Open Access
Add to BibSonomy
Abstract
We demonstrated the design of two different structures, a two-sided structure and a top-surface structure, of glucose waveguide Bragg grating (WBG) sensors in a single-mode silicon-on-insulator (SOI) chip. A two-sided WBG structure was fabricated, and chip preparation was realized by lithography and other processes. A photonic platform for testing the two-sided WBG using glucose was built and completed. When the blood glucose concentration changed by 1 mg/mL, the two-sided WBG had a wavelength offset of 78 pm. The experimental results show that the two structures can achieve the sensing of different blood glucose concentrations. The two-sided WBG had better sensing performance and thus has a wide range of application prospects.
© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement
1. Introduction
Integrated circuits have evolved to the current era of nanoscale nanotechnology, and new breakthroughs in materials and processes are necessary to further improve the integration and operation speed of chips. Silicon-on-insulator (SOI) materials, the research of which is currently focused on material applications, have multifunctional monolithic integration, and bufferless III-V lasers grown on 220 nm SOI platforms can seamlessly connect active III-V light sources and passive silicon-based photonic devices [1]. Their easy compatibility with complementary metal oxide semiconductor (CMOS) processes has also been widely studied [2,3], and SOI-based platforms for planar optical waveguide sensing technology [4,5], the development of which has been strongly driven mainly by the development of integrated optical circuits, involve the integration of optical devices on a monolithic substrate.
Bragg gratings have been widely used in various optical devices, communication, and sensing systems. Waveguide Bragg grating (WBG) integration into SOI platforms has attracted increasing research interest over the past decade. People have started to explore the value of WBGs, which are now widely used to make photonic filters [6,7], polarization splitters/synthesizers [8], and various sensors, such as stress sensors [9–11] and temperature sensors [12], due to their grating properties and high integration. The available shapes of WBG sensors are not fixed, and new designs and types are still available [13]. In addition, glucose sensing is an important biosensor research direction.
In the field of glucose biosensing, the current optical detection methods are infrared spectroscopy, optical polarization and laser Raman spectroscopy. Infrared spectroscopy is used to measure the blood glucose concentration by collecting the infrared light reflected or transmitted by the blood in the human body, but because the infrared absorption spectrum of blood glucose in the human body only accounts for a small part, the accuracy of this method is not high [14–16]. The optical polarization method linearly polarizes light passing through glucose solution to detect the spin effect; this method is more difficult to measure the blood glucose concentration because measuring the polarization angle requires high adjustment and stability of the optical path [17–19]. Laser Raman spectroscopy uses the difference between the multiple Raman characteristic peaks of glucose and the signal peaks of other substances in the skin tissue to perform a quantitative analysis of the blood glucose concentration, but because the collagen in the dermis and melanin in the epidermis of the skin are sensitive to the absorption effects of excitation light and Raman light, etc., applying this technique is difficult [20–22]. In addition, in 2016, Ming-jie Yin et al. proposed embedding a long-period grating (LPG) into a small-diameter single-mode fiber [23] and then fixing a glucose oxidase upper cladding layer in the outer layer for glucose sensing. However, single-mode optical fibers prevent the core layer from directly contacting the external refractive index change due to the presence of its upper cladding layer, and glucose oxidase alone cannot survive for a long time, affecting the sensitivity. The addition of optical sensors has led to the proposal of more noninvasive methods for glucose monitoring [24–26]. While WBG sensors have gradually entered the limelight and achieved the measurement of various biological as well as chemical parameters due to their high resistance to electromagnetic interference, so WBG research is increasing and developing.
In this paper, the research we have done is based on etching gratings in waveguides of the SOI platform to form a refractive index sensitive layer and immobilizing glucose oxidase for glucose concentration detection. We also introduced a method to immobilize glucose oxidase to achieve the detection of the glucose content in an optical device and fabricated a chip and a real object to verify the results, which showed that this optical device can achieve the detection of the glucose concentration.
2. WBG design principles
A Bragg grating is an optical sensor that periodically modulates the effective refractive index in the propagation of an optical pattern. Effective reflection can only occur if the Bragg wavelength satisfies the following conditions.
