_appiled sciences_  
_Communication_  
**Flow Cell Coupled Dynamic Light Scattering for Real-Time Monitoring of Nanoparticle Size during Liquid Phase Bottom-Up Synthesis**  
**[PERSON] 1, [PERSON] 1, [PERSON] 1, [PERSON] 1, [PERSON] 2,3, [PERSON] 4, [PERSON] 4 and [PERSON] 1,5,6,***  
1 The Netherlands Organisation for Applied Scientific Research (TNO), De Rondon 1, 5612 AP Eindhoven, the Netherlands; [EMAIL_ADDRESS] (N.M.); [EMAIL_ADDRESS] (R.v.E.); [EMAIL_ADDRESS] (R.S.); [EMAIL_ADDRESS] (M.M.)  
2 Philips Innovation Labs, High Tech Campus 11, 5656 AE Eindhoven, the Netherlands; [EMAIL_ADDRESS] or [EMAIL_ADDRESS]  
3 Department of Applied Physics, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, the Netherlands  
4 LS Instruments AG, Passage du Cardinal 1, CH-1700 Fribourg, Switzerland; [EMAIL_ADDRESS] (N.K.); [EMAIL_ADDRESS] (R.A.)  
5 Hasselt University, Institute for Materials Research, Inorganic and Physical Chemistry, Agoralaan Building D, B-3590 Diepenbeek, Belgium  
6 Zuyd University of Applied Sciences, Nieuw Eyckholt 300, Postbus 550, 6400 AN Heerlen, the Netherlands  
* Correspondence: [EMAIL_ADDRESS] or [EMAIL_ADDRESS]; Tel.: +31-888-662-990  
Received: 18 December 2017; Accepted: 10 January 2018; Published: 13 January 2018  
**Featured Application: A unique set-up for real-time monitoring of the size of nanoparticles during bottom-up liquid phase synthesis is presented in this article. The analysis method applied to study the size of dispersed nanoparticles during synthesis is dynamic light scattering (DLS). In contrast to conventional DLS, the DLS set-up presented in this article comprises a modulated 3D cross correlation geometry, and therefore allows accurate measurements of particle size in flow at flow rates of at least up to 17 mL-min\({}^{-1}\). This is essential for obtaining real-time information on the size of the dispersed nanoparticles. The DLS system could be connected to reactors of various sizes using the analysis loop presented in this article, which is coupled to a flow cell in the DLS set-up. Thus, the DLS set-up presented here is suited to study the nucleation and growth of nanoparticles in dispersion, facilitates a rational scale-up, and allows intervention in the production process of nanoparticle dispersions to minimize the number of off-spec batches.**  
**Abstract: To tailor the properties of nanoparticles and nanocomposites, precise control over particle size is of vital importance. Real-time monitoring of particle size during bottom-up synthesis in liquids would allow a detailed study of particle nucleation and growth, which provides valuable insights in the mechanism of formation of the nanoparticles. Furthermore, it facilitates a rational scale-up, and would enable adequate intervention in the production process of nanoparticle dispersions to minimize the number of off-spec batches. Since real-time monitoring requires particle size measurements on dispersions in flow, conventional dynamic light scattering (DLS) techniques are not suited: they rely on single scattering and measure the Brownian motion of particles dispersed in a liquid. Here, we present a set-up that allows accurate measurements in real-time on flowing dispersions using a DLS technique based on modulated 3D cross-correlation. This technique uses two simultaneous light scattering experiments performed at the same scattering vector on the same sample volume in order to extract only the single scattering information common to both. We connected the reactor to a flow-cell in the DLS equipment using a tailor-made analysis loop, and successfully demonstrated the complete set-up through monitoring of the size of spherical silica nanoparticles during Stober synthesis in a water-alcohol mixture starting from the molecular precursor tetraethyl orthosilicate.**  
**Keywords:** dynamic light scattering; 3D cross correlation; real-time analysis; colloids; nanoparticle synthesis