Direct electrochemical biosensing in gastrointestinal fluids

  • Víctor Ruiz-Valdepeñas Montiel
  • Juliane R. Sempionatto
  • Susana Campuzano
  • José M. Pingarrón
  • Berta Esteban Fernández de ÁvilaEmail author
  • Joseph WangEmail author
Paper in Forefront
Part of the following topical collections:
  1. Young Investigators in (Bio-)Analytical Chemistry


Edible electrochemical biosensors with remarkable prolonged resistance to extreme acidic conditions are described for direct glucose sensing in gastrointestinal (GI) fluids of different pH ranges and compositions. Such direct and stable glucose monitoring is realized using carbon-paste biosensors prepared from edible materials, such as olive oil and activated charcoal, shown to protect the activity of the embedded glucose oxidase (GOx) enzyme from strongly acidic conditions. The enzymatic resistance to low-pH deactivation allowed performing direct glucose monitoring in strong acidic environments (pH 1.5) over a 90-min period, while the response of conventional screen-printed (SP) biosensors decreased significantly following 10-min incubation in the same fluid. The developed edible biosensor displayed a linear response between 2 and 10 mM glucose with sensitivity depending on the pH of the corresponding GI fluid. In addition, coating the electrode surface with pH-responsive enteric coatings (Eudragit® L100 and Eudragit® E PO), of different types and densities, allows tuning the sensor activation in gastric and intestinal fluids at specific predetermined times. The attractive characteristics and sensing performance of these edible electrochemical biosensors, along with their pH-responsive actuation, hold considerable promise for the development of ingestible devices towards the biosensing of diverse target analytes after prolonged incubation in challenging body fluids.

Graphical Abstract

Edible biosensors allow direct electrochemical sensing in different gastrointestinal fluids and display remarkable prolonged resistance to extreme acidic conditions.


Edible electrode Biosensor Gastrointestinal fluids Acid resistant surfaces Selective activation 


