14.8 Supplementary reading [DNA top]

Several excellent texts on polymer dynamics, including Flory’s [149], Doi’s [156, 66] and deGennes’ texts [148], provide a useful background. Doi [66], in particular, provides relations for polymer mobility matrices and partition functions, facilitating more detailed analysis of several of the concepts presented in this chapter. The classical models for linear polymers are treated in all of these texts, albeit with a different approach as compared to this chapter; readers will benefit from experiencing both approaches. Rubinstein and Colby [10] provide an accessible introduction with derivations of many relations and descriptions of experimental techniques for measuring . The physics of random walk processes is largely ignored in this chapter but is fundamental to most descriptions of polymer properties and dynamics; Refs. [10, 7] discuss these processes.

Sincecountless bioanalytical techniques (including Sangersequencing, as described in Section 14.6.2) use DNA separations, separations require DNA transport properties that are dependent on intrinsic DNA properties. DNA diffusivity varies with DNA contour length, but that is generally a difficult property to use for separation. Electrophoretic mobility, on the other hand, is relatively straightforward to employ for separations (see Chapter 12) but varies with DNA length only for small DNA molecules. Consequently, bulk electrophoretic separations for DNA are rare.

Because of the relative insensitivity of bulk electrophoretic mobility to contour length, DNA separations on molecules with more than approximately 200 base pairs are instead performed in gels made of agarose or polyacrylamide. The molecular structure of the gel forces the DNA to travel through the interstitial spaces between gel molecules, resulting in an electrophoretic mobility that is dependent on DNA size.

Gel electrophoresis separation of DNA is a workhorse technique that has been widely successful experimentally. Analytically, the process of predicting DNA mobility in gels has been a difficult one, owing to the confluence of (a) the irregular structure inherent in gels, (b) complex and interdependent physical phenomena, and (c) the dearth of experimental data resolving DNA conformation and transport with base pair resolution. A thorough review of the work and modeling in this area is provided in [151]. Since the dependence of the electrophoretic mobility on DNA contour length is complicated, most experiments are performed using simultaneous calibration samples with known contour lengths.

The recent growth of nanofluidic devices and their impact on study of DNA physics has led to an explosion of work on the physics of DNA, a small subset of which can be found at [143, 144, 157, 158, 142, 159].

DNA separation in micro/nanofluidic structures and gels has been summarized in a number of reviews, for example from a polymer dynamics point of view in [151] and from a system integration standpoint in [152]. A number of nanofluidic DNA separation and analysis applications are discussed in Edel and de Mello’s text [160] and some examples of note include [150, 153, 154].

DNA’s biochemical properties are discussed in [161].

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