*Microfluidics for Time-Resolved Small-Angle X-Ray Scattering DOI: http://dx.doi.org/10.5772/intechopen.95059*

shaped geometries can be employed, where the central flow is focused from both incoming side channels (**Figure 2F**). This provides good control over the thickness of the central stream. Furthermore, it allows a well-defined sample composition that can be adapted by variation of the volume flow in each inlet individually. To adapt the device design to multi-step synthesis, several side channels can be added to introduce additional reactants (**Figure 2G**). Thus planar on-chip hydrodynamic focusing is more highly favoured for flexible mixing devices, and is used much

However, there are further considerations that need to be taken into account, particularly for chemical reactions or self-assembly processes. In coaxial and 2D channel geometries the interface of reacting solutions is in contact with the channel walls, and particles or macromolecules can stick and agglomerate on the channel surface and disturb the laminar flow conditions. Furthermore, this accumulation interferes with analytical investigations and, in the worst case, can cause complete

To avoid channel contact, three-dimensional channel geometries can be used. 3D hydrodynamic focusing requires both horizontal and vertical focusing of the central

All previously described device geometries can be used to produce droplets,

Many different technologies exist for the production of microfluidic devices. In general, fabrication of microfluidic devices in hard materials is often very timeconsuming and cost-intensive, thus polymers are generally preferred, particularly when cost and ease of fabrication are considerations in the design process. In most cases, designs are started in silicon, with a Computer-Aided Design (CAD) model of the device. The device is then fabricated using any of a number of different technologies following a process of rapid prototyping. We focus here on some of the

liquid jets and sprays under the right flow conditions, including ultra-high flowrates. These devices are not limited to constrained flows inside channels, and for time-dependent studies the use of free liquid jets is preferred. Measurements of free jets have significant advantages in many optical measurements, as there is little to no background signal from surrounding material. When employing free jet devices, the parabolic flow profile from laminar flow within channels turns into a plug flow profile after passing the nozzle outlet. The liquid–solid interface of the noslip condition resulting in parabolic flow is replaced by the liquid–gas interface in air, which has lower friction with the fluid and can be accelerated in flow direction. Free jets, however, are also quite difficult to work with, and despite the advantages

reactant stream, leading to a complete enclosure with liquid from all sides (**Figure 2H** and **J**). The device design can be optimised to reach homogeneous mixing without integrating specific mixing regions before the measurement part of the microfluidic chip. Additionally, these devices are simple to fabricate and have easily adjustable designs. The most common design to achieve 3D hydrodynamic focusing is through multi-layer on-chip devices, which require precise alignment as part of the fabrication process. Alternate methods are single layer devices or novel fluid manipulation technologies like "microfluidic drifting", which introduces lateral drifts or counter-rotating vortex forces to achieve vertical and horizontal flow focusing. These alternatives require less alignment in manufacturing and are thus

more often in general microfluidic designs.

*Advances in Microfluidics and Nanofluids*

much more user friendly in regards to fabrication.

in background have not found widespread use in the field.

blockage of the channel.

**2.2 Fabrication**

*2.2.1 Fabrication techniques*

more common approaches.

**20**

**Lithography.** One of the most powerful methods in microfabrication is lithography. It can be differentiated by the type of radiation used, e.g. photolithography, electron-beam lithography, or X-ray lithography. With these different lithography methods, structures with sizes between 0.2 and 500 μm in hard materials like glass, or between 0.5 and 500 μm in soft materials like polymers, can be achieved. In the most common form of lithographic fabrication, a UV blocking mask is generated from the CAD model, and adhered to a silicon wafer. The master model for fabrication is then generated by photolithography, where the masked wafer is coated in a photosensitive epoxy monomer solution, and UV-cured. In general these silicon masters are then used to generate working devices via soft lithographic replication. The most common approach is to use the master chip as a mould, and poly (dimethylsiloxane) (PDMS) to form an imprinted device, which can be bonded to a glass-slide or a second PDMS part to form the final microfluidic device [16–18]. The replicated structure can be a positive or negative of the initial design, depending on which part of the structure was UV-cured on the silicon master.

**Hot embossing and micromoulding.** Hot embossing is a micromoulding technique that uses thermoplastic polymers to imprint structures at elevated temperatures. It usually uses high-temperature polymers, e.g. PMMA, PC, PI, PE, PVC or PEEK, which are heated above their glass transition temperature (*Tg*) before being pressed into a mould with high pressure. The moulds have to withstand the applied pressure and high temperatures, and are often made of metal or silicon, fabricated via etching, lithography in combination with electroforming and moulding or CNC (Computerised Numerical Control)-machining. The accuracy of hot embossing is in the order of tens of nanometres, making it possible to obtain high aspect ratios of structure, while being a low cost and easy procedure. It is often used with a defined and tested device design as high throughput method with a very short fabrication time [19, 20].

