WO2019232858A1 - Fabry-perot structure having nanopore array, preparation method and operation method - Google Patents

Abstract

A Fabry-Perot structure having a nanopore array, a preparation method and a processing method, the structure comprising: a first glass layer (100), a first gold film (200), a second gold film (300) and a second glass layer (400) which are provided in sequence; a first nanopore array (210) is provided on the first gold film (200), a first through hole (310) and a second through hole (320) are provided on the second gold film (300), and a third through hole (410) and a fourth through hole (420) are provided on the second glass layer (420); a cavity (500) is provided between the first gold film (200) and the second gold film (300), and at least a part of pore array in the nanopore array (210) is provided on the lower side of the cavity (500); the first through hole (310), the third through hole (410), the cavity (500), and the fourth through hole (420) are in communication with the second through hole (320); and the first gold film (200) and the second gold film (300) constitute a first reflective surface and a second reflective surface of the Fabry-Perot structure. The present invention has the following advantages: a gold film nanopore array (210) is configured as a double-layer structure, and a super-transmission resonance signal is generated by means of the gold film nanopore array to increase the signal intensity, and at the same time, the signal-to-noise ratio can be improved by means of a double-layer microcavity, thereby obtaining a high-quality optical measurement signal.

Description

Fabry-Perot structure with nanopore array, preparation method and operation method

Cross-reference to related applications

This application claims the priority of Chinese patent application number "201810587937.1", filed on June 08, 2018, with the invention name "Fabry-Perot Structure with Nanopore Array, Preparation Method and Operation Method" .

Technical field

The invention relates to the technical field of label-free biochemical molecular detection, in particular to a Fabry-Perot structure with a nanopore array, a preparation method and an operation method.

Background technique

Biochemical sensors based on plasmon resonance (SPR) technology have special advantages in high-precision biomolecule detection. Because of the use of reflective measurement, the optical path of the biosensor device based on SPR technology is located on the same side of the SPR chip, which has hindered the miniaturization of the device. Recently, a gold film nanopore array chip structure has appeared internationally, that is, a gold film with a sub-wavelength diameter nanohole array is formed on a substrate (generally glass). When light is incident from either side of the chip, the light emitted from the other side will have resonance peaks at certain specific wavelengths (called super-transmission EOT); if the amount of particles adsorbed around the gold film hole array changes, the resonance peak The wavelength will shift accordingly, and the amount of shift has an approximately linear relationship with the amount of adsorption. Using this principle, because the incident and outgoing light is distributed on both sides of the chip, and the angle of the light is not high, the detection equipment is easy to miniaturize, so it has a good prospect.

After more than ten years of development, the gold film nanopore array structure is still mainly single layer. The detection performance indicators of single-layer gold film nanopore array-based biosensing technology, such as refractive index sensitivity and quality factor, are gradually stabilizing, and the space for improvement is limited.

Summary of the Invention

In view of this, a first object of the present invention is to provide a Fabry-Perot structure with a nanopore array, which can significantly improve the signal light quality and can improve the sensitivity.

To achieve the above object, the technical solution of the present invention is implemented as follows:

A Fabry-Perot structure with a nanopore array includes: a first glass layer; a first gold film formed on the first glass layer, and a first nanometer is disposed on the first gold film A hole array; a second gold film formed on the first gold film, the first gold film being provided with a first through hole and a second through hole; a first gold film formed on the second gold film Two glass layers, a third through hole and a fourth through hole are provided on the second glass layer, the first through hole is in communication with the third through hole, and the second through hole is in communication with the fourth through hole The holes communicate with each other, wherein there is a cavity between the first gold film and the second gold film, and the first gold film and the second gold film are adhered by an adhesive on the outside of the cavity. Then, at least a part of the hole array in the first nanohole array is disposed on the lower side of the cavity, and the third through hole, the first through hole, the cavity, the second through hole and The fourth through hole communicates, and the first gold film and the second gold film constitute a first reflecting surface and a second reflecting surface of a Fabry-Perot structure.

Further, a second nanohole array is disposed on the second gold film, and the second nanohole array is located between the third through hole and the fourth through hole.

Further, the adhesive is a photoresist.

Compared with the prior art, the Fabry-Perot structure with a nanopore array according to the present invention has the following advantages:

According to the Fabry-Perot structure with the nanopore array according to the embodiment of the present invention, the gold film nanopore array is configured into a double-layer structure, and the gold film nanopore array generates a super transmission resonance signal to increase the signal intensity. A layer of gold film forms a Fabry-Perot microcavity reflective layer to generate interference effects to improve the signal-to-noise ratio, thereby obtaining high-quality optical measurement signals. At the same time, using the good conductivity of the double-layered gold film, a voltage (DC or AC) is applied to the double-layered gold film, thereby forming an electric or dielectric field in the cavity, and promoting the enrichment of particles in the nanopore array to increase the speed of adsorption. And quantity to improve detection rate and sensitivity. In addition, using microfluidic technology, the microcavity is made into a microchannel, the sample flow rate is controlled, the biochemical sample is detected under the sample flow state, and the problem of baseline offset of the optical signal caused by thermal effects in the measurement environment is solved, improving accuracy .

