On-demand Milifluidic Synthesis of Quantum Dots in Digital Droplet Reactors

Abstract

Colloidal quantum dots (QDs) offer dramatic potential due to their size-dependent optical properties. Lack of facile synthesis methods for precise and reproducible size and composition, however, present an extant barrier to their widespread use. Here we report the use of droplet microfluidics for the simple and highly reproducible synthesis of cadmium sulfide (CdS) and cadmium selenide (CdSe) QDs without the use of harsh solvents and in ambient conditions. Our approach uses a liquid-liquid barrier between two immiscible liquids to generate a digital droplet reactor. This reaction droplet is easily controlled and manipulated and offers enhanced mixing when coupled to a helical mixer, resulting in a significant reduction in size distribution compared to benchtop procedures. Furthermore, QD characteristics have modeled and predicted based on the parameters of the microfluidic device. We believe this method overcomes the current manufacturing challenges with synthesizing nanostructures, which is required for the next generation of nanosensors.

Graphical Abstract

Introduction

Over the last decade, the range of applications for nanomaterials has increased tremendously, especially in the area of electronics, biosensing, drug delivery, light sources, and photovoltaic production.^1–5 Quantum dots (QDs) are one such class of nanomaterials whose unique optical properties are dictated by their size, composition and homogeneity. Compared to traditional fluorophores QDs exhibit bright, stable, and narrow band emission ^6–7 However, the synthesis of QDs require precise control of temperature, mixing volume, diffusion rate and concentration of precursors in an inert atmosphere. These conditions are conventionally controlled in benchtop synthesis utilizing Schlenk lines. Due to the high degree of spatial control afforded by microfluidic systems, they have also been implemented in the production of nanomaterials including gold and silver nanoparticles ⁸, and various quantum dots systems. ^9–11 Similarly, a subclass of microfluidic devices called droplet fluidics has also been established as an excellent tool for NP synthesis ^{9, 12–14} for example, the synthesis of a library of CdS QDs⁹ was achieved by changing concentrations, flow rates and temperatures for facile synthesis.

For batch syntheses, the inability to control the reaction volumes and the rate of mixing contribute to the variations in different batches.^15–17 Additionally batch processes require a significant degree of post processing to focus nanoparticle size, remove unreacted precursors and excess ligands that are ultimately time consuming and can affect the stability and quality of the final product. Microfluidic reactors improve upon this by providing controlled reaction conditions with improved heat and mass transfer rates for the synthesis of NPs.^{14, 17–19} Utilizing these devices allows for rapid prototyping and optimization as they permit rapid screening of parameters in relatively short periods of time while minimizing the amounts of reagents.^20–22 However, continuous flow reactors suffer from axial dispersion that increases the residence time in devices and decreases the overall quality of nanoparticles from them hence, significant effort is usually expended in fluidic mixing²³ to achieve homogeneity. Droplet-based fluidics provide local control over mixing and homogeneity of reaction conditions in small volumes. This has been demonstrated in studies that used inert gases to develop plug flow reactors for the synthesis of CdSe QDs.²⁴

Here we report the use of digitally regulated fluidic device to ensure the delivery of precise amounts of reagents and the development of droplets within a device using two-phase fluid flow. Fluid mechanical properties such as Dean and Reynolds numbers allow quantification of device mixing performance. We exploit the formation of dean vortices to induce mixing facilitated by a 3-dimensional helix which allows the use of lower flow rates which facilitate the use of discrete reaction droplets. We have previously demonstrated that efficient mixing occurs in helical channel paths and seek to combine this with droplet based reactors.²⁵

