Single ion detection method and device

Abstract

A single ion imaging-based detection method and device are provided. After being reflected by an electromodulation singularity coupling differential imaging reaction unit, a probe beam from a total internal reflection ellipsometry imager converges on a CCD or CMOS detector, the acquired sensing surface image data is transmitted to a signal processing unit, the common mode noise is eliminated by performing spectral analysis on differential signals of a working sensing surface and a reference sensing surface, the peak intensity of a modulating signal is selected on the spectrum for wave filtering to obtain a real-time signal of interaction of single ions or charged molecules at a solid-liquid interface. Based on the singularity effect at a surface plasma resonance angle of an ellipsometry phase and a corresponding optical signal noise suppression scheme, the present application can achieve real-time observation of the adsorption of single ions or charged molecules at a solid surface.

Claims

1. A single ion imaging detection method, comprising: (1) applying, by a signal generator (3), a high-frequency sinusoidal modulating signal to a working sensing surface (W1) of an electromodulation singularity coupling differential imaging reaction unit (2), wherein the signal generator comprises a positive pole (31) connected to a sensing surface (W1) of a working unit (21) and a negative pole (32) connected to a platinum wire counter electrode (22) of the working unit and is configured to apply a sinusoidal modulating signal to the surface of the working unit; (2) after a probe beam from a total internal reflection ellipsometry imager (1) is reflected by the electromodulation singularity coupling differential imaging reaction unit (2), converging the probe beam on a detector of the total internal reflection ellipsometry imager (1), (3) transmitting sensing surface image data acquired via a CCD or CMOS detector to a signal processing unit (4), and (4) selecting, by the signal processing unit (4), area images of a same size on the working sensing surface and a reference sensing surface (R2) in the electromodulation singularity coupling differential imaging reaction unit (2), so as to obtain a working area signal intensity I.sub.0(t) and its mean value Ī.sub.0, a reference area signal intensity I.sub.r(t) and its mean value Ī.sub.r within a specific integration time, carrying out a $\begin{array}{cc}S=I_0\left(t\right)-\frac{\stackrel{\_}{I_0}}{\stackrel{\_}{I_r}}\left(I_r\left(t\right)-\stackrel{\_}{I_r}\right)& \end{array}$  inversion to calculate a differential signal S of a single ion or a charged molecule at a solid-liquid interface on the working sensing surface (W1) of the electromodulation singularity coupling differential imaging reaction unit, carrying out a Fourier transform on the differential signal S, and selecting a peak of a modulating signal on a spectrum for filtering and a noise reduction.

2. The single ion imaging detection method according to claim 1, wherein in the step (1), a reference solution and a solution containing target ions are transported through a micro-channel unit into the electromodulation singularity coupling differential imaging reaction unit (2).

3. A single ion imaging detection device, using the single ion imaging detection method according to claim 1, comprising: the total internal reflection ellipsometry imager (1), the electromodulation singularity coupling differential imaging reaction unit (2), the signal generator (3), and the signal processing unit (4), wherein the total internal reflection ellipsometry imager (1) generates the probe beam and acquires real-time image data of an interaction of the single ion or the charged molecule at the solid-liquid interface on the working sensing surface, the electromodulation singularity coupling differential imaging reaction unit (2) acquires real-time signals of the working unit (W1) and a reference unit (R2) near an ellipsometry phase transition singularity in a vicinity of a surface plasmon resonance angle, the signal generator (3) comprises the positive pole connected to the sensing surface of the working unit and the negative pole connected to the platinum wire counter electrode of the working unit and applies the sinusoidal modulating signal to the surface of the working unit, the signal processing unit (4) carries out a differential spectrum analysis on acquired optical image signals of the working sensing surface (W1) and the reference sensing surface (R2) of the electromodulation singularity coupling differential imaging reaction unit (2) and carries out an inversion to obtain physicochemical reaction information of the single ion and the charged molecule at the solid-liquid interface.

