A THZ-SPRi biosensor system and its negative feedback algorithm

Abstract

The present invention discloses a THZ-SPRi biosensor system and its negative feedback algorithm, including: a terahertz emission module, a sensor module, a terahertz detection module and a signal display module; the sensor module is arranged between the terahertz emission module and the terahertz detection module, the terahertz emission module includes a terahertz emitter and an adjustable filter arranged between the terahertz emitter and the sensor module, the signal display module is respectively connected to the terahertz detector and the adjustable filter, the sensor module includes a metal film, a biosensor chip and a prism, the metal film is arranged on the prism, the biosensor chip is coupled to the metal film, and the terahertz light beam emitted by the terahertz emitter enters the sensor module from the prism and is refracted from the prism. The terahertz surface plasmon resonance imaging sensing technology is used to realize the detection of biological tissues, and has the performance of high sensitivity, high throughput and rapid detection in biosensing, and solves the technical problem of slow imaging speed in the current SPRi sensing technology.

Description

Technical Field

[0001] The present invention relates to the technical field of optical sensing, and in particular to a THZ-SPRi biosensor system and a negative feedback algorithm thereof. Background Art

[0002] Terahertz (THz) is a type of electromagnetic radiation in a specific band, which is mainly between microwaves and infrared radiation. It generally refers to electromagnetic waves with a frequency range of 0.1-10THZ and a wavelength range of 0.3-3mm. With the continuous maturity and commercialization of ultrafast laser technology, numerous terahertz pulse radiation and detection methods have been studied one after another. Due to the many characteristics of terahertz radiation, such as wide spectrum, narrow pulse width, non-destructiveness, coherence, hydrophobia, perspective, fingerprint absorption spectrum, etc., it is determined that it has huge development space in many industrial, military and basic research fields.

[0003] SPR sensing technology has become an important tool for exploring molecular interactions with its advantages of label-free, high time resolution, non-invasiveness, and high sensitivity, and has been widely used in biochemical analysis, drug development and other fields. With the development of biotechnology, people are increasingly in need of high-throughput sensing methods that can detect multiple samples at the same time. SPRi combines sensing technology with imaging technology to improve the SPR sensing flux and achieve high-throughput detection of multiple samples at the same time. SPRi sensing technology has been widely used to detect heteroaffinity and the kinetic binding process of macromolecules. Summary of the invention

[0004] The main purpose of the present invention is to provide a THZ-SPRi biosensor system and its negative feedback algorithm, which uses terahertz surface plasmon resonance imaging sensing technology to realize biological tissue detection. It has the performance of high sensitivity, high throughput and rapid detection in biosensing, and solves the technical problem of slow imaging speed in the current SPRi sensing technology.

[0005] To achieve the above-mentioned purpose, the first aspect of the present invention provides a THZ-SPRi biosensor system, comprising: a terahertz emission module, a sensing module, a terahertz detection module and a signal display module; the sensing module is arranged between the terahertz emission module and the terahertz detection module, the terahertz emission module comprises a terahertz emitter and an adjustable filter arranged between the terahertz emitter and the sensing module, the signal display module is respectively connected to the terahertz detector and the adjustable filter, the sensing module comprises a metal film, a biosensor chip and a prism, the metal film is arranged on the prism, the biosensor chip is coupled to the metal film, and the terahertz light beam emitted by the terahertz emitter enters the sensing module from the prism and is refracted from the prism.

[0006] Furthermore, the terahertz transmitting module further includes a polarizer arranged between the tunable filter and the sensing module, and the terahertz detecting module includes a terahertz detector and an analyzer arranged between the terahertz detector and the sensing module.

[0007] Furthermore, the terahertz transmitting module also includes an aperture stop, and the aperture stop is arranged between the terahertz generator and the tunable filter.

[0008] Furthermore, a first lens is arranged between the terahertz emitter and the aperture stop, and the first lens is arranged between the aperture stop and the tunable filter.

[0009] Furthermore, a second lens is arranged between the analyzer and the terahertz detector, and the second lens is arranged between the analyzer and the sensor module.

[0010] Furthermore, the sensor module also includes a circulation pool arranged on the metal film, an injection tube connected to the circulation pool, and a peristaltic pump connected to the circulation pool.

[0011] Furthermore, the second aspect of the present invention provides a negative feedback algorithm for a THZ-SPRi biosensor system, comprising the steps of:

[0012] S1: setting the scanning times to n, and performing a large-range scanning on the sensing module to obtain an initial resonance wavelength λ0;

[0013] S2: Select a scanning range from λ0-x to λ0+x, and scan the sensor module;

[0014] S3: Determine whether the refractive index of the sensor module changes, if yes, go to S4, if no, go to S2;

[0015] S4: Determine the new resonance wavelength λ by changing the refractive index i ;

[0016] S5: Determine whether i>n is true, if true, go to S6, if not true, go to S51;

[0017] S51: Select scanning range from λ i -x~λ i +x, and scan the sensor module;

[0018] S52: Determine whether the refractive index of the sensing module has changed, if so, go to S4, if not, go to S51;

[0019] S6: In a series of resonant wavelengths λ0~λ iThe minimum resonance wavelength is set to λ min , take out the maximum resonance wavelength and set it as λ max , then the range of the resonance wavelength is λ min -x~λ max +x.

