**4.2. Magnetophoretic manipulation of bioparticles**

trapping, while long rectangular light bar is used to attract other untargeted cells. Adams et al. [21] perform sorting of neural stem and progenitor cells using microfluidic DEP device. The sorting is based on the cell membrane capacitance variation, which specifically determines the future forming cells, either neuron or astrocyte. Bacteria manipulation using DEP microfluidic device is shown by D'Amico et al. [14], in which they isolate and enrich *Escherichia coli* (*E. coli*) which spiked into whole blood sample. The device integrates membraneless dialysis process and dielectrophoretic trapping, presented in **Figure 1b**. Ding et al. [22] demonstrate the capture and enrich of *Sindbis* virus in a gradient insulator-based DEP microfluidic device, i.e., electric signal source is applied across both microchannel ends while insulating polydimethylsiloxane (PDMS) used to distort electric field, hence forming a nonuniform electric field. By tuning the voltage of applied signal, they can capture or release the virus from the saw-shaped electrode tip. Nucleic acid manipulation has been conducted by Jones et al. [23], in which they perform size-based sorting of a wide range of nucleic acid analytes, i.e., 1.0, 10.2, 19.5, and 48.5 kbp double-stranded DNA (dsDNA) analytes, including both plasmid and genomic DNA in a continuous flow microfluidic platform, by using an insulator-based DEP to tune the deflection of the nucleic acids. Viefhues et al. [24] perform dielectrophoretic mobility shift assay of DNA complexes as well as pure DNA in a nanofluidic DEP system to demonstrate new technique in detection of different DNA variants, including protein-DNA complexes. Manipulation of proteins has been achieved by Mohamad et al. [25]. They use DEP to capture and characterize the electrical properties of colloidal protein molecule, i.e., bovine serum albumin (BSA), based on the molecule dispersion impedance exhibited at particular frequencies, which are influenced by the electrical double layer surrounding the molecule. Liao et al. [26] developed a DEP nanofluidic device to perform selective pre-concentration of functional proteins within bio-fluid medium, which in general is a high ionic strength medium. The device is advantageous in the enhancement of DEP trapping forces against electrothermal flow which is chal-

Magnetophoresis (MAG) is the motion of particles under the influence of a nonuniform magnetic field, as the particles being magnetized cause them to be attracted toward the regions of high magnetic flux density or repelled away [8]. Magnetic field is generated by either a

is the free space permeability [8].

(*B* ∙ ∇)*B* (7)

and *χm* are the magnetic sus-

is the particle volume, *B* is the

lenging in nanoscale device design.

permanent magnet or an electromagnetic coil.

*FMAG* <sup>=</sup> (*χ<sup>p</sup>* <sup>−</sup> *<sup>χ</sup>m*) *Vp* \_\_\_\_\_\_\_\_ *<sup>μ</sup>*<sup>0</sup>