For WBGs, this periodic modulation is usually achieved by changing the waveguide dimensions. As the signal propagates through the Bragg grating, the reflection of light occurs at all interfaces, creating a relative phase difference between the input signal and the reflected light. Therefore, after multiple reflections, only those that obtain constructive interference tend to be highly reflected, while the others cancel each other out and propagate through the grating. These reflected signals are in a narrow band around the Bragg wavelength, and when the refractive index of the surrounding environmental medium changes, the reflected wavelength is shifted, enabling biosensing by monitoring the shift or intensity change of the resonant wavelength peak.
The structure of the silicon-based waveguide grating consists of only a core layer and a lower cladding layer, while an upper cladding layer is etched away to facilitate the experimental addition of glucose oxidase (GOD). The corresponding theoretical analysis process requires the use of coupled-mode theory to analyze and infer the SOI WBG sensing characteristics with regard to the refractive index change of the surrounding medium. The relationships between the effective refractive index of the waveguide grating surface, the GOD layer, and the ambient refractive index are studied. The structures of the core layer, cladding layer, and GOD layer are selected in this paper with regard to blood glucose sensing, as shown in Fig. 1(a). Moreover, when the external blood glucose concentration increases or decreases, the GOD layer undergoes a reaction and the external refractive index changes, thus affecting the effective refractive index of the WBG core and shifting the resonant wavelength of the WBG, which becomes a sensing element that can be used to measure blood glucose.
Fig. 1. Single-mode transmission conditions in the WBG. (a) WBG cross-sectional view in the 2D x-z direction and its related parameter representation. (b) Effective refractive index representation in the horizontal direction and parameter representation. (c) Effective refractive index representation in the vertical direction and parameter representation. (d) When W = 0.55 µm, the electric field diagram of the waveguide at a wavelength of 1550 nm is shaped as a single lobe, which meets the single-mode transmission condition.
The geometric model of the silicon waveguide is determined according to the single-mode transmission condition of the rectangular waveguide. The thickness of the silicon waveguide in the selected device layer is 220 nm. Silicon is selected as the waveguide core material, and the refractive index of the core at 1550 nm is 3.46. Silicon dioxide is used as the waveguide cladding material, and the cladding refractive index at 1550 nm is 1.45. Single-mode transmission is mainly determined by the refractive index of the waveguide core cladding and the waveguide geometry. Then, the waveguide core cladding material is determined. Through the effective refractive index method and the guided mode cutoff condition, the parameters of the width W and height H of the rectangular waveguide core layer are determined. Considering the waveguides in Fig. 1(a) as two planar two-dimensional waveguides, it is determined that n1 = 3.46 and n2 = n3 = n4 = n5 = 1.45. Figures 1(b) and 1(c) show the effective refractive index decomposition method. In Fig. 1(b), the refractive index of the waveguide core layer is nm, which is the effective refractive index of the heavy waveguide in Fig. 1(c) in transverse electric (TE) mode, and Neff is the effective refractive index of Fig. 1(b) in transverse magnetic (TM) mode, which is the effective refractive index of the rectangular waveguide.
Figure 1(d) shows the electric field diagram under a wavelength of 1550 nm when the waveguide width is 0.55 µm (W = 0.55 µm). The shape of the facula is a single lobe, which means that the waveguide can realize single-mode transmission. In the design of the WBG simulation model, we choose the waveguide width of the Bragg grating to be less than W = 0.55 µm to ensure that the mode transmitting in the waveguide is single-mode.
3. Design and simulation
In our study, two kinds of WBG structures (top-surface and two-sided) are used. To measure human blood glucose, a GOD layer is coated on the top surface of the WBG. GOD can catalyze the reaction between glucose and oxygen. Under the catalysis of the enzyme, gluconic acid will be generated to realize the change in the coating layer refractive index. We set the initial GOD concentration to 15 mg/mL.
Two different 3D WBG optical models (COMSOL Multiphysics) were developed. Figure 2(e) represents the top-surface WBG model, and Fig. 2(f) represents the two-sided WBG model. The figure indicates what each parameter represents when designing the 3D model.
Fig. 2. Representation of 2D and 3D WBG models and related parameters in the model. (a) Cross-sectional view of the top-surface WBG in the y-z direction. (b) Cross-sectional view of the two-sided WBG in the y-z direction. (c) Top view of the top-surface WBG in the x-y direction. (d) Top view of the two-sided WBG in the x-y direction. (e) Schematic of the top-surface WBG. (f) Schematic of a two-sided WBG.
