基于反向离子电渗透原理的无创血糖检测研究进展

【摘要】无创血糖检测是近年来血糖检测的主要发展方向。基于反向离子电渗透原理的检测技术是进行血糖无创检测的方法之一,它可以实现糖尿病患者血糖浓度的实时监控和及时检测,对预防并发症的发生有重要意义。详细介绍了反向离子电渗透的原理、组织间液的提取以及低浓度葡萄糖传感器的设计方法;概述了基于反向离子电渗透原理的无创血糖检测的国内外研究现状以及利用这项技术进行皮下组织液里其它物质提取与检测的相关研究;最后讨论了反离子电渗透无创血糖检测技术存在的关键问题和解决方法,为进行组织液的提取和葡萄糖浓度的检测以及基于反离子电渗透技术无创血糖检测仪的研制打下基础。     

血糖无创检测原理及仪器实现研究

阐明了无创血糖检测是血糖检测技术的发展方向。它可以实现对血糖浓度更加及时地监控,减少或减轻糖尿病人的并发症,对糖尿病的诊断和治疗具有重大意义。对人体血糖无创检测方法和仪器的现状进行了讨论,重点介绍了三种有仪器面世的方法,包括实现血糖无创检测的基本原理、试验验证结果以及仪器研究进展,并讨论了每种方法在实现血糖无创检测中存在的问题。最后对当前无创血糖检测中的难点进行了进一步的讨论,并在此基础上分析指出了未来无创血糖检测技术的发展方向。     

微创及无创血糖检测方法研究现状

血糖检测已成为我国糖尿病综合管理中最薄弱的环节，对糖尿病患者的血糖水平进行长期监测是控制糖尿病及其并发症发展的重要手段，血糖检测方法的技术革新对实现血糖精准检测有着深远意义。本文论述了微创及无创血糖检测方法包括尿糖检测法、泪液检测法、组织液外渗法以及光学检测等方法的基本原理，重点分析了微创及无创血糖检测方法的优势及最新成果，归纳总结了各类检测方法目前存在的问题并对未来发展趋势进行展望。     

基于近红外光谱法的无创血糖检测原理与研究现状

研究血糖的无创检测具有重要的临床意义,近红外无创血糖检测技术作为最具潜力的检测方法之一,已成为当今一大研究热点。本文介绍了基于近红外光谱法的无创血糖检测的基本原理与研究方法,通过比较近年来国内外相关研究的发展现状,针对近红外光谱法无创血糖检测中在测量方式选取、测量部位选择、测量波长选择以及定标建模等方面存在的关键性问题进行了较为深入的总结和探讨。     

血糖检测方法的研究现状

掌握血糖的变化是了解糖尿病病情和评价治疗效果的重要途径。本文从有创、微创和无创三个方面对血糖检测方法及存在问题进行了陈述;从技术方面对目前的血糖仪进行分析,着重介绍了无创检测方式的原理及发展前景。虽然无创血糖检测方法很多,但目前仍然缺乏一种无创伤、连续、动态、准确、重复性良好的方法,使之能够广泛应用于家庭保健,并取代传统的有创血糖检测仪。有创、微创、无创血糖检测方法目前各有优劣,尚无法相互取代,而无创血糖检测是未来血糖检测技术发展的方向,有待于多学科的综合研究。     

无创伤法测量血糖浓度的技术及其发展前景

对国际上无创血糖测量技术的研究现状进行了综述和分析 ,主要包括 :电化学法、光学法 (透射式、偏振式和后向散射式 ) ,并着重分析了光学法中的近红外光谱测量方法。最后 ,讨论了当前无创血糖检测存在的问题 ,并进行了分析 ,初步确定了检测方法和测量仪器的设计框图 ,包括 :入射光源波长的选择 ;确定接收点 ;建立生物组织的光学模型 ;仪器设计。     