Magnetophoretic force experienced by a particle is governed by

where *FMAG* is the effective magnetic force upon the particle; *χ<sup>p</sup>*

ceptibility of the particle and the medium, respectively; *Vp*

**4. Magnetophoresis**

88 Microfluidics and Nanofluidics

**4.1. Fundamentals of MAG**

magnetic flux density, and *μ*<sup>0</sup>

Lee et al. [27] magnetically functionalize living yeast cells, *Saccharomyces cerevisiae* (*S. cerevisiae*), as micro-magnets, by performing coating of several groups of them with different thicknesses of magnetic silica film (single layer up to seven layers), to control the magnetization degree of the cells as shown in **Figure 2b**. By doing so, multiple subgroups are being formed which can be manipulated independently in the pool of heterogeneous cell mixtures. Magnetophoretic separation of erythrocytes, i.e., maturing RBCs from the mixture with reticulocytes and immature RBCs, in hematopoietic stem cell (HSC) culture, has been performed by Jin et al. [30]. They exploit the paramagnetic property of deoxygenated hemoglobin of maturing erythrocytes compared to reticulocyte which is diamagnetic for the MAG-based separation. Jack et al. [31] demonstrate immunomagnetic isolation of diverse groups of magnetic bead-labeled tumor cells (with different levels of labeling), based on the surface protein expressions. The sample is introduced to multiple levels of magnetic sorter according to the adjustment of external permanent magnet distance to flowing magnetic-labeled cells, resulting in separation of the cells according to their epithelial cell adhesion molecule (EpCAM) levels into low, moderate, and high expression. Bacteria manipulation using MAG has been achieved by Wang et al. [32], who demonstrate the trapping of *Bacillus megaterium*, which are nonmagnetic bioparticles in a ferrofluid suspension while experiencing uniform external magnetic field. The sample continuously flows in a microfluidic channel with nonmagnetic island located in the middle of the channel. Due to the magnetic susceptibility difference between the island and the surrounding ferrofluid, the nonmagnetic bacteria experience magnetophoretic force and, thus attract the bacteria to the island, while the ferrimagnetic particle which comprises the ferrofluid is also attracted to the island; however, the bacteria and the magnetic particles are accumulated at different regions. Wang et al. [33] perform magnetophoretic concentration of avian influenza virus (H5N1) in continuous flow microfluidic system. The H5N1 magnetic nanoparticle complexes are formed using aptamerbiotin-streptavidin binding and injected to three-dimensionally printed magnetophoretic platform which experiences magnetic field from external neodymium magnets, to migrate the complexes from the original sample flow to phosphate-buffered saline carrier flow. Shim et al. [34] demonstrate the magnetophoretic capture of DNA-conjugated magnetic particles in microfluidic device by short-range magnetic field gradient exerted by micro-patterned nickel array on the bottom surface of the separation channel, as well as enhancement with oppositely oriented array of external permanent magnet for a long-range magnetic field gradient at the interfaces between magnets. The DNA is then collected by performing detachment from the captured DNA magnetic particle conjugates by enzymatic reaction with uracil-specific excision reagent enzyme. Magnetophoretic manipulation of protein has been achieved by Lim et al. [35] in which manipulation of Atto-520 biotin-streptavidin-magnetic particle conjugates is demonstrated. The magnetic force is applied by external rotating magnetic field, while soft permalloy (Ni80Fe20) magnetic tracks composed of radii and spiral tracks, known as spider web network, are patterned underneath the manipulation plane. The structure facilitates the directional transportation of magnetic particles, which is of potential application as biomolecule cargo, to the desired path, either converging to the spider web center or dispersing away, according to the external rotating magnetic field, i.e., clockwise or counterclockwise.

**5.1. Fundamentals of ACT**

number (2*πflc*<sup>0</sup>

where *ρ<sup>p</sup>*

2016 American Chemical Society).

Acoustophoretic force, *FACT*, experienced by a particle is determined by.

), and *ϕ* is the acoustic contrast factor [9].

erned by the sign of the acoustic contrast factor, *ϕ*, given by

*<sup>ϕ</sup>* <sup>=</sup> *<sup>ρ</sup><sup>p</sup>* <sup>+</sup> \_\_2

antinode, and it is called as negative ACT (nACT).

where *FACT* is the acoustic radiation force, *EACT* is the acoustic energy density, *a* is the particle radius, *x* is the distance from pressure antinode in the wave propagation axis, *k* is the wave

The direction of the particle motion, either toward the pressure node or the antinode, is gov-

3(*ρ<sup>p</sup>* <sup>−</sup> *<sup>ρ</sup>m*) \_\_\_\_\_\_\_\_\_\_ <sup>2</sup> *<sup>ρ</sup><sup>p</sup>* <sup>+</sup> *<sup>ρ</sup><sup>m</sup>*

and *ρm* are the density of the particle and medium, respectively, while *cp*

the speed of sound within the particle and medium, respectively. As shown in **Figure 3a**, for a condition with positive acoustic contrast factor (*ϕ*>0), the particles are pushed toward the pressure node, and the phenomenon is known as positive ACT (pACT). In contrast, for a negative acoustic contrast factor condition (*ϕ*<0), the particles are pushed toward the pressure

**Figure 3.** (a) Acoustophoresis. (Left) Bioparticles are randomly dispersed in the suspending medium without the presence of acoustic radiation pressure. (Right) Bioparticles experience acoustic radiation pressure when SAW transducer is turned on. Bioparticles A (purple) are pushed toward the pressure node due to positive acoustic pressure contrast (*φ<sup>A</sup>* > 0). Bioparticles B (yellow) which experience the opposite (*φ<sup>B</sup>* < 0) are pushed toward the pressure antinodes (Reprinted with permission from Md Ali et al. [13]. Copyright 2016 Royal Society of Chemistry). (b) Manipulation of bacteria in blood by acoustophoresis. Separation of bacteria from RBCs is performed by acoustic separation chip. Bacteria enrichment from blood plasma is performed subsequently at acoustic trapping capillary before the release for detection and identification by dry-reagent PCR chips (Reprinted with permission from Ohlsson et al. [38]. Copyright

− \_\_1 3 *ρ*<sup>m</sup> *c*<sup>m</sup> 2 \_\_\_\_*ρ<sup>p</sup> cp*

*FACT = 4πa3 EACT ksin(2kx)ϕ* (8)

Biological Particle Control and Separation using Active Forces in Microfluidic Environments

<sup>2</sup> (9)

http://dx.doi.org/10.5772/intechopen.75714

and *c*<sup>0</sup>

are

91