We observed the 3D WBG optical model from the 2D direction. To improve the ascendant sensing properties of the WBG, parameter selection must be considered. Generally, parameterized scanning is used to select better parameters. The meanings represented by the specific parameters are shown in Figs. 2(a), 2(b), 2(c) and 2(d).
The parameter set of the WBG is shown in Table 1. Table 1 lists the relevant parameters of the top-surface WBG and the two-sided WBG, and the specific parameters are expressed in the 3D model (COMSOL Multiphysics).
Table 1. Design parameters of SOI WBGs
In the establishment of the 3D model and parameters (COMSOL Multiphysics) to simulate the changes in blood glucose concentration, we need to add parametric scanning to the GOD layer refractive index to simulate the changes in the GOD layer refractive index due to the changes in the external blood glucose concentration [27]. Under normal conditions, the fasting glucose range for normal humans is 3.9∼6.1 mmol/L, corresponding to a mg/mL concentration unit range of 0.702∼1.098 mg/mL, the one-hour postprandial glucose range is 6.7∼9.4 mmol/L, corresponding to a mg/mL concentration unit range of 1.2∼1.69 mg/mL, and the two-hour postprandial glucose range is ≤7.8 mmol/L, corresponding to a mg/mL concentration unit range of ≤1.4 mg/mL. Therefore, the measurement range of glucose concentration selected for our test was 0.5∼1.5 mg/mL. The refractive index of the coating layer is the refractive index of the solution after the reaction of glucose with fixed glucose oxidase. We used an Abbe refractometer to test the refractive indices after the reaction between different concentrations of glucose and glucose oxidase and found that the refractive indices of the GOD layer were 1.3381∼1.3371, corresponding to glucose concentrations of 0.5∼1.5 mg/mL. The GOD layer refractive index changed from 1.3381 to 1.3371, the central wavelength of the top-surface WBG changed from 1438.71 nm to 1438.58 nm, and the central wavelength of the two-sided WBG changed from 1543.59 nm to 1543.49 nm. Figure 3(a) shows the GOD layer refractive index with the dropwise addition of different concentrations of glucose, and Figs. 3(b) and 3(c) represent the variation curves of the central wavelengths of the two structures with the dropwise addition of different concentrations of glucose and the value of the output optical power. Figure 4 shows the variation curve of the central wavelength with the GOD layer refractive index.
Fig. 3. (a) Variation in the refractive index of the top cladding solution with the concentration of glucose. (b) The central wavelength of the top-surface WBG shifts toward the short-wave direction as the glucose solution concentration increases. (c) The central wavelength of the two-sided WBG shifts toward the short-wave direction as the glucose solution concentration increases.
Fig. 4. (a) Variation curve of the central wavelength of the WBG with the glucose concentration for the top-surface structure. (b) Variation curve of the central wavelength of the WBG with the glucose concentration for the two-sided structure.
It is not difficult to see that as the concentration of glucose solution increases, the refractive index of the GOD layer decreases, and the central wavelength of the WBG moves in the short-wave direction, with the top structure WBG resonance wavelength shifted by 0.13 nm and the bilateral structure WBG resonance wavelength shifted by 0.1 nm; thus, monitoring the change of glucose concentration can be achieved. The simulation results in the simulator device are shown in Table 2.
Table 2. Simulation test results
4. Device fabrication and experiments
By comparing the simulation results of the two structures, it is seen that the loss of the two-sided WBG is smaller, and the detection band of the broadband light source is the 1500 nm-1600 nm band; therefore, we choose the two-sided WBG for fabrication and testing. The silicon photonic platform we use is the Institute of Microelectronics of the Chinese Academy of Sciences (IMECAS) platform. The waveguide etching process uses a typical SOI layer thickness of 220 nm. The silicon-based optical waveguide device preparation process is roughly divided into the cleaning of the silicon substrate, fabrication of the waveguide lower cladding film, fabrication of the waveguide core layer film, bonding, cleaning, photolithography of the waveguide pattern, dry etching to fabricate the waveguide core layer structure, and filling of the upper cladding layer with GOD. The period of the two-sided WBG is 380 nm, the number of cycles is 1000, the grating length is 380 µm, the duty cycle is 0.5, the full etching process reaches 220 nm, the modulation depth is 275 nm, and the device size is 380 µm × 1.1 µm × 0.22 µm after the flow plate. The scanning electron microscopy (SEM) image is shown in Fig. 5.
