Technical Field

The invention refers to medical equipment, in particular, to optical device development for non-invasive determination of glucose concentration in human organism and it can be applied in medical equipment industry. The glucose concentration determination in human by non-invasive method is very important for diabetes patients, as well as in tissue engineering to control cells evolution.

Background Art

A variety of devices for non-invasive determination of glucose concentration are known, based on the principle of Raman [1], infrared [2, 3], fluorescent [1, 2] light spectroscopies, as well as polarimetric [4-6] and optical coherence tomography (OCT) [7, 8].

The devices for determination of glucose concentration in blood are known, based on the phenomenon of optical rotatory dispersion (ORD), whereby a chiral molecule in an aqueous solution will rotate the plane of linearly polarized light passing through the solution [1 , 4, 5]. The angle of rotation depends linearly on the concentration of the chiral molecules, the pathlength through the sample, and a constant for the molecule that is called the specific rotation. The net rotation in degrees is expressed as [4]

<P = axLC, (1) where αχ is the specific rotation for the species at wavelength λ, L is the pathlength, and C is the concentration. The specific rotation for any wavelength can be determined based on two wavelength measurements in the spectral range free of absorption bands of a given chiral molecule using the expression [5]: ax = o/(X ² - h ⁱ ) , (2) where the constants ko and λο are computed by determining the specific rotation at two different wavelengths. The specific rotation of a particular chiral molecule depends also on the pH and temperature of the medium. At a fixed pH and temperature, this equation allows for separate evaluation of the contribution of the particular analyte (glucose) on the background of the other analytes if multispectral measurements and the corresponding regression model are provided [5]. However, in the common physiological measurements the monochromatic beam polarization vector rotation (equal to 10 ^"3 deg) is about 40 times smaller compared to estimated limit of rotated tissue. Therefore, using a polarization sensitive optical technique makes it difficult to measure in vivo glucose concentration in blood through the skin because of the strong light scattering which causes light depolarization. A tissue thickness of 4mm is sufficient to prompt about 95% depolarization [9]. For this reason, devices have been suggested, by .means of which the glucose concentration in human is determined by method of polarization change of monochromatic beam reflected from an eye [1, 4-6, 9]. These devices functioning is based on the physical phenomena that polarization of monochromatic beam reflected from the eye is changed to the incident beam polarization, as well as, that a high correlation exists between the glucose in the blood and in the aqueous humor. On average the glucose concentration in the aqueous humor is about 70% of that of blood. There is a time-delay in the range of 20-30 min between glucose concentrations in blood vessel walls and aqueous humor [10, 11].

There are several devices, based on registration of polarization change of monochromatic beam, reflected from the eye. Mainly these devices are based on optical systems, where polarization change is registered by means of crossed analyzer-polarizer [4]. In the given device the input beam phase modulation phenomenon is used, which is realized by electrooptical modulator. The use of electrooptical modulator leads to additional error in determination of polarization vector rotation angle.

The device for glucose concentration measurement in human by non-invasive method, the operating principle of which is determination of polarization state of monochromatic beam reflected from the eye, is chosen as the closest prototype [12].

There is an optical system in this device, consisting of polarizer, investigated sample and analyzer crossed with polarizer. In the system the phase of linearly polarized monochromatic beam is preliminarily modulated and, passing through the eye, acquires an additional phase shift, corresponding to the glucose concentration in eye. The glucose concentration in human is determined by measuring the beam intensity, using a photo receiver placed at the output of analyzer crossed with polarizer. The determination is based on the physical phenomenon, according to which polarization vector rotation of monochromatic beam passed along the eye, is proportional to the glucose concentration in the aqueous humor. Since in this case the beam optical path is small, respectively, the rotation of polarization vector conditioned by birefringence is small as well. For this reason the requirement of precision for determination of beam polarization vector rotation increase.

In the prototipe the value of the current, registered at the output of photoreceiver is proportional to the glucose concentration. The measurement precision of glucose concentration using the prototype is limited by usage of electrooptical modulator.

The objective of this invention is to develop a simple device for non-invasive determination of glucose concentration, where only optical elements are used.

