WO2016101697A1 - 微流控表面增强拉曼散射透明器件结构及其制备方法 - Google Patents

微流控表面增强拉曼散射透明器件结构及其制备方法 Download PDF

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WO2016101697A1
WO2016101697A1 PCT/CN2015/092799 CN2015092799W WO2016101697A1 WO 2016101697 A1 WO2016101697 A1 WO 2016101697A1 CN 2015092799 W CN2015092799 W CN 2015092799W WO 2016101697 A1 WO2016101697 A1 WO 2016101697A1
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substrate
microchannel
microfluidic channel
raman scattering
layer
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PCT/CN2015/092799
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English (en)
French (fr)
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毛海央
吴文刚
欧文
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江苏物联网研究发展中心
南京瑟斯检测科技有限公司
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Publication of WO2016101697A1 publication Critical patent/WO2016101697A1/zh

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering

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  • the invention relates to a Raman scattering transparent device structure and a preparation method thereof, in particular to a microfluidic surface-enhanced Raman scattering transparent device structure and a preparation method thereof, and belongs to the technical field of semiconductor devices.
  • the detection technique based on Raman scattering spectroscopy is a material structure analysis method that does not require marking of a sample to be tested, and has the characteristics of non-destructive and non-contact.
  • Raman scattering spectroscopy is expected to gain practical results in the fields of biological detection, disease diagnosis, environmental monitoring, and chemical analysis. A wide range of applications.
  • the analytical sensitivity of Raman scattering spectroscopy detection is low, and Raman spectroscopy of many molecules or groups is difficult to obtain.
  • the intensity of the Raman scattering spectrum can be increased to some extent by increasing the excitation laser power, for biological samples, a laser with too much intensity will destroy the biological activity of the sample, so many applications turn to the surface-enhanced Raman scattering effect. Increase the Raman scattering spectral intensity of the sample.
  • the surface-enhanced Raman scattering effect refers to a phenomenon in which a rough noble metal surface enhances a Raman scattering spectrum signal of a substance molecule adsorbed on the surface thereof upon excitation of incident light.
  • the enhancement of the molecular Raman scattering signal is derived from the surface electron oscillation generated by the rough surface under the illumination of light. When the frequency of the incident light matches the frequency of the plasma of the metal itself, the electron oscillation reaches the maximum, so a metal surface is generated. An additional local electromagnetic field with the same frequency as the incident light, which covers the region where the incident light and the surface plasma are excited to be superimposed together.
  • the Raman scattering of the molecule originates from the interaction between the polarization of the molecule itself and the external electric field, the molecule in this superimposed electric field is affected by the localized electromagnetic field in addition to the effect of the original incident electromagnetic field, thus stimulating The Raman scattering signal is also correspondingly enhanced.
  • the intensity of the surface-enhanced Raman scattering signal is enhanced by multiple orders of magnitude, and even the detection of single-molecule Raman scattering signals can be achieved.
  • a layer of the analyte molecule can be uniformly adsorbed on the nano-rough surface or the nanostructure of the open active substrate, but the reagent amount required for this method is large, and the time required for the immersion often requires several Hours are even longer.
  • the required reagent dose only needs to cover the entire surface of the active substrate in the horizontal direction, but the height may reach the order of millimeters, so the reagent dosage is still large; and the method is also the same It takes a long time to evaporate the solvent; in addition, when the method is used to distribute molecules on the open active substrate, the distribution of the molecules on the active substrate cannot be well uniformed due to the influence of the coffee ring effect and the like, thereby affecting Consistency of detected Raman scattering signals; In a perspective, the distribution of analyte molecules by evaporation is not suitable for in vivo detection of biomolecules that have special requirements for liquid environments.
  • the microfluidic surface-enhanced Raman scattering detection device can realize the detection of molecules in a liquid environment, and has the advantages of high measurement consistency and short test time.
  • the reported SERS (Surface-enhanced Raman scattering) detection device has a complicated preparation process, and various process steps are involved, and the active substrate is generally prepared by using a material with visible light opacity, and then for a large-sized material.
  • the laser enters the device from the front, but the detection of the material covering the nano-forest structure often causes the laser to pass through the material and smoothly reach the nano-forest structure, thereby invalidating the detection of the device.
  • the reported microfluidic SERS detection device has been exposed to material deposition, physical etching and the like throughout the process because the bonding regions for bonding other than the SERS active substrate are exposed, resulting in a large surface roughness of the region. Achieve effective bonding.
  • the object of the present invention is to overcome the deficiencies in the prior art, and provide a microfluidic surface-enhanced Raman scattering transparent device structure and a preparation method thereof, which are compact in structure and can improve the consistency of surface enhanced Raman scattering detection signals.
  • the detection time is shortened, the signal-to-noise ratio of the surface-enhanced Raman scattering detection signal can be improved, the simultaneous real-time detection of various substances can be realized, and the detection of macromolecules, polymers and crystalline substances can be realized, and the adaptation range is wide. , safe and reliable features.
  • the microfluidic surface-enhanced Raman scattering transparent device structure comprises a transparent active substrate and a microfluidic channel structural layer supported on the transparent active substrate, in the microfluidic channel structural layer a plurality of detecting microchannels are disposed, wherein the detecting microchannels are connected to the liquid inlet and the liquid outlet of the microfluidic channel structural layer; the surface of the transparent active substrate corresponding to the detecting microchannel is provided with a metal In the nano forest structure, the metal nano forest structure is located between the liquid inlet and the liquid outlet.
  • the transparent active substrate and nano-forest structure are permeable to laser light used to generate Raman spectral signals, and the transmittance ranges from 20% to 100%.
  • the number of the detection microchannels in the same microfluidic surface-enhanced Raman scattering transparent device structure is 2-20.
  • the thickness of the metal layer is 5 to 30 nm, and the diameter of each nanostructure in the nano forest structure is less than 300 nm, and the height of each nanostructure is 100 nm to 2 ⁇ m.
  • a method for preparing a microfluidic surface-enhanced Raman scattering transparent device structure comprises the following steps:
  • microfluidic channel structural layer b. providing a microchannel substrate, and preparing a microfluidic channel structural layer by using the microchannel substrate, wherein the microfluidic channel structural layer has a detection microchannel corresponding to the number of metal nanoforest structures, and detecting the microchannel
  • the liquid inlet on the microfluidic channel structural layer is in communication with the liquid outlet;
  • the microfluidic channel structural layer is supported on the transparent active substrate, and the detecting microchannel is located directly above the metal nano forest structure.
  • An inlet pipe is arranged in the liquid inlet, and a liquid outlet pipe is arranged in the liquid outlet.
  • the microfluidic channel junction is prepared by the following steps:
  • a prepolymer of polydimethylsiloxane is cast on the first microchannel substrate, and the prepolymer of polydimethylsiloxane is cross-linked and solidified to be in the first microchannel
  • a polymer is obtained on the substrate; the polymer is peeled off from the first microchannel substrate, and a detection microchannel is formed at a position corresponding to the microfluidic channel mold in the polymer body, and is prepared at the both ends of the detection microchannel The opening of the polymer in which the microchannels are connected is detected.
  • the microfluidic channel structural layer is prepared by the following steps:
  • 2-a' providing a second microchannel substrate, and spin-coating a photoresist on a surface of the second microchannel substrate, and exposing and developing the photoresist to obtain a second microchannel substrate Required photoresist pattern;
  • a liquid inlet and a liquid outlet are provided at both ends of each of the detection microchannels to obtain a microchannel structure layer.
  • the width of the metal nano-forest structure is not greater than the width of the detection micro-channel above the metal nano-forest structure; the height direction of the metal nano-forest structure is perpendicular to the transparent active substrate;
  • the metal nano-forest structure includes a nano-forest structure and a metal layer covering the nano-forest structure, the material of the metal layer being gold, platinum or silver.
  • the material of the transparent active substrate comprises glass, and the thickness of the glass is from 200 ⁇ m to 2 mm.
  • the detection micro-channel can effectively reduce or even avoid the noise introduced by the test environment on the basis of uniform distribution of the molecules to be analyzed, and improve the signal-to-noise ratio of the surface-enhanced Raman scattering detection signal, thereby effectively ensuring the detection signal of the device. consistency;
  • the laser can be incident from the back surface of the transparent active substrate into the detecting device, thereby obtaining good detection results without being affected by the size of the molecule or substance to be tested.
