NonInvasive Glucose Fiber Sensor Based on Self-Imaging Technique: Proof of Concept

. This paper proposes a proof of concept for a reflective fiber optic sensor based on multimode interference, designed to measure glucose concentrations in aqueous solutions that mimic the range of glucose concentrations found in human saliva. The sensor is fabricated by splicing a short section of coreless silica fiber into a standard single-mode fiber. By studying the principles of multimode interference and Self-imaging it was developed a sensing head that has a total length of 29.1 mm , approximately equal to the second self-image cycle. This sensing head allowed us to detect low concentrations of glucose (ranging from 0 to 268 mg/dl ).


Introduction
Diabetes is a chronic disease that occurs when the human body is unable to effectively use the insulin it produces [1].Monitoring glucose levels is critical not only for prevention but also for assessing the progression of the disease.Glucose monitoring can be mainly divided into noninvasive and invasive methods, depending on whether any part of a sensor system is inserted into the body.Noninvasive methods may include measurements in sweat, saliva, or urine, while invasive methods require the insertion of a device under the skin.Therefore, noninvasive methods can be seen as more user-friendly and stress-free.Different studies have shown a significant correlation between glucose levels in blood and saliva in both normal and diabetic subjects meaning that salivary glucose levels can be used as an index to monitor diseases such as diabetes [2].In recent decades, optical fiber sensors (OFS) have arisen as a promising option for glucose measurements due to their simplicity, low cost, compact size, high sensitivity, and proficiency.Several reports of successful glucose measurements using MMIbased sensors have been presented in the research and development community [3].This paper proposes an experimental study on a no-core fiber (NCF) tip reflective sensor with a 125 µm diameter, based on MMI and the self-image phenomenon, and the potential of this type of sensor for the detection of glucose levels in saliva, as a noninvasive method is demonstrated.

Fundamentals of Sensor Design and Operation
The sensor design consists of an NCF section with a 125 µm diameter and length of 29.1 mm spliced into a singlemode fiber (SMF) section, as illustrated in Figure 1.When the light is coupled from the input SMF into the NCF different modes with different propagation constants are excited leading to an interference pattern.The modes interfere constructively and destructively leading to the formation of self-image points.These self-image points occur periodically in the NCF, and their position can be determined by the following equation [4]: Where  is the self-image index,   is the NCF refractive index (RI),   is the NCF diameter and  0 is the interference wavelength.To achieve a self-image the length of the NCF (Lncf) needs to be precise since a small variation in the scale of microns can be enough to lose the self-image point.The self-image point studied in the sensor corresponded to  = 2, making   = 29.1 mm (  = 1.4444,   = 125 µ,  0 = 1.55 µ).The experimental setup, presented in Figure 2, was utilized for glucose measurements and temperature experiments using a reflection scheme.The setup comprises a broadband optical source (1520-1620 nm), a sensing head, and an optical spectrum analyzer (OSA) connected to an optical circulator.To maintain stability and avoid sample tube contact, the sensing head was placed in a capillary tube.A lifting platform was used for vertical movement, enabling immersion of the static sensing head in glucose solutions.

Results
The glucose aqueous solutions ranged from 0-268 mg/dl and were prepared in a controlled laboratory environment at room temperature (∼21 °C).The sensing probe was immersed in the solutions and the optical spectra were obtained with the OSA. Figure 3 shows the resulting spectra for the different concentrations of glucose aqueous solutions.The analysis of the spectra shows that the sensor is sensitive in intensity and in wavelength.As the glucose concentrations increase, it leads to a decrease in the optical power causing a red shift; this is due to the increase of the RI surrounding the NCF and the increase in the spectral absorption of light in the liquid.Since the optical power is low and it also considers the optical source fluctuations, the analysis presented is only regarding the wavelength shifts.Figure 4 shows the fitting curve for the resonant wavelength peaks under the different solutions.It can be concluded that it follows a linear relationship with R 2 =0.98 and a sensitivity of 1.31 pm/(mg/dl).The response to temperature was measured by placing the sensing probe inside the water bath whose temperature was around 40 ºC.The study range was between 22-35 ºC since it's a typical range in which glucose in the saliva is measured.Figure 5 shows the response of the sensor to the temperature.It can be concluded that the sensor has a residual sensitivity to this range of temperature that can be solved when the sensor is measured by a photodetector.

Conclusion
In conclusion, it can be observed that the NCF tip is sensitive to various glucose concentrations within the physiological range of salivary glucose.However, its sensitivity is still low, nevertheless, this study serves as a proof of concept.Due to the complexity of saliva components, it is crucial to enhance the sensitivity and specificity of the sensor.The first objective is to functionalize the sensor to improve its performance.To achieve this, the coreless section will be coated with graphene oxide, followed by the deposition of glucose oxidase enzyme.This process is expected to enhance the sensor's sensitivity and enable it to specifically detect glucose in saliva.To further improve the sensor's performance, it may be necessary to conduct more elaborate experiments, such as optimizing the concentration of the coating materials or the enzyme loading, and testing the sensor's response to various concentrations of glucose in saliva.By refining the sensor's design and performance, we can unlock its full potential for noninvasive glucose monitoring, which can greatly benefit individuals with diabetes or other conditions requiring frequent glucose monitoring.

Fig. 1 .
Fig. 1.Schematic of the sensor head design, where Lncf is the length of the NCF section.

Fig. 2 .
Fig. 2. Schematic diagram of the experimental setup (image not to scale).

Fig. 3 .
Fig. 3. Output spectra of the sensor under different glucose concentrations.