Ophthalmic Glucose Monitoring Using Disposable Contact Lenses—A Review

We have developed a range of disposable and colorless tear glucose sensing contact lenses, using off-the-shelf lenses embedded with new water soluble, highly fluorescent and glucose sensitive boronic acid containing fluorophores. The new lenses are readily able to track tear glucose levels and therefore blood glucose levels, which are ideally suited for potential use by diabetics. The fluorescence responses from the lenses can be monitored using simple excitation and emission detection devices. The novelty of our approach is two fold. Firstly, the notion of sensing extremely low glucose concentrations in tears, which track blood levels, by our contact lens approach, and secondly, the unique compatibility of our new glucose signaling probes with the internal mildly acidic contact lens environment. The new lenses are therefore ideal for the non-invasive and continuous monitoring of tear glucose, with about 15-min response time, and a measured shelf life in excess of 3 months. In this review article, we show that fluorescence based signaling using plastic disposable lenses, which have already been industrially optimized with regard to vision correction and oxygen/analyte permeability etc, may a notable alternative to invasive and random finger pricking, the most widely used glucose monitoring technology by diabetics.     

Low-field nuclear magnetic resonance spectrometer for non-invasive monitoring of fluctuations in blood glucose in the human finger

A low-field nuclear magnetic resonance spectrometer for non-invasive monitoring of human finger blood glucose fluctuations was developed. Saline solution and blood serum samples with different glucose concentrations were first detected by the spectrometer and it has been found that there was a high-linear correlation between the glucose concentration and the transverse relaxation time. Then, the spectrometer was employed to noninvasively measure a finger from each of the several volunteers. The experiment results showed that the transverse relaxation time of the human finger increases with human blood glucose concentration. In conclusion, the human finger nuclear magnetic resonance spectrometer could be a potential tool to noninvasive monitoring of human body’s blood glucose fluctuations in the future.     

A review of optical methods for continuous glucose monitoring

Frequent glucose monitoring is a fundamental part of diabetes management, and good glucose control is important for long-term health outcomes. New types of electrochemical sensors that allow for continuous glucose monitoring (CGM) have become an important tool for diabetes management, although they still have drawbacks such as short lifetime and a need for frequent calibration. Other technologies are still being researched for CGM, in an attempt to replace the electrochemical sensors. Optical methods have several advantages for CGM, including potentially long sensor lifetimes and short measurement times, and many developments have been made over the last decades. This paper will review optical measurement methods for CGM, their challenges, and the current research status. The different methods will be compared, and the future prospects for optical methods will be discussed.     

Optical monitoring of glucose concentration

A device for the monitoring of blood glucose levels is investigated. It measures the sugar concentration using the effect of the glucose on the optical refractive index. Light is transmitted along an optical fibre, and, as most of the internal rays are incident at the fibre surface at an angle less than the critical angle, the refractive index of the surrounding liquid can be calculated. The device can measure glucose concentrations with a sensitivity of better than 0.1%.     

论无创血糖监测的红外光谱方法(特邀)

介绍了无创血糖监测的几种光学方法以及红外光谱法用于无创血糖监测的优势。分析了无创血糖监测红外光谱法的主要问题,包括光在人体组织中的复杂传播;葡萄糖吸收信号微弱,且与人体中其它生化成分吸收光谱重叠;人体组织背景吸收干扰严重等。总结了无创血糖监测红外光谱法的最新进展,给出抑制人体组织背景吸收干扰的方法,并认为组织液可代替血液用于血糖水平的测量。展望了该领域未来研究趋势,主要涉及精确描述光子在组织中的传输、测量皮肤表皮内或表皮与真皮浅层光谱信息,以及提高光谱仪器信噪比,建立葡萄糖吸收带定标模型。     

Glucose-Sensitive Nanoassemblies Comprising Affinity-Binding Complexes Trapped in Fuzzy Microshells

