RU2341785C1 - Method of registration of biological, chemical and biochemical processes on boundary liquid-photon crystal and device for its realisation - Google Patents

Abstract

FIELD: chemistry, biology.

SUBSTANCE: invention relates to field of biological, chemical and biochemical surface sensors, based on excitation of surface waveguide electromagnetic waves on separation boundary liquid-solid body. Essence of invention lies in the following: at least part of said solid body near said separation boundary is composed of layers with periodically changing refraction indices, i.e. as solid body, "photon crystal" is used, thickness of layers being chosen in such way that said electromagnetic radiation excites more than one surface waveguide mode on said boundary of separation liquid-photon crystal.

EFFECT: simultaneous registration of two or more surface waveguide modes, with different depths of penetration of electromagnetic wave into liquid volume, allows separating surface and volume effects.

3 cl, 6 dwg

Description

Technical field

The invention relates to the field of registration of biological, chemical and biochemical processes at the liquid-solid boundary, i.e. to the field of biological, chemical and biochemical surface sensors.

State of the art

Currently, the majority of “labelless” (“label-free”) surface optical sensors are based on the excitation of surface electromagnetic waves propagating along the studied liquid-solid interface [1]. In the Surface Plasmon Resonance (SPR) method, these waves are surface plasmon polariton modes (2] propagating along a metal surface, and in the Resonant Mirror (RM) method these waves are waveguide modes excited in a dielectric layer with a high refractive index deposited on a layer with a low refractive index [3].

The reactions that occur at a given liquid-solid interface or (more often) in an additional near-surface sensitive layer that selectively interacts with a specific component dissolved in a liquid are recorded by measuring the wave vector of a given surface waveguide electromagnetic mode propagating along this interface.

The closest analogue of the invention is a method of excitation and detection of surface waveguide electromagnetic waves on the surface of a photonic crystal [4]. Photonic crystals (FCs) are materials with a refractive index that periodically varies over a length of the order of the wavelength of light [5]. In these materials there are forbidden energy bands, very similar to forbidden energy bands for electrons propagating in an ordinary crystal. In both cases, there is a frequency range where wave propagation is prohibited. This analogy can also be extended to surface levels that can exist in the forbidden energy bands of ordinary crystals. In PC, they correspond to surface optical modes with dispersion curves located inside the forbidden zones. We will use a one-dimensional (1D) FC, i.e. ordinary multilayer dielectric mirror of alternating layers with high and low refractive index.

The disadvantage of all the above methods for recording processes at the liquid-solid boundary (including the closest analogue [4]) is the sensitivity of these methods not only to the surface properties at the liquid-solid boundary, but also to bulk properties of the liquid, such as the refractive index of the liquid. This is due to the penetration of a damped electromagnetic wave into the liquid volume to a depth of more than 100 nm. Since the refractive index of a liquid varies greatly with temperature (for water, a temperature change of 1 ° C leads to a change in the refractive index by 10 ^-4 ) and with a change in the composition of the liquid, this problem becomes fundamental when the detection sensitivity of surface waveguide electromagnetic waves increases.

Since the wave vector of only one surface waveguide electromagnetic mode is recorded in all the above methods, it is impossible to extract two parameters (a change in the volume refractive index of the liquid and a change in the thickness of the surface layer) from one recorded parameter.

Consequently, there is a need to develop such a method for detecting near-surface processes in which at least two near-surface waveguide electromagnetic modes with different penetration depths of a damped electromagnetic wave into the liquid volume are detected. From these (at least two) different wave vectors recorded on the same surface area, one can extract both a change in the volumetric refractive index of the liquid and a change in the thickness of the surface layer.

SUMMARY OF THE INVENTION

The objective of the invention is to develop such a method of exciting electromagnetic waves at the liquid-solid interface, which would lead to the above desired technical result: simultaneous registration on the same surface area as changes in the near-surface sensitive layer (useful signal), and changes in the volumetric refractive index of the liquid (interfering signal) and thus to the possibility of separating these signals from each other.

This requires the simultaneous excitation of at least two surface waveguide modes. The problem is solved due to the fact that we choose the thickness of the FC layers so that incident electromagnetic radiation can excite several (two or more) electromagnetic modes on its surface with very different penetration depths of a damped electromagnetic wave into the liquid volume.

The ability to change the parameters of the FC by changing the thickness of their dielectric layers is an attractive distinguishing feature of the FC. By varying the parameters of the photonic crystal, we can choose a photonic crystal in which the excitation of several long-range modes at the same part of its surface will be possible. This is much more difficult to achieve using surface plasmons or conventional waveguide modes.

