Skip to main content
SpringerLink
Log in

Recirculation—a novel approach to quantify interstitial analytes in living tissue by combining a sensor with open-flow microperfusion

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

We report a novel approach to quantify interstitial analytes in living tissue by combining open-flow microperfusion (OFM) with a sensor and the re-circulation method. OFM is based on the unrestricted exchange of molecules between the interstitial fluid (ISF) and a perfusion medium through macroscopic perforations that enables direct access to the ISF. By re-circulating the perfusate and monitoring the changes of the analytes’ concentration with a sensor, the absolute analyte concentration in the ISF can be calculated. In order to validate the new concept, the absolute electrical conductivity of the ISF was identified in six subjects to be 1.33 ± 0.08 S/m (coefficient of variation CV = 6 %), showing the robustness of this approach. The most striking feature of this procedure is the possibility to monitor several compounds simultaneously by applying different sensors which will allow not only the determination of the concentration of a single substance in vivo but also the simultaneous dynamics of different analytes. This will open new fields in analytical chemistry, pharmacology, as well as clinical experimental research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ao X, Sellati TJ, Stenken JA (2004) Enhanced microdialysis relative recovery of inflammatory cytokines using antibody-coated microspheres analyzed by flow cytometry. Anal Chem 76:3777–3784

    Article  CAS  Google Scholar 

  2. Rogers ML, Brennan PA, Leong CL, Growers SAN, Aldridge T, Mellor TK, Boutelle MG (2013) Online rapid sampling microdialysis (rsMD) using enzyme-based electroanalysis for dynamic detection of ischaemia during free flap reconstructive surgery. Anal Bioanal Chem 405:3881–3888

    Article  CAS  Google Scholar 

  3. Ikeoka DT, Pachler C, Mader JK, Bock G, Neves AL, Svehlikova E, Feichtner F, Koehler G, Wrighton CJ, Pieber TR, Ellmerer M (2011) Lipid-heparin infusion suppresses the IL-10 response to trauma in subcutaneous adipose tissue in humans. Obesity (Silver Spring) 19:715–721

    Article  CAS  Google Scholar 

  4. Kotanen CN, Moussy FG, Carrara S, Guiseppi-Elie A (2012) Implantable enzyme amperometric biosensors. Biosens Bioelectron 35:14–26

    Article  CAS  Google Scholar 

  5. Mastrototaro J, Shin J, Marcus A, Sulur G (2008) The accuracy and efficacy of real-time continuous glucose monitoring sensor in patients with type 1 diabetes. Diabetes Technol Ther 10:385–390

    Article  CAS  Google Scholar 

  6. Lönnroth P, Smith U (1990) Microdialysis—a novel technique for clinical investigations. J Intern Med 227:295–300

    Article  Google Scholar 

  7. Baldini F (2010) Microdialysis-based sensing in clinical applications. Anal Bioanal Chem 397:909–916

    Article  CAS  Google Scholar 

  8. Linhares MC, Kissinger PT (1992) Capillary ultrafiltration: in vivo sampling probes for small molecules. Anal Chem 64:2831–2835

    Article  CAS  Google Scholar 

  9. Tiessen RG, Tio RA, Hoekstra A, Venema K, Korf J (2001) An ultrafiltration catheter for monitoring of venous lactate and glucose around myocardial ischemia. Biosens Bioelectron 16:159–167

    Article  CAS  Google Scholar 

  10. Ellmerer M, Schaupp L, Trajanoski Z, Jobst G, Moser I, Urban G, Skrabal F, Wach P (1998) Continuous measurement of subcutaneous lactate concentration during exercise by combining open-flow microperfusion and thin-film lactate sensors. Biosens Bioelectron 13:1007–1013

    Article  CAS  Google Scholar 

  11. Wisniewski N, Moussy F, Reichert WM (2000) Characterization of implantable biosensor membrane biofouling. Fresenius J Anal Chem 366:611–621

