CN112763457A - Preparation method of silicon-based cascaded double-ring resonant cavity chip for detecting PCA3 - Google Patents

Preparation method of silicon-based cascaded double-ring resonant cavity chip for detecting PCA3 Download PDF

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CN112763457A
CN112763457A CN202011564787.6A CN202011564787A CN112763457A CN 112763457 A CN112763457 A CN 112763457A CN 202011564787 A CN202011564787 A CN 202011564787A CN 112763457 A CN112763457 A CN 112763457A
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pca3
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李秋顺
董文飞
李力
葛明锋
常智敏
从瑛哥
姜琛昱
宁珊珊
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Jinan Guoke Medical Engineering Technology Development Co ltd
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Abstract

The invention discloses a preparation method of a silicon-based cascaded double-ring resonator chip for detecting PCA3, belonging to the technical field of cascaded double-ring resonator sensing, and the invention prepares the silicon-based cascaded double-ring resonator chip for detecting PCA3 by sequentially modifying epoxy silane, a glucan film and a PCA3 gene probe on the surface of a sensing ring in the silicon-based cascaded double-ring resonator chip, so as to modify the glucan film, increase the fixed amount of the PCA3 gene probe, improve the specific combination amount of the chip and the PCA3, enhance the response signal of the silicon-based cascaded double-ring resonator sensor to the PCA3, and realize the high-sensitivity selective detection of the PCA 3. The chip for detecting PCA3, which is prepared without the need of labeling with fluorescent or luminescent groups, is expected to be widely applied to diagnosis and treatment of prostate cancer.

Description

Preparation method of silicon-based cascaded double-ring resonant cavity chip for detecting PCA3
Technical Field
The invention relates to the technical field of cascaded double-ring resonant cavity sensing, in particular to a preparation method of a silicon-based cascaded double-ring resonant cavity chip for detecting PCA 3.
Background
Prostate cancer is one of the major malignant tumors threatening the health of men worldwide, and the incidence rate of prostate cancer is the first and the second in European and American countries for years. In recent decades, the incidence of prostate cancer in our country has also been on the rise year by year with the aging of our country's population and the change of dietary structure. Prostate cancer gene 3(PCA3) is a non-coding RNA with high expression in prostate cancer tissues, has high specificity for prostate cancer detection, can reflect the progression of prostate cancer, and is one of the currently known important biological markers for diagnosing prostate cancer. The prostate massage can lead a small amount of prostate cells to enter urine, and the detection of the PCA3 gene expression level in the urine cells can realize early screening of prostate cancer and avoid over-puncture biopsy, thereby relieving the pain of patients. The suspected prostate cancer patients are a considerable part of old men over 50 years old, and the prostate cancer biopsy is undoubtedly a great pain for the suspected prostate cancer patients, and even the prostate biopsy cannot be performed, so that the PCA3 gene test can easily solve the problems of the suspected prostate cancer patients. Therefore, the detection of PCA3 is of great significance for early diagnosis and timely treatment of prostate cancer.
To date, researchers at home and abroad have conducted many studies on the detection of PCA3 for the purpose of finding and treating prostate cancer as early as possible, and the methods mainly include RT-PCR fluorescence quantification, chemiluminescence, magnetic nanoparticle-mediated assay, Lateral Flow Analysis (LFA) strip assay, for example, the document "DD 3(PCA3) -based molecular urea analysis for the diagnosis of cancer" uses time-resolved fluorescence quantification RT-PCR assay to measure PCA3 in urine samples, "APTIMA PCA3 molecular urea concentration of a method to aid in the diagnosis of cancer" uses a DNA probe labeled with a chemiluminescent molecule to perform specific target capture to detect PCA3, and the document "magnetic nanoparticle-mediated detection of prostate cancer antigen 3 to diagnose prostate cancer" uses magnetic nanoparticle-mediated PCA 3. Wherein: RT-PCR fluorescence quantitative method has high sensitivity, but because the method has some insurmountable limitations such as operation requiring professional technicians, harsh experimental conditions, long turnaround time and the like, the application of the method in low-resource environment is severely limited. Furthermore, since the thermocycling amplification step risks falsely amplifying non-specific contaminants, false positive results may occur and the sensitivity and specificity of the test is not ideal. Lateral Flow Assay (LFA) strips are of great interest because of their advantages of convenient use, short detection time, low cost, ease of mass production, and the like. However, this method has some limitations in quantitative analysis and is low in sensitivity. The chemiluminescence method needs to label groups with chemiluminescence performance, and the magnetic nanoparticle mediated method needs to use magnetic nanoparticles. Therefore, in order to make a more accurate early diagnosis of prostate cancer, it is necessary to find a new method for quantitative analysis of PCA 3.