A second object of the present invention is to provide a method for operating a Fabry-Perot structure with a nanopore array. The operation method can be applied to the Fabry-Perot structure with a nanopore array in the above embodiment. The double-layer gold film structure applies an electric field to enrich the particles.

To achieve the above object, the technical solution of the present invention is implemented as follows:

A method for operating a Fabry-Perot structure with a nanopore array includes the following steps: pouring a test liquid into the cavity through the third through hole and the first through hole; and The first gold film and the second gold film serve as electrodes to apply an electric field to enrich particles in the measured liquid.

Further, after the step of enriching the particles in the measured liquid, the method further includes: providing a fluid driving device and a fluid circulation pipeline, wherein one end of the fluid circulation pipeline passes through the third communication pipe in order. The hole and the first through hole penetrate deep into the cavity, and the other end of the fluid circulation pipeline penetrates into the cavity through the fourth through hole and the second through hole in sequence, and the fluid drives The device is arranged on the fluid circulation pipeline; when detecting the peak wavelength of the measured liquid under preset detection conditions, the fluid driving device controls the flow rate of the measured liquid in the fluid circulation pipeline to eliminate Detection errors due to thermal effects.

According to the method for operating a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention, particles can be achieved by applying an electric field to a double-layered gold film structure in the Fabry-Perot structure with a nanopore array. Enrichment.

A third object of the present invention is to provide a method for preparing a Fabry-Perot structure with a nanopore array. The preparation method can prepare a Fabry-Perot structure with high-quality optical signals and high sensitivity.

To achieve the above object, the technical solution of the present invention is implemented as follows:

A method for preparing a Fabry-Perot structure with a nanopore array includes the following steps: providing a first glass layer; forming a first gold film on the first glass layer; and forming a first gold film on the first gold layer Forming a first nanohole array on the substrate; providing a second glass layer; forming a first through hole and a second through hole on the second glass layer; forming a second gold film on the second glass layer; The second gold film has a third through hole and a fourth through hole, the first through hole is in communication with the third through hole, and the second through hole is in communication with the fourth through hole; Forming a photoresist layer on the two gold films; bonding the second glass layer with the second gold film; aligning the first gold film and the second gold film, and A glass layer and the second glass are laminated, so that the first glass layer, the first gold film, the photoresist layer, the second gold film, and the second glass layer are sequentially laminated. ; Wherein there is a cavity between the first gold film and the second gold film, and at least a part of the hole array in the first nanohole array is disposed on the lower side of the cavity, and A third through hole, the first through hole, the cavity, the second through hole and the fourth through hole are in communication, and the first gold film and the second gold film constitute a Fabry-Perot The first reflecting surface and the second reflecting surface of the structure.

Further, according to an embodiment of the present invention, the step of forming a first gold film on the first glass layer includes: forming a first chromium film on the first glass layer by sputtering, and the first A chromium film is provided with through holes at the vertical projection positions of the first through hole and the second through hole; a first gold film is formed on the first chromium film.

Further, the step of forming a first gold film on the first chromium film includes: performing deposition sputtering on the first chromium film at a first rate to form a first unit gold film; Deposition sputtering is performed on the first unit gold film at a second rate to form a second unit gold film; wherein the first gold film includes the first unit gold film and the second unit gold film, so The first rate is greater than the second rate.

Further, a focused particle beam process is performed on the first gold film to form the first nanopore array.

Further, the step of forming the second gold film on the second glass layer includes: forming a second chromium film on the second glass layer, and the second chromium film is on the third A through hole is opened in a vertical projection position of the through hole and the fourth through hole; a second gold film is formed on the second chromium film.

Further, the step of forming the second gold film on the second chromium film includes: performing deposition sputtering on the second chromium film at a third rate to form a third unit gold film; Depositing and sputtering on the third unit gold film at a fourth rate to form a fourth unit gold film; wherein the second gold film includes the third unit gold film and the fourth unit gold film, The third rate is greater than the fourth rate.

