Skip to main content

A novel galactose electrochemical biosensor intended for point-of-care measurement of quantitative liver function using galactose single-point test


Liver disease has emerged as a healthcare burden because of high hospitalization rates attributed both to steatohepatitis and to severe hepatic toxicity associated with changes of drug exposure. Early detection of hepatic insufficiency is critical to preventing long-term liver damage. The galactose single-point test is recommended by the US FDA as a sensitive means to quantify liver function, yet the conventional method used for quantitation of circulating galactose still relies on the standard colorimetric method, requiring time-consuming and labor-intensive processes, and is confined to the medical laboratory, thus limiting prevalence. To facilitate time- and cost-effective disease management particularly during a pandemic, a pocket-sized rapid quantitative device consisting of a biosensor and electrochemical detection has been developed. An in vitro validation study demonstrated that the coefficient of variation was less than 15% and deviations were between −4 and 14% in the range of 100–1500 μg/mL. The device presented good linear fit (correlation coefficient, r = 0.9750) over the range of 150–1150 µg/mL. Moreover, the device was found to be free from interference of common endogenous and exogenous substances, and deviated hematocrit, enabling a direct measurement of galactose in the whole blood without sample pre-treatment steps. The clinical validation comprising 118 subjects showed high concordance (r = 0.953) between the device and the conventional colorimetric assay. Thus, this novel miniaturized device is reliable and robust for routine assessment of quantitative liver function intended for follow-up of hepatectomy, drug dose adjustment, and screening for galactosemia, allowing timely and cost-effective clinical management of patients.

Graphical abstract

This is a preview of subscription content, access via your institution.

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


  1. Wong RJ, Singal AK. Trends in liver disease etiology among adults awaiting liver transplantation in the United States, 2014–2019. JAMA Network Open. 2020;3(2):e1920294-e.

    Article  Google Scholar 

  2. Franz CC, Hildbrand C, Born C, Egger S, Rätz Bravo AE, Krähenbühl S. Dose adjustment in patients with liver cirrhosis: impact on adverse drug reactions and hospitalizations. Eur J Clin Pharmacol. 2013;69(8):1565–73.

    CAS  Article  Google Scholar 

  3. US Department of Health and Human Services, Food and Drug Administration. Guidance for industry-pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling. Rockville, MD, USA. 2003.

  4. Tang HS, Hu OY. Assessment of liver function using a novel galactose single point method. Digestion. 1992;52(3–4):222–31.

    CAS  Article  Google Scholar 

  5. Keiding S. Galactose clearance measurements and liver blood flow. Gastroenterology. 1988;94(2):477–81.

    CAS  Article  Google Scholar 

  6. Pang KS, Rowland M. Hepatic clearance of drugs. I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokinet Biopharm. 1977;5(6):625–53.

    CAS  Article  Google Scholar 

  7. Pang KS, Rowland M. Hepatic clearance of drugs. II. Experimental evidence for acceptance of the “well-stirred” model over the “parallel tube” model using lidocaine in the perfused rat liver in situ preparation. J Pharmacokinet Biopharm. 1977;5(6):655–80.

    CAS  Article  Google Scholar 

  8. Keiding S, Johansen S, Winkler K, Tonnesen K, Tygstrup N. Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver. Am J Physiol. 1976;230(5):1302–13.

    CAS  Article  Google Scholar 

  9. Takahashi H, Shigefuku R, Yoshida Y, Ikeda H, Matsunaga K, Matsumoto N, et al. Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis. World J Gastroenterol. 2014;20(45):17065–74.

    Article  Google Scholar 

  10. Dupont S, Schiffer ERC, White MJ, Diaper JRA, Licker MJ, Masouye PC. Changes in hepatic blood flow and liver function during closed abdominal hyperthermic intraperitoneal chemotherapy following cytoreduction surgery. Gastroenterol Res Pract. 2018;2018:8063097.

    Article  Google Scholar 

  11. Cohn JN, Khatri IM, Groszmann RJ, Kotelanski B. Hepatic blood flow in alcoholic liver disease measured by an indicator dilution technic. Am J Med. 1972;53(6):704–14.

    CAS  Article  Google Scholar 

  12. Sun H, Zhao H. Drug elimination and hepatic clearance. In: Shargel L, Yu A, editors. Applied biopharmaceutics & pharmacokinetics. 7th ed. McGraw-Hill/Appleton & Lange, USA. 2015.

