TW558635B - Fiber optic biosensor using phase tracking - Google Patents

Abstract

The present invention discloses a fiber optic biosensor using phase tracking to detect the existence and degree of variation of some specific biological (or chemical) material. The biological probe of the sensor uses fiber as the substrate, the tip of the fiber is coated with one or more layers of materials different from that of the fiber and the tested material, which can be the sensing standard of the thin-film reflection interferometer, wherein at least one layer is the compensated material which can absorb the target biological (or chemical) molecules to be tested. When the molecules to be tested are absorbed on the surface or interior of the complementary material, the spectrum distribution of the reflection/interference light will vary. The spectral line shift is for analyzing quantitatively or qualitatively the concentration, adhesion rate and geometrical size of the sample molecules.

Description

558635 A7 B7 V. Description of the Invention (Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economics. Field of the Invention The present invention relates to a detection device in the field of photoelectric detection technology, and further relates to the detection of a specific biological (or chemical) substance. Presence and change of an optical fiber bio-detector using phase tracking method. The detector uses optical fiber as a biological probe for the substrate. The bio-coating on the probe and the coating (directly coated or processed) can be used. As the sensing standard of the thin-film reflection interferometer, at least one layer is a complementary material capable of adsorbing the target biological (or chemical) molecules to be measured. After the molecules to be measured are adsorbed on the surface or inside of the complementary material, the spectral distribution of the reflected interference light will be changed. This spectral line shift is used to quantitatively or qualitatively analyze changes in the concentration, attachment rate, and geometric dimensions of sample molecules. BACKGROUND OF THE INVENTION The detection of the presence or absence of a particular biological or chemical substance in a sample is in life science research, Methods often used in drug development and medical diagnostics. For example, in immunoassays It is necessary to check whether there is a certain kind of antibody in the plasma. Antigen is a substance that can react with its complementary antibody, so it can be used to check the presence of its complementary antibody in the plasma. Diffusion and electrophoresis can be used for biological detection , F-ray method and other methods to detect the presence of certain antibodies, each method will be briefly explained below. Immunodiffusion method (mmunocHffusion) is generally used for immunoassay. It is a type A processing process, antibodies and antigens The solution diffuses between each other through the cell coagulation layer. The effect between the antigen and its complementary antibody is shown as a precipitation line between the two liquids.! ---------- pack-- (please first Read the note on the back side ^^^ This page) Threading --- an M-sheet scale is applicable to China National Standard (CNS) A4 specifications (210 ^ 97 Xi | I: \ Patent \ tangtang \ 625 invention patent (anna). doc 558635 A7 B7 V. Description of the invention (The electrophoresis method (11111111110416 忖 0? 110 "5 丨 5) is widely used in a variety of biological detection. It is also a sample processing process, using the ions generated by electrophoresis to move the measured component Separate out , And then observe them through the diffusion or labeling of their complementary organisms. Immuno florescence is a process that recognizes biological responses. An antigen is attached to a special label and is exposed to a certain wavelength of light (such as ultraviolet light). ) Fluorescence is generated upon irradiation, so this antigen can be easily identified. Other labels include radioactive isotopes, electronic, magnetic, and enzyme labels. The most common method for optical fiber testing is to identify organisms by fluorescence. Fiber optic fluorescent and chemi_iuminescent biosensors. This fiber optic sensor is the most widely used in commercial applications and research and development. There are two types of fiber optic biosensors: sandwich biosensors and displacement biosensors, which are actuated through different modes of action. The use of sandwich optical fiber biosensors and displacement biosensors are illustrated in the diagrams ", lb, u, and Η, respectively. For the sake of convenience, we take the antigen-antibody test as an example to illustrate various biosensors. As shown in Fig. 1a, a sandwich optical fiber biosensor is produced in the following manner: an optical fiber coated with a reagent 102 (such as an antigen) at its end is immersed in a solution 104 to detect the solution 104 Is there an antibody 106 complementary to the reagent 102? There is indeed a complementary antibody 106 in the right Luo solution 104, then the antibody system is combined with the reagent 102. The optical fiber 100 must be in the solution 104 The immersion time is long enough to ensure a long reaction time, and then 'wash with water such as saline. ---------- install-(Please read the precautions on the back first ^ ^^ This page) Ordered by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs

I: \ Patent \ tangtang \ 625 The invention patent is called as 558635 A7 B7 Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention () As shown in Figure 1b, the optical fiber 1 coated with reagent 1 〇 2 〇 and the antibody bound to it are immersed in a reagent i (such as an antigen). The substance labeled 丨 丨 2 (such as a fluorescent indicator) is adsorbed by the reagent 1 10. When the antibody 〇〇6 is combined with the reagent 102, the reagent 1 〇 with the label 1 12 will be related to the antibody 〇〇 ^ So, the optical fiber 〇〇 is paid to its root light source (in the figure (Not shown in the illustration). At the end of the optical fiber 100, first, the antibody 106 bound to the reagent 102, and then the fluorescently labeled reagent 1 110 bound to the antibody 106 are used. Reagent 1 10 is excited by light. Returns a fluorescent signal. In the end, the optical fiber biosensor will have a reagent 1 〇 2, an antibody 1 06, and a reagent 1 10 with a mark at the end, so it is called a sandwich fiber biosensor. For a sandwich optical fiber biosensor, the higher the concentration of antibody 106 in the test sample, the more reagents with fluorescent markers 丨 〖〇 will be combined with it, so the stronger the fluorescent signal returned. As shown in Fig. 1c, the displacement fiber biosensor is composed of an optical fiber and a reagent 120 (such as an antigen) coated on its end. Enzyme-labeled reagents 1 2 4 (antibodies) are sealed in a dialysis-capable membrane 1 3 0. The reagent 1 2 2 (antibody) is complementary to the reagent layer 1 2 0 (antigen). Therefore, the reagent 1 2 2 tends to be combined with the reagent layer. The set was immersed in the sample solution 150, and the sample solution 501 was checked for any antibody 14 that was also complementary to the reagent 120. As shown in Fig. 1d, if the sample solution contains the antibody ', this antibody has a tendency to compete with the reagent 1 2 with fluorescent cursors and to bind to the antigen layer 120 at the end of the optical fiber 100. At this time, in the fiber! A light source (not shown in the figure) is added to the root of the 〇 〇, combined with the reagent layer 1 2 0 and the labeled reagent 122 is excited by light, and returns an antibody Η in the fluorescent signal soil. Say $ 想 a,! ---------- ^! (Please read the precautions on the back ^^ € this page first) Line ·-