  • one or more pairs of liquid inlets and outlets can be made, which can be used for the test of a molecule to be analyzed or the mixing and reaction of different analytes before and after the signal detection and comparison. .
  • the real-time detection of multiple materials can be simultaneously realized by designing a plurality of sets of metal nano-forest structure graphic regions on the transparent first substrate and by making a plurality of detection micro-flow channels.
  • microfluidic surface-enhanced Raman scattering transparent device prepared by the invention can be widely applied to the fields of biological, chemical, medical, agricultural and the like for detecting liquid analytes and/or colloidal analytes and/or gas analytes. .
  • FIG. 1 to 12 are cross-sectional views showing specific implementation steps of Embodiment 1 of the present invention, in which
  • Figure 1 is a cross-sectional view showing the first substrate after cleaning according to the present invention.
  • Figure 2 is a cross-sectional view of the present invention after obtaining a hollow substrate using a second substrate.
  • Figure 3 is a cross-sectional view showing the first substrate and the hollow substrate of the present invention after being pasted.
  • Figure 4 is a cross-sectional view showing anisotropic etching of the present invention.
  • Figure 5 is a cross-sectional view showing the nano-forest structure on the first substrate of the present invention.
  • Figure 6 is a cross-sectional view showing the structure of a metal nano-forest obtained in the present invention.
  • Figure 7 is a cross-sectional view showing the transparent active body of the present invention.
  • Figure 8 is a cross-sectional view showing the first microfluidic channel substrate after cleaning according to the present invention.
  • Figure 9 is a cross-sectional view of the present invention after obtaining a microfluidic channel mold.
  • Figure 10 is a cross-sectional view of the present invention after casting a prepolymer.
  • Figure 11 is a cross-sectional view showing the polymer obtained in the present invention.
  • Figure 12 is a cross-sectional view showing the first microfluidic channel structure bonded to a transparent active body in the present invention.
  • FIG. 13 to FIG. 15 are cross-sectional views showing specific implementation steps of a second embodiment of the present invention, wherein
  • Figure 13 is a cross-sectional view showing the second microfluidic channel substrate after cleaning according to the present invention.
  • Figure 14 is a cross-sectional view showing the second microfluidic channel structure of the present invention.
  • Figure 15 is a cross-sectional view showing the second microfluidic channel structure bonded to the transparent active material in the present invention.
  • Figure 16 is a schematic view showing the structure of the present invention.
  • the signal-to-noise ratio of the surface-enhanced Raman scattering detection signal can be improved, and simultaneous real-time detection of various substances can be realized.
  • the invention includes a transparent active substrate 1605 and a microfluidic channel structure layer 1606 supported on the transparent active substrate 1605, in which a plurality of detection microchannels 1201 are disposed, the detection microchannels 1201 and The liquid inlet 1601 and the liquid outlet 1603 of the microfluidic channel structure layer 1606 are connected to each other; the surface of the region corresponding to the transparent active substrate 1605 and the detecting microchannel 1201 is provided with a metal nano forest structure 601, the metal nano forest The structure 601 is located between the liquid inlet 1601 and the liquid outlet 1603.
  • the width of the metal nano-forest structure 601 is not greater than the width of the detection micro-channel 1201 directly above the metal nano-forest structure 601; the height direction of the metal nano-forest structure 601 is perpendicular to the transparent active substrate 1605.
  • the metal nano-forest structure 601 includes a nano-forest structure 501 and a metal layer overlying the nano-forest structure 501, the material of which is gold, platinum or silver.
  • the thickness of the metal layer is 5 to 30 nm, and the diameter of each nanostructure in the nano forest structure 501 is less than 300 nm, and the height of each nanostructure is 100 nm to 2 ⁇ m.
  • the detection microchannel 1201 has a width of 1 mm and a depth of 10 to 50 ⁇ m, preferably 20 ⁇ m or 50 ⁇ m.
  • the transparent active substrate 1605 and the microfluidic channel structure layer 1606 together form a device structure having a length of 10 mm.
  • 2 to 20 detection microchannels 1201 are disposed in the microfluidic channel structure layer 1606.
  • the width of the device structure is determined by the number of detection microfluidic channels 1201 provided, and as the number increases, the width of the device can be correspondingly widened.
  • laser light can be incident from the lower surface of the transparent active substrate 1605.
  • the transparent active substrate 1605 and the nano forest structure 501 are permeable to laser light for generating Raman spectral signals, and the transmittance is The range is 20%-100%.
  • the liquid inlet pipe 1602 is placed in the liquid inlet 1601, and the liquid outlet pipe 1604 is built in the liquid outlet 1603 to inject the test agent into the detection microchannel 1201 through the liquid inlet pipe 1602, and the liquid can be discharged.
  • Tube 1604 flows out.
  • the test agent is injected into the detection microchannel 1201 from the liquid inlet tube 1602 inserted into the liquid inlet 1601 through a syringe, and the test agent flows from the liquid inlet 1601 to the liquid outlet 1603.
  • the substance or molecule contained in the test agent is uniformly distributed in the detection microchannel 1201 as the fluid flows, because the bottom of the detection microchannel 1201 is the metal nano forest structure 601, so the test agent contains The substance or molecule will settle to the surface of the metallic nanoforest structure 601 after a few minutes of standing.
  • the laser incident from the front cannot penetrate the substance or molecule to reach the surface of the metal nano-forest structure 601.
  • Surface plasmon oscillation effects cannot be produced.
  • laser light may be incident from the bottom surface of the transparent active substrate 1605.
  • the bottom surface of the transparent active substrate 1605 is the other surface connected to the microfluidic channel structure layer 1606, and the transparent active substrate 1605 is transparent. The material ensures that the incident laser penetrates the transparent active substrate 1605 to the metal nanoforest structure 601.
  • the transparent active substrate 1605 of the device is placed face up in the laser light path of the Raman scattering spectrum, and the laser penetrates the transparent active group 1605 to reach the metal nano forest structure 601, thereby generating a surface plasmon oscillation effect. Since the substance or molecule to be tested is adsorbed on the surface of the metal nano-forest structure 601, the surface plasmon oscillation effect is effective, and then the SERS line can be tested, and the test agent is obtained from the wave number corresponding to the position of the peak in the line. The composition of the substance or molecule contained in the substance, and the concentration of the substance or molecule is obtained from the intensity of the peak.
  • microfluidic surface-enhanced Raman scattering transparent device structure can be obtained by the following specific steps of the first embodiment and the second embodiment.
  • the experimental methods described in the following embodiments are conventional methods unless otherwise specified.
  • the reagents and materials are commercially available unless otherwise stated.
  • the first substrate 101 is made of a glass material, and the second substrate 201 is a glass piece; the first microfluidic channel substrate 801 uses a single crystal silicon wafer; the microfluidic channel structural layer 1606 material is polydimethylsiloxane.
  • the first substrate 101 is used to finally obtain a metal nano-forest structure 601 on the surface thereof; the second substrate 201 is used to realize the hollow structure; and the first micro-flow channel substrate 801 is used to fabricate the micro-flow channel mold 901.
  • the specific steps are:
  • Step 1 Prepare a surface-enhanced Raman scattering active substrate based on the metal nano-forest structure 601 on the first substrate 101, that is, prepare a transparent active substrate 1605, and at least one metal nano-forest structure 601 is disposed on the transparent active substrate 1605.
  • the first substrate 101, the second substrate 201, and the first microfluidic channel substrate 801 are prepared and cleaned. As shown in Fig. 1, the prepared first substrate 101 is shown in Fig. 8, and the prepared first microfluidic channel substrate 801 is cleaned.
  • a through structure 203 is disposed on the second substrate 201, and a first substrate similar material layer 202 is disposed on a lower surface of the second substrate 201 to form a hollow substrate;
  • a punch-through structure 203 is formed on the second substrate 201 by laser drilling.
  • the punch-through structure 203 is a through hole penetrating the second substrate 201.
  • the width of the punch-through structure 203 is 60 ⁇ m to 500 ⁇ m, preferably 120 ⁇ m. .
