Blood Glucose Sensors

The accurate measurement of blood glucose is essential in the diagnosis and long term management of diabetes. In this article, we discuss the use of biosensors for the continuous measurement of glucose levels in the blood and other body fluids.

Glucose is the main circulating carbohydrate in the body. In normal individuals, the concentration of glucose in blood is very tightly regulated – usually between 80 – 90 mg/100 ml during the first hour or so following a meal. The hormone insulin which is normally produced by beta cells in the pancreas, promotes the glucose transport in the skeletal muscle and adipose tissue. In those suffering from diabetes mellitus, insulin-regulated uptake is compromised, and blood glucose can reach concentrations ranging from 300 to 700 mg/100 ml (hyperglycemia).

The accurate determination of glucose levels in body fluids such as blood, urine and cerebrospinal fluid, is a major aid in diagnosing diabetes and improving the treatment of this disease.

The various measurement methods/sensors employed in measurement of blood glucose are:

• Glucose Oxidase Method
• Electroenzymatic Approach
• Optical Approach
• Attenuated Total Reflection (ATR) & Infrared Absorption Spectroscopy

Glucose Oxidase Method

This method is used in a large number of commonly available simple test strip meters and allows quick and easy blood glucose measurements.

 For example a test strip meter depends on the glucose oxidase-peroxidase chromogenic reactions. After a drop of blood is combined with reagents on the test strip, the following reaction occurs:                              

Adding the enzymes peroxidase and o-dianiside, a chromogenic oxygen, results in the formation of a colored compound that can be evaluated visually.

The glucose oxidase chemistry in conjunction with reflectance photometry produces a system for monitoring blood glucose levels.

Electroenzymatic Approach

The Electroenzymatic Sensors based on polarographic principles utilize the phenomenon of glucose oxidation with a glucose enzyme. The chemical reaction of glucose with oxygen is catalyzed in the presence of glucose oxidase. This causes a decrease in the partial pressure of oxygen (Po₂) and an in increase in pH, and the production of hydrogen peroxide by the oxidation of glucose to Gluconic acid according to the equation:

All the changes, in all of these chemical components are measured in order to determine the concentration of glucose.

The basic glucose enzyme electrode utilizes a glucose oxidase enzyme immobilized on a membrane or a gel matrix and oxygen-sensitive polarographic electrode. The changes in oxygen concentration at the electrode, which are due to the catalytic reaction of glucose and oxygen can be measured either potentiometrically or amperometrically.

The major problem with enzymatic glucose sensors is the instability of the immobilized enzyme and the fouling of the membrane surface under physiological conditions. Most glucose sensors operate effectively only for short periods of time.

Optical Approach

We have several, innovative glucose sensors that are based on different optical techniques that have been developed. One of them is the fluorescence-based affinity sensor that has been designed for monitoring the various metabolites especially glucose in the blood plasma. The method is based on the immobilized competitive binding of a particular metabolite and fluorescein-labelled indicator with receptor sites specific for the measured metabolite and the labelled ligand (the molecule that binds).

The figure below shows an affinity sensor in which the immobilized reagent is coated on the inner wall of a glucose-permeable hollow fiber fastened to the end of an optical fiber.

The Affinity sensor measures glucose concentration by detecting the changes in fluorescent light intensity caused by competitive binding of a fluorescent labelled indicator.

The fiber-optic catheter is used to detect the changes in fluorescent light intensity which is related to the concentration of glucose.

The advantage of this approach is that it has the potential for miniaturization and for implantation through a needle. Besides, no electric connections to the body are necessary.

The major problems that comes with this approach are the lack of long-term stability of the reagent; the slow response time of the sensor, and the dependence of the measured  light intensity on the amount of reagent, which is usually very small and may change over time.

Related: Biomedical sensors

Attenuated Total Reflection (ATR) & Infrared Absorption Spectroscopy

The application of multiple infrared (ATR) spectroscopy to biological media is another potentially appealing non-invasive technique. By this means, the infrared spectra of blood can be recorded from tissue independently of the sample of thickness, whereas other optical-transmission techniques are strongly dependent on the optical-transmission properties of the medium. Additionally, employing a laser light source makes possible considerable improvement of the measuring sensitivity, especially when measuring the transmission of the light in aqueous solution, because it counteracts the intrinsic attenuation of water, which is high in most wavelength ranges.

Absorption spectroscopy in the infrared (IR) region is an important technique for the identification of unknown biological substances in aqueous solutions. Because of vibrational and rotational oscillations of the molecule, each molecule has specific resonance absorption peaks, which are known as fingerprints. These spectra are not uniquely identified; rather, the IR absorption peaks of biological molecules often overlap.

The absorption-peak magnitude is directly related to the glucose concentration in the sample; and its spectral position is within the wavelength range emitted by a CO₂ laser. Thus a CO₂ laser can be used as a source of energy to excite this bond; and the IR absorption intensity at this peak provides via Beer’s law a quantitative measure of the glucose concentration in a sample.