Send 5 2 g \ 6 I a do (a) · 558635 A7 B7 V. Description of the invention (Printed at the end of the optical fiber 1 0 0 by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, there will be more reagents with signs 丨2 2 Leaving the reagent 1 2 0 combined with it, the weaker the intensity of the fluorescent signal returned. Therefore, the concentration of 'antibody 1 4 0 is inversely proportional to the intensity of the returned light. The fiber optic biosensor described above has Many shortcomings. As for the sandwich fiber biosensor, the optical fiber 100 must be immersed in the sample solution 104, washed, and then immersed in the solution 108 containing the reagent 110 (with the mark 112). The test needs to go through two different The reaction step is more troublesome. Moreover, it can only be detected when the concentration of the analyte is higher than a certain threshold value. The rate of binding of the antibody 106 to the reagent 102 cannot be real-time (real "magic assay" Moreover, due to the troublesome laboratory tests and most of the signs (such as fluorescent indicators) are toxic, sandwich optical fiber biosensors cannot be used for direct detection in vivo. Most signs are not stable during storage, especially in storage. Under the light. The light intensity signal in the above method is easily affected by the environment and the system including noise, such as unstable light sources, temperature changes, and optical loss caused by fiber bending. For the displacement fiber biosensor, the thin film 13 series adds biological The cost and size of the sensor. Due to the large size of the sensor, the standard of the reagent may be toxic, so it is not suitable for in vivo detection. Another type of optical sensor is called surface plasmon resonance (Surface Plasma Resonance or "SPR" for short 1), as shown in Figure 2a, it includes a prism 202 coated with a very thin metal layer 204, which is a prism and an insulator 208. The interface between a beam of transversely magnetized polarized monochromatic light (magnetlcally polanzed monochromatic light) incident on prism 202-(Please read the precautions on the back first ^^^ this page) Order-line · -δ ~ ~ Glass house, layer 9 0 4 shot, but to-fortunately? This paper size applies Chinese National Standard (CNS) A4 specifications (210X 297 Xi Li I: \ Patent \ tangtang \ 625 invention patent (an 558635 A7 B7 V. Description of invention The intensity printed by the Intellectual Property Bureau employee consumer cooperative can be measured to calculate the incident angle 0 of the incident beam 20. As shown in Figure 2b, the intensity of the refracted beam suddenly drops at a special incident "SP At this particular angle, the surface plasmons (Surface Plasma * sp) waves generated by the excitation of the parent interface of the metal and the insulator will co-exist with the energy of the incident light. If a thin film sinks on the thin metal layer 204, The effective refractive index of the insulating material will change, especially near the metal layer. The effective refractive index is related to the thickness and density of the insulating material and the deposited film. Therefore, if the thickness of the precipitated film changes, the refractive index changes and the critical incident angle 0Sp also changes. By measuring the critical incident angle 0SP, the thickness and density of the precipitation film can be deduced. For the fiber-based SPR sensor, the signal detection method is similar to that of the optical SPR sensor. In addition to monochromatic light sources, multicolor light sources with a range of wavelengths can also be used for illumination. Here, the optical coupling efficiency changes with different wavelengths. At a certain wavelength, the intensity of the reflected light reaches a minimum. In addition, the thickness and density of the precipitation film changed, and the wavelength of the light wave at the minimum value of the reflected light intensity changed from one value to another. In this way, the wavelength shift at the minimum value of the reflection intensity can be tracked, and the thickness and density of the Shen Dian film on the surface of the fiber cylinder can be measured. In his article "a Novel Surface Plasmon Resonance Based Fiber Optic Sensor Applied to Biochemical Sensing", R. C. Jogenson et al. Discuss an SPR fiber optic sensor that can measure protein excitability. This article was published in Fiber Optic Sensors in Medical Diagnostics, SPIE Vol. 1 8 86, (1 QQ3) ~ Figure 7. There is no S PR sensor in this article. The paper size is applicable to Chinese national standards (CNS> M specification (referred to as static). Shipside \ 625 invention patent (_ ---------- install -(Please read the note on the back page first) Order-line 558635 A7 B7 V. Description of the invention (Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs including a multi-film optical fiber 210. The outer layer of one of the optical fibers is cut off, leaving The core of the optical fiber underneath is coated with a metal film, such as silver. Figure 2d is a schematic diagram of a detector, similar to Figure 2c. The system includes a light source 22 8 that is connected to a beam splitter 222 via an optical fiber 234 The light source 228 is a polychromatic light with a certain wavelength range. The output of the spectral state 2 2 2 is connected to a mode scrambler 226 via a connector 2 2 4 and an optical fiber 2 3 8. The mode encoder 2 2 6 It is connected to the core wire 2 丨 0 of the detector fiber and the casing 2 丨 2, and the fiber is inserted into the liquid sample 2 16. A signal system reflected by the 3 000 AQ silver mirror 2 18 at the bottom of the fiber core 2 10 Via mode encoder 226, fiber 2 3 8, connector 224 The spectroscope 222 and the optical fiber 23 6 are provided to a spectrograph (5? 0 (^ (^ 1 ^? 11) 23). The spectrograph 230 is used to measure light intensity, and the light intensity is a function of wavelength Based on these data, the thickness of the 5500A 〇 silver layer or metal 2 1 4 can be measured. Although the SPR sensor has many advantages, such as it does not require marking, the measurement can be performed continuously, but it is not sufficient The reason is that when manufacturing the spR sensor, after cutting the surface of the fiber, a thin, high-reflectivity metal layer must be plated on the fiber core, which increases the production cost. In addition, the spR sensor is a relatively large Cylindrical surface, such a large cylindrical surface area requires a larger capacity of reagents and more test samples. At the same time, the structure of this type of sensor is difficult to achieve array parallel testing. In addition, this design can not be used for In vivo detection. Another type of biosensor is a grating biosensor. W Lukosz et al. Entitled "〇utput Grating Couplers on (Please read the precautions on the back before this page})

