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Near infrared spectroscopy (NIR) is a promising technique for continuous blood glucose monitoring for diabetic patients. Four interferents, at physiological concentrations, were introduced to study how the glucose predictions varied with a standard multivariate calibration model. Lactate and ethanol were found to interfere strongly with the glucose predictions unless theywere included in the calibration models. Lactate was mistaken for glucose and gave erroneously high glucose predictions, with a dose response of 0.46 mM/mM. The presence of ethanol resulted in too low glucose predictions, with a dose response of -0.43 mM/mM. Acetaminophen (APAP), a known interferent in the glucose monitoring devices used for diabetes management today, was not found to be an interferent in NIR spectroscopy, nor was caffeine. Thus, interferents that may appear in high concentrations, such as ethanol and lactate, must be included in the calibration or model building of future NIR-based glucose measurement devices for diabetes monitoring. © 2021 The Authors. Journal of Biophotonics published by Wiley‐VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

We present the fabrication and characterization of optical fiber reflection probes based on surface-enhanced Raman scattering (SERS) and micro-lensed multimode fibers. For the SERS substrate, a nano-sphere lithography method is used. Comparison of SERS measurements with three different fiber probe configurations is presented. The proposed optimized structure shows a five times increase in SERS signal for dried Rhodamine 6G (R6G) and two times for aqueous R6G in comparison to a standard reflection configuration. Measurements of different concentrations of R6G in a water solution with an limit of detection (LOD) equal to 10 -7 M are demonstrated. This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see http://creativecommons.org/licenses/by/4.0/

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.

Diabetes mellitus 1 requires tight control of the blood glucose levels to avoid harmful effects of either too high (hyperglycemia) or too low (hypoglycemia) blood sugar. Due to the availability of low-cost components, fiber- coupled near infrared (NIR) absorption spectroscopy could be a feasible measurement method. From the molar absorptivity of glucose, it is shown that to achieve high accuracy using near infrared spectroscopy for glucose sensing, relative noise levels should not exceed 0:003 %. Two supercontinuum (SC) sources and one broadband lamp were investigated with a low-cost portable spectrometer. The SNR of the two SC sources was limited by amplitude fluctuations and could be improved by averaging. The SNR of the broadband source was found to be largely limited by the detector noise due to the weak intensity. 16 aqueous glucose samples ranging from 0 to 500mm were measured with the broadband source and an SC laser. A partial least squares regression (PLSR) model was built for both measurement sets, yielding root mean square errors of 49 and 54mm, illustrating how the limit of detection is restrained by the high relative intensity noise. A reference arm setup was built and could account for much of the variability of the SC source. A glucose measurement series using this setup and five samples (100 to 500mm) yielded a root mean square error of 10:6mm. The results indicate that an SC source can be feasible for absorption spectroscopy in a reference arm setup. © 2019 Society of Photo Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.

In classical approaches for an artificial pancreas, continuous glucose monitoring (CGM) is the only measured variable used for insulin dosing and additional control functions. The CGM values are subject to time delays and slow dynamics between blood and the sensing location. These time lags compromise the controller’s performance in maintaining (near to) normal glucose levels. Meal information could enhance the control outcome. However, meal announcement by the user is not reliable, and it takes 30 min to 40 min from meal onset until a meal is detected by methods based on CGM. In this pilot study, the use of bowel sounds for meal detection was investigated. In particular, we focused on whether bowel sounds change qualitatively during or shortly after meal ingestion. After fasting for at least 4 h, 11 healthy volunteers ingested a lunch meal at their usual time. Abdominal sound was recorded by a condenser microphone that was attached to the right upper quadrant of the abdomen by medical tape. Features that describe the power distribution over the frequency spectrum were extracted and used for classification by support vector machines. These classifiers were trained in a leave-one-out cross-validation scheme. Meals could be detected on average 10 min (std: 4.4 min) after they had started. Half of these were detected without false alarms. This shows that abdominal sound monitoring could provide an early meal detection. Further studies should investigate this possibility on a larger population in more general settings., Spectrogram of a recording in the training set. Windows with a length of 20 s and overlap of 10 s were analyzed using spectrogram function in MATLAB. The meal started at minute 51.

In patients with diabetes mellitus type 1, the pancreatic insulin production ceases, causing raise in blood glucose level (BGL) and potentially severe long-term complications. The "holy grail" of diabetes treatment is the artificial pancreas (AP), a closed-loop control system that regulates the user’s BGL by infusing insulin, and possibly glucagon. Numerous attempts have been largely unsuccessful, mainly due to slow dynamics that make it difficult to avoid unwanted BGL excursions. System performance has been improved through improved sensor technology and faster-acting insulin types, but the risk of hypoglycemia is still significant unless the glucose setpoint is unnaturally high. We argue that this problem can be circumvented by choosing appropriate sites for glucose measurement and insulin infusion. While intravascular measurement and infusion provides the fastest dynamics and thus the best conditions for closed-loop control, it is only viable in inpatients mainly due to danger of infections and limited sensor durability. On the other extreme, state-of-the-art subcutaneous systems exhibit significant time delays and diffusion dynamics, yielding poor BGL control in the event of disturbances like meals and physical activity. Avoiding dangerous hypoglycemia therefore comes at the expense of daily episodes of elevated BGL (typically 10-15 mmol/L) that increase the risk of long-term complications. Furthermore, slow insulin uptake from subcutis remains as a major challenge. Hence we advocate the double intraperitoneal (IP) AP. Here, insulin is released into the abdominal cavity (peritoneum) through a semi-permanent port, which also allows access for IP glucose sensing. This improves both sensing and absorption dynamics. Thus the closed-loop control may be significantly tighter, allowing a setpoint closer to the healthy normal BGL of approximately 4.5 mmol/L whilst potentially improving system safety. These statements are supported by results from our own research and the literature.

Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC) glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP) sensor sites, as an alternative to the SC location. Intraarterial (IA) and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70--360 mg/dL (approximately 3.8--20 mmol/L). Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA) to IP sensor location was found to be in the range 0--26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s), and the time constant was found to be 0.5--10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min). IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

The artificial pancreas requires fast and reliable glucose measurements. The peritoneal space has shown promising results, and in one of our studies we detected glucose changes in the peritoneal space already at the same time as in the femoral artery. The peritoneal lining is highly vascularised, covered by a single layer of mesothelial cells and therefore easily accessible for proper sensor technology, e.g. optical technology. We hypothesize that the rapid intraperitoneal glucose dynamics observed in our study was possible because the sensors were located directly at the peritoneal lining, at the point where the glucose molecules entered the peritoneal space. Glucose travels slowly in fluids by diffusion, and a longer distance between the sensor and the peritoneal lining would consequently result in slower dynamics. We therefore propose to place the glucose sensor in an artificial pancreas as closely to the peritoneal lining as possible, or even utilize appropriate sensor technology to measure glucose in the peritoneal lining itself.

Closed-loop glucose control has the potential to improve the glycemic control in patients with diabetes mellitus type 1. Such an artificial pancreas (AP) should keep the user safe despite all disturbances and faults. The objective of this paper is to analyze those perturbations according to their effects on the glycemic status, and thereby supporting an informed design process of the control system. As suggested by the international standard ISO 14971 for risk management of medical devices, the well proven failure modes and effects analysis (FMEA) was chosen as instrument. An FMEA scheme was modified for this purpose and applied to a single-hormone system with subcutaneous and intraperitoneal routes for glucose sensing and insulin administration. Faults that imply urgent danger and thus require fast detection and diagnosis were identified and distinguished from disturbances that can be sufficiently addressed by basic control functions, e.g. by adaptive control algorithms. Requirements and testing criteria for basic control functions as well as fault detection and diagnosis functions can be derived from the provided overview.

A novel ball-lensed fiber transmission sensor is presented aimed at in vivo continuous glucose monitoring of diabetics. Preliminary results yield 20 mM RMSE, limited by mechanical instability. The design enables flexibility and further miniaturization. © 2018 The Author(s). One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibited.

We demonstrate a multimode optical fiber sensor for spectroscopic Raman measurements of glucose concentration for the application in intraperitoneal glucose detection in diabetic patients. A regression model with a RMSEC of 2.2 mM was obtained. © [2018] Optical Society of America]. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modifications of the content of this paper are prohibited.

Introduction Patients with diabetes type 1 (DM1) struggle daily to achieve good glucose control. The last decade has seen a rush of research groups working towards an artificial pancreas (AP) through the application of a double subcutaneous approach, i.e., subcutaneous (SC) continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion. Few have focused on the fundamental limitations of this approach, especially regarding outcome measures beyond time in range. Methods Based on insulin physiology, the limitations of CGM, SC insulin absorption, meal challenge, and physical activity in DM1 patients, we discuss the limitations of the double SC approach. Finally, we discuss safety measures and the achievements reported in some recent AP studies that have utilized the double SC approach. Results Most studies show that a double SC AP increases the time in range compared to a sensor-augmented insulin pump and shortens the time in hypoglycemia. Despite these achievements, the proportion of time spent in hyperglycemia is still roughly 20–40%, and hypoglycemia is still present 1–4% of the time. The main factors limiting further progress are the latency of SC CGM (at least 5–10 min) and the slow pharmacokinetics of SC-delivered fast-acting insulin. The maximum blood insulin level is reached after 45 min and the maximum glucose-lowering effect is observed after 1.5–2 h, while the glucose-lowering effect lasts for at least 5 h. Conclusions Although using a double SC AP leads to significant improvements in glucose control, the SC approach has severe limitations that hamper further progress towards a robust AP. © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/)

The bulkiness of common transmission spectroscopy probes prevents applicability at remote locations such as within the body. We present the fabrication and characterization of lensed fibers for transmission spectroscopy in the near-infrared. Eigenmode simulations and measurements of the coupling efficiency are presented and applied to design the setup corresponding to the sample absorption. Sensing capabilities are demonstrated on aqueous glucose samples ranged 80 to 500 mM, obtaining a mean absolute percentage error of calibration of 4.3%. With increased flexibility, transmission spectroscopic sensors at remote locations may be achievable, for example, applied to in vivo continuous glucose monitoring.

Semiconductor laser injection locking transients are analyzed. By adiabatically eliminating the carrier dynamics, a single nonlinear stochastic differential equation is obtained for the relative phase between the master and slave lasors. The corresponding Fokker-Planck equation is used to study the steady-state locked conditions as well as phase transients of the locking process. Noise causes the steady-state relative phase between the master and the slave lasers to be a random variable with a standard deviation of approximately a few degrees for typical injection levels. The standard deviation can be reduced by using a phase detector with a limited bandwidth. The mean locking time in the presence of noise is slightly less than the deterministic prediction. Noise also causes the locked lasers to have a finite probability to momentarily unlock. >

The mode hopping dynamics of a two-mode laser are investigated through numerical simulations. The authors derive an algorithm, based on autocorrelation techniques, by which the average mode hopping rate can be estimated from time sequences of the numbers of photons of the two modes. The method works both for symmetric and asymmetric gain conditions. The results show that the average mode hopping rate decreases with increasing asymmetry in the gain coefficients of the two modes. These results are in agreement with what one would expect from physical considerations. In the case of symmetric gain conditions, the results are compared to theoretically derived formulas, showing reasonable agreement in current dependence and in the dependence on the gain saturation coefficients. >