Devices and Materials in the Continuous Monitoring of Metabolites

Advances in Biomaterials and Medical Devices Panel SessionThe importance and need for continuous monitoring of metabolites cannot be overemphasized. Most recent developments for in vivo monitoring devices have focused on miniaturization and the exploratory use of new functional materials. As most biosensors tend to drift and degrade over time, the development of a simple, dependable, on-demand, in situ (and possibly in vivo) self-calibration/self-diagnosis technique is a key obstacle for convenient, continuous monitoring with minimum intervention. The availability of this "weak link" would greatly improve the reliability and convenience of continuous monitoring technology. Work at Missouri S&T addresses these issues and provides solutions toward reliable and continuous monitoring of metabolites (glucose, lactate, etc.) with minimal human attendance using either optical or electrochemical detection methods

Continuous Monitoring of Tissue Regrowth Using Optical Biosensors

Biomedical Tissue Engineering, Biomaterials, and Medical Devices Poster SessionThe engineered regeneration of bone is a significant challenge being undertaken to treat conditions such as traumatic casualties, bone cancer, osteoporosis, etc. Advances in regrowth of hard tissue may potentially lead to significantly improved lives for millions of people. Recent work has focused on the use of bioactive glasses as potential materials in the fabrication of scaffolds for hard tissue regeneration. Bone regrowth requires maintenance of optimal levels of oxygen, glucose, phosphate, calcium, and pH. Current work at Missouri University of Science and Technology's Center for Bone and Tissue Repair and Restoration focuses on developing optical biosensors to monitor: conversion of bioactive glass to hydroxyapatite, ease of nutrient transport through the scaffold, diffusion of bioconversion byproducts from the wound site, and general health of the growing cells. Feedback from these sensors aids in material design, allowing researchers to understand how desired levels of analyte molecules are maintained in the complex process of tissue ingrowth. Our work currently focuses on development of pH and oxygen fluorescent biosensor elements. A CCD camera and processing software is used to colorimetrically quantify levels of these two at the microscale. Image processing is done in either the RGB (red, green, blue - native to the camera) or the HSI (hue, saturation, intensity) color space, giving detailed information about analyte concentration throughout the scaffolds and allowing for real time, in situ monitoring of cellular ingrowth. For pH detection, a sensitive ionophore is immobilized in a flexible polymer membrane and cast to form a 2 - dimensional film. Fluorimetric analysis of this film allows us to generate a color-coded picture of the pH gradient that exists in the degrading bioactive glass scaffold. Specifically, the pH sensitive membrane employs a ratiometric fluorophore, 9-(Diethylamino)-5-[(2octyldecyl)imino]benzo[a]phenoxazine (ETH5350), entrapped in a poly(vinyl chloride) matrix, with bis(2-ethylhexyl) sebacate to promote membrane plasticity and a lipophilic salt, tetrakis (4-chlorophenly) borate, for aiding proton selectivity. The fluorophore is uniquely suited for colorimetric analysis with off-the-shelf CCD camera equipment as excitation occurs in the blue region and emission, dependent on pH, has peaks in the green and red regions. The ratio of the red and green intensities therefore may be used to quantify pH, making the technique relatively insensitive to variations in excitation strength. Current work on oxygen quantification employs the Pt(II) meso-tetra(pentafluorophenyl)porphine complex immobilized in a poly(dimethylsiloxane) membrane. Porphyrin fluorescence quenches with increases in surrounding oxygen levels, and this difference leads to an image of oxygen gradients which develop in the matrix. The near - term goal is to develop a sensor platform to monitor bioactive conversion process in simulated physiological saline solution environment. Future work will focus on the implantation of sensor membranes at the site of bone injury to study its in vivo operation. Levels of pH and oxygen at the wound sites will be monitored and correlated with optical images of tissue regrowth

Ketamine Pharmacokinetics: A Systematic Review of the Literature, Meta-analysis, and Population Analysis

Background: Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model. Methods: Extracted pharmacokinetic parameters from the literature (volume of distribution and clearance) were standardized to allow comparison among studies. A meta-analysis was performed on studies that performed a mixed-effect analysis to calculate weighted mean parameter values and a meta-regression analysis to determine the influence of covariates on parameter values. A pharmacokinetic population model derived from a subset of raw data sets was constructed and compared with the meta-analytical analysis. Results: The meta-analysis was performed on 18 studies (11 conducted in healthy adults, 3 in adult patients, and 5 in pediatric patients). Weighted mean volume of distribution was 252 l/70 kg (95% CI, 200 to 304 l/70 kg). Weighted mean clearance was 79 l/h (at 70 kg; 95% CI, 69 to 90 l/h at 70 kg). No effect of covariates was observed; simulations showed that models based on venous sampling showed substantially higher context-sensitive half-times than those based on arterial sampling. The pharmacokinetic model created from 14 raw data sets consisted of one central arterial compartment with two peripheral compartments linked to two venous delay compartments. Simulations showed that the output of the raw data pharmacokinetic analysis and the meta-analysis were comparable. Conclusions: A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available