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Measuring transdermal glucose levels in neonates by passive diffusion: an in vitro porcine skin model

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Abstract

Current glucose monitoring techniques for neonates rely heavily on blood glucose monitors which require intermittent blood collection through skin-penetrating pricks on the heel or fingers. This procedure is painful and often not clinically conducive, which presents a need for a noninvasive method for monitoring glucose in neonates. Our motivation for this study was to develop an in vitro method for measuring passive diffusion of glucose in premature neonatal skin using a porcine skin model. Such a model will allow us to initially test new devices for noninvasive glucose monitoring without having to do in vivo testing of newborns. The in vitro model is demonstrated by comparing uncompromised and tape-stripped skin in an in-line flow-through diffusion apparatus with glucose concentrations that mimic the hypo-, normo-, and hyper-glycemic conditions in the neonate (2.0, 5.0, and 20 mM, respectively). Transepidermal water loss (TEWL) of the tape-stripped skin was approximately 20 g m−2 h−1, which closely mimics TEWL for neonatal skin at about 190 days post-conceptional age. The tape-stripped skin showed a >15-fold increase in glucose diffusion compared to the uncompromised skin. The very small concentrations of collected glucose were measured with a highly selective and highly sensitive fluorescent glucose biosensor based on the glucose binding protein (GBP). The demonstrated method of glucose determination is noninvasive and painless, which makes it especially desirable for glucose testing in neonates and children. This study is an important step towards an in vitro model for noninvasive real-time glucose monitoring that may be easily transferred to the clinic for glucose monitoring in neonates.

Glucose diffusion through model skin was measured using an in-line flow-through diffusion apparatus with glucose solutions mimicking hypo-, normo- and hyperglycemia in the neonate. Phosphate buffered saline was added to the top chamber and the glucose that diffused through the model skin into the buffer was measured using a fluorescent glucose binding protein biosensor.

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Acknowledgements

The authors acknowledge Science, Technology, Research and Innovation for Development (STRIDE) Program of USAID for Cristina Tiangco’s research support. They would also like to thank Sean Najmi for helping with the experimental work and UMB-UMBC for seed funding.

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Authors and Affiliations

  1. Center for Advanced Sensor Technologycsm, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD, 21250, USA

    Cristina Tiangco, Abhay Andar, Xudong Ge, Govind Rao & Leah Tolosa

  2. Department of Pharmaceutical Sciences, University of Maryland, 20 North Pine Street, Baltimore, MD, 21201, USA

    Abhay Andar, Juliana Quarterman & Audra Stinchcomb

  3. The Graduate School, University of Santo Tomas, España Boulevard, 1015, Manila, Philippines

    Cristina Tiangco & Fortunato Sevilla III

  4. Chemical and Biological Engineering Department, Colorado School of Mines, 1500 Illinois Street, Golden, CO, 80401, USA

    Annette Bunge

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  1. Cristina Tiangco
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Correspondence to Leah Tolosa.

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There are no conflicts of interest that exist for this manuscript.

Yucatan minipig skin was purchased from Sinclair BioResources. Sinclair complies with a number of agencies. They are USDA licensed as a breeder (43-A-5793). The company is in full compliance with the Animal Welfare Act and has maintained accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) since 1995. Further information can be found on their website www.sinclairbioresources.com/about-us/facilities/ and can be contacted directly via email: info@sinclairbioresources.com, or phone: 573-387-4400.

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Cristina Tiangco and Abhay Andar contributed equally to this work.

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Tiangco, C., Andar, A., Quarterman, J. et al. Measuring transdermal glucose levels in neonates by passive diffusion: an in vitro porcine skin model. Anal Bioanal Chem 409, 3475–3482 (2017). https://doi.org/10.1007/s00216-017-0289-7

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  • DOI: https://doi.org/10.1007/s00216-017-0289-7

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