DNA for Biosensing Applications

DNA is the genetic material of human and numerous other species closely relevant to our health. It is thus a central material to biosensing, which is the basis for disease diagnosis, prognosis, and treatment. Although various DNA biosensing techniques have been developed, the demand for higher throughput and sensitivity methods is ever increasing. Nanotechnology offers great potential to meet the need by providing unprecedented tools that can precisely detect, manipulate, and assemble DNA.

An ability to retrieve genetic information from single DNA molecules promises to significantly enrich our understanding of many critical biological and pathological processes. Molecular Combing is a technique that can stretch and immobilize genome DNA on a solid surface for single molecule analysis. However, conventional Molecular Combing technique can only generate randomly distributed DNA chains that are not suitable for large scale and automated data acquisition.

Professor Jingjiao Guan and his colleagues from the Integrative NanoScience Institute have developed an approach capable of stretching and patterning DNA molecules into large arrays with each DNA chains precisely positioned and aligned. This technique holds potential to become a new platform for analysis of single DNA in a large-scale and automated fashion.

Fluorescence image of an array of stretched DNA

Not only a biomolecule, DNA is also a nanomaterial with a unique set of structures and properties such as high length-to-width ratio, double helical structure, base pairing ability, and sequence-specific interactions with other molecules. DNA has thus been used to construct nanowires, which are widely regarded as a new class of biosensing structures.

To build a functional sensor, nanowires typically need to be precisely assembled into a designed architecture. Lack of robust and low-cost techniques for nanowire assembly is currently hindering the advance of this field.

Professor Jingjiao Guan and his colleagues have developed a method for generating arrays of DNA-based nanowires. Compared to others, this method is robust, inexpensive, and intrinsically capable of generating highly-ordered over a large area. It also allows functionalization of the nanowires by various methods such as surface coating by vapor deposition, chemical conjugation, and physical entrapment of nanoparticles.

Fluorescence image of an array of DNA (green) nanowires embedded with fluorescent nanocrystal quantum dots (yellow)

Nanochannels constitute another class of nanostructures for next-generation biosensing. They have been demonstrated with unique advantages for probing single DNA dynamics, detecting DNA-protein interactions, mapping genes on single DNA molecules, and separating DNA of different sizes. However, advance of this nanochannel-based biosensing is also hindered by the lack of inexpensive, simple, and reliable approaches for fabricating the nanostructures and integrating them into functional devices.

Professor Jingjiao Guan and his colleagues have developed a technique capable of producing a large array of nanochannels by using the DNA nanowires as templates. This method promises to be used to construct low cost, parallel, and high-throughput sensors for linear analysis of single chromosomal DNA.

Scanning Electron Micrograph of a nanochannel converted from a DNA nanowire

References

• Jingjiao Guan, L. James Lee, Generating highly ordered DNA nanostrand arrays. Proc Natl Acad Sci U S A. 2005, 102, (51), 18321-18325.
• Jingjiao Guan, Bo Yu, L. James Lee, Forming highly ordered arrays of functionalized polymer nanowires by dewetting on micropillars. Adv Mater. 2007, 19, (9), 1212-1217.
• Jingjiao Guan, Nick Ferrell, Bo Yu, Derek Hansford, L. James Lee, Simultaneous generation of hybrid Arrays of micro/nanoparticles and nanowires by dewetting on micropillars. Soft Matter. 2007, 3, 1369-1371.
• C. H. Lin, J. Guan, S. W. Chau, L. J. Lee, Experimental and numerical analysis of DNA nanostrand array formation by molecular combing on microwell-patterned surface. J Phys D: Appl Phys. 2009, 42, (2), 025303.
• Jingjiao Guan, Pouyan E. Boukany, Orin Hemminger, Nan-Rong Chiou, Weibin Zha, Megan Cavanaugh, L. James Lee, Large laterally ordered nanochannel/nanostrand arrays from DNA combing and imprinting, submitted.