Method for preparing gold nanoparticles based on two-phase flow microfluidic control

Abstract

The invention relates to the field of microfluid chemical synthesis, and discloses a method for preparing gold nanoparticles based on two-phase flow microfluid control. The method comprises the following steps: 1) converging a gold precursor water phase, a reducing agent water phase and an organic phase in a micro-fluidic chip at 0-25 DEG C to form water-in-oil liquid drops; (2) conveying the fluid to a mixing area channel of a micro-fluidic chip, and carrying out instantaneous nucleation reaction to form a gold nanoparticle prototype; 3) conveying the fluid into a capillary reactor, and further nucleating, growing and curing the gold nanoparticle prototype; and (4) the fluid is subjected to phase splitting, and a gold nanoparticle solution is obtained. A three-in-one micro-fluidic chip is adopted, process parameters are optimized, and a gold precursor and a reducing agent are wrapped in an organic phase before reaction to form water-in-oil liquid drops, so that on one hand, the situation of adsorption and scaling of the inner wall of a channel can be avoided, and on the other hand, the heat and mass transfer efficiency of a material can be improved through the generated liquid drops; and the uniformity of a reaction nucleation environment is ensured.

Description

Technical Field

[0001] The invention relates to the field of microfluidic chemical synthesis, and in particular to a method for preparing gold nanoparticles based on two-phase flow microfluidic control. Background Art

[0002] In recent decades, gold nanoparticles have been widely used in many fields such as catalysis, analytical chemistry, medical diagnosis and treatment due to their unique optical, electronic, biocompatible and catalytic properties. The process of synthesizing gold nanoparticles by traditional chemical methods is usually carried out in containers such as beakers. Protective ligand-stabilized gold nanoparticles are prepared by reducing the corresponding gold precursors or gold ions in the presence of stable ligands (such as citrate). However, under such conditions, any changes in local conditions (such as temperature and metal precursor concentration) will affect the growth of gold nanoparticles, making the size distribution of gold nanoparticles polydisperse, and having problems such as low reaction efficiency, poor batch reproducibility, and difficulty in flexibly adjusting the preparation scale.

[0003] In order to solve these problems, the use of continuous micro-reaction technology to synthesize gold nanoparticles is an effective method. The high specific surface area of ​​the microreactor can greatly improve the mass transfer and heat transfer efficiency of the reaction solution, and can improve the repeatability of product performance by precisely controlling the reaction conditions.

[0004] However, the high specific surface area of ​​the microreactor also brings a direct disadvantage, that is, the interaction between the reaction solution and the inner wall of the reactor increases, which makes it easier for gold nanoparticles to be adsorbed and deposited on the inner wall of the reaction channel, affecting the concentration and quality of the product. Therefore, the current technology of using microreactors to prepare gold nanoparticles still has many inconveniences and defects, and it is necessary to further develop an effective and universal method for high-quality continuous preparation of gold nanoparticles. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides a method for preparing gold nanoparticles based on two-phase flow microfluidics. The present invention uses a three-in-one microfluidic chip and optimizes the process parameters to encapsulate the gold precursor and the reducing agent in the organic phase before the reaction to form oil-in-water droplets. On the one hand, it can greatly shorten the time that the aqueous phase material directly contacts the flow channel after merging, thereby avoiding adsorption and scaling on the inner wall of the channel as much as possible. On the other hand, the generated droplets can also improve the heat and mass transfer efficiency of the material, ensuring the uniformity of the reaction nucleation environment.

[0006] The specific technical scheme of the present invention is: In a first aspect, the present invention provides a method for preparing gold nanoparticles based on two-phase flow microfluidics, which specifically comprises the following steps: 1) The gold precursor aqueous phase, the reducing agent aqueous phase and the organic phase are allowed to converge at the junction of two aqueous phase channels and one oil phase channel of the microfluidic chip at 0-25° C. to form a fluid containing water-in-oil droplets.

[0007] 2) The fluid is transported to the mixing zone channel at 90-95°C in the microfluidic chip, where an instantaneous nucleation reaction occurs to form the prototype of gold nanoparticles.

[0008] 3) The fluid is transported into the capillary reactor, and the gold nanoparticle prototypes are further nucleated, grown, and matured.

[0009] 4) The fluid is phase-separated to obtain a gold nanoparticle solution with a Z average particle size of 20-30 nm and a PDI of ≤0.21.

[0010] As described in the background technology section of this application, the main method for preparing gold nanoparticles is batch production, which has the disadvantages of poor batch-to-batch repeatability, wide particle size distribution, and difficulty in amplification. The method for preparing gold nanoparticles based on microreaction technology can overcome these problems in the batch production process. The excellent mass transfer and heat transfer performance and laminar flow characteristics of the microreaction system can prepare gold nanoparticles with a narrow size distribution, providing a new dimension for the preparation research of gold nanoparticles. However, the high specific surface area of ​​the microreactor will also increase the interaction between the reaction solution and the inner wall of the reactor, thereby causing the gold nanoparticles to be more easily adsorbed and deposited on the inner wall of the reaction channel, affecting the product concentration and quality.