We give specific parameters of the photonic crystal, in which two long-range modes propagate along the surface of the crystal to a distance of several millimeters. We also describe a device for the practical implementation of this method of excitation of electromagnetic waves localized near the liquid-photon crystal interface (see Fig. 2).

List of drawings

The invention and examples, confirming the possibility of its implementation, are explained below using the drawings.

Figure 1. - The calculated values for the dispersion of the photonic crystal structure and experimental data (white stars) at wavelengths λ = 442 nm (He-Cd laser) and λ = 532 nm (second harmonic of the Nd-YAG laser).

Figure 2. - Diagram of a biosensor device with excitation of two long-range surface waveguide modes at the liquid-photon crystal interface.

Figure 3. - The signal from the receiver of electromagnetic radiation (from the diode array), recording changes in the wave vectors of the surface waveguide electromagnetic modes.

Figure 4. - The experimentally observed change in the thickness of the surface layer during the deposition of streptavidin on the surface.

Figure 5. - The experimentally observed change in the thickness of the surface layer upon binding of biotin to streptavidin on the surface.

6. - The experimentally observed change in the refractive index of a liquid upon injection of biotin into the liquid.

Information confirming the possibility of carrying out the invention

For a more complete understanding of the invention and for the purpose of illustrating it, an example of its experimental implementation is given below. However, it should be understood that its various modifications are possible, obvious to a person skilled in the art, not changing the essence of the invention and not beyond the scope of the invention defined by the attached claims.

First of all, we give mathematical justifications for the possibility of carrying out the invention. First, we calculate the dispersion of the following PC structure: substrate / (LH) ³ L '/ water, where the layer thicknesses L (consisting of SiO ₂ ) with a low refractive index n ₁ = 1.49 are d ₁ = 154.0 nm, and the layer thicknesses H (consisting of Ta ₂ O ₅ ) with a high refractive index n ₂ = 2.12 are d ₂ = 89.4 nm and the thickness of the last layer L '(consisting of SiO ₂ ) is d ₃ = 638.5 nm.

Such a 7-layer SiO ₂ / Ta ₂ O ₅ FC structure was deposited on a VK-7 glass substrate with a refractive index n ₀ = 1.52, and the excitation angles of the surface waveguide modes were measured in water with a refractive index n _e = 1.335. Figure 1 shows good agreement between the theoretical dispersion curve and experimental points (white stars) measured at wavelengths λ = 442 nm (He-Cd laser) and λ = 532 nm (second harmonic of the Nd-YAG laser).

The variance of the photonic crystal is represented in the coordinates λ (ρ), where λ is the wavelength and ρ is the numerical aperture ρ = n ₀ sin (θ ₀ ). The numerical aperture ρ can be used as an angular variable instead of angles θ _j in different layers. This will be a universal angular parameter for all layers, since, according to the Snell law, ρ = n ₀ sin (θ ₀ ) = n _j sin (θ _j ) for any layer j. The parameter ρ at which surface modes are excited is equal to the effective refractive index of these modes. Therefore, the two dark curves in FIG. 1 (with a gain of the order of 1000) represent the dispersion of two optical surface modes.

Figure 1 shows that it is possible to excite one of the surface modes of the photonic crystal in the immediate vicinity of the angle of total internal reflection (Total Internal Reflection - TIR), if you choose the laser wavelength and / or structure of the photonic crystal. The depth of penetration of a damped electromagnetic wave into the volume of the external environment, equal to

can be very large for this mode if the difference (ρ ₁ -ρ _TIR ) = (ρ ₁ -n _е ) is very small. This property of the FC is very important for achieving the technical result we need, since such a surface wave will be much more sensitive to the volumetric refractive index of the liquid and can be used as a measure of volumetric fluctuations in the liquid.

Figure 2 shows a diagram of a biosensor device with excitation of two long-range surface waveguide modes at the liquid-photon crystal interface. The optical electromagnetic radiation from laser 1 is split into two parts and, through a prism 2, excites two surface waveguide modes at the interface between FC 3 and liquid 4 in the liquid cell. Reflected electromagnetic radiation is incident on the optical radiation receiver - diode array 5.

A typical signal from the electromagnetic radiation receiver (with diode array), registering changes angular parameters ρ ₁ and ρ ₂ of surface electromagnetic waveguide modes (and thus their wave vectors k _1,2 = ωρ _1,2 / s), is shown in FIG. 3.

Interference on the resonance curve is a hallmark of long-range surface optical waves. It means that the propagation length of surface optical waves is longer than the constriction of a Gaussian beam incident on the PC surface. In our recent work [6], the origin of this interference is explained in more detail.