  • a layer of amorphous silicon is deposited on the upper surface of the second substrate 201 as a first substrate-like material layer 202 by a plasma enhanced chemical vapor deposition (PECVD) technique, and the amorphous silicon layer has a thickness of 0.5 ⁇ m. 3 ⁇ m. Since the opening structure 203 has a large opening, the PECVD amorphous silicon does not fill the opening to close it.
  • PECVD plasma enhanced chemical vapor deposition
  • the conditions for preparing amorphous silicon by the PECVD method are as follows: a pressure of 2300 mTorr, a gas flow rate of 30 sccm of silane, an operating frequency of 13 MHz, and a power of 15 W.
  • the hollow substrate is pasted onto the first substrate 101 with the first substrate similar material layer 202 facing down, and the upper surface of the first substrate 101 and the lower surface of the hollow substrate are bonded by the adhesive tape 301. Introduce a certain distance between them;
  • the hollow substrate obtained above is pasted onto the first substrate 101 with the first substrate-like material layer 202 facing downward, and the first substrate 101 and the second substrate 201 are bonded during the pasting process.
  • the alignment edges are aligned with each other, and the edge of the substrate is also aligned with each other; when the two substrates are pasted with the adhesive tape 301, a certain distance is introduced between the two surfaces, that is, between the second substrate 201 and the first substrate 101.
  • a distance is formed, that is, a distance 302 is introduced which will change the concentration of the etching gas plasma at different locations within the via.
  • the surface of the first substrate 101 is etched through the through structure 203 on the hollow substrate by an anisotropic RIE technique to obtain a nano-forest structure 501 of glass material.
  • the nano-forest structure 501 of the obtained glass material has a height of 200 nm to 2 ⁇ m, preferably 1 ⁇ m.
  • the gas used in the RIE first substrate 101 is an Ar/CF 4 /CHF 3 mixed gas, the flow rate is 300/15/35 sccm, the RF power is 450 W, the chamber pressure is set to 250 mTorr, and the etching time is 30-180 s. 60s.
  • a metal material is sputtered on the first substrate 101 to which the hollow substrate is pasted.
  • the metal layer is Ag and has a thickness of 5 to 30 nm, preferably 10 nm. Due to the presence of the hollow substrate, a mask layer is disposed on the first substrate 101 such that the metal layer is covered only on the surface of the nano-forest structure 501 to form the metal nano-forest structure 601, and in the first substrate 101 The remaining position of the upper surface is not covered with the metallic material, that is, the patterning of the metallic nano-forest structure 601 is formed.
  • a substrate metal layer 602 is formed on the second substrate 201.
  • the hollow substrate is removed from the upper surface of the first substrate 101 after the sputtered metal layer, and the metal nano-particle is obtained in a region corresponding to the punch-through structure 203 on the upper surface of the first substrate 101.
  • the hollow substrate is removed from the upper surface of the first substrate 101 on which the patterned metal nano-forest structure 601 is implemented, on the upper surface of the first substrate 101 and the punch-through structure.
  • a pattern of the metal nano-forest structure 601 is obtained in the corresponding region of 203, and then a surface-enhanced Raman scattering transparent substrate is obtained, that is, a transparent active body 701 is obtained, and the transparent active substrate 1605 can be formed by using the transparent active body 701.
  • Step 2 preparing a microfluidic channel structure layer 1606 including at least one detecting microfluidic channel 1201; wherein the width of each of the detecting microfluidic channels 1201 is not less than that of the metal nanoforest structure 601 of the step 1 in the transparent The width occupied by the active substrate 1605;
  • Preparing the microfluidic channel structure layer 1606 includes the following steps:
  • Step 1-b corresponding to the photoresist pattern corresponding to the structure 203;
  • the photoresist layer is pre-baked and then applied to the photoresist layer.
  • the photoresist pattern corresponding to the punch-through structure 203 of the step 1-b is obtained after the development; thereafter, the first microfluidic channel substrate 801 is performed by using the photoresist pattern as a mask.
  • the main purpose of the pre-baking is to dry the glue for exposure, and the specific process conditions of the pre-baking are well known to those skilled in the art, and are not described herein again.
  • the first microfluidic channel substrate 801 with the microfluidic channel mold 901 is placed in a predetermined volume of the container, and the polydimethylsiloxane which is thoroughly mixed and has been removed from the bubbles is shown.
  • the prepolymer 1001 is poured onto the mold and baked in an oven at 60 ° C for 60 minutes to crosslink and cure the polydimethylsiloxane to obtain a polymer 1101 of polydimethylsiloxane, which is then tested.
  • the siloxane polymer 1101 is peeled off from the first microfluidic channel substrate 801, and at least one pair of polymer openings 1102 are formed by mechanical perforation at corresponding positions of each microfluidic channel to obtain the microfluidic channel structural layer. 1606.
  • the position of the polymer 1101 corresponding to the micro flow channel mold 901 can form the detection micro flow channel 1201, and the polymer opening 1102 includes the liquid inlet 1601 and the liquid outlet 1603, the liquid inlet 1601, and the liquid outlet. 1603 is respectively located at both ends of the formation detecting microfluidic channel 1201 and is in communication with the detecting microfluidic channel 1201.
  • the polymer 1101 forms the first microfluidic channel structure 1202, and the microfluidic channel structural layer 1606 can be formed by the first microfluidic channel structure 1202.
  • Step 3 Align the transparent active substrate 1605 obtained in the step 1 with the microfluidic channel structure layer 1606 obtained in the step 2.
  • the detection microchannel 1201 in the microfluidic channel structure layer 1606 is located on the transparent active substrate 1605.
  • the microfluidic surface-enhanced Raman scattering transparent device is obtained directly above the upper metal nano-forest structure 601.
  • the polymer 1101 of the polydimethylsiloxane with the polymer opening 1102 is placed face up with an oxygen plasma bombardment chamber with a power of 250 W and an oxygen flow rate of 30 sccm.
  • the surface of the polymer 1101 of dimethylsiloxane is bombarded for 10 s, and the structural surface of the polymer 1101 of the polydimethylsiloxane is rapidly aligned with the upper surface of the transparent active substrate as shown in FIG.
  • the bonding is effected by a chemical bond (as shown in FIG. 12) to obtain the microfluidic surface-enhanced Raman scattering transparent device.
  • the first substrate 101 is made of a glass piece; the second substrate 201 is a single crystal silicon piece; the second micro flow channel substrate 1301 is made of a glass piece; and the micro flow channel structure layer 1606 is made of glass.
  • the first substrate 101 is used to finally obtain a metal nano-forest structure 601 on the surface thereof; the second substrate 201 is used to realize the hollow structure; and the second micro-flow channel substrate 1301 is used to fabricate the micro-flow channel structure layer 1606.
  • Step 1 Prepare a surface-enhanced Raman scattering active substrate based on the metal nano-forest structure 601 on the first substrate 101, that is, prepare a transparent active substrate 1605, and at least one metal nano-forest structure 601 is disposed on the transparent active substrate 1605.
  • the first substrate 101, the second substrate 201, and the second microfluidic channel substrate 1301 are prepared, and the substrate is cleaned.
  • the prepared first substrate 101 is shown in Fig. 1
  • the prepared second microfluidic channel substrate 1301 is shown in Fig. 13 and washed.
  • a punch-through structure 203 is disposed on the second substrate 201, and a first substrate-like material layer 202 is disposed on the lower surface of the second substrate 201 to form a hollow substrate;
  • a layer of 500 nm - 3 ⁇ m silicon dioxide is grown on the surface of the second substrate 201 by a low pressure chemical vapor deposition (LPCVD) technique as an etch mask layer, followed by etching.
  • LPCVD low pressure chemical vapor deposition
  • a photoresist is spin-coated on the upper surface of the mask layer, and a stripe opening is formed on the photoresist layer by a photolithography process, and then the pattern of the strip-shaped opening on the photoresist is transferred to the etch mask layer by RIESiO2.
  • the photoresist is anisotropically etched by the DRIE technique, and the strip-shaped opening pattern on the etch mask layer is transferred onto the second substrate 201 to form a strip on the second substrate 201.
  • the feedthrough structure 203 has a width of from 60 ⁇ m to 500 ⁇ m, preferably 120 ⁇ m.
  • the remaining etch mask layer simultaneously forms a first substrate-like material layer 202.