基于正交双偏振光的无创血糖检测方法及初步实验研究

针对光电外差探测法和直接探测法偏振光无创血糖检测方法存在的缺点,本文提出了一种新的正交双偏振光无创血糖检测方法,将正交双偏振光通过血糖引起的微小偏振角的变化转化为两个方向上偏振光的能量差,由相关原理高灵敏锁相放大器检测,控制法拉第线圈电流补偿血糖引起的偏转角变化,利用血糖浓度与法拉第线圈电流的线性关系,计算获得血糖浓度。以LX-20全自动生化分析仪测得的数据作为标准进行对比实验,葡萄糖溶液实验的相关系数为0.9777,血清实验的相关系数为0.952。研究表明本方法具有较高的检测灵敏度和准确度,为研制实用的新型无创血糖检测仪打下了基础。     

无创血糖检测技术及仪器

概述了现有主要的无创血糖检测技术及仪器.重点介绍了各种技术的基本物理原理、局限性和测量部位及其优缺点,并以列表形式展现了各种仪器的认证状况(美国FDA认证或/和欧洲CE标志)和所采用的技术、制造商、互联网上提及该仪器的情况等信息.尽管目前已存在一些有希望的无创血糖测量技术和仪器.但仍需进一步研究更满意的无创血糖检测解决方案.     

近红外光谱技术在临床检测中的应用

近红外光谱（near infrared spectroscopy,NIRS）分析技术是近年来发展最快、最引人注目的 分析技术,广泛应用于石油、化工、食品等分析化学各领域.本文在介绍NIRS技术基本原理、技术特点的基础上,阐述了NIRS技术在临床检测领域的研究情况,主要包括在无创血糖监测、无创血氧测量、乳腺肿块检测、尿液成分分析等方面的应用与进展,最后初步探讨了该技术在应用中存在的局限性,并对NIRS分析技术在临床检测领域中的应用前景进行了展望.     

颅内压检测技术的研究

现将无创检测颅内压技术的现状与发展作一综述。今后检测颅内压，主要靠无创检测，并将与图像处理和信号处理相结合进行。     

Noninvasive blood glucose monitoring: new technology using metabolic heat conformation method

Self-monitoring of blood glucose has become an essential aspect of management of patients with diabetes mellitus. Although several approaches for noninvasive blood glucose monitoring(NIGM) have been proposed including near infrared spectrophotometry. Body heat generated by glucose oxidation is based on the subtle balance of capillary glucose and oxygen supply to the cells. Hence, the blood glucose can be estimated by measuring the body heat and the oxygen supply. Development of the metabolic heat conformation (MHC) method consists of a sensor pickup and a calibration model. The calibration model incorporates mathematical procedures to process signals from the sensor pickup to final glucose value. The patients group was classified into clusters (calibration functions). Each subject patient was assigned to one of calibration functions. The assigned calibration function for the patient was later used for calculating the glucose values. Regression analysis involving 127 data points at random timing (109 data points from diabetic patients, 18 data points from non-diabetic patients) ranging 54mg/dl to 405mg/dl by the non-invasive method against the hexokinase photometric method for plasma as a reference method was performed. The correlation coefficient (r) was 0.91. Repeatability of the non-invasive method was measured for healthy fasting persons. The standard deviations were ranged from 5 to 6mg/dl around the concentration of 100mg/dl. These data provide preliminary evidence that the MHC method can be used to estimate blood glucose concentrations non-invasively.     

Blood glucose measurement by infrared spectroscopy

For the development of an implantable artificial endocrine pancreas, a sensor for blood glucose measurement is needed providing a long-term stability. This goal can be achieved by the application of infrared spectroscopy which, unlike electrochemical sensors, responds directly to the glucose molecule. An investigation under physiological conditions revealed five glucose absorption bands in the near and middle infrared range. These are 1040, 1085, 1109, 1160 and 1365 cm-1. Only the 1040 cm-1 frequency coincides with none of the other infrared-active blood substances like proteins, lipids and urea. Nevertheless, the other absorption bands too, especially the 1109 cm-1 frequency, can be used for blood glucose measurement, if the superimposed absorptions are compensated. Methods for the compensation have been found. Technically feasible embodiments of an infrared glucose sensor are described.     