Silk ... ι. I w η ι vv nvc: Dagger I vertical U r; \ This paper size applies to China National Non-standard (CNS) A4 size (210 x 297 public) I: \ Patent \ tangtang \ 625 Invention patent (anna), doe 558635 A7 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention () Immunosensors "Biosensors and Bioelectronics, V. 6, pp.227-232 (1 99 1) This type of inductor is described in Figure 3. As shown in Figure 3, an incident laser beam 3 02 enters one end of a planar wave guide 3 04. The planar waveguide 3 04 includes a very thin layer of high refraction The film 3 06 and the glass substrate 308 on which the film is placed. Part of the surface of the film 3 06 is provided with a grating 310. The surface protruding grating 310 causes the laser 3 to emit a plane wave at an angle of α Where α is the angle between the waveguide normal and the light. The size of α is related to the effective refractive index of the laser guided mode. Surface relief grating 31 (surface relief grating) can be coated with a layer of reagent. Can be filled with liquid Container for sample 3 1 4 3 1 2 Carrying surface The grating element 310 is carved. If the substance in the sample 314 reacts with the reagent layer, the effective refractive index will change, thereby changing the reflection angle α. The lens 3 1 6 focuses the outgoing beam onto a one-dimensional position-sensitive imaging detector (one- dimentional position sensitive Photodetector (or "PSD") 31 8. PSD31_ output is sampled by an analog digital converter (anal〇g_t〇_dlgltal converter) 320, and the result is sent to a personal computer 3 22 for analysis. The change in the angle of the reflected light beam caused by the change in the effective refractive index is related to the thickness of the thin film generated by the reagent and its combined substances. Grating biosensors have many shortcomings. First, the response of the sensor is relatively slow, the so-called "drift effect" (Drifteffect) ,,. If the concentration of the test substance in the test sample is low, it is difficult to judge the increase in effective refractive index caused by the drift effect. Second, the grating biosensor cannot be used for various paper sizes. Applicable to China National Standard (CNS) A4 specifications (210 X 297 male, -------------- install --- (please first Read the note on the back and write this page) Order: Printed by the line · Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 558635 A7-B7 5. Description of the invention () Distance measurement. In addition, because of its large size, it is not suitable for doing In-vivo detection. Such a large size is not conducive to multiple tests on a single sample. Moreover, the sensor is too long and requires a large amount of test samples. Finally, the manufacture of a planar waveguide with a built-in grating is more complicated and expensive, especially When the process is miniaturized. Another type of biosensor is a biosensor based on the principle of microtubule Fabry-Per 〇t interference (microcuvette-based Fabry-Perot interferometer). In the heading "Direct Monitoring of Antigen Antibody Interactions In the article by Spectral Interferometry,-Sensors and Actuators, Vol. 6? pp. 9 6- 1 00 (1 9 92), Brecht et al. introduced an example, as shown in Figure 5. A substrate made of glass or quartz 514 Cover a layer of polystyrene film 5 0 2, as shown in FIG. 6, the substrate 5 1 4 and the film 5 2 are placed at the bottom of the flow cell 6 0 2 and the top of the cell is made of silicon. Forked multi-stranded quartz optical fiber 6 0 4 It is connected to the substrate 514. The first branch 606 of 604 is connected to the spectrophotometer 61. The other branch 60 8 is connected to the light source 61 2 (such as a xenon lamp or a 20 watt halogen lamp). Next, it contains a predetermined concentration of reagent A solution of 504 (such as an immune antigen) flows through the flow cell 602, so that a layer of antigen 504 is adsorbed on the membrane 502. The flow cell is washed to keep the thickness of the increased antigen layer 504 fixed. At this time, use protein to block the reaction. Then wash it again. ------ I ------- pack --- (Please read the note on the back first to write this page) ιδτ · --line · final 'Let the sample solution flow through the flow cell 6 () 2 within a certain period of time. If the sample solution contains the antibody 5 〇6 complementary to the antigen 504, they will bind in the tank, so that the thickness of the inner membrane of the tank will be Increase. Due to protein content

558635 A7

Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, which is usually smaller than the wavelength of the light wave emitted by the light source 612. The added single-molecule protein layer can be considered to just increase the thickness of the membrane. The spectrograph 6 1 0 is used to determine the spectrum and intensity of reflected light waves at different times. As shown in Fig. 4, when the thickness of the film is increased, the first output of the spectrum camera 61 is A, and the second output is B. The film thickness increase Δ can be determined by Fresnel's theorem (Fresnel, s law). That is, the light intensity I of the interference light reflected by the thin film can be expressed as follows: /-/ J + / 2 + 2 λ! I ll 2 cos () λ 7 where Δ is the optical path difference (effectlve 〇ptlcal path difference), λ is the wavelength of the incident light. Due to the closeness of the intensity of the “worker 2”, the two can be regarded as equal. Let I 1 = I 2 = IR, the above formula can be simplified as: I = 2 Ir (1 + cos (-)) λ Therefore, the effective optical path The difference Δ (and the thickness of the film) can be determined by the intensity of the reflected light and the wavelength of the light wave. Although the advantages of the microtube Fabry_Per ot interferometer discussed above are that no marking is needed, and the detection results are not limited to the final Data, etc. But it still has many disadvantages. First, the size of the microtubules is still large, which requires a larger number of test samples, or requires a high sample concentration. Second, this method has certain difficulties for achieving a large number of parallel tests. Finally, the larger size Make it unsuitable for in vivo testing. -------------- Installation -------- Order (Please read the note on the back first and write this page) + 目 @ $ standard (CNS) A4 specification (210 X 297 public change) 1: \ ^ aieni \ iangtang \ 6i 4- M (anna), c oc Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 558635 5. Description of the invention () The summary of the invention should be based on redundant problems or shortcomings. Biosensors are simple in structure, low in cost, and easy to use. , Small probe type; (2) can achieve multiple and parallel testing purposes at the same time, · (3) do not use unstable or toxic reagents or indicators; (4) can perform in vivo testing; ⑴ can be continuously sampled to monitor The reaction process can also test the final value of the reaction; (6) Allow immediate data analysis; ⑺ For in vivo inspection, for safety, ensure electrical isolation '. (8) Can perform immediate correction; (9) Smaller size; (10) Can prevent non-complementary adsorption; (11) 咼 Sensitivity and large linear range. The purpose of the present invention is to provide an improved optical fiber biological detector using the phase tracking method, which uses optical fiber biological The sensor overcomes the shortcomings of the known biosensors described above. In particular, this biosensor method can detect the concentration of a substance in a sample solution through an optical fiber probe, at least one of which is capable of adsorbing the target biological (or chemical) molecules to be measured Complementary materials. ^ After the molecules to be measured are adsorbed on the surface or inside of the complementary materials, the spectral distribution of the light involved in reflection S will be changed. This line shift is used to analyze the sample quantitatively or qualitatively. Concentration, adhesion rate, and geometry changes. Probe tip of the optical fiber to be coated with a biochemical reagent capable of reacting with the test substance.