A new design for glucose monitoring with "smart" materials based on self assembly, competitive binding, and resonance energy transfer (RET) is presented. The basic transduction principle is changing RET efficiency from fluorescein isothiocyanate (FITC) to tetramethylrhodamine isothiocyanate (TRITC), as FITC-dextran is displaced from TRITC-Concanavalin A (Con A) with the addition of glucose. Nanoscale fabrication by self-assembly of Con A/dextran into multilayer films, followed by polymer multilayers. The advantages of this approach include physical localization and separation of sensing molecules from the environment via entrapment of the biosensorelements in a semi-permeable polymeric shell, and only functional molecules are included in the sensors. To realize these nanostructures, dissolvable resin microparticles were coated with FITC-dextran+TRITC-Con A multilayers, followed by polyelectrolyte multilayers, and the core particles were then dissolved to yield hollow capsules. The nanoassembly process was studied using microbalance mass measurements, fluorescence spectroscopy, confocal fluorescence microscopy, and zeta-potential measurements. The key findings are that the specific binding between Con A and dextran can be used to deposit ultrathin multilayer films, and these exhibit changing RET in response to glucose. Fluorescence spectra of a microcapsules exhibited a linear, glucose-specific, 27% increase in the relative fluorescence of FITC over the 0-1800 mg/dL range. These findings demonstrate the feasibility of using self-assembled microcapsules as optical glucose sensors, and serve as a basis for work toward better understanding the properties of these novel materials.     

Fiber-optic sensor based on evanescent wave absorbance around 2.7 μm for determining water content in polar organic solvents

The feasibility of sapphire fiber-optic sensors based on evanescent wave absorption spectroscopy in the infrared range for quantitative determination of water content in polar organic solvents has been investigated. Evanescent wave absorption spectra of sapphire fiber-optic sensors in glycerol, ethanol, and glycol with different water concentrations obtained and analyzed, respectively. Evanescent absorbance of the sensors in those organic solvents has been utilized to implement for in situ monitoring water concentration in organic solvents. The evanescent absorbance of sensors in glycerol and glycol has been found to vary linearly with water content in the range 0–30 % and in ethanol in the range 0–10 %, respectively. The fiber-optic sensors based on evanescent absorbance for monitoring water concentrations in those organic solvents are acceptably accurate, cost-effective, and reliable. Some methods to improve the accuracy of predicated water content in those organic solvents are also suggested. Overall, the results demonstrate that the sapphire fiber-optic sensor based on evanescent absorption spectroscopy is a promising candidate for prediction of water content in polar organic solvents in on-line and remote situation.     

Effect of decreasing glucose concentration in blood plasma after blood saturation with oxygen

It was experimentally detected that the glucose concentration in blood plasma decreases after venous blood saturation with oxygen (oxygenation process). This effect was recorded for several tens of donor blood samples using IME-DC (Germany) and Optium Omega (USA) portable glucometers, as well as an optical method using holographic sensors based on hydrogel polymer films, independent of the presence of oxygen in plasma. During blood oxygenation in the organism, glucose is redistributed between blood plasma and erythrocyte cytoplasm in favor of cytoplasm. The observed effect is explained by an increase in the electric field during blood oxygenation in lipids of the erythrocyte cytoplasmic membrane, which orients dipoles of asymmetric glucose molecules along the normal to the membrane surface. This results in erythrocytemembrane permeability asymmetry.     

A Glucose Sensing Contact Lens: A Non-Invasive Technique for Continuous Physiological Glucose Monitoring

We have developed a range of glucose sensing contact lenses, using a daily, disposable contact lens embedded with newly developed boronic acid containing fluorophores. Our findings show that our approach may be suitable for the continuous monitoring of tear glucose levels in the range 50–1000 M, which typically track blood glucose levels, which are 5–10 fold higher. Our non-invasive approach may well offer an alternative solution to current invasive glucose monitoring techniques for diabetes, such as finger pricking.     

