Investigation of the effect of clinically relevant interferents on glucose monitoring using near‐infrared spectroscopy

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

Feasibility of early meal detection based on abdominal sound.

Background 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. Methods 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. Results Meals could be detected on average after less than 10 min with the best parameter choice. Conclusion 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

Glucose sensing by absorption spectroscopy using lensed optical fibers

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

Feasibility of supercontinuum sources for use in glucose sensing by absorption spectroscopy

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

Optimization of SERS Sensing With Micro-Lensed Optical Fibers and Au Nano-Film

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

The Artificial Pancreas: A Dynamic Challenge

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

Risk Analysis for the Design of a Safe Artificial Pancreas Control System

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 Review of Optical Methods for Continuous Glucose Monitoring

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

A miniaturized ball-lensed fiber optic NIR transmission spectroscopy-based glucose sensor

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