    Article  CAS  Google Scholar 

  12. Schaupp L, Ellmerer M, Brunner GA, Wutte A, Sendlhofer G, Trajanoski Z, Skrabal F, Pieber TR, Wach P (1999) Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion. Am J Physiol 276:E401–E408

    CAS  Google Scholar 

  13. Ellmerer M, Schaupp L, Brunner GA, Sendlhofer G, Wutte A, Wach P, Pieber TR (2000) Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion. Am J Physiol Endocrinol Metab 278:E352–E356

    CAS  Google Scholar 

  14. Bodenlenz M, Schaupp LA, Druml T, Sommer R, Wutte A, Schaller HC, Sinner F, Wach P, Pieber TR (2005) Measurement of interstitial insulin in human adipose and muscle tissue under moderate hyperinsulinemia by means of direct interstitial access. Am J Physiol Endocrinol Metab 289:E296–E300

    Article  CAS  Google Scholar 

  15. Kehr J (1993) A survey on quantitative microdialysis: theoretical models and practical implications. J Neurosci Methods 48:251–261

    Article  CAS  Google Scholar 

  16. Stenken JA, Topp EM, Southard MZ, Lunte CE (1993) Examination of microdialysis sampling in a well-characterized hydrodynamic system. Anal Chem 65:2324–2328

    Article  CAS  Google Scholar 

  17. Jacobson I, Sandberg M, Hamberger A (1985) Mass transfer in brain dialysis devices—a new method for the estimation of extracellular amino acids concentration. J Neurosci Methods 15:263–268

    Article  CAS  Google Scholar 

  18. Lönnroth P, Jansson PA, Smith U (1987) A microdialysis method allowing characterization of intercellular water space in humans. Am J Physiol 253:E228–E231

    Google Scholar 

  19. Schaupp L (1998) Monitoring of biofluids in microsamples investigations for glucose monitoring using open-flow microperfusion. [ Dissertation ] Graz University of Technology

  20. Hsieh YC, Zahn JD (2007) On-chip microdialysis system with flow-through sensing components. Biosens Bioelectron 22:2422–2428

    Article  CAS  Google Scholar 

  21. Geddes LA, Baker LE (1967) The specific resistance of biological material—a compendium of data for the biomedical engineer and physiologist. Med Biol Eng 5:271–293

    Article  CAS  Google Scholar 

  22. Altman PL, Dittmer DS (1961) Blood and other body fluids. Federation Amer. Soc. Exp. Biol., Washington, D.C

  23. Bungay PM, Morrison PF, Dedrick RL (1990) Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vitro. Life Sci 46:105–119

    Article  CAS  Google Scholar 

  24. Oppenheim AV, Schafer RW (1989) Discrete time signal processing. Prentice Hall, Englewood Cliffs, NJ, pp 311–312

    Google Scholar 

Download references

Acknowledgment

The authors express their gratitude to Thomas Eibl for his help in performing the experiments.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Stiftingtalstrasse 24, 8010, Graz, Austria

    Lukas Schaupp, Selma Mautner, Martin Ellmerer & Thomas R. Pieber

  2. Joanneum Research Forschungsgesellschaft mbH, HEALTH, Institute for Biomedicine and Health Sciences, Elisabethstrasse 5, 8010, Graz, Austria

    Franz Feichtner, Roland Schaller-Ammann, Selma Mautner & Thomas R. Pieber

Authors
  1. Lukas Schaupp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franz Feichtner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roland Schaller-Ammann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Selma Mautner
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin Ellmerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas R. Pieber
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lukas Schaupp.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 1.06 mb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schaupp, L., Feichtner, F., Schaller-Ammann, R. et al. Recirculation—a novel approach to quantify interstitial analytes in living tissue by combining a sensor with open-flow microperfusion. Anal Bioanal Chem 406, 549–554 (2014). https://doi.org/10.1007/s00216-013-7493-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-013-7493-x

Keywords

Search

Navigation