TWI770836B - Biological sensing apparatus, biological sensing system, and method of using the same - Google Patents

Abstract

A biological sensing apparatus includes an optical waveguide substrate, a surface plasmon resonance (SPR) layer, and a lossy mode resonance (LMR) layer. The optical waveguide substrate includes a light input end and a light output end opposite to each other, and a biological sensing area is formed on one surface of the optical waveguide substrate between the light input end and the light output end. The SPR layer includes a metal layer and a plurality of biological probes. The metal layer is arranged on a part of the biological sensing area, and the plurality of biological probes are evenly arranged on the metal layer. The LMR layer is arranged on part of the biological sensing area and does not overlap with the SPR layer. The present disclosure further includes a biological sensing system and a method of using the same.

Description

Biosensing device, biosensing system and method of using the same

The present invention relates to a biological sensing device, a biological sensing system and a method of using the same, in particular to a biological sensing device, biological Sensing system and method of use thereof.

The way of life of human beings changes with the development of the country and society. In the era of rapid technological development and convenient medical services, many countries have never developed or are developing countries. Enjoying the convenience brought by technology is no longer a priority. Dream, the distance between countries is no longer distance, whether it is industry, information, culture and food are all benefited. With the convenience and longevity of life, civilized diseases such as heart disease, cancer, obesity and diabetes have also appeared. Taking diabetes as an example, its main feature is that the blood sugar of the patient is higher than the standard value for a long time; normally, when the blood sugar of the human body rises, the blood sugar should be controlled by insulin to reduce it. In the detection of diabetes, glycated hemoglobin (HbA1c) can be detected as the basis for the blood sugar status in the past 3 months.

In the past few years, surface plasmon resonance (SPR) technology has made great progress, and its high sensitivity makes it widely used in biological and chemical fields for molecular-level detection. in many research work Among them, the sensor of surface plasmon resonance (SPR) technology is generally constructed with high refractive index prism, and the incident angle of light can be changed in a wide range, so any medium and the object to be measured can be changed. A suitable angle can be found to excite the surface plasmon, so that the incident light will undergo total internal reflection (TIR) at the interface between the optical waveguide and the resonant film, and an evanescent wave will be generated. Among them, the incident light includes transverse electric (TE) waves and transverse magnetic (TM) waves, and surface plasmon resonance (SPR) technology can only be excited by TM waves.

However, the sensor structure with a high-end design usually has a huge volume and requires expensive optical equipment (such as a lens group) and precision mechanical equipment (such as an air-cushion optical shock-proof device), which is not easy to achieve miniaturization and product volume. Produce. In addition, in the detection process using surface plasmon resonance (SPR) technology, there are two possible shifts in the resonance wavelength. It is caused by taking (or being adsorbed) to the surface to be measured, and another displacement amount (hereinafter referred to as environmental interference signal) is caused by the change of the refractive index of the liquid with temperature fluctuations, or caused by the disturbance of the light source. The aforementioned environmental interference signals and biological signals will be superimposed on each other, resulting in signal distortion, resulting in inaccurate biological sensing results.

Therefore, how to design a biosensing device, a biosensing system and a method for using the same to solve the aforementioned technical problems is an important subject studied by the inventor of the present application.

The purpose of the present invention is to provide a biosensing device, a biosensing system and a method for using the same, which can avoid the use of a huge volume of ion and can instantly remove environmental interference signals, thereby solving the problem of the prior art that it is not easy to achieve miniaturization And the technical problem of easily causing signal distortion, so as to achieve the purpose of being convenient to carry, easy to mass-produce and accurate biological sensing results.

In order to achieve the aforementioned purpose, a biological sensing device proposed by the present invention includes: an optical waveguide substrate, a surface plasmon resonance layer and a lossy mode resonance layer. Wherein, the optical waveguide substrate includes an optical input end and an optical output end opposite to each other, and a biological sensing area is formed on one surface of the optical waveguide substrate between the optical input end and the optical output end. The surface plasmon resonance layer includes a metal layer and a plurality of biological probes, the metal layer covers part of the biological sensing area, and the plurality of biological probes are evenly arranged on the metal layer. The lossy mode resonance layer is overlaid on part of the biological sensing area, and does not overlap with the surface plasmon resonance layer. Among them, a plurality of biological probes are self-assembled on the metal layer after surface modification of the metal layer.