According to the method for preparing a Fabry-Perot structure with a nanopore array according to the embodiment of the present invention, the Fabry-Perot structure with a nanopore array is prepared, and the gold film nanopore array is configured into a double-layer structure. A gold film nanopore array generates a super transmission resonance signal to increase the signal intensity, and a double-layer gold film forms a Fabry-Perot microcavity reflective layer to generate an interference effect to improve the signal-to-noise ratio, thereby obtaining high-quality optical measurement signals . At the same time, using the good conductivity of the double-layered gold film, a voltage (DC or AC) is applied to the double-layered gold film, thereby forming an electric or dielectric field in the cavity, and promoting the enrichment of particles in the nanopore array to increase the speed of adsorption. And quantity to improve detection rate and sensitivity. In addition, using microfluidic technology, the microcavity is made into a microchannel, the sample flow rate is controlled, the biochemical sample is detected under the sample flow state, and the problem of baseline offset of the optical signal caused by thermal effects in the measurement environment is solved, improving accuracy .

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings constituting a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and the descriptions thereof are used to explain the present invention, and do not constitute an improper limitation on the present invention. In the drawings:

1 is a schematic structural diagram of a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention;

2 is a working principle diagram of a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention;

3 is a comparison diagram of interference transmission spectra of a Fabry-Perot structure using a double-layer gold film of the present invention and a single-layer gold film nanopore array structure in the related art;

FIG. 4 is a dynamic shift diagram of peak wavelengths of a Fabry-Perot microcavity under fluidic and flowing conditions in an embodiment of the present invention

FIG. 5 is a dynamic shift diagram of peak wavelengths of BSA protein solutions of different concentrations under a dielectrophoresis effect according to an embodiment of the present invention; FIG.

6 is a schematic structural diagram of a Fabry-Perot structure with a nanopore array in another embodiment of the present invention;

7 is a flowchart of a method for preparing a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention.

Detailed ways

It should be noted that, in the case of no conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

The present invention will be described in detail below with reference to the drawings and embodiments.

FIG. 1 is a schematic structural diagram of a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention. As shown in FIG. 1, the Fabry-Perot structure with a nanopore array according to an embodiment of the present invention includes a first glass layer 100, a first gold film 200 formed on the first glass layer 100, and a A second gold film 300 on the first gold film 200 and a second glass layer 400 formed on the second gold film 300. The first gold film 200 is provided with a first nano-hole array 210. The second gold film is provided with a first through hole 310 and a second through hole 320. The second glass layer 400 is provided with a third through hole 410 and a fourth through hole 420, the first through hole 310 is in communication with the third through hole 410, and the second through hole 320 is in communication with the fourth through hole 420. A cavity 500 is provided between the first gold film 200 and the second gold film 300. On the outside of the cavity 500, the first gold film 200 and the second gold film 300 are bonded by an adhesive 600, and the adhesive 600 may be a photoresist. At least a part of the first nano-hole array 210 is disposed on the lower side of the cavity 500. The third through hole 410, the first through hole 310, the cavity 500, the second through hole 320, and the second through hole 420 communicate with each other. The first gold film 200 and the second gold film 300 constitute a first reflection surface and a second reflection surface of the Fabry-Perot structure.

FIG. 2 is a working principle diagram of a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention. As shown in FIG. 2, the first glass layer 100, the first gold film 200, the second gold film 300 and the second glass layer 400 are placed in parallel. The relative distance between the two sides of the first gold film 200 and the second gold film 300 is L, and L is defined as the cavity length of the Fabry-Perot microcavity. The pores in the first nanopore array 210 may have various shapes, including circular, triangular, rectangular, and irregular shapes. For the sake of convenience, without loss of generality, the following layer of gold film has nano-circular hole array as an example. The intervals of the hole array uniformly distributed along the x / y axis are a and b, respectively. The peak wavelength of the transmission spectrum is:

Among them, the integers i and j are the resonance levels in the x-axis and y-axis directions, respectively, and ε _m and ε _d are the dielectric constants of gold and the measured medium, respectively.

For a Fabry-Perot microcavity with a cavity length of L, the reflectance of the upper and lower layers can be regarded as the same R, then the transmittance of the transmitted light relative to the incident light is:

among them,

Is the phase difference generated by light traveling back and forth once in the Fabry-Perot microcavity, n is the refractive index of the medium in the Fabry-Perot microcavity, and λ is a specific wavelength. when

(k is a positive integer, indicating the interference order; λ _k is the wavelength of a certain interference order), the maximum transmittance T _max = 1, corresponding to the interference bright fringe; when

In this case, the minimum transmittance T _min = [(1-R) / (1 + R)] ² , corresponding to the interference dark fringe. The interference contrast ratio γ of the Fabry-Perot microcavity is defined as:

When the transmittance is maximum,

It can be obtained that n = kλ _k / 2L. During the refractive index sensing detection, k and L are kept constant. At this time, the refractive index change is:

