Modeling the relative impact of capsular tissue effects on implanted glucose sensor time lag and signal attenuation
Open accessAbstract
Little is known mechanistically about why implanted glucose sensors lag behind blood glucose levels in both the time to peak sensor response and the magnitude of peak sensor response. A mathematical model of glucose transport from capillaries through surrounding tissue to the sensor surface was constructed to address how different aspects of the tissue affect glucose transport to an implanted sensor. Physiologically relevant values of capsule diffusion coefficient, capsule porosity, cellular glucose consumption, capsule thickness, and subcutaneous vessel density were used as inputs to create simulated sensor traces that mimic experimental instances of time lag and concentration attenuation relative to a given blood glucose profile. Using logarithmic sensitivity analysis, each parameter was analyzed to study the effect of these variables on both lag and attenuation. Results identify capsule thickness as the strongest determinant of sensor time lag, while subcutaneous vessel density and capsule porosity had the largest effects on attenuation of glucose that reaches the sensor surface. These findings provide mechanistic insight for the rational design of sensor modifications that may alleviate the deleterious consequences of tissue effects on implanted sensor performance.
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The thickness of the FBR was reduced to less than 100 μM, which could allow for enhanced diffusion of small molecules.
“Of potential clinical importance, the thickness of the FBR was reduced to less than 100 μM, which could allow for enhanced diffusion of small molecules (29).”
From Inflammasome components Asc and caspase-1 mediate biomaterial-induced inflammation and foreign body response (2011) · cites this paper as [29]
The Methods (Transport and kinetic parameters; page unavailable) use 75 μm as a typical capsule thickness in a model, not as a measured reduction of the foreign body response. The Results and Discussion (pages unavailable) indicate that thinner capsules shorten the time for glucose to reach a sensor, supporting the proposed transport benefit for glucose. The paper does not report that an intervention reduced FBR thickness below 100 μm or test small molecules generally. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThese model results identify the histological parameters of key interest when assessing the biocompatibility of materials for glucose sensors.
“the results do identify the histological parameters of key interest when assessing the biocompatibility of materials for glucose sensors.”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [111]
The two greatest factors in reducing sensor attenuation were low capsule density and a high degree of angiogenesis.
“The two greatest factors in reducing sensor attenuation were a low capsule density and high degree of angiogenesis.111”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [111]
In Novak and coworkers' model, changes in cellular glucose uptake and the capsule diffusion coefficient of glucose had little effect on simulated sensor performance.
“Changes in cellular glucose uptake and the capsule diffusion coefficient of glucose had little effect on simulated sensor performance.111”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [111]
The positive correlation between lag time and capsule thickness supported the models described above.
“The positive correlation between lag time and capsule thickness supported the models described above.107,110–111”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [111]
The Novak model concluded that collagen capsule thickness was the primary source of sensor lag time and had little impact on sensor response attenuation.
“The model was ultimately used to conclude that collagen capsule thickness, a common histological parameter, was the primary source of sensor lag time with little impact on sensor response attenuation.111”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [111]
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- Authors
- Novak, M. T., Yuan, F., & Reichert, W. M.
- Affiliations
- Duke University (US)
- Corresponding author
- Reichert, William M.
- Venue
- Analytical and Bioanalytical Chemistry
- Published
- 2010-08-28
- Volume
- 398
- Issue
- 4
- Pages
- 1695-1705
- ISSN
- 1618-2642 (ISSN-L)
- 1618-2650
- PMC
- PMC2966551
- OpenAlex
- W2092269870
- Cited by
- 55
- References
- 32
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Analytical and Bioanalytical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008555, T32 GM-8555)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK54932, R01DK054932, R56DK054932)
- Topics
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Electrochemical sensors and biosensors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Physical Sciences › Chemical Engineering › Bioengineering › Analytical Chemistry and Sensors
- Keywords
- signal attenuation, subcutaneous tissue, capsule thickness, diffusion coefficient, sensitivity analysis, sensor design
- MeSH terms
- Animals, Biological Transport, Diffusion, Glucose, Kinetics, Models, Biological, Biosensing Techniques, Prostheses and Implants, Rats, Microvessels
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