Fig. 5. Top SEM magnified images of the two-sided silicon-based WBG. (a) The overall structure of the two-sided WBG. (b) Two-sided WBG grating structure.
Experimental processes mainly involve fixing GOD on the grating, injecting glucose of different concentrations to simulate the change in blood glucose, and finally observing the shift in the wavelength on the spectrometer [28].
Since enzymes in the free state are less stable and easily inactivated and it is difficult to purify the enzyme after completing the enzyme-catalyzed reaction, it is difficult to reuse the enzyme; thus, it is necessary to immobilize the enzyme. The main fixation methods for glucose oxidase within the cross-linking method are the glutaraldehyde cross-linking fixation method and silane coupling fixation method. The cross-linking conditions of the glutaraldehyde cross-linking method are more violent, and the enzyme molecule is cross-linked by several groups, so it has a greater impact on the enzyme activity, and the glutaraldehyde solution contains an irritating odor. Using the more stable silane solution as the cross-linking agent, the coupling efficiency is higher, the detection limit is higher, and it is nontoxic, nonhazardous and not easily subjected to photolysis. The silane coupling method mainly uses cross-linking between the enzyme molecule and bifunctional or multifunctional cross-linking reagents to bind the enzyme molecule directly to the carrier. In the experiment, the materials for making the silane solution were isobutyltriethoxysilane (I833847, Macklin, China) and high-purity GOD (G810485, Macklin, China), which is easily soluble in water and can specifically catalyze β-D glucose (G6500, Innochem, China) under aerobic conditions.
In mg-level GOD and glucose solution preparation, errors will inevitably occur in the preparation process. Therefore, a method is used to prepare a solution with a higher concentration first, and then this solution is diluted with deionized water to obtain a solution of the desired concentration to verify the changing trend of the refractive index of the whole solution after the GOD catalyzes the glucose reaction. Using a digital Abbe refractometer, its measurement resolution is also completely in line with the refractive index change of this design.
The specific experimental steps are described below:
- (1) A 15 mg/mL GOD solution and 11 concentration gradients of glucose solution from 0.5 mg/mL to 1.5 mg/mL were prepared. In this study, both the glucose solution and GOD solution were prepared using a phosphate solution as the solvent. When preparing a certain concentration of glucose or GOD solution, a certain mass of powder was obtained using an electronic balance with an accuracy of milligrams and dissolved in the phosphate solution. After stirring or shaking for a while, the solution became transparent, which indicated that the solution had been mixed well.
- (2) When preparing a certain concentration of silane solution, 99.7% absolute ethanol (G00004, Innochem, China), deionized water (W820537, Macklin, China), and isobutyltriethoxysilane were used in a volume ratio of 78:20:2. A microsampler was used to drop the prepared silane solution on the surface of the fabricated grating, the solution was allowed to stand for 10-20 min, and a desiccant silica gel was used to dry the solution for 12-24 h. The drying process was conducted in a sealed environment to prevent it from reacting with moisture and impurities in the air.
- (3) After surface modification with the silane solution, it was necessary to use 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (H109330, Aladdin, China) and N-hydroxy-succinimide (NHS) (A12042, Innochem, China) to form the surface of the grating, which was further modified by a protein cross-linking agent. A microinjector was used to drop the protein cross-linking agent solution so that the grating surface was completely immersed in the solution. After drying, a specific concentration of GOD solution needs to be added immediately to the grating surface. The fixation time was generally 60 min, and phosphate solution was used to rinse it. After removing the remaining mobilized GOD, GOD immobilization was completed.
Fig. 6. Preparation process of the chemical reagents required for the assay and the process of fixing the envelope of GOD.
We established a light-sensing system to test the sensitivity and output optical power of the WBG glucose sensor. A superradiant light-emitting diode (SLED) broadband light source is connected via an optical fiber to port 1 of a multimode interference (MMI) coupler. Port 2 of the MMI coupler is laterally coupled to the two-sided WBG with tapered fiber optics to reduce coupling losses. The WBG selectively reflects light back. The light reflected from the two-sided WBG is connected to the spectrometer through port 3 of the MMI coupler. Port 4 is connected to the matching fluid. The function of the matching fluid is to reduce light reflection losses. The central wavelength and output optical power of the two-sided WBG reflection are observed with a spectrometer. By the dropwise addition of a glucose solution with a concentration of 0.5∼1.5 mg/mL, the change in the central wavelength of the spectrometer is observed. Each drop of glucose needs to rinse the grating surface with the phosphate solution for 20 min to test the transmission of the silicon-based two-sided WBG with respect to glucose. A schematic diagram of the experimental system is shown in Fig. 7.