In the above formula, Δn is the change amount of the refractive index, n ₀ is the initial value of the refractive index of the measured medium in the Fabry-Perot microcavity, λ _k0 is the initial wavelength of k-order interference bright lines, and Δλ _k is k-order interference The shift of the peak wavelength of the light streaks. The refractive index sensitivity of the Fabry-Perot microcavity k-order interference fringe is:

At polychromatic light incident polychromatic light when the two wavelengths λ ₁ and ₂ differ by a large [lambda], [lambda] such that ₂ k-th stage interference fringes λ + k ₁ 1 of the first-stage interference fringes overlap, causing various The streaks of the order are confusing and do not achieve the purpose of spectroscopy. Therefore, for a Fabry-Perot microcavity with a fixed cavity length, there is a maximum allowable difference in spectral wavelength, which is called the free spectral range Δλ _f . At normal incidence of the incident light, when λ λ m-th stripe and the m + 1 stage ₂ of stripe ₁ overlap, the optical path difference equal, at this time are:

(k + 1) λ ₁ = kλ ₂ = k (λ ₁ + Δλ _f ) (6)

The expression that yields the free spectral range Δλ _f is as follows:

In the visible light range, the smaller the cavity length L, the larger the free spectral range, and the stronger the resolution of the spectrum. This is that the Fabry-Perot microcavity is millimeter-level or more compared with the conventional cavity length. The advantages of a large Fabry-Perot cavity.

The half-value line width of the interference peak Δλ _FWHM (that is, the full width at half _{maximum of} the interference peak line, in nm) is an important parameter. The half-value line width of the interference peak at the peak wavelength λ _k is:

According to the definition of figure of merit (FOM), the theoretical value of the figure of merit of refractive index sensing technology based on Fabry-Perot microcavity,

For this structure, corresponding to incident white light, if the Fabry-Perot microcavity is deionized water, the spectral signal observed at the end of the spectrometer is equivalent to the transmission line package obtained by Extraordinary Optical Transmission (EOT) Interference signal. The resonance peak wavelength in the transmission line is given by Equation 1; the free spectrum between the interference peak wavelengths in the interference signal can be given by Equation 7, the corresponding half-value spectral line width is given by Equation 8, and the figure of merit is given by Equation 9 Out.

The influence of the thickness of the first gold film 200 on the transmission interference peak is mainly due to the intensity of the optical signal. An excessively thick gold layer may have a low transmittance due to the depth of the skin of the metal, and the thickness is preferably 10 to 50 nm. The second gold film 300 should satisfy the nanopore array to produce a better EOT phenomenon, and the thickness is preferably 60-200 nm. From the perspective of the free spectral range, the cavity length L is as small as possible, but in practical detection applications, the cavity length L is too small to facilitate the entry of the solution. The smaller the distance is, the larger the flow resistance is. 6 to 20 nm.

The invention also discloses a method for operating a Fabry-Perot structure with a nanopore array, which includes the following steps:

Pour the measured liquid into the cavity through the third through hole and the first through hole;

The first gold film and the second gold film are used as electrodes to apply an electric field to enrich the particles in the measured liquid.

According to an embodiment of the present invention, after the step of enriching the particles in the measured liquid, the method further includes:

A fluid driving device and a fluid circulation pipeline are provided, wherein one end of the fluid circulation pipeline penetrates into the cavity through the third through hole and the first through hole in sequence, and the other end of the fluid circulation pipeline through the fourth through hole and the first through Two through holes penetrate into the cavity, and the fluid driving device is arranged on the fluid circulation pipeline;

When detecting the peak wavelength of the measured liquid under the preset detection conditions, the fluid driving device controls the flow rate of the measured liquid in the fluid circulation pipeline to eliminate the detection error caused by the thermal effect.

The following examples illustrate the beneficial effects of the Fabry-Perot structure of the nanopore array.

FIG. 3 is a comparison diagram of interference transmission spectra of a Fabry-Perot structure using a double-layer gold film of the present invention and a single-layer gold film nanopore array structure in the related art. As shown in FIG. 3, deionized water was injected into the microcavity 500, and the Fabry-Perot microcavity nanopore array structure and the single-layer nanopore array spectral signals were measured. It can be seen that the transmission spectrum of the Fabry-Perot microcavity gold film nanopore array with a 20nm thick gold film and a glass substrate is subject to the modulation envelope of the transmission spectrum of the single-layer gold film nanopore array, and its interference spectrum exists A series of discrete interference peaks, and the free spectral range increases with increasing wavelength, which is consistent with the results derived from Equation 7 of the free spectral range of the Fabry-Perot microcavity interference peak. In addition, it can be seen from Figure 3 that the full width at half maximum of the Fabry-Perot microcavity double-layer gold film nanopore array interference peak is reduced by nearly 10 times compared to a single-layer gold film, indicating that the quality factor is correspondingly close to 10 Times increase.