  13. Ranek L, Lindskov J, Tygstrup N, Winkler K. Splanchnic galactose uptake in patients with cirrhosis following single injection. Clin Physiol (Oxford, England). 1983;3(2):173–8.

    CAS  Article  Google Scholar 

  14. Hu OY, Hu TM, Tang HS. Determination of galactose in human blood by high-performance liquid chromatography: comparison with an enzymatic method and application to the pharmacokinetic study of galactose in patients with liver dysfunction. J Pharm Sci. 1995;84(2):231–5.

    CAS  Article  Google Scholar 

  15. Sun L, Bulter T, Alcalde M, Petrounia IP, Arnold FH. Modification of galactose oxidase to introduce glucose 6-oxidase activity. Chembiochem Eur J Chem Biol. 2002;3(8):781–3.

    CAS  Article  Google Scholar 

  16. Tang Z, Louie RF, Lee JH, Lee DM, Miller EE, Kost GJ. Oxygen effects on glucose meter measurements with glucose dehydrogenase- and oxidase-based test strips for point-of-care testing. Crit Care Med. 2001;29(5):1062–70.

    CAS  Article  Google Scholar 

  17. Cuatrecasas P, Segal S. Mammalian galactose dehydrogenase. II. Properties, substrate specificity, and developmental changes. J Biol Chem. 1966;241(24):5910–8.

    CAS  Article  Google Scholar 

  18. Fingerhut R, Torresani T. Determination of total galactose from dried blood spots—extensive assay evaluation of a CE-marked test-kit. J Anal Sci Methods Instrum. 2013;03:163–6.

    CAS  Google Scholar 

  19. Sun H, Zhao H. Drug elimination and hepatic clearance. In: Shargel L, Yu A, editors. Applied biopharmaceutics and pharmacokinetics. 4th ed. United Kingdom: Prentice-Hall International, Inc.; 1999. p. 566.

    Google Scholar 

  20. Curry SH, Whelpton R. Drug disposition and pharmacokinetics: from principles to applications. 2nd ed. USA: WILEY-BLACKWELL; 2010.

    Book  Google Scholar 

Download references


We thank the Tri-Service General Hospital and the National Defense Medical Center for supporting this study. We would also like to thank Dr. Qui-Lim Choo and Dr. Tammy Pang for their diligent proofreading of this manuscript.


This study was supported by Avalon HepaPOC Limited, Hong Kong, and Jacob Biotech Limited, Taiwan.

Author information

Authors and Affiliations



K-M Yu and O. Y-P. Hu conceived and designed the trial. T-Y. Huang was the principal investigator for the clinical trial. P. Yang and O. Y-P. Hu were responsible for laboratory studies, assay development, and sample collection. J. Y-N. Lau and O. Y-P. Hu provided guidance of the study. K-M. Yu, J. Y-N. Lau, and O. Y-P. Hu prepared the manuscript and contributed to data analysis and interpretation; T. Y-S. Shen, J. Y-N. Lau, and O. Y-P. Hu contributed to the device design and manufacturing. O. Y-P. Hu assumed final responsibilities for the manuscript.

Corresponding author

Correspondence to Oliver Yoa-Pu Hu.

Ethics declarations

Ethics approval and source of biological material

Blood samples were collected from clinical participants undergoing GSP test performed in the Tri-Service General Hospital, Taipei, Taiwan ( NCT03457311, registered on March 7, 2018). The protocol was approved by the Institutional Review Board of the Tri-Service General Hospital. Written informed consent was obtained from all participants, and the trial was conducted in accordance with the Declaration of Helsinki and under good clinical practice.

Conflict of interest

Avalon HepaPOC Limited owns the intellectual property rights of this technology, and J. Y-N. Lau and O. Y-P. Hu are shareholders of this entity. No conflict of interest has been declared by the other coauthors.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Kuo-Ming Yu and Ping Yang are the co-first authors.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yu, KM., Yang, P., Huang, TY. et al. A novel galactose electrochemical biosensor intended for point-of-care measurement of quantitative liver function using galactose single-point test. Anal Bioanal Chem 414, 4067–4077 (2022).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Bioassay
  • Biological samples
  • Biosensors
  • Biotechnological product
  • Catalysts
  • Enzymes