II installed! (Please read the notes on the back first to write this page) 1-T · • Line-

This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 MM 558635 -------------- installed · 1 · (please read the notes on the back first to write this page) Order _: Line · Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A7 V. Description of the invention () ^ a ----- In order to achieve the above purpose, the optical fiber biological detector adopting the phase tracking method of the present invention, including the technical scheme is: The application should be a) a light source 804; b) a fiber-optic bioprobe 700; c) a detector 818,829 used to detect the reflected light beam; 卞 " first detect the spectrum pattern d) one for the surface Combine the light source and the fiber probe, the coupler port of the pin and the detector, or the connector 802; e)-a phase used to determine the phase pattern of the interference light level detected by the line detector 818, and A signal processor that detects the concentration of the substance to be determined determined by the phase shift of the two patterns; the signal processor includes a microprocessor 8 3 0 program memory 8 2 2 and a RAM 834, and is connected in accordance with a conventional method; f) A phase tracker 8 2 2; g)-an output device 824; h) a periodic signal generator 8 2 0; 0 optical coupling 808, 812; j) optical waveguides 806, 828, 816, 814, 810; characterized in that: the optical fiber bioprobe 700 is an optical fiber coated with a reagent at the end, including a section of optical fiber, the root of which is used for The end of the incident beam is coated with one or more layers of materials and reagents. The fiber-optic bioprobe must generate at least a reflected beam generated by the incident beam. The fiber-optic bioprobe 700 passes through the connector 80 2 and the optical waveguide of the fiber-optic biodetector. 8 1 4 connected; This paper size applies Chinese National Standard (CNS) A4 specification (210 X 297 public variable) u㈣3㈣ Patent 558635 A7 V. Description of the invention () The light beam emitted by the light source 804 enters an optical waveguide such as an optical fiber 'Through an optical light coupler 80, an optical waveguide 8 06 is optically connected to another optical waveguide 82 8, the optical waveguide 8 8 is connected to a detector 829, and the detector 829 is connected to a periodic signal generator 82 Optics I Ma Hejie 812 also connects the optical waveguide 814 with another optical waveguide 8 16, the optical waveguide 816 is connected with the detector 818, and the detector 818 is connected with the periodic signal generator 8 2 0. Yi 808 also optically couples the optical waveguide with another optical waveguide 810, and the optical coupler 812 optically couples the optical waveguide 810 and the other optical waveguide 8 14; the optical waveguide 814 is connected to the biological probe 700 through the coupler 802 The phase tracker 8 2 2 is interconnected with the periodic signal generator 8 2 0, the output device 824, and the signal processor; the periodic signal generator 820 is also interconnected with the signal processor; the light source 8 0 4 and the detector 8 8 The output devices 8 2 4 are interconnected with the signal processor. Other features of the present invention are that the detectors 8 1 8 and 8 2 9 are spectrometers and also include a one-dimensional charge coupled element (CCD); the optical coupler 8 0 8 is "Y, , The light source 804 is a broadband light source or a tunable laser diode. The optical waveguides 806, 828, 816, 814, and 810 are single-mode optical fibers, which may also be single-mode optical fibers. Multi-mode optical fiber is used, and the fiber diameter is at least 3, preferably 100 / zm. Another technical solution for implementing the optical fiber bio-detector using the phase tracking method of the present invention is that in the above technology The plan also includes the scale of the scale applicable to the Chinese National Standard (CNS) A4 specification ⑵ G χ 297 male short) Yu uWUglangV | Tr]: 1 叨 Paper ^ installed --- (Please read the notes on the back first to write this page) Order -• Line · Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 558635 A7 V. Description of the invention () a) A rate adjuster used to adjust the frequency of the light beam provided by the light source and the light source 1 0 0 6; '^ b )-One for detecting the second in the sample solution The first fiber-optic probe for measuring substances; ~ c) an optical multiplexing multiplexer (optlcal multlplexe0ll02), which is used to connect the light source and each fiber-optic probe, that is, the light source and the fiber-optic probe are connected in a time division manner D) an optical demultiplexer (〇ptlcal demultiplexer *) 110, for connecting each fiber probe and detection as · σσ, the laser source 804 is driven by the frequency signal generator 106 Diode 1 0 0 4; phase tracker 8 2 2 is synchronized with the frequency signal generator 〇〇〇6. The optical ^ number multiplexer and optical signal distributor require synchronization to ensure that there is only one at any time The fiber optic probe is connected to the light source.

The optical waveguides 806, 828, 816, 814, 810 may be mouth-mode fiber or multi-mode fiber. H Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ------------- Installation --- (Please read the note on the back to write this page) i-line-The preparation of the fiber probe includes The following steps: (1) immerse the end of the fiber probe in the sample solution; (2) add a light source to the root of the fiber; (3) detect at least two beams of light, the first beam of light is the interface between the fiber end surface and the reagent layer Reflected, the second beam is reflected from the interface between the reagent layer and the sample solution; (4) The interference pattern formed by the two beams is checked for the first time; (5) The beam formed by the second beam is checked for the second time Interference pattern; U) determine whether the sample solution contains the substance to be measured by whether the interference pattern moves. The concentration of the substance can be determined by the amount of movement of the interference pattern and the difference between the fringes obtained from the two inspections. This paper scale applies the Chinese National Standard (CNS) A4 specification (21G X 297 male 1i 558635 A7. V. Description of the invention) Steps. As a result, each step of detection should include the following steps. ⑴ Interference formed by two beams of light It is determined according to the distribution of the spectrogram—Ga / Yi 7 instrument, (2) phase. ¥ surely a periodic function '· 〇) The detector that determines the periodic function has another peak, which is only 种For example, the frequency of the light source at the root of the fiber probe: 疋 ..., check whether the sample solution contains the light source and the frequency change is performed simultaneously. Qiaobei's / succinct and quality test substance contained in this solution There are only two optical fibers with a complete head and tail, the end of the fiber: h 彳 layer. The reagent layer reacts with the job title. The fiber section has a refractive index. As long as the test substance is attached to the reagent layer, a new film layer composed of the test substance is ordered. The new layer can be considered to have two = radiation !: the fiber part can be single-mode or multi-mode fiber, the diameter is at least 3mm, and the clothing can reach 100 microns. The reagent applied to the end can be an antibody, an antigen, a synthetic substance or a natural protein, RNA, a DNA fragment, or a chemical reagent. &Amp; Month can be used to detect the concentration of a substance in a sample solution. The detection method includes a light source that provides a light beam. , Fiber probe detector, fiber coupling mouth, fiber connector and signal processor. The first fiber coupled to the fiber is used to receive incident light, and the root coupled to the second fiber is used to reflect the light. The speculation of the interference beam transmission is that the bottom end of the second optical fiber is used to connect the optical fiber probe. The root of the optical fiber probe is connected to the optical fiber coupler, and the end is coated with a layer of treated test fiber. The incident light produces the interference of the first reflected light and the second reflected light 558635 A7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention () Pattern. The optical fiber coupler transmits the light from the light source to the optical fiber probe A fiber-optic probe is connected to the detector. The signal processor can be used to determine the phase of the pattern twice and the phase of the interference pattern. It is also necessary to determine the concentration of the substance to be measured. In order to better implement the system, the detector should choose a spectrometer, which is composed of a spectrometer and a one-dimensional CCD element (such as i * i〇24 CCD). To better implement the detection Instrument, the signal processor should include a periodic signal generator, a phase tracker and a personal computer. The periodic signal generator is used to generate two periodic signals, the first periodic signal is the interference pattern first detected by the detector It is obtained that the second periodic signal is obtained from the interference pattern detected by the detector for the second time. The phase follower is used to determine the phase of the first periodic signal and the second periodic signal, and the calculator is used to determine the phase difference, and The concentration of the substance to be measured in the sample solution is calculated from the phase difference. In order to better implement the present invention, the coupler is a “γ,” type coupler, and the light source is a broadband light source or an advanced light-emitting diode. There is another embodiment of the detector. The detector includes a frequency adjuster associated with the disk light source for adjusting the frequency of the light beam provided by the light source. At this time, the signal processor is synchronized with the frequency regulator. " There is also a form in which the detector includes another fiber-optic probe, a multiplexer and an optical multiplexer. The second fiber-optic probe f determines the concentration of the second test substance in the sample solution. The optical multiplexer is used to connect the light source and the two fiber probes, and the light source and the two fiber probes are connected in a time division manner. Multiple optical data distributors are used to connect two fiber optic probes and detectors. The multiplexer and the multiplexer must be synchronized. ‘Paper Size Turned Tii ^ _CNS) A4 Specifications⑽: (Please read the notes on the back s --install — W to fill out this page) Order:-· Line · 558635

Brief description of diagrams Figures la, lb, lc, and Id show traditional sandwich-type, displacement-type, and competitive-type fiber-optic fluorescent biosensors. Fig. 2a is a schematic cross-sectional view of a conventional surface plasmon sensor. Figure 2b is the relationship between the incident angle of incident light and the reflected light intensity in a surface plasmon sensor. Figure 2c is a cross-sectional view of a fiber surface plasmon sensor probe. Figure 2d is a block diagram of a system using a fiber-optic surface plasmon reaction bioprobe. Figures 2a to 2d show conventional devices. Fig. 3 is a working process diagram of a conventional output grating biological probe. Fig. 4 is a conventional microtubular reflection interferometer. The relationship between the reflection wavelength and the light intensity of the biosensor at the first time t1 and the second time t2. Fig. 5 is a schematic sectional view of a flow cell used in a conventional microtubule biosensor. Fig. 6 is a system implementation diagram of the conventional micro-groove biosensor method. Figs. 7a and 7b show the working process of the bioprobe used in the biosensor of the present invention. FIG. 8 shows a first embodiment of the biosensor of the present invention. Figures 9a and 9b show the shifted spectral distribution received by the spectrometer used in this biosensor. Fig. 10 shows a second embodiment of the biosensor. Fig. 11 shows a multiplexer method for this biosensor. 17 This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ----—— — — — — Chapter — II Packing · I (Please read the note on the back first, write this page by Amsjc) Order Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 558635 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs Reagents (antigens) 112, 120 reagents (antigens), 122 reagents (antibodies), 124 enzyme labels, 130 films, 140 and 120 complementary antibodies, 150 sample solutions, 202 prisms, 204 metal layers, 206 incident light, 208 insulators, 210 optical fiber cores, 212 fiber housings, 214 metals, and 216 Sample solution 21 8 Silver mirror 222 Beamsplitter 18------------ II --- (Please read the notes on the back first and write this page) · --- · This paper size applies to Chinese national standards ( CNS) A4 specification (210 X 297 mm) 558635 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of the invention () 224 connector 226 mode encoder 3 0 4 planar waveguide 3 0 6 high refraction Film 3 0 8 Glass substrate 3 1 0 Grating 3 1 2 Container 3 1 4 Liquid sample 3 1 6 Lens 3 1 8 — Element position sensitive image detector 3 2 0 Analog digital converter 3 2 2 Personal computer 500 Interferometer 5 0 2 Polyethylene film 5 0 4 Reagent (antigen) 5 0 6 Complementary antibody 5 0 8 Incident light 5 1 0 Reflected interference light intensity 5 1 2 Reflected interference light intensity 5 1 4 Substrate 6 0 2 Flow Slot 6 0 4 fiber 6 0 6 branch 6 0 8 branch 19 (please read the note on the back first to write this page)-installation-line · This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ) 558635 A7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs_B7 V. Description of the invention () 6 1 0 Spectrometer 6 1 2 Light source 6 1 4 Personal computer 7 0 0 Fiber optic probe 7 0 2 Fiber optic 7 0 4 Reagent (Antigen ) 7 0 6 Interface 7 0 8 External surface exposed by the reagent 7 1 0 Incident light 7 1 2 Reflected light 7 1 4 Part of the incident light 7 1 6 Second reflected light 7 1 8 Another part of the incident light Part of 7 2 0 part of incident light 7 2 2 part of incident light 724 second reflected light 7 2 6 7 2 4 part of reflected light 7 2 8 outer surface of antibody 7 3 0 Antigen and antibody layer interface 7 3 2 Antibody layer 7 3 4 Sample solution 7 3 6 Complementary antibody 7 3 8 Non-complementary antibody 7 6 0 7 1 6 Part of reflected light 20 (Please read the note on the back first (This page is written on this page) Assembling and threading 丨 This paper size is applicable to the Chinese National Standard (CNS) A4 (210 X 297 mm) 558635 A7 B7 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 5. Description of invention () 7 8 0 Test tube 8 0 0 Biosensor optical analyzer 8 0 2 connector 8 0 2 'connector 8 0 4 light source 8 0 6 optical waveguide 8 0 6' optical waveguide 8 0 8 optical coupler 8 0 8 'optical coupler 8 1 0 optical waveguide 8 1 0 'optical waveguide 8 1 2 optical coupler 8 1 2' optical coupler 8 1 4 optical waveguide 8 1 4 'optical waveguide 8 1 6 optical waveguide 8 1 6' optical waveguide 8 1 8 spectrometer 8 1 8 'spectrometer 8 2 0 periodic signal generator 8 2 0' period signal generator 8 2 2 phase tracker 8 2 2 'phase tracker 8 2 4 output device 21

(Please read the note on the back S-I Pack --- I fill in this page first) ·-· · This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) 558635 Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs Printed by the Consumer Cooperative A7 B7 V. Description of the invention 824 'output device 826 computer / network 826' computer / network 828 optical waveguide 828 'optical waveguide 829 optional spectrometer 829' optional spectrometer 830 microprocessor / ASIC 830 'Microprocessor / ASIC 832 Program Memory 832' Program Memory 834 RAM 834, RAM 836 Command and Data Channel 836 'Command and Data Channel 1000 Biosensor Optical Analyzer 1004 Laser Diode 1006 Frequency Signal Generator 1102 Optical Multiplexer multiplexer 1104 counter 1106a probe 1 1106b probe 2 1106c probe η 1108 optical multiplexer (please read the precautions on the back first and then this page) Binding and binding The paper size is applicable to the Chinese National Standard (CNS) Α4 specifications (210X297 2) 558635 A7 -----------5. Description of the invention () 1110a optical input / output coupler 1110b optical input / output coupler 1110c optical input / output coupler Combiner S 1 reagent thickness S2 antigen + antibody layer total thickness Detailed description of the invention The following detailed description will be given with reference to the attached drawings 7a, 7b, 8, 9a, 9b, 1 (^ mga). Figures 7a and 7b show The schematic diagram of the present invention. As shown in the figure, the biosensor probe 700 includes an optical fiber 702 and a reagent 704 coated on the end of the optical fiber 702. The reagent 704 may be an antigen such as an immune antigen. It may also be It is a special antibody, chemical substance, DNA fragment, or protein shell. Apply a certain concentration of reagent 704 to the end of optical fiber 702 within a certain time, make sure that the end of optical fiber 2 does form a layer of reagent 704, and then The device is cleaned and packaged. The experienced person can also apply reagent 704 to the end of optical fiber 702 by other methods. Different coating methods can be determined according to different reagents. The incident beam 71 ° is transmitted from the root of the fiber to the end of the fiber. At the interface between the reagent layer 704 and the optical fiber 702, a first reflected light 712 will be reflected back, and at the same time, a portion 714 of the incident light beam 710 will continue to pass through the reagent 704. On the exposed outer surface 708 of the reagent 704 , The second beam The reflected light 716 is reflected back, and another portion 718 of the incident light beam 710 will continue to be directed to the medium adjacent to the reagent layer 704. A portion 760 of the reflected light 716 reflected by a portion 714 of the incident light beam 71 will pass through the optical fiber 702 To the basic paper size, the Chinese National Standard (CNS) A4 specification (210 X 297 mm) is applicable -------------- ^ i — (Please read the notes on the back to write this page). Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 558635 5. In the Invention Description () Department, the other part of the reflected light 7 1 6 will be reflected back to the reagent layer 7 04 at the interface 7 0 (not shown). As will be discussed in detail below, at the root of the fiber 702, the reflected light 712 and 760 are detected and analyzed. Along any given point of the fiber 70, including its root, the reflected light 7 12 and 760 will have a phase difference. Based on this phase difference, the thickness of the reagent layer 704 can be detected. As shown in Fig. 7b, the probe 700 is immersed in the sample solution 734 to detect the presence of the antibody 73 6 complementary to the antigen 70 4 and the concentration of the antibody 7 3 6 in the sample solution 734. Because the characteristics of the antibody 7 3 6 and the antigen 704 determine that a special reaction will occur between them, the antibody 73 6 will adhere to the reagent layer 704, so that within a certain time, the reagent layer 704 An antibody layer 732 is formed. However, the non-complementary antibody 7 38 does not adhere to the reagent layer 704. For the sample solution 734, it is necessary to reduce the possibility that the probe 700 and (except the antibody) stick to each other. That is, it is necessary to make the reagent 700 on the probe 700 to reduce the possibility of adhesion to the non-complementary antibody 7 38. Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs For example, a representative example is that the size of molecules to be detected (such as antigens and antibodies) should be much smaller than the wavelength of incident light of 71 °. Therefore, from an optical point of view, the reagent layer 704 and the antibody layer 732 can be regarded as a single layer. That is, from an optical point of view, the interface 73 0 of the reagent layer 704 and the antibody layer 732 shown in FIG. 7b is usually not obvious. In this way, the combined layer of the reagent layer 704 and the antibody layer 732 shown in Fig. 7 is similar to the reagent layer 704 in Fig. 7a. However, the total thickness s 2 of the two layers is larger than the thickness of the individual reagent layer 704. Therefore, similar to the probe 700 in FIG. 7a, when the incident light 7 10 enters the end of the optical fiber 702, 'on the interface 706 between the optical fiber 702 and the combination layer, a part 712 of the incident light 710 is reflected back. At the same time, the incident light & Zhang scale is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 male * ^) Hcm \ uingiaiig \ o "issued 558635 A7 V. Description of the invention () Another part 710 720 continues to be combined The layer and sample solution 734. A portion 724 of 720 is reflected back, while another portion m of 720 continues through sample solution 734. For the reflected light 724, its-part 726 is returned to the optical fiber 702, while another part (not shown) is reflected by the interface ^ = in the composite layer. At any given point along the fiber 702, including its roots, the reflected beams 7 and 2 and 726 will exhibit a phase difference. Based on this phase difference, the thickness S 2 of the combined layer can be detected. By comparing the thickness S2 of the combined layer and the thickness si of the reagent layer 704, the thickness of the antibody layer 732 can be determined. Based on this thickness, the presence or absence of the complementary body in the sample solution 7 3 4 can be determined. Furthermore, the thickness S2 of the group layer can be sampled at discrete time points. The rate at which the thickness difference between the thickness S 2 of the square layer and the thickness S 1 of the reagent layer 704 increases (for example, the rate of increase in the thickness of the antibody layer 732) can be obtained. Based on this rate, the concentration of the complementary antibody 736 in the sample solution 734 can be measured in a short period of culture. Fig. 8 depicts a first improved method for implementing the biosensor using the above-mentioned bioprobe 700. Repeat again, the bioprobe 700 including the optical fiber 7 and the reagent layer 704 coated on the end of the optical fiber 702 should be immersed in the sample solution 734. As can be seen from the enlarged part in the figure, the optical fiber casing surrounds the optical fiber core until The end of the fiber core. More specifically, the fiber housing is wrapped with the fiber core from beginning to end, the sample solution is contained in the test tube 7 80, and the fiber probe 700 is connected to the biosensor analyzer 800 through the connector 802. Make order

This button scale applies to China National Standard (CNS) A4 specifications (210 X 297 male iY 558635 A7 B7 printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the invention () Optical sensor optical analyzer 8 0 0 including light source 8 0 4. Spectrometer 8 1 8. Periodic signal generator 8 2 0, phase tracker 8 2 2 and wheel out clothes set 8 2 4. Biosensor optical analyzer 8 00 can be implemented in many ways. For example, '(1 ) Commands from an external computer or computer network 8 2 6; (2) Commands from a microprocessor 83 0, which executes instructions issued by the program memory 832. This device also includes RAM 83 4; (3) or A command issued through a special application specific integrated circuit (ASIC) 830. In the first embodiment, the light source 804 is a broadband light source, such as a light emitting diode. The light source 804 may also be a tungsten halogen lamp. The light source The light beam emitted by 804 enters an optical waveguide such as an optical fiber, and an optical coupler 808 'can also be added to optically connect the optical waveguide 806 with another optical waveguide 828, the optical waveguide 8 28. An optional spectrometer 829 is connected. The spectrometer 829 preferably includes a one-dimensional charge coupled device (ccd), such as ι * 1024 CCD, and is connected to a periodic signal generator 82. The optional spectrometer 829 can It is a spectrometer from 600 to 700nrn. The optical coupler 8 0 also couples the optical waveguide 8 0 with another optical waveguide 10 light. The optical coupler 812 combines the optical waveguide 810 with another light Yubo V814 is optically coupled. The optical waveguide 814 is connected to the bioprobe 700 via a coupler 802. The optical surface Hopi 812 also connects the optical waveguide 814 to another optical waveguide 8 16. The optical waveguide 816 and the spectrometer 818. Like the spectrometer 829, the spectrometer 8 1 8 preferably includes a one-dimensional cc D, such as 1 * 1 0 2 4 CCD 'and is connected to the periodic signal generator. This paper ruler has not used the Chinese national standard ( CNS) A4 specification (21G X 297 male ^)

(Please read the note S on the back first --- --- π to fill out this page)-line · 558635 A7 B7 V. Description of the invention (The light emitted by the light source 804 printed by the staff consumer cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, through the optical The waveguide 800, the optical light coupler 800, the optical waveguide 810, the optical coupler 812, the optical waveguide 814, and the optical coupler 802 are received by the bioprobe 700. From the discussion of Fig. 7b above, The two reflected beams 7 2 and 726 pass through the bioprobe and return, and are received by the spectrometer 8 1 8 after passing through the coupler 802, the optical waveguide 814, and the optical waveguide 816. As described above, since the combined layer has With thickness s 2, the reflected beams 7 1 2 and 7 2 6 will have a weak out-of-phase phenomenon. Therefore, according to Fresnel theory, the reflected beams 712 and 72 6 will form a diffraction on the spectrometer 8 1 8 Diffraction pattern. As the thickness of the combined layer S2 increases, the diffraction pattern will move. When the spectrometer 8 18 records the pixels of the CCD, a periodic signal of 820 will generate a periodic signal waveform. The periodic k-blunt waveform determined by the radiograph (such as positive The phase of a sine wave can be detected by the phase tracker 8 2 2. By comparing the phase of the sine wave, the diffraction patterns obtained by the spectrometer sampling at different times are determined, and the increase rate of the combined layer thickness S2 can be double measured. After phase data is obtained or at the same time, the rate of increase of s 2 can be determined. Returning to FIG. 7 a, after the bioprobe 700 is immersed in the sample solution 734 of the month 'J, the thickness si of the delta-type agent layer 704 is also A diffraction pattern formed by the reflected beams 712 and 76 can be obtained. Figure 9 shows a part of the diffraction pattern displayed by the one-dimensional CCD device on the spectrometer 820 (that is, before the biological probe is immersed in the sample solution 734). Fig. 9b shows a part of the diffraction pattern displayed by the one-dimensional C (: D device on the spectrometer 820. Compare the figure "and the figure shown by Tupu (please read the precautions on the back page first) Binding. I : \ Patent \ tangtang \ 625 Invention patent (anna > 558635 A7 B7 V. Description of the invention () Whether the antibody 7 3 complementary to the antigen 7 〇 4 in the sample / hybrid 7 3 4 exists. Bio bismuth needle 7 0 〇 After immersing in the sample solution 7 3 4 The time spectrometer's sampling result of one-dimensional C CD can measure the rate of change of the pattern movement, and thus determine the concentration of the complementary antibody 7 3 6 in the sample solution 7 3 4. In the first implementation shown in FIG. 8 For example, the optical waveguides 806, 810, 814, 816, and 828 are preferably single-mode fibers, such as communication-grade single-mode fibers. However, multimode fibers can also be used, such as gradient fibers. The fiber diameter is at least 3 / zm, and it is best achieved. The optical coupling is 8 0 8 and 8 1 2 is preferably a "γ" type fiber, or an X-type optical coupler. However, if a second type of optical coupler is used, it is necessary to provide an index matching gel, which is used to remove the reflection noise at the open end. The spectrometer 829 coupled to the light source 804 is needed only when the spectrum of the laser diode of the light source 804 is unstable. A special case is to use a spectrometer 8 2 9 to distinguish the phase shift caused by the change in the thickness of the end of the biological slave needle 700 from the phase shift caused by the frequency shift of the light source. However, if the spectrum of the laser diode of the light source $ 0 * is very stable, the light source 804, the optical coupler 808, and the optical waveguide 828 are no longer needed. FIG. 10 is a second embodiment of the biosensor. Includes a supplementary biosensor optical analyzer 1,000. The composition of the system is basically similar to the system shown in Figure 8, except: 〇) the broadband light source 804 is a laser diode driven by the frequency signal generator 1 006; (2) the phase tracker 822 must be connected with the frequency signal generator 1 006 synchronization. The frequency signal generator 1006 produces a ramped frequency (or linear I, chlrp) driving signal. The working process of the system is shown in Figure 8. The paper size applies to the Chinese National Standard (CNS) A4 specification. ⑽χ 挪 公公.-* --- V. The invention description () is similar. However, the phase tracker 822 must be synchronized with the frequency signal generator I 006. In addition, the optical waveguides 806, 81, 814, Multi-mode optical fibers must also be used for ，, and 82 8 '. Because the bioprobe 700 is relatively small and allows movement, it can be detected instantly, or multiple bioprobes can be used instead of one to check different substances in the same solution. As shown in Figure Η, an optical multiplexer 1102 receives a beam of light (such as a mixed-frequency beam) emitted from a light source (out of daylight) at an input end. Through an input control signal, the optical multiplexer The multiplexer II 02 connects the input signal with the output signal through a single-pole multi-throw switch. The input control signal can be provided by the clock counter 1104. The optical multiplexer 1 1 02 passes a waveguide and connector 丨丨 〇 Connect one or more output signals to one or more bioprobes. Each of the one or more bioprobes 1106 ^ passes through the connector 111〇 and its corresponding optical sub-wave gas. The input of the worker 1108 is connected. The connector 1110 can be similar to the above-mentioned Υ type connection. According to the content of the input control signal, the optical demultiplexer 1108 outputs one of its N inputs to the spectrometer (not shown) Out). Although this example only shows a time division multiplexer device, the frequency division multiplexer is obviously also feasible. In the same way, when the volume of the biomolecule attached to the test end of the fiber changes, by detecting the reflection The phase of the spectral profile generated by the interference can be used to estimate the rate and magnitude of the volume change.

