**2.1. Fabrication using either crystalline Si (c-Si) or other substrates**

Microchannel fabrication technology has been borrowed from the semiconductor industry. Initially, *bulk micromachining* [1–17, 48–51] was employed on crystalline Si (c-Si) substrates and on amorphous glass. To use it, a photolithographically patterned wafer was dipped into a chemical etching solution to etch-away (or subtract) material from the substrate, thus forming microchannels of desired geometry. This method is often referred to as *wet chemical etching* [48–51]. Inadequate control of channel depth (resulting unevenly etched channels) due to spatial etch-rate variations and to pyramid formation when crystalline-Si (c-Si) substrates and deep microchannels were etched are two key disadvantages. In contrast, *surface micromachining* [52–54] involves repetitive patterning, thin layer deposition and selective etching of sacrificial layers. The challenge here stems from the many photolithography steps involved and from the precautions required so that previously deposited layers are not damaged.

We used (as far back as the 1990's) cleanroom-based photolithography, bulk micromachining and **wet chemical etching** [48–51] to fabricate shallow-depth microchannels (with relatively low width-to-depth **aspect ratio**). This approach is often referred to as 2D sculpting of Manhattan-like structures and it offers a planar, 2D- rather than a 3D-perspective. Some examples will be briefly discussed later.

For completeness, other methods of microchannel fabrication on inorganic substrates (either crystalline or amorphous) have been described. A short list includes **laser machining** [55– 58]; lithographie galvanoformung adformung (LIGA) or lithography electroplating molding [59–61] which is well suited for fabrication of high aspect ratio channels; deep reactive ion etching (DRIE) [62–65] often used for fabrication of microchannels with a high aspect ratio; and, **SU-8** (an epoxy-based negative photoresist) and its variants such as SU-8 series 2000 and SU-8 Series 3000) [66–68].

Technologies involving polymeric substrates [69–83] include replication via **imprinting** [69–73] or **embossing** [74–76]. Polymeric substrates are selected due to their bio-compatibility or to reduce cost of ownership. Examples will be shown later. The terms disposable or recyclable microfluidic devices is often used for microfluidic channels on polymeric substrates. **Soft lithography** [77–83] (defined as a collection of fabrication techniques for replication of microchannels) is a technology that does not require access to a clean room. It is called soft because it uses soft and flexible (primarily) elastomeric materials such as poly di methyl siloxane (PDMS) and often cyclic olefin copolymer (COC).

There are other techniques that are rather difficult to classify either according to fabrication technology or according substrate. Despite of being brief, the list includes **droplet microfluidics** [84–89], in which discrete droplets or small volumes of immiscible liquids are guided through microchannels. In the early literature, this approach was often called digital microfluidics. As it is known now, **digital microfluidics** [90–95] is an outgrowth of electrowetting [90, 92] and it involves use of discrete droplets on arrays of electrodes, with individual droplets manipulated by electrical means. The list also includes **centrifugal microfluidics** [96–101], a technique that enables micro-flow manipulation by using rotational forces (e.g., Coriolis) obtained by spinning a CD on top of which there are microfluidic channels. This technique is often called *"lab on a CD"*. It also includes **paper microfluidics** [102–108], a technique that uses paper for development of microfluidic approaches intended for use in resource limited situations (e.g., remote geographical areas or resource-limited locations).

**Rapid prototyping via 3D-printing** [109–122] involves both a technology (e.g., a 3D printer) and a materials platform (e.g., a polymer) for formation (primarily) of mill-sized fluidic (and recently) micro-sized channels [115, 117, 120]. An example of 3D printing will be discussed later in this chapter.