Further, in the above-mentioned bio-sensing device, along the direction from the light input end to the light output end, the bio-sensing area sequentially forms a first to-be-measured area and a second to-be-measured area. Wherein, the surface plasmon resonance layer is covered on the first test area, and the loss mode resonance layer is covered on the second test area.

Further, in the above-mentioned biological sensing device, the lossy mode resonance layer is made of metal oxide or polymer material.

Further, in the above-mentioned biological sensing device, the optical waveguide substrate is one of glass, quartz or polymer materials.

In order to achieve the purpose disclosed above, a biological sensing system proposed by the present invention includes: a broadband light source, an input optical fiber, a biological sensing device, an output optical fiber, and a spectrometer. Wherein, the input optical fiber is coupled to the broadband light source. The biological sensing device is coupled to the input optical fiber, and the biological sensing device includes: an optical waveguide substrate, a surface plasmon resonance layer, and a lossy mode resonance layer. Wherein, the optical waveguide substrate includes an optical input end and an optical output end opposite to each other, and a biological sensing area is formed on one surface of the optical waveguide substrate between the optical input end and the optical output end. The surface plasmon resonance layer includes a metal layer and For the plurality of biological probes, the metal layer is covered on part of the biological sensing area, and the plurality of biological probes are evenly arranged on the metal layer. The lossy mode resonance layer is overlaid on part of the biological sensing area, and does not overlap with the surface plasmon resonance layer. The output fiber is coupled to the light output end. The spectrometer is coupled to the output fiber. Among them, most of the biological probes are self-assembled on the metal layer after surface modification, and the incident light emitted by the broadband light source enters the optical waveguide substrate through the input fiber for loss modal resonance in the biological sensing area.

Further, in the bio-sensing system, along the direction from the light input end to the light output end, the bio-sensing area sequentially forms a first to-be-measured area and a second to-be-measured area. Wherein, the surface plasmon resonance layer is covered on the first test area, and the loss mode resonance layer is covered on the second test area.

Further, in the above-mentioned biosensing system, the lossy mode resonance layer is formed of metal oxide or polymer material.

In order to achieve the purpose disclosed above, a method of using a biosensing system proposed by the present invention includes: disposing an object to be tested in a biosensing device including parallel and non-overlapping surface plasmon resonance layers and lossy modal resonance layers area, and the object to be tested is brought into contact with the surface plasmon resonance layer and the lossy mode resonance layer at the same time. The incident light emitted by the broadband light source is input into the biological sensing area, the incident light generates a surface plasmon resonance signal on the surface plasmon resonance layer, and at the same time, the incident light on the lossy modal resonance layer generates a lossy modal resonance signal. The spectrometer is made to receive the surface plasmon resonance signal and the loss modal resonance signal simultaneously, and the biological signal is obtained after subtracting the loss modal resonance signal from the surface plasmon resonance signal. The surface plasmon resonance layer includes a metal layer and a plurality of biological probes, and the plurality of biological probes are self-assembled on the metal layer after surface modification of the metal layer.

Further, in the method of using the bio-sensing system, along the transmission direction of the incident light, the bio-sensing area sequentially forms a first to-be-measured area and a second to-be-measured area. Wherein, the surface plasmon resonance layer is covered on the first test area, and the loss mode resonance layer is covered on the second test area. The lossy modal resonance layer is made of metal oxide or polymer material.