基于红外光谱技术的经皮二氧化碳分压检测仪的设计原理与可行性研究

本文介绍了根据红外光谱技术设计与研制成功的经皮二氧化碳分压(tcPco_2)监护仪的实验样机。此样机由经皮二氧化碳红外光探测器,红外光纤和经皮二氧化碳分压分析仪等几部分组成。我们认为:采用CO_2光学传感器的经皮血气检测仪连续、无创性地监测tcPco_3是可行的。实验样机的各项测试性能均优于商品化基于电化学原理的经皮血气监护仪。通过放置在皮肤表面的断型tcPco_2传感器来监测动脉二氧化碳分压(Pco_2)将对危重病人和手术临床监护,以及对运动医学等研究具有重要意义。通过对基于光物理原理的经皮血气监测新方法的进一步临床研究与实践必将开拓更为广阔的应用前景。     

Monitoring set-up for selection of parameters for detection of hypoglycaemia in diabetic patients

Recurrent severe hypoglycaemia is often an unsolved problem in diabetic patients under intensified insulin treatment. As no reliable long-term stable blood glucose sensor has yet been developed, registration of other body function changes could help to detect severe hypoglycaemia. A measuring system is described, capable on the one hand of recording EEG, heart rate, peripheral pulse, skin temperature, respiratory movements, skin impedance and arterial blood pressure, and capable of registering plasma glucose, counter-regulatory hormones, symptoms and cognitive performance under experimental conditions during hypoglycaemia, on the other. In a clinical study involving both insulin-induced hypoglycaemia in healthy subjects and insulin-dependent diabetic patients, the practical value and the character of changes of the recorded parameters are investigated. Currently insensitivity to hypoglycaemia, impracticability, complexity or susceptibility to artefacts make use of most parameters unsuitable for hypoglycaemia prevention. It is believed, however, that future efforts could result in indirect registration of hypoglycaemia, including a qualified combination of different parameters, individual adaptation in accordance with particular responses of individual patients, together with new measuring and sensor techniques.     

基于生物电阻抗法的人体成分测量系统的研究与评价

目的：本文探讨了生物电阻抗测量系统对人体成分的测量效果与适用性。从而为测量人体成分时选择合适的测量系统提供了技术支持与理论依据。方法：对生物电阻抗测量系统进行了深人的研究与评价,剖析总结了生物电阻抗法测量系统存在的问题,并对生物电阻抗法测量人体成分的影响因素进行了归纳与总结,最后对生物电阻抗法测量人体成分的未来发展进行了展望。结果：生物电阻抗法测量系统经历了从单频率全身测量系统到多频率人体分段电阻抗测量系统的发展过程,测量系统本身所具有的特性及外界因素都会对整个测量系统有一定干扰,所以针对不同的测量需要选择合适的测量系统与测量方案可以最大限度的减少干扰。结论：生物电阻抗法是测量人体成分的理想方法,生物电阻抗法测量系统的选择是人体成分测量的关键。随着研究推进,将会出现适用于人体局部的电阻抗测量系统。     

无创性动态测定血糖的动物实验

探索一种无创性动态测定血糖的原理和建立实验方法。使用共价键固定法 ,制作葡萄糖氧化酶传感器 ,选择传感器最佳制作方法和稳定的工作条件。设立超声前、后组 ,注射葡萄糖前、后及高频、低频超声对照组。在 10只日本大耳兔的皮肤表面 ,用高频或低频超声波处理皮肤 5 m in后 ,用葡萄糖氧化酶传感器测定其微电流信号的变化。采用葡萄糖氧化酶传感器和微电流检测仪 ,可观察到经超声波处理后 ,兔皮肤表面 ,微电流信号明显增高变化(P<0 .0 1)和在注射葡萄糖后的进一步增高变化 (P<0 .0 1)。兔皮肤表面经超声波处理后 ,对葡萄糖的通透性明显增高 ,经葡萄糖氧化酶传感器转化为微电流信号的变化 ,与兔体内的葡萄糖水平呈正相关。在活体动物皮肤表面 ,用葡萄糖氧化酶传感器测定血糖是可行的     

Calibration of a wearable glucose sensor.

