Continuous glucose detection has a great significance for diabetics. On the one hand, it can fully reflect the patient blood glucose change level. On the other hand, it can better guide the insulin dosage, and achieve closed-loop control of insulin pump. A continuous detection method of glucose concentration by borate polymer fluorescent indicator is proposed in the paper. The principle of this method is based on the competing reaction between alizarin, glucose and borate polymer. The borate polymer has high specific reaction with glucose, meanwhile reacts with non fluorescent alizarin. The product of the reaction between borate polymer and alizarin is fluorescent, called as fluorescent indicator. When glucose was introduced, the glucose molecules could react with the borate polymer in fluorescent indicator because of the high specificity. This competing process leads to the decomposition of fluorescent indicator into the non-fluorescent alizarin, and the fluorescent intensity gets loss. Therefore, the change of fluorescent intensity can reflect the glucose concentration level. In this method, the fluorescent indicator can well identify the glucose molecules. According to the experiment, we know that there is a high specific and good linear reaction between glucose and borate polymer. The linear fitting is up to 0.97 and the detection limitation can reach to 10 mg/dL. The fluorescent intensity reaches strongest with the optimal proportion of alizarin: borate polymer as 1:3. The reaction of the fluorescent indicator identifying glucose molecules has a good linear relationship, the linear fitting of which can reach to 0.98. The detection limitation can reach to 30 mg/dL, which fulfills the detection
requirements of glucose concentration in vivo.
A new borate polymer PAA-ran-PAAPBA that can adsorb glucose specifically is introduced into the glucose
measurement based on surface plasmon resonance. Six and twelve layers of borate polymer are bound onto the SPR
sensors respectively through the layer-by-layer self-assembly binding method, and then the effect of different layers on
the glucose concentration measurement is studied. The experiment is conducted in three concentration ranges,
1~10mg/dL, 10~100mg/dL and 100~1000mg/dL. The Results show that the performance of 12-layer-polymer sensor is
better than that of the 6-layer-polymer sensor in the first two ranges, and the measuring result has no big difference in the
range of 100~1000mg/d. It indicates that the enhancement of polymer layer on the surface of SPR sensor can
dramatically improve the glucose measurement in the low concentration range.
According to the requirement of the calibration in minimally invasive blood glucose monitoring, a method based on microdialysis was presented to monitor glucose level in interstitial fluid continuously. An experimental system simulating the continuous change of glucose concentration in vivo was built. The influences on recovery of microdialysis caused by flow rate, glucose concentration, and temperature etc. were studied. The results led to the conclusion that the recovery fell by 71.7% when perfusion rate increased from 0.3 μL/min to 3.0 μL/min, while the different concentrations of glucose solutions scarcely contribute to the recovery instead, and the temperatures from 25 to 58 °C caused the recovery to increase by 34.6%.
A measurement method of glucose concentration based on fiber-optic surface plasmon resonance (FO-SPR) is proposed to achieve online, real-time detection of human blood glucose concentration. The end-reflection structure of FO-SPR sensor was simulated and the impact of different parameters on sensor performance was analyzed. Then the FO-SPR sensor was manufactured according to the optimized parameters. A glucose concentration measurement system with SPR sensor was set up. Glucose solutions with different concentrations were measured and the experiment results showed that the correlation coefficient of fitting curve between the glucose concentration and resonance wavelength was above 0.95 at the human blood glucose range of 0~200mg/dL. The measurement repeatability was also proved to be able to meet the requirements of blood glucose concentration detection in clinics.
To realize the online, rapid distinguishing of different petrol in transportation pipelines, a method based on fiber-optic surface plasmon resonance (FO-SPR) sensor is proposed. The calculation and simulation of FO-SPR end-reflection
structure were carried out through fiber theoretical model and SPR principle. The impact of different parameters on
sensor performance was analyzed. According to the optimized structure parameters, the FO-SPR sensor was
manufactured. A wavelength modulation optical measurement system with FO-SPR sensor was established. Sample
petrol of 90#, 93# and 97# and their mixture were measured. Different types of petrol were distinguished through the
changes of the resonance wavelength. The experiment results showed that the measurement method could distinguish different petrol and had a good degree of distinction and repeatability. It lays the foundation for the identification of mixed product oil in transportation pipelines.