The optical biosensor has great commercial prospect due to the advantages of high sensitivity, electromagnetic interference resistance, good electrical insulation and the like. Meanwhile, with the rapid development of technologies such as biology, materials science, microelectronics, optoelectronics and the like, the optical biosensor gradually develops towards miniaturization, batch, intellectualization and commercialization, the application range is increasingly expanded, and the optical biosensor has been deeply applied to various fields such as clinical diagnosis, environmental monitoring, food safety and the like. The silicon-based cascaded double-ring resonant cavity sensor is one of optical biosensors, changes the effective refractive index of a ring resonant cavity waveguide by using the change of the concentration or other characteristics of a liquid to be detected, further causes the resonant wavelength or power intensity of a resonant cavity to change, and obtains the basic information of the liquid to be detected by analyzing the variation of the resonant wavelength or the variation of the power intensity. At present, biochemical substances such as IgG, testosterone, progesterone and the like are detected by using a cascade bicyclic resonant cavity sensor, but PCA3 detection based on a silicon-based cascade bicyclic resonant cavity is not reported.
The silicon-based cascaded double-ring resonant cavity sensor has very high refractive index sensitivity and can realize unmarked high-sensitivity detection on an object to be detected, but the cascaded double-ring resonant cavity sensor can show the same spectral signal to substances with the same refractive index, so that the selective detection on PCA3 can not be realized. If the method of directly reacting and connecting the PCA3 gene probe with the hydroxyl functional group on the surface of the resonant cavity is adopted, the quantity of the immobilized PCA3 gene probe is usually too small, so that the signal change of the cascade bicyclic resonant cavity sensor can not be observed or the observed signal change is very weak when the PCA3 is detected. Therefore, in order to perform more accurate and high-sensitivity detection and diagnosis on the PCA3 by using the cascaded double-ring resonator sensor, a preparation method of a cascaded double-ring resonator chip with a functionalized PCA3 probe with excellent performance is required.
Disclosure of Invention
In view of the above prior art, the present invention aims to provide a method for preparing a silicon-based cascaded dual-ring resonator chip for detecting PCA 3.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect of the present invention, a silicon-based cascaded dual-ring resonator chip for detecting PCA3 is provided, which includes: a first waveguide, a second waveguide, and a third waveguide; a reference ring is arranged between the first waveguide and the second waveguide and is respectively coupled with the first waveguide and the second waveguide; a sensing ring is arranged between the second waveguide and the third waveguide and is respectively coupled with the second waveguide and the third waveguide; the method comprises the following steps that incident light enters a first waveguide to be coupled with a reference ring, light led out from the reference ring is further coupled with a second waveguide, part of the light coupled with the reference ring and the second waveguide leaks from a mid end of the second waveguide, part of the light is further coupled with a sensing ring, and the light led out from the sensing ring is further coupled with a third waveguide and then is output from a pass end;
and the surface of the sensing ring is sequentially modified and fixed with epoxy silane, a glucan film and a PCA3 gene probe.
Preferably, the epoxysilane is 3- (2, 3-glycidoxy) propyltrimethoxysilane or 3- (2, 3-glycidoxy) propyltriethoxysilane.
Preferably, the molecular weight of the glucan used for preparing the glucan film is between 1000-2500000.
Preferably, the PCA3 gene probe is designed by using 4 exons of PCA3 as templates.
Preferably, the sequence of the PCA3 gene probe includes but is not limited to that shown in SEQ ID NO.1, SEQ ID NO.2 or SEQ ID NO.3, and specifically is as follows:
NH2-(CH2)6-AAAAATTGTTCAAAGACCCTTCGTGTT；(SEQ ID NO.1)
NH2-(CH2)6-AAAAACTGCTGACTTTACCATCTGAGGCCAC；(SEQ ID NO.2)
NH2-(CH2)6-AAAAATCCTGGTCTCCCTCGGCTGCA；(SEQ ID NO.3)
the second aspect of the present invention provides a method for preparing the silicon-based cascaded dual-ring resonator chip, which comprises the following steps:
(1) cleaning the silicon-based cascaded double-ring resonant cavity;
(2) carrying out plasma treatment on the surface of the cleaned sensing ring;
(3) modifying epoxy silane on the surface of the sensing ring;
(4) further modifying glucan on the surface of the sensing ring modified by the epoxy silane;
(5) the PCA3 gene probe was further modified on the surface of dextran.