Results and Discussion

Device Design for Aqueous QD Synthesis

Mercury (Hg) and Cadmium (Cd) QDs have previously been reported using many methods^35–37, however, complex air-free conditions are usually required to provide an inert environment for the reaction. Figure 1(a) illustrates a schematic of our compact aqueous reactor system that is easy to set up using readily available syringes, syringe pump and high temperature silicon tubing. As opposed to previously reported porous PDMS chips, the silicon tubing in combination with the paraffin oil encapsulation helps to facilitate inert conditions and the entire system can be set up in a general laboratory, without the need for any specialized infrastructure. Figure 1(b) shows an expanded view of the setup where the reactant transport and reaction occur. First, a flow of paraffin oil meets a flow of metals (aqueous solution of Hg(NO₃)₂, or Cd(NO₃)₂ and mercaptopropionic acid solutions), forming the reaction droplet. This droplet subsequently meets a flow of reducing agent (Na₂S solution) before travelling through a helical mixer, where controlled nucleation and growth of the NPs occurred. Figure 2a top shows the obtained absorption spectra from CdS QDs synthesized using our method. These results are in agreement with results reported in literature for synthesis via hydrothermal routes³⁸.Size was estimated from TEM images. Obtained QDs were 4.736 nm with a standard deviation of 1.500 nm. Figured 2b details Raman spectra of longitudinal phonon modes of CdS at 300 cm⁻¹, which correspond with reported values in literature³⁹. This, together with TEM images such as in Figure 2c would suggest the formation of nanocrystals of cadmium and sulfur. CdS nanocrystals from our proposed design are compared against data obtained from literature in Table 1. To further evaluate the efficacy of the device, we attempted the synthesis of ternary alloyed quantum dots. Specifically, we focused on the challenge of synthesizing alloys of mercury/cadmium/sulfide (HgCdS) without the need for harsh solvents, high temperatures or external and complex air-free conditions. Figure S1 and Table S1 demonstrates the influence of altering parameters such as flow rate temperature and precursor concentration on the QDs.

Figure 1:

Schematic representation of the droplet reactor microfluidic device. Flow was visualized in the devices by replacing the metal and chalcogen precursors with water soluble dyes. The inset are images obtained during each of the conditions. The righthand schematic is an image based on those observations. (Case 1 and Case 2) Images of the formation of droplets as different flow rates. (Case 1) Demonstrates the merging of droplets at low flow rate value. Droplets merge within the junction of the device. (Case 2) Demonstrates the merging of droplets at a selected high flow rate. A train of unmixed droplets emerge from the junction that later merge.

Figure 2.

(a) Absorbance spectra of synthesized CdS and CdSe QDs (b) Raman spectra of synthesized CdS and CdSe QDs (c) representative TEM images synthesized CdS QDs(d) representative TEM images synthesized CdSe QDs

Table 1.

Data obtained from literature comparing various micro and milifluidic and batch synthesis approaches to data from current study.

	Aqueous Batch CdS	Microfluidic synthesis CdS	Batch CdSe	Microfluidic synthesis CdSe	Current Study CdS	Current Study CdSe
Parameters
Size Distribution	2–6 nm ± 25% – 75%	1 – 7 nm ± 20% – 30%	2nm – 8 nm ± 5% – 20%	2 nm – 5 nm ± 8% – 50%	3.05 nm ± 6.3%	5.134 nm ± 16.3%
Length of synthesis	45 minutes to hours	40 minutes to 2 hours	Not listed	45 minutes to 87 minutes	45 minutes	9 minutes + additional heating time 10 – 60 minutes
Rxn environment	N2 Atmosphere, Room temp - 160°C	pH 10.2 N2 glovebox, silanized micropatterned channels, steel mixing region, Room temperature - 270°C	Inert gas purged systems 150°C - 280°C	No prior treatment, steel mixing region, PMMA mixing region, T >250°C	No prior treatment, Room temp - 100°C	No prior treatment, Room 230 °C
References	5, 26–29	9, 14, 19	30–31	24, 32–34	Presented work	Presented work