Application of transcutaneous diffuse reflectance spectroscopy in the measurement of blood glucose concentration

In this paper, the propagation characteristics of near-infrared (NIR) light in the palm tissue are analyzed,and the principle and feasibility of using transcutaneous diffuse reflectance spectroscopy for non-invasive blood glucose detection are presented. An optical probe suitable for measuring the diffuse reflectance spectrum of human palm and a non-invasive blood glucose detection system using NIR spectroscopy are designed. Based on this system, oral glucose tolerance tests are performed to measure the blood glucose concentrations of two young healthy volunteers. The partial least square calibration model is then constructed by all individual experimental data. The final result shows that correlation coefficients of the two experiments between the predicted blood glucose concentrations and the reference blood glucose concentrations are 0.9870 and 0.9854, respectively. The root mean square errors of prediction of full cross validation are 0.54 and 0.52 mmol/1, respectively.     

Noncontact characterization of glucose by a waveguide microwave probe

We investigate the electromagnetic field interaction with a glucose aqueous solution using a microwave dielectric waveguide probe to evaluate the glucose concentrations. A microwave dielectric waveguide probe allows observation of the small variation of the glucose concentration changes in the range of 0–300 mg/ml by measuring the change of the microwave reflection coefficient. We could observe the effect of concentration change of glucose with a detectable resolution up to 0.5 mg/ml at an operating frequency of about f = 2.0–2.5 GHz. The change of the glucose concentration is directly related to the change of the reflection coefficient due to the electromagnetic interaction between the dielectric waveguide resonator and the glucose aqueous solution. The operational principal is explained by a plane-wave solution model. A glucose biosensor using a microwave dielectric waveguide probe provides a unique approach for glucose monitoring.     

Correlation between blood glucose concentration in diabetics and noninvasively measured tissue optical scattering coefficient

Diabetics would benefit greatly from a device capable of providing continuous noninvasive monitoring of their blood glucose levels. The optical scattering coefficient of tissue depends on the concentration of glucose in the extracellular fluid. A feasibility study was performed to evaluate the sensitivity of the tissue reduced scattering coefficient in response to step changes in the blood glucose levels of diabetic volunteers. Estimates of the scattering coefficient were based on measurements of the diffuse reflectance on the skin at distances of 1-10 mm from a point source. A correlation was observed between step changes in blood glucose concentration and tissue reduced scattering coefficient in 30 out of 41 subjects measured.     

葡萄糖浓度对THz频段血液光学特性的影响

无创性血糖检测仍是糖尿病患者护理安全舒适的现实科学任务。本文研究了血糖光学特性与血糖浓度之间的相关性。用时域THz光谱研究了全血在0.3~0.5 THz频率范围内的透射谱。在注射胰岛素后的短时间内,由同一糖尿病患者产生了生物样品。得到了血液光学特性的频散特性。基于频散,给出了血糖浓度与折射率和介电常数的关系式。这项工作是复杂研究的一部分,重点是无创葡萄糖测量技术的发展。记录血糖水平与血液光学参数之间的依赖关系,使得将来可以使用反射光谱技术进行无创血糖水平检测。     

Measurement of diabetic sugar concentration in human blood using Raman spectroscopy

This study demonstrates the use of Raman spectroscopy for the direct measurement of diabetic sugar in human blood using 532 nm laser system. Raman spectra were collected from whole blood drawn from 21 individuals. We have elicited a reliable glucose signature in diabetic patients, and measured glucose levels in blood serum of normal, healthy diabetic and diabetic patients with other malignancies like cancer and hepatitis. Quantitative predictions of glucose spectra illustrate the predictions based on molecular information carried by the Raman light in highly light-scattering and absorbing media. Raman spectrum peaks for diabetic blood serum are observed at 1168, 1531, 1463, 1021 cm^?1 with intensity level 17000 to 18500 pixels attributed to carbohydrates, proteins, lipids, collagen, and skeletal C-C stretch of lipids acyl chains. Raman spectra for normal, diabetic patients having cancer and hepatitis were also recorded. This in vitro glucose monitoring methodology will lead in vivo noninvasive on-line monitoring having painless and at the same time the data will be displayed on-line and in real time. The measured Raman peaks provides detailed bio-chemical fingerprint of the sample and could confer diagnostic benefit in a clinical setting.     