Calibration of glucose sensors proved difficult for electrodes with immobilized glucose-oxidase. The correlation between the sensitivity of the electrodes in vitro and in vivo appeared to be poor. We developed a new type of glucose sensor, based on a microdialysis system, in which an oxygen electrode is used as detector outside the body and the enzyme glucose-oxidase dissolved in water is used as a dynamic selector. The enzyme solution is pumped through a hollow fiber placed subcutaneously, before the fluid passes the detector. The glucose sensor was tested in the subcutaneous abdominal tissue of 12 healthy volunteers and 12 type I diabetic patients. Blood glucose was clamped at two levels to permit a two-point calibration of the sensor in vivo. These values correlated well with the in vitro calibration factors (r = 0.949). In subcutaneous tissue the sensor measures 43 +/- 9% of the blood glucose value, using the in vitro calibration factor. No differences were detected between healthy volunteers and diabetic patients.     

Microwave sensor for the investigation of glucose-dependent reflection properties in aqueous samples

Abstract

The reported paper presents the development of a microwave sensor with a resonant frequency 2.4?GHz. The sensor is also demonstrated in vitro to investigate the variation in its response as a function of glucose concentration. The sensor could be used for the monitoring of blood glucose level in diabetics through non-invasive technology. The approach followed is based on the notion that, change in glucose concentration in the blood affects dielectric properties of blood which in turn produce an impact on reflection properties of the sensor. This effect on response of sensor will be ultimately used to estimate blood glucose concentration. The design specifications considered for the development of sensor are defined in the paper. The experimental setup for in vitro experiment and procedure employed for the investigation of the reflection properties of the sensor as a function of glucose concentration are also discussed in detail. The shift in resonance frequency and the change in the magnitude of the reflection coefficient of proposed sensor have been observed. The reported measurement results are the preliminary results in exploring the implementation of proposed sensor for non-invasive blood glucose monitoring.     

A refractometry-based glucose analysis of body fluids

In principle, refractometry appears to be a suitable method for the measurement of glucose concentrations in body fluids (such as blood and the intercellular fluid), even though the refractive index of the measured samples, as an additive property, is not specific. But, if certain conditions are fulfilled, the glucose content can be calculated using the refractive index in combination with values from a further measurement. This study describes the determination of the glucose content using refractometry in human blood serum derivates, which were selected - due to their ready availability - to be used as a model for interstitial fluid. Refractometry of body fluids requires the elimination of disturbing components from the measurement sample. First of all, a homogenous fluid (i.e. consisting of one phase) is required, so that all cells and components in suspension need to be separated out. Furthermore, certain dissolved macromolecular components which are known to disturb the measurement process must also be removed. In human serum samples which had been ultrafiltrated with a range of ultrafilters of different pore sizes, a comparative evaluation showed that only ultrafiltration through a filter with a separation limit of between 3 and 30kDa resulted in maximal reduction of the refractive index (compared to native serum), whereas ultrafilters with greater separation limits did not. The total content of osmotically active solutes (the tonicity) also exerts a clear influence. However, exemplary measurements in blood plasma fluid from one volunteer showed that the electrical conductivity is (without an additive component) directly proportional to the osmolality: physiological changes in the state of body hydration (hyperhydration and dehydration) do not lead to any considerable changes in the relation between ionised and uncharged solute particles, but instead result in a sufficiently clear dilution or concentration of the blood fluid's low molecular components. This finding allows the use of the--technically easy to measure--electrical conductivity as a measure for the tonicity of the measurement samples. Using measurements of these two parameters--refractive index and electrical conductivity--in blood serum obtained from a healthy volunteer, a two-dimensional calibration function (calibration matrix) for the assessment of the glucose content of ultrafiltrated human blood serum was constructed, and the measurement of blood glucose levels in non-diabetic (four females and four males) volunteers in comparison to a reference method was evaluated showing (as a proof of concept) a linear association. Assessment of the inaccuracy of these measurements made with the described measuring devices and methods showed a deviation from the reference values of less than 10%. An estimation of the maximum possible error showed relative deviations (maximum measurement uncertainties) of up to 20%.