When using the aforementioned bio-sensing device, bio-sensing system and method of using the same, the structure adopted is to configure a surface plasmon resonance layer and a lossy mode resonance layer on an optical waveguide substrate to form the bio-sensing region , so as to avoid the use of a large volume of the chimney. Moreover, since the surface plasmon resonance signal can be obtained through the surface plasmon resonance layer and the loss modal resonance signal can be obtained through the loss modal resonance layer at the same time in the biological sensing area in a single detection process, the spectrometer can be used. The biological signal is obtained by subtracting the loss modal resonance signal from the surface plasmon resonance signal, and the environmental interference signal can be removed immediately, thereby solving the technical problems of the prior art that it is difficult to achieve miniaturization and easily cause signal distortion.

Therefore, the biosensing device, the biosensing system and the method for using the biosensing device of the present invention can achieve the goals of being convenient to carry, easy to mass-produce, and having accurate biosensing results.

In order to further understand the techniques, means and effects adopted by the present invention to achieve the predetermined purpose, please refer to the following detailed descriptions and accompanying drawings of the present invention. It is believed that the features and characteristics of the present invention can be used to gain an in-depth and specific understanding. However, the accompanying drawings are only provided for reference and description, and are not intended to limit the present invention.

1: Biosensing device

2: Broadband light source

3: Input fiber

4: Output fiber

5: Spectrometer

7: Analyze the host

10: Optical waveguide substrate

11: Optical input terminal

12: Optical output terminal

13: Biosensing area

20: Surface Plasmon Resonance Layer

21: Metal layer

22: Biological Probes

30: Loss Mode Resonant Layer

131: The first area to be tested

132: The second test area

S1~S3: Steps

L1: SPR signal

L2: LMR signal

L11: SPR signal

L21: LMR signal

FIG. 1 is a schematic structural diagram of the biosensing device of the present invention; FIG. 2 is a functional block diagram of the biosensing system of the present invention; 3 is a flow chart of a method of using the biosensing system of the present invention; FIG. 4 is a schematic diagram of the sensitivity of glycerol detection in the biosensing system of the present invention; and FIG. 5 is a schematic diagram of the sensitivity of protein detection in the biosensing system of the present invention.

The technical content and detailed description of the present invention are described as follows in conjunction with the drawings.

Please refer to Figure 1 and Figure 2. 1 is a schematic structural diagram of a biological sensing device of the present invention; and FIG. 2 is a functional block diagram of a biological sensing system of the present invention.

The biosensing device 1 of an embodiment of the present invention can be applied to protein detection, and can include: an optical waveguide substrate 10 , a surface plasmon resonance (SPR) layer 20 and a lossy mode resonance (lossy mode resonance) layer , LMR) layer 30 . The optical waveguide substrate 10 may include an optical input end 11 and an optical output end 12 opposite to each other, and a biological sensing area 13 is formed on one side of the optical waveguide substrate 10 between the optical input end 11 and the optical output end 12 . The biological sensing area 13 is used for placing a device under test (DUT). In this embodiment, the analyte may be a phosphate buffered solution (PBS) including glycosylated heme (HbA1c). In the embodiment of the present invention, the optical waveguide substrate 10 may be one of glass, quartz, and other materials that can guide light or polymer materials (eg, PET, PMMA, etc.), or it may be made of other optical loss Made of small materials.

Although optical fiber sensors are currently the mainstream of development, the production process of optical fiber sensors requires grinding and coating, which is not easy to manufacture. Even if the plastic optical fiber (POF) is used as an example, although the toughness is better, it is difficult to resist the organic solution and high temperature in the process. The wavelength range of the absorption spectrum of the upper POF is between red light and infrared light, which is a commonly used wavelength, and it is not easy to judge the phenomena of surface plasmon resonance (SPR) and loss modal resonance (LMR). Taking glass optical fiber (GOF) as an example, although it can resist the organic solution and high temperature in the process, and its absorption spectrum is in ultraviolet light, which is not a commonly used wavelength, it is not easy to grind and easy to break. To sum up, the present invention proposes that a planar waveguide made of glass can be used as a sensor, and the glass substrate is first coated and then cut into an appropriate size. Glass is resistant to organic solutions and high temperatures in the process, and does not require grinding. Compared with optical fiber-based sensors, planar waveguides are easier to fabricate, less prone to damage, and have higher yields.