The range of the SLED broadband light source and the reflected Bragg wavelength of the two-sided WBG grating can be seen on the spectrum analyzer, as shown in Fig. 8(a) and Fig. 8(b). It can be seen that the SLED broadband light source can only scan the light in the 1500-1600 nm band, and at 1550 nm, the optical power reaches its maximum, and there is a wave peak of 1542.988 nm in the reflected wavelength of the waveguide Bragg grating. The measured optical power of the wave peak is -19.13 dB, the measured insertion loss of the tapered fiber is 9.8 dB, and the insertion loss of the MMI coupler is 4.6 dB. From the results, it can be observed that the Bragg reflection wavelength of the waveguide shows wavelength selectivity.
Fig. 8. Experimental characterizations of two-sided WBG. (a) Output spectrum of the SLED broadband light source on the spectrometer. (b) Output spectrum of the two-sided WBG with the cladding on the GOD fixed on the spectrometer.
The blood glucose concentration is set to 0.5-1.5 mg/mL with a concentration interval of 0.2 mg/mL. As shown in Fig. 9(a) and Table 3, the spectra of the two-sided WBG reflections drift with changing glucose concentration. The resonance peak with a central wavelength of 1542.988 nm is observed at 0.5 mg/mL, and the 3-dB bandwidth and lateral mode rejection ratio of the resonance peak are 0.21 nm and 17.2 dB, respectively. The central wavelength of the two-sided WBG shifts toward the short-wave direction with increasing glucose concentration and varies linearly. The sensing sensitivity of the two-sided WBG is 78 pm/(mg/mL), and the results are shown in Fig. 9(b). The results show that the device has a good wavelength selection function for sensing the glucose concentration.
Fig. 9. Two-sided WBG glucose sensor sensitivity test. (a) Output spectra of two-sided WBG tests with different glucose concentrations. (b) Relationship between the central wavelength of bilateral WBG and glucose concentration.
Table 3. Characteristic parameters of the WBG at different glucose concentrations.
5. Discussion
A WBG sensing device based on the SOI platform can realize blood glucose measurement, which triggers a change in the effective refractive index of the waveguide when the simulated blood glucose concentration changes and thus causes the central wavelength change, realizing a more sensitive and convenient measurement. In addition, the designed device is fabricated and tested. Bragg grating sensors are commonly used in fiber Bragg gratings, and on-chip Bragg sensors based on SOI materials are less used, but SOI-based waveguide Bragg grating sensors are important in integrated optics and micro- and nanodevices. The research we have done is based on etching gratings in waveguides of SOI platforms to form a refractive index-sensitive layer for biosensing.
The shortcomings of the device are limited by the preparation process. Its function and preparation have certain defects. Moreover, the test results and simulation results are different. When the input light source is 1 mW, the two-sided WBG output optical power simulation results are −0.4278 dBm, while the corresponding test results are −19.13 dBm. The large difference in output optical power is due to the coupling fiber loss of the waveguide, the end-coupling loss and the loss of the tapered optical waveguide spot-size converter. The simulated sensitivity of the designed two-sided blood glucose WBG sensor is 100 pm/(mg/mL), and the actual sensitivity of the test is 78 pm/(mg/mL). This difference in sensitivity and wavelength mismatch is due to the actual fabrication process, which leads to uneven surfaces for the core layer waveguide and silica. In future research, we should design the device according to the requirements of the process, simulate the sidewalls generated by lithography, and consider both the waveguide sidewall formability and the influence of the upper cladding solution so that the wavelength of the processed Bragg grating corresponds to the theoretical Bragg grating wavelength. Due to the limited activity time of GOD, a more rapid experiment is needed, which can be considered in future research. The environment and time of enzyme immobilization should be controlled, such as in a sterile room, and a lower temperature will be necessary to immobilize the enzyme and extend the time of immobilization.
