Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

Summary

Millifluidic devices are utilized for controlled synthesis of nanomaterials, time-resolved analysis of reaction mechanisms and continuous flow catalysis.

Abstract

Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst.

Introduction

Lab-on-a-chip (LOC) devices for chemical synthesis have demonstrated significant advantage in terms of increased mass and heat transfer, superior reaction control, high throughput and safer operation environment¹. These devices can be broadly classified into chip based fluidics and nonchip based fluidic devices. Among the chip-based fluidics, microfluidics is well investigated and a topic well-covered in the literature^2-5. Nonchip based LOC systems use tubular reactors⁶. Conventionally, microfluidic systems are used for precise control and manipulation of fluids that are geometrically constrained to submillimeter scale. We have recently introduced the concept of chip-based millifluidics, which can be used for manipulation of fluids in channels in millimeter scale (either width or depth or both of the channels are at least a millimeter in size)^7-9. Furthermore, the millifluidic chips are relatively easy to fabricate while offering similar control over flow-rates and manipulation of reagents. These chips could also be operated at higher flow-rates, creating smaller residence times, thereby, offering the possibility for scale-up of controlled synthesis of nanoparticles with narrower size distribution. As an example, we have recently demonstrated the synthesis of ultra-small copper nanoclusters and characterized them using in situ X-ray absorption spectroscopy as well as TEM. Ability to obtain small residence times within millifluidic channels in combination with the use of MPEG, which is very efficient bidentate PEGylated stabilizing agent for the formation of stable colloids of copper nanoclusters⁷ .

In addition to the synthesis of chemicals and nanomaterials, the millifluidics could offer, due to higher volume and concentration at the probe area, a synthetic platform that is more generalized and efficient for time-resolved kinetic studies and also achieves better signal to noise ratio than microfluidic systems^7,10. We show the use of millifluidic chip as an example for time resolved analysis of the growth of gold nanostructures from solution using in situ XAS with a time resolution as small as 5 msec¹¹.

Also, majority of the micro reactors developed to date for catalysis applications are based on silicon^12,13. Their expensive fabrication in addition to small volumes generated makes them unsuitable for large scale manufacturing. The two general methods for coating the channels with nanocatalysts - chemical and physical, often referred to as silicon coating procedures, are currently in vogue^14,15 . In addition to expensive micro fabrication, clogging of the channels makes micro reactor catalysis may be unsuitable for large-scale manufacturing. Although microreactors have been used for heterogeneous catalysis in micro continuous flow-through processes earlier^16-18 , the ability to control the dimension, and morphology of the embedded gold nanostructured catalysts within continuous flow channels was never explored before. We have recently developed a technology for coating the millifluidic channels with Au catalysts, having controlled nano morphology and dimensions (Figure 5)¹¹, for carrying out catalysis of industrially important chemical reactions. As an example we have demonstrated conversion of 4-nitrophenol into 4-aminophenol catalyzed by nanostructured gold coated within the millifluidic channels. Considering that a single millifluidic reactor chip can produce flow-rates of 50-60 ml/hr,⁷ high-throughput and controlled synthesis of chemicals is possible either through continuous flow operation or parallel processing.

In order to capitalize on the possibilities the millifluidics offer, with few examples described as above, we also demonstrate a user-friendly millifluidic device that is portable and has the all the required components such as millifluidic chips, manifolds, flow controllers, pumps and electrical connections integrated. Such a millifluidic device, as shown in the Figure 7, is now available from the company Millifluidica LLC (www.millifluidica.com). The manuscript also provides protocols using the hand-held millifluidic device, as described below, for controlled synthesis of nanomaterials, time-resolved analysis of reaction mechanisms and continuous flow catalysis.

Protocol

Millifluidics set-up: Purchase a millifluidic chip (made of polyester terephthalate polymer) from Microplumbers Microsciences LLC, which has serpentine channels with dimensions of 2 mm (W) x 0.15 mm (H) x 220 mm (L). Use FEP Tubing  with dimensions of 0.25 mm I.D., 1/16 in O.D., for connecting the chip to the pump. Use two different pumps for the two different experiments. Use P-Pump for the first experiment (copper nanoparticles) and the millifluidic device for the second experiment (gold nanoparticles). To minimize the problem of gas bubbles within the channels, freshly prepared NaBH₄ solution was left open to stand for ~10-15 min before pumping into the chip so that the gas bubbles escape from the solution. This step was followed for all of our experiments.