[0011] To this end, the present invention provides a method for preparing gold nanoparticles based on two-phase flow microfluidics. The microfluidic chip used in the present invention comprises a refrigeration zone (water phase channel, oil phase channel) and a heating zone (mixing zone channel), which can realize precise zoning temperature control. The preparation process and principle of the present invention are roughly as follows: first, the gold precursor water phase and the reducing agent water phase are respectively transported to the two water phase inlets in the microfluidic chip, and the two water phases are immediately separated into uniform oil-in-water droplets by the organic phase entering the microfluidic chip from the organic phase inlet after merging in the three-way (the confluence of the two water phase channels and the oil phase channel) in the refrigeration zone of the microfluidic chip, forming a fluid similar to a "slug flow". This process of water phase merging and droplet generation is controlled to be carried out at a temperature of ≤ room temperature, which can not only improve the stability of the gold precursor, but more importantly, it can also inhibit the reaction of the gold precursor after contact with the reducing agent, and avoid the reaction before being wrapped by the droplets, resulting in the adsorption of nanogold particles on the inner wall of the channel (if the temperature is higher than room temperature, the gold precursor will react with the reducing agent before being wrapped by the organic phase). After the droplets are generated, the fluid immediately enters the mixing channel area in the second half of the microfluidic chip. The mixing channel area is in a high temperature environment, which can achieve instantaneous mixing and nucleation reactions. After the fluid flows out of the outlet of the microfluidic chip, it enters the capillary reactor to complete the nucleation, growth, and maturation of the gold nanoparticles. Then, the product and the organic phase are separated by a phase separator, thereby achieving continuous and stable synthesis of gold nanoparticles.

[0012] Preferably, in step 1), the organic phase is n-decane, n-nonane or liquid paraffin; more preferably n-decane and / or n-nonane.

[0013] The present invention finds that the type of organic phase is crucial for whether the gold precursor aqueous phase and the reducing agent aqueous phase can be well wrapped by the organic phase before the reaction after confluence. The present invention finds through research that only the above-mentioned types of organic phases have better effects, among which liquid alkanes are better than oleic acid and mineral oil. The reason is that in the process of preparing colloidal gold, liquid alkanes are non-polar liquids with high chemical stability, which can provide a relatively stable environment for the reaction, thereby reducing the possibility of clogging the microchannel due to precipitation, impurities, etc. caused by chemical reactions. At the same time, the viscosity and fluidity of liquid alkanes are moderate, and an effective isolation layer can be formed in the microchannel without affecting the flow properties of the two-phase flow, so that the reaction is carried out more evenly. The present invention further finds that not all liquid alkanes have ideal effects, and only n-decane and n-nonane have the best effects. Chemical stability is an advantage that all liquid alkanes have. When selecting an organic phase, boiling point and viscosity are mainly considered. Under the conditions for preparing colloidal gold, the organic phase first contacts the reaction solution at a relatively low temperature, and then enters a water bath (90-98°C) together with the reaction solution. Therefore, the viscosity of the selected organic phase must remain stable between 0-98°C, and it will neither condense under excessive cooling nor vaporize under excessive heat. Therefore, the selected alkane ranges from octane (6 carbons) to tridecane. When the carbon number of the alkane is higher than 10, such as undecane and tridecane, the viscosity will increase, and the pressure in the reaction system will also increase accordingly. The present invention has tested alkanes such as heptane, octane, nonane, and decane, and found that when heptane is used as an organic phase, partial vaporization will occur in the capillary, which directly leads to unstable product liquid. Among octane, nonane, and decane, the colloidal gold prepared with decane as the oil phase has the highest quality, followed by nonane. Therefore, decane is the most preferred.

[0014] Preferably, in step 1), the flow rate ratio of the gold precursor aqueous phase, the reducing agent aqueous phase and the organic phase is 1:(0.8-1.5):(0.3-3).

[0015] The present invention team found that the flow rate ratio of the above three fluids is crucial to whether the ideal encapsulation effect can be formed instantaneously after their confluence. Specifically: when the two aqueous phases are mixed and then encapsulated by the oil phase to form droplets, it is necessary to proceed under reasonable flow rate ratio conditions. When the water-oil ratio is smaller, the generated droplets are smaller. At this time, the specific surface area of ​​the droplets increases, and the internal mass transfer and heat transfer effects are enhanced. However, the impurities that may exist in the organic phase further aggravate the influence of the preparation of gold nanoparticles, thereby affecting the stability of the colloidal gold preparation. On the contrary, if the water-oil ratio is too large, the generated aqueous phase droplets are larger, the internal mass transfer efficiency of the droplets is reduced, and the final quality of the gold nanoparticles is also affected.

[0016] Preferably, in step 1), the gold precursor aqueous phase is an aqueous solution of chloroauric acid; the reducing agent aqueous phase is an aqueous solution of sodium citrate; Preferably, in step 1), the concentration of gold element in the gold precursor aqueous phase is 0.5-5 mol / L; the concentration of reducing agent in the reducing agent aqueous phase is 1-10 mol / L.