The surface plasmon resonance layer 20 may include a metal layer 21 and a plurality of biological probes 22 , the metal layer 21 is overlaid on a part of the biological sensing area 13 , and the plurality of biological probes 22 are evenly arranged on the metal layer 21 . The plurality of biological probes 22 are self-assembled on the metal layer 21 after the surface modification is performed on the metal layer 21 . The surface modification may be performed in the following order: removing surface contaminants of the indium tin oxide layer, hydroxylating the indium tin oxide layer, silanizing the indium tin oxide layer, and decarboxylating the indium tin oxide layer reaction treatment. Details are as follows.

The lossy mode resonance layer 30 is disposed on a part of the bio-sensing region 13 and does not overlap with the surface plasmon resonance layer 20 . The lossy mode resonance layer 30 can be selected from a metal oxide whose real part of the dielectric constant is much larger than the imaginary part, that is, a lossy mode can be generated. In the embodiment of the present invention, the lossy mode resonance layer 30 may be composed of metal oxides (eg, indium tin oxide ITO, titanium oxide TiO _x , zinc oxide ZnO _x , etc.) or polymer materials. The loss mode resonance (LMR) is similar to the principle of surface plasmon resonance (SPR). When the incident light enters the loss mode resonance layer 30 at a critical angle and total reflection (TIR) occurs, the incident light ( incident light) will cause an evanescent wave to be generated on the surface of the modal resonant layer 30 . When the evanescent wave matches the effective refractive index of the lossy modal resonant layer 30, the light intensity loss of a part of the wavelength can be observed from the spectrum of the reflected light when the two are coupled, and the wavelength of the light intensity loss is called the LMR wavelength And it is the focus of observation when the present invention is used. In addition, both the TE wave and the TM wave can resonate with the lossy modal resonance layer 30, so there is no need to polarize or filter the incident light, and the sensitivity is high and the use is convenient. In the embodiment of the present invention, the indium tin oxide (ITO) layer as the lossy modal resonance layer 30 may be disposed on the glass substrate as the optical waveguide substrate 10 by RF magnetron sputtering. The RF sputter is a well-known and mature technology with ordinary knowledge in the art, and will not be described in detail here.

Further, in the bio-sensing device 1 of the present invention, along the direction from the light input end 11 to the light output end 12 , the bio-sensing area 13 sequentially forms a first test area 131 and a second test area 132. Wherein, the surface plasmon resonance layer 20 is disposed on the first area to be tested 131 , and the lossy mode resonance layer 30 is disposed on the second area to be measured 132 . That is, the lossy modal resonance layer 30 does not overlap with the surface plasmon resonance layer 20 .

As shown in FIG. 2 , the biological sensing system of the present invention may further include a broadband light source 2 , an input optical fiber 3 , an output optical fiber 4 , a spectrometer 5 and an analysis host 7 based on the biological sensing device 1 described above. The input optical fiber 3 is coupled to the broadband light source 2 for transmitting the light output by the broadband light source 2, and the broadband light source 2 may be a halogen light source. The biological sensing device 1 is coupled to the input optical fiber 3 , so that the light output by the broadband light source 2 enters the light input end 11 of the optical waveguide substrate 10 as shown in FIG. 1 . The output optical fiber 4 is coupled to the light output end 12 of the optical waveguide substrate 10 for receiving the light output from the optical waveguide substrate 10 . The spectrometer 5 is coupled to the output fiber 4 for receiving and analyzing the light output from the optical waveguide substrate 10 . The light output from the optical waveguide substrate 10 may include light that resonates with the surface plasmon resonance layer 20 and light that resonates with the lossy mode resonance layer 30 . The analysis host 7 is coupled to the spectrometer 5 .