In theory, any interference peak in the measurable spectral range of the spectrometer can be used for refractive index sensing measurement, but in order to make the refractive index sensitivity as high as possible, the interference peak with a larger wavelength is generally selected. It is found from Equation 5 that each interference peak in the interference spectrum corresponds to the refractive index sensitivity increasing with the wavelength. In actual measurement, the light intensity of the EOT interference peak modulated by a single-layer gold film nanopore array must also be considered: the larger the light intensity of the interference peak, the higher the signal-to-noise ratio during detection. Therefore, a single-layer gold film nanopore array gold water (1,0) level resonance peak envelope can be selected for the actual detection.

By using the gold films in the upper and lower layers as electrodes, an electric field can be applied to the Fabry-Perot microcavity to enrich the particles in the liquid. Taking dielectrophoresis as an example, for a Fabry-Perot microcavity with a cavity length of 10 μm, the range of dielectrophoretic force is very limited under the effect of positive dielectrophoresis, after exceeding the effective near-field range of the surface EOT (about 200 nm) The electric field force is almost negligible, so only particles adsorbed around the nanopore array can be detected, thereby ensuring the correctness of the detection.

In the detection, the typical thermal effect comes from the light source or the electrode is energized. The heat generated by the two will increase the temperature in the Fabry-Perot microcavity and cause the refractive index of the medium to decrease. Causes the transmission spectrum to include a blue shift in the spectral peaks, causing baseline errors. In order to eliminate the blue-shift measurement error of the spectrum caused by the thermal effect in the Fabry-Perot microcavity, the method of removing heat by fluid flow is used to eliminate it. The method is to calculate the appropriate flow rate, so that the sample above the working area of the nanopore array is completely washed away in a measurement period. The thermal effect and the elimination of the effect are verified by a case experiment. A control test using stationary and flowing deionized water (conductivity 0.95 μs / cm). First, deionized water was pumped into the Fabry-Perot microcavity for a total of 500 seconds and the flow rate was maintained at 10 μL / min. It was observed that the peak wavelength of the characteristic interference peak remained stable during this time. Then the microflow pump was stopped to de-ionize the water. At this time, the peak wavelength of the characteristic interference peak was blue-shifted with time, and the blue-shift amount was nearly stable at 2500s. Finally, the microflow pump was turned on again to restore the volume flow rate to 10 μL / min. At this time, the peak wavelength of the transmission spectrum interference peak instantly returned to the stable value when the initial volume flow rate was 10 μL / min, and the peak wavelength offset returned to 0. The signal recording during the entire measurement process is shown in Figure 4. The results show two problems: one is that the thermal effect will affect the refractive index of the medium in the Fabry-Perot microcavity, and the other is that the sample flow can take away the heat. This effectively eliminates the effects of thermal effects.

The following example experiments verify that the adsorption of BSA protein solution is accelerated and the sensitivity is increased under the effect of dielectrophoresis. During the experiment, the BSA solution flowed through the Fabry-Perot microcavity double-layer gold film nanopore array at a flow rate of 10 μL / min to eliminate the effect of thermal effects on the detection signal. Four low-concentration BSA protein solutions were used in the experiment. The concentration values were 0 pM (that is, deionized water), 1 pM, 10 pM, and 100 pM. The dielectrophoresis frequency was set to 1 MHz and the voltage peak-to-peak value was set to 1 V. In order to demonstrate the effect of dielectrophoresis, in the experiment, the measurement was continued for 500s without dielectrophoresis, and then the measurement was continued for 1250s without dielectrophoresis.

The experimental results are shown in Figure 5. It can be seen from Figure 5 that when there is no dielectrophoretic force (0-500s), the peak wavelengths of the characteristic interference peaks remain stable for the four low-concentration BSA protein solutions, that is, the peak wavelengths are biased. The shift amount is 0. At this time, the adsorption of BSA protein on the gold membrane nanopore array is undetectable (the detection sensitivity is 0). Under the condition of applying dielectrophoretic force (500-1750s), because there is no BSA protein particles for adsorption in the deionized aqueous solution (BSA protein concentration is 0 pM), the peak wavelength of the characteristic interference peak in the transmission spectrum remains unchanged; compared to Below, the redshifts of the interference peak-to-peak wavelengths of the deionized aqueous solutions with BSA protein concentrations of 1 pM, 10 pM, and 100 pM were 0.352 nm, 1.768 nm, and 5.647 nm, respectively. The time to reach equilibrium was 80s, 100s, and 400s. It can be seen that under the effect of the dielectrophoretic force, the peak wavelength of the characteristic interference peak of deionized water does not change, the peak wavelength of the BSA protein solution will red shift, and the higher the BSA protein concentration, the red shift amount of the corresponding peak wavelength The larger it is, the longer it takes for the peak wavelength to reach equilibrium. Compared with the case where the BSA protein adsorption detection signal is 0 when there is no dielectrophoresis, the BSA protein solution concentration detection signals at 1 pM, 10 pM, and 100 pM are significantly increased after dielectrophoresis, that is, lower concentrations can be detected after dielectrophoresis. BSA protein solution, the detection sensitivity was effectively improved.