[0017] Preferably, the inner diameters of the water phase channel, the oil phase channel and the mixing zone channel are 0.1-2 mm; and the inner diameter of the channel of the capillary reactor is 0.6-3 mm.

[0018] Preferably, the flow channel in the microfluidic chip is divided into a cooling zone and a heating zone; wherein the water phase channel and the oil phase channel are located in the cooling zone; and the is located in the heating zone.

[0019] Preferably, in step 1), an organic phase is passed into the microfluidic chip or the capillary microreactor in advance to wet the inner wall of the channel.

[0020] Pre-wetting the channel can reduce fluid transport resistance and lower the probability of gold nanoparticle adsorption and deposition.

[0021] Preferably, in step 2), the residence time of the fluid in the mixing zone channel is 0.1-60 s.

[0022] Preferably, in step 3), the residence time of the fluid in the capillary reactor is 3-15 min.

[0023] Compared with the prior art, the beneficial effects of the present invention are: (1) The present invention uses a three-in-one microfluidic chip to encapsulate the gold precursor and the reducing agent in the organic phase to form oil-in-water droplets. On the one hand, the encapsulation of the organic phase can greatly shorten the time that the aqueous phase material directly contacts the flow channel after merging, thereby avoiding adsorption and scaling as much as possible. On the other hand, the generated droplets can also improve the heat and mass transfer efficiency of the material, ensuring the uniformity of the reaction nucleation environment.

[0024] (2) The present invention designs the microfluidic chip into a cooling zone and a heating zone, which can achieve precise temperature control. Controlling the temperature of the cooling zone at ≤ room temperature can not only improve the stability of the gold precursor, but more importantly, it can also inhibit the reaction of the gold precursor after contact with the reducing agent, preventing it from reacting before being wrapped by the droplets and causing the nano-gold particles to be adsorbed on the inner wall of the channel; and when the fluid enters the heating zone, the gold precursor and the reducing agent in the droplets can be instantaneously mixed and nucleated.

[0025] (3) The method of the present invention can achieve scale-up production by connecting multiple microfluidic chips in parallel and adjusting parameters, and the scale-up effect is much smaller than that of the traditional stirring method. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is a diagram of the architecture of the gold nanoparticle preparation system based on a two-phase flow microreactor of the present invention.

[0027] Figure 2 The figure is a schematic diagram of the structure of the flow channel in the microfluidic chip of the present invention.

[0028] Figure 3-1 This is a photo of the colloidal gold solution obtained in Comparative Example 1.

[0029] Figure 3-2 This is a photo of the microfluidic chip and capillary reactor of Comparative Example 1 after a period of reaction.

[0030] Figure 4 The photo of the colloidal gold solution (left) and the capillary reactor (right) obtained in Comparative Example 2 are shown.

[0031] Figure 5 This is a photo of the colloidal gold solution obtained in Example 1.

[0032] Figure 6 This is a photo of the colloidal gold solution obtained in Comparative Example 3.

[0033] Figure 7 This is a photo of the colloidal gold solution obtained in Comparative Example 4.

[0034] Figure 8 This is a photo of the colloidal gold solution obtained in Comparative Example 5.

[0035] Fig. 9 This is a photo of the colloidal gold solution obtained in Comparative Example 6.

[0036] Fig.10 This is a photo of the colloidal gold solution obtained in Example 2.

[0037] The accompanying drawings are marked as: gold precursor aqueous phase storage bottle 1, reducing agent aqueous phase storage bottle 2, organic phase storage bottle 3, gold precursor fluid driving pump 4, reducing agent fluid driving pump 5, organic phase fluid driving pump 6, microfluidic chip 7, chip temperature control clamp 8, capillary reactor 9, water bath thermostat 10, phase separator 11, product bottle 12, waste liquid bottle 13, aqueous phase channel 14, organic phase channel 15, outlet 16, mixing channel area 17, droplet generation area 18. DETAILED DESCRIPTION

[0038] The present invention will be further described below in conjunction with the embodiments.

[0039] Overall embodiment In a first aspect, the present invention provides a method for preparing gold nanoparticles based on two-phase flow microfluidics, which specifically comprises the following steps: 1) The gold precursor aqueous phase, the reducing agent aqueous phase and the organic phase are allowed to converge at the junction of two aqueous phase channels and one oil phase channel of the microfluidic chip at 0-25° C. to form a fluid containing water-in-oil droplets.

[0040] In some preferred implementation cases, in step 1), an organic phase is passed into the microfluidic chip or the capillary microreactor in advance to wet the inner wall of the channel.

[0041] In some preferred implementation cases, in step 1), the organic phase is n-decane, n-nonane or liquid paraffin, and more preferably n-decane and / or n-nonane.

[0042] In some preferred implementation cases, in step 1), the flow rate ratio of the gold precursor aqueous phase, the reducing agent aqueous phase and the organic phase is 1:(0.8-1.5) 0.8-1.5:(0.3-3).