6. Conclusion
We designed and prepared an SOI-based on-chip WBG sensor that can detect blood glucose concentrations in the range of 0.5 mg/mL∼1.5 mg/mL. The results of several experiments showed that the GOD layer refractive index decreased from 1.3381 to 1.3371 with increasing glucose concentration, at which time the central wavelength of the reflection spectrum shifted toward the short-wave direction, and the GOD layer refractive index varied in the interval of (1.3381-1.3371). The central-wavelength range corresponding to Λ=380 nm was 1542.988 nm∼1542.91 nm, and its central wavelength reached a linear variation of 0.078 nm/(mg/mL) between glucose concentrations of 0.5 mg/mL-1.5 mg/mL. Its sensitivity was 78 pm/(mg/mL). A two-sided WBG-based glucose measurement system was integrated into a photonic integrated interrogator for potential wearable and portable glucose measurement.
Funding
Tianjin Key Research and Development Program (19YFZCSY00180); Tianjin Science and Technology Program (20YDTPJC01380); National Natural Science Foundation of China (61177078, 61675154, 61711530652).
Acknowledgments
Hongqiang Li acknowledges the support from the Tianjin Talent Special Support Program. Joan Daniel Prades acknowledges the support from the Serra Hunter Program, the ICREA Academia Program and the Tianjin Distinguished University Professor Program.
Disclosures
The authors declare no conflicts of interest.
Data availability
Data underlying the results presented in this paper are not publicly available at this time but may be obtained from the authors upon reasonable request.
References
1. H. Yu, Y. Zhao, W. K. Ng, Y. Xue, K. S. Wong, and K. M. Lau, “Bufferless 1.5 µm III-V lasers grown on Si-photonics 220 nm silicon-on-insulator platforms,” Optica 7(2), 148–153 (2020). [CrossRef]
2. X. Wang, W. Shi, H. Yun, S. Grist, N. A. F. Jaeger, and L. Chrostowski, “Narrow-band waveguide Bragg gratings on SOI wafers with CMOS-compatible fabrication process,” Opt. Express 20(14), 15547–15558 (2012). [CrossRef]
3. Y. Hung, C. Tang, T. Chen, T. Yen, M. Tsai, and S. Lee, “Low-loss polysilicon subwavelength grating waveguides and narrowband Bragg reflectors in bulk CMOS,” Opt. Express 28(6), 7786–7798 (2020). [CrossRef]
4. Z. Chen, J. Flueckiger, X. Wang, F. Zhang, H. Yun, Z. Lu, M. Caverley, W. Yun, N. A. F. Jaeger, and L. Chrostowski, “Spiral Bragg grating waveguides for TM mode silicon photonics,” Opt. Express 23(19), 25295–25307 (2015). [CrossRef]
5. M. Burla, L. R. Cortés, M. Li, X. Wang, L. Chrostowski, and J. Azaña, “Integrated waveguide Bragg gratings for microwave photonics signal processing,” Opt. Express 21(21), 25120–25147 (2013). [CrossRef]
6. Y. Liu, A. Choudhary, D. Marpaung, and B. J. Eggleton, “Integrated microwave photonic filters,” Adv. Opt. Photonics 12(2), 485–555 (2020). [CrossRef]
7. T. Park, J. Shin, G. Huang, W. Chu, and M. Oh, “Tunable channel drop filters consisting of a tilted Bragg grating and a mode sorting polymer waveguide,” Opt. Express 24(6), 5709–5714 (2016). [CrossRef]
8. E. Simova and I. Golub, “Polarization splitter/combiner in high index contrast Bragg reflector waveguides,” Opt. Express 11(25), 3425–3430 (2003). [CrossRef]
9. J. Poulin and R. Kashyap, “Novel tuneable on-fiber polymeric phase-mask for fiber and planar waveguide Bragg grating fabrication,” Opt. Express 13(12), 4414–4419 (2005). [CrossRef]
10. K. Kim, J. Seo, and M. Oh, “Strain-induced tunable wavelength filters based on flexible polymer waveguide Bragg reflector,” Opt. Express 16(3), 1423–1430 (2008). [CrossRef]