FIG. 6 is a schematic structural diagram of a Fabry-Perot structure with a nanopore array in another embodiment of the present invention. As shown in FIG. 6, in this embodiment, a second nano hole array 330 is disposed on the second gold film 300, and the second nano hole array 330 is located between the third through hole 310 and the fourth through hole 320.

According to the Fabry-Perot structure with the nanopore array according to the embodiment of the present invention, the gold film nanopore array is configured into a double-layer structure, and the gold film nanopore array generates a super transmission resonance signal to increase the signal intensity. A layer of gold film forms a Fabry-Perot microcavity reflective layer to generate interference effects to improve the signal-to-noise ratio, thereby obtaining high-quality optical measurement signals. At the same time, using the good conductivity of the double-layered gold film, a voltage (DC or AC) is applied to the double-layered gold film, thereby forming an electric or dielectric field in the cavity, and promoting the enrichment of particles in the nanopore array to increase the speed of adsorption. And quantity to improve detection rate and sensitivity. In addition, using microfluidic technology, the microcavity is made into a microchannel, the sample flow rate is controlled, the biochemical sample is detected under the sample flow state, and the problem of baseline offset of the optical signal caused by thermal effects in the measurement environment is solved, improving accuracy .

7 is a flowchart of a method for preparing a Fabry-Perot structure with a nanopore array according to an embodiment of the present invention. As shown in FIG. 7, an embodiment of the present invention also discloses a method for preparing a Fabry-Perot structure with a nanopore array, including the following steps:

A1: Provide a first glass layer.

Specifically, a first glass layer is made and the first glass layer is cleaned. The cleaning method is: after soaking the first glass layer in a potassium dichromate solution for 24 hours, sonicating with acetone for 5min, alcohol for 5min, deionized water for 2 times for 5min each time, and finally drying on a 150 ° C hot plate Bake for 2h.

A2: A first gold film is formed on the first glass layer.

In one embodiment of the present invention, step A2 includes:

A2-1: A first chromium film is formed on the first glass layer by sputtering, and the first chromium film is provided with through holes in the vertical projection positions of the first and second through holes. The first chromium film is used for bonding the first glass layer and the first gold film.

A2-2: A first gold film is formed on the first chromium film.

Specifically, deposition sputtering is performed on the first chromium film at a first rate to form a first unit gold film; deposition sputtering is performed on the first unit gold film at a second rate to form a second unit gold membrane. The first gold film includes a first unit gold film and a second unit gold film, and the first rate is greater than the second rate. The second unit gold film on the upper side is used to reflect light. Therefore, sputtering at a second rate lower than the first rate can make the surface of the second unit gold film smooth and dense, and improve the reflection effect.

In an example of the present invention, a JR-2B type sputter etcher is used to first sputter 5nm chromium on glass, and then sputter a 100nm thick gold film. The first 30nm gold film is sputtered at a deposition rate of 4nm / min. (RF power 50W, vacuum 0.1Pa, argon flow 80sccm, sputtering time 7 minutes and 30 seconds), and subsequent 70nm sputtering at a deposition rate of 9nm / min (RF power 100W, vacuum 0.1Pa, argon flow 80sccm, (Sputter time: 7 minutes and 47 seconds).

A3: A first nanopore array is formed on the first gold film.

In one embodiment of the present invention, a focused particle beam (Focused Ion Beam, FIB) process is performed on the first gold film to form a first nanopore array. The number of hole arrays is 80 × 80, the diameter of a single hole is 200 nm, and the horizontal and vertical interval (a / b) of the hole array is 500 nm.

B1: Provide a second glass layer.

Specifically, a second glass layer is made and the second glass layer is cleaned. The cleaning method is: after immersing the second glass layer in a potassium dichromate solution for 24 hours, sonicating with acetone for 5 min, alcohol for 5 min, deionized water for two times for 5 min each, and finally drying on a 150 ° C hot plate and baking Bake for 2h.

B2: forming a first through hole and a second through hole on the second glass layer.

Specifically, a bench drill with a glass drill is used to drill two circular holes with a diameter of 3 mm on the glass substrate to serve as the inlet and outlet of the flow channel, and the center distance between the two circular holes is 12 mm.

