MEMS based cantilever biosensors for cancer detection using potential bio-markers present in VOCs: a survey

  • KurmendraEmail author
  • Rajesh Kumar
Review Article


The biosensors are being used for detection of various dangerous biomarkers present in water, air and human body, etc. Invasive and non-invasive methods are discussed. In non-invasive method, the early detection of any disease involves detection of available biomarkers in exhaled breath at ppb level. The biomarkers for different disease are presented here and the methods involved are also provided. This study mainly focuses on systematic review of various cancer disease with biomarkers and also provides the comparative review of different traditional biosensors such as FET based biosensor with micro–electro-mechanical systems (MEMS) based Biosensors capable of detecting biomarkers even at ppb level in exhaled breath. This study also concludes that the cantilever or array of cantilever-based biosensors is simple and very precise for early detection of cancer disease. Cantilever surfaces with pores are highly desirable since it increases sensitivity of biosensors.



  1. Alix-Panabières C, Pantel K (2013) Circulating tumor cells: liquid biopsy of cancer. Clin Chem 59(1):110–118. (Epub 26 Sep 2012) CrossRefGoogle Scholar
  2. Amal H, Ding L, Liu BB, Tisch U, Xu ZQ, Shi DY, Zhao Y, Chen J, Sun RX, Liu H et al (2012) The scent fingerprint of hepatocarcinoma: in-vitro metastasis prediction with volatile organic compounds (VOCs). Int J Nanomed 7(4135–4146):109Google Scholar
  3. American Cancer Society (2017) Cancer prevention and early detection facts and figures 2017–2018. American Cancer Society, AtlantaGoogle Scholar
  4. Bray F, Ren JS, Masuyer E et al (2013) Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 132(5):1133–1145CrossRefGoogle Scholar
  5. Capelli L, Sironi S, Barczak R, Il Grande M, del Rosso R (2012) Validation of a method for odor sampling on solid area sources. Water Sci Technol 66:1607–1613CrossRefGoogle Scholar
  6. Chen X, Pan Y, Liu H, Bai X, Wang N, Zhang B (2015) Label-free detection of liver cancer cells by aptamer-based microcantilever biosensor. Biosens Bioelectron 79:353–358CrossRefGoogle Scholar
  7. Datar R, Passian A, Desikan R, Thundat T (2007) Microcantilever biosensors. In: SENSORS, 2007 IEEE. Atlanta, GA, pp 5–5.
  8. Faegh Samira, Jalili Nader, Sridhar Srinivas (2013) A self-sensing piezoelectric microcantilever biosensor for detection of ultrasmall adsorbed masses: theory and experiments. Sensors 13:6089–6108. CrossRefGoogle Scholar
  9. Ferlay J, Soerjomataram I, Ervik M et al (2013) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer, LyonGoogle Scholar
  10. Gao Y, Gan Q, Bartoli FJ (2014) Breakthroughs in photonics 2013: research highlights on biosensors based on plasmonic nanostructures. IEEE Photonics J 6(2):1–5. CrossRefGoogle Scholar
  11. Giannoukos S, Agapiou A, Taylor S (2018) Advances in chemical sensing technologies for VOCs in breath for security/threat assessment, illicit drug detection, and human trafficking activity. J Breath Res 12(2):027106CrossRefGoogle Scholar
  12. GOI (2010) Report on causes of deaths in India 2001–2003. Office of the Registrar General of India, Govt. of India, 2010Google Scholar
  13. Gopinath PG, Mastani SA, Anitha VR (2014) Optimum design and analysis of rectangular microcantilever for human immunodeficiency virus detection. J Biomed Pharm Res 3:50–54Google Scholar
