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J. Xu et al.
surface of the microfluidic structures to ensure sufficient optical quality [63]. Fabrication of hollow microstructures with smooth internal surfaces can also be utilized
to obtained 3D buried micro-optical elements such as optical mirrors, microlenses,
splitters and fibers in glass substrates [62, 63]. In addition, this technique can form
micro-mechanical components, including microvalves and micropumps, to control
fluid flow inside microfluidic structures [64]. Unlike FLAE of Foturan, fused silica
does not require thermal treatment prior to selective etching. However, it requires
higher laser power and longer etching times, since this process relies on photophysical
reaction. The etching selectivity of glass substrate has also been enhanced by using
a KOH solution instead of HF as the etchant [65, 66]. Obtaining smooth surfaces
in fused silica following FLAE is challenging, and several post-thermal treatment
methods have been proposed to address this issue, including oxygen/hydrogen flame
polishing [67], oven annealing [68], and CO 2 laser annealing [69].
It should be noted that, in many microfluidic biochip applications, control of the
cross-sectional shapes of the microchannels is important because it determines the
fluid dynamics as well as channel functionality. During fabrication of large channels, the cross-sections can be controlled with significant flexibility by adjusting the
multiple laser scanning process in 3D space. However, narrow microchannels fabricated by single scan transverse writing (in which the sample is translated perpendicular to the incident beam) tend to have highly elliptical cross-sections due to
elongation of the focal spot in the direction of the incident laser beam. To overcome this problem and thereby fabricate microchannels with circular cross-sections,
several beam shaping techniques have been developed, including astigmatic [70],
slit [71], crossed [72], and spatiotemporal beam shaping [73].
3D microfluidic devices manufactured by fs laser 3D direct writing have many
interesting applications in biological research, such as the determination of microorganism functions, manipulation of bio-cells, and detection and analysis of liquid
samples. Hanada et al. reported the FLAE manufacturing of Foturan microchips
with embedded 3D hollow microstructures, termed “nano-aquariums,” for the efficient and dynamic observation of living microorganisms and cells in fresh water
(Fig. 8.2a) [21]. In this work, a 3D microchannel buried inside a glass substrate was
employed to analyze the continuous motion of Euglena gracilis. The Euglena gracilis
were confined to a limited volume in the channel but were still able to move freely,
making it much easier to capture images of their movement. These biochips reduced
the required observation time by a factor of greater than 10 compared to conventional
methods using a Petri dish, and front view images of Euglena cell movement were
obtained for the first time. In addition, a microchamber integrated with a movable
microneedle was used to elucidate the information transmission process in Pleurosira laevis. Choudhury et al. demonstrated a 3D mammalian cell separator biochip
fabricated by the FLAE of fused silica [24]. Cell sorting in this device was based on
differences in the deformability of cell types having varying cytoskeletal architectures. Figure 8.2b illustrates the working principle of the biochip, which consisted of
T-junctions formed by two microchannels with narrow constrictions. These constrictions, whose cross-sections were narrower than the average cell size, functioned
as filters for sorting. This overall structure enabled accurate, pressure-driven flow
J. Xu et al.
surface of the microfluidic structures to ensure sufficient optical quality [63]. Fabrication of hollow microstructures with smooth internal surfaces can also be utilized
to obtained 3D buried micro-optical elements such as optical mirrors, microlenses,
splitters and fibers in glass substrates [62, 63]. In addition, this technique can form
micro-mechanical components, including microvalves and micropumps, to control
fluid flow inside microfluidic structures [64]. Unlike FLAE of Foturan, fused silica
does not require thermal treatment prior to selective etching. However, it requires
higher laser power and longer etching times, since this process relies on photophysical
reaction. The etching selectivity of glass substrate has also been enhanced by using
a KOH solution instead of HF as the etchant [65, 66]. Obtaining smooth surfaces
in fused silica following FLAE is challenging, and several post-thermal treatment
methods have been proposed to address this issue, including oxygen/hydrogen flame
polishing [67], oven annealing [68], and CO 2 laser annealing [69].
It should be noted that, in many microfluidic biochip applications, control of the
cross-sectional shapes of the microchannels is important because it determines the
fluid dynamics as well as channel functionality. During fabrication of large channels, the cross-sections can be controlled with significant flexibility by adjusting the
multiple laser scanning process in 3D space. However, narrow microchannels fabricated by single scan transverse writing (in which the sample is translated perpendicular to the incident beam) tend to have highly elliptical cross-sections due to
elongation of the focal spot in the direction of the incident laser beam. To overcome this problem and thereby fabricate microchannels with circular cross-sections,
several beam shaping techniques have been developed, including astigmatic [70],
slit [71], crossed [72], and spatiotemporal beam shaping [73].
3D microfluidic devices manufactured by fs laser 3D direct writing have many
interesting applications in biological research, such as the determination of microorganism functions, manipulation of bio-cells, and detection and analysis of liquid
samples. Hanada et al. reported the FLAE manufacturing of Foturan microchips
with embedded 3D hollow microstructures, termed “nano-aquariums,” for the efficient and dynamic observation of living microorganisms and cells in fresh water
(Fig. 8.2a) [21]. In this work, a 3D microchannel buried inside a glass substrate was
employed to analyze the continuous motion of Euglena gracilis. The Euglena gracilis
were confined to a limited volume in the channel but were still able to move freely,
making it much easier to capture images of their movement. These biochips reduced
the required observation time by a factor of greater than 10 compared to conventional
methods using a Petri dish, and front view images of Euglena cell movement were
obtained for the first time. In addition, a microchamber integrated with a movable
microneedle was used to elucidate the information transmission process in Pleurosira laevis. Choudhury et al. demonstrated a 3D mammalian cell separator biochip
fabricated by the FLAE of fused silica [24]. Cell sorting in this device was based on
differences in the deformability of cell types having varying cytoskeletal architectures. Figure 8.2b illustrates the working principle of the biochip, which consisted of
T-junctions formed by two microchannels with narrow constrictions. These constrictions, whose cross-sections were narrower than the average cell size, functioned
as filters for sorting. This overall structure enabled accurate, pressure-driven flow