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

Abstract

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.

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Acknowledgements

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.

Funding

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

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Authors and Affiliations

Authors

Contributions

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.

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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 (ClinicalTrials.gov: 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.

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

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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). https://doi.org/10.1007/s00216-022-04051-1

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  • DOI: https://doi.org/10.1007/s00216-022-04051-1

Keywords

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