Employing a microfluidic setup, it is possible to carry out experiments in very different conditions. You can run chemical reactions for synthesis, assembly or loading processes within a closed microfluidic channel at moderate flow rates.10 Moreover, there are jet devices available using ultra-high flow velocities which often result in an open free jet environment after passing a nozzle outlet. These aforementioned examples (see Figure 2) are two of several possibilities that aim to show the versatility of microfluidics. Both conditions, the closed channel system as well as the open liquid jet system, are used in this work.
Figure 2 | Images of two basic microfluidic methodologies. (a) Closed microchannel chip design.
(b) Nozzle-chip for free liquid microjet systems.
Microfluidics is based on the treatment and control of very small volumes of liquids or gases via specific devices.20 As these volumes are on a microliter scale or less, the physical laws concerning the flow behavior are completely different from those on macro scale. Consequently, the flow in a microfluidic setup is laminar and not turbulent which basically leads to very well controllable conditions regarding the treatment of chemicals. But what are the specific parameters influencing laminar flow in microfluidic devices? One of the basic parameters is the channel dimension that finally restricts scaling down to micrometer and leads to micro scale properties. Aside from the channel dimension, the flow rate and the viscosity of the liquid, or the gas, respectively, play a key role. Generally, the flow is laminar for lower flow rates as well as for higher viscosities and the mixing of compounds can be achieved by simple diffusion. A measure for the amount of turbulence is given by the dimensionless Reynolds-Number (Re) which is fully explained in chapter 2.2.2. Based on simple parameters, microfluidics can provide well-defined model environments which makes it adaptable to many fields of science such as chemistry, biology, pharmacy, medicine and any other analytical or technological field.
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The ability to carry out quantitative and qualitative analysis with high resolution and sensitivity while using very small amounts of substances led to the rise of microfluidics during the last decade of the 20th century.21,22 After the growing interest on low cost and fast analytical processes as well as the emergence of lithographical and rapid prototyping processes during that time, microfluidics became quite attractive for industry and science.23,24 One of the first and certainly the most famous pioneer on scientific microfluidics is George M. Whitesides who introduced poly(dimethylsiloxane) (PDMS) as a polymeric fabrication material on which a huge majority of the following research was carried out.25,26 The next decades, much scientific work was done on microfluidic setups especially for drug delivery and drug targeting systems. Here, the synthesis, assembly and loading processes as well as effective separation methods are the main focus of this research field.
Many studies on synthesis in microfluidic devices have been carried out using biomaterials, nanoparticles or enzymes.27-29 Currently, especially nanoparticles are of highest interest because they can be synthesized via microfluidics with a huge variety of functionalized groups in order to create for example lipid nanoparticles (LNPs) that have a higher circulation time in the blood stream, low cytotoxicity, good biocompatibility and transfection efficiency.30,31 However, nanoparticles can also be used to load different types of super-structured and self-assembled systems by employing a microfluidic chip in order to increase their pharmaceutical efficiency as drug-targeting systems.32,33 Such self-emulsifying delivery systems, liposomes, polymeric nanoparticles, microemulsions and micellar solutions can be compounded within complex and individually designed microfluidic chip labs. Those labs on a chip are predestinated for mixing different substances and particle systems under highly controlled laminar flow conditions.9,34 In this context, hydrodynamic flow focusing is indispensable to achieve a good quality for the reaction process of these colloidal systems. Such processes encompass nucleation, growth by aggregation, stabilization, or self-assembly.35 Consequently, colloids of various shape and elasticity, e.g. microdroplets and vesicles, core-shell structures, or Janus particles are available at high monodispersity.
Another important topic is flow- as well as shear-induced orientation and the associated separation. Thus, a given polydisperse colloidal system can be sorted by size for instance.11,36 This separation in turn increases the quality of drug delivery and the manufacturing process of high-performance materials like composite materials in which the different particle systems need to have maximized alignment within a matrix. In most cases, batch synthesized particles have rather high polydispersities which calls for effective post-processing. This processing may include particle separation with respect to their size, shape or elasticity. The goal is to finally
11 receive one homogeneous species for effective drug targeting and mechanical material enhancement.37-39 Microfluidic colloid separation is diverse and ranges from active sorting processes via chemical, electrical or magnetic impact to gentle passive systems using various physical forces without the need of modifications of the particle itself.40-42 For that, many different microchannel geometries have already been tested with several colloids to figure out the best method for their separation.43-45 Nevertheless, there is still room for improvement to achieve maximum efficacy for all kinds of particles. A basic prerequisite to particle separation is to understand why colloids are going to flow on certain trajectories.46 Here, very often the size-, shape- and elasticity-induced orientation behavior of each particle plays an important role.47 Knowledge about colloidal distribution and orientation helps to improve particle separation as well as sorting and also offers a powerful tool to adjust particle order in process engineering for many soft matter and material applications.
To attain all these specific requirements, this work presents two major microfluidic setups that are mainly used to perform tailor-made experiments. The first and common system is a closed microchannel chip device which gives maximum control of liquid or gaseous flows. Today, there is a huge variety of channel designs including 2D- but also highly complex 3D-channel structures which leads to a great flexibility for all kinds of experiments. However, channel walls are found to be critical as they may cause agglomeration of particles which ultimately leads to clogging of the device. Moreover, chemicals leeching from the chip material might interfere with highly sensitive analytical methods. For example, commonly used PDMS is not X-ray transparent thus making an experimental investigation via SAXS impossible. A solution to these problems is a modern free liquid jet system – the second setup. Free jets lack channel walls over a wide range except for the inlet part consisting of a nozzle.48,49 Consequently, virtually every analytical method can be used without any disturbance.50 However, the flow conditions are slightly different when comparing closed streams and free jets: a higher flow rate is necessary to achieve a free jet and the missing walls change the originally no-slip conditions to free-slip conditions which again enable new possibilities.
As mentioned above, a fully established methodology requires powerful analytical methods.
Ideally, an elaborated microfluidic platform should be used on which you can integrate different techniques of analysis such as optical, scattering or spectroscopic methods potentially used simultaneously and in situ.51 State-of-the-art devices are designed to be mobile microfluidic platforms that can be integrated temporarily in intense synchrotron sources like DESY, ESRF, MAX or Diamond to achieve effective time management, as illustrated in following Figure 3.
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Figure 3 | Portable complex microfluidic platforms for simultaneous in situ analysis techniques at intern and extern research institutions like synchrotrons. (a) Pressure-based pump setup for a closed microchannel chip system. (b) Micro gear pump recycling built-up for free liquid microjets.