A Pharmacokinetic Model of a Tissue Implantable Insulin Sensor

Abstract

While implantable sensors such as the continuous glucose monitoring system have been widely studied, both experimentally and mathematically, relatively little attention has been applied to the potential of insulin sensors. Such sensors can provide feedback control for insulin infusion systems and pumps and provide platforms for the monitoring of other biomarkers in vivo. In this work, the first pharmacokinetic model of an affinity sensor is developed for insulin operating subcutaneously in the limit of where mass transfer across biological membranes reaches a steady state. Using a physiological, compartmental model for glucose, insulin, and glucagon metabolism, the maximum sensor response and its delay time relative to plasma insulin concentration, are calculated based on sensor geometry, placement, and insulin binding parameters for a sensor localized within adipose tissue. A design relation is derived linking sensor dynamics to insulin time lag and placement within human tissue. The model should find utility in understanding dynamic insulin responses and forms the basis of model predictive control algorithms that incorporate sensor dynamics.

Chirality dependent corona phase molecular recognition of DNA-wrapped carbon nanotubes

“…3 presents the chirality dependent sensor responses to 100 lM epinephrine, 100 lM norepinephrine and 1 lM riboflavin. Consistent with the catecholamine results, the (9,4) and (7,6) chiralities of (ATTT) 3 -wrapped SWNTs were nearly unresponsive to riboflavin, exhibiting a 5% decrease in fluorescence compared to a 40% decrease exhibited by (GT) 15 -wrapped SWNTs ( Supplementary Fig. S6) and a 30% decrease exhibited by (TAT) 4 -wrapped SWNTs.…”

“…While each DNA-SWNT hybrid exhibited some degree of variability in the response of each chirality, as demonstrated for the (GT) 15 -SWNT data in Fig. 2, most wrappings did not exhibit systematic chirality dependence attributable to their recognition abilities during ion exchange chromatography ( Supplementary Fig.…”

“…Although 23 of the 24 sequences used in this study were DNA, many sequences were much shorter than the 30-mer oligonucleotides used in the previous work and may not bind as tightly. To rule out equilibration artifacts, the fluorescence spectra of (GT) 15 -, (TAT) 4 -and (ATTT) 3 -wrapped SWNTs were collected every 10 min for 4 h after dilution to 1 mg/L with PBS, and were then deconvoluted and inspected for chirality dependent stability. We found that the oligonucleotide wrappings were remarkably stable after PBS dilution over the course of the experiment, demonstrated by an invariant fluorescent emission signal over time (see Supplementary Fig.…”

“…These data further support our earlier results of chirality-dependent CoPhMoRe, and in particular, our findings that the (TAT) 4 and (ATTT) 3 ssDNA wrappings induce a reduction in sensor responsivity for their respective chirality partners. [17], while riboflavin was previously reported to quench fluorescence for (GT) 15 -wrapped SWNTs [5]. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)…”

“…The inherent fluorescence of semiconducting single-walled carbon nanotubes has prompted their widespread use as signal transducers for optical sensing applications [7][8][9]. Their nearly indefinite fluorescence profile provides a significant advantage over conventional fluorophore-based detection platforms that are susceptible to photobleaching [10], and the overlap of their near infrared (nIR) fluorescence profile with the tissue transparency window makes them especially useful for in vivo applications [11][12][13][14][15]. These properties, along with the capability of single molecule detection [16], have made SWNT nanosensors valuable tools to study physical, chemical and biological processes at short length and time scales otherwise not obtainable from other detection platforms.…”