1. Synthesis of Ultra-small Copper Nano Clusters (UCNCs)

1. Chemicals required: Obtain copper(II) nitrate hydrate, sodium borohydride, sodium hydroxide pellets and O-[2-(3-mercaptopropionylamino)ethyl]-O'-methylpolyethylene glycol (MW=5,000) [MPEG] and use all chemicals without further purification. Use nanopure water (18.2 MΩ-cm) for the experiment.
2. Use P-Pump regulated under nitrogen pressure for the experiment. Test the pumps with water as solvent at different pressures prior to the experiment to correlate with the corresponding flow-rates (ml/hr). Rinse the millifluidic reactor and tubing with deionized water before initiation of the experiment.
3. Dissolve 174 mg (0.95 mmol) of copper(II) nitrate and 610 mg (0.122 mmol) of O-[2-(3-mercaptopropionylamino)ethyl]-O'-methylpolyethylene glycol in 28 ml of nanopure water and keep them in a vial to be connected with one input channel
4. Keep another solution of 111 mg (2.93 mmol) of sodium borohydride and 102 mg (2.78 mmol) sodium hydroxide in 28 ml (pH ~13) in a different vial and connect it with the other input channel.
5. Flow both the solutions simultaneously within the millifluidic reactor at different flow-rates (given below) and collect the resulting UCNCs at the outlet in glass vial. Purge the solution with nitrogen and store it under nitrogen.
6. Operate the pumps under different constant pressures of 50 mbar (6.81 ml/hr), 100 mbar (14.31 ml/hr), 200 mbar (32.7 ml/hr) and 300 mbar (51.4 ml/hr) at room temperature for the synthesis of UCNCs at different flow-rates.

While the synthesis procedure was demonstrated using the millifluidic set-up with P-Pump, it can also be carried out using the hand-held millifluidic device from Millifluidica.

2. Time Resolved In situ Kinetic Studies on Gold Nanoparticle Formation

1. Chemicals required: Obtain chloroauric acid (HAuCl₄^.3H₂O) meso-2,3-dimercaptosuccinic acid (DMSA) and sodium borohydride and use all chemicals without further purification. Use nanopure water (18.2 MΩ-cm) for the experiment.
2. Use high precision, fully automated, pulsation free syringe pumps to flow the liquids within the chip. Test the pumps with water as solvent at different flow-rates prior to the experiment to optimize the required flow-rate.
3. Prepare standard solutions of (i) HAuCl₄^.3H₂O (10 mmol, 118.2 mg/30 ml) and (ii) DMSA (20 mmol, 109.2 mg/30 ml) with 50 mg of sodium hydroxide (pH 12) in nanopure water.
4. Feed the two solutions through two separate syringes into the millifluidic chip at a constant flow-rate of 10 ml/hr using the automated pump.
5. Couple the millifluidic chip to the synchrotron beam line using a metal stage that has access to movement in XYZ directions and collect the XAS data at different zones on the chip as the solutions were pumped through the chip.

While the in situ analysis procedure was demonstrated using the millifluidic set-up with P-Pump, it can also be carried out using a hand-held millifluidic device.

3. Continuous Flow Gold Catalysis

This procedure was demonstrated using a hand-held millifluidic device.