  14. Gopinath PG, Anitha VR, Mastani SA (2015) Microcantilever based biosensor for disease detection applications. J Med Bioeng 4(4):34Google Scholar
  15. Grabowska-Polanowska B, Faber J, Skowron M, Miarka P, Pietrzycka A, Sliwka I, Amann A (2013) Detection of potential chronic kidney disease markers in breath using gas chromatography with mass-spectral detection coupled with thermal desorption method. J Chromatogr A 1301:179–189. Epub 2013 May 14 CrossRefGoogle Scholar
  16. Joshi AK, Tomar A, Tomar M (2014) A review paper on analysis of electrocardiograph (ECG) signal for the detection of arrhythmia abnormalities. Int J Adv Res Electr Electron Instrum Eng 10:12466–12475Google Scholar
  17. Kaisti Matti (2017) Detection principles of biological and chemical FET sensors. Biosens Bioelectron 98:437–448CrossRefGoogle Scholar
  18. Karthigeyan K (2012) Cervical cancer in India and HPV vaccination. Indian J Med Paediatr Oncol 33(1):7–12CrossRefGoogle Scholar
  19. Konvalina G, Haick H (2014) Sensors for breath testing: from nanomaterials to comprehensive disease detection. Acc Chem Res 47(1):66–76. CrossRefGoogle Scholar
  20. Korovesi I, Kotanidou A, Papadomichelakis E, Livaditi O, Sotiropoulou C, Koutsoukou A, Marczin N, Orfanos SE (2016) Exhaled nitric oxide and carbon monoxide in mechanically ventilated brain-injured patients. J Breath Res 10(1):017107. CrossRefGoogle Scholar
  21. Kurmendra S, Kumar R (2017) Design analysis, modeling and simulation of novel rectangular cantilever beam for MEMS sensors and energy harvesting applications. Int J Inform Tecnol 9:295. CrossRefGoogle Scholar
  22. Lechner M, Karlseder A, Niederseer D, Lirk P, Neher A, Rieder J (2005) H. pylori infection increases levels of exhaled nitrate. Helicobacter 10:385–390CrossRefGoogle Scholar
  23. Loo L, Wu W, Shih WY, Shih WH, Borghaei H, Pourrezaei K, Adams GP (2011) A rapid method to regenerate piezoelectric microcantilever sensors (PEMS). Sensors 11(5):5520–5528CrossRefGoogle Scholar
  24. Luka G, Ahmadi A, Najjaran H, Alocilja E, DeRosa M, Wolthers K, Malki A, Aziz H, Althani A, Hoorfar M (2015) Microfluidics integrated biosensors: a leading technology towards lab-on-a-chip and sensing applications. Sensors 15(12):30011–30031. CrossRefGoogle Scholar
  25. Mascaux C, Peled N, Garg K, Kato Y, Wynes MW, Hirsch FR (2010) Early detection and screening of lung cancer. Expert Rev Mol Diagn 10(6):799–815CrossRefGoogle Scholar
  26. Mehrotra P (2016) Biosensors and their applications—a review. J Oral Biol Craniofac Res 6(2):153–159. CrossRefGoogle Scholar
  27. Mohd Firdaus Sh, Omar H, Abd Azid I (2012) High sensitive piezoresistive cantilever MEMS based sensor by introducing stress concentration region (SCR). In: Ebrahimi F (ed) Finite element analysis. IntechOpen, London. Google Scholar
  28. Murugaiyan SB, Ramasamy R, Gopal N, Kuzhandaivelu V (2014) Biosensors in clinical chemistry: an overview. Adv Biomed Res 3:67. CrossRefGoogle Scholar
  29. Nemirovsky Y, Shemesh A, Stolyarova S (2008) NEMS/MEMS cantilever-based biosensors: addressing the open issues. In: Proceedings SPIE 6993, MEMS, MOEMS, and Micromachining III
  30. Pandya HJ, Park K, Desai JP (2015) Design and fabrication of a flexible MEMS- BASED electro mechanical sensor array for breast cancer diagnosis. J Micromech Microeng 25:075025CrossRefGoogle Scholar
  31. Phillips M, Gleeson K, Hughes JM, Greenberg J, Cataneo RN, Baker L, McVay WP (1999) Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 353(9168):1930–1933CrossRefGoogle Scholar
