A Microfabricated Gas–Liquid Segmented Flow Reactor for High‐Temperature Synthesis: The Case of CdSe Quantum Dots

Monodisperse CdSe quantum dots (QDs) with excellent optical properties can be prepared with a gas–liquid segmented flow microreactor with multiple temperature zones (see picture; red=heated; blue=cooled quench zone). The enhanced mixing and narrow residence time distributions of segmented flow produce QDs superior to those prepared in single-phase operations. Microfluidic reactors enable a number of advantages over conventional chemical processes including enhanced control of heat and mass transfer, lower reagent consumption during optimization, and sensor integration for in-situ reaction monitoring.1, 2 Reactors are usually fabricated from either silicon, glass, or polymers; those made of silicon or glass are advantageous because they can tolerate a broad range of chemistries and high temperatures. Microreactors for the large class of homogeneous liquid-phase reactions are often based on single-phase laminar flow designs in which reagent streams are brought into contact. However, such designs are limited in terms of slow diffusive reagent mixing and broad residence time distributions (RTDs). Recirculation within segments in a two-phase segmented flow approach (gas–liquid or liquid–liquid) overcomes such limitations by providing a mechanism of exchanging fluid elements located near the channel walls with those at the center.3–5 This recirculatory motion has the dual effect of narrowing the RTD and improving reactant mixing. In contrast to single-phase designs, segmentation makes it possible to drive reactions to required yields over significantly shorter times owing to the enhanced mixing, while maintaining narrow RTDs. Gas–liquid rather than liquid–liquid segmented flow offers the most versatility in terms of the range of chemistries that can be performed in a microfluidic system. Gas–liquid flow is preferable for performing reactions at elevated temperatures, as most solvents experience increased miscibility at higher temperatures. Moreover, it is possible to obtain uniform segmentation in gas–liquid flows over a very large range (over two orders of magnitude) of bubble velocities and therefore reaction timescales.4, 5 Liquid–liquid segmented flow systems are operated over a much narrower range with typical droplet velocities varying over one order of magnitude.3, 6 Finally, in gas–liquid segmented flow, the reaction solution is present as a continuous liquid phase within the channel (Figure 1) so that it is possible to inject additional reactants or withdraw reaction aliquots in a continuous, controllable manner. In liquid–liquid segmented flow, the reaction solution is usually the dispersed (droplet) phase; subsequent addition of reactants is challenging, as it requires synchronized merging of discrete droplets.6 The withdrawal of small aliquots without disturbing the flow is also difficult. Herein, we demonstrate a silicon-based microreactor that incorporates both gas–liquid segmented flow and multiple temperature zones. The reactor represents a general platform for high-temperature synthesis under very well-defined reaction conditions (mixing times and narrow RTDs). Mixing and residence time distribution (RTD) effects in a) single-phase and b) segmented gas–liquid flow. In the single-phase laminar flow, diffusion is the only means of mixing. As a result of the parabolic fluid-velocity profile, particles near the wall spend more time in the reactor than those in the center, resulting in broad RTDs. In the two-phase case, recirculation within each liquid slug brings material from the wall to the center of the channel. This facilitates mixing, which narrows the RTD, and results in narrower size distributions. As a model system for the reactor, the preparation of CdSe quantum dots (QDs) was chosen, as the chemistry a) requires high temperatures and b) highlights the advantages of the segmented-flow approach over single-phase and conventional batch processes. In the batch method, semiconductor QDs (diameters=2–10 nm) are synthesized by the rapid injection of precursors into a heated flask containing a mixture of solvents and ligands.7–10 Factors such as the injection process, local temperature and concentration gradients, mixing rate, and cooling rate strongly influence QD nucleation and growth, but are difficult to control. Single-phase continuous flow reactors in which precursor solutions are delivered into a heated reaction section have addressed some of these reproducibility problems.11 However, these reactors suffer from slow mixing and broad RTDs, which are detrimental to the particle size distribution (Figure 1). It has been challenging to adapt QD chemistry to a chip-based segmented flow system owing mainly to the reaction temperatures required (>250 °C). Liquid–liquid segmented flow has been used to prepare QDs at room temperature in a polydimethylsiloxane device,6 but solvent miscibility and polymer degradation at high temperatures make it difficult to use this approach to prepare monodisperse, luminescent particles. The introduction of segmenting gas into heated capillaries has also been implemented, but the uniformity of such gas–liquid flows and their effect on QD formation were not extensively characterized.12, 13 We demonstrate herein the success of our microreactor design in rapid mixing and extremely uniform segmentation behavior at the high temperatures required for QD synthesis. The QD sample size distributions and reaction yields are superior to those attainable in single-phase flow, with the improvement significantly more pronounced at short reaction times. As the improvement is a direct consequence of the rapid mixing and narrow RTD features of segmented flow, the reactor greatly decreases the time required to produce high-quality particles in comparison with existing single-phase approaches. Moreover, the reactor is applicable to a variety of nanoparticle chemistries because it offers access to a wide range of reaction timescales without a compromise in acceptable size distributions. The reactor shown in Figure 2 allows rapid initial mixing of the precursors, controlled QD growth, and on-chip quenching of the reaction. The silicon reactor accommodates a reaction channel length of approximately 1 m (hydraulic diameter≈380 μm) and two shallow side channels for collecting reaction aliquots. A halo etch region makes it possible to localize multiple temperature zones for reaction (>260 °C) and quenching (99 %, Alfa) at 150 °C for 10 min. The optically clear solution was then placed under vacuum at 100 °C for ≈1.5 h before the addition of 4 mL oleylamine (97 %, Pfaltz and Bauer). A stock solution of tri-n-octylphosphine selenide (TOPSe, 1.5 M) was prepared by dissolving an appropriate amount of selenium shot (99.999 %, Alfa) in tri-n-octylphosphine (TOP, 97 %, Strem). The Se precursor solution consisted of the suitable amount of TOPSe (1.5 m) diluted in squalane. The two precursor solutions were degassed thoroughly at 90 °C before loading into separate syringes. Samples for the measurement of absorbance and PL spectra were prepared by diluting the raw QD solutions in hexanes. Optical absorption spectra were with a spectra were with an and a UV as an yields were determined from the optical at nm and the absorbance for CdSe