[0043] In some preferred implementation cases, in step 1), the gold precursor aqueous phase is an aqueous solution of chloroauric acid; and the reducing agent aqueous phase is an aqueous solution of sodium citrate.

[0044] In some preferred implementation cases, in step 1), the concentration of gold element in the gold precursor aqueous phase is 0.5-5 mol / L; the concentration of the reducing agent in the reducing agent aqueous phase is 1-10 mol / L.

[0045] 2) The fluid is transported to the mixing zone channel at 90-98°C in the microfluidic chip, where an instantaneous nucleation reaction occurs to form the prototype of gold nanoparticles.

[0046] In some preferred implementation cases, the flow channel in the microfluidic chip is divided into a cooling zone and a heating zone; wherein the water phase channel and the oil phase channel are located in the cooling zone; and the mixing zone channel is located in the heating zone.

[0047] In some preferred implementation cases, the inner diameters of the water phase channel, the oil phase channel, and the mixing zone channel are 0.1-2 mm; and the inner diameter of the channel of the capillary reactor is 0.6-3 mm.

[0048] In some preferred implementation cases, in step 2), the residence time of the fluid in the mixing zone channel is 0.1-60 s.

[0049] 3) The fluid is transported into the capillary reactor, and the gold nanoparticle prototypes are further nucleated, grown, and matured.

[0050] In some preferred implementation cases, in step 3), the residence time of the fluid in the capillary reactor is 3-15 min.

[0051] 4) The fluid is phase-separated to obtain a gold nanoparticle solution with a Z average particle size of 20-30 nm and a PDI of ≤≤0.21.

[0052] Specific Examples and Comparative Examples Figure 1The gold nanoparticle preparation system architecture diagram based on the two-phase flow microreactor of the present invention is exemplarily shown. Figure 2 The schematic diagram of a flow channel in the microfluidic chip of the present invention is exemplarily shown. The system mainly includes: a gold precursor aqueous phase storage bottle 1, a reducing agent aqueous phase storage bottle 2, an organic phase storage bottle 3, a gold precursor fluid driving pump 4, a reducing agent fluid driving pump 5, an organic phase fluid driving pump 6, a microfluidic chip 7 with two aqueous phase channels 14, an organic phase channel 15 and an outlet 16 and a matching chip temperature control fixture 8, a capillary reactor 9, a water bath thermostat 10, a phase separator 11, a product bottle 12 and a waste liquid bottle 13. The organic phase is preliminarily introduced into the microfluidic chip 7 and the capillary microreactor 9 through the organic phase fluid driving pump 6 to wet the inner wall of the chip and the reactor channel. The gold precursor fluid driving pump 4 and the reducing agent fluid driving pump 5 are connected to the inlets of the two aqueous phase channels of the microfluidic chip 7 through pipelines. The chloroauric acid solution delivered by the gold precursor fluid driving pump 4 and the reducing agent solution delivered by the reducing agent fluid driving pump 5 are immediately transported into the organic phase of the microfluidic chip by the organic phase fluid driving pump 6 after merging in the microfluidic chip 7, and are separated into oil-in-water droplets of uniform size (occurring in the droplet generation area 18). In this process, the fluid is controlled at ≤ room temperature by the chip temperature control fixture 8. On the one hand, the stability of the chloroauric acid solution can be ensured, and on the other hand, the reaction between the chloroauric acid solution and the reducing agent is inhibited, thereby avoiding the adsorption and scaling of gold particles here. Subsequently, the droplets enter the mixing channel area 17 of the second half of the microfluidic chip 7 for full mixing and rapid heating. The discrete droplets have excellent heat and mass transfer efficiency, which ensures the controllability of the nucleation environment of the gold nanoparticles and can achieve instantaneous nucleation reaction to the greatest extent. After the fluid flows out from the outlet of the microfluidic chip 7, it enters the capillary reactor 9 for further nucleation and growth. In the capillary microreactor 9, the residence time of the reaction solution can be controlled by changing the flow rate conditions or the length of the capillary reactor, so that the size of the prepared gold nanoparticles is more uniform. Multiple microfluidic chips are connected in parallel, and the inner diameter and length of the capillary are changed, and process amplification can also be achieved to improve the preparation efficiency and production capacity of the gold nanoparticle solution. The water bath thermostat 10 provides accurate temperature control for the capillary reactor 9 to ensure the normal progress of the gold precursor and the reducing agent reaction, nucleation, growth, and maturation process. Thereafter, the fluid enters the phase separator 11 from the outlet of the capillary reactor 9, and the two-phase fluid separated by the phase separator 11 flows into the product bottle 12 and the waste liquid bottle 13 respectively for collection.

