Optics: measuring and testing – With sample preparation – Depositing particles on optical surface
Reexamination Certificate
1999-12-10
2003-09-30
Nguyen, Tu T. (Department: 2877)
Optics: measuring and testing
With sample preparation
Depositing particles on optical surface
Reexamination Certificate
active
06628376
ABSTRACT:
TECHNICAL FIELD
The invention refers to methods of examining biological, biochemical, and chemical characteristics of media, mainly of biological origin, or media that are in contact with biological objects whose living is influenced by the media characteristics.
BACKGROUND ART
In a known analogue [B. Liedberg, C. Nylander, and I. Lundstrom, Surface plasmon resonance for gas detection and biosensing,
Sensors and Actuators,
4 (1983) 299-304] of the proposed method, a solution that contains an antigen is brought into contact with a thin layer of antibodies immobilised on a silver film adjacent to a glass prism. The film is exposed to laser radiation incident through the prism. Surface plasmon polaritons (SPP) are excited at the antibody layer-silver interface. One observes a resonant minimum in the reflected radiation intensity dependence on the angle of the radiation incidence on the film. The minimum is due to the pumping of radiation power into that of SPP. The interaction of the antigen and the antibody is recorded as a shift of the resonant contour of the dependence. The drawbacks of both the method and the apparatus of the analogue [B. Liedberg, C. Nylander, and I. Lundstrom, Surface plasmon resonance for gas detection and biosensing,
Sensors and Actuators,
4 (1983) 299-304]. are associated with that it necessitates mechanical rotation units to scan and adjust the incidence angle, as well as to compensate for a displacement of the irradiation spot and to follow a rotation of the reflected beam. This makes the method and the apparatus cumbersome and unpractical, results in insufficient reliability, low accuracy of measurements, and weak sensitivity of the method.
In another analogue [WO 89/07252, G01N 21/17, 1989], radiation is fed into an optical waveguide with the output face bevelled at an angle that ensures the excitation of SPP at the interface of a sensitive layer and a metal film deposited on the face. The layer is capable of reacting with the medium component under test and changing by this means the conditions of the resonant SPP excitation. An information signal is extracted from the analysis of the radiation reflected back into the waveguide. The drawbacks of the analogue [WO 89/07252, G01N 21/17, 1989] are complexity of the method and the apparatus, connected with the techniques and means to analyse the output optical signal, and the need for selection of radiation modes and frequencies. These restrict the areas of application, lowers the accuracy of measurements and the sensitivity of the method.
The closest to the proposed invention is the analogue method of examining biological, biochemical, and chemical properties of media [EP 0 305 109 B1, G01N 21/55, 1993]. It comprises:
introducing a volume or a constituent of a medium under test into the region where it interacts with a sensitive material;
acting by electromagnetic radiation through a block transparent to the radiation on a metal layer located on a boundary surface of the block, said sensitive material being placed over the metal layer directly or on an intermediate material;
exciting surface plasmon polaritons by means of said acting;
reflecting partially said radiation from the surface of said metal layer, resulting in the formation of a beam of reflected electromagnetic radiation;
producing with said beam such a spatial distribution of electromagnetic field intensity that the distribution comprises features whose positions depend on the interaction of the medium under test with said sensitive material;
recording parameters of said distribution, from comparison of which with predetermined reference relationships the examined characteristics are judged.
The basis of the method is that in a spatial distribution of electromagnetic intensity that is formed using the reflected beam over an extended photodetector array there is a feature associated with the excitation of SPP, namely, a resonant intensity minimum. In a one-dimensional distribution, it is revealed as a dark band on the illuminated background area. The method of the analogue allows to record the spatial intensity distribution with the resonant contour of the reflectance minimum as a whole at every instant of time and obtain information on characteristics under study by the analysis of the position and the shape of the resonant contour. In so doing the method avoids mechanical rotations and displacements. Besides, the output signal is insensitive to radiation intensity drifts. The mentioned features are among important advantages of the analogue.
The main drawback of the analogue is low sensitivity of the output signal to variations in optical parameters of the sensitive material layer. This results in low resolution of the method. As reported in literature, such schemes enable one to achieve resolution no better than 3×10
−6
in terms of effective refraction index, and 10
−8
in terms of albumin aHSA concentration detected by immunological binding HSA-aHSA directly on a gold surface. However, there is a number of problems in which lowering of a detection limit of biologically active components is of crucial importance. The example is hepatitis virus detection since even a single virus can cause infection. But, fundamental limitation on the prototype's resolution limit is imposed by the physical principle used, namely, sensitivity of the spatial position and/or the level of the reflected intensity minimum to variations in optical parameters of the sensitive material layer.
Besides, the detection of shifts of the position or the level of a resonant minimum involves the necessity to record all the resonant contour or the most part of it. The reason is that it is difficult to describe analytically the shape of the contour and actually impossible to find the position and the level of the minimum from few points of the contour. Thus, the detectability threshold of small shifts of the resonant contour is the lower, the greater is the spatial scale of the produced intensity distribution and the less is the size of each discrete element of the extended photodetector array. Since the angular width of the resonant contour is a fixed value defined by the physical mechanism of SPP excitation, lowering of the detectability threshold can be achieved only at the expense of increasing the spatial scale (and, consequently, the size of the photodetector array and the overall apparatus) or decreasing the size of each element of the array. Both approaches lead to a raise in the cost of the method and the apparatus, as well as to a fall in signal-to-noise ratio, and appear to be hardly acceptable.
Thus, the required technical result that eliminates the drawbacks of the known methods consists in rising the sensitivity and lowering the resolution threshold of the method, or, more concretely, in the following:
a) taking advantage of a superior physical principle to yield a parameter to be measured, which pertains to a spatial electromagnetic intensity distribution, so that the principle would ensure a higher sensitivity of this parameter to the characteristics of media under examination;
b) taking advantage of a more flexible technique to record small variations of said parameter, which would allow to lower the detectability threshold.
The known methods described above have been embodied in the apparatus for examining biological, biochemical, chemical characteristics of media. Their drawbacks are mentioned above as well as the required technical results eliminating them. The closest to the proposed apparatus is an analogue apparatus [EP 0 305 109 B1, G01N 21/55, 1993]. It comprises:
a source of electromagnetic radiation directed through a block transparent to the radiation on to a metal layer located on a boundary surface of said block so that there takes place a configuration for excitation of surface plasmon polaritons and partial reflection of said radiation from the surface of said metal layer, with formation of a reflected radiation beam;
a sensitive material placed over said m
Beloglazov Anatoly A.
Kabashin Andrei V.
Nikitin Petr Ivanovich
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