1. Chemicals required: Obtain chloroauric acid (HAuCl₄^.3H₂O), meso-2,3-dimercaptosuccinic acid (DMSA), sodium borohydride, 4-nitrophenol, 4-aminophenol and use all the chemicals without further purification. Use nanopure water (18.2 MΩ-cm) for the experiment.
2. Catalyst preparation: Prepare standard solutions of HAuCl₄^.3H₂O (10 mmol, 118.2 mg/30 ml), DMSA (20 mmol, 109.2 mg/30 ml) and NaBH₄ (10 mmol, 11.34 mg/30 ml) in Nanopure water.
3. Take 10 ml each of HAuCl₄ and DMSA solutions into two separate vials and flow them within the chip using the hand-held millifluidic device with a uniform flow-rate of 12 ml/hr for 45 min.
4. Flow 10 mmol NaBH₄ within the chip at 12 ml/hr flow-rate for 15 min to reduce the Au(I) to Au(0).
5. Finally, wash the chip with nanopure water for 30 min at the same flow-rate before conducting the catalysis experiments.
6. Catalysis reaction: Perform the chemical conversion reaction (reduction) of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) within the gold catalyst (prepared above) coated millifluidic channel as given below.
7. Mix 15 ml of 9 x 10^-5 mol solution of 4-NP with 3.3 ml of 0.65 mol NaBH₄ solution to form 4-nitrophenolate ion (4-NPI).
8. Pass the resultant solution over the gold catalyst deposited within chip at a constant flow-rate of 5 ml/hr to evaluate the catalytic activity. Analyze the UV-Vis spectra of the collected products within the wavelength range of 250-500 nm to confirm the conversion of 4-NP.
9. Estimate the catalytic activity of the reaction by obtaining the calibration curve of 4-NPI. Calibration curve can be acquired by plotting the experimentally observed absorption intensity (I) of 4-NPI at different standard concentrations. The peak heights (at 399 nm) for the UV-Vis absorption curves represent the absorption intensity (I) values and according to the Beer Lambert's law, any change in the peak height value would show corresponding change in its concentration. Therefore, estimate the catalytic activity by finding the difference in initial and final concentrations of the reactant from the calibration curve. For example, if the peak height is 1 unit (Figure 6) it corresponds to a catalytic conversion of 90% (based on the calibration plot).

Results

Well dispersed and uniform sized copper nanoclusters with a narrow size distribution were obtained using the millifluidic chip setup (Fig. 1a). The different flow-rates used for synthesis did not have a significant effect on the size of the clusters. Nevertheless, with increase in the flow-rate, there is an observable improvement in the narrowing of the size distribution. UCNCs with a best narrow size distribution were obtained at a flow-rate of 32.7 mL/hr. The size of UCNCs formed at 32.7 mL/hr flow-rate has an average ...

Discussion

The UCNCs were formed by the reduction reaction of copper nitrate with sodium borohydride in the presence of the polymeric capping agent O-[2-(3-Mercaptopropionylamino)ethyl]-O'-methylpolyethylene glycol (MW=5,000) [MPEG]. The reaction was performed within the millifluidic chip reactor at different flow-rates such as 6.8 ml/hr, 14.3 ml/hr, 32.7 ml/hr, and 51.4 ml/hr to study the effect of flow-rates on the UCNCs formed. The respective residence times for the above flow-rates are 47.49, 24.44, 16.56, and 9.02 sec. The...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Copper (II) nitrate hydrate	Sigma-Aldrich	13778-31-9	99.999% pure
O-[2-(3-mercaptopropionylamino)ethyl]-O′-methylpolyethylene glycol	Sigma-Aldrich	401916-61-8	MW=5,000
HAuCl4.3H2O (Chloroauric acid)	Sigma-Aldrich	27988-77-8	99.999% pure
meso-2,3-dimercaptosuccinic acid (DMSA)	Sigma-Aldrich	304-55-2	~98% pure
4-Nitrophenol	Sigma-Aldrich	100-02-7	spectrophotometric grade
4-Aminophenol	Sigma-Aldrich	123-30-8	>99% pure (HPLC grade)
Sodium borohydride	Sigma-Aldrich	16940-66-2	98% pure
Sodium hydroxide pellets	Sigma-Aldrich	1310-73-2	99.99% pure
EQUIPMENT
Millifluidic Chips	Microplumbers Microsciences LLC	SDC-01	Made from polyester terephthalate polymer
Pressure Pump	Mitos P-Pump, Dolomite	3200016
Automated Syringe Pump	Cetoni Automation and Microsystems, GmbH		Syringe pump neMESYS
UV-3600 UV-VIS-NIR Spectrophotometer	Shimadzu
Hand-held Millifluidic Device	Millifluidica	SCMD-1008	Figure 7