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Microneedle-Based Detection of Ketone Bodies along with Glucose and Lactate: Toward Real-Time Continuous Interstitial Fluid Monitoring of Diabetic Ketosis and Ketoacidosis
Abstract
Diabetic ketoacidosis (DKA), a severe complication of diabetes mellitus with potentially fatal consequences, is characterized by hyperglycemia and metabolic acidosis due to the accumulation of ketone bodies, which requires people with diabetes to monitor both glucose and ketone bodies. However, despite major advances in diabetes management mainly since the emergence of new-generation continuous glucose monitoring (CGM) devices capable of in vivo monitoring of glucose directly in the interstitial fluid (ISF), the continuous monitoring of ketone bodies is yet to be addressed. Here, we present the first use of a real-time continuous ketone bodies monitoring (CKM) microneedle platform. The system is based on the electrochemical monitoring of β-hydroxybutyrate (HB) as the dominant biomarker of ketone formation. Such real-time HB detection has been realized using the β-hydroxybutyrate dehydrogenase (HBD) enzymatic reaction and by addressing the major challenges associated with the stable confinement of the enzyme/cofactor couple (HBD/NAD + ) and with a stable and selective low-potential fouling-free anodic detection of NADH. The resulting CKM microneedle device displays an attractive analytical performance, with high sensitivity (with low detection limit, 50 μM), high selectivity in the presence of potential interferences, along with good stability during prolonged operation in artificial ISF. The potential applicability of this microneedle sensor toward minimally invasive monitoring of ketone bodies has been demonstrated in a phantom gel skin-mimicking model. The ability to detect HB along with glucose and lactate on a single microneedle array has been demonstrated. These findings pave the way for CKM and for the simultaneous microneedle-based monitoring of multiple diabetes-related biomarkers toward a tight glycemic control.
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“ISF can be used for continuous monitoring of biomarkers, including in a recent work by Teymourian et al. [163] for continuous glucose monitoring (CGM) and continuous ketone monitoring using a microneedle sensor array.”
From The emergence of AI-based wearable sensors for digital health technology: a review (2023) · cites this paper as [163]
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“Moreover, they detected lactate in ISF using a similar platform and lactate oxidase enzyme.”
From The emergence of AI-based wearable sensors for digital health technology: a review (2023) · cites this paper as [163]
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Metadata
- Authors
- Teymourian, H., Moonla, C., Tehrani, F., Vargas, E., Aghavali, R., Barfidokht, A., Tangkuaram, T., Mercier, P. P., Dassau, E., & Wang, J.
- Affiliations
- University of California San Diego (US)
- Maejo University (TH)
- Harvard University (US)
- Corresponding author
- Mercier, Patrick P.
- Dassau, Eyal
- Wang, Joseph
- ORCID
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-12-24
- Volume
- 92
- Issue
- 2
- Pages
- 2291-2300
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W2996840266
- Cited by
- 278
- References
- 35
- Citations by year
- 2026: 30 · 2025: 50 · 2024: 53 · 2023: 53 · 2022: 44 · 2021: 27 · 2020: 21
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Analytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust (7505508-5108014 (2018PG-TI0061))
- Center for Wearable Sensors, University of California San Diego
- Topics
- Physical Sciences › Chemistry › Analytical Chemistry › Electrochemical sensors and biosensors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Keywords
- ketone bodies, beta-hydroxybutyrate, diabetic ketoacidosis, diabetic ketosis, microneedle sensors, interstitial fluid, electrochemical biosensor, beta-hydroxybutyrate dehydrogenase, NADH detection, glucose monitoring, lactate monitoring, diabetes mellitus
- MeSH terms
- Glucose, Humans, Ketone Bodies, Ketosis, Needles, Time Factors, Blood Glucose Self-Monitoring, Biosensing Techniques, Diabetic Ketoacidosis, Lactic Acid, Extracellular Fluid, Electrochemical Techniques
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