  32. Phillips M, Cataneo RN, Condos R, Ring Erickson GA, Greenberg J, La Bombardi V, Munawar MI, Tietje O (2007a) Volatile biomarkers of pulmonary tuberculosis in the breath. Tuberculosis 87(1):44–52 (Epub 25Apr 2006) CrossRefGoogle Scholar
  33. Phillips M, Cantaneo RN, Condos R, Gerald A, Erickson R, Greenberg J, La Bombardi V, Munawar MI, Tietje O (2007b) Volatile biomarkers of pulmonary tuberculosis in the breath. Tuberculosis 87:44–52CrossRefGoogle Scholar
  34. Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK, Natividad MPR, Schmitt P, Wai J (2010a) Breath biomarkers of active pulmonary tuberculosis. Tuberculosis 90:145–151CrossRefGoogle Scholar
  35. Phillips M, Cataneo RN, Saunders C, Hope P, Schmitt P, Wai J (2010b) Volatile biomarkers in the breath of women with breast cancer. J Breath Res 4:026003CrossRefGoogle Scholar
  36. Phillips M, Basa-Dalay V, Blais J, Bothamley G, Chaturvedi A, Modi KD, Pandya M, Natividad MPR, Patel U, Ramraje NN, Schmitt P, Udwadia ZF (2012) Point-of-care breath test for biomarkers of active tuberculosis. Tuberculosis 92:314–332CrossRefGoogle Scholar
  37. Phillips M, Beatty JD, Cataneo RN et al (2014) Rapid point-of-care breath test for biomarkers of breast cancer and abnormal mammograms. PLoS One 9:e90226CrossRefGoogle Scholar
  38. Probert CS, Ahmed I, Khalid T, Johnson E, Smith S, Ratcliffe N (2009) Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases. J Gastrointestin Liver Dis 18(3):337–343Google Scholar
  39. Rabis T, Sommerwerck U, Anhenn O, Darwiche K, Freitag L, Teschler H, Bödeker B, Madulla S, Baumbach JI (2011) Detection of infectious agents in the airways by ion mobility spectrometry of exhaled breath. Int J Ion Mobil Spectrom 14:187–195CrossRefGoogle Scholar
  40. Reddy KS, Gupta PC (2004) Report on tobacco control in India. Ministry of Health and Family Welfare, Government of India, New DelhiGoogle Scholar
  41. Rinaldi G, Packirisamy M, Stiharu I (2007) Tuning the dynamic behaviour of cantilever MEMS based sensors and actuators. Sens Rev 27(2):142–150. CrossRefGoogle Scholar
  42. Rydosz A, Wincza K, Gryszczynski S (2016) Microsystem in LTCC technology for the detection of acetone in healthy and diabetes breath. In: 2016 IEEE ANDESCON, Arequipa, pp 1–4.
  43. Saeed MA, Khan SM, Ahmed N, Khan MU, Rehman A (2016) Design and analysis of capacitance based Bio-MEMS cantilever sensor for tuberculosis detection. In: International conference on intelligent systems engineering (ICISE), Islamabad, pp 175–180.
  44. Sebastian R, Muniraj NJR (2015) Design and implementation of cancer cells elimination using MEMS. Middle East J Sci Res 23(11):2773–2775Google Scholar
  45. Sethi S, Nanda R, Chakraborty T (2013) Clinical application of volatile organic compound analysis for detecting infectious diseases. Clin Microbiol Rev 26(3):462–475. CrossRefGoogle Scholar
  46. Smith D, Spaněl P, Fryer AA, Hanna F, Ferns GA (2011) Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus? J Breath Res 5(2):022001. (Epub 21 Apr 2011) CrossRefGoogle Scholar
  47. Sree Vidhya E, Kumar GP, Mathew L (2010) Design and TEM simulation of a MEMS based micro cantilever cardiac market sensor. J Nanotechnol Eng Med 1(1):014501–0145014CrossRefGoogle Scholar
  48. SreeVidhya E, Kumar GP, Mathew L (2010) Micro-cantilever based microdiagnostic kit for bio-medical applications—a cost-benefit outlook. J Nanotechnol Eng Med 1(3):034501–034504CrossRefGoogle Scholar
  49. Srinivasaraghavan V, Strobl J, Agah M (2011) Detection of breast cancer cells in try culture using impedance spectroscopy. In: 15th International Conference on Miniaturized Systems for Chemistry and Life Sciences, October 2–6, 2011, Seattle, WA, USAGoogle Scholar