Preferably, in the step (4), the glucan modified on the surface of the sensing ring is immobilized by covalent reaction between the glucan and the epoxy silane on the surface of the sensing ring.
Preferably, in the step (5), the PCA3 gene probe is immobilized on the surface of the dextran film through the covalent reaction of the PCA3 gene probe and dextran.
In a third aspect of the invention, the silicon-based cascaded double-ring resonator chip is provided for use in preparing a PCA3 diagnosis and/or detection product.
The fourth aspect of the invention provides a preparation method of a silicon-based cascaded double-ring resonator chip for detecting PCA3, which comprises the following steps:
and contacting the sensing ring of the silicon-based cascade double-ring resonant cavity chip with liquid to be detected, and qualitatively or quantitatively detecting the PCA3 in the liquid to be detected according to the wavelength change signal or the optical power intensity change signal.
The invention has the beneficial effects that:
(1) according to the preparation method of the silicon-based cascade bicyclic resonant cavity chip for detecting PCA3, when the chip is used for detecting PCA3, fluorescent labeling, amplification, harsh experimental conditions and longer turnover time are not needed, and compared with a magnetic nanoparticle medium method and an RT-PCR fluorescence quantitative method, the detection conditions, the detection steps and the detection time are greatly simplified.
(2) Compared with a chemiluminescence method, the preparation method of the silicon-based cascade bicyclic resonant cavity chip for detecting PCA3 does not need screening and marking of luminescent groups when the chip is used for detecting PCA3, simplifies detection procedures and reduces detection cost.
(3) When the silicon-based cascade double-ring resonator chip for detecting PCA3 is used for detecting PCA3, compared with a lateral flow analysis strip analysis method, the preparation method of the silicon-based cascade double-ring resonator chip for detecting PCA3 has the advantages that the fixing amount of a PCA3 probe is increased through glucan, and the vernier amplification effect caused by a cascade reference ring and a sensing ring is achieved, so that the sensitivity of PCA3 detection is greatly improved.
(4) The preparation method of the silicon-based cascade bicyclic resonant cavity chip for detecting the PCA3 has the advantages of real-time, direct, label-free and high-sensitivity detection of the PCA3 when the chip is used for detecting the PCA3, is expected to play an important role in the prevention and treatment of the PCA3, and has wide commercial application prospect.
Drawings
FIG. 1: the invention discloses a cross-sectional schematic diagram of a silicon-based cascaded double-ring resonant cavity; in the figure, 1-incident light, 2-first waveguide, 3-reference ring, 4-second waveguide, 5-mid end of second waveguide, 6-sensing ring, 7-third waveguide, 8-drop end of third waveguide.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
As described in the background section, the detection of PCA3 is important for early diagnosis and timely treatment of prostate cancer. PCA3 localized to chromosome 9, was approximately 25kb in length, and contained 3 introns and 4 exons, and studies showed that PCA3 is a non-coding RNA gene with very few protein products and is therefore more targeted for gene testing of PCA 3.
Biosensors based on optical ring resonators are currently receiving a lot of attention. In the ring resonant cavity, light waves are continuously and circularly transmitted around the micro-ring, and the evanescent waves passing through the surface of the waveguide contact with a tested sample to act. Different from the traditional planar optical waveguide sensor, in the annular resonant cavity sensor, because the optical wave is continuously transmitted around the ring, the action length of the optical wave and the measured sample is not the physical actual length of the resonant cavity any more, but is related to the quality factor Q of the resonant cavity, therefore, the annular resonant cavity can realize great sensing sensitivity with a very small physical size, not only low cost and miniaturization are realized, but also expensive medicines are saved to a great extent in the biological sensing process.
