in heart failure. Biochim Biophys Acta –Mol Basis Dis. 2013 Dec 1;1832(12):2442–50.

  5. Weber M, Hamm C. , Role of B‐type natriuretic peptide (BNP) and NT‐proBNP in clinical routine. Heart. 2006 Jun;92(6):843–9.

  6. Maalouf R, Bailey S. , A review on B-type natriuretic peptide monitoring: assays and biosensors. Heart Fail Rev. 2016;(21):567–78.

  7. Wolf M, Juncker D, Michel B, Hunziker P, Delamarche E. Simultaneous detection of C-reactive protein and other cardiac markers in human plasma using micromosaic immunoassays and self-regulating microfluidic networks. Biosens Bioelectron. 2004 May 15;19(10):1193–202.

  8. Heller WT, Abusamhadneh E, Finley N, Rosevear PR, Trewhella J., The solution structure of a cardiac troponin C−troponin I−troponin T complex shows a somewhat compact troponin C Interacting with an extended troponin I−troponin T component. Biochemistry (Mosc). 2002 Dec 1;41(52):15654–63.

  9. Horwich TB, Patel J, MacLellan WR, Fonarow GC. , Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation. 2003 Aug 19;108(7):833–8.

  10. Ilva T, Lassus J, Siirilä‐Waris K, Melin J, Peuhkurinen K, Pulkki K, Nieminen MS, Mustonen H, Porela P, Harjola V. , Clinical significance of cardiac troponins I and T in acute heart failure. Eur J Heart Fail. 10(8):772–9.

  11. Lam Q, Black M, Youdell O, Spilsbury H, Schneider HG. , Performance evaluation and subsequent clinical experience with the Abbott Automated Architect STAT troponin- I assay. Clin Chem. 2006 Mar 1;52:298–300.

  12. Sherwood MW, Newby LK. , High-sensitivity troponin assays: evidence, indications, and reasonable use. J Am Heart Assoc. 2014 Jan 3;3(1):e000403.

  13. Sabatine MS, Morrow DA, Jablonski KA, Rice MM, Warnica JW, Domanski MJ, Hsia J, Gersh BJ, Rifai N, Ridker PM, Pfeffer MA, Braunwald E, Prognostic significance of the Centers For Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation. 2007 Mar 27;115(12).

  14. Hennessey H, Afara N, Omanovic S, Padjen AL. , Electrochemical investigations of the interaction of C-reactive protein (CRP) with a CRP antibody chemically immobilized on a gold surface. Anal Chim Acta. 2009 Jun 8;643(1):45–53.

  15. Lisdat F, Schäfer D. , The use of electrochemical impedance spectroscopy for biosensing. Anal Bioanal Chem. 2008 Jul 1;391(5):1555.

  16. Belle JTL, Demirok UK, Patel DR, Cook CB. , Development of a novel single sensor multiplexed marker assay. Analyst. 2011 Mar 14;136(7):1496–501.

  17. Lin C, Ryder L, Probst D, Caplan M, Spano M, LaBelle J. , Feasibility in the development of a multi-marker detection platform. Biosens Bioelectron. 2017 Mar 15;89:743–9.

  18. Fairchild AB, McAferty K, Demirok UK, Belle JTL. , A label-free, rapid multimarker protein impedance-based immunosensor. In: 2009 ICME International Conference on Complex Medical Engineering. 2009. p. 1–5.

  19. Adamson TL, Cook CB, LaBelle JT. , Detection of 1,5-anhydroglucitol by electrochemical impedance spectroscopy. J Diabetes Sci Technol. 2014;8(2):350–5.

  20. La Belle JT, Fairchild A, Demirok UK, Verma A. , Method for fabrication and verification of conjugated nanoparticle- antibody tuning elements for multiplexed electrochemical biosensors. Methods San Diego Calif. 2013 May 15;61(1):39–51.

  21. Troponin I,, cardiac:protein overview: UCSD-nature molecule pages [Internet]. [cited 2018 May 26]. Available from: http://www.signaling-gateway.org/molecule/ query?afcsid=A002325.

  22. CRP (human) [Internet]. [cited 2018 May 26]. Available from: https://www.phosphosite.org/proteinAction?id=512 6327&showAllSites=true.

  23. CRP-clinical: C-reactive protein (CRP), serum [Internet]. [cited 2018 May 26]. Available from: https://www.mayomedicallaboratories. com/test-catalog/Clinical+and+Interpretive/ 9731.

  24. Honikel MM, Lin C-E, Cardinell BA, LaBelle JT, Penman AD. , Direct measurement of a biomarker’s native optimal frequency with physical adsorption based immobilization. ACS Sens. 2018 Apr 27;3(4):823–31.

  25. Wijbenga JA, Balk AH, Boomsma F, Man in ’t Veld AJ, Hall C. , Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice. Eur Heart J. 1999 Oct 1;20(19): 1424–8.

  26. Zaphiriou A, Robb S, Murray‐Thomas T, Mendez G, Fox K, McDonagh T, Hardman SMC, Dargie HJ, Cowie MR, The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study. Eur J Heart Fail. 7(4):537–41.

  27. Wu AHB, Christenson RH, Greene DN, Jaffe AS, Kavsak PA, Ordonez-Llanos J, Apple FS., Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers.

  28. C-reactive protein test–Mayo Clinic [Internet]. [cited 2018 May 26]. Available from: https://www.mayoclinic. org/tests-procedures/c-reactive-protein-test/about/pac- 20385228.

Articles with similar content:

Biomarkers for Serum Diagnosis of Infectious Diseases and Their Potential Application in Novel Sensor Platforms
Critical Reviews™ in Immunology, Vol.30, 2010, issue 2
Ana Graci Brito-Madurro, Carlos U. Vieira, Juliana F. Almeida, Luiz R. Goulart, Isabela M.B. Goulart, Ana Paula P. Freschi, Lucas F. Ferreira, Joao M. Madurro, Patricia T. Fujimura, Fausto E. Capparelli
Toward a Label-Free Electrochemical Impedance Immunosensor Design for Quantifying Cortisol in Tears
Critical Reviews™ in Biomedical Engineering, Vol.47, 2019, issue 3
Brittney A. Cardinell, Mark L. Spano, Jeffrey T. La Belle
Microwave-Induced Thermal Lesion Detection via Ultrasonic Scatterer Center Frequency Analysis with Autoregressive Cepstrum
Critical Reviews™ in Biomedical Engineering, Vol.48, 2020, issue 2
Lei Sheng, Wei Rao, Guolin Ma, Zhuhuang Zhou, Shuicai Wu
Facilitating Earlier Diagnosis of Cardiovascular Disease through Point-of-Care Biosensors: A Review
Critical Reviews™ in Biomedical Engineering, Vol.46, 2018, issue 1
David Probst, Mackenzie M. Honikel, Jeffrey T. La Belle, Chi-En Lin
Multi-Biomarker Detection Following Traumatic Brain Injury
Critical Reviews™ in Biomedical Engineering, Vol.47, 2019, issue 3
Brittney A. Cardinell, Jeffrey T. La Belle, Sarah E. Stabenfeldt, Caroline P. Addington