Summary of Invention

The essence of the invention is that the device for non-invasive determination of glucose concentration in human has a light source, analyzer and photoreceiver. Acording to the invention it has a beam splitter, radial symmetric liquid crystal phase retarder and polarization diffraction grating, symmetrically placed relative to light sour.ce and beam splitter, used as analyzer, and as photo detector four CCD cameras are used, which are placed in pairs at the output of each diffraction grating perpendicularly to diffracted beams.

To propose a device for registration the change of polarization vector of monochromatic light beam, reflected from the eye, determined by the eye birefringence. This change is caused by the glucose concentration in the aqueous humor.

In contrast to the prototype, in the proposed device a arbitrary polarized light beam is directed to the eye, and the beam, reflected from the eye, is directed at first to radial symmetric liquid crystal phase retarder, then passes through the polarization diffraction grating, placed after the retarder, at the output of which the rotation of images, corresponding to radial symmetric right- and left-circularly polarized components intensities is registered by the digital camera, this rotation is in direct proportion to glucose concentration in human.

In the proposed device in polarizer - sample - analyzer - photo receiver system instead of polarizer, analyzer and photo receiver the new generation optical elements are used - liquid crystal polarization diffraction grating (PDG), axial symmetric liquid crystal phase retarder and digital camera, leading to simplification of determination of rotation angle of monochromatic beam polarization vector and to increase the accuracy of measurement. Moreover, in contrast to the prototype, where the linearly polarized beam is used, in the proposed device the semiconductor laser beam is used with arbitrary polarization. In the Fig.l the optical scheme of device is presented. According to the figure, the beam of monochromatic light source - semiconductor laser (1), is divided into two parts by the beam splitter

(2), the one part of which is used as a reference signal (3), and the other is used as a test signal (4), after reflecting from the eye. The left- and right-circularly polarized components of the beam, reflected from the eye, acquire different phase delays, recorded by registration system.

It consists of axial symmetric liquid crystal phase retarder (LCPR, 5), liquid crystal polarization diffraction grating (LC PDG, 6), and two digital cameras (CCD, 7). The difference between phase delays is conditioned by birefringence, which is proportional to glucose concentration.

By the registration system the rotation of images, corresponding to intensities of radial symmetric left- and right-circularly polarized components of the investigated beam, which is directly proportional to glucose concentration, is registered.

In the reference part the rotation of images, corresponding to intensities of the beam left- and right- circularly polarized components, is used as reference for rotation angle determination.

As it is shown in the method, patented by the authors [13], the application of LCPR allows creating a unique correspondence between the state of incident beam polarization vector and registered intensities of left- and right-circularly polarized beams, obtained at the output of PDG, placed after LCPR.

It is important, that the rotations of two-dimension images of registered radial symmetric intensities correspond to rotation of polarization vector of investigated beam. That is, there is a unique correspondence between the vector of polarization state of the investigated beam and the radial symmetric distributions of intensities, corresponding to left- and right-circularly polarized beams. For the quantitative description of the mentioned correspondence our patented method [13] is used, where Radon transform for the intensities distribution [14] is used. The Radon transform is a projection of symmetric image on the given axis, which is one-dimension function from the axis rotation angle and the maximum values of which are periodic.

This corresponds to the transformation of intensity distribution along circle - intensity distribution along horizontal axis. That is, the shift of maximal values of the Radon transform along the angular axis will correspond to rotation of radial symmetric image.

The device registers the rotation of images, corresponding to intensities of reflected from the eye and passed through LCPR and PDG radial symmetric left- and right-circularly polarized components. This rotation is directly proportional to the glucose concentration in human organism. The level of accuracy of this method depends on determination accuracy of maxima coordinates of one-dimension function, corresponding to the Radon transform [15].

According to previously given digital estimations [13, 15], in the case with four-petal LCPR, when the angular distance between the maxima is 90°, the precision of determination of one maximum is 0.1°, and in the case of averaging over the number of maxima the precision is 0.025°. To improve the measurement precision of the proposed device LCPR with 10 and more petals can be used.

Thus, the proposed device registers the rotation of images, corresponding to intensities of reflected from the eye and passed through LCPR and PDG radial symmetric left- and right-circularly polarized components. This rotation is directly proportional to the glucose concentration in human organism.

References

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