Interstitial fluid (ISF) can be transdermally extracted using low-frequency ultrasound and continuous vacuum pressure
on skin surface. But the tiny volume of transdermally extracted ISF makes the transdermal extraction, collection,
transport, volumetric detection and glucose concentration measurement of the ISF very difficult. Based on a microfluidic chip for transdermally extraction of interstitial fluid and a micro glucose sensor for glucose concentration measurement, a continuous glucose monitoring instrumentby ISF transdermal extraction with minimally invasive way is developed. In the paper, various parts of the device and their interface circuits are designed; the hardware and software of the instrument are built; the simulating experiments of transdermal ISF extraction, collection and volume measurement with full-thickness pig skin are performed using this integrated system; and the functionalities of this device is verified for future clinical application.
Minimally-invasive human blood glucose detection can be realized by measuring the glucose concentration of interstitial fluid to predict the blood glucose level. As the amount of transdermally extracted interstitial fluid was minimal and its composition was complex, a glucose measurement method by surface plasmon resonance (SPR) based on PAA-ran-PAAPBA polymer binding was proposed. The polymer was immobilized on the gold film of SPR sensor using layer-by-layer self-assembly technique to capture the glucose molecules in interstitial fluid to realize the detection of glucose concentration with high precision. 2~1000mg/dL glucose solutions were measured utilizing the SPR sensor by polymer binding. The fitting degrees were 0.90177 and 0.99509 in the range of 2~10mg/dL and 25~1000mg/dL respectively. The dynamic dissociation process of glucose molecules from PAA-ran-PAAPBA was verified to be able to satisfy the requirements of the human blood glucose continuous monitoring in clinics.
The application of tunable Mid-infrared laser system based on fiber-optic ATR sensor to regent-free quantification of glucose concentration was presented. The five laser emission wavelengths, including 1081, 1076, 1051, 1041 and 1037 cm-1, were employed for glucose determination. In our experiments, absorbance at the five wavelengths correlates strongly well with glucose concentration (R2>0.99, SD<0.0004, P<0.0001), and the noise-equivalent concentration is as low as 3.8 mg/dL. Compared with the conventional FT-IR spectrometer, higher sensitivity was aquired because of the laser higher power and spectral resolution, and it is about 4 times as high as that of FT-IR spectrometer. All the results of this investigation suggested that the tunable CO2 laser spectroscopy is a powerful method for glucose measurement. Especially, the multiple tunable wavelengths, which makes it possible for glucose determination in blood or interstitial fluide with complicated components.
In recent years, using the detection of interstitial fluid glucose concentration to realize the real-time continuous
monitoring of blood glucose concentration gets more and more attention, because for one person, the relationship
between blood glucose concentration and interstitial fluid glucose concentration satisfies specific rules. However, the
glucose concentration in interstitial fluid is not entirely equal to the glucose concentration in blood and has a
physiological lag because of the physiological difference of cells in blood and interstitial fluid. Because the clinical
diagnostic criteria of diabetes are still blood glucose concentration, the evaluation model of the physiological lag
parameter between the glucose concentration in blood and the glucose concentration in interstitial fluid should be
established. The physiological difference in glucose molecules uptake, utilization, and elimination by cells in blood and
interstitial fluid and the diffusion velocity of glucose molecule from blood to interstitial fluid will be induced to the mass
transfer model to express the physiological lag parameter. Based on the continuous monitoring of glucose concentration
in interstitial fluid, the project had studied the mass transfer model to establish the evaluation model of the physiological
lag parameter between the glucose concentration in blood and the glucose concentration in interstitial fluid. We have
preliminary achieved to evaluate the physiological lag parameter exactly and predict the glucose concentration in blood
through the glucose concentration in interstitial fluid accurately.