The cascade dicyclic resonant cavity waveguide sensor consists of two ring resonant cavities with different radiuses, including sensing ring and reference ring, where the sensing ring has no spin coating upper cladding layer to contact directly with the liquid to be measured and the reference ring is covered with one upper cladding layer. When the concentration of the liquid to be detected changes, the mode characteristic of light transmitted in the waveguide is influenced, the change of resonance wavelength or the change of power intensity is further influenced, and the parameter change of the liquid to be detected can be obtained by analyzing the change of the resonance spectrum. The cascaded double-ring resonant cavity sensor has a unique double-ring structure, and the sensor ring and the reference ring form a vernier amplification effect similar to a vernier caliper, so that the sensitivity of the device is greatly improved compared with that of the traditional single-ring sensor.
At present, no report that the PCA3 is detected by using a cascaded double-ring resonant cavity waveguide sensor exists, and based on the report, the invention provides a preparation method of a silicon-based cascaded double-ring resonant cavity chip for detecting the PCA 3.
In one embodiment of the present invention, a silicon-based cascaded dual ring resonator waveguide chip comprises: the detection method comprises the steps that a first waveguide 2, a reference ring 3, a second waveguide 4, a sensing ring 6 and a third waveguide 7 are adopted, incident light 1 enters the first waveguide 2 to be coupled with the reference ring 3, light led out from the reference ring 3 is further coupled with the second waveguide 4, part of light coupled by the reference ring 3 and the second waveguide 4 leaks from a mid end 5 of the second waveguide, part of light is further coupled with the sensing ring 6, light led out from the sensing ring 6 is further coupled with the third waveguide 7 and then is output from a pass end 8 (figure 1), epoxy silane, a glucan film and a PCA3 gene probe are sequentially modified and fixed on the surface of the sensing ring 6 in the silicon-based cascade double-ring resonant cavity chip, so that the glucan film is modified to increase the fixed amount of the PCA3 gene probe, and signal change caused by combination of the PCA3 and the PCA3 gene probe is utilized to realize high-sensitivity and high-selectivity detection on the PCA 3.
The silicon-based cascade double rings of the invention refer to a reference ring 3 and a sensing ring 6, and a micro-ring resonant cavity used for modifying epoxy silane, a glucan film and a PCA3 gene probe is the sensing ring 6 instead of the reference ring 3.
The detection of PCA3 as described herein is accomplished by sensing the change in refractive index of sensing ring 6.
The epoxy silane used for modifying the surface of the sensing ring is 3- (2, 3-epoxypropoxy) propyl trimethoxy silane or 3- (2, 3-epoxypropoxy) propyl triethoxy silane.
The glucan film is fixed on the surface 6 of the sensing ring through covalent reaction between the glucan and epoxy silane on the surface of the sensing ring 6.
The immobilization of the PCA3 probe is realized by the covalent reaction of the PCA3 probe and glucan on the surface of a glucan film.
The molecular weight of glucan used for preparing the glucan film is 1000-2500000.
The PCA3 probe is designed by using 4 exons of PCA3 as templates.
The preparation of the PCA3 probe on the surface of the sensing ring 6 comprises the following steps:
cleaning a silicon-based cascaded double-ring resonant cavity chip;
secondly, carrying out plasma treatment on the surface of the cleaned sensing ring 6;
modifying epoxy silane on the surface of the sensing ring 6;
fourthly, further modifying glucan on the surface of the sensing ring 6 modified by the epoxy silane;
modifying PCA3 probe on the surface of dextran.
When the silicon-based cascade double-ring resonant cavity chip is used for detecting the PCA3 content in a sample, the adopted signal is a wavelength change signal or a power intensity change signal.
The PCA3 probe on the surface of the silicon-based cascade double-ring resonant cavity chip sensing ring 6 has the performance of being specifically combined with the PCA3, and the selective detection of the PCA3 is realized through the signal change caused by the specific combination of the silicon-based cascade double-ring resonant cavity sensor.
The preparation process of the PCA3 probe on the surface of the sensing ring 6 can be specifically as follows: carrying out plasma treatment on a sensing ring of the silicon-based cascaded double-ring resonant cavity sensor, dropwise adding a solution containing epoxy silane on the surface of the sensing ring after the plasma treatment, treating for 30-60min, and modifying and fixing the epoxy silane on the surface of the sensing ring; then, the sensing ring is placed into a solution containing glucan, the reaction is carried out for 3-5h at the temperature of 90-110 ℃, and the glucan is further modified on the surface of the sensing ring modified by the epoxy silane; then, putting the sensing ring into a solution containing succinic anhydride and DMAP, and reacting for 3-4h at 40-110 ℃; and then transferring the sensing ring into EDC/NHS solution, standing for 30-90min, then transferring into solution containing PCA3 gene probe, and further modifying PCA3 gene probe on the surface of glucan.