Figure 3 shows that the resonance curves are very narrow (due to the long range of surface waves) and this, therefore, allows their bias to be detected with high accuracy. A change in P ₁ and P ₂ can be converted into a change in the angular parameters of the surface modes Δρ ₁ and Δρ ₂ . To bring the change of volume of fluid of refractive index Δn = Δn (Δρ _1, Δρ ₂₎ and the change of the adsorption layer thickness Δd = Δd (Δρ _1, Δρ ₂₎ as a function of detected values Δρ ₁ and Δρ _2, we may use a linear method based on the expansion of the detected values Δρ ₁ and Δρ ₂ in a Taylor series in Δn and Δd:

From here we get the quantities Δn and Δd we need as a function of the measured quantities Δρ ₁ and Δρ ₂ :

where K _d and K _n is the ratio of the corresponding partial derivatives:

To obtain a dimensionless quantity proportional to Δn in one channel and a dimensionless quantity proportional to Δd in another channel, we need only the coefficients K _d and K _n (see the right-hand side of equations 3a-3b). If we want to have Δn in units of refractive index and Δd in units of length, then we also need the coefficients ∂ρ ₁ / ∂n and ∂ρ ₂ / ∂d, respectively. All these coefficients can be obtained, for example, from theoretical modeling of a real FC structure. For the structure presented by us, these coefficients are equal: K _d = 0.415; K _n = 0.1; ∂ρ _{1 /} ∂n=0.5 [1 / RI] and ∂ρ _{2 /} ∂d=0.06 [1 / μm] (assuming that the refractive index of the adsorption layer is n _a = 1.43).

As a test demonstration of the sensitivity of our method, we present a change in the thickness of the surface layer during the deposition of streptavidin on the surface (Fig. 4). In Fig.5 and Fig.6 presents a simultaneous recording of both changes in the thickness of the surface layer (Fig.5) and a change in the refractive index of a liquid upon injection of a given biotin into a liquid (Fig.6). Arrow 6 shows the moment of injection of streptavidin into the liquid, and arrows 7 and 8 indicate the moment of injection of biotin into the liquid. After the first biotin injection, it is evident that the layer thickness changes due to conformational changes in streptavidin molecules when biotin molecules penetrate them. It can be seen that the second injection of biotin does not lead to such significant changes, since most of the "binding pockets" in the streptavidin molecule are already occupied by biotin molecules.

Information sources

1. G. Robinson, "The commercial development of planar optical biosensors," Sensors and Actuators B, vol. 29, pp.31-36, OST 1995.

2. H. Raether, Surface Plasmons. Berlin: Springer, 1988.

3. R. Cush, J. Cronin, W. Stewart, C. Maule, J. Molloy, and N. Goddard, "The resonant mirror - a novel optical biosensor for direct sensing of biomolecular interactions. I. Principle of operation and associated instrumentation, "Biosensors & Bioelectronics, vol. 8, no. 7-8, pp. 347-353, 1993.

4. W.M. Robertson and M.S. May, "Surface electromagnetic waves on one-dimensional photonic band gap arrays," Appl. Phys. Lett., Vol. 74, pp. 1800-1802, March 1999.

5. E. Yablonovitch, "Photonic band-gap structures," J. Opt. Soc. Am. B, vol. 10, no.2, pp. 283-295, 1993.

6. V.N. Konopsky and E.V. Alieva, "Long-range propagation of plasmon polaritons in a thin metal film on a one-dimensional photonic crystal surface," Phys. Rev. Lett., Vol. 97, p. 2553904, December 2006.

Claims (2)

1. The method of optical registration of biological, physical, chemical and biochemical processes at the interface between the liquid and the solid and in the sensor layers located at this interface, which consists in the fact that electromagnetic radiation is excited at this interface, exciting surface waveguide electromagnetic modes at this interface, the processes taking place at this interface are judged by the change in the wave vectors of these surface waveguide electromagnetic modes, I distinguish in that at least a part of a given solid near a given interface is made up of layers with periodically varying refractive indices, the layer thickness being chosen so that this electromagnetic radiation excites more than one surface waveguide mode at a given interface. 2. A device for recording biological, physical, chemical and biochemical processes at the interface between a liquid and a solid and in sensor layers located at a given interface, containing a source of electromagnetic radiation with which this interface is irradiated, an electromagnetic radiation detector detecting wave changes vectors of surface waveguide electromagnetic modes excited by a given source of electromagnetic radiation at a given interface, characterized in that at least a part of a given solid near a given interface consists of layers with periodically varying refractive indices, and the layer thickness is chosen so that this electromagnetic radiation excites more than one surface waveguide mode at a given interface.

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