  • the etching gas used in the RIE silicon substrate is an alternating gas of C 4 F 8 and SF 6 having a flow rate of 550 and 1000 sccm, an RF power of 2000 W, and a chamber pressure of 150 mTorr.
  • the hollow substrate is pasted onto the first substrate 101 with the first substrate-like material layer 202 facing down, and the upper surface of the first substrate 101 and the hollow substrate are pasted by the adhesive tape 301. Introducing a certain distance between the surfaces;
  • the hollow substrate obtained above is pasted onto the first substrate 101 with the first substrate-like material layer 202 facing downward, and the first substrate 101 and the second substrate 201 are bonded during the pasting process.
  • the alignment edges are aligned with each other, and the edge of the substrate is also aligned with each other; when the two substrates are pasted with the adhesive tape 301, a certain distance is introduced between the two surfaces, that is, between the second substrate 201 and the first substrate 101.
  • a distance is formed, that is, a distance 302 is introduced which will change the concentration of the etching gas plasma at different locations within the via.
  • the surface of the first substrate 101 is etched through the through structure 203 on the hollow substrate by an anisotropic RIE technique to obtain a glass material nano forest structure 501.
  • the resulting glass material nanoforest structure 501 has a height of from 200 nm to 2 ⁇ m, preferably 1 ⁇ m.
  • the gas used in the RIE first substrate 101 is an Ar/CF 4 /CHF 3 mixed gas, the flow rate is 300/15/35 sccm, the RF power is 450 W, the chamber pressure is set to 250 mTorr, and the etching time is 30-180 s. 60s.
  • a metal material is sputtered on the first substrate 101 to which the hollow substrate is pasted, the metal layer being Ag having a thickness of 5 to 100 nm, preferably 50 nm.
  • a mask layer is disposed on the first substrate 101 such that the metal layer is covered only on the surface of the nano-forest structure 501 to form the metal nano-forest structure 601, and in the first substrate 101 The remaining positions of the upper surface do not cover the metal layer, that is, the patterning of the metal nano-forest structure 601 is formed.
  • the hollow substrate is removed from the upper surface of the first substrate 101 after the sputtered metal layer, and the metal nano-particle is obtained in a region corresponding to the punch-through structure 203 on the upper surface of the first substrate 101.
  • the hollow substrate is removed from the upper surface of the first substrate 101 on which the patterned metal nano-forest structure 601 is implemented, on the upper surface of the first substrate 101 and the punch-through structure.
  • a pattern of the metal nano-forest structure 601 is obtained in the region corresponding to 203, and then a transparent substrate based on surface-enhanced Raman scattering is obtained, that is, a transparent active body 701 is obtained, and a transparent active substrate 1605 is formed by using the transparent active body 701.
  • Step 2 preparing a microfluidic channel structure layer 1606 including at least one detecting microfluidic channel 1201; wherein the width of each of the detecting microfluidic channels 1201 is not less than that of the metal nanoforest structure 601 of the step 1 in the transparent The width occupied by the active substrate 1605;
  • the photoresist layer is pre-baked, and then exposed on the photoresist layer to obtain a solution.
  • the punch-through structure 203 described in the step 1-b corresponds to the opposite photoresist pattern;
  • the photoresist layer is pre-baked and then exposed on the photoresist layer.
  • a photoresist pattern corresponding to the punch-through structure 203 of the step 1-b is obtained.
  • the second microfluidic channel substrate 1301 is oriented by using the photoresist pattern as a mask.
  • the etching of the surface of the second microfluidic channel substrate 1301 is performed by using an oxygen plasma dry degumming method and a sulfuric acid/hydrogen peroxide wet degumming method to obtain a microfluidic channel structure 1401.