4. The single ion imaging detection device according to claim 3, wherein the electromodulation singularity coupling differential imaging reaction unit (2) comprises a coupling prism with an inclination angle being a surface plasmon resonance angle of the probe beam (2-1), a total internal reflection sensing substrate (2-2), and a differential imaging reaction unit, wherein a reflection surface of the coupling prism (2-1) coincides with a glass substrate (2-21) of the total internal reflection sensing substrate (2-2), and a coating layer (2-22) of the total internal reflection sensing substrate (2-2) is in contact with the differential imaging reaction unit.

5. The single ion imaging detection device according to claim 4, wherein the coupling prism (2-1) has an inclination angle of about 58° for an incident probe beam of 633 nm.

6. The single ion imaging detection device according to claim 4, wherein the differential imaging reaction unit comprises at least two independent reaction chambers, a diameter of each of the at least two independent reaction chambers is set to 5 mm, and a spacing between the at least two independent reaction chambers is equal to or smaller than 1 mm, and one of the at least two independent reaction chambers is used as the working unit, while the other of the at least two independent reaction chambers is used as the reference unit.

7. The single ion imaging detection device according to claim 4, wherein the total internal reflection sensing substrate (2-2) is cut along a center line to be separated into two substrate surfaces, one of the two substrate surfaces is the working surface and the other pf the two substrate surfaces is a reference surface.

8. The single ion imaging detection device according to claim 3, further comprising: a micro-channel unit, configured to transport a solution containing target ions to the working sensing surface of the electromodulation singularity coupling differential imaging reaction unit (2) and transport a reference solution to the reference sensing surface.

9. The single ion imaging detection device according to claim 3, further comprising: a noise isolation system (5), wherein the total internal reflection ellipsometry imager (1) and the electromodulation singularity coupling differential imaging reaction unit (2) are assembled in the noise isolation.

10. The single ion imaging detection device according to claim 3, wherein in the step (1) of the single ion imaging detection method, a reference solution and a solution containing target ions are transported through a micro-channel unit into the electromodulation singularity coupling differential imaging reaction unit (2).

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a schematic diagram of a single ion imaging detection method;

(2) FIG. 2 is a schematic diagram of a single ion imaging detection device;

(3) FIG. 3 is a schematic diagram of an electromodulation singularity coupling differential imaging reaction unit;

(4) FIG. 4 is a schematic diagram of an embodiment of the single ion imaging detection device; and

(5) FIG. 5 is an exemplary diagram of a single ion imaging reaction unit.

(6) Where 1 indicates a total internal reflection ellipsometry imager; 2 indicates a sinusoidal potential modulation singularity coupling differential imaging reaction unit; 3 indicates a signal generator; 4 indicates a signal processing unit; 5 indicates a noise isolation system; 6 indicates a working chamber; and 7 indicates a reference chamber;

(7) In FIG. 5, area 1 indicates the selected image of the working sensing surface, and area 2 indicates the selected image of the reference sensing surface.

DETAILED DESCRIPTION OF THE EMBODIMENTS

(8) The specific embodiments of the present application will be further described below with reference to the accompanying drawings and examples. The following examples are intended to illustrate the application, but not to limit the scope of the application.

(9) As shown in FIG. 1, a single ion imaging detection method in this embodiment comprises the following steps: (1) applying, by a signal generator 3, a high-frequency sinusoidal modulating signal to a working sensing surface W1 of an electromodulation singularity coupling differential imaging reaction unit 2, so as to perform Fourier analysis and filtering on the acquired signals, (2) after a probe beam from a total internal reflection ellipsometry imager 1 is reflected by the electromodulation singularity coupling differential imaging reaction unit 2, converging the reflected light, which contains adsorption information of single ions on the sensing surface W1 to a CCD or CMOS detector of the total internal reflection ellipsometry imager 1, so as to obtain original images of target-containing samples adsorbed on the surface, (3) transmitting sensing surface image data acquired via the CCD or CMOS detector to a signal processing unit 4, so as to process the original image signal acquired in the step (1), (4) selecting, by the single processing unit 4, area images of the same size on the working sensing surface W1 and a reference sensing surface R2 in a differential imaging reaction unit 2, so as to obtain a working area signal intensity I.sub.0(t) and its mean value Ī.sub.0, a reference area signal intensity I.sub.r(t) and its mean value Ī.sub.r, carrying out

(10) $S=I_0\left(t\right)-\frac{\stackrel{\_}{I_0}}{\stackrel{\_}{I_r}}\left(I_r\left(t\right)-\stackrel{\_}{I_r}\right)$  inversion to calculate a differential signal S of a single ion or charged molecule at the solid-liquid interface on the sensing surface W1 of the reaction unit 2, carrying out Fourier transform on the differential signal S, and selecting the peak of a modulating signal on the spectrum for filtering and noise reduction, so as to obtain the sensing signal acquired when the single ion is adsorbed on the sensing surface.

