A dual modulation optical polarimetry system utilizing both laser intensity and polarization modulation was designed, built, and tested. The system was designed to reduce complexity and enhance the speed in order to facilitate the reduction of motion-induced time-varying birefringence, which is one of the major limitations to the realization of polarimetry for glucose monitoring in the eye. The high-speed less complex technique was tested using in vitro phantom studies with and without motion artifact introduced. The glucose concentration ranged from 0 to 600 mg/dl and the glucose measurements demonstrated a standard error of prediction to within 8.1 mg/dl without motion and to within 13.9 mg/dl with motion. Our feedback control systems took less than 10 ms to reach stabilization, which is adequately fast to eliminate the effect of time-varying birefringence. The results indicate that this new optical polarimetric approach has improved the speed and reduced the complexity, showing the potential for it to be used for noninvasive glucose measurements.
Optical polarimetry is a promising noninvasive means of assessing glucose concentration in the aqueous humor of the eye. One the major limiting factors is time-varying cornea birefringence due to motion artifact, which prevents the realization of this device. In this study, we simultaneously utilize laser intensity modulation and Faraday polarization rotation modulation for a real-time closed-loop multi-spectral polarimeter for glucose monitoring in vitro. In this report, a real-time closed-loop dual-modulation dual-spectral polarimeter was presented and in vitro glucose measurements were performed demonstrating the accuracy and repeatability of this polarimeter.
Optical polarimetry in the anterior chamber of the eye has emerged as a potential technique to non-invasively measure glucose levels for diabetes. Time varying corneal birefringence due to eye motion artifact confounds the optical signal ultimately limiting the polarimetric technique from accurately predicting glucose concentrations. In this study, a high speed dual-wavelength optical polarimetric approach was developed and in vitro phantom studies were performed with and without motion. The glucose concentrations ranged from 0-600 mg/dL at 100 mg/dL increments. The polarimeter produced glucose measurements with less than a 10 msec stabilization time and yielding standard errors of less than 10 mg/dL without motion and standard errors less than 26 mg/dL with motion. The results indicate a high speed dual-wavelength polarimetric approach has the potential to be used for non-invasive glucose measurements.
Millions of people worldwide are affected by diabetes. While glucose sensing technology has come a long way over the past several decades, the current commercially available techniques are still invasive, often leading to poor patient compliance. To minimize invasiveness, focus has been placed on optical techniques to ascertain blood glucose concentrations. Optical polarimetry has shown promise and progress as a viable technique for glucose sensing. Recent developments in polarimetric glucose sensing have been focused on overcoming time varying corneal birefringence due to motion artifacts. Beyond corneal birefringence, the next hurdle toward making this approach viable is the ability to couple polarized light across the eye’s anterior chamber. The eye is ideally suited to couple light to the retina. The index mismatch between the air and cornea is partially responsible for the beam bending toward the retina and, while good for vision, it complicates our ability to couple light across the anterior chamber without using an index matching device when performing polarimetric glucose monitoring. In this report, we have designed and modeled a non-index matched coupling scheme constructed with commercially available optics. The optical ray tracing model was performed using CODE V to verify the feasibility of a reflective based non-index matched coupling scheme with respect to index of refraction and anatomical restraints. The ray tracing model was developed for a dual-wavelength system and the effect of refraction and reflection at each optical interface within the setup was evaluated. The modeling results indicate a reflective based optical coupling design could be added to existing polarimetric glucose systems thus removing the need for placing an index matched eye-coupling mechanism over the eye prior to data collection.
Optical polarimetry as a method to monitor glucose levels in the aqueous humor has shown promise as a way
to noninvasively ascertain blood glucose concentration. A major limiting factor to polarimetric approaches for
glucose monitoring in the aqueous humor is time varying birefringence due to motion artifact. Here, we present a
modulation approach for real-time polarimetry that is capable of glucose monitoring in vitro at optical modulation
frequencies of tens of kHz and includes the DC-compensation in a single device. Such higher frequency modulation
has the potential benefit of improving the signal-to-noise ratio of the system in the presence of motion artifacts. In
this report we present a near real-time closed-loop single wavelength polarimeter capable of glucose sensing in vitro
at an optical modulation frequency of 32 kHz. The single wavelength polarimetric setup and in vitro glucose
measurements will be presented demonstrating the sensitivity and accuracy of the system. Our PID control system
can reach stability in less than 10 ms which is fast enough to overcome motion artifact due to heart beat and
respiration. The the system can predict the glucose concentration with a standard error of less than 18.5 mg/dL and a
MARD of less than 6.65% over the physiologic glucose range of 0-600 mg/dL. Our results indicate that this optical
modulation approach coupled with dual-wavelength polarimetry has the potential to improve the of the dual-wavelength
approach for in vivo glucose detection applications.
Noninvasive glucose monitoring is being investigated as a tool for effectively managing diabetes mellitus. Optical polarimetry has emerged as one such method, which can potentially be used to ascertain blood glucose levels by measuring the aqueous humor glucose levels in the anterior chamber of the eye. The key limitation for realizing this technique is the presence of sample noise due to corneal birefringence, which in the presence of motion artifact can confound the glucose signature in the aqueous humor of the eye. We present the development and characterization of a real-time, closed-loop, dual-wavelength polarimetric system for glucose monitoring using both a custom-built plastic eye phantom (in vitro) and isolated rabbit corneas (ex vivo) mounted in an artificial anterior chamber. The results show that the system can account for these noise sources and can monitor physiologic glucose levels accurately for a limited range of motion-induced birefringence. Using the dual-wavelength system in vitro and ex vivo, standard errors were 14.5 mg/dL and 22.4 mg/dL, respectively, in the presence of birefringence with motion. The results indicate that although dual-wavelength polarimetry has a limited range of compensation for motion-induced birefringence, when aligned correctly, it can minimize the effect of time-varying corneal birefringence for a range of motion larger than what has been reported in vivo.
The application of optical polarimetry to glucose sensing in the anterior chamber of the eye has emerged as a
potential technique to noninvasively ascertain blood glucose levels. One of the major limiting factors preventing the
realization of such a device is the time varying corneal birefringence due to motion artifact in the eye. The varying
birefringence confounds the optical activity of glucose, and thus, needs to be taken into account in order to successfully
predict the glucose concentration in the aqueous humor of the eye. Our group has developed a multi-spectral optical
polarimetric approach which can minimize the effect of corneal birefringence coupled with motion artifact by treating it
as common mode noise to multiple wavelengths. Here, we present the application of a real-time closed-loop dual
wavelength polarimeter to ex vivo glucose sensing in excised New Zealand White rabbits' corneas mounted on an
artificial anterior chamber. Our PID control system can reach stability in less than 100 ms which is fast enough to
overcome motion artifact due to heart beat and respiration. The system can predict the glucose concentration with a
standard error of less than 26 mg/dL in the physiologic glucose range of 0 - 500 mg/dL. Our results indicate that dualwavelength
polarimetry has the potential to noninvasively probe glucose through the anterior chamber of the eye.
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