**3D printing.** Within the last decade, 3D printing technologies have advanced to astonishing precision, in size-regimes down to the micrometre scale. Additive manufacturing technologies like fused deposition modelling (FDM), stereolithography (SLA) or selective laser sintering (SLS), have been developed for various materials like polymers, resins, ceramics or metals. It is possible with these techniques to produce a complete microfluidic device in one step. The device material and process can thereby be selected with regard to required mechanical and chemical properties of the device. A channel size resolution of few hundred micrometres can be achieved, making this approach preferred for devices with wider channels [21, 22].

#### *2.2.2 Device materials*

Based on the desired purpose of the microfluidic chip, device materials must fulfil specific criteria. The most important requirements which will be addressed in this chapter are solvent stability, ease of fabrication, and optical and X-ray transparency.

**Solvent stability.** Microfluidics deals with the manipulation of liquids, which means that the device material has to be resistant and inert to the solvent. This becomes especially relevant when using organic solvents, as they often cause swelling or dissolution of standard polymeric device materials. Swelling leads to deformation, which can cause channel closure. A number of device materials have been tested with regard to resistance to some common solvents for nanoparticle synthesis and self-assembly processes (**Table 1**). It is clear from these results that careful selection of polymer is necessary for long term stability.

**Ease of fabrication.** While the solvent is important, it is also essential to consider the difficulty of working with the various polymers, and the end


*Stability test of various polymers and the corresponding solvents.*

characteristics of the device. For example, NOA 81 is a turbid, commercially available, UV curable polymer mixture from Norland Optical Adhesive, which is relatively easy to work with. However, devices made from NOA 81 are thin and relatively flexible, even after sealing top and bottom half, so it should be avoided if stiff or thick devices are required. In comparison, SIFEL (SIFEL2610) is a fluorinated polymer distributed by Shin-Etsu that is liquid at room temperature and hardens at higher temperature, and is stable against all tested organic solvents. The device fabrication however, is time consuming, requiring the additional step of sputtering the silicon wafer with an inert chemical layer to allow release of the

Materials can also dictate the method of fabrication, for example THVs (fluorothermoplastics of blended tetrafluoro ethylene, hexafluoro propylene and vinylidene) must be fabricated by hot embossing. Glass or hard material devices are made with difficult fabrication techniques, like etching. In many cases prototypes are made with cheap, easy to fabricate materials, with the more difficult fabrication

**Optical and X-ray transparency.** The most commonly used method for alignment of device parts and analysis of ongoing reactions is optical microscopy. Hence, the optical properties, e.g. transparency, of the microfluidic devices should be considered. Further, the final measurement modality must be considered in material selection. For example, if three-dimensional confocal microscopic investigations of the whole channel volume are required, the selected device material should provide a low absorption behaviour in the range of the sample-specific selected laser wavelength, and low fluorescence background. Or as the focus of this chapter is SAXS, the material of the device should have high X-ray transmission, and low scattering in the q-range of interest. The material should also be able to withstand the X-ray radiation, which is present on high flux SAXS beamlines. In our experience, the lowest background scattering for higher q measurements above 0.05 Å

were achieved with glass, NOA81, PDMS and Kapton. Other polymers such as THV

that interfere with background subtraction, and worsen signal to noise. For mea-

NOA81 and TOPAS display flat scattering curves. All other tested materials at this q-range showed significant scattering signals from the device [23]. Furthermore, although showing a low scattering background at high scattering vectors, PDMS was extremely sensitive to radiation, deforming the channel and showing an increasing and changing scattering profile with exposure. This material is typically

Hybrid microfluidic devices can marry the best characteristics of materials, to achieve a successful device. For example, the complex mixing cross section can be made from easy to handle materials, e.g. PDMS, and a robust X-ray transparent, low background scattering material inserted as an outlet channel after the last crosssection, e.g. a glass capillary (**Figure 2K**). These devices have the advantage of high optical and X-ray transparency in the measurement region, while allowing adjust-

A key practical consideration for the use of microfluidics is the method for introducing fluid into the device. For the most part, each interface channel should have its own fluid handling system, which should be capable of smooth, pulse free

and TOPAS showed diffraction and correlation peaks in the high q region

surements at low scattering angles with *q* values under 0.05 Å<sup>1</sup>

ment to the mixing cross design in the polymer part [23, 24].

**2.3 Practical considerations for device handling**

unsuitable for SAXS measurements.

*2.3.1 Fluid handling*

**23**

1

>0.1 Å 1 ,

, glass, PMMA, PS,

SIFEL device from the mould.

only for the final working devices where needed.

*Microfluidics for Time-Resolved Small-Angle X-Ray Scattering*

*DOI: http://dx.doi.org/10.5772/intechopen.95059*

**Table 1***.*
