Affinity-Based Turbidity Sensor for Glucose Monitoring by Optical Coherence Tomography: Toward the Development of an Implantable Sensor
ABSTRACT We investigated the feasibility of constructing an implantable optical-based sensor for seminoninvasive continuous monitoring of analytes. In this novel sensor, analyte concentration-dependent changes induced in the degree of optical turbidity of the sensing element can be accurately monitored by optical coherence tomography (OCT), an interferometric technique. To demonstrate proof-of-concept, we engineered a sensor for monitoring glucose concentration that enabled us to quantitatively monitor the glucose-specific changes induced in bulk scattering (turbidity) of the sensor. The sensor consists of a glucose-permeable membrane housing that contains a suspension of macroporous hydrogel particles and concanavalin A (ConA), a glucose-specific lectin, that are designed to alter the optical scattering of the sensor as a function of glucose concentration. The mechanism of modulation of bulk turbidity in the sensor is based on glucose-specific affinity binding of ConA to pendant glucose residues of macroporous hydrogel particles. The affinity-based modulation of the scattering coefficient was significantly enhanced by optimizing particle size, particle size distribution, and ConA concentration. Successful operation of the sensor was demonstrated under in vitro condition where excellent reversibility and stability (160 days) of prototype sensors with good overall response over the physiological glucose concentration range (2.5-20 mM) and good accuracy (standard deviation 5%) were observed. Furthermore, to assess the feasibility of using the novel sensor as one that can be implanted under skin, the sensor was covered by a 0.4 mm thick tissue phantom where it was demonstrable that the response of the sensor to 10 mM glucose change could still be measured in the presence of a layer of tissue shielding the sensor aiming to simulate in vivo condition. In summary, we have demonstrated that it is feasible to develop an affinity-based turbidity sensor that can exhibit a highly specific optical response as a function of changes in local glucose concentration and such response can be accurately monitored by OCT suggesting that the novel sensor can potentially be engineered to be used as an implantable sensor for in vivo monitoring of analytes.
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ABSTRACT: One of the critical path initiatives of the Food and Drug Administration (FDA) is to accelerate the development and availability of a safe and effective artificial pancreas for the treatment of diabetes mellitus. The FDA has established a multidisciplinary group of scientists and clinicians, in partnership with the National Institutes of Health (NIH), to address the clinical, scientific and regulatory challenges related to this unique medical product.Section editor:Janet Woodcock – Food and Drug Administration, Rockville, MD, USADrug Discovery Today Technologies 03/2007; 4(1-4):25-28. DOI:10.1016/j.ddtec.2007.10.007
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ABSTRACT: The reliability of optical techniques for non-invasive monitoring of glucose can be significantly improved by the deployment of a subcutaneous implantable sensor that can closely track the changes in the local concentration of glucose in skin. We have developed a novel implantable sensor that can track glucose-induced changes in the optical turbidity of the implant. In this sensor, optical turbidity decreases significantly with increased glucose concentrations. We performed comparative measurements by optical coherence tomography (OCT) used to monitor backscattering or specular reflection originated from specific structures within the sensor and by collimated light transmission measurement technique to measure the changes in light attenuation as function of glucose concentration within the sensor as well as when the sensor was implanted in phantom media or in tissue samples. These measurements showed that glucose-induced changes in the transmission values derived from OCT monitoring of the sensor turbidity differed up two times from those obtained by collimated transparency measurement (CTM) technique. These results were used to determine the values for scattering coefficients of tissue and the sensor and to estimate the relative loss in sensor sensitivity as a function of implantation depth in tissue. The results suggest that the implantable sensor can be placed in turbid medium such as skin up to an optical depth of 12 mean free paths (mfp), one could expect. For a turbid medium such as skin with a scattering coefficient (ÃÂµs ) of 10mm-1, this would result in geometrical depth of implantation at 1.2 mm beneath the tissue where sensor sensitivity of 50% or higher is expected. The study demonstrates that it could be feasible to engineer a novel optical sensor for glucose monitoring that can be implanted under the skin while providing a high degree of sensitivity and specificity for non-invasive glucose monitoring.Society of Photo-Optical Instrumentation Engineers (SPIE) - Photonics West; 01/2008
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ABSTRACT: Noninvasive imaging of glucose in tissues could provide important insights about glucose gradients in tissue, the origins of gluconeogenesis, or perhaps differences in tissue glucose utilization in vivo. Direct spectral detection of glucose in vivo by (1)H NMR is complicated by interfering signals from other metabolites and the much larger water signal. One potential way to overcome these problems is to use an exogenous glucose sensor that reports glucose concentrations indirectly through the water signal by chemical exchange saturation transfer (CEST). Such a method is demonstrated here in mouse liver perfused with a Eu(3+)-based glucose sensor containing two phenylboronate moieties as the recognition site. Activation of the sensor by applying a frequency-selective presaturation pulse at 42 ppm resulted in a 17% decrease in water signal in livers perfused with 10 mM sensor and 10 mM glucose compared with livers with the same amount of sensor but without glucose. It was shown that livers perfused with 5 mM sensor but no glucose can detect glucose exported from hepatocytes after hormonal stimulation of glycogenolysis. CEST images of livers perfused in the magnet responded to changes in glucose concentrations demonstrating that the method has potential for imaging the tissue distribution of glucose in vivo.Magnetic Resonance in Medicine 11/2008; 60(5):1047-55. DOI:10.1002/mrm.21722 · 3.57 Impact Factor