Review Yang-Wei Lin Ming-Feng Huang Huan-Tsung Chang Department of Chemistry, National Taiwan University, Taipei, Taiwan, R.O.C. Nanomaterials and chip-based nanostructures for capillary electrophoretic separations of DNA Capillary electrophoresis (CE) and microchip capillary electrophoresis (MCE) using polymer solutions are two of the most powerful techniques for the analysis of DNA. Problems, such as the difficulty of filling polymer solution to small separation channels, recovering DNA, and narrow separation size ranges, have put a pressure on developing new techniques for DNA analysis. In this review, we deal with DNA separation using chip-based nanostructures and nanomaterials in CE and MCE. On the basis of the dependence of the mobility of DNA molecules on the size and shape of nanostructures, several unique chip-based devices have been developed for the separation of DNA, particularly for long DNA molecules. Unlike conventional CE and MCE methods, sieving matrices are not required when using nano- structures. Filling extremely low-viscosity nanomaterials in the presence and absence of polymer solutions to small separation channels is an alternative for the separations of DNA from several base pairs (bp) to tens kbp. The advantages and shortages of the use of nanostructured devices and nanomaterials for DNA separation are carefully addressed with respect to speed, resolution, reproducibility, costs, and operation. Keywords: DNA / Microchip capillary electrophoresis / Nanomaterials / Nanostructures / Review DOI 10.1002/elps.200406171 Contents 1 Introduction ............................. 320 2 Chip-based nanostructures for DNA separation .............................. 323 2.1 Surface electrophoresis ................... 323 2.2 Entropy-based separation systems .......... 323 2.3 Obstacle array ........................... 325 2.4 Magnetic self-assembling sieves ............ 326 3 Nanomaterials for DNA separation .......... 326 3.1 Polymer solutions containing nanoparticles . . . 326 3.2 Polymers adsorbed on gold nanoparticles .... 327 3.3 Nanopacking medium .................... 328 4 Conclusions............................. 328 5 References ............................. 329 1 Introduction Rapid, efficient, and sensitive separation techniques are important for DNA analysis. Numerous capillary electro- phoresis (CE)- and microchip capillary electrophoresis (MCE)-based approaches have been tested and validated for DNA sequencing [1, 2], genotyping [3, 4], mutation analysis [5, 6], characterization of single nucleotide poly- morphisms (SNPs) [7, 8], forensic human identification [9, 10], diagnosis of diseases [11, 12], and other applications [13, 14]. When compared to slab-gel electrophoresis, these techniques provide the advantages of comparable resolving power, rapidity, high throughout, minute sample requirement, and ease of integration [10, 15, 16]. Using these techniques, small separation channels/capillaries are often filled with polymer solutions that are advanta- geous over cross-linked gels, including relatively low vis- cosity, ease of preparation, and flexibility. Polymer solu- tions are commonly prepared from linear polymers, including cellulose and its derivatives [17], linear poly- (acrylamide) (LPA) [18], poly(ethylene oxide) (PEO) [19], and poly(vinylpyrrolidone) (PVP) [20]. In order to provide great resolving power for small DNA fragments, the con- centration of a polymer solution is usually higher than its Correspondence: Dr. Huan-Tsung Chang, Department of Chem- istry, NationalTaiwan University, Taipei, Taiwan, R. O. C. E-mail: changht@ntu.edu.tw Fax: 111-886-2-23621963 Abbreviations: GNP , gold nanoparticles; MCE, microchip capil- lary electrophoresis; PDMA, poly(N,N-dimethylacrylamide); PEO, poly(ethylene oxide) 320 Electrophoresis 2005, 26, 320–330  2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim