A biosensor, a detection system, and a detection method

Abstract

The present invention discloses a biosensor, a detection system, and a detection method, which relate to the field of optical biosensing technology; the biosensor comprises an input optical fiber, a sensing optical fiber, and an output optical fiber connected in sequence, the input optical fiber transmits an optical pulse signal to the sensing optical fiber, the sensing optical fiber generates a mid-infrared light source and a Mach-Zehnder interference spectrum, and the output optical fiber outputs the spectrum generated by the sensing optical fiber. The detection system comprises a pump light source module, a biosensor, and a detection module connected in sequence; the pump light source module provides an optical pulse signal to pass through the biosensor, generates a mid-infrared light source and a Mach-Zehnder interference spectrum in sequence, and transmits the light pulse signal to the detection module to detect the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biomolecules, thereby realizing biosensing, and applying it in the mid-infrared band, which greatly improves the sensitivity of the sensor, reduces the damage to the activity of biomolecules, and provides ideas for developing new detection technologies.

Description

Technical Field

[0001] The present invention relates to the field of optical biosensor technology, and in particular to a biosensor, a detection system, and a detection method. Background Art

[0002] The mid-infrared band (2-16 μm) covers the molecular characteristic absorption fingerprint region of most organic and inorganic substances, providing a powerful optical analysis tool for understanding molecular structure and related disciplines. In addition, this band covers the two most important atmospheric windows of 3-5 μm and 8-14 μm, further expanding its wide application in many fields such as atmospheric monitoring, biosensing and military remote sensing. Mid-infrared optical fiber has excellent wide infrared band transmission performance and high nonlinear characteristics. It is a nonlinear optical fiber that can produce supercontinuum spectra covering the mid- and far-infrared bands. Fiber optic biosensors are a combination of fiber optic sensing technology and biorecognition technology. They can realize the specific detection and monitoring of various biochemical substances such as trace proteins, small organic molecules and nucleic acids in body fluids. In order to explore online analysis, label-free, small sample detection and widely used biosensors, a wave of research on new fiber optic sensing technology has emerged.

[0003] The optical fiber-based Mach-Zehnder interferometer structure is a common means of achieving biosensing. This type of sensor consists of a light source, a coupler, and a detector. At the first coupler, the optical path is divided into two beams, namely the reference arm and the sensor arm. When the external environment changes, the optical path and phase of the transmission light in the reference arm do not change, while the optical path in the sensor arm changes. Therefore, when the light emitted by the light source is transmitted to the first coupler, it is divided into two beams in the reference arm optical path and the interference arm optical path. When the two beams meet the corresponding interference conditions, they will interfere when transmitted to the second coupler, and thus be received by the detector. The interference signal obtained by analysis can form a sensor. However, traditional optical fiber biosensors usually work in the near-infrared band, have low sensitivity and slow response speed, especially in the near-infrared band, which greatly damages the activity of biological molecules and is limited in detecting the expression of biological information. Therefore, it is urgent to develop high-performance biosensors with high sensitivity and low damage. Summary of the invention

[0004] In view of the shortcomings of the current optical fiber biosensor technology, the present invention provides a biosensor, a detection system, and a detection method. Based on the mid-infrared light source generated by the self-phase modulation effect of the sensing optical fiber, an interference spectrum is generated through an embedded Mach-Zehnder interference structure, and the concentration change of the biomolecule to be tested is detected by the detection module. The wavelength of the interference spectrum drifts, and biosensing is realized. It is applied in the mid-infrared band, which greatly improves the sensitivity of the sensor and reduces the damage to the activity of biomolecules.

[0005] In a first aspect, the present invention proposes a biosensor, comprising an input optical fiber, a sensing optical fiber and an output optical fiber connected in sequence, wherein the input optical fiber and the output optical fiber are connected at both ends of the sensing optical fiber; the input optical fiber transmits an optical pulse signal to the sensing optical fiber, the sensing optical fiber generates a mid-infrared light source and a Mach-Zehnder interference spectrum, and the output optical fiber outputs the spectrum generated by the sensing optical fiber.

[0006] The sensing optical fiber comprises a core and a cladding covering the core, and the sensing optical fiber has a full normal dispersion distribution.

[0007] The input optical fiber and the output optical fiber are single-mode optical fiber or multi-mode optical fiber.

[0008] The sensing optical fiber adopts mid-infrared optical fiber, and the mid-infrared optical fiber adopts tellurite optical fiber, sulfide optical fiber, fluoride optical fiber or selenide optical fiber, and the structure adopts step refractive index optical fiber or gradient refractive index optical fiber.

[0009] The core diameter of the sensing optical fiber is in the range of 5 to 8 μm, the cladding outside the core has a diameter in the range of 100 to 130 μm, and the length is in the range of 5 to 10 cm.

[0010] The sensing optical fiber adopts a Mach-Zehnder interference structure, and a microcavity is formed by removing the core and cladding of a set microcavity position in a first optical arm through a femtosecond laser, and the second optical arm is in the core of the sensing optical fiber.

[0011] The core size of the sensing optical fiber removed from the microcavity ranges from 2 to 4 μm, and the cavity length ranges from 50 to 70 μm.

[0012] In a second aspect, the present invention also provides a biosensor detection system, which is implemented using the biosensor, and includes: a pump light source module, a biosensor and a detection module connected in sequence; the pump light source module provides a light pulse signal that is transmitted to the sensing fiber of the biosensor through the input optical fiber of the biosensor, and the sensing optical fiber generates a mid-infrared light source and a Mach-Zehnder interference spectrum in sequence, which is transmitted to the detection module through the output optical fiber of the biosensor, and the detection module detects the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biological molecules.

[0013] The sensing optical fiber generates a mid-infrared light source through a self-phase modulation effect, and the mid-infrared light source is a mid-infrared supercontinuum light source.

[0014] The pump light source module adopts a femtosecond pulse laser, and the central wavelength range of the femtosecond pump pulse is 4000-6000nm, the frequency range is 60-90MHz, and the pulse width range is 150-200fs.

[0015] The detection module uses a spectrometer to detect the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biomolecules.

[0016] In a third aspect, the present invention provides a biosensor detection method, comprising:

[0017] The pump light source module emits a femtosecond pump pulse, which is transmitted to the sensing fiber in the biosensor through the input optical fiber; the wavelength of the femtosecond pump pulse is in the normal dispersion region of the sensing fiber, the sensing fiber produces a self-phase modulation effect, and outputs a mid-infrared light source; the mid-infrared light source is transmitted along the sensing fiber through the embedded Mach-Zehnder interference structure, generates a Mach-Zehnder interference spectrum and outputs it to the detection module; the microcavity in the Mach-Zehnder interference structure is filled with biomolecules, and when the concentration of biomolecules changes, the wavelength drift of the Mach-Zehnder interference spectrum with the concentration of biomolecules is detected to achieve biosensing.

[0018] The beneficial effects of adopting the above technical solution are:

[0019] 1. The present invention proposes a biosensor integrating a mid-infrared light source and Mach-Zehnder interferometry, which has high sensitivity and fast response speed, and greatly reduces the damage to the activity of biological molecules.

[0020] 2. The biosensor designed by the present invention integrates a mid-infrared light source and Mach-Zehnder interferometry, which not only generates a mid-infrared supercontinuum light source, but also generates an interference spectrum with an embedded interference structure, providing a new idea for the development of multifunctional optical fiber equipment and facilitating large-scale production in practical applications.

[0021] 3. The system designed by the present invention integrates mid-infrared light source and Mach-Zehnder interferometry and is applied to the mid-infrared band. The modules are independent and the fiber nonlinear technology is combined with the interference technology in fiber optic sensing, which provides ideas for the development of new detection technology. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 A schematic diagram of the structure of an optical fiber sensor in an embodiment of the present invention;

[0023] Figure 2 is a transverse cross-sectional view of a sulfide step-index optical fiber according to an embodiment of the present invention;

[0024] Figure 3 This is a schematic diagram of the overall structure of a system integrating a mid-infrared light source and Mach-Zehnder interferometry in an embodiment of the present invention;

[0025] Figure 4 A flow chart of a measurement method provided by an embodiment of the present invention;

[0026] Figure 5 This is a dispersion distribution diagram of a sulfide step-index optical fiber in an embodiment of the present invention;

[0027] Figure 6 This is a spectrum diagram of a mid-infrared supercontinuum light source generated by a sulfide step-index optical fiber in an embodiment of the present invention;

[0028] Figure 7 The output spectrum of Mach-Zehnder interferometry at different biomolecule concentrations in an embodiment of the present invention;

[0029] Figure 8 The central wavelength and fitting curve of the interference trough at different biomolecule concentrations in the embodiment of the present invention; DETAILED DESCRIPTION

[0030] The specific implementation of the present invention is further described in detail below in conjunction with the drawings and examples.

[0031] The present invention provides a biosensor, a detection system, and a detection method. A mid-infrared light source generated based on the self-phase modulation effect of a sensing optical fiber 23 generates an interference spectrum through an embedded Mach-Zehnder interference structure 24 and is detected by a detection module. When the concentration of the biomolecule to be measured changes, the wavelength of the interference spectrum drifts, and biosensing is realized. When applied in the mid-infrared band, the sensitivity of the sensor is greatly improved, and the damage to the activity of the biomolecule is reduced.

[0032] In a first aspect, the present invention provides a biosensor 2, such as Figure 1 As shown, it includes an input optical fiber 21, a sensing optical fiber 23 and an output optical fiber 22 connected in sequence, wherein the input optical fiber 21 and the output optical fiber 22 are connected at both ends of the sensing optical fiber 23; the input optical fiber 21 transmits the optical pulse signal to the sensing optical fiber 23, the sensing optical fiber 23 generates a mid-infrared light source and a Mach-Zehnder interference spectrum, and the output optical fiber 22 outputs the spectrum generated by the sensing optical fiber 23.

[0033] In this embodiment, two ends of the sensing optical fiber 23 in the optical fiber sensor are fused with the input optical fiber 21 and the output optical fiber 22 respectively to form a three-section overall structure.

[0034] The sensing optical fiber 23 includes a core and a cladding covering the core. Figure 2 As shown, the sensing optical fiber 23 has a fully normal dispersion distribution, such as Figure 5 shown.

[0035] The input optical fiber 21 and the output optical fiber 22 are single-mode optical fibers or multi-mode optical fibers. In this embodiment, single-mode optical fibers are used.

[0036] The sensing optical fiber 23 is a mid-infrared optical fiber, which is a tellurite optical fiber, a sulfide optical fiber, a fluoride optical fiber, or a selenide optical fiber, and has a step-index optical fiber or a gradient-index optical fiber. In this embodiment, a sulfide step-index optical fiber is used.

[0037] The core diameter of the sensing optical fiber 23 is in the range of 5 to 8 μm, the diameter of the cladding outside the core is in the range of 100 to 130 μm, and the length is in the range of 5 to 10 cm.

[0038] The sensing optical fiber 23 adopts a Mach-Zehnder interference structure 24 , and a microcavity is formed by removing the core and cladding of the microcavity position by femtosecond laser in the first optical arm, and the second optical arm is in the core of the sensing optical fiber 23 .

[0039] The core size of the sensing optical fiber 23 removed from the microcavity is in the range of 2 to 4 μm, and the cavity length is in the range of 50 to 70 μm.

[0040] In a second aspect, the present invention also provides a biosensor detection system, such as Figure 3 As shown, the biosensor is implemented, including: a pump light source module 1, a biosensor 2 and a detection module 3 connected in sequence; the pump light source module 1 provides a light pulse signal that is transmitted to the sensing fiber 23 of the biosensor 2 through the input optical fiber 21 of the biosensor 2, and the sensing optical fiber 23 generates a mid-infrared light source and a Mach-Zehnder interference spectrum in sequence, which are transmitted to the detection module 3 through the output optical fiber 22 of the biosensor 2, and the detection module 3 detects the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biological molecules.

[0041] The sensing optical fiber 23 generates a mid-infrared light source through a self-phase modulation effect, and the mid-infrared light source is a mid-infrared supercontinuum light source.

[0042] The pump light source module 1 adopts a femtosecond pulse laser, and the central wavelength range of the femtosecond pump pulse is 4000-6000nm, the frequency range is 60-90MHz, and the pulse width range is 150-200fs.

[0043] The detection module 3 uses a spectrometer to detect the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biomolecules.

[0044] In a third aspect, the present invention provides a biosensor detection method, such as Figure 4 As shown, including:

[0045] The pump light source module 1 emits a femtosecond pump pulse, which is transmitted to the sensing fiber 23 in the biosensor 2 through the input optical fiber 21; the wavelength of the femtosecond pump pulse is located in the normal dispersion region of the sensing optical fiber 23, and the sensing optical fiber 23 produces a self-phase modulation effect and outputs a mid-infrared light source; the mid-infrared light source is transmitted along the sensing optical fiber 23 through the embedded Mach-Zehnder interference structure 24, generates a Mach-Zehnder interference spectrum and outputs it to the detection module 3; the microcavity in the Mach-Zehnder interference structure 24 is filled with biomolecules, and when the concentration of the biomolecules changes, the wavelength drift of the Mach-Zehnder interference spectrum with the concentration of the biomolecules is detected to achieve biosensing.

[0046] In this embodiment, a preferred structure of an optical fiber sensor is as follows: the input optical fiber 21 and the output optical fiber 22 of the optical fiber sensor are single-mode optical fibers, the sensing optical fiber 23 is a sulfide step-index optical fiber, the sulfide step-index optical fiber has a Mach-Zehnder interference structure 24 embedded therein, the removed core size is 3 μm, the cavity length size is 50 μm, the diameter of the sulfide step-index optical fiber core 231 is 6 μm, the diameter of the cladding 232 outside the core is 120 μm, and the length is 5 cm. The transverse cross-sectional view is as shown in FIG. Figure 2 The fully normal dispersion distribution obtained by numerical simulation is shown in Figure 3 shown.

[0047] A system integrating mid-infrared light source and Mach-Zehnder interferometry is designed using the above sensor, such as Figure 4 As shown, it includes: a pump light source module 1, a biosensor 2, and a detection module 3. The pump light source module 1 is connected to the biosensor 2, and the biosensor 2 is connected to the detection module 3.

[0048] In this embodiment, the pump light source module 1 uses a femtosecond laser, model TOPOL, and the emitted pump pulse has a central wavelength of 5000nm, a frequency of 80MHz, and a pulse width of 200fs. The detection module 3 uses a spectrometer, model YOKOGAWAAQ6375B.

[0049] The pump light source mode 1 emits a femtosecond pump pulse, which is coupled into the sulfide step fiber 23 in the biosensor 2 through the input single-mode fiber 21; the wavelength of the femtosecond pump pulse is located in the normal dispersion region of the sulfide step fiber 23, and the sulfide step fiber 23 produces a self-phase modulation effect, and outputs a mid-infrared supercontinuum light source, such as Figure 6 As shown; the mid-infrared supercontinuum light source is transmitted along the sensing optical fiber 23 through the embedded Mach-Zehnder interference structure 24, generating a Mach-Zehnder interference spectrum and finally outputting it to the detection module 3; the microcavity in the Mach-Zehnder interference structure 24 is filled with biomolecules, and when the concentration of biomolecules changes, the detection module 3 detects the drift of the output interference spectrum wavelength, thereby realizing biosensing technology.

[0050] At room temperature (20°C), when the biomolecule concentrations are 5000ppm, 10000pm, 15000ppm, 20000ppm, 24000ppm, 29000ppm, 34000ppm, and 38000ppm, the output interference spectra detected by the spectrometer are as follows: Figure 7 As shown, the preferred center wavelength of the last interference trough is shown in Table 1:

[0051] Table 1. Biomolecule concentrations and central wavelengths of interference troughs.

[0052] Biomolecule concentration (ppm) Wavelength (nm) 5000 8838 10000 8726.1 15000 8620 20000 8515.5 24000 8407.6 29000 8300 34000 8215.7 38000 8158.8

[0053] The biosensor sensitivity obtained by fitting is -0.025nm / ppm, such as Figure 8 shown.

Claims

1. A biosensor comprising an input optical fiber, a sensing optical fiber and an output optical fiber connected in sequence, characterized in that: The input optical fiber and the output optical fiber are connected at both ends of the sensing optical fiber; the input optical fiber transmits the optical pulse signal to the sensing optical fiber, the sensing optical fiber generates a mid-infrared light source and a Mach-Zehnder interference spectrum, and the output optical fiber outputs the spectrum generated by the sensing optical fiber; The sensing optical fiber comprises a core and a cladding covering the core, and the sensing optical fiber has a full normal dispersion distribution; The sensing optical fiber adopts mid-infrared optical fiber, and the mid-infrared optical fiber has a built-in Mach-Zehnder interference structure. In the first optical arm, the core and cladding of the microcavity position are removed by femtosecond laser to form a microcavity, and the second optical arm is in the core of the sensing optical fiber; The optical pulse signal is transmitted into the sensing optical fiber, a self-phase modulation effect is generated in the sensing optical fiber, and a mid-infrared light source is output; when the mid-infrared light source is transmitted along the sensing optical fiber, it passes through the embedded Mach-Zehnder interference structure to generate a Mach-Zehnder interference spectrum.

2. The biosensor according to claim 1, characterized in that: The input optical fiber and the output optical fiber are single-mode optical fiber or multi-mode optical fiber.

3. The biosensor according to claim 1, characterized in that: The mid-infrared optical fiber adopts tellurite optical fiber, sulfide optical fiber, fluoride optical fiber or selenide optical fiber, and the structure adopts step refractive index optical fiber or gradient refractive index optical fiber.

4. The biosensor according to claim 3, characterized in that: The core diameter of the sensing optical fiber is in the range of 5 to 8 μm, the cladding outside the core has a diameter in the range of 100 to 130 μm, and the length is in the range of 5 to 10 cm; The core size of the sensing optical fiber removed from the microcavity ranges from 2 to 4 μm, and the cavity length ranges from 50 to 70 μm.

5. A biosensor detection system, implemented by the biosensor according to claim 1, comprising a pump light source module, a biosensor and a detection module connected in sequence; characterized in that: The pump light source module provides a light pulse signal which is transmitted to the sensing fiber of the biosensor through the input fiber of the biosensor. The sensing fiber generates a mid-infrared light source and a Mach-Zehnder interference spectrum in turn, which are transmitted to the detection module through the output fiber of the biosensor. The detection module detects the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biological molecules.

6. The biosensor detection system according to claim 5, characterized in that: The sensing optical fiber generates a mid-infrared light source through a self-phase modulation effect, and the mid-infrared light source is a mid-infrared supercontinuum light source.

7. The biosensor detection system according to claim 6, characterized in that: The pump light source module adopts a femtosecond pulse laser, the central wavelength range of the femtosecond pump pulse is 4000-6000nm, the frequency range is 60-90MHz, and the pulse width range is 150-200fs; The core diameter of the sensing optical fiber is in the range of 5 to 8 μm, the cladding outside the core has a diameter in the range of 100 to 130 μm, and the length is in the range of 5 to 10 cm.

8. The biosensor detection system according to claim 7, characterized in that: The detection module uses a spectrometer to detect the wavelength of the Mach-Zehnder interference spectrum along with the concentration of biomolecules.

9. A biosensor detection method, implemented by the biosensor detection system according to claim 5, characterized in that: The pump light source module emits a femtosecond pump pulse, which is transmitted to the sensing fiber in the biosensor through the input optical fiber; the wavelength of the femtosecond pump pulse is in the normal dispersion region of the sensing optical fiber, the sensing optical fiber produces a self-phase modulation effect, and outputs a mid-infrared light source; The mid-infrared light source is transmitted along the sensing optical fiber through the embedded Mach-Zehnder interference structure to generate a Mach-Zehnder interference spectrum and output it to the detection module; the microcavity in the Mach-Zehnder interference structure is filled with biomolecules. When the concentration of biomolecules changes, the wavelength drift of the Mach-Zehnder interference spectrum with the concentration of biomolecules is detected to achieve biosensing.

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