Please refer to Figure 3 to Figure 5. 3 is a flow chart of a method of using the biosensing system of the present invention; FIG. 4 is a schematic diagram of the sensitivity of glycerol detection of the biosensing system of the present invention; FIG. 5 is a schematic diagram of the sensitivity of protein detection of the biosensing system of the present invention. For the numbers of other components other than the aforementioned FIG. 3 to FIG. 5 , please refer to the aforementioned contents, and will not be repeated here.

When using the aforementioned bio-sensing system and bio-sensing device 1 thereof, the object to be tested (not shown in the figure) is firstly disposed on the surface including the surface plasmon resonance layer 20 and the lossy mode resonance layer 30 which are juxtaposed and not overlapped. the biological sensing area 13, and the object to be tested contacts the surface plasmon resonance layer 20 and the lossy mode resonance layer 30 at the same time (step S1). Then, the incident light emitted by a broadband light source (eg, a halogen light source) can be input to the biological sensing area 13 through the aforementioned input optical fiber 3 . So that the incident light on the surface plasmon resonance layer 20 generates a surface plasmon resonance (SPR) signal, and the incident light on the lossy mode resonance layer 30 generates a lossy mode resonance (LMR) signal at the same time (step S2 ). Finally, the spectrometer 5 is made to receive the surface plasmon resonance (SPR) signal and the loss modal resonance (LMR) signal simultaneously through the output fiber 4, and the loss modal resonance (LMR) signal is subtracted from the surface plasmon resonance (SPR) signal The biological signal is obtained after the signal (step S3). Since the resonant wavelength shift of the surface plasmon resonance (SPR) signal includes two signals: biological signal and environmental interference signal, the removal of the surface plasmon resonance (LMR) signal can be achieved by subtracting the loss modal resonance (LMR) signal that is completely dependent on the environment. The purpose of environmental interference signals in plasma resonance (SPR) signals.

As shown in FIG. 4 , in the embodiment of the present invention, when the test object is selected as the test object with different refractive indices, the resonance wavelength shift of the SPR signal L1 can be simultaneously detected (the left side shown in FIG. 4 ) Δλ) and the resonance wavelength shift of the LMR signal L2 (right Δλ as shown in FIG. 4 ) to calculate the sensitivity of the surface plasmon resonance layer 20 and the sensitivity of the lossy modal resonance layer 30 respectively. In the embodiment of the present invention, the sensitivity of the surface plasmon resonance layer 20 is S _SPR , and the sensitivity of the lossy mode resonance layer 30 is S _LMR .

As shown in FIG. 5 , when the analyte is changed to protein, for example, a bovine serum albumin (BSA) solution is used. After the simultaneous detection of the SPR signal L11 and the LMR signal L21, the SPR layer 20 can capture proteins because of surface modification (with biological probes), so the resonance wavelength shift (Δλ _SPR ) of the SPR signal contains the biological signal The resonance wavelength shift (Δλ _SPR,bio ) and the resonance wavelength shift of the environmental interference signal (Δλ _SPR,noise ). The LMR layer 30 cannot capture proteins because it has not undergone surface modification (no biological probes), so only the resonance wavelength shift (Δλ _LMR,noise ) of the environmental interference signal can be used as reference data for environmental changes. To this end, the equivalent refractive index change ( Δn _noise ) of the environmental disturbance signal and the resonant wavelength shift (Δλ _SPR,noise ) of the SPR signal caused by the equivalent refractive index change can be calculated, which can be regarded as SPR The amount of environmental interference in the signal is as follows:

For this, the resonance wavelength shift (Δλ _SPR,bio ) of the real biological signal can be obtained: Δλ _SPR,bio =Δλ _{SPR -Δλ SPR,noise}

Since the structure adopted in the present invention is to configure the surface plasmon resonance layer 20 and the lossy mode resonance layer 30 on the optical waveguide substrate 10 to form the bio-sensing region 13, the use of a large volume of fluorine can be avoided. In addition, the surface plasmon resonance (SPR) signal can be obtained through the surface plasmon resonance layer 20 and the loss mode through the loss mode resonance layer 30 can be obtained simultaneously in the bio-sensing region 13 in a single detection process. Resonance (LMR) signal, so that the spectrometer 5 can obtain the biological signal after subtracting the loss modal resonance signal from the surface plasmon resonance signal, which can remove the environmental interference signal immediately, thus solving the problems of the prior art that are not easy to achieve miniaturization and easy to cause. Technical issues with signal distortion.