558635 A7 —-----__ 2Z_____ 5. Description of the invention () Indicator. Also, the biosensor system allows the system to collect data continuously, collect data from the last 2 data, and analyze the data over time. Because the data measurement is communicated through the optical letter 5 tiger, the biosensor system must be electrically insulated from the patient, so that direct in vivo testing can be performed. Since this biosensor = the bioprobe used is trivial compared to the sample solution (that is, it can be ignored), ‘other (non-complementary) adhesion can be minimized. Because this biosensor method uses the Fresnel reflection law, it is not only highly sensitive, but also very linear (please read the note on the back first to write this page) Binding · --Line · Intellectual Property Bureau of the Ministry of Economic Affairs The paper size printed by the employee consumer cooperative is applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 public meals ^ i: \ ment \ tangiang \ t) zb invention special anna) .cioc

Claims (1)

558635 A8 B8 C8 D8 Patent application scope Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, an optical fiber bio-detector using the phase tracking method, which includes: · a)-light source; b)-first fiber optic probe; 〇 —the first and a second detector, which are used to detect the interference light spectrum pattern formed by the reflected beam; d) —a connector; 〇 a signal processor, which is used to determine the performance of the first detector 0 is detected twice; the phase of the light spectrum pattern is detected, and the concentration of the substance to be measured determined by the phase shift of the two patterns is detected; the signal processor includes a microprocessor, a program memory, and a RAM; f) a Phase tracker; g)-an output device; h)-a periodic signal generator; 0-a first and a second optical coupler; j) a first optical waveguide, a second optical waveguide, a third optical one A fourth optical waveguide and a fifth optical waveguide; and the feature is that the first optical fiber probe is an optical fiber coated with a reagent at the end, including a section of optical fiber, and the root is used to receive the incident light beam Its end is coated with one or more layers of materials and reagents. The first optical fiber probe must generate at least a reflected beam generated by the incident beam. The first optical fiber probe is connected to the optical fiber biodetector via the connector. The fourth optical waveguide is connected; the light beam emitted by the light source is directed into the first optical waveguide, and the first optical waveguide is optically combined with the second optical waveguide (please read the note on the back first) Matters ^: ^ ^ This page) Binding · Binding-Thread-See the paper to identify the Hi logo, the second I: \ Patent \ tangtang \ 625 invention patent (am 558635 patent application scope waveguide system and the second detector The periodic signal generator is connected; the second optical converter is also connected with the first guide, the fourth optical waveguide system and the first detection optical wave-pump system are connected with the periodic signal generator; The first: optical-coupling coupler also couples the first optical waveguide in the form of an optical fiber, and the second optical waveguide and the fourth optical waveguide. Learn this brother Wuguang / brother four first The guides are optically coupled. The phase tracker is connected to the perimeter and the south-port of the loop. The output device, the Logic " "M; the periodic signal generator is also connected to the signal everywhere. The light source, the detector, the output device and the signal 2d are exclusively used in the field biological funeral device described in item 1. The characteristics, soil, the first and the second detectors are spectrometers. There are one-dimensional charge-combining devices (C is called; the first optical consumable is a Υ-type I coupler. F According to the optical fiber biological detector described in the first patent application scope, Ministry of Economic Affairs Printed by the Intellectual Property Office's Employee Cooperative Cooperative 4 The reason is that the light source is a broadband light source or an adjustable laser diode. According to the fiber optic bio-detector described in the scope of the patent application, its # 征 ： 于The first, second, third, fourth, and fifth waveguide systems are single-mode fibers or multi-mode fibers, and the minimum fiber diameter is 2 // m. ’, According to the declared patent scope! The optical fiber biological detector according to the item, its agronomic department is that the optical fiber biological detector further includes: " ^ frequency and the source. I: \ Patent \ tangtang \ 625 invention patent (ann second detector ^-(Please read the precautions on the back first, then this page)-Order-Thread · 1 ·-I! — Two · 558635 Patent-applicable frequency regulator for testing sample needles; The second optical signal of the material is multiplexed and multiplexed. The first and the first, are used to connect the light source and the chip-I and the ready-to-use time-division connection between the light source and the first- and second-fiber optical fibers. Probes; /, 乂 罘 1 光 'which is produced by connecting the probes to the first and second detectors; and the brother = :: laser diode driven by the staff member Qiqiu generator; The phase lun. Is not synchronized with the frequency signal generator. According to the fiber-optic biological detector described in Item 5 of the declared patent scope, the decaying phenomenon is that the optical signal multiplexer and the optical division multiplexer are synchronized to ensure that only the first And one of the first optical fiber vibrating pins is connected to the light source. 7 1¾ of Note • According to the optical fiber bio-detector according to item 5 of the patent scope, the U-series is that the first, second, third, fourth, and fifth optical waveguide systems are single-mode fiber or multi-mode fiber Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs, the paper size is applicable to the Chinese National Standard (CNS) A4 specification (210X297 race) I: \ Patent \ tangtang \ 625 Invention patent (face ^ d〇c