Instrumental Requirements for Non-Invasive Blood Glucose Measurement Using NIR Spectroscopy

The magnitude of spectral change in blood glucose measurements with diffuse reflectance spectroscopy is investigated. Spectral change is estimated by simulation of light propagation in skin tissue and measurements of absorbance spectra of aqueous glucose solution. Required sensitivity of spectrophotometers for monitoring change in the blood glucose concentration as small as 10 mg/dL has been obtained using the estimated change in the absorbance spectrum and mean pathlength of light in tissue.     

Active incremental Support Vector Machine for oil and gas pipeline defects prediction system using long range ultrasonic transducers

This work proposes a long range ultrasonic transducers technique in conjunction with an active incremental Support Vector Machine (SVM) classification approach that is used for real-time pipeline defects prediction and condition monitoring. Oil and gas pipeline defects are detected using various techniques. One of the most prevalent techniques is the use of “smart pigs” to travel along the pipeline and detect defects using various types of sensors such as magnetic sensors and eddy-current sensors. A critical short coming of “smart pigs” is the inability to monitor continuously and predict the onset of defects. The emergence of permanently installed long range ultrasonics transducers systems enable continuous monitoring to be achieved. The needs for and the challenges of the proposed technique are presented. The experimental results show that the proposed technique achieves comparable classification accuracy as when batch training is used, while the computational time is decreased, using 56 feature data points acquired from a lab-scale pipeline defect generating experimental rig.     

基于光纤布拉格光栅传感器的光纤光栅智能夹层试验研究

传感元件与复合材料的一体化是智能结构研究的最终目标之一。设计一种具有自诊断功能的标准化、模块化光纤智能夹层系统,正是实现这种一体化最有潜力的技术途径。采用聚酰亚胺薄膜制作了基于光纤布拉格光栅（FBG）传感器的光纤光栅智能夹层,对智能夹层中光纤布拉格光栅传感器的应变、温度特性进行了标定试验,并建立了基于光纤布拉格光栅传感器光纤光栅智能夹层的应变、温度测量模型。试验表明,智能夹层内布拉格光栅波长偏移与应变、温度之间具有良好的线性关系。不过在温度测量时,必须考虑被埋人结构的热膨胀效应。利用光纤光栅智能夹层内光纤布拉格光栅传感器网络和先进信息处理技术,可以建立结构损伤主动、在线和实时监测系统。     

Multiple-Scattering-Free Optical Glucose Monitoring Based on Femtosecond Pulse Interferometry

We have designed a novel multiple-scattering-free optical glucose monitoring system based on femtosecond pulse interferometry. The glucose concentration is determined by a time-of-flight method, while multiple-scattering light is rejected by a coherence gate. The resultant accuracy and precision were 94.7 and 24.5 mg/dl, respectively, for physiological-equivalent glucose concentrations in a scattering medium of 1.0% intralipid solution, while the accuracy and precision for a reference sample containing no scattering medium were 65.3 and 23.8 mg/dl, respectively. Comparing these results, we conclude that the proposed method is effective for glucose measurement in a scattering medium.     

一种新型的振荡场光化学传感器

利用法布里珀罗振荡模构造了一种新型的光化学传感器。与传统的以表面等离子模和光导模为探针的迅衰场传感器不同 ,这种新型结构中被传感介质处于法布里珀罗腔的振荡场中 ,其能量在全部入射光能中的比重占得很大 ,使得这种传感器具有很高的灵敏度。实验证实这类传感器对葡萄糖溶液浓度和折射率的测量精度皆可达 10 - 5数量级以上