[0020] The present invention provides a THZ-SPRi biosensor system, which has the following beneficial effects: a terahertz light beam emitted by a terahertz transmitter enters a sensing module through a prism and is refracted from the prism; when a biological sample on a metal film interacts with a molecule modified on a biosensor chip, the refractive index of the sensing module will change, and a signal of the refractive index change will be displayed by a signal display module. By processing the received signal, a negative feedback modulation is performed on an adjustable filter to control the range of the scanning spectrum, thereby realizing rapid scanning biosensing. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without paying any creative work.

[0022] Figure 1 It is a structural schematic block diagram of a THZ-SPRi biosensor system of the present invention;

[0023] Figure 2 Schematic diagram of the flow of a negative feedback algorithm of a THZ-SPRi biosensor system of the present invention.

[0024] The above drawings include the following reference numerals:

[0025] 11. Terahertz emitter; 12. Tunable filter; 13. Polarizer; 14. Aperture stop; 15. First lens; 21. Metal film; 22. Prism; 23. Circulation cell; 24. Injection tube; 31. Terahertz detector; 32. Analyzer; 33. Second lens; 40. Signal display module. DETAILED DESCRIPTION

[0026] In order to make the purpose, features and advantages of the present invention more obvious and easy to understand, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0027] See also Figure 1 , which is a THZ-SPRi biosensor system, comprising: a terahertz emission module, a sensing module, a terahertz detection module and a signal display module 40; the sensing module is arranged between the terahertz emission module and the terahertz detection module, the terahertz emission module comprises a terahertz emitter 11 and an adjustable filter 12 arranged between the terahertz emitter 11 and the sensing module, the signal display module 40 is respectively connected to the terahertz detector 31 and the adjustable filter 12, the sensing module comprises a metal film 21, a biosensor chip and a prism 22, the metal film 21 is arranged on the prism 22, the biosensor chip is coupled to the metal film 21, and the terahertz light beam emitted by the terahertz emitter 11 enters the sensing module from the prism 22 and is refracted from the prism 22.

[0028] In the present invention, the terahertz light beam emitted by the terahertz transmitter 11 enters the sensor module through the prism 22 and is refracted from the prism 22; when the biological sample on the metal film 21 interacts with the modified molecules on the biosensor chip, the refractive index of the sensor module will change, and the signal of the refractive index change is displayed by the signal display module 40. The adjustable filter 12 is negatively feedback modulated by the received signal processing to control the range of the scanning spectrum, thereby realizing fast scanning biosensing. This technical solution uses terahertz surface plasmon resonance imaging sensing technology to realize biological tissue detection and reduce damage to biological tissue. It has high sensitivity, high throughput and fast detection performance in biosensing, and solves the technical problem of slow imaging speed in the current SPRi sensing technology.

[0029] Furthermore, the terahertz emission module also includes a polarizer 13 arranged between the adjustable filter 12 and the sensor module, and the terahertz detection module includes a terahertz detector 31 and an analyzer 32 arranged between the terahertz detector 31 and the sensor module. Polarized light is obtained through the polarizer 13, and the polarized light produces a SPRI effect with the biological sample on the metal film 21. The reflected terahertz light beam is checked by the analyzer 32 to see whether it is polarized light, and finally received by the terahertz detector 31.

[0030] Preferably, the terahertz transmitting module also includes an aperture diaphragm 14, which is arranged between the terahertz generator and the tunable filter 12, and a first lens 15 is arranged between the terahertz emitter 11 and the aperture diaphragm 14, and a first lens 15 is arranged between the aperture diaphragm 14 and the tunable filter 12; the first lens 15 collimates and focuses the terahertz light beam emitted by the terahertz emitter 11, and the aperture diaphragm 14 performs spatial filtering on the focused terahertz light beam, and the terahertz light beam filtered by the aperture diaphragm 14 is further focused by the first lens 15 and enters the tunable filter 12.

[0031] Similarly, a second lens 33 is disposed between the analyzer 32 and the terahertz detector 31 , and a second lens 33 is disposed between the analyzer 32 and the sensor module. The second lens 33 collimates and focuses the refracted terahertz light beam before entering the analyzer 32 .