(11) A device shown in FIG. 2, FIG. 3, and FIG. 4, which is adopted to carry out the single ion imaging detection, comprises a total internal reflection ellipsometry imager 1, an electromodulation singularity coupling differential imaging reaction unit 2, a signal generator 3, a signal processing unit 4, and a noise isolation system 5.

(12) The total internal reflection ellipsometry imager 1 in the present embodiment generates a quasi-parallel probe beam for 633 nanometers detection, which is incident to the electromodulation singularity coupling differential imaging reaction unit 2 at 58°, and the reflected light wave is recorded and imaged by a CCD, of which the imaging time resolution is 0.1 s.

(13) The electromodulation singularity coupling differential imaging reaction unit 2 includes a coupling prism of which the inclination angle is a surface plasmon resonance angle of the probe beam 2-1, a total internal reflection sensing substrate 2-2, and a differential imaging reaction unit 2, wherein a reflection surface of the coupling prism 2-1 coincides with a glass substrate 2-21 of the total internal reflection sensing substrate 2-2, and a coating layer 2-22 of the total internal reflection sensing substrate 2-2 is in contact with the differential imaging reaction unit 2.

(14) The said total internal reflection sensing substrate 2-2 is cut along the center line to be separated into two substrate surfaces, one of which is the working surface and the other is the reference surface, as shown in FIG. 5.

(15) Specifically, in the present embodiment, the sinusoidal potential modulation singularity coupling differential imaging reaction unit 2 includes an SF10 singularity coupling prism with an inclination angle of 58°, an SF10 substrate coated with a 48-nanometer gold film, and a differential imaging reaction unit 2, which includes a working chamber 6 and a reference chamber 7 independent of each other. The diameters of the working chamber 6 and the reference chamber 7 are both equal to or smaller than 5 mm, the spacing between the two chambers is equal to or smaller than 1 mm, and the capacities are both about 200 microliters. A wire, which is provided in the contact part between the working chamber 6 and the sensing surface W1, is connected to the positive electrode of the signal generator. The working chamber 6 is provided with a platinum wire as a counter electrode 22 connected to the negative electrode of the signal generator, and is configured to acquire real-time optical signal of adsorption of the solution containing target ions at the solid-liquid interface. The reference chamber 7 is configured to acquire the optical signal of the solvent at the solid-liquid interface during the sampling process.

(16) The signal generator includes a positive pole 31 connected to the sensing surface W1 of the working unit 21, and a negative pole 32 connected to a platinum wire counter electrode 22 of the working unit 21, so as to apply a sinusoidal modulating signal to the surface of the working unit 21. In the present embodiment, the modulation frequency of the signal generator is 1.1 Hz, the signal amplitude is 1 V, and the signal reference bias is 0 V.

(17) The signal processing unit carries out differential and spectrum expansion on the acquired optical image signals of the working area 1 and the reference area 2 in FIG. 5, and carries out filtering for the peak of the modulating signal, and performs inversion to obtain physicochemical reaction information of single ions and charged molecules at the solid-liquid interface.

(18) A micro-channel unit is further comprised, which transports the solution containing target ions to a working sensing surface W1 of the electromodulation singularity coupling differential imaging reaction unit 2, and transports reference solutions to a reference sensing surface R2.

(19) As shown in FIG. 4, the noise isolation system 5 is configured to isolate low-frequency noise such as temperature and foundation vibration. According to the system, the temperature drift within the measurement period is kept less than <0.1° C.

(20) Finally, the method of the present application is merely shown as a preferred embodiment, but is not intended to limit the protection scope of the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application shall fall within the protection scope of the present application.