KR100460202B1 - A system of pH image detection based on the line scanning - Google Patents

Abstract

In the conventional pH image detection method for obtaining diffusion rate and two-dimensional concentration distribution caused by the metabolism of microorganisms and cells, the two-dimensional pH distribution was measured by moving a laser beam on the sensor surface. However, this requires precise positioning control of the light source because two-dimensional fine-tuning of the position of the light source is required, and a large amount of time is required for photocurrent measurement for all pixels in order to obtain one image.

The present invention relates to an image detecting apparatus and method for detecting a two-dimensional distribution of pH at high speed, comprising: a potentiometer 310 for applying a specific potential to a sensor surface, and an electrode portion 330 for maintaining and compensating a desired potential difference. The sensor unit 340 for detecting hydrogen ions and generating a corresponding photocurrent, the current detector 350 for analyzing frequency components of the complex photocurrent generated for each position, and the detected current for each frequency component are displayed. It relates to a line scan type pH image detection device and method characterized in that it comprises a display unit 360 for displaying a, and a line optical unit 370 for modulating to have a different frequency for each position.

Description

A system of pH image detection based on the line scanning}

The biosensor refers to a sensor capable of quickly quantifying concentrations of various bioactive substances by using selective reactivity between molecules of a biomaterial only. Recently, a method of detecting and processing a signal combining a bio sensor and a semiconductor sensor has been developed, and a light-addressable potentiometric sensor (LAPS) using an oxidation / reduction reaction of a structure formed by interaction with a substance to be detected is developed. ), Surface plasmon resonance (SPR) devices using the photophysical characteristics of the radiation reaching the sensor, and surface acoustic wave (SAW) devices that detect the change in frequency of the vibrator due to the adsorption of materials. There is this.

Among them, LAPS measures the electrical signals generated by photo-stimulation and chemical reactions applied to the semiconductor. Since the position of the measurement target is selected by the photo-stimulation, the structure is simple because no separate driving circuit is required when constructing the sensor array. The advantage is that multiple materials can be analyzed simultaneously on the same device. In addition, it can be easily standardized and integrated by fabrication using a semiconductor process.

LAPS is used to change the amount of hydrogen ions generated by the biochemical reaction according to the concentration of the microorganism, and indirectly measures the concentration of the microorganism by detecting the pH change. Therefore, it is recently used for the detection of the concentration of microorganisms and toxins that need to measure several objects simultaneously with a simple structure, and is expected to be widely used for environmental, military, and biological research.

In addition, in order to obtain the diffusion rate and two-dimensional concentration distribution caused by the metabolism of microorganisms and cells, a high resolution pH image sensor for pH image detection and microstructure observation, which measures the two-dimensional pH distribution by moving the laser beam on the surface of the LAPS. A study was conducted.

pH image sensors are sensors that can visualize the two-dimensional distribution of pH and the concentration of specific ions or microbial molecules.

A conceptual diagram of such a pH image sensor is shown in FIG. 1. The pH image can be obtained by using the principle of LAPS, which measures the change in capacitance of the depletion layer by the alternating photocurrent generated by the modulated light.

Since the width of the depletion layer existing in the sensor 110 depends on the ion concentration by the microorganism, when the modulated light 120 scans the sensing surface, the photocurrent corresponding to each pixel is measured using the detection circuit 130. This detects the pH distribution on the sensor surface. Such pH images can be used to visualize chemical changes that occur during biochemical reactions in the electrochemical and biological fields.

In the conventional method for observing the spatial distribution of pH, the photocurrent generated by the photoreaction for each pixel is detected. A conventional system and conceptual diagram for pixel-by-pixel pH image detection are shown in FIG. 2.

In FIG. 2 (a), the conventional pH image detection system is generated by a potentiometer 210 and a potentiometer 210 composed of a DC voltage varying unit 211 and a DC voltage applying unit 212 for generating a desired DC voltage on a sensor surface. An electrode unit 230 including a reference electrode 231 for applying a DC voltage to the sensor surface and a control electrode 232 for compensating for the voltage change of the reference electrode, a sensing film 241 for detecting hydrogen ions, and an insulator ( 242 and a sensor unit 240 composed of a silicon wafer 243 in which an electron-hole pair is generated and a capacitance change occurs due to the movement thereof, a signal detector 250 for amplifying and detecting a modulation signal component, and a detected pixel. The display unit 260 for collecting the measured values of each star and displaying them in a two-dimensional image, the light source unit 271 for generating light applied to the sensor, and the position adjusting units 272 and 273 for adjusting the irradiation position of the generated light source. Broad It consists of a light applying unit 270 composed of a lens 274 for focusing.