B3: A second gold film is formed on the second glass layer. The second gold film has a third through hole and a fourth through hole. The first through hole is in communication with the third through hole, and the second through hole is in communication with the fourth through hole.

In one embodiment of the present invention, step A2 includes:

B3-1: A second chromium film is formed on the second glass layer, and the second chromium film has through holes in the vertical projection positions of the third and fourth through holes. The second chromium film is used for bonding the second glass layer and the second gold film.

B3-2: A second gold film is formed on the second chromium film.

Specifically, deposition sputtering is performed on the second chromium film at a third rate to form a third unit gold film; deposition sputtering is performed on the third unit gold film at a fourth rate to form a fourth unit gold film. The second gold film includes a third unit gold film and a fourth unit gold film, and the third rate is greater than the fourth rate. The fourth unit gold film on the upper side is used to reflect light. Therefore, sputtering at a fourth rate lower than the third rate can make the surface of the fourth unit gold film smooth and dense, and improve the reflection effect.

In an example of the present invention, JR-2B type sputter etching is used to sputter a 5nm chromium film, and then a 20nm thick gold film is sputtered at a deposition rate of 4nm / min (RF power 50W, vacuum degree 0.1) Pa, argon flow rate 80 sccm, sputtering time 5 minutes).

B4: A photoresist layer is formed on the second gold film.

Specifically, a photoresist layer having a thickness of 10 μm was used.

B5: Bonding the second glass layer to the second gold film.

Specifically, the photoresist layer is bonded by thermocompression (coating machine, temperature is set to 100 ° C); the photoresist layer just pasted on the second gold film is used with a H94-37 double-sided photolithography machine. The exposure time is 15 seconds (the light power of the light source with a wavelength of 365nm is 7.8mJ / cm2), and then the film is placed on a hot plate at 150 ° C for half an hour; two PDMS with inlet and outlet (diameter 1mm) will be provided The square (5mm × 5mm × 5mm) and the side of the second glass layer are placed under a plasma cleaner (JSD200) for cleaning treatment, with a power of 25W and a time of 45s. Then, two PDMS blocks with an inlet and an outlet are aligned and bonded to two circular holes with a diameter of 3 mm on the upper glass substrate, respectively.

C: Align the first gold film and the second gold film, and use a pair of ring-shaped (center with holes) strong magnets on the first glass layer and the second glass layer to clamp and press together to make the first The glass layer, the first gold film, the photoresist layer, the second gold film and the second glass layer are sequentially bonded. Wherein, there is a cavity between the first gold film and the second gold film, at least a part of the hole array in the nanohole array is disposed on the lower side of the cavity, and the first through hole, the third through hole, the cavity, and the fourth through The hole is in communication with the second through hole, and the first gold film and the second gold film constitute a first reflecting surface and a second reflecting surface of the Fabry-Perot structure.

According to the method for preparing a Fabry-Perot structure with a nanopore array according to the embodiment of the present invention, the Fabry-Perot structure with a nanopore array is prepared, and the gold film nanopore array is configured into a double-layer structure. A gold film nanopore array generates a super transmission resonance signal to increase the signal intensity, and a double-layer gold film forms a Fabry-Perot microcavity reflective layer to generate an interference effect to improve the signal-to-noise ratio, thereby obtaining high-quality optical measurement signals. . At the same time, using the good conductivity of the double-layered gold film, a voltage (DC or AC) is applied to the double-layered gold film, thereby forming an electric or dielectric field in the cavity, and promoting the enrichment of particles in the nanopore array to increase the speed of adsorption. And quantity to improve detection rate and sensitivity. In addition, using microfluidic technology, the microcavity is made into a microchannel, the sample flow rate is controlled, the biochemical sample is detected under the sample flow state, and the problem of baseline offset of the optical signal caused by thermal effects in the measurement environment is solved, improving accuracy .

Further, an embodiment of the present invention discloses a device, which includes: one or more processors; a memory; one or more programs, one or more programs are stored in the memory, and are processed by one or more When the device is executed, the operation method of the Fabry-Perot structure with the nanopore array in the above embodiment is performed. The device can realize the enrichment of particles by applying an electric field to the double-layer gold film structure in the Fabry-Perot structure with a nanopore array.

Further, an embodiment of the present invention discloses a non-volatile computer storage medium. The non-volatile computer storage medium stores one or more programs. When the one or more programs are executed by a device, the device makes the device A method for operating a Fabry-Perot structure with a nanoporous array in the foregoing embodiment of the present invention is performed. The non-volatile computer storage medium can realize particle enrichment by applying an electric field to a double-layered gold film structure in a Fabry-Perot structure with a nanopore array.

The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention shall be included in the present invention. Within the scope of protection.