[0053] In summary, the present invention allows chloroauric acid and a reducing agent to be wrapped by an organic phase in a microfluidic chip to form a plug flow and be fully mixed, and a reaction, nucleation, growth, and maturation process occur in a capillary reactor to obtain a gold nanoparticle solution with uniform particle size distribution and high stability. The reaction time is short, and the output can be amplified with almost no amplification effect by connecting multiple chips in parallel or adjusting the flow channel size, thereby overcoming many disadvantages of using traditional batch production.

[0054] Comparative Example 1 (Single-phase flow) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution.

[0055] (2) Add 50 mL of HAuCl4 aqueous solution and 50 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively.

[0056] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.4 mL / min.

[0057] (4) The microfluidic chip and the capillary reactor were placed in a constant temperature water bath at 98° C. The channel of the microfluidic chip used in this comparative example had an inner diameter of 0.25 mm. The channel of the capillary reactor used was a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0058] (5) The gold precursor fluid driving pump and the reducing agent fluid driving pump were turned on simultaneously. After 5 minutes, the solution in the capillary reactor gradually changed from colorless at the front end to light red at the end. The reaction continued for 90 minutes, and then the experiment was stopped.

[0059] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12min-17min corresponds to sample 1, 42min-47min corresponds to sample 2, and 72min-77min corresponds to sample 3.

[0060] Figure 3-1 The colloidal gold solution obtained in Comparative Example 1 is shown. It can be seen that as the preparation time increases, the color of the collected colloidal gold gradually becomes lighter; Figure 3-2 The figure shows the microfluidic chip and the capillary reactor prepared in Comparative Example 1 after 90 minutes. It can be seen that serious gold scaling has occurred on the inner wall of the microfluidic chip channel and the inner wall of the capillary reactor.

[0061] Table 1 shows the particle size results of the colloidal gold solution collected at different time periods obtained in Comparative Example 1 after being diluted 150 times. It can be seen that the colloidal gold particle size collected in the early stage of preparation (12-17min) is 25.72nm, and the PDI is 0.118. After a period of preparation, the gold nanoparticles are adsorbed and scaled on the inner channel of the microfluidic chip and the inner wall of the capillary reactor ( Figure 3-2 ), the color of the colloidal gold collected in the corresponding time period becomes significantly lighter, and the PDI becomes significantly larger. The test results show that the colloidal gold prepared based on the microfluidic method has better particle size uniformity than the colloidal gold prepared by the traditional stirring method. However, under this condition, after a long time of preparation, obvious adsorption and scaling will occur inside the channel, and the particle size uniformity of the prepared colloidal gold product will deteriorate accordingly.

[0062] Table 1 Sample name Z-average particle size (d.nm) PDI Figure 3-1 Left 1: 12min-17min 25.72 0.118 Figure 3-1 Left 2: 42min-47min 29.08 0.531 Figure 3-1 Left third: 72min-77min 5312.44 0.682 Traditional stirring method 22.63 0.502 Comparative Example 2 (two-phase flow + three-in-one microfluidic chip (microfluidic chip 98°C, capillary reactor 98°C)) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution.

[0063] (2) Add 50 mL of HAuCl4 aqueous solution and 50 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 50 mL of organic reagent n-decane to the organic phase storage bottle.

[0064] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.4 mL / min, and the flow rate of the organic phase fluid driving pump was set to 0.3 mL / min.

[0065] (4) The three-channel microfluidic chip and the capillary reactor were placed in a constant temperature water bath at 98° C. The channel of the microfluidic chip used in this embodiment has an inner diameter of 0.25 mm. The capillary reactor used is a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0066] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump are turned on in sequence, and the solution forms a stable slug flow in the channel. After 5 minutes, the solution in the capillary reactor gradually changes from colorless at the front end to light red at the end. The reaction continues for 90 minutes, and the experiment is stopped.

[0067] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12min-17min corresponds to sample 1, 42min-47min corresponds to sample 2, and 72min-77min corresponds to sample 3.

[0068] Figure 4 Table 2 shows the colloidal gold solution and particle size test results obtained in Comparative Example 2. It can be seen that the color of the colloidal gold prepared does not change significantly with the extension of the preparation time ( Figure 4 Left); Compared with the colloidal gold prepared by the traditional method, the colloidal gold prepared by the two-phase flow based on microfluidics has no significant change in average particle size, smaller PDI, and better particle size uniformity. After the organic phase was introduced into the microfluidic chip, after 90 minutes of reaction, there was no obvious scaling inside the capillary reactor ( Figure 4 Right), only a small amount of adsorption occurs in the droplet generation area of ​​the microfluidic chip.

[0069] Table 2 Sample name Z-average particle size (d.nm) PDI Figure 4 Left 1: 12min-17min 27.18 0.212 Figure 4 Left 2: 42min-47min 23.27 0.272 Figure 4 Third from left: 72min-77min 21.38 0.303 Traditional stirring method 22.63 0.502 Example 1 (two-phase flow + three-in-one microfluidic chip (microfluidic chip cooling zone 25°C, capillary reactor 98°C)) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution.

[0070] (2) Add 50 mL of HAuCl4 aqueous solution and 50 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 50 mL of organic reagent n-decane to the organic phase storage bottle.