Minimally-invasive blood glucose monitoring is a very efficient and important way to control blood glucose level of
diabetes. An implantable fiber-optic surface plasmon resonance sensor for minimally-invasive blood glucose monitoring
is presented. As the fiber-optic SPR sensor is sensitive to temperature and moreover the human body temperature drift
plays a great effect on measurement results when the sensor is implanted in human body, long period fiber grating (LPFG)
is utilized for temperature compensation to improve measurement accuracy. The fiber-optic surface plasmon resonance
sensor is theoretically analyzed and the parameters such as the length of sensor, diameter of fiber, thickness of Chrome
and gold are calculated and simulated. The parameters of LPFG is analyzed and simulated, such as length, period and
modulation depth. The structural parameters of the sensor are optimized through the calculation and simulation.
Volume measurement of interstitial fluid transdermally extracted is important in continuous glucose monitoring
instrument. The volume of transdermally extracted interstitial fluid could be determined by a skin permeability
coefficient. If the skin impedance which is the indicator of skin permeability coefficient can be accurately measured, the
volume of interstitial fluid can be calculated based on the relationship between the indicator and the skin permeability
coefficient. The possibility of using the skin impedance to indicate the skin permeability coefficient is investigated. A
correlation model between the skin impedance and the skin permeability coefficient is developed. A novel non-invasive
method for in vivo, real-time, and accurate measurement of skin impedance within a micro skin area is brought forward.
The proposed measurement method is based on the theory that organisms saliva and interstitial fluid are equipotential.
An electrode is put on the surface of a micro skin area and another one is put in the mouth to be fully contacted with
saliva of an animal in the experiments. The electrode in mouth is used to replace the implantable subcutaneous electrode
for non-invasive measurement of skin impedance in vivo. A biologically compatible AC current with amplitude of
100mv and frequency of 10Hz is applied to stimulate the micro skin area by the two electrodes. And then the voltage and
current between the two electrodes are measured to calculate the skin impedance within a micro skin area. The
measurement results by electrode in mouth are compared with the results by subcutaneous electrode in animal
experiments and they are consistent so the proposed measurement method is verified well. The effect of moisture and
pressure for the measurement is also studied in the paper.
With the improvement of living standard, the incidence of diabetes increases year by year. Minimally invasive blood
glucose monitoring is an effectively way to control diabetes, and it is achieved by measuring the glucose concentration of
interstitial fluid in human body. This paper presents a portable minimally-invasive human glucose detection instrument
which is based on a miniature integrated surface plasmon resonance (SPR) sensor. D-galactose/D-glucose Binding
Protein (GGBP) which can specifically absorb glucose moleculars is used to modify the gold surface of SPR sensor for
higher sensitivity and stability. The instrument includes an interstitial fluid extraction unit, a liquid flow unit, a SPR
sensor unit and a circuit control unit. Interstitial fluid is extracted from human body using the interstitial fluid extraction
unit, and it is then transported to the SPR sensor by the liquid flow unit, and the SPR sensor can detect the glucose
concentration in the interstitial fluid. The acquisition and process of data is controlled by the circuit control unit, which
controls the operation of the whole system as well. The glucose detection resolution could reach 6.25mg/L, and the
experiment result has good linearity when the glucose concentration ranges from 6.25mg/L to 50mg/L.
A novel minimally invasive way to measure blood glucose concentration is proposed by combining interstitial fluid
transdermal extraction and surface plasma resonance (SPR) detecting. 55K Hz low-frequency ultrasound pulse is applied
for less than 30 seconds to enhance the skin permeability and then interstitial fluid is extracted out of skin by vacuum.
The mathematical model to express the correlation between interstitial fluid glucose and blood glucose is also developed
by considering the changes of the skin conductivity. The glucose concentration in the interstitial fluid is determined
using an optical SPR biological sensor that measures the refractive index. A protein-glucose binding technology using Dgalactose/
D-glucose Binding Protein for specific absorption of glucose is employed to increase SPR measurement
precision. By immobilizing GGBP onto the surface of the SPR sensor, the experimental result indicates the detecting
resolution of glucose rises to 1mg/L, the system succeeds in distinguishing glucose from other components in mixture.