Funding information

This work was supported by the Center for Wearable Sensors. J.R.S. acknowledges fellowship from CNPq (216981/2014-0).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Opportunities and challenges in digestive diseases research: recommendations of the national commission on digestive diseases. Maryland: National Institutes of Health; Washington DC: US Department of Health and Human Services; 2009.Google Scholar
  2. 2.
    Haghiashtiani G, McAlpine MC. Sensing gastrointestinal motility. Nat Biomed Eng. 2017;1:775–6.CrossRefGoogle Scholar
  3. 3.
    Traverso G, Langer R. Perspective: special delivery for the gut. Nature. 2015;519:S19.CrossRefGoogle Scholar
  4. 4.
    Wang J. Electrochemical glucose biosensors. Chem Rev. 2008;108:814–25.CrossRefGoogle Scholar
  5. 5.
    Matzeu G, Florea L, Diamond D. Advances in wearable chemical sensor design for monitoring biological fluids. Sensors Actuators B Chem. 2015;211:403–18.CrossRefGoogle Scholar
  6. 6.
    Gao W, Emaminejad S, Nyein HYY, Challa S, Chen K, Peck A, et al. Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature. 2016;529:509–14.CrossRefGoogle Scholar
  7. 7.
    Xiao T, Wu F, Hao J, Zhang M, Yu P, Mao L. In vivo analysis with electrochemical sensors and biosensors. Anal Chem. 2017;89:300–13.CrossRefGoogle Scholar
  8. 8.
    Wang B, Li B, Cheng G, Dong S. Acid-stable amperometric soybean peroxidase biosensor based on a self-gelatinizable grafting copolymer of polyvinyl alcohol and 4-vinylpyridine. Electroanalysis. 2001;13:555–8.CrossRefGoogle Scholar
  9. 9.
    Dong S, Wang B. Electrochemical biosensing in extreme environment. Electroanalysis. 2002;14:7–16.CrossRefGoogle Scholar
  10. 10.
    Wang J, Musameh M, Mo J-W. Acid stability of carbon paste enzyme electrodes. Anal Chem. 2006;78:7044–7.CrossRefGoogle Scholar
  11. 11.
    Wang J, Liu J, Cepra G. Thermal stabilization of enzymes immobilized within carbon paste electrodes. Anal Chem. 1997;69:3124–7.CrossRefGoogle Scholar
  12. 12.
    Valdés-Ramírez G, Li YC, Kim J, Jia W, Bandodkar AJ, Nuñez-Flores R, et al. Microneedle-based self-powered glucose sensor. Electrochem Commun. 2014;47:58–62.CrossRefGoogle Scholar
  13. 13.
    Mohan AMV, Windmiller JR, Mishra RK, Wang J. Continuous minimally-invasive alcohol monitoring using microneedle sensor arrays. Biosens Bioelectron. 2017;91:574–9.CrossRefGoogle Scholar
  14. 14.
    Jeerapan I, Sempionatto JR, You J-M, Wang J. Enzymatic glucose/oxygen biofuel cells: use of oxygen-rich cathodes for operation under severe oxygen-deficit conditions. Biosens Bioelectron. 2018;122:284–9.CrossRefGoogle Scholar
  15. 15.
    Švancara I, Vytřas K, Kalcher K, Walcarius A, Wang J. Carbon paste electrodes in facts, numbers, and notes: a review on the occasion of the 50-years jubilee of carbon paste in electrochemistry and electroanalysis. Electroanalysis. 2009;21:7–28.CrossRefGoogle Scholar
  16. 16.
    Kim J, Kumar R, Bandodkar AJ, Wang J. Advanced materials for printed wearable electrochemical devices: a review. Adv Electron Mater. 2017;3:1600260.CrossRefGoogle Scholar
  17. 17.
    Kim J, Jeerapan I, Ciui B, Hartel MC, Martin A, Wang J. Edible electrochemistry: food materials based electrochemical sensors. Adv Healthcare Mater. 2017;6:1700770.CrossRefGoogle Scholar
  18. 18.
    Bettinger CJ. Materials advances for next-generation ingestible electronic medical devices. Trends Biotechnol. 2015;33:575–85.CrossRefGoogle Scholar
  19. 19.
    Kalantar-zadeh K, Ha N, Zhen Ou J, Berean KJ. Ingestible sensors. ACS Sens. 2017;2:468–83.CrossRefGoogle Scholar
  20. 20.
    Tahirbegi IB, Mir M, Samitier J. Real-time monitoring of ischemia inside stomach. Biosens Bioelectron. 2013;40:323–8.CrossRefGoogle Scholar
  21. 21.
    Bandodkar AJ, Jia W, Yardımcı C, Wang X, Ramirez J, Wang J. Tattoo-based noninvasive glucose monitoring: a proof-of-concept study. Anal Chem. 2015;87:394–8.CrossRefGoogle Scholar
  22. 22.
    Kim J, Sempionatto JR, Imani S, Hartel MC, Barfidokht A, Campbell AS, et al. Simultaneous monitoring of sweat and interstitial fluid using a single wearable biosensor platform. Adv Sci. 2018:1800880.Google Scholar
  23. 23.
    Moustafine RI, Bukhovets AV, Sitenkov AY, Kemenova VA, Rombaut P, Van den Mooter G. Eudragit E PO as a complementary material for designing oral drug delivery systems with controlled release properties: comparative evaluation of new interpolyelectrolyte complexes with countercharged Eudragit L100 copolymers. Mol Pharm. 2013;10:2630–41.CrossRefGoogle Scholar
  24. 24.
    Cetin M, Atila A, Kadioglu Y. Formulation and in vitro characterization of Eudragit® L100 and Eudragit® L100-PLGA nanoparticles containing diclofenac sodium. AAPS PharmSciTech. 2010;11:1250–6.CrossRefGoogle Scholar
  25. 25.
    Ruiz-Valdepeñas Montiel V, Sempionatto JR, Esteban-Fernández de Ávila B, Whitworth A, Campuzano S, Pingarrón JM, et al. Delayed sensor activation based on transient coatings: biofouling protection in complex biofluids. J Am Chem Soc. 2018;140:14050–3.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Víctor Ruiz-Valdepeñas Montiel
    • 1
    • 2
  • Juliane R. Sempionatto
    • 1
  • Susana Campuzano
    • 2
  • José M. Pingarrón
    • 2
  • Berta Esteban Fernández de Ávila
    • 1
    Email author
  • Joseph Wang
    • 1
    Email author
  1. 1.Department of NanoengineeringUniversity of California San DiegoLa JollaUSA
  2. 2.Department of Analytical ChemistryComplutense University of MadridMadridSpain

Personalised recommendations