  • the RIE second microfluidic channel substrate 1301 was made of a gas of Ar/CF 4 /CHF 3 mixed gas, a flow rate of 300/15/35 sccm, an RF power of 450 W, and a chamber pressure of 250 mTorr.
  • At least one pair of liquid inlets 1601 and a liquid outlet 1603 are formed by laser perforation at corresponding positions of each microfluidic channel, thereby obtaining a microfluidic channel structural layer 1606 containing at least one detecting microfluidic channel 1201.
  • Step 3 Aligning the transparent active substrate 1605 obtained in the step 1 with the microfluidic channel structure layer 1606 obtained in the step 2, and forming a micro-flow between the detecting microfluidic channel 1201 and the metal nano-forest structure 601 In the track body, the detecting microchannel 1201 in the microfluidic channel structure layer 1606 is located directly above the metal nano-forest structure 601 on the transparent active substrate 1605, that is, the microfluidic surface-enhanced Raman scattering transparent device is obtained.
  • the microfluidic channel structure layer 1606 and the transparent active substrate 1605 are registered and bonded together by electrostatic bonding to obtain the microfluidic surface-enhanced Raman scattering transparent device.
  • the present invention forms a microfluidic surface-enhanced Raman scattering transparent device structure from a transparent active substrate 1605 and a microfluidic channel structure layer 1606 supported on the transparent active substrate 1605.
  • the microfluidic channel 1201 in the microfluidic channel structure layer 1606 is formed.
  • the transparent active substrate 1605 can allow visible light to pass through, and the microfluidic channel structure layer 1606 can be a visible light transmissive material or a visible light opaque material.
  • the device structure and the preparation method thereof have the advantages of high yield, low cost, good detection consistency, no noise interference, and real-time monitoring of the microfluidic surface-enhanced Raman scattering transparent device, which can be used for the detection of large volume and crystal analytes. .

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Abstract

一种微流控表面增强拉曼散射透明器件结构及其制备方法，所述微流控表面增强拉曼散射透明器件结构，包括透明活性基底（1605）以及支撑在所述透明活性基底（1605）上的微流通道结构层（1606），在所述微流通道结构层（1606）内设置若干检测微流道（1201），所述检测微流道（1201）与微流通道结构层（1606）上的入液口（1601）以及出液口（1603）相连通；透明活性基底（1605）与检测微流道（1201）相对应的区域表面上均设置有金属纳米森林结构（601），所述金属纳米森林结构（601）位于入液口（1601）与出液口（1603）之间。结构紧凑，能提高表面增强拉曼散射检测信号的一致性，缩短检测时间，能提高表面增强拉曼散射检测信号的信噪比，能实现对多种物质的同时实时检测，适应范围广，安全可靠。

Description

微流控表面增强拉曼散射透明器件结构及其制备方法 技术领域
本发明涉及一种拉曼散射透明器件结构及其制备方法，尤其是一种微流控表面增强拉曼散射透明器件结构及其制备方法，属于半导体器件的技术领域。
背景技术
基于拉曼散射光谱的检测技术是一种不需要对待检测样品进行标记的物质结构分析手段，具有非破坏性、无需接触等特点。随着激光技术和弱信号探测接收技术的发展，作为一种可实现物质结构分子水平检测的手段，拉曼散射光谱检测技术有望在生物检测、疾病诊断、环境监测、化学分析等领域获得实际和广泛的应用。然而，由于拉曼散射截面小，拉曼散射光谱检测的分析灵敏度低，很多分子或者基团的拉曼光谱很难获得。虽然通过提高激励激光功率可以在一定程度上提高拉曼散射光谱的强度，但对于生物样品，强度太大的激光会破坏样品的生物活性，因此很多应用转而利用了表面增强拉曼散射效应来提高样品的拉曼散射光谱强度。
表面增强拉曼散射效应是指粗糙的贵金属表面在入射光激发的情况下增强吸附在其表面的物质分子的拉曼散射光谱信号的一种现象。分子拉曼散射信号的增强来源于粗糙表面在光照射下所产生的表面电子振荡，当入射光的频率与金属自身的等离子体的频率相匹配时，电子振荡达到最大，于是在金属表面产生一个与入射光频率相同的附加局域电磁场，它所覆盖的区域存在着入射光和表面等离子体被激发后叠加在一起的电磁场。由于分子的拉曼散射源于分子自身的极化与外界电场的相互作用，所以处在这个叠加电场中的分子除了受原入射电磁场的作用外还受这个局域增强电磁场的作用，因此激发出的拉曼散射信号也相应地得到了加强。与普通拉曼散射光谱信号相比，表面增强拉曼散射信号的强度有多个量级的增强，甚至可以实现对单分子拉曼散射信号的探测。
截至目前，已经报道了多种多样的基于纳米粗糙面或纳米结构的开放式表面增强拉曼散射活性基底的制备方法，包括溶胶颗粒法、金属电极的电化学氧化还原法、金属纳米小球排布法、气液固化学生长法及物理化学刻蚀法等等。在这些开放式活性基底上尤其是在纳米粗糙面或纳米结构上分布待测试剂时，一般采用浸泡-蒸发法和滴定-蒸发法。当采用浸泡-蒸发法时，可以在开放式活性基底的纳米粗糙面或纳米结构上均匀吸附一层待分析物分子，但是这种方法所需要的试剂剂量大，同时浸泡耗费的时间往往需要几个小时甚至更长。当采用滴定-蒸发法分布待分析物时，所需的试剂剂量在水平方向上只需要覆盖活性基底整个表面，但其高度可能达到毫米量级，因此试剂用量仍旧较大；且该方法也同样需要耗费较长的溶剂蒸发时间；此外，采用该方法在开放式活性基底上分布分子时，由于咖啡环效应等因素的影响，分子在活性基底上的分布不能达到很好的均匀性，从而影响所检测到的拉曼散射信号的一致性；另外，从应 用角度上说，采用蒸发法分布待分析物分子不适用于对液体环境有特殊要求的生物分子的活体检测。
微流控表面增强拉曼散射检测器件可以实现液体环境中的分子在片检测，具有测量一致性高，测试时间短等显著优点。但已报道的微流控SERS(Surface-enhanced Raman scattering)检测器件其制备流程复杂，所涉及的工艺步骤繁多，且其活性基底一般采用可见光不透明的材料制备得到，继而在对较大尺寸物质进行检测时，激光从正面进入器件，却往往因为被测物质覆盖纳米森林结构导致激光无法透过该物质顺利到达纳米森林结构，从而使器件的检测失效。另外，已报道的微流控SERS检测器件因为SERS活性基底以外用于键合的键合区域在整个流程中一直暴露于材料沉积、物理刻蚀等步骤中，导致该区域表面粗糙度大，难以实现有效键合。
发明内容