Claims (10)

1. A Fabry-Perot structure with a nanopore array is characterized in that it includes:

   First glass layer

   A first gold film formed on the first glass layer, and a first nanohole array is disposed on the first gold film;

   A second gold film formed on the first gold film, the first gold film is provided with a first through hole and a second through hole;

   A second glass layer formed on the second gold film, a third through hole and a fourth through hole are provided on the second glass layer, and the first through hole is in communication with the third through hole, The second through hole is in communication with the fourth through hole;

   Wherein, there is a cavity between the first gold film and the second gold film, and the first gold film and the second gold film are bonded by an adhesive on the outside of the cavity, so that At least a part of the first nanohole array is disposed on the lower side of the cavity, and the third through hole, the first through hole, the cavity, the second through hole, and the first The four through holes communicate with each other, and the first gold film and the second gold film constitute a first reflecting surface and a second reflecting surface of the Fabry-Perot structure.
2. The Fabry-Perot structure with a nanopore array according to claim 1, wherein a second nanopore array is provided on the second gold film, and the second nanopore array is located in the second gold film. Between the third through hole and the fourth through hole.
3. The Fabry-Perot structure with a nanopore array according to claim 1, wherein the adhesive is a photoresist.
4. A method for operating a Fabry-Perot structure with a nanopore array according to claim 1, comprising the following steps:

   Pouring the measured liquid into the cavity through the third through hole and the first through hole;

   The first gold film and the second gold film are used as electrodes to apply an electric field to enrich particles in the measured liquid.
5. The processing method according to claim 4, further comprising: after the step of enriching particles in the measured liquid, further comprising:

   A fluid driving device and a fluid circulation pipeline are provided, wherein one end of the fluid circulation pipeline penetrates into the cavity through the third through hole and the first through hole in sequence, The other end penetrates into the cavity through the fourth through hole and the second through hole in sequence, and the fluid driving device is disposed on the fluid circulation pipeline;

   When detecting the peak wavelength of the measured liquid under a preset detection condition, the fluid drive device controls the flow rate of the measured liquid in the fluid circulation pipeline to eliminate detection errors caused by thermal effects.
6. A method for preparing a Fabry-Perot structure with a nanopore array is characterized in that it includes the following steps:

   Providing a first glass layer;

   Forming a first gold film on the first glass layer;

   Forming a first nanohole array on the first gold film;

   Providing a second glass layer;

   Forming a first through hole and a second through hole on the second glass layer;

   A second gold film is formed on the second glass layer, the second gold film has a third through hole and a fourth through hole, the first through hole is in communication with the third through hole, and the first Two through holes communicate with the fourth through hole;

   Forming a photoresist layer on the second gold film;

   Bonding the second glass layer with the second gold film;

   Align the first gold film and the second gold film, and laminate the first glass layer and the second glass, so that the first glass layer, the first gold film, the The photoresist layer, the second gold film, and the second glass layer are sequentially bonded;

   Wherein, a cavity is provided between the first gold film and the second gold film, and at least a part of the nano-hole array is arranged on the lower side of the cavity. The third through hole, the cavity, the fourth through hole and the second through hole are in communication, and the first gold film and the second gold film constitute a first reflection of a Fabry-Perot structure. Surface and second reflecting surface.
7. The method for preparing a Fabry-Perot structure with a nanopore array according to claim 6, wherein the step of forming a first gold film on the first glass layer comprises:

   Forming a first chromium film on the first glass layer by sputtering, and the first chromium film is provided with a through hole at a vertical projection position of the first through hole and the second through hole;

   A first gold film is formed on the first chromium film.
8. The method for preparing a Fabry-Perot structure with a nanopore array according to claim 7, wherein the step of forming a first gold film on the first chromium film comprises:

   Performing deposition sputtering on the first chromium film at a first rate to form a first unit gold film;

   Performing deposition sputtering on the first unit gold film at a second rate to form a second unit gold film;

   The first gold film includes the first unit gold film and the second unit gold film, and the first rate is greater than the second rate.
9. The method for preparing a Fabry-Perot structure with a nanopore array according to claim 6, wherein the step of forming the second gold film on the second glass layer comprises:

   Forming a second chromium film on the second glass layer, and the second chromium film is provided with through holes at the vertical projection positions of the third through hole and the fourth through hole;

   A second gold film is formed on the second chromium film.
10. The method for preparing a Fabry-Perot structure with a nanopore array according to claim 9, wherein the step of forming the second gold film on the second chromium film comprises:

    Performing deposition sputtering on the second chromium film at a third rate to form a third unit gold film;

    Depositing and sputtering on the third unit gold film at a fourth rate to form a fourth unit gold film;

    The second gold film includes the third unit gold film and the fourth unit gold film, and the third rate is greater than the fourth rate.

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