[0071] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.4 mL / min, and the flow rate of the organic phase fluid driving pump was set to 0.3 mL / min.

[0072] (4) The three-channel microfluidic chip was placed at room temperature (the temperature of the cooling zone was 25°C and the temperature of the heating zone was 98°C), and the capillary reactor was placed in a constant temperature water bath at 98°C. The channel of the microfluidic chip used in this embodiment has an inner diameter of 0.25 mm. The capillary reactor used was a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0073] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump are turned on in sequence, and the solution forms a stable slug flow in the channel. After 5 minutes, the solution in the capillary reactor gradually changes from colorless at the front end to light red at the end. The reaction continues for 90 minutes, and the experiment is stopped.

[0074] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12 min-17 min corresponds to sample 1, 42 min-47 min corresponds to sample 2, and 72 min-77 min corresponds to sample 3.

[0075] Figure 5 Table 3 shows the colloidal gold solution and particle size test results obtained in Example 1. It can be seen that the color of the prepared colloidal gold does not change significantly with the extension of the preparation time; compared with the colloidal gold prepared in Comparative Example 2, the PDI of the colloidal gold with separate temperature control in the microfluidic chip area is further reduced, and the particle size uniformity is better.

[0076] Table 3 Sample name Z-average particle size (d.nm) PDI Figure 5 Left one: 12min-17mmin 25.42 0.118 Figure 5 Left 2: 42min-47min 25.67 0.092 Figure 5 Left third: 72min-77min 24.88 0.121 Traditional stirring method 22.63 0.502 Comparative Example 3 (Compared with Example 1, the difference is that the organic solvent is mineral oil) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution.

[0077] (2) Add 50 mL of HAuCl4 aqueous solution and 50 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 50 mL of mineral oil to the organic phase storage bottle.

[0078] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.4 mL / min, and the flow rate of the organic phase fluid driving pump was set to 0.3 mL / min.

[0079] (4) The three-channel microfluidic chip was placed at room temperature (the temperature of the cooling zone was 25°C and the temperature of the heating zone was 98°C), and the capillary reactor was placed in a constant temperature water bath at 98°C. The channel of the microfluidic chip used in this comparative example had an inner diameter of 0.25 mm. The capillary reactor used was a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0080] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump are turned on in sequence, and the solution forms a stable slug flow in the channel. After 5 minutes, the solution in the capillary reactor gradually changes from colorless at the front end to light red at the end. The reaction continues for 90 minutes, and the experiment is stopped.

[0081] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12 min-17 min corresponds to sample 1, 42 min-47 min corresponds to sample 2, and 72 min-77 min corresponds to sample 3.

[0082] Figure 6 Table 4 shows the colloidal gold solution and particle size test results obtained in Comparative Example 3. It can be seen that the color of the colloidal gold prepared with the preparation time does not change significantly; compared with the colloidal gold prepared by the traditional method, the colloidal gold prepared with mineral oil as the oil phase is purple in color, has a larger PDI, and golden oily substances float on the surface of the colloidal gold, indicating that dead gold occurs. After the organic phase is introduced into the microfluidic chip, after 90 minutes of reaction, there is no obvious scaling inside the capillary reactor.

[0083] Table 4 Sample name Z-average particle size (d.nm) PDI Figure 6 Left 1: 12min-17min 17.35 0.682 Figure 6 Left 2: 42min-47min 15.32 0.687 Figure 6 Third from left: 72min-77min 14.26 0.727 Traditional stirring method 22.63 0.502 Comparative Example 4 (Compared with Example 1, the difference is that the organic solvent is n-heptane) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution.

[0084] (2) Add 50 mL of HAuCl4 aqueous solution and 50 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 50 mL of organic reagent n-heptane to the organic phase storage bottle.

[0085] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.4 mL / min, and the flow rate of the organic phase fluid driving pump was set to 0.3 mL / min.

[0086] (4) The three-channel microfluidic chip was placed at room temperature (the temperature of the cooling zone was 25°C and the temperature of the heating zone was 98°C), and the capillary reactor was placed in a constant temperature water bath at 98°C. The channel of the microfluidic chip used in this embodiment has an inner diameter of 0.25 mm. The capillary reactor used was a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0087] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump were turned on in sequence. The solution formed an unstable slug flow in the channel, and bubbles appeared in the tube. After 5 minutes, the solution in the capillary reactor gradually changed from colorless at the front end to light purple at the end. The reaction continued for 90 minutes, and the experiment was stopped.

[0088] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12 min-17 min corresponds to sample 1, 42 min-47 min corresponds to sample 2, and 72 min-77 min corresponds to sample 3.