本发明的目的是克服现有技术中存在的不足，提供一种微流控表面增强拉曼散射透明器件结构及其制备方法，其结构紧凑，能提高表面增强拉曼散射检测信号的一致性，缩短检测时间，能提高表面增强拉曼散射检测信号的信噪比，能实现对多种物质的同时实时检测，还可实现对大分子、高分子以及结晶类物质的实现检测，具有适应范围广，安全可靠的特点。
按照本发明提供的技术方案，所述微流控表面增强拉曼散射透明器件结构，包括透明活性基底以及支撑在所述透明活性基底上的微流通道结构层，在所述微流通道结构层内设置若干检测微流道，所述检测微流道与微流通道结构层上的入液口以及出液口相连通；透明活性基底与检测微流道相对应的区域表面上均设置有金属纳米森林结构，所述金属纳米森林结构位于入液口与出液口之间。
所述透明活性基底和纳米森林结构为对用于产生拉曼光谱信号的激光可透过，透过率的范围为20％-100％。
所述检测微流道在同一个微流控表面增强拉曼散射透明器件结构中的数量为2-20条。
所述金属层的厚度为5～30nm，纳米森林结构中每个纳米结构的直径小于300nm，每个纳米结构的高度为100nm～2μm。
一种微流控表面增强拉曼散射透明器件结构的制备方法，所述拉曼散射透明器件结构的制备方法包括如下步骤：
a、提供透明活性基底，在所述透明活性基底上通过间隙引入非均匀刻蚀的方法设置若干金属纳米森林结构；
b、提供微通道基板，并利用所述微通道基板制备得到微流通道结构层，所述微流通道结构层内具有与金属纳米森林结构数量相一致的检测微流道，检测微流道与微流通道结构层上的入液口与出液口相连通；
c、将上述透明活性基底与微流通道结构层对准键合，微流通道结构层支撑在透明活性基底上，且所述检测微流道位于金属纳米森林结构的正上方。
所述入液口内设有入液管，在出液口内设有出液管。
所述步骤b中，微流通道结构层的材料为聚二甲基硅氧烷时，微流通道结 构层通过如下步骤制备得到：
2-a、提供第一微通道基板，并在所述第一微通道基板表面涂覆光刻胶，且对所述光刻胶进行曝光，以得到所需的光刻胶图形；
2-b、利用第一微通道基板上的光刻胶图形为掩膜，对所述第一微通道基板进行各向异性刻蚀，去除第一微通道基板上的光刻胶图形，以在所述第一微通道基板上得到微流通道模具；
2-c、以聚二甲基硅氧烷为材料的预聚体浇注在上述第一微通道基板上，使聚二甲基硅氧烷的预聚体交联固化，以在第一微通道基板上得到聚合体；将上述聚合体从第一微通道基板上剥离，聚合体内与微流通道模具相对应的位置形成检测微流道，在所述检测微流道的两端制备与所述检测微流道相连通的聚合体开口。
所述步骤b中，微流通道结构层的材料为硅或玻璃时，微流通道结构层通过如下步骤制备得到：
2-a’、提供第二微通道基板，并在所述第二微通道基板的表面旋涂光刻胶，并对所述光刻胶进行曝光显影，以在第二微通道基板上得到所需的光刻胶图形；
2-b’、以上述第二微通道基板上的光刻胶图形为掩膜，对第二微通道基板进行各向异性刻蚀，在去除第二微通道基板上的光刻胶图形后，得到所需的检测微通道；
2-c’、在每个检测微通道的两端设置入液口以及出液口，以得到微通道结构层。
所述金属纳米森林结构的宽度不大于所述金属纳米森林结构正上方的检测微流道的宽度；金属纳米森林结构的高度方向垂直于透明活性基底；
所述金属纳米森林结构包括纳米森林结构以及覆盖在所述纳米森林结构上的金属层，所述金属层的材料为金、铂或银。
所述透明活性基底的材料包括玻璃，玻璃的厚度为200μm-2mm。
本发明由于采取以上技术方案，其具有以下优点：
1、利用检测微流道与金属纳米森林结构配合实现被检测试剂在表面增强拉曼散射活性基底上的均匀分布，从而提高了表面增强拉曼散射检测信号的一致性，较浸泡-蒸发法和滴定-蒸发法的检测时间显著缩短；
2、采用检测微流道在实现待分析物分子均匀分布的基础上可有效减少甚至避免测试环境引入的噪声，提高表面增强拉曼散射检测信号的信噪比，从而可有效保障器件检测信号的一致性；
3、采用透明活性基底，激光可以从透明活性基底的背面入射到检测器件中，进而可以不受被测分子或物质尺寸的影响，获得良好的检测结果。
4、可通过设计不同的检测微流道，制作一对或多对入液口、出液口，可用于一种待分析物分子的测试或不同待分析物混合和反应前后的信号检测与对比。
5、可通过在透明第一基片上设计多组金属纳米森林结构的图形区域，并通过制作多个检测微流道，可同时实现对多种物质的同片实时检测。
总之，本发明所制备的微流控表面增强拉曼散射透明器件，可广泛应用于生物、化学、医学、农业等领域检测液体待分析物和/或胶体待分析物和/或气体待分析物。
附图说明
图1～图12为本发明实施例1的具体实施步骤剖视图，其中
图1为本发明对第一基片清洗后的剖视图。
图2为本发明利用第二基片得到镂空基片后的剖视图。
图3为本发明第一基片与镂空基片粘贴后的剖视图。
图4为本发明进行各向异性刻蚀的剖视图。
图5为本发明在第一基片上得到纳米森林结构的剖视图。
图6为本发明得到金属纳米森林结构的剖视图。
图7为本发明得到透明活性体后的剖视图。
图8为本发明对第一微流通道基板清洗后的剖视图。
图9为本发明得到微流通道模具后的剖视图。
图10为本发明浇注预聚体后的剖视图。
图11为本发明得到聚合体后的剖视图。
图12为本发明将第一微流通道结构体与透明活性体键合后的剖视图。
图13～图15为本发明实施例2的具体实施步骤剖视图，其中
图13为本发明第二微流通道基板清洗后的剖视图。
图14为本发明形成第二微流通道结构体后的剖视图。
图15为本发明将第二微流通道结构体与透明活性体键合后的剖视图。
图16为本发明的结构示意图。
附图标记说明：101-第一基片、201-第二基片、202-第一基片相似材料层、203-穿通结构、301-粘贴胶带、302-引入距离、401-刻蚀气体等离子体、501-纳米森林结构、601-金属纳米森林结构、602-基片金属层、701-透明活性体、801-第一微流通道基板、901-微流通道模具、1001-预聚体、1101-聚合体、1102-聚合体开口、1201-检测微流道、1202-第一微流通道结构体、1301-第二微流通道基板、1401-第二微流通道结构体、1601-入液口、1602-入液管、1603-出液口、1604-出液管、1605-透明活性基底以及1606-微流通道结构层。
具体实施方式
下面结合具体附图和实施例对本发明作进一步说明。
如图16所示：为了能提高表面增强拉曼散射检测信号的一致性，缩短检测时间，能提高表面增强拉曼散射检测信号的信噪比，能实现对多种物质的同时实时检测，本发明包括透明活性基底1605以及支撑在所述透明活性基底1605上的微流通道结构层1606，在所述微流通道结构层1606内设置若干检测微流道1201，所述检测微流道1201与微流通道结构层1606上的入液口1601以及出液口1603相连通；透明活性基底1605与检测微流道1201相对应的区域表面上均设置有金属纳米森林结构601，所述金属纳米森林结构601位于入液口1601与出液口1603之间。
具体地，所述金属纳米森林结构601的宽度不大于所述金属纳米森林结构601正上方的检测微流道1201的宽度；金属纳米森林结构601的高度方向垂直于透明活性基底1605。所述金属纳米森林结构601包括纳米森林结构501以及覆盖在所述纳米森林结构501上的金属层，所述金属层的材料为金、铂或银。所述金属层的厚度为5～30nm，纳米森林结构501中每个纳米结构的直径小于300nm，每个纳米结构的高度为100nm～2μm。
所述检测微流道1201的宽度为1mm，深度为10-50μm，优选20μm或50μm。透明活性基底1605与微流通道结构层1606共同构成器件结构的长度为10mm，一般地，微流通道结构层1606内设置2～20条检测微流道1201。所述器件结构的宽度由所设置的检测微流通道1201的数量决定，随着数量的增大，所述器件的宽度可相应增宽。在检测时，激光能从透明活性基底1605下表面入射，为了提高检测效果，即所述透明活性基底1605和纳米森林结构501为对用于产生拉曼光谱信号的激光可透过，透过率的范围为20％-100％。
在检测时，在入液口1601内放置入液管1602，在出液口1603内置入出液管1604，以通过入液管1602向检测微流道1201内注入被测试剂，且能通过出液管1604流出。
具体检测时，将被测试剂通过注射器从插置于入液口1601内的入液管1602压入检测微流道1201内，被测试剂会从入液口1601向出液口1603的方向流动；被测试剂中所含的物质或分子随着流体的流动在检测微流道1201内会实现均匀分布，因为检测微流道1201的底部为金属纳米森林结构601，所以被测试剂所含的物质或分子在静置几分钟之后会沉降到金属纳米森林结构601的表面。
由于被测试剂中所含物质或分子有可能存在较大的尺寸，当其覆盖金属纳米森林结构601后，从正面入射的激光无法穿透该物质或分子到达金属纳米森林结构601表面，因此，无法产生表面等离子体振荡效应。本发明实施例中，为了能够实现检测，可以从透明活性基底1605的底面入射激光，所述透明活性基底1605的底面即为与微流通道结构层1606相连的另一面，透明活性基底1605的透明材质能保证入射的激光穿透透明活性基底1605到达金属纳米森林结构601。
具体过程为：将器件的透明活性基底1605面朝上放置于拉曼散射光谱激光光路路径内，激光穿透透明活性基1605到达金属纳米森林结构601，产生表面等离子体振荡效应。由于被测物质或分子被吸附于金属纳米森林结构601的表面，因此表面等离子体振荡效应对其有效，继而可测试得到SERS谱线，由谱线中的峰所在位置对应的波数获得被测试剂中所含物质或分子的成分，由峰的强度得到物质或分子的浓度。
上述的微流控表面增强拉曼散射透明器件结构，可以通过下述实施例1以及实施例2的具体工艺步骤得到，下述实施例中所述实验方法，如无特殊说明，均为常规方法；所述试剂和材料，如无特殊说明，均可从商业途径获得。
实施例1