The feasibility of this method is validated for clinical application with the requirements of bloodless, painless,
continuous glucose monitoring and a prototype microfluidic diabetes-monitoring device is under development.
The continuous blood glucose monitoring system using interstitial fluid (ISF) extracted by ultrasound and vacuum is
proposed in this paper. The skin impedance measurement is introduced into the system to monitor the skin permeability
variation. Low-frequency ultrasound is applied on skin surface to enhance the skin permeability by disrupting the lipid
bilayers of the stratum corneum (SC), and then ISF is extracted out of skin continuously by vacuum. The extracted ISF is
diluted and the concentration of glucose in it is detected by a biosensor and used to predict the blood glucose
concentration. The skin permeability is variable during the extraction, and its variation affects the prediction accuracy.
The skin impedance is an excellent indicator of skin permeability in that the lipid bilayers of the SC, which offer
electrical resistance to the skin, retard transdermal transport of molecules. So the skin impedance measured during the
extraction is transformed to skin conductivity to estimate correlation coefficient between skin conductivity and
permeability. Skin conductivity correlates well with skin permeability. The method and experiment system mentioned
above may be significative for improving the prediction accuracy of continuous blood glucose monitoring system.
The concentration of glucose in interstitial fluid determined by using the surface plasmon resonance (SPR) biosensor
with chemical bonding D-Galactose/D-Glucose Binding Protein (GGBP) is proposed in this paper.
D-Galactose/D-Glucose Binding Protein (GGBP), a kind of protein which has the ability to absorb the glucose
specifically, is immobilized on the gold film of the SPR sensor to improve the sensitivity of glucose detecting. The
GGBPs mutated at different points have different association abilities with glucose, which bring different measurement
range and precision. So the selection of proteins is a critical problem of the determination of glucose by using SPR
biosensor. Using different mutated GGBPs, the samples with different concentrations of glucose are measured in the
experiment, and the prediction error and precision are discussed. Furthermore, the light intensity of sensor is instable, so
the baseline of SPR responses is tracked and adjusted accordingly using the methods - fixing points and fixing areas'
ratio. The experiment results show that GGBPs mutated at different points have its corresponding working curves and
different measurement precision. In conclusion, the study is significant for the application of SPR biosensor to the
minimally invasive diabetes testing and other detection of human body components.
Noninvasive and minimally invasive blood glucose sensing is one of most interesting research fields. For the noninvasive measurement using near-infrared spectroscopy, the optical signal was impaired by the uncertain physiological noise and systematical drift. A floating reference method by differentially processing two signals from reference point and measuring point was used to deal with these uncertain noises. For the minimally invasive measurement, interstitial fluid extracted by ultrasound and vacuum is investigated. Low-frequency ultrasound was applied to enhance the skin permeability to interstitial fluid by disrupting the stratum corneum lipid bilayers. In this paper, a kind of protein absorbing the glucose specifically called D-galactose/D-glucose Binding Protein (GGBP) was introduced to construct a novel surface plasmon resonance (SPR) measuring system. By immobilizing GGBP onto the surface of the SPR sensor, a new detecting system for glucose testing in mixed solution was developed. The experimental result indicated that, the SPR system succeeded in distinguishing glucose resolution of 0. 1 mg/L, and had linear relationship between 0.5 mg/L and 5 mg/L.
Glucose is one of the most important substances widely contained in organism and food, thus people pay much attention
in researching and improving the way for the detection of glucose. Traditional ways, although precise and reliable when
in high concentration and large amount of sample, have unconvincing performance in detecting mixture and solution
with low concentration and micro-volume. As far as the ideal way is concerned, it should not only specifically detect the
glucose and exclude other components in solution, but also meet the need of micro-sample (approximately 5μL) and low
concentration. We introduced D-galactose/D-glucose Binding Protein (GGBP) - a kind of protein which has the ability
to absorb the glucose specifically, to construct a novel surface plasmon resonance measuring system. By immobilizing
GGBP onto the surface of the SPR sensor, we develop a new detecting system for glucose testing in mixed solution. The
experimental result indicates that compared with 0.1g/L before immobilization of GGBP, the detecting limit or the
resolution of glucose testing rises to 1mg/L after the immobilization, the system succeeds in distinguishing glucose from
other components in mixture, which reveals a bright future to apply SPR in the minimally invasive diabetes testing and
food quality control.