[0032] Furthermore, the sensing module also includes a circulation pool 23 arranged on the metal film 21, an injection tube 24 connected to the circulation pool 23, and a peristaltic pump connected to the circulation pool 23. The biological sample is injected into the circulation pool 23 through the injection tube 24 and then contacts the metal film 21; preferably, a p625 peristaltic pump is used, which has high stability and can be used with different peristaltic tubes to select the flow rate. The peristaltic tube can be a No. 020 peristaltic tube.

[0033] like Figure 2 As shown, the present invention provides a negative feedback algorithm of a THZ-SPRi biosensor system, comprising the steps of:

[0034] S1: Set the number of scans to n, and perform a large-scale scan of the sensor module to obtain the initial resonance wavelength λ0;

[0035] S2: Select the scanning range from λ0-x to λ0+x and scan the sensor module;

[0036] S3: Determine whether the refractive index of the sensing module has changed. If so, go to S4; if not, go to S2;

[0037] S4: Determine the new resonance wavelength λ by changing the refractive index i ;

[0038] S5: Determine whether i>n is true, if true, go to S6, if not true, go to S51;

[0039] S51: Select scanning range from λ i -x~λ i +x, and scan the sensor module;

[0040] S52: Determine whether the refractive index of the sensing module has changed, if so, go to S4, if not, go to S51;

[0041] S6: In a series of resonant wavelengths λ0~λ i The minimum resonance wavelength is set to λ min , take out the maximum resonance wavelength and set it as λ max , then the range of the resonance wavelength is λ min -x~λ max +x.

[0042] In this technical solution, the initial resonance wavelength is obtained by scanning a large range, and the band near the resonance wavelength is continuously scanned locally, which can ensure that when the biological sample changes, the resonance wavelength position is always within the scanning range, reducing the scanning area and improving the scanning efficiency. The THZ-SPRi biosensor system uses a negative feedback step tracking algorithm and broadband terahertz attenuated total reflection technology to achieve refractive index detection of biological samples, improving the limitation of the slow imaging speed of existing SPRi.

[0043] The above is a description of a THZ-SPRi biosensor system and its negative feedback algorithm provided by the present invention. For those skilled in the art, according to the ideas of the embodiments of the present invention, there may be changes in the specific implementation methods and application scopes. In summary, the content of this specification should not be understood as limiting the present invention.

Claims

1. A negative feedback algorithm for a THZ-SPRi biosensor system, characterized in that: The system comprises: a terahertz emission module, a sensing module, a terahertz detection module and a signal display module; The sensing module is arranged between the terahertz transmitting module and the terahertz detecting module, the terahertz transmitting module comprises a terahertz transmitter and an adjustable filter arranged between the terahertz transmitter and the sensing module, the signal display module is connected to the terahertz detecting module and the adjustable filter respectively, the sensing module comprises a metal film, a biosensor chip and a prism, the metal film is arranged on the prism, the biosensor chip is coupled to the metal film, and the terahertz light beam emitted by the terahertz transmitter enters the sensing module from the prism and is refracted from the prism; The negative feedback algorithm comprises the steps of: S1: setting the scanning times to n, and performing a large-range scanning on the sensing module to obtain an initial resonance wavelength λ0; S2: Select a scanning range from λ0-x to λ0+x, and scan the sensor module; S3: Determine whether the refractive index of the sensor module changes, if yes, go to S4, if no, go to S2; S4: Determine the new resonance wavelength λi by changing the refractive index; S5: Determine whether i>n is true, if true, go to S6, if not true, go to S51; S51: Select a scanning range from λi-x to λi+x, and scan the sensor module; S52: Determine whether the refractive index of the sensing module has changed, if so, go to S4, if not, go to S51; S6: From a series of resonance wavelengths λ0~λi, the minimum resonance wavelength is taken out and set as λmin, and the maximum resonance wavelength is taken out and set as λmax, so that the range of the resonance wavelength is obtained to be λmin-x~λmax+x.

2. The negative feedback algorithm according to claim 1, characterized in that: The terahertz transmitting module further includes a polarizer arranged between the tunable filter and the sensing module, and the terahertz detecting module includes a terahertz detector and an analyzer arranged between the terahertz detector and the sensing module.

3. The negative feedback algorithm according to claim 2, characterized in that: The terahertz emission module further includes an aperture stop, which is arranged between the terahertz emitter and the tunable filter.

4. The negative feedback algorithm according to claim 3, characterized in that: A first lens is arranged between the terahertz emitter and the aperture stop, and the first lens is arranged between the aperture stop and the tunable filter.

5. The negative feedback algorithm according to claim 4, characterized in that: A second lens is arranged between the analyzer and the terahertz detector, and the second lens is arranged between the analyzer and the sensor module.

6. The negative feedback algorithm according to claim 1, characterized in that: The sensor module further includes a circulation pool disposed on the metal film, an injection tube communicating with the circulation pool, and a peristaltic pump connected to the circulation pool.

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