第一基片101采用玻璃材料，第二基片201为玻璃片；第一微流通道基板 801采用单晶硅片；所述微流通道结构层1606材料为聚二甲基硅氧烷。其中，第一基片101用于最终在其表面得到金属纳米森林结构601；第二基片201用于实现镂空结构；第一微流通道基板801用于制作微流通道模具901。具体步骤为：
步骤1、在第一基片101上制备基于金属纳米森林结构601的表面增强拉曼散射活性基底，即制备得到透明活性基底1605，透明活性基底1605上至少设置一个金属纳米森林结构601。
其具体步骤为：
1-a、准备并清洗第一基片101、第二基片201和第一微流通道基板801；
在结构加工之前，准备第一基片101、第二基片201和第一微流通道基板801，并进行清洗。如图1所示为准备的第一基片101，图8所示为准备的第一微流通道基板801，并对其进行清洗后的结果。
1-b、在所述第二基片201上设置穿通结构203，并在第二基片201下表面设置第一基片相似材料层202，以形成镂空基片；
如图2所示，通过激光打孔的方法在第二基片201上形成穿通结构203，穿通结构203为贯通第二基片201的通孔，穿通结构203的宽度为60μm～500μm，优选120μm。随后采用等离子体增强化学气相沉积(PECVD)技术在第二基片201的上表面淀积一层非晶硅作为第一基片相似材料层202，所述非晶硅层的厚度为0.5μm～3μm。因穿通结构203开口较大，所以PECVD的非晶硅不会填堵开口使之闭合。PECVD方法制备非晶硅的条件为：压强为2300mTorr，气体流量为硅烷30sccm，工作频率为13MHz，功率为15W。
1-c、将上述镂空基片以第一基片相似材料层202面朝下粘贴到所述第一基片101上，通过粘贴胶带301使第一基片101上表面和镂空基片下表面之间引入一定的距离；
如图3所示，将以上得到的镂空基片以第一基片相似材料层202面朝下粘贴到第一基片101上，粘贴过程中，使第一基片101与第二基片201的对准边相互对准，基片边缘亦相互对准；用粘贴胶带301粘贴两层基片时在两表面之间引进一定的距离，即在第二基片201与第一基片101之间形成一段距离，即引入距离302，此引入距离302将改变刻蚀气体等离子体在通孔内不同位置的浓度。
1-d、采用各向异性刻蚀技术穿过所述镂空基片上的穿通结构203对所述第一基片101上表面进行刻蚀，在第一基片101上表面与所述穿通结构203对应的区域内形成纳米森林结构501；
如图4和图5所示，采用各向异性RIE技术穿过所述镂空基片上的穿通结构203对第一基片101表面进行刻蚀，得到玻璃材料的纳米森林结构501。所得到的玻璃材料的纳米森林结构501高度为200nm-2μm，优选1μm。RIE第一基片101时采用的气体为Ar/CF4/CHF3混合气体，流量为300/15/35sccm，RF功率为450W，腔体压力设为250mTorr，刻蚀时间为30-180s，优选60s。
1-e、在所述粘贴了镂空基片的第一基片101上溅射金属材料；
如图6所示，在所述粘贴了镂空基片的第一基片101上溅射金属材料，所 述金属层为Ag，厚度为5-30nm，优选10nm。由于镂空基片的存在，相当于在第一基片101上设置了掩模层，使得仅在纳米森林结构501的表面上覆盖金属层，形成金属纳米森林结构601，而在第一基片101上表面的其余位置不覆盖金属材料，也即形成了金属纳米森林结构601的图形化。在第二基片201上形成基片金属层602。
1-f、将所述镂空基片从溅射金属层后的所述第一基片101上表面揭除，在第一基片101上表面与所述穿通结构203对应的区域内得到金属纳米森林结构601。
如图7所示，将所述镂空基片从实现了图形化金属纳米森林结构601的所述第一基片101上表面揭除，在所述第一基片101上表面与所述穿通结构203对应的区域内得到金属纳米森林结构601的图形，继而得到表面增强拉曼散射透明基底，即得到透明活性体701，利用透明活性体701能形成后续的透明活性基底1605。
步骤2、制备含有至少一个检测微流通道1201的微流通道结构层1606；其中，所述每个检测微流通道1201的宽度不小于所述步骤1所述金属纳米森林结构601在所述透明活性基底1605上占据的宽度；
制备微流通道结构层1606包括如下步骤：
2-a、在第一微流通道基板801表面旋涂一层光刻胶后，对所得光刻胶层进行前烘处理，然后在所述光刻胶层上曝光，显影后得到与所述步骤1-b所述穿通结构203相对应的光刻胶图形；
2-b、以所述步骤2-a所得光刻胶图形为掩模，对所述第一微流通道基板801进行各向异性刻蚀，然后除去所述第一微流通道基板801上的光刻胶图形，得到微流通道模具901；
如图9所示，在第一微流通道基板801的单晶硅片上表面旋涂一层光刻胶后，对所述光刻胶层进行前烘处理，然后在所述光刻胶层上曝光，显影后得到与所述步骤1-b所述穿通结构203相对应的光刻胶图形；此后，以所述光刻胶图形为掩模，对所述第一微流通道基板801进行各向异性刻蚀；利用氧等离子体干法去胶与硫酸/双氧水湿法去胶相结合的方法去除第一微流通道基板801表面的光刻胶，得到微流通道模具901。本发明实施例中，前烘的主要目的是将胶烘干，用于曝光，前烘的具体工艺条件为本技术领域人员所熟知，此处不再赘述。
2-c、以聚二甲基硅氧烷材料的预聚体1001浇注所述步骤2-b所得微流通道模具901，使聚二甲基硅氧烷交联固化，得到聚二甲基硅氧烷的聚合体1101，然后将聚二甲基硅氧烷的聚合体1101从所述微流通道模具901上剥离，并在每个微流通道相应位置制作至少一对聚合体开口1102，得到所述含有至少一个检测微流通道1201的微流通道结构层1606；
如图10和图11所示，将所述带有微流通道模具901的第一微流通道基板801置于预定体积的容器中，将充分混合并已去除气泡的聚二甲基硅氧烷的预聚体1001倒在该模具上，在60℃的烘箱中烘焙60分钟使聚二甲基硅氧烷交联固化，得到聚二甲基硅氧烷的聚合体1101，再将带有检测微流通道1201的聚二甲 基硅氧烷聚合体1101从第一微流通道基板801上剥离，并在每个微流通道相应位置通过机械打孔的方式制作至少一对聚合体开口1102，得到所述微流通道结构层1606。本发明实施例中，聚合体1101与微流通道模具901相对应的位置能形成检测微流通道1201，聚合体开口1102包括入液口1601以及出液口1603，入液口1601、出液口1603分别位于形成检测微流通道1201的两端，并与所述检测微流通道1201相连通。此时，聚合体1101形成第一微流通道结构体1202，通过第一微流通道结构体1202能形成微流通道结构层1606。
步骤3、将所述步骤1所得透明活性基底1605与所述步骤2所得微流通道结构层1606对准键合，所述微流通道结构层1606内的检测微流道1201位于透明活性基底1605上金属纳米森林结构601的正上方，即得到所述微流控表面增强拉曼散射透明器件。
将如图12所示，带有聚合体开口1102的聚二甲基硅氧烷的聚合体1101结构面朝上放入功率为250W，氧气流速为30sccm的氧等离子体轰击腔体中，对聚二甲基硅氧烷的聚合体1101的表面进行10s的轰击，并迅速将聚二甲基硅氧烷的聚合体1101的结构面与如图7所示的透明活性基底上表面对准贴合，使之在化学键的作用下实现键合(如图12所示)，得到所述微流控表面增强拉曼散射透明器件。
实施例2
第一基片101采用玻璃片；第二基片201为单晶硅片；第二微流通道基板1301采用玻璃片；所述微流通道结构层1606材料为玻璃。其中，第一基片101用于最终在其表面得到金属纳米森林结构601；第二基片201用于实现镂空结构；第二微流通道基板1301用于制作微流通道结构层1606。
步骤1、在第一基片101上制备基于金属纳米森林结构601的表面增强拉曼散射活性基底，即制备得到透明活性基底1605，透明活性基底1605上至少设置一个金属纳米森林结构601。
其具体步骤为：
1-a、准备并清洗第一基片101、第二基片201和第二微流通道基板1301；
在结构加工之前，准备第一基片101、第二基片201和第二微流通道基板1301，并对基片进行清洗。如图1所示为准备的第一基片101，图13所示为准备的第二微流通道基板1301，并对其进行清洗后的结果。
1-b、在所述第二基片201上设置穿通结构203，并在第二基片201下表面设置第一基片相似材料层202，形成镂空基片；
如图2所示，通过在第二基片201的表面利用低压化学气相沉积(LPCVD)技术在硅衬底表面生长一层500nm-3μm的二氧化硅作为刻蚀掩模层，随后在刻蚀掩模层上表面旋涂光刻胶，并通过光刻工艺在光刻胶层上形成条形开口，随后利用RIESiO2的方法将光刻胶上条形开口的图形转移到刻蚀掩模层上，形成位于刻蚀掩模层上的条形开口图形，即形成衬底刻蚀窗口；利用氧等离子体干法去胶与硫酸/双氧水湿法去胶相结合的方法去除刻蚀掩模层表面的光刻胶；采用DRIE技术各向异性刻蚀第二基片201，将刻蚀掩模层上的条形开口图形转移 到第二基片201上，形成第二基片201上的条形穿通结构203，其宽度为60μm-500μm，优选120μm。残留的刻蚀掩模层同时形成第一基片相似材料层202。RIE硅衬底时采用的刻蚀气体为C4F8和SF6交替的气体，其流量分别为550和1000sccm，RF功率为2000W，腔体压力为150mTorr。
1-c、将所述镂空基片以第一基片相似材料层202面朝下粘贴到所述第一基片101上，通过粘贴胶带301使第一基片101上表面和镂空基片下表面之间引入一定的距离；
如图3所示，将以上得到的镂空基片以第一基片相似材料层202面朝下粘贴到第一基片101上，粘贴过程中，使第一基片101与第二基片201的对准边相互对准，基片边缘亦相互对准；用粘贴胶带301粘贴两层基片时在两表面之间引进一定的距离，即在第二基片201与第一基片101之间形成一段距离，即引入距离302，此引入距离302将改变刻蚀气体等离子体在通孔内不同位置的浓度。