11. P. Cheben, D.-X. Xu, S. Janz, and A. Densmore, “Subwavelength waveguide grating for mode conversion and light coupling in integrated optics,” Opt. Express 14(11), 4695–4702 (2006). [CrossRef]
12. N. P. Vishwaraj, C. T. Nataraj, R. P. K. Jagannath, P. Gurusiddappa, and S. Talabattula, “Chip-scale Temperature-compensated Superstructured Waveguide Bragg Grating Based Multiparametric Sensor,” Curr. Opt. Photon. 4(4), 293–301 (2020). [CrossRef]
13. K. Ogawa, N. Guan, K. Goi, K. Sakuma, Y. Tan, M. Yu, S. Teo, and G. Lo, “New design and analysis of Bragg grating waveguides,” Opt. Express 18(3), 2002–2009 (2010). [CrossRef]
14. G. Eerdekens, S. Rex, and D. Mesotten, “Accuracy of blood glucose measurement and blood glucose targets,” J. Diabetes Sci. Technol. 14(3), 553–559 (2020). [CrossRef]
15. K. J. Ward, D. M. Haaland, M. R. Robinson, and R. P. Eaton, “Post-Prandial blood glucose determination by quantitative Mid-Infrared spectroscopy,” J. Appl. Spectrosc. 46(6), 959–965 (1992). [CrossRef]
16. D. C. Klonoff, “Continuous glucose monitoring: roadmap for 21st century diabetes therapy,” Diabetes Care 28(5), 1231–1239 (2005). [CrossRef]
17. Q. Wan, G. L. Coté, and J. B. Dixon, “Dual-wavelength polarimetry for monitoring glucose in the presence of varying birefringence,” J. Biomed. Opt. 10(2), 024029 (2005). [CrossRef]
18. B. Rabinovitch, W. F. March, and R. L. Adams, “Noninvasive Glucose Monitoring of the Aqueous Humor of the Eye: Part I. Measurement of Very Small Optical Rotations,” Diabetes Care 5(3), 254–258 (1982). [CrossRef]
19. B. D. Cameron and G. L. Coté, “Noninvasive glucose sensing utilizing a digital closed-loop polarimetric approach,” IEEE Trans. Biomed. Eng. 44(12), 1221–1227 (1997). [CrossRef]
20. D. Qi and A. J. Berger, “Chemical concentration measurement in blood serum and urine samples using liquid-core optical fiber Raman spectroscopy,” Appl. Opt. 46(10), 1726–1734 (2007). [CrossRef]
21. R. J. McNichols and G. L. Cote, “Optical glucose sensing in biological fluids: an overview,” J. Biomed. Opt. 5(1), 5–16 (2000). [CrossRef]
22. O. S. Khalil, “Spectroscopic and Clinical Aspects of Noninvasive Glucose Measurements,” Clin. Chem. 45(2), 165–177 (1999). [CrossRef]
23. M. Yin, B. Huang, S. Gao, A. P. Zhang, and X. Ye, “Optical fiber LPG biosensor integrated microfluidic chip for ultrasensitive glucose detection,” Biomed. Opt. Express 7(5), 2067–2077 (2016). [CrossRef]
24. K. Maruo, T. Oota, M. Tsurugi, T. Nakagawa, H. Arimoto, M. Tamura, Y. Ozaki, and Y. Yamada, “New methodology to obtain a calibration model for noninvasive Near-Infrared blood glucose monitoring,” J. Appl. Spectrosc. 60(4), 441–449 (2006). [CrossRef]
25. G. Budinova, J. Salva, and K. Volka, “Application of molecular spectroscopy in the Mid-Infrared region to the determination of glucose and cholesterol in whole blood and in blood serum,” J. Appl. Spectrosc. 51(5), 631–635 (1997). [CrossRef]
26. Y. Zheng, X. Zhu, Z. Wang, Z. Hou, F. Gao, R. Nie, X. Cui, J. She, and B. Peng, “Noninvasive blood glucose detection using a miniature wearable Raman spectroscopy system,” Chin. Opt. Lett. 15(8), 083001 (2017). [CrossRef]
27. G. Freckmann, M. Link, and S. Pleus, “Measurement performance of two continuous tissue glucose monitoring systems intended for replacement of blood glucose monitoring,” Diabetes Technol. Ther. 20(8), 541–549 (2018). [CrossRef]
28. L. H. Lin, “Optical detection of glucose concentration in samples with scattering particles,” Appl. Opt. 54(35), 10425–10431 (2015). [CrossRef]