[0089] Figure 7Table 5 shows the colloidal gold solution and particle size test results obtained in Comparative Example 4. It can be seen that the color of the prepared colloidal gold does not change significantly with the extension of the preparation time, and the overall color is purple; compared with the colloidal gold prepared in Comparative Example 2, after the organic phase is changed to n-heptane, the Z-average particle size of the prepared colloidal gold is significantly smaller. However, the overall color is purple and the PDI is large. This indicates that the quality of the colloidal gold prepared under the organic phase conditions is significantly reduced relative to Comparative Example 2. The above results show that only liquid alkanes (n-decane, n-nonane) of a specific chain length have ideal technical effects. If the liquid alkane chain length is too short or too long, the effect will deteriorate.

[0090] Table 5 Sample name Z-average particle size (d.nm) PDI Figure 7 Left 1: 12min-17min 13.47 0.448 Figure 7 Left 2: 42min-47min 15.67 0.498 Figure 7 Third from left: 72min-77min 17.55 0.521 Traditional stirring method 22.63 0.502 Comparative Example 5 (Compared with Example 1, the difference is that the water phase / oil phase flow rate ratio is too high) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution. (2) Add 50 mL HAuCl4 aqueous solution and 50 mL C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 50 mL n-decane to the organic phase storage bottle.

[0091] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.5 mL / min, and the flow rate of the organic phase fluid driving pump was set to 0.1 mL / min.

[0092] (4) The three-channel microfluidic chip was placed at room temperature (the temperature of the cooling zone was 25°C and the temperature of the heating zone was 98°C), and the capillary reactor was placed in a constant temperature water bath at 98°C. The channel of the microfluidic chip used in this comparative example had an inner diameter of 0.25 mm. The capillary reactor used was a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0093] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump are turned on in sequence, and the solution forms a stable slug flow in the channel. After 5 minutes, the solution in the capillary reactor gradually changes from colorless at the front end to light red at the end. The reaction continues for 90 minutes, and the experiment is stopped.

[0094] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12 min-17 min corresponds to sample 1, 42 min-47 min corresponds to sample 2, and 72 min-77 min corresponds to sample 3.

[0095] Figure 8Table 6 shows the colloidal gold solution and particle size test results obtained in Comparative Example 5. It can be seen that the color of the colloidal gold prepared by the preparation time does not change significantly; compared with the colloidal gold prepared by the traditional method, the colloidal gold prepared when the two-phase flow rate ratio is 1:1:0.2 is purple in color and the PDI is slightly larger. After the organic phase is introduced into the microfluidic chip, after 90 minutes of reaction, there is no obvious scaling inside the capillary reactor.

[0096] Table 6 Sample name Z-average particle size (d.nm) PDI Figure 8 Left 1: 12min-17min 20.47 0.572 Figure 8 Left 2: 42min-47min 20.41 0.546 Figure 8 Left third: 72min-77min 19.42 0.581 Traditional stirring method 22.63 0.502 Comparative Example 6 (Compared with Example 1, the difference is that the water-oil flow rate ratio is too low) (1) Prepare 0.5-5 mol / L HAuCl4 aqueous solution and 1-10 mol / L C6H5Na3O7 aqueous solution.

[0097] (2) Add 50 mL of HAuCl4 aqueous solution and 50 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 50 mL of n-decane to the organic phase storage bottle.

[0098] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 0.2 mL / min, and the flow rate of the organic phase fluid driving pump was set to 0.7 mL / min.

[0099] (4) The three-channel microfluidic chip was placed at room temperature (the temperature of the cooling zone was 25°C and the temperature of the heating zone was 98°C), and the capillary reactor was placed in a constant temperature water bath at 98°C. The channel of the microfluidic chip used in this comparative example had an inner diameter of 0.25 mm. The capillary reactor used was a PTFE capillary with an inner diameter of 0.8 mm, an outer diameter of 1.6 mm, and a length of 10 m.

[0100] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump are turned on in sequence, and the solution forms a stable slug flow in the channel. After 5 minutes, the solution in the capillary reactor gradually changes from colorless at the front end to light red at the end. The reaction continues for 90 minutes, and the experiment is stopped.

[0101] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12 min-17 min corresponds to sample 1, 42 min-47 min corresponds to sample 2, and 72 min-77 min corresponds to sample 3.

[0102] Fig. 9Table 7 shows the colloidal gold solution and particle size test results obtained in Comparative Example 6. It can be seen that the color of the prepared colloidal gold does not change significantly with the extension of the preparation time; compared with the colloidal gold prepared by the traditional method, the colloidal gold prepared with a two-phase flow rate ratio of 1:1:3.5 is purple in color and has a larger PDI. Compared with the colloidal gold results prepared with a two-phase flow rate ratio of 1:1:0.75, the Z-average particle size is consistent and the PDI is too large. After the organic phase was introduced into the microfluidic chip, after 90 minutes of reaction, there was no obvious scaling inside the capillary reactor.

[0103] Table 7 Sample name Z-average particle size (d.nm) PDI Fig. 9 Left 1: 12min-17min 26.3 0.569 Fig. 9 Left 2: 42min-47min 24.26 0.593 Fig. 9 Third from left: 72min-77min 21.94 0.572 Traditional stirring method 22.63 0.502 Example 2 (enlargement experiment) (1) Prepare 0.558 mol / L HAuCl4 aqueous solution and 1.02 mol / L C6H5Na3O7 aqueous solution.

