ABSTRACT

Current microarray technology produces spots ~100 μm in di ameter, with a spacing of 300-400 μm. Reading of the assay results are based mostly on fluorescence; thus detection is done using a microscope objective with a typical viewfield ~1.5 mm in diameter. The spot size and spacing lead to imaging of only ~9 spots simultaneously in one such viewfield; therefore, the microarray is rasterscanned in front of the objective to allow collection of the whole array image. Scanning is performed over several centimeters in the horizontal directions. However, the Z (vertical) direction must be controlled with micrometer precision in order to avoid defocusing of the sample. To achieve this precision, large and complex machines-scanners-are employed, which use high precision robotic components. This fact makes scanners heavy, large, and expensive and thus not portable. Miniaturization of the active spots by two or three orders of magnitude would allow the observation of an array consisting of hundreds of spots in one view field, thus avoiding the need for large scanning machines. This alone can reduce considerably the biochip’s basic investment and constitutes a big step toward portable chips.Nanoarrays will furthermore reduce the amount of biomaterials used as capture molecules (which constitute a disproportionately large component of a biochip’s cost) and thus reduce the biochip’s production price. Moreover, since the reactions take place in small volumes, mass (and heat) transfer durations are dramatically reduced, leading to shortening of the incubation. This will lead to more rapid diagnostics [4].Due to these considerations, there is a search for the most practical way to fabricate nanostructures of biological molecules, using several nanolithography techniques explained later. 52.4 Nanolithography

Lithography can be classified in a number of ways: (1) Positive/negative: Positive lithography involves deposition of materials that accumulate on the surface. Negative lithography is the removal of material or the creating of depressions in the surface.