The plasma treatment specifically comprises the following steps: the plasma treatment was carried out at a power of 10-12W and a vacuum of 50Pa for 5 min.
The solution containing the epoxysilane includes, but is not limited to: 95% ethanol with 2% 3- (2, 3-glycidoxy) propyltrimethoxysilane, a solution of 1% 3- (2, 3-glycidoxy) propyltrimethoxysilane in dry toluene or 100% 3- (2, 3-glycidoxy) propyltriethoxysilane.
The dextran-containing solution includes, but is not limited to: aqueous solution containing dextran and zinc acetate, DMSO containing dextran, or DMF solution containing dextran.
In order to make the technical solutions of the present application more clearly understood by those skilled in the art, the technical solutions of the present application will be described in detail below with reference to specific embodiments.
Example 1
Sequentially cleaning the silicon-based cascaded double-ring resonant cavity with acetone, ethanol and deionized water for 15min, performing plasma treatment for 5min at a power of 10.2W and a vacuum degree of 50pa (about 375mTor), dropwise adding 95% ethanol containing 2% (volume percent) of 3- (2, 3-epoxypropoxy) propyltrimethoxysilane on a sensing ring of the plasma-treated silicon-based cascaded double-ring resonant cavity for treatment for 1h, and then putting the sensing ring into 5ml containing 0.14g of Zn (AC)20.75g of aqueous dextran solution was reacted at 100 ℃ for 4 hours. The sensor ring was then placed in 5ml of a DMSO solution containing 0.5g succinic anhydride and 0.15g DMAP, purged with nitrogen, and reacted at 110 ℃ for 3 hours. The sensor ring was then transferred to a freshly prepared EDC (0.04M)/NHS (0.01M) solution for 1h and subsequently transferred to a probe NH containing 1. mu.M PCA32-(CH2)6And (4) carrying out refrigerator reaction at 4 ℃ in PBS (phosphate buffer solution) of-AAAAATTGTTCAAAGACCCTTCGTGTT overnight to prepare the silicon-based cascade bicyclic resonant cavity chip for detecting PCA 3.
Example 2
Sequentially cleaning the silicon-based cascaded double-ring resonant cavity for 15min by using acetone, ethanol and deionized water, performing plasma processing for 5min under the power of 10.2w and the vacuum degree of 50pa (about 375mTor), dropwise adding an anhydrous toluene solution containing 1% (volume percentage) of 3- (2, 3-epoxypropoxy) propyl trimethoxy silane on the surface of a sensing ring of the silicon-based cascaded double-ring resonant cavity subjected to plasma processing for 30min, drying for 1h at 110 ℃, putting the sensing ring into 5ml of DMSO containing 1g of glucan, and reacting for 4h at 100 ℃. The sensor ring was then placed in 10ml of a DMSO solution containing 0.2g succinic anhydride, 0.036g DMAP, purged with nitrogen, and reacted at 110 ℃ for 4 h. The sensor ring was then transferred to a freshly prepared EDC (0.02M)/NHS (0.01M) solution for 1h and subsequently to 1. mu.M of PCA3 probe NH2-(CH2)6And (4) carrying out refrigerator reaction at 4 ℃ in PBS (phosphate buffer solution) of-AAAAACTGCTGACTTTACCATCTGAGGCCAC overnight to prepare the silicon-based cascade bicyclic resonant cavity chip for detecting PCA 3.
Example 3
Sequentially cleaning the silicon-based cascaded double-ring resonant cavity for 15min by using acetone, ethanol and deionized water, performing plasma processing for 5min under the power of 10.2w and the vacuum degree of 50pa (about 375mTor), dropwise adding 100% 3- (2, 3-epoxypropoxy) propyltriethoxysilane on a sensing ring of the plasma-processed silicon-based cascaded double-ring resonant cavity for processing for 30min, then putting the sensing ring into 5ml of DMF solution containing 150mg of glucan, and reacting for 4h at 100 ℃. The sensor ring was then placed in 4ml of a nitrogen sparged THF solution containing 51.6mg succinic anhydride and 15.7mg DMAP and reacted at 40 ℃ for 4 h. The sensor ring was then transferred to a freshly prepared EDC (0.2M)/NHS (0.05M) solution for 1h and subsequently to 1. mu.M of PCA3 probe NH2-(CH2)6And (4) carrying out refrigerator reaction at 4 ℃ in PBS (phosphate buffer solution) of-AAAAATCCTGGTCTCCCTCGGCTGCA overnight to prepare the silicon-based cascade bicyclic resonant cavity chip for detecting PCA 3.
