**8. Conclusion and future perspectives**

is refracted when passing through a particle with a refractive index, *n*<sup>2</sup>

an equal and opposite rate of momentum change of the particle, producing a force by Newton's second law due to conservation of momentum. When a particle is placed in a light gradient, the sum of all rays passing through it creates an imbalance in force, pushing the particle toward the region with higher intensity of light. A focus constructs a trap as the strong light gradient points to the center. *Rayleigh* regime governs for bioparticles with dimension far less than the wavelength (*d << λ*), such as protein and nucleic acids. In this regime, the particles are treated as extremely small point dipoles polarized by a uniform electric field, which then interacts with

> <sup>2</sup> *ε*<sup>0</sup> *a* <sup>3</sup> ( *m*<sup>2</sup> \_\_\_\_\_ − 1

\_\_\_\_\_\_\_\_ 3*c* (

\_\_\_\_\_\_ *<sup>c</sup>* (

where *Fscat* is the scattering force, *Fgrad* is the gradient force, *I* is the light intensity, *c* is the speed of light, *k* is the wave number (*k* = 2*π*/*λ*), and *λ* is the wavelength. Trapping is achieved at the

OPT can be created by light emission through a high numerical aperture number (NA) of microscope objective (MO), which focuses light tightly and results in a force along the highest intensity axis, but in the backward direction, which causes the bioparticle to be demobilized,

Favre-Bulle et al. [53] use optical trapping in vivo to manipulate otoliths in larval zebrafish to stimulate the vestibular system. Lateral and medial forces upon the otolith cause complementary corrective tail motion, while lateral force on either otolith causes a rolling correction in both eyes. Fascinating manipulation of blood has been demonstrated by Zhong et al. [54], who perform manipulation of RBCs in vivo, i.e., within subdermal capillaries in living mice, using infrared optical tweezers. They demonstrate the optical trapping and three-dimensional manipulation of single RBC in the capillary, as well as multiple RBC trapping, forming capillary blockage and clearance, by turning on and off the optical tweezer. Pradhan et al. [55] use optical trapping to bring a single cell of neural tumor cell lines into close proximity of another and measure the time required for cell-cell adhesion to form, as this method can be used to assess the differentiation

are refractive indices of the suspending medium and the particle, respec-

*/nm*. The magnitudes of scattering force, *Fscat*, and gradient force, *Fgrad*, based

*m*<sup>2</sup> \_\_\_\_\_ − 1

*m*<sup>2</sup> \_\_\_\_\_ − 1

is the vacuum permittivity, and *m* is the contrast ratio of the

light field. The dipole moment, *pdipole*, induced by a uniform electric field *E*, is given by

the surrounding medium, *n*<sup>1</sup>

96 Microfluidics and Nanofluidics

where *n*1*<sup>m</sup>* and *n*2*<sup>p</sup>*

indices, i.e., *m = np*

tively, *a* is the particle radius, *ε*<sup>0</sup>

*pdipole* = 4*πn*<sup>m</sup>

*Fscat* <sup>=</sup> <sup>8</sup>*πn*<sup>m</sup> *<sup>k</sup>*<sup>4</sup> *<sup>a</sup>* <sup>6</sup>

*Fgrad* <sup>=</sup> <sup>2</sup>*πn*<sup>m</sup> *<sup>a</sup>* <sup>3</sup>

**7.2. Optical tweezing or trapping of bioparticles**

highest intensity axis when *Fgrad* > *Fscat*.

as presented in **Figure 5a**.

on point dipole interaction with light field method are given by

, which is greater than

*<sup>m</sup>*<sup>2</sup> <sup>+</sup> <sup>2</sup>)*<sup>E</sup>* (13)

*<sup>m</sup>*<sup>2</sup> <sup>+</sup> <sup>2</sup>)*<sup>I</sup>* (14)

*<sup>m</sup>*<sup>2</sup> <sup>+</sup> <sup>2</sup>)∇*<sup>I</sup>* (15)

. The rate of the momentum change in the detected rays develops

Manipulation of bioparticles in micro-/nanofluidic, integrated with active manipulation mechanisms, i.e., dielectrophoresis, magnetophoresis, acoustophoresis, thermophoresis, and optical tweezing/trapping, has been discussed in this chapter. Description of the underlying fundamental theory is provided at the beginning, and state-of-the-art implementations into a wide range of bioparticles are carefully introduced. DEP has shown rapid progress into exploration of extremely small bioparticle manipulation, i.e., virus, nucleic acids, and protein. In particular, demonstration of DNA sorting [23] and impedance-based protein capturing [25] prove the potential for nanoscale application, as well as genetic and molecular biology studies. MAG is advantageous in selective manipulation benefited by biofunctionalization of magnetic micro-/ nanoparticle for affinity binding to target bioparticles. Novel achievement in customization of target bioparticle magnetization using predefined multiple layers of magnetic particles [27] is promising for application into heterogeneous suspension manipulation, such as whole blood, progenitor, and cancerous cell detection and sorting. ACT's greatest progress is in the integration with other mechanisms, e.g., DEP, to establish a complete biomedical device [42], showing that transformation from conventional devices to microfluidic biomedical devices which are superfast, precise, and portable is soon to be realized. THM technology particularly is matured enough in extremely small bioparticle manipulation, i.e., protein and nucleic acids, specifically as a measurement tool for binding interaction between molecules. In fact, the recent exploration of thermal gradient-based DNA translocation [50], as well as cell arbitrary manipulation benefited from permittivity gradient in the electric double layer of cell membrane [47], potentially open for new path in THM research. OPT has emerged into in vivo studies [53, 54], indicating that the clinical application is promising and soon to be achieved. In addition, OPT capability in application to genetic and stem cell studies is of high potential, as demonstrated in construction of three-dimensional bioparticle assemblies [55, 56]. Rapid progress of studies on these micro-/nanofluidic active manipulation mechanisms toward bioparticles has a significant impact to biomedical research and technology development. Evolution into high-precision, superfast, and portable miniaturized biomedical devices is pretty soon to be achieved.

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