  50. Syhre M, Manning L, Phuanukoonnon S, Harino P, Chambers ST (2009) The scent of mycobacterium tuberculosis—part II breath. Tuberculosis 2009(89):263–266CrossRefGoogle Scholar
  51. Timurdogan E, Alaca BE, Kavakli IH, Urey H (2011) MEMS biosensor for detection of Hepatitis A and C viruses in serum. Biosens Bioelectron 28:189–194CrossRefGoogle Scholar
  52. Van den Velde S, Nevens F, Van Hee P, van Steenberghe D, Quirynen M (2008) GC-MS analysis of breath odor compounds in liver patients. J Chromatogr B Anal Technol Biomed Life Sci 875:344–348CrossRefGoogle Scholar
  53. Vijverberg SJ, Hilvering B, Raaijmakers JA, Lammers JW, van der Zee AHM, Koenderman L (2013) Clinical utility of asthma biomarkers: from bench to bedside. Biologics 7:199–210. (Epub 29 Aug 2013) Google Scholar
  54. Wang S, Wang J, Zhu Y, Yang J, Yang F (2014) Cantilever with immobilized antibody for liver cancer biomarker detection. J Semicond 35:104008CrossRefGoogle Scholar
  55. Wang S, Wang J, Zhu Y, Yang J, Yang F (2015a) A new device for liver cancer biomarker detection with high accuracy. Sens Bio-Sens Res 4:40–45CrossRefGoogle Scholar
  56. Wang S, Wang J, Zhu Y, Yang J, Yang F (2015b) A new device for liver cancer biomarker detection with high accuracy. Sens Bio-Sens Res 4:40–45. CrossRefGoogle Scholar
  57. Wang J, Zhu Yinfang, Zhang Jinying, Yang Jinling (2016a) Development of microcantilever sensors for liver cancer detection. Adv Cancer Prev 1:103. Google Scholar
  58. Wang Jingjing, Wang Lihao, Zhu Yinfang, Jinying Zhang Ju, Liao Shuaipeng Wang, Yang Jinling, Yang Fuhua (2016b) A high accuracy cantilever array sensor for early livercancer diagnosis. Biomed Microdevices 18:110. CrossRefGoogle Scholar
  59. WHO (2008) Summary report on HPV and cervical cancer statistics in India 18 Mar 2008Google Scholar
  60. World Health Organization (2009) The global burden of disease: 2004 update. WHO, GenevaGoogle Scholar
  61. Xue R, Dong L, Zhang S, Deng C, Liu T, Wang J, Shen X (2008) Investigation of volatile biomarkers in liver cancer blood using solid-phase microextraction and gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom 22:1181–1186CrossRefGoogle Scholar
  62. Yamagiwa H et al (2014) detection of volatile organic compounds by weight-detectable sensors coated with metal-organic frameworks. Sci Rep 4:6247. CrossRefGoogle Scholar
  63. Yan L, Wang Y, Li J, Ma H, Liu H, Li T, Zhang Y (2014) Comparative study of different electrochemical methods for petroleum refinery wastewater treatment. Desalination 341:87–93CrossRefGoogle Scholar
  64. Yavuz Y, Koparal AS, Ogutveren UB (2010) Treatment of petroleum refinery wastewater by electrochemical methods. Desalination 258:201–205CrossRefGoogle Scholar
  65. Zakaria NH, Nordin AN, Mel M, Arifuzzaman SM, Voiculescu I (2009) MEMS Biosensor for Potential Cancer Cell Detection. In: ASME 2009 International Mechanical Engineering Congress and Exposition.
  66. Zhang F, Qu G, Mohammadi E, Mei J, Diao Y (2017) Solution-processed nanoporous organic semiconductor thin films: toward health and environmental monitoring of volatile markers. Adv Funct Mater 25:25. Google Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Electronics and Communication EngineeringRajiv Gandhi University (A Central University)ItanagarIndia
  2. 2.Department of Electronics and Communication EngineeringNorth Eastern Regional Institute of Science and TechnologyItanagarIndia

Personalised recommendations