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"The main reason for developing in vivo glucose sensors is for the detection of hypoglycemia in diabetes. Patients with insulin dependent (type 1) diabetes have always feared low blood glucose concentrations, especially during the night, when self monitoring of blood glucose concentration with finger prick methods cannot be performed, and those without warning symptoms (hypoglycemia unawareness) are especially vulnerable. But automatic hypoglycemia detection has become a
major goal for glucose sensing research since it became clear that strict blood glucose control is usually accompanied by a clearly increased frequency of hypoglycaemia. It is simply very difficult indeed to achieve and maintain near normal glycemia in people with type 1 diabetes without incurring the penalty of potentially dangerous low blood glucose concentrations. One example of the major clinical benefit of hypoglycemia detection with an implantable glucose sensor can be seen by studies that have shown that falls in tissue concentrations of glucose (measured by a sensor) often precedes the fall in blood glucose and may act as an early warning to the patient of impending hypoglycaemia.
The notion that an in vivo glucose sensor might be coupled via a computer to a portable insulin infusion pump to create an artificial endocrine pancreas controlled by feedback is appealing, of course. Indeed, a glucose sensor is a prerequisite for a totally implantable artificial pancreas but such systems have been put to one side for the moment as an ambition for routine management. Safe delivery of insulin in this way will require glucose sensors that have proved totally reliable after many years of ¡§open loop¡¨ testing
". 1  Below is a picture of typical light detection of glucose.

There are three main issues in non-invasive (NI) glucose measurements: namely, specificity,
compartmentalization of glucose values, and calibration. There has been progress in the use of
near-infrared and mid-infrared spectroscopy. Recently new glucose measurement methods have
been developed, exploiting the effect of glucose on erythrocyte scattering, new photo-acoustic
phenomenon, optical coherence tomography, thermo-optical studies on human skin, Raman
spectroscopy studies, fluorescence measurements, and use of photonic crystals. In addition to
optical methods, in vivo electrical impedance results have been reported. Some of these methods
measure intrinsic properties of glucose; others deal with its effect on tissue or blood properties.
Recent studies on skin from individuals with diabetes and its response to stimuli, skin
thermo-optical response, peripheral blood flow, and red blood cell rheology in diabetes shed
new light on physical and physiological changes resulting from the disease that can affect NI
glucose measurements. There have been advances in understanding compartmentalization of
glucose values by targeting certain regions of human tissue. Calibration of NI measurements
and devices is still an open question. More studies are needed to understand the specific glucose
signals and signals that are due to the effect of glucose on blood and tissue properties. These
studies should be performed under normal physiological conditions and in the presence of other
co-morbidities.2 A sample device used is shown in the diagram below.


Raman Spectroscopy is a recent advancement in the optical detection of glucose. It is a spectroscopic technique used in condensed matter physics and chemistry to study vibrational, rotational, and other low-frequency modes in a system. It relies on inelastic scattering, or Raman scattering of monochromatic light, usually from a laser in the visible, near infrared, or near ultraviolet range. Photons or other excitations in the system are absorbed or emitted by the laser light, resulting in the energy of the laser photons being shifted up or down. The shift in energy gives information about the phonon modes in the system. Infrared spectroscopy yields similar, but complementary information.

Typically, a sample is illuminated with a laser beam. Light from the illuminated spot is collected with a lens and sent through a monochromator. Wavelengths close to the laser line (due to elastic Rayleigh scattering) are filtered out and those in a certain spectral window away from the laser line are dispersed onto a detector.Image:Raman energy levels.jpg

Spontaneous Raman scattering is typically very weak, and as a result the main difficulty of Raman spectroscopy is separating the weak non-elastically scattered light from the intense Rayleigh scattered laser light. Raman spectrometers typically use holographic diffraction gratings and multiple dispersion stages to achieve a high degree of laser rejection. A photon-counting photomultiplier tube (PMT) or, more commonly, a CCD camera is used to detect the Raman scattered light.3

The conventional Raman techniques for detection of body level constituents are generally associated with long exposure time (several ten minutes), high power laser pump fluency which is much above the safety limitation of the laser illumination for human body applications, and strong noise background. Conventional Raman is too weak to determine analyte (glucose) level in humans due to the background.

In order to apply Raman spectroscopy to achieve high sensitivity for glucose level detection for diabetes diagnosis, and other body level analyte detection in blood, we have investigated fingerprint Raman modes for glucose and other Raman-active blood analytes using a novel approach. A method called low power cw excitation raman spectroscopy as well as difference Raman spectroscopy were developed to find the body level glucose and enable a glucose fingerprint to be formed. Currently the figure to the right shows various viable "fingerprints" that can used. The figure below was obtained via a human fingertip. Thus showing the possibility of obtaining non-invasive blood glucose optically.3


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[1]L. Heinemann1, G. Schmelzeisen-Redeker "Non-invasive continuous glucose monitoring in Type I diabetic patients with optical glucose sensors"  Non-invasive task force (NITF) 1 Department of Metabolic Diseases and Nutrition, Heinrich-Heine-University Düsseldorf, Germany

[2]OMAR S. KHALIL, Ph.D. "Non-Invasive Glucose Measurement Technologies: AnUpdate from 1999 to the Dawn of the New Millennium" DIABETES TECHNOLOGY & THERAPEUTICS Volume 6, Number 5, 2004

[3]R. R. Alfano, "Detection of Glucose Levels Using Excitation and Difference Raman Spectroscopy at the IUSL"