1-d、采用各向异性刻蚀技术穿过所述镂空基片上的穿通结构203对所述第一基片101上表面进行刻蚀，在第一基片101上表面与所述穿通结构203对应的区域内形成纳米森林结构501；
如图4和图5所示，采用各向异性RIE技术穿过所述镂空基片上的穿通结构203对第一基片101表面进行刻蚀，得到玻璃材料纳米森林结构501。所得到的玻璃材料纳米森林结构501高度为200nm-2μm，优选1μm。RIE第一基片101时采用的气体为Ar/CF4/CHF3混合气体，流量为300/15/35sccm，RF功率为450W，腔体压力设为250mTorr，刻蚀时间为30-180s，优选60s。
1-e、在所述粘贴了镂空基片的第一基片101上溅射金属材料；
如图6所示，在所述粘贴了镂空基片的第一基片101上溅射金属材料，所述金属层为Ag，厚度为5-100nm，优选50nm。由于镂空基片的存在，相当于在第一基片101上设置了掩模层，使得仅在纳米森林结构501的表面上覆盖金属层，形成金属纳米森林结构601，而在第一基片101上表面的其余位置不覆盖金属层，也即形成了金属纳米森林结构601的图形化。
1-f、将所述镂空基片从溅射金属层后的所述第一基片101上表面揭除，在第一基片101上表面与所述穿通结构203对应的区域内得到金属纳米森林结构601。
如图7所示，将所述镂空基片从实现了图形化金属纳米森林结构601的所述第一基片101上表面揭除，在所述第一基片101上表面与所述穿通结构203对应的区域内得到金属纳米森林结构601的图形，继而得到基于表面增强拉曼散射透明基底，即得到透明活性体701，利用透明活性体701形成后续的透明活性基底1605。
步骤2、制备含有至少一个检测微流通道1201的微流通道结构层1606；其中，所述每个检测微流通道1201的宽度不小于所述步骤1所述金属纳米森林结构601在所述透明活性基底1605上占据的宽度；
包括如下步骤：
2-a、在第二微流通道基板1301表面旋涂一层光刻胶后，对所述光刻胶层进行前烘处理，然后在所述光刻胶层上曝光，显影后得到与所述步骤1-b中所述穿通结构203对应相反的光刻胶图形；
2-b、以所述步骤2-a中所得光刻胶图形为掩模，对所述第二微流通道基板1301进行各向异性刻蚀，然后除去所述第二微流通道基板1301上的光刻胶图形；
2-c、在每个微流通道相应位置制作至少一对入液口1601、出液口1603，得到所述含有至少一个检测微流通道1201的微流通道结构层1606；
图14所示，在用作第二微流通道基板1301的玻璃片上表面旋涂一层光刻胶后，对所述光刻胶层进行前烘处理，然后在所述光刻胶层上曝光，显影后得到与所述步骤1-b所述穿通结构203对应相反的光刻胶图形；此后，以所述光刻胶图形为掩模，对所述第二微流通道基板1301进行各向异性刻蚀；利用氧等离子体干法去胶与硫酸/双氧水湿法去胶相结合的方法去除第二微流通道基板1301表面的光刻胶，得到微流通道结构1401。RIE第二微流通道基板1301玻璃材料时采用的气体为Ar/CF4/CHF3混合气体，流量为300/15/35sccm，RF功率为450W，腔体压力设为250mTorr。
在每个微流通道相应位置通过激光打孔的方式制作至少一对入液口1601、出液口1603，即得到含有至少一个检测微流通道1201的微流通道结构层1606。
步骤3、将所述步骤1所得透明活性基底1605与所述步骤2所得微流通道结构层1606对准键合，所述检测微流通道1201与所述金属纳米森林结构601之间形成微流通道体，所述微流通道结构层1606内的检测微流道1201位于透明活性基底1605上金属纳米森林结构601的正上方，即得到所述微流控表面增强拉曼散射透明器件。
如图15所示，采用静电键合的方式将微流通道结构层1606与透明活性基底1605套准后键合在一起，得到所述微流控表面增强拉曼散射透明器件。
本发明由透明活性基底1605以及支撑在所述透明活性基底1605上的微流通道结构层1606形成微流控表面增强拉曼散射透明器件结构，微流通道结构层1606内的检测微流道1201位于透明活性基底1605上的金属纳米森林结构601的正上方，透明活性基底1605能允许可见光透过，微流通道结构层1606可以采用可见光透光材料或可见光不可透光材料。该器件结构及其制备方法成品率高、成本低廉、检测一致性好、无噪声干扰、可实时监测的微流控表面增强拉曼散射透明器件，可用于大体积、晶体类待分析物的检测。

Claims (10)

  1. 一种微流控表面增强拉曼散射透明器件结构，其特征是：包括透明活性基底(1605)以及支撑在所述透明活性基底(1605)上的微流通道结构层(1606)，在所述微流通道结构层(1606)内设置若干检测微流道(1201)，所述检测微流道(1201)与微流通道结构层(1606)上的入液口(1601)以及出液口(1603)相连通；透明活性基底(1605)与检测微流道(1201)相对应的区域表面上均设置有金属纳米森林结构(601)，所述金属纳米森林结构(601)位于入液口(1601)与出液口(1603)之间。
  2. 根据权利要求1所述的微流控表面增强拉曼散射透明器件结构，其特征是：所述透明活性基底(1605)和纳米森林结构(501)为对用于产生拉曼光谱信号的激光可透过，透过率的范围为20％-100％。
  3. 根据权利要求1或2所述的微流控表面增强拉曼散射透明器件结构，其特征是：所述检测微流道(1201)在同一个微流控表面增强拉曼散射透明器件结构中的数量为2-20条。
  4. 根据权利要求3所述的微流控表面增强拉曼散射透明器件结构，其特征是：所述金属层的厚度为5～30nm，纳米森林结构(501)中每个纳米结构的直径小于300nm，每个纳米结构的高度为100nm～2μm。
  5. 一种微流控表面增强拉曼散射透明器件结构的制备方法，其特征是，所述拉曼散射透明器件结构的制备方法包括如下步骤：
    (a)、提供透明活性基底(1605)，在所述透明活性基底(1605)上通过间隙引入非均匀刻蚀的方法设置若干金属纳米森林结构(601)；
    (b)、提供微通道基板，并利用所述微通道基板制备得到微流通道结构层(1606)，所述微流通道结构层(1606)内具有与金属纳米森林结构(601)数量相一致的检测微流道(1201)，检测微流道(1201)与微流通道结构层(1606)上的入液口(1601)与出液口(1603)相连通；
    (c)、将上述透明活性基底(1605)与微流通道结构层(1606)对准键合，微流通道结构层(1606)支撑在透明活性基底(1605)上，且所述检测微流道(1201)位于金属纳米森林结构(601)的正上方。
  6. 根据权利要求5所述微流控表面增强拉曼散射透明器件结构的制备方法，其特征是：所述入液口(1601)内设有入液管(1602)，在出液口(1603)内设有出液管(1604)。
  7. 根据权利要求5所述微流控表面增强拉曼散射透明器件结构的制备方法，其特征是，所述步骤(b)中，微流通道结构层(1606)的材料为聚二甲基硅氧烷时，微流通道结构层(1606)通过如下步骤制备得到：
    (2-a)、提供第一微通道基板(801)，并在所述第一微通道基板(801)表面涂覆光刻胶，且对所述光刻胶进行曝光，以得到所需的光刻胶图形；
    (2-b)、利用第一微通道基板(801)上的光刻胶图形为掩膜，对所述第一微通道基板(801)进行各向异性刻蚀，去除第一微通道基板(801)上的光刻胶图形，以在所述第一微通道基板(801)上得到微流通道模具(901)；
    (2-c)、以聚二甲基硅氧烷为材料的预聚体(1001)浇注在上述第一微通道基板(801)上，使聚二甲基硅氧烷的预聚体(1001)交联固化，以在第一微通道基板(801)上得到聚合体(1101)；将上述聚合体(1101)从第一微通道基板(801)上剥离，聚合体(1101)内与微流通道模具(901)相对应的位置形成检测微流道(1201)，在所述检测微流道(1201)的两端制备与所述检测微流道(1201)相连通的聚合体开口(1102)。
  8. 根据权利要求7所述微流控表面增强拉曼散射透明器件结构的制备方法，其特征是，所述步骤(b)中，微流通道结构层(1606)的材料为硅或玻璃时，微流通道结构层(1606)通过如下步骤制备得到：
    (2-a’)、提供第二微通道基板(1301)，并在所述第二微通道基板(1301)的表面旋涂光刻胶，并对所述光刻胶进行曝光显影，以在第二微通道基板(1301)上得到所需的光刻胶图形；
    (2-b’)、以上述第二微通道基板(1301)上的光刻胶图形为掩膜，对第二微通道基板(1301)进行各向异性刻蚀，在去除第二微通道基板(1301)上的光刻胶图形后，得到所需的检测微通道(1201)；
    (2-c’)、在每个检测微通道(1201)的两端设置入液口(1601)以及出液口(1603)，以得到微通道结构层(1606)。
  9. 根据权利要求5所述微流控表面增强拉曼散射透明器件结构的制备方法，其特征是，所述金属纳米森林结构(601)的宽度不大于所述金属纳米森林结构(601)正上方的检测微流道(1201)的宽度；金属纳米森林结构(601)的高度方向垂直于透明活性基底(1605)；
    所述金属纳米森林结构(601)包括纳米森林结构(501)以及覆盖在所述纳米森林结构(501)上的金属层，所述金属层的材料为金、铂或银。
  10. 根据权利要求5所述微流控表面增强拉曼散射透明器件结构的制备方法，其特征是：所述透明活性基底(1605)的材料包括玻璃，玻璃的厚度为200μm-2mm。
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