Prediction of blood glucose using interstitial fluid extracted by ultrasound and vacuum is proposed by the paper.
Low-frequency ultrasound with 55 KHz is applied for about 30 seconds to enhance the skin permeability to interstitial
fluid by disrupting the stratum corneum lipid bilayers and then interstitial fluid is extracted out of skin successfully by
10in.Hg vacuum for 15 minutes. The glucose concentration in the interstitial fluid is measured by an instrument with
immobilized enzyme sensor. And then a method of data analysis is set up to prediction the glucose concentration in the
blood by the measurement of the glucose concentration in the interstitial fluid. At last, Clarke Error Grid analysis is
performed to assess if the prediction accuracy could satisfy the requirements of clinical application. The whole method
and experimental system above is set up in the article and the feasibility of this way for blood glucose detecting is
primarily validated for clinical application with the requirements of bloodless, painless, continuous glucose monitoring.
Additional a prototype of miniature diabetes monitoring device with the technique of surface plasma resonance to
measure the glucose concentration in the interstitial fluid is also being developed.
In this paper, tunneling phenomena of tunneling junctions are studied and analyzed. Tunneling junction is the basic
structure of single electric transistor (SET) and other nano devices. Ultra fine oxidized titanium (Ti) lines are formed on
the Ti layer, which is 3nm thick and sputtered on a SiO2 substrate by magnetron sputtering. The atomic force microscope
(AFM)'s tip is used as a selective anodization electrode to oxidate the Ti film between electrode structures that are
formed by photo lithography. Ti-TiOx-Ti forms metal-insulator-metal (MIM) tunneling junction, and TiOx works as an
energy barrier for the electron. Different number of TiOx lines is fabricated between two electrodes by controlling
fabrication condition and environment at the same value. And then, the I-V characteristics of tunneling junctions with
different number of TiOx lines are measured. The results indicate that the tunneling phenomena of tunneling junctions
with different number of TiOx lines are different.
A kind of 0°-90° tilting micro-mirror with fiber holding structures monolithically, which is composed of a metal-coated polysilicon or single crystal silicon film, is fabricated by the MEMS process technology based on regular silicon wafers as well as SOl wafers using the mixed micromachining of surface and bulk silicon microelectronics. According to the scalar scattering theory, a mathematical model, which describes the effects of the surface roughness on reflectivity and scattering, is constructed to analyze the optical properties of micro-mirrors. Then the surface roughness of a series of micro-mirrors with different coated metals is measured by the AFM. The diffraction effect of etching holes and the optical power transmission through MEMS multi-layer membranes are analyzed in theory preliminarily. To characterize the dynamic response of the micro-mirrors and optimize the design of driving system, a novel reduced order model of micro-mirrors is brought forward to fulfilled the mechanics-electrics coupling simulation to verify the theoretical analysis and the experimental results easily. Based on the investigation on theory, simulation and experiments together, some ameliorated processing methods of producing the micro-mirrors are advanced to improve the total performances.
The electromechanical characteristics of a novel micro torsion-mirror actuator and the optical properties about the light scattering and reflection of its micro-mirror under the influence of mirror surface roughness are investigated experimentally and theoretically. The electrostatic yielding voltages for driving the metal-coated polysilicon or single crystal silicon micro-mirrors suspended by elastic torsion beams to tilt from 0° to 90° spontaneously are in the range of 270~290 V and the minimum holding voltages for keeping the tilting angle of the mirrors to be in 90° are found 55 V or so when the thickness of the torsion-beams is about 1 ?m. The lifetime and the estimated shortest actuating time of the micro torsion-mirror actuators can reach 108 at least and less than 2 ms, respectively. The maximum value of the surface roughness of the micro-mirrors is 69.443 nm and the distribution of the surface roughness is smooth, which is acceptable for wavelength division multiplexing applications basically. In general, the novel torsion-mirror actuators can be applied as optical switches for optical networking.
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