The operation of the pH image sensor having the above structure is as follows. In order to detect a specific two-dimensional pH image distributed on the sensor sensing film of the EIS structure, when the DC voltage applied to the electrolyte 220 is fixed through the electrode part 230 in the potentiometer 210, the output current depends on the surface pH. Will appear differently. In addition, the light applying unit 270 simultaneously applies a photo stimulus to the sensor surface. At this time, a photocurrent corresponding to a pH value at the position where the photostimulation is applied is generated, and the photocurrent is detected by the signal detector 250 to store the pH value at the position.

After detecting the pH value corresponding to the specific position, the photostimulation position is moved by the position adjusting units 272 and 273 of the light applying unit, and the pH value for the next pixel is detected by detecting the pH value at the moved position as described above. You get This process can be performed for each pixel to display the pH in two dimensions.

Figure 2b shows such a conventional pH image detection conceptual diagram that the light output of a specific position is the current according to the light irradiation position And

[Equation 1]

Same as This is the amplitude of the current, including the frequency component of the irradiated light Appears. That is, the pH image with the number of pixels in the horizontal X and vertical Y Is the current value displayed at each pixel By representing the two-dimensional distribution of

[Equation 2]

Appears as

In this conventional method, the output values are sequentially read out and reconstructed by moving the position of the light source to grasp the position information of each pixel or by moving the fine mirror to change the position of the light source in the horizontal and vertical directions. However, this method requires a long measurement time because the output must be detected for each pixel in order to construct an image, and fine adjustment of the X and Y scanning mirrors for position shift of the light source and control for driving the high spatial resolution are required. And complex optics are needed to guide the light source to the sensor surface.

The present invention relates to an image detection system and method for detecting a two-dimensional distribution of pH at high speed. In the proposed pH image detection method, a signal component of one line can be measured simultaneously by applying a modulated light with a different frequency for each pixel and then confirming the position for each frequency component. In addition to high-speed pH distribution detection, it could be used for high-speed digital signal analysis of DNA or protein chips of interest.

1 is a conceptual diagram of a pH image sensor.

2A and 2B show a detection system and a conceptual diagram of a conventional pH image sensor.

3A and 3B show an image detection system and a conceptual diagram of the present invention.

Figure 4 shows the configuration of the optical signal modulator used in the present invention.

5a and 5b shows the frequency characteristics according to the distance and the rotation grating used in the present invention.

6A and 6B illustrate a process of detecting an image and a process of detecting a line image according to the present invention.

The present invention relates to a pH image detection system and method by line-by-line in order to solve the problems appearing in the conventional method. Instead of detecting the output of each pixel, the output of one line can be obtained at a time by reconstructing the output of the frequency component by the frequency component for each pixel.

The pH image detection system of the present invention is shown in FIG. The pH image detection system according to the present invention includes a potentiometer 310 composed of a DC voltage varying unit 311 and a DC voltage applying unit 312 for generating a desired DC voltage on the sensor surface, and a DC voltage generated by the potentiometer. An electrode portion 330 comprising a reference electrode 331 for applying to the control electrode and a control electrode 332 for compensating for the voltage change of the reference electrode, a sensing film 341 and an insulator 342 for detecting hydrogen ions, and an electron- The sensor unit 340 composed of the silicon wafer 343 in which the hole pairs are generated and the capacitance changes by the movement thereof, the signal detector 350 for signal amplification, frequency component analysis and detection, and the detected pixel-specific measurement values are The display unit 360 for collecting and displaying the 2D image and the light to be applied to the sensor surface are extended with the light source unit 371 for generating and the extension lens 372 for extending the light generated from the light source to the sensor length. Line optics 370 comprising a rotating grating 373 for modulating the light to have different frequencies for each position and a slit 374 for applying the light modulated by the rotating grating to one line of the sensor. It is composed.

The operation of the pH image sensor having the above structure is as follows.

In order to detect a specific two-dimensional pH image distributed on the sensor sensing film of the EIS structure, when the DC voltage applied to the electrolyte 220 is fixed through the electrode part 230 in the potentiometer 210, the output current depends on the surface pH. Will appear differently. In addition, the light applying unit 270 simultaneously applies a photo stimulus to the sensor surface. At this time, a photocurrent corresponding to a pH value at the position where the photostimulation is applied is generated, and the photocurrent is detected by the signal detector 250 to store the pH value at the position.

After detecting the pH value corresponding to the specific position, the photostimulation position is moved by the position adjusting units 272 and 273 of the light applying unit, and the pH value for the next pixel is detected by detecting the pH value at the moved position as described above. You get This process can be performed for each pixel to display the pH in two dimensions.