Device design for organic QD synthesis

A modified design was implemented to conduct organic synthesis syntheses of CdSe QDs. First a metal ion containing solution was prepared by dissolving cadmium acetate dihydrate or lead (II) acetate trihydrate in oleic acid and 1-octadecene. This flow combined with a second flow of 1-octadecene. This flow meets a third flow containing an immiscible liquid such as water, forming droplets that then flow through a heated oil bath. A solution of Se and TOP is added to a fourth flow which merges with a fifth stream containing DPP and TOP. These flows merge and enter the helical mixing region and the product was then collected. The collected solution was then heated for up to 60 minutes, with aliquots collected periodically to monitor the growth of the nanocrystals through examination of the shift in absorbance spectra. Figure 2d shows the absorbance spectra of CdSe isolated at the 40-minute timepoint. CdSe nanocrystals from the proposed design was again compared to values obtained from literature and are detailed in Table 1. The estimated size from TEM images suggests the particles were 3.752nm with a standard deviation of 0.541 nm. Raman spectroscopy of the sample shown in figure 2b demonstrated a longitudinal optical mode at 205 cm⁻¹. This is in good agreement with values reported in literature⁴⁰.

Conclusions

QDs have tremendous potential as imaging probes; however, specialized infrastructure is needed to avail of these benefits. The simple continuous droplet reactor reported here overcomes this drawback and is a key component to automated synthesis of probes on demand. We have demonstrated the efficacy of this approach by synthesizing commonly reported quantum dot systems. This method has produced stable, very reproducible QDs which paves the way for widespread synthesis, enables facile optimization of nanoparticle properties and fine control over delivery of reagents and reactions. This is accomplished without the use of Schlenk based synthetic methods which requires vacuum and inert gas handling. This eliminates the risk of glassware implosion or explosions due to oxygen condensation in cold traps. Constructing this milifluidic system also did not require the fabrication of patterning templates or molds and was constructed using readily sourced parts. Chemicals such as strong acids are incompatible with these devices due to being composed of silicone rubber. The design of the device, however, allows for replacement with more resistant tubing and connection materials such as PVDF or PTFE. Devices were flushed with paraffin oil following the end of a synthesis and this enabled them to be utilized for many further reaction runs without fouling. The ease at which this system can be constructed has the potential to enable the expansion of the use of quantum dot to other disciplines as it enables their production without advanced synthesis skills or equipment.

Materials and Methods

Microfluidic Device Fabrication

The microfluidic device was fabricated using components purchased from McMaster-Carr unless otherwise stated. Tubing was composed of high temperature rated peroxide cured silicone rubber (product number 5236K208) with an inner diameter 1/16 inch (1.5875 mm) and outer diameter 3/16 inch (4.7625 mm). Tubing was assembled with polycarbonate barbed wye tube fittings matching the inner diameter of the tubing inner diameter. 1/16-inch PVDF barbed luer lock couplings were added to the inlets of the tubing provide attachments for syringes. To create the helical geometry for the mixing region, a 3D printed supported was designed in Autodesk Inventor and printed with a Formlabs Form 2 SLA 3D Printer. Tubing was cut, such that each input stream was of equal length. For aqueous synthesis, the device consisted of three inputs, with one for the solution containing the metal of interest and capping ligand, one for the immiscible fluid and one for a reducing agent. Streams containing the metal salt and immiscible carrier meet upstream of the reducing agent stream and form discrete reaction droplets. The droplet stream then merged with the reducing agent stream immediately preceding the helical mixing region.

Experimental Section

Chemicals:

All reagents as follows were purchased from Sigma Aldrich and used without further modification; Cadmium nitrate tetrahydrate (99.0+%), Cadmium acetate dihydrate (98.0+%), Mercury(II) nitrate monohydrate (98.5+%), selenium powder (Se, ~100 mesh, 99.5%), sodium sulfide, Diphenylphosphine (DPP, 98%), Trioctylphosphine (TOP, 97%), 1-octadecene(ODE, 95.0≥%, GC), Tris(hydroxymethyl)aminomethane (Tris, ACS reagent, ≥99.8%) and Oleic acid,(OAc, 90% tech.)

