A method for fabricating a solid-phase surface-enhanced Raman scattering substrate with adjustable spacing
By controlling the spacing between nanoparticles in an ultrafast microfluidic mixer, a solid-phase SERS substrate with high sensitivity, high uniformity, and long-term stability was prepared, solving the problems of uneven and uncontrollable hot spots in the prior art and achieving high efficiency and stability in SERS detection.
Patent Information
- Application Number
- CN202211278502.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-10-19
- Publication Date
- 2025-11-14
- Estimated Expiration
- 2042-10-19
AI Technical Summary
Existing technologies struggle to prepare solid-phase SERS substrates with uniform hotspots and controllable nanoparticle spacing, resulting in insufficient sensitivity and stability of SERS detection.
By injecting metal nanoparticles and aggregators into an ultrafast microfluidic mixer, the aggregator alters the repulsive force between nanoparticles, thereby controlling the spacing between nanoparticles and forming uniform SERS hotspots. Uniform deposition of nanoparticles is achieved by employing a cascaded split-recombination C-SAR mixer and specific flow control.
A highly sensitive, highly uniform, and long-term stable SERS substrate was achieved. The operation is simple, the repeatability is good, and the spacing between nanoparticles is adjustable.
Smart Images
Figure CN115901716B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for fabricating a solid-phase SERS substrate with adjustable spacing, belonging to the technical field of functionalized microfluidic devices. Background Technology
[0002] Surface-enhanced Raman scattering (SERS) has been widely applied in various fields due to its advantages in providing ultrasensitive detection and fingerprint information. The signal amplification of SERS is mainly due to the huge electromagnetic enhancement caused by localized surface plasmon resonance (LSPR) associated with metal nanostructures, also known as plasma "hot spots". However, it is strongly dependent on the size of the nanogap. Reducing the width of the nanogap leads to a great enhancement of the local field. Therefore, controlling the size of the nanogap is crucial for its practical application.
[0003] Typical methods for preparing SERS substrates include solid-phase nanoarray substrates and liquid-phase colloidal substrates. To simultaneously meet the requirements of hotspot uniformity and controllability, various methods for preparing tunable SERS substrates have been developed. For example, solid-phase substrates stimulate responsive materials to generate strain through external conditions such as temperature, magnetic fields, and electric fields. However, due to the shape memory of some materials, once the external force disappears, the material returns to its original shape, exhibiting instability and operational complexity. For liquid-phase substrates, agglomerating agents can be directly added to the colloid to induce the aggregation of nanoparticles to generate hotspots, but this is difficult to control and the signal reproducibility is poor.
[0004] Therefore, preparing SERS substrates with uniform hotspots and easily adjustable nanoparticle spacing is a major research challenge, which is of great significance for achieving highly sensitive, highly uniform, good repeatability and long-term stable SERS detection. Summary of the Invention
[0005] Technical Problem: The purpose of this invention is to develop a method for fabricating a solid-phase surface-enhanced Raman scattering (SERS) substrate with adjustable spacing, which solves the problem of uncontrollable induced nanoparticle aggregation in liquid-phase SERS substrates, enables active control of "hot spots," and forms a highly sensitive, highly uniform, reproducible, and long-term stable SERS substrate.
[0006] Technical Solution: This invention provides a method for fabricating a solid-phase surface-enhanced Raman scattering (SERS) substrate with adjustable spacing. Metal nanoparticles and an aggregator are injected separately into an ultrafast microfluidic mixer. The aggregator alters the repulsive forces between the metal nanoparticles, thereby controlling the spacing of the metal nanoparticles by changing the concentration of the aggregator, thus actively controlling the SERS "hot spots." Furthermore, the mixing speed of the ultrafast microfluidic mixer ensures uniform adsorption of the aggregator on the surface of each nanoparticle, preventing uncontrolled aggregation of the metal nanoparticles and forming a SERS substrate with uniform SERS "hot spots."
[0007] The method specifically includes the following steps:
[0008] 1) Aggregator and metal nanoparticle sol are introduced into the ultrafast microfluidic mixer from the central channel and the two side channels respectively, with a total flow rate ranging from 360 μl / min to 890 μl / min to ensure uniform mixing. The flow rate ratio of the aggregate in the central channel to the metal nanoparticle sol on both sides is 1:5:5 to 1:1.7:1.7.
[0009] 2) After continuous flow for 15 min to 7 min, corresponding to low and high flow rates respectively, metal nanoparticles are uniformly deposited in the detection area of the microfluidic mixer, forming a monolayer metal nanoparticle SERS substrate.