3 (b) shows a conceptual diagram of an image detection process according to the present invention, in which a light source signal having different frequency components in a horizontal direction of a corresponding line is applied by an optical signal modulator to a sensor surface. That is, the light modulated in the horizontal direction Modulation frequencies Each has When the modulated light is irradiated onto the sensor surface

[Equation 3]

Output signal corresponding to the sum of different frequency components You get Horizontal direction using this output signal The pixel component of

[Equation 4]

Same as here, Is the frequency component modulated by the optical modulator. FFT [] shows the fast Fourier transform for frequency component analysis. Therefore, the frequency-specific amplitude appears by frequency component analysis, and the amplitude of each frequency at this time becomes the magnitude of the current according to each pixel position on the sensor surface. Thus, an image of one line can be obtained simultaneously.

PH image with four pixels Is the current of each line obtained from Equation 4 To be configured in a two-dimensional distribution by scanning with respect to a pixel component in the vertical direction y

[Equation 5]

Will be obtained as Thus, the line image This is a two-dimensional extension of the y direction.

The proposed line scan type image detection system requires a modulated optical signal having different frequency components in the same line. In the present invention, the optical signal is modulated using a rotating grating widely used for optical signal processing. The configuration diagram of the optical signal modulator used in the proposed method is shown in FIG. 4. The light from the light source is extended through the expansion lens to the sensor length and modulated in such a way that the frequency increases as it moves away from the center by the rotating grating, and then one line through the slit to apply it to the measuring surface of the LAPS line by line. Modulated light is irradiated onto the sensor surface. After obtaining the output signal for one line on the sensor surface, the FFT for frequency component analysis is performed to spatially display the amplitude for each frequency to detect the line image. To measure the next line, move the sensor horizontally by the line resolution, then perform the measurement.

The rotating grating used in the present invention is to generate modulated light in which several frequency components are distributed at regular intervals in the same line as shown in FIG. The transmission function of this rotating grid is represented by polar coordinates

[Equation 6]

Same as here, Is the number of gratings included in the rotating grating and changes with distance from the center, and sgn (·) is a sigmoid function for binarization. Thus, the modulation frequency of the light Is the number of rotations rot of the rotating grid and the number of grids composed of one rotating grid By

[Equation 7]

Is determined as follows. Therefore, to design a rotating grating, the range, the number of gratings, and the number of rotations of the optical modulation frequency should be considered. Optical modulation frequency for each pixel position for the rotating grating design to be used in the present invention of

[Equation 8]

It is defined as follows. here, Is the modulation frequency at the innermost circumference from the center, Is the frequency difference from adjacent pixels, Is the position of the pixel.

6 shows a method for detecting a line scan type pH image using such an apparatus. In the line scan type pH image detection method according to the present invention, a frequency component analysis is performed on an optical stimulus applying step 610 for applying a line photostimulus having a different frequency to each sensor surface and a sensor output generated by the applied photostimulus. A line image detection step 620 for detecting an image for one line through the image position shifting step 630 for moving the image detection position for image detection of the next detected line.

The line image detection step includes a complex signal detection step 621 for detecting a complex sensor output signal having different frequencies added to each location, and a frequency analysis step for analyzing frequency components for each location in the detected complex signal. 622 and a line image reconstruction step 623 for reconstructing an image corresponding to one line using the frequency-analyzed result.

In the present invention, a signal acquisition-processing method of a line scan type image detection system for detecting two-dimensional distribution of pH at high speed is proposed. In the proposed line scan type pH image detection method, the signal components of one line can be measured at the same time by applying the modulated light with different frequency for each pixel by using the optical grating rotation grating. Was used. The image detection by the proposed method using the LAPS device can be detected earlier than the conventional method. This could be used for high speed digital signal analysis of DNA or protein chips of interest, as well as detection of fast pH distribution.

Claims (4)

In the system for detecting the two-dimensional distribution of the pH image at high speed, A DC voltage variable part for generating a desired DC voltage on the sensor surface for detecting the pH image; A reference electrode for applying a voltage generated at the DC voltage variable part to the sensor surface; A control electrode for compensating for the voltage change of the reference electrode; A light source unit generating light to give a light stimulus on the sensor surface; A sensor unit for interlocking the potentiometer, the light source unit, the sensing film, and the insulator to detect a pH change in each pixel on the sensor surface and output a current signal; A frequency analyzer for analyzing frequency components of the current signal output from the sensor unit; A display unit for displaying the current signal detected by the sensor unit for each frequency component; And a line optical unit for modulating the light generated by the light source unit to have different frequencies for each position. The method of claim 1, The line optics and the expansion lens for extending the light generated by the light source to the sensor length; A rotating grating for modulating the expanded light to have different frequencies for each position on a sensor surface; And a slit for restricting and applying light modulated by the rotating grating to a line on a sensor surface. delete delete