**2.2. Fabrication technology examples**

to fabrication technology or according to the type of substrate used (e.g., c-Si, amorphous, polymeric) or according to application. Within each technology, the reference list has been sorted out chronologically to help interested readers follow the origin and evolution of ideas and technologies. Despite of the relatively large number of references included, this is not a comprehensive review. The reference list simply offers starting points. Getting back to the main theme, the question still remains: why does microfluidics continue to receive increased attention? What are

The science and technology mentioned above are widely exploited and applied to give microfluidics a host of advantages. A brief list includes use of small volumes of sample and reagents (thus reducing cost per analysis and minimizing waste disposal); rapid sample processing; potential for automation (thus reducing cost); reduced risk of contamination; short analysis time (e.g., by increasing speed of separations); small footprint and light-weight thus enabling development of future portable microfluidic-based, portable micro-instruments that can be employed *on-site* or for personal use or for personal dosimetry; potential for massive parallelism (for high sample throughput); and overall, lower ownership and operating costs (vis-à-vis conventional, lab-sized systems). Application areas (to name but a few), include analytical chemistry, synthetic chemistry (including nanomaterials synthesis), microbiology, biotechnology, point-of-care diagnostics, drug delivery, immunoassays and medicine, health-monitoring and health-diagnostics, agriculture, food safety and environmental monitoring [30–47].

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

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

the advantages of using microfluidics, especially for chemical analysis applications?

**1.3. Advantages and selected applications of microfluidics**

4 Microfluidics and Nanofluidics

**2. Technology for fabrication of microfluidic channels**

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

the precautions required so that previously deposited layers are not damaged.

examples will be briefly discussed later.

To highlight substrate-dependence of fabrication, the fabrication steps required for microchannels on c-Si and on amorphous glass or quartz substrates are compared and contrasted in **Figure 2**. It should be noted that depending on crystallographic orientation of the substrate and of the chemical cocktail used in the etching solution, isotropic or anisotropic etching may be obtained [48–51].

**Example 1:** *Planar 2D-chips* **and wet chemical etching for fabrication of microchannels on crystalline and amorphous substrates** (**Figure 2**).

**Figure 2.** Simplified steps used for fabrication of microchannels on a) a c-Si wafer as a substrate and on b), a wafer made from an amorphous material (abbreviated as a-wafer-above, such as glass).

For completeness, an example of wet chemically etched microchannels on glass is shown in **Figure 3**.

The quality of the etched microchannels depended on the composition of the etching solution and on the geometric-primitives that were used to define the channels. To enclose the microchannel of **Figure 3**, a cover plate was used (but is not shown in **Figure 3**). Depending on the required optical transparency, a UV-transparent quartz cover plate was employed for most of the work described here. Furthermore, depending on the substrate (e.g., c-Si or glass), a variety of bonding methods can be employed [2–17].

and time-delays involved. There is another limitation if microchannels are to be used with biological samples, because many biosamples adhere to substrates. Thus, functionalized surfaces

**Figure 3.** (a) Part of a 14.5 mm by 25.6 mm chip of an etched microfluidic channel on corning 7059 glass with the photoresist removed and (for clarity) without a cover plate. Also omitted are pipette-tips used as sample reservoirs that are attached to the sample well. A coin was included for size. (b) Part of a Mylar mask used for photo-lithography. (c) Part of a washed meandering microchannel shown under 10x magnification and (d) shown under 60-fold magnification. (e) an unwashed microchannel immediately after etching showing etching by-products inside the microchannels, thus requiring their removal. (f) a sample-well and a washed microchannel showing the quality of etching, in particular for the round sample-well. For (d), (e) and (f) the photoresist was not removed to provide contrast for the photographs.