[0104] (2) Add 250 mL of HAuCl4 aqueous solution and 250 mL of C6H5Na3O7 aqueous solution prepared in step (1) to the gold precursor aqueous phase storage bottle and the reducing agent aqueous phase storage bottle, respectively, and add 250 mL of organic reagent n-decane to the organic phase storage bottle.

[0105] (3) The flow rates of the gold precursor fluid driving pump and the reducing agent fluid driving pump were set to 1.41 mL / min, and the flow rate of the organic phase fluid driving pump was set to 1.05 mL / min.

[0106] (4) The three-channel microfluidic chip was placed at room temperature (the temperature of the cooling zone was 25° C., and the temperature of the heating zone was 98° C.), and the capillary reactors were placed in a constant temperature water bath at 98° C. The channel of the microfluidic chip used in this embodiment had an inner diameter of 0.25 mm, and the capillary reactor used was a PTFE capillary with an inner diameter of 1.2 mm, an outer diameter of 2.5 mm, and a length of 10 m.

[0107] (5) The organic phase fluid driving pump, the gold precursor fluid driving pump, and the reducing agent fluid driving pump are turned on in sequence, and the solution forms a stable slug flow in the channel. After 5 minutes, the solution in the capillary reactor gradually changes from colorless at the front end to light red at the end. The reaction continues for 90 minutes, and the experiment is stopped.

[0108] (6) The liquid discharged from the end of the capillary reactor in step (5) at different times was collected into 5 mL glass bottles to obtain colloidal gold nanoparticle solutions. 12 min-17 min corresponds to sample 1, 42 min-47 min corresponds to sample 2, and 72 min-77 min corresponds to sample 3.

[0109] Fig.10Table 8 shows the test results of the colloidal gold particle size obtained in Example 2. It can be seen that the size of the colloidal gold particles prepared in Example 2 does not change significantly with the extension of the preparation time; compared with the colloidal gold prepared in Example 1, the colloidal gold particle size and PDI results prepared after the flow rate was amplified in this embodiment did not change significantly, and there was almost no amplification effect.

[0110] Table 8 Sample name Z-average particle size (d.nm) PDI Fig.10 Left 1: 12min-17min 26.28 0.159 Fig.10 Left 2: 42min-47min 25.11 0.114 Fig.10 Third from left: 72min-77min 27.09 0.202 Traditional stirring method 22.63 0.502 The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art.

[0111] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent transformation made to the above embodiment based on the technical essence of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing gold nanoparticles based on two-phase flow microfluidics, characterized in that include: 1) allowing the gold precursor aqueous phase, the reducing agent aqueous phase and the organic phase to converge at the confluence of two aqueous phase channels and one oil phase channel of the microfluidic chip at 0-25° C. to form a fluid containing water-in-oil droplets; The organic phase is oleic acid, mineral oil or liquid alkane; 2) The fluid is transported to the mixing zone channel at 90-98°C in the microfluidic chip, where an instantaneous nucleation reaction occurs to form the prototype of gold nanoparticles; 3) The fluid is transported to the capillary reactor, where the gold nanoparticles are further nucleated, grown, and matured; 4) The fluid is phase-separated to obtain a gold nanoparticle solution with a Z-average particle size of 20-30 nm and a PDI ≤ 0.

21.

2. The method according to claim 1, characterized in that: In step 1), the liquid alkane is n-decane and / or n-nonane.

3. The method according to claim 1, characterized in that: In step 1), The flow rate ratio of the gold precursor aqueous phase, the reducing agent aqueous phase and the organic phase is 1:(0.8-1.5):(0.3-3).

4. The method according to claim 1, characterized in that: In step 1), The gold precursor aqueous phase is an aqueous solution of chloroauric acid; The reducing agent aqueous phase is a sodium citrate aqueous solution.

5. The method according to claim 1 or 4, characterized in that: In step 1), The concentration of gold element in the gold precursor aqueous phase is 0.5-5 mol / L; The concentration of the reducing agent in the reducing agent aqueous phase is 1-10 mol / L.

6. The method according to claim 1, characterized in that: The inner diameters of the water phase channel, the oil phase channel, and the mixing zone channel are 0.1-2 mm; The inner diameter of the channel of the capillary reactor is 0.6-3 mm.

7. The method according to claim 1, characterized in that: The flow channel in the microfluidic chip is divided into a cooling zone and a heating zone; wherein the water phase channel and the oil phase channel are located in the cooling zone; and the mixing zone channel is located in the heating zone.

8. The method according to claim 1, characterized in that: In step 1), an organic phase is passed into the microfluidic chip and the capillary microreactor in advance to wet the inner wall of the channel.

9. The method according to claim 1, characterized in that: In step 2), the residence time of the fluid in the mixing zone channel is 0.1-60s.

10. The method according to claim 1, characterized in that: In step 3), the residence time of the fluid in the capillary reactor is 3-15 min.

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