[0010] 3) By changing the concentration of the aggregator, the spacing between nanoparticles can be controlled to form a solid monolayer SERS substrate with controllable SERS "hot spots"; increasing the concentration of the aggregator can reduce the spacing between metal nanoparticles and enhance the intensity of SERS "hot spots"; under the optimized concentration of the aggregator, the sensitivity of the SERS substrate can reach its best.
[0011] The agglomerating agent is phosphoric acid or a soluble metal halide, soluble phosphate, or soluble sulfate.
[0012] The metal nanoparticles mentioned are gold nanoparticles, silver nanoparticles, copper nanoparticles, iron nanoparticles, aluminum nanoparticles, nickel nanoparticles, or titanium nanoparticles.
[0013] The ultrafast microfluidic mixer used has a mixing time on the order of milliseconds.
[0014] The ultrafast microfluidic mixer used is a cascaded split-recombination C-SAR mixer.
[0015] The increase in agglomerating agent concentration is as follows: when using phosphoric acid as agglomerating agent, the concentration range of phosphoric acid is no higher than 2.2 mM; when using NaCl as agglomerating agent, the concentration range of NaCl is no higher than 11 mM.
[0016] Beneficial effects: Compared with the prior art, the present invention has the following advantages:
[0017] 1. The present invention introduces an agglomerating agent into an ultrafast microfluidic mixer to regulate the spacing between nanoparticles, i.e., the intensity of SERS "hot spots". The method is simple to operate. By changing the concentration of the agglomerating agent, the repulsive force between nanoparticles can be regulated, inducing the spacing between nanoparticles to decrease, thereby forming a large number of "hot spots".
[0018] 2. The ultrafast microfluidic mixer can fully mix the agglomerant and metal nanoparticles on a millisecond timescale, so that the diffusion rate and adsorption rate of the agglomerant are matched, thereby ensuring that the agglomerant is uniformly adsorbed on the surface of each nanoparticle and avoiding uncontrolled aggregation of nanoparticles.
[0019] 3. Form a highly sensitive, highly uniform, good repeatability and long-term stable SERS substrate. Attached Figure Description
[0020] Figure 1 A schematic diagram of the fabrication of a solid-phase SERS substrate with adjustable spacing;
[0021] Figure 2 The images show SERS substrates of silver nanoparticles prepared in Example 1 with and without phosphoric acid and with different concentrations of phosphoric acid, where: (a) without phosphoric acid, (b) 0.22 mM phosphoric acid, and (c) 2.2 mM phosphoric acid.
[0022] Figure 3 The images show SERS substrates of gold nanoparticles prepared in Example 2 with and without NaCl and with different concentrations of NaCl, where: (a) without NaCl, (b) 1.1 mM NaCl, and (c) 11 mM NaCl. Detailed Implementation
[0023] The technical solution of the present invention will be further described in detail below with reference to the embodiments and accompanying drawings.
[0024] The ultrafast microfluidic mixer used in the embodiments is a cascaded split-recombination C-SAR mixer (Chem. Eng. Res. Des., 2018, 132, 338–345.), with mixing time on the order of milliseconds; the silver nanoparticle sol used in this invention was prepared by a pH-controlled method that separates nucleation and growth, resulting in particles with an average size of 57 nm (RSC Adv., 2017, 7, 8771-8878); the gold nanoparticles were synthesized using the Frens method, resulting in 15 nm spherical particles (Nature Phys., 1973, 241, 20-22).
[0025] Example 1: Fabrication of a solid-phase SERS substrate based on phosphoric acid-regulated spacing of silver nanoparticles
[0026] (1) 2% APTMS-anhydrous ethanol solution was passed into a microfluidic mixer for surface modification, making the channel wall more likely to adsorb silver nanoparticles. Excess APTMS solution was washed away to obtain a hydrophilic microfluidic mixing chip.
[0027] (2) Deionized water ( Figure 2 a) and concentrations of 0.22 mM ( Figure 2 b), 2.2mM Figure 2 c) Phosphoric acid solution is introduced from the main channel at a flow rate of 40 μl / min, and silver nanoparticle colloidal solution is introduced into the two side channels of the microfluidic mixer at a flow rate of 200 μl / min.
[0028] (3) After 10 minutes, deionized water is introduced through the outlet channel at a rate of 50 μl / min to remove excess unadsorbed silver nanoparticles, resulting in a uniform monolayer of silver nanoparticles in the detection area, controlled by the phosphoric acid concentration. Figure 2 As shown.