Aqueous QD Synthesis:

For aqueous syntheses all solutions were prepared in Milli-Q grade water. 3-Mercaptopropionic acid solutions (5 mM, pH 8.7, 5 ml) were buffered with tris(pH 9.5) and used as a capping ligand for the QDs. This was added to Hg(NO₃)₂ (5 mM, 5 ml) or Cd(NO₃)₂ (5 mM, 5 ml) and was taken up by a syringe. The reducing agent, Na₂S (5 mM, 10 ml) was then placed in a second syringe. Both syringes were placed into a syringe pump along with a third syringe containing paraffin oil (10 ml). The desired flow rate was then input and if heating was desired, the mixing region was submerged in a heated oil bath set to the desired temperature. Synthesis was quenched by placing the collection vessel in cold water. See supplemental figure 1a for a detailed schematic representation of the device used for aqueous syntheses. Quantum dots were purified by filtration in a centrifugation column (Pierce™ Protein Concentrator PES, 3K MWCO, 2–6 mL) and redispersed in water.

Organic QD Synthesis:

To synthesize quantum dots through organic routes a separate device designed was proposed. See supplemental figure 2 for detailed schematic. Cadmium acetate dihydrate, oleic acid (220ul), and 1-octodecene (1.58 ml) were mixed until the metal salt was sufficiently dissolved. This was then loaded into a syringe. Into another syringe, 1.8ml of 1-octadecene was loaded. In a third syringe, an equal amount of water was loaded. This was chosen to be the immiscible carrier liquid. Into a 4^th syringe, Selenium powder was dissolved in 1.8ml of TOP. And in a 5^th syringe, approximately 100mg of DPP and 1.8ml of TOP was loaded. The syringes were loaded into a syringe pump and 7-inch portion of tubing was placed in an oil bath

The synthesis of CdSe required additional heating after emerging from the device to produce quantum dots, as the collected solution acted as a precursor solution. This could be accomplished by placing the device outlet in an oil bath or collecting the solution and heating separately.

The purification procedure for organically synthesized quantum dot was adapted from a procedure outline by Smith et al 2016. Briefly, a mixture of 1:1 acetone and methanol were added to the quantum dots and vortexed. This mixture was then centrifuged at 7000 rpm for 5 minutes. The upper portion was decanted the quantum dots were redispersed in hexane or toluene and then precipitated with methanol and redispersed in hexane or toluene. This process was repeated at least once. The final hexane or toluene QD dispersion acted as a stock solution which was used for subsequent analysis including for Raman, TEM and UV-vis spectroscopy.

Optical and structural Characterization:

Absorption spectra of the QDs were obtained using a Jasco V-670 UV/VIS/NIR Spectrophotometer. All spectra were collected in a quartz cuvette with the appropriate solvent for background correction. Fluorescence and Raman spectra were acquired using a Horiba Confocal Raman Imaging Microscope in the Beckman Institute microscopy suite.

Dynamic Light Scattering:

DLS measurements were obtained in triplicate using a Malvern Zetasizer equipped with a 633 nm red laser. Measurement parameters were set to the 173° non-invasive backscatter default and the measurement duration was automatically selected. This analysis was conducted in the Fredrick Seitz Materials Research Laboratory Central Research Facilities at the University of Illinois.

Raman Spectroscopy:

Samples were prepared by drying onto lowE glass slides (Kevley Technologies, USA). The spectra shown was obtained using 532 nm laser excitation for 30 s on a Horiba confocal microscope using a 100x objective lens and 1800 gr/mm grating.

TEM:

Sample solutions (10ul) were drop cast onto 300 mesh ultra-thin Carbon Film carbon grids (Electron Microscopy Sciences) and excess was removed after approximately 10 seconds. TEM images were obtained using a JEOL 2010 LaB₆ electron microscope operated at 200 kV in the Fredrick Seitz Materials Research Laboratory Central Research Facilities at the University of Illinois.