Therefore, the biosensing device, the biosensing system and the method for using the biosensing device of the present invention can achieve the goals of being convenient to carry, easy to mass-produce, and having accurate biosensing results.

In addition, lossy modal resonance (LMR) has the following characteristics compared to surface plasmon resonance (SPR): both TE waves and TM waves can resonate with the lossy modal resonance layer 30 , while using SPR technology only Can resonate with TM waves.

The above is only the detailed description and drawings of the preferred specific embodiments of this creation, but the features of this creation are not limited to this, and are not intended to limit this creation. The entire scope of this creation shall be the following patent application scope All the embodiments that conform to the spirit of the patented scope of this creation and its similar changes shall be included in the scope of this creation. Modifications can be covered by the following patent scope of this creation.

The structures, proportions, sizes, number of components, etc. shown in the drawings in this specification are only used to cooperate with the contents disclosed in the specification for the understanding and reading of those who are familiar with the technology, and are not intended to limit the implementation of this creation. Therefore, it has no technical substantive significance. Any modification of structure, change of proportional relationship or adjustment of size shall fall within the scope of this creation without affecting the effect and purpose of this creation. The disclosed technical content must be within the scope of coverage.

1: Biosensing device

10: Optical waveguide substrate

11: Optical input terminal

12: Optical output terminal

13: Biosensing area

20: Surface Plasmon Resonance Layer

21: Metal layer

22: Biological Probes

30: Loss Mode Resonant Layer

131: The first area to be tested

132: The second test area

Claims (9)