The above description is only a preferred embodiment of the present application and is not intended to limit the present application, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.
SEQUENCE LISTING
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<130> 2020
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Claims (10)

1. A preparation method of a silicon-based cascaded double-ring resonant cavity chip for detecting PCA3 is characterized in that the silicon-based cascaded double-ring resonant cavity chip comprises the following steps: a first waveguide, a second waveguide, and a third waveguide; a reference ring is arranged between the first waveguide and the second waveguide and is respectively coupled with the first waveguide and the second waveguide; a sensing ring is arranged between the second waveguide and the third waveguide and is respectively coupled with the second waveguide and the third waveguide; the method comprises the following steps that incident light enters a first waveguide to be coupled with a reference ring, light led out from the reference ring is further coupled with a second waveguide, part of the light coupled with the reference ring and the second waveguide leaks from a mid end of the second waveguide, part of the light is further coupled with a sensing ring, and the light led out from the sensing ring is further coupled with a third waveguide and then is output from a pass end;
and the surface of the sensing ring is sequentially modified and fixed with epoxy silane, a glucan film and a PCA3 gene probe.
2. The method for preparing the silicon-based cascaded dual-ring resonator chip for detecting the PCA3 as claimed in claim 1, wherein the epoxy silane is 3- (2, 3-glycidoxy) propyltrimethoxysilane or 3- (2, 3-glycidoxy) propyltriethoxysilane.
3. The method as claimed in claim 1, wherein the dextran film is prepared by using dextran with molecular weight of 1000-2500000.
4. The method for preparing a silicon-based cascade bicyclic resonator chip for detecting PCA3 as claimed in claim 1, wherein the PCA3 gene probe is designed by using 4 exons of PCA3 as templates.
5. The method for preparing a silicon-based cascaded dual-ring resonator chip for detecting PCA3 as claimed in claim 1, comprising the steps of:
(1) cleaning the silicon-based cascaded double-ring resonant cavity;
(2) carrying out plasma treatment on the surface of the cleaned sensing ring;
(3) modifying epoxy silane on the surface of the sensing ring;
(4) further modifying glucan on the surface of the sensing ring modified by the epoxy silane;
(5) the PCA3 gene probe was further modified on the surface of dextran.
6. The method for preparing the silicon-based cascade bicyclic resonator chip for detecting the PCA3 as claimed in claim 5, wherein in the step (4), the modified glucan on the surface of the sensing ring is immobilized by covalent reaction of the glucan and the epoxy silane on the surface of the sensing ring.
7. The method for preparing a silicon-based cascade bicyclic resonator chip for detecting PCA3 of claim 5, wherein in step (5), the PCA3 gene probe is immobilized on the surface of the dextran film through covalent reaction between the PCA3 gene probe and dextran.
8. Use of a silicon-based cascaded bicyclic resonator chip for testing PCA3 as claimed in any of claims 1-4 in the preparation of PCA3 diagnostic and/or testing products.
9. A preparation method of a silicon-based cascade double-ring resonant cavity chip for detecting PCA3 is characterized in that,
contacting the sensing ring of the silicon-based cascaded dual-ring resonator chip of any one of claims 1 to 4 with a liquid to be detected, and performing qualitative or quantitative detection on PCA3 in the liquid to be detected according to a wavelength change signal or an optical power intensity change signal.
10. The method of claim 9, wherein the PCA3 probe of the silicon-based cascade bicyclic resonator chip has the property of specifically binding to PCA3, and the signal change caused by the specific binding is used to realize the selective detection of PCA 3.
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CN103911443A (en) * 2014-03-18 2014-07-09 烟台毓璜顶医院 Gene chip for detecting 11 types of common infectious diarrheal disease pathogen and application thereof
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CN103911443A (en) * 2014-03-18 2014-07-09 烟台毓璜顶医院 Gene chip for detecting 11 types of common infectious diarrheal disease pathogen and application thereof
CN108414448A (en) * 2018-05-30 2018-08-17 苏州联讯仪器有限公司 One kind being based on the cascade optical sensor of dual resonant cavity
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