[0029] Figure 2 Electron microscopy images of SERS substrates without phosphoric acid (a) and with different concentrations of phosphoric acid. The phosphoric acid concentrations are 0.22 mM (b) and 2.2 mM (c), respectively. As the phosphoric acid concentration increases, the spacing between silver nanoparticles on the SERS substrate decreases.
[0030] Example 2: Fabrication of a solid-phase SERS substrate based on NaCl-controlled spacing of gold nanoparticles
[0031] (1) 2% APTMS-anhydrous ethanol solution was passed into a microfluidic mixer for surface modification, making the channel wall more likely to adsorb gold nanoparticles. Excess APTMS solution was washed away to obtain a hydrophilic microfluidic mixing chip.
[0032] (2) Deionized water ( Figure 3 a) and concentrations of 1.1 mM ( Figure 3 b), 11mM ( Figure 3 c) The NaCl solution is introduced from the main channel at a flow rate of 40 μl / min, and the gold nanoparticle colloidal solution is introduced into the two side channels of the microfluidic mixer at a flow rate of 200 μl / min.
[0033] (3) After 10 minutes, deionized water was introduced through the outlet channel at a rate of 50 μl / min to remove excess unadsorbed gold nanoparticles, resulting in a uniform monolayer of gold nanoparticles in the detection area, controlled by the NaCl concentration. Figure 3 As shown.
[0034] Figure 3 The images show SERS substrates without NaCl (a) and with different NaCl concentrations (b and c), respectively. The NaCl concentrations are 1.1 mM and 11 mM, respectively. As the NaCl concentration increases, the spacing between gold nanoparticles on the SERS substrate decreases.
Claims
1. A method for fabricating a solid-phase surface-enhanced Raman scattering substrate with adjustable spacing, characterized in that, By injecting metal nanoparticles and aggregators into an ultrafast microfluidic mixer, the spacing between metal nanoparticles can be controlled by changing the concentration of the aggregator, thereby actively controlling the SERS "hot spots". Furthermore, the mixing speed of the ultrafast microfluidic mixer ensures that the aggregator is uniformly adsorbed on the surface of each nanoparticle, avoiding the uncontrollable aggregation of metal nanoparticles and forming a SERS substrate with uniform SERS "hot spots". The method specifically includes the following steps: 1) Aggregator and metal nanoparticle sol are introduced into the ultrafast microfluidic mixer from the central channel and the two side channels respectively, with a total flow rate ranging from 360 μl / min to 890 μl / min to ensure uniform mixing. The flow rate ratio of the aggregate in the central channel to the metal nanoparticle sol on both sides is 1:5:5 to 1:1.7:1.
7. 2) After continuous flow for 15 min-7 min, corresponding to low flow rate and high flow rate respectively, metal nanoparticles were uniformly deposited in the detection area of the microfluidic mixer, forming a monolayer metal nanoparticle SERS substrate. 3) By changing the concentration of the aggregator, the spacing between nanoparticles can be controlled to form a solid monolayer SERS substrate with tunable SERS "hot spots"; increasing the concentration of the aggregator can reduce the spacing between metal nanoparticles and enhance the intensity of SERS "hot spots"; under the optimized concentration of the aggregator, the sensitivity of the SERS substrate can be maximized. The agglomerating agent is phosphoric acid or a soluble metal halide, a soluble phosphate, or a soluble sulfate; The ultrafast microfluidic mixer used is a cascaded split-recombination C-SAR mixer.
2. The method for fabricating a solid-phase surface-enhanced Raman scattering substrate with adjustable spacing according to claim 1, characterized in that, The metal nanoparticles mentioned are gold nanoparticles, silver nanoparticles, copper nanoparticles, iron nanoparticles, aluminum nanoparticles, nickel nanoparticles, or titanium nanoparticles.
3. The method for fabricating a solid-phase surface-enhanced Raman scattering substrate with adjustable spacing according to claim 1, characterized in that, The ultrafast microfluidic mixer used has a mixing time on the order of milliseconds.
4. The method for fabricating a solid-phase surface-enhanced Raman scattering substrate with adjustable spacing according to claim 1, characterized in that, The increase in agglomerating agent concentration is as follows: when using phosphoric acid as agglomerating agent, the concentration range of phosphoric acid is no higher than 2.2 mM; when using NaCl as agglomerating agent, the concentration range of NaCl is no higher than 11 mM.