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**Example 2. Imprinting microchannels on planar polymeric 2D-chips.** 2D-microchannel fabrication on polymeric substrates is one way of overcoming some of the limitations mentioned above. But polymers may contain additives, fillers or plasticizers that may contaminate the samples, and they may display auto-fluorescence. As for fabrication (**Figure 4**), it may be achieved by using Si-stamp imprinting (**Figure 4**) or by imprinting (by pressing) a wire on a substrate [69] (**Figure 5**). In the example shown in **Figure 4**, a c-Si stamp (or master or hard

or microfluidic channels on polymeric substrates are preferred.

mold) was developed and was employed for replication by imprinting.

Despite of the ability to fabricate low aspect ratio microchannels, wet chemical etching has shortcomings arising from costs, from limited access by many to photolithography and to cleanrooms, and from time-delays between mask-design (**Figure 3b**) and receipt of finished prototype (e.g., **Figure 3a**). At present, access to cleanrooms is not required because microfluidic chips can now be ordered from specialized foundries. In spite of this, there are still costs Microfluidics and Nanofluidics: Science, Fabrication Technology (From Cleanrooms to 3D... http://dx.doi.org/10.5772/intechopen.74426 7

**Figure 3.** (a) Part of a 14.5 mm by 25.6 mm chip of an etched microfluidic channel on corning 7059 glass with the photoresist removed and (for clarity) without a cover plate. Also omitted are pipette-tips used as sample reservoirs that are attached to the sample well. A coin was included for size. (b) Part of a Mylar mask used for photo-lithography. (c) Part of a washed meandering microchannel shown under 10x magnification and (d) shown under 60-fold magnification. (e) an unwashed microchannel immediately after etching showing etching by-products inside the microchannels, thus requiring their removal. (f) a sample-well and a washed microchannel showing the quality of etching, in particular for the round sample-well. For (d), (e) and (f) the photoresist was not removed to provide contrast for the photographs.

For completeness, an example of wet chemically etched microchannels on glass is shown in

**Figure 2.** Simplified steps used for fabrication of microchannels on a) a c-Si wafer as a substrate and on b), a wafer made

The quality of the etched microchannels depended on the composition of the etching solution and on the geometric-primitives that were used to define the channels. To enclose the microchannel of **Figure 3**, a cover plate was used (but is not shown in **Figure 3**). Depending on the required optical transparency, a UV-transparent quartz cover plate was employed for most of the work described here. Furthermore, depending on the substrate (e.g., c-Si or glass),

Despite of the ability to fabricate low aspect ratio microchannels, wet chemical etching has shortcomings arising from costs, from limited access by many to photolithography and to cleanrooms, and from time-delays between mask-design (**Figure 3b**) and receipt of finished prototype (e.g., **Figure 3a**). At present, access to cleanrooms is not required because microfluidic chips can now be ordered from specialized foundries. In spite of this, there are still costs

a variety of bonding methods can be employed [2–17].

from an amorphous material (abbreviated as a-wafer-above, such as glass).

**Figure 3**.

6 Microfluidics and Nanofluidics

and time-delays involved. There is another limitation if microchannels are to be used with biological samples, because many biosamples adhere to substrates. Thus, functionalized surfaces or microfluidic channels on polymeric substrates are preferred.

**Example 2. Imprinting microchannels on planar polymeric 2D-chips.** 2D-microchannel fabrication on polymeric substrates is one way of overcoming some of the limitations mentioned above. But polymers may contain additives, fillers or plasticizers that may contaminate the samples, and they may display auto-fluorescence. As for fabrication (**Figure 4**), it may be achieved by using Si-stamp imprinting (**Figure 4**) or by imprinting (by pressing) a wire on a substrate [69] (**Figure 5**). In the example shown in **Figure 4**, a c-Si stamp (or master or hard mold) was developed and was employed for replication by imprinting.

