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: In this paper, we describe the concept of a novel implantable fiber-optic Turbidity Affinity Sensor (TAS) and report on the findings of its in-vitro performance for continuous glucose monitoring. The sensing mechanism of the TAS is based on glucose-specific changes in light scattering (turbidity) of a hydrogel suspension consisting of small particles made of crosslinked dextran (Sephadex G100), and a glucose- and mannose-specific binding protein - Concanavalin A (ConA). The binding of ConA to Sephadex particles results in a significant turbidity increase that is much greater than the turbidity contribution by the individual components. The turbidity of the TAS was measured by determining the intensity of light passing through the suspension enclosed within a small semi-permeable hollow fiber (OD: 220μm, membrane thickness: 20μm, molecular weight cut-off: 10kDa) using fiber optics. The intensity of measured light of the TAS was proportional to the glucose concentration over the concentration range from 50mg/dL to 400mg/dL in PBS and whole blood at 37°C (R>0.96). The response time was approximately 4min. The stability of the glucose response of the TAS decreased only slightly (by 20%) over an 8-day study period at 37°C. In conclusion, this study demonstrated proof-of-concept of the TAS for interstitial glucose monitoring. Due to the large signal amplitude of the turbidity change, and the lack of need for wavelength-specific emission and excitation filters, a very small, robust and compact TAS device with an extremely short optical pathlength could be feasibly designed and implemented for in-vivo glucose monitoring in people with diabetes.Biosensors & bioelectronics. 05/2014; 61C:280-284.
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ABSTRACT: The progressive scaling in semiconductor technology allows for advanced miniaturization of intelligent systems like implantable biosensors for low-molecular weight analytes. A most relevant application would be the monitoring of glucose in diabetic patients, since no commercial solution is available yet for the continuous and drift-free monitoring of blood sugar levels. We report on a biosensor chip that operates via the binding competition of glucose and dextran to concanavalin A. The sensor is prepared as a fully embedded micro-electromechanical system and operates at GHz frequencies. Glucose concentrations derive from the assay viscosity as determined by the deflection of a 50 nm TiN actuator beam excited by quasi-electrostatic attraction. The GHz detection scheme does not rely on the resonant oscillation of the actuator and safely operates in fluidic environments. This property favorably combines with additional characteristics—(i) measurement times of less than a second, (ii) usage of biocompatible TiN for bio-milieu exposed parts, and (iii) small volume of less than 1 mm3—to qualify the sensor chip as key component in a continuous glucose monitor for the interstitial tissue.Journal of Applied Physics 06/2013; 113(24). · 2.21 Impact Factor
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ABSTRACT: Body sensor networks (BSN) are an important research topic due to various advantages over conventional measurement equipment. One main advantage is the feasibility to deploy a BSN system for 24/7 health monitoring applications. The requirements for such an application are miniaturization of the network nodes and the use of wireless data transmission technologies to ensure wearability and ease of use. Therefore, the reliability of such a system depends on the quality of the wireless data transmission. At present, most BSNs use ZigBee or other IEEE 802.15.4 based transmission technologies. Here, we evaluated the performance of a wireless transmission system of a novel BSN for biomedical applications in the 433MHz ISM band, called Integrated Posture and Activity NEtwork by Medit Aachen (IPANEMA) BSN. The 433MHz ISM band is used mostly by implanted sensors and thus allows easy integration of such into the BSN. Multiple measurement scenarios have been assessed, including varying antenna orientations, transmission distances and the number of network participants. The mean packet loss rate (PLR) was 0.63% for a single slave, which is comparable to IEEE 802.15.4 BSNs in the proximity of Bluetooth orWiFi networks. Secondly, an enhanced version is evaluated during on-body measurements with five slaves. The mean PLR results show a comparable good performance for measurements on a treadmill (2.5%), an outdoor track (3.4%) and in a climate chamber (1.5%).Sensors 01/2013; 13(1):898-917. · 2.05 Impact Factor