A biological sensing device, comprising: an optical waveguide substrate, comprising an optical input end and an optical output end opposite to each other, and a surface of the optical waveguide substrate between the optical input end and the optical output end forms a Bio-sensing area; a surface plasmon resonance layer, including a metal layer and a plurality of biological probes, the metal layer covers part of the bio-sensing area, and the plurality of biological probes are evenly arranged on the on the metal layer; and a lossy mode resonance layer covering part of the bio-sensing area and not overlapping the surface plasmon resonance layer; wherein, the plurality of biological probes are carried out on the metal layer After surface modification, self-assembly is formed on the metal layer; wherein, the surface plasmon resonance layer and the lossy mode resonance layer are in adjacent contact with each other, so that a test object simultaneously contacts the surface plasmon resonance layer and the loss modal resonance layer, to simultaneously obtain a surface plasmon resonance signal and a loss modal resonance signal; wherein, the resonant wavelength shift of the surface plasmon resonance signal is Δλ _SPR , the resonant wavelength of the loss modal resonance signal The displacement is △λ _LMR,noise , the resonant wavelength displacement of an environmental interference signal is △λ _SPR,noise , the resonant wavelength displacement of a biological signal is △λ _SPR,bio , and the following relationship is satisfied: △λ _LMR,noise =△ λ _SPR,noise ; Δλ _SPR,bio =Δλ _{SPR -Δλ SPR,noise} . The biosensing device of claim 1, wherein, along the direction from the light input end to the light output end, the biosensing area sequentially forms a first to-be-measured area and a second to-be-measured area, wherein, The surface plasmon resonance layer is overlaid on the first region to be tested, and the lossy mode resonance layer is overlaid over the second region to be tested. The biological sensing device according to claim 1, wherein the lossy mode resonance layer is composed of metal oxide or polymer material. The biological sensing device of claim 1, wherein the optical waveguide substrate is one of glass, quartz or polymer materials. A biological sensing system includes: a broadband light source; an input optical fiber coupled to the broadband light source; a biological sensing device coupled to the input optical fiber, and the biological sensing device includes: an optical waveguide substrate, including mutually opposite a light input end and a light output end, and a bio-sensing area is formed on one side of the optical waveguide substrate between the light input end and the light output end; a surface plasmon resonance layer, including a metal layer and a plurality of biological probes, the metal layer is covered on a part of the biological sensing area, and the plurality of biological probes are evenly arranged on the metal layer; and a lossy mode resonance layer is covered on the a part above the biological sensing area and not overlapped with the surface plasmon resonance layer; an output optical fiber, coupled to the light output end; and a spectrometer, coupled to the output optical fiber; wherein, the plurality of biological probes Self-assembly is formed on the metal layer after the surface modification of the metal layer; wherein, an incident light emitted by the broadband light source enters the optical waveguide substrate through the input fiber, and is used for loss mode in the biological sensing area. Resonance; wherein, the surface plasmon resonance layer and the lossy mode resonance layer are in adjacent contact with each other, so that a test object simultaneously contacts the surface plasmon resonance layer and the lossy mode resonance layer to obtain a Surface plasmon resonance signal and a loss modal resonance signal; wherein, the resonance wavelength shift of the surface plasmon resonance signal is Δλ _SPR , the resonance wavelength shift of the loss modal resonance signal is Δλ _LMR,noise , an environmental disturbance The resonance wavelength shift of the signal is Δλ _SPR,noise , the resonance wavelength shift of a biological signal is Δλ _SPR,bio , and the following relationship is satisfied: Δλ _LMR,noise =Δλ _SPR,noise ; Δλ _SPR,bio = Δλ _SPR - Δλ _SPR,noise . The biosensing system of claim 5, wherein, along the direction from the light input end to the light output end, the biosensing area sequentially forms a first to-be-measured area and a second to-be-measured area, wherein, The surface plasmon resonance layer is overlaid on the first region to be tested, and the lossy mode resonance layer is overlaid over the second region to be tested. The biological sensing system according to claim 5, wherein the lossy mode resonance layer is made of metal oxide or polymer material. A method of using a biosensing system, comprising: disposing a test object in a biosensing area including a surface plasmon resonance layer and a lossy mode resonance layer that are juxtaposed and not overlapped, and make the test object The object simultaneously contacts the surface plasmon resonance layer and the lossy mode resonance layer; an incident light emitted by a broadband light source is input into the biological sensing area, and the incident light generates a surface plasmon in the surface plasmon resonance layer resonance signal, and simultaneously the incident light generates a lossy modal resonance signal in the lossy modal resonance layer; and a spectrometer simultaneously receives the surface plasmon resonance signal and the lossy modal resonance signal, and the surface plasmon resonance signal A biological signal is obtained after subtracting the loss mode resonance signal from the plasmonic resonance signal; wherein, the surface plasmon resonance layer includes a metal layer and a plurality of biological probes, and the plurality of biological probes are subjected to surface modification on the metal layer The post self-assembly is formed on the metal layer; wherein, the surface plasmon resonance layer and the loss mode resonance layer are in adjacent contact with each other, so that a test object simultaneously contacts the surface plasmon resonance layer and the loss mode resonance layer a resonance layer, to simultaneously obtain a surface plasmon resonance signal and a loss modal resonance signal; wherein, the resonance wavelength shift of the surface plasmon resonance signal is Δλ _SPR , and the resonance wavelength shift of the loss modal resonance signal is Δ λ _LMR,noise , the resonance wavelength shift of an environmental interference signal is Δλ _SPR,noise , and the resonance wavelength shift of a biological signal is Δλ _SPR,bio , and the following relationship is satisfied: Δλ _LMR,noise =Δλ _{SPR, noise} ; Δλ _SPR,bio =Δλ _{SPR -Δλ SPR,noise} . The method for using a biosensing system according to claim 8, wherein, along the transmission direction of the incident light, the biosensing area sequentially forms a first test area and a second test area The test area, wherein the surface plasmon resonance layer is covered on the first test area, and the loss mode resonance layer is covered on the second test area; the loss mode resonance layer is a metal composed of oxides or polymer materials.

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