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9.2 Microfluidic system 231

biological applications. Spatial homogeneity of the temperature profile is desirable
in both cases [34].
PCR is widely used in molecular biology to amplify target DNA in vitro [34]. As
well, the generation of temperature gradients to drive droplets is another approach.
Indeed, droplet-based microfluidics is a viable alternative to manage small volumes
(typically a few hundreds of a nanoliter). Generally, thermal regulation has found
application in a wide range of various fields such as the development of efficient
and rapid mixing technics, or the screening of solubility diagrams to study protein
crystallization. The external heating and integrated heating are two ways that heat
diffuses from sources such as microwave or laser, toward the liquid either.

9.2.1.6 Cell washing
Cell and bead washing are the main experimental method which has extensive usage
in biomedical research and biological studies. Cell/bead washing is an essential
sample preparation method used in diverse cell studies and analysis. Advantages of
standing surface acoustic wave (SSAW)-based washing device include label-free
manipulation, simplicity, high biocompatibility, high recovery rate, high washing
efficiency, and compatibility with other on-chip components. It is useful for lab-on-
a-chip applications [35,36].
As well, bead washing has been regularly used in molecular biology and immu-
nology. For example, multiple bead-washing steps are required for reagents changing
when affinity-based DNA purification is performed using QIAEX® beads [37].
Commonly, the centrifugation method is used for cells or beads washing. To over-
come the limitations of centrifugation-based cell washing methods such as low bio-
compatibility and its difficulty for in-line integration, which is necessary to realize
automatic, µTAS, microfluidic technics have been developed to wash cells and beads
in a continuous flow. In order to have more control of the movement of cell/bead
during the washing process, significant efforts have been made to use external forces
to manipulate cells/ beads, leading to the development of several active cell washing
technics [38,39]. External forces such as magnetic forces, dielectrophoretic (DEP)
forces, or acoustic forces are applied to cells/beads flowing in these devices [40].
As a consequence, cells/beads are extracted from their original medium stream and
placed into a wash solution. Of all these methods, acoustic methods offer remarkable
advantages in terms of label-free manipulation, biocompatibility, and versatility.
Recently, SSAWs have been used to accomplish label-free manipulation of vari-
ous micro/nano-objects such as beads, cells, droplets, microorganisms, and nanow-
ires [41,42]. Exclusively, a unique formation of tilted-angle standing surface acoustic
wave (taSSAW) has been introduced that the IDTs are inclined at a specific angle to
the flow direction [43]. In comparison with previous SSAW approaches where the
IDTs are aligned in parallel with the flow direction [44,45].The taSSAW approach
presents a significantly larger lateral displacement for particles. Consequently, cells/
beads can be effectively separated due to differences in size, density, and/or com-
pressibility. The potential application of taSSAW approach has been investigated
in the development of a SSAW-based cell/bead washing device. By optimizing the