**Example 3: 3D-printed, milli-sized fluidic channels on polymeric materials for hybrid 3D chips.** 3D printing technology [109–122] using polymeric materials is receiving attention for rapid prototyping [109] including fabrication of mm channels (often called **millifluidics**) and more recently for sub-mm channels (using specialized printers) [120, 121]. We used 3D-printing due to reduced fabrication and ownership costs and due to quick turn-around times (often from concept to prototype in hours). A simple, hybrid, 3D-printed 3D-chip containing a millifluidic channel is shown in **Figure 6**. The word *hybrid* was used because the two

**Figure 6.** Sugar cube-sized, 3D-printed hybrid-chip with a millifluidic channel to be fitted with a quartz cover plate (selected for UV transparency). A sample introduction system is also shown and it has been included to provide an overall size for this "critical" component of a potential future micro-instrument. An actual sugar-cube (~1 cm by ~1 cm)

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In my laboratory, some of the fabrication technologies discussed thus far have been used to constrain plasmas in microfluidic or in millifluidic channels. But why plasmas and why

There are four states of matter: gases, liquids, solids and plasmas [123–131]. To generalize, atmospheric pressure plasmas are ionized gases that are either hot or cold (about room temperature or somewhat above it). Plasmas occur in nature, for example those found in inter-stellar space, in the ionosphere, in auroras and in lightening. There are also artificially-generated plasmas that are being used in many every-day-life applications. Neon signs and fluorescent lights in which low-pressure plasmas are formed either in Neon (Ne) gas or in Argon (Ar) gas) are two such examples. Other examples include plasmas employed for device fabrication by the semiconductor industry or for materials synthesis in nanoscience and nanotechnology [129–131]. **It has been estimated that over 50%** of whatever goes inside any electronic device

**Conventional-scale** (or **lab-scale**) atmospheric pressure plasmas are widely used in **chemical analysis**, primarily in the form of atmospheric-pressure, **6000–10,000 K hot** Inductively Coupled Plasmas or ICPs [132]. Due to their size and weight (e.g., in the few 100's of pounds),

(e.g., a tablet, a smartphone, TV) is fabricated using a low-pressure plasma.

needle electrodes and the quartz cover plate were not 3D-printed.

microplasmas?

**3. Why plasmas?**

has been included for scale comparisons.

**Figure 4.** (a) Mask; (b) mask on c-Si chip, coin has been added for size; (c) chemically etched c-Si chip (serving as a stamp), the meandering pattern is protruding from the surface of the chip; (d) imprint generated by pressing the stamp and the polymeric chip together by placing them in a hydraulic press and by applying pressure at room temperature; (e) imprinted sample-well on a polymer chip shown under magnification; and (f), part of an imprinted meandering channel shown under magnification. For (d) and (e) and (f) different polymeric materials were used.

**Figure 5.** (a) Imprinted channel on a polymeric chip (60x magnification), (b) sample-well (60x magnification) and (c) Venturi micropump with no moving parts and no electrical power requirements fabricated by imprinting (coin included for size) [73].

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**Figure 6.** Sugar cube-sized, 3D-printed hybrid-chip with a millifluidic channel to be fitted with a quartz cover plate (selected for UV transparency). A sample introduction system is also shown and it has been included to provide an overall size for this "critical" component of a potential future micro-instrument. An actual sugar-cube (~1 cm by ~1 cm) has been included for scale comparisons.

**Example 3: 3D-printed, milli-sized fluidic channels on polymeric materials for hybrid 3D chips.** 3D printing technology [109–122] using polymeric materials is receiving attention for rapid prototyping [109] including fabrication of mm channels (often called **millifluidics**) and more recently for sub-mm channels (using specialized printers) [120, 121]. We used 3D-printing due to reduced fabrication and ownership costs and due to quick turn-around times (often from concept to prototype in hours). A simple, hybrid, 3D-printed 3D-chip containing a millifluidic channel is shown in **Figure 6**. The word *hybrid* was used because the two needle electrodes and the quartz cover plate were not 3D-printed.

In my laboratory, some of the fabrication technologies discussed thus far have been used to constrain plasmas in microfluidic or in millifluidic channels. But why plasmas and why microplasmas?
