Nanoarray

Moreover, for many of these, the microscopy techniques are not only used for research and development but also for the readout (e.g., confocal microscopes for microarrays) and even for the fabrication (e.g., AFM) of nanoarrays. Also, the continuous miniaturisation of biodevices will eventually reach the desired single molecule detection level—another strong incentive for the general use of advanced microscopy techniques. 

The analysis of biomolecules by AFM is sometimes [3] referred to as surface biology, as opposed to the so-called test-tube biology, because the immobilisation of oligonucleotides on sohd surfaces is central to the design, fabrication and operation of DNA-based microdevices, such as biosensors, DNA micro- and nanoarrays, microPCR and lab-on-a-chip devices. As the analysed biomolecules are in close contact and very often in intimate interaction with the surface, sample preparation for the AFM analysis of surface-immobihsed biomolecules is both critical and dehcate. The biomolecules need to be firmly anchored on the substrate, which has to have a sufficiently minimal or easily discriminated topography [1]. The Kleinschmidt method [6] for the DNA... 

From the point of view of the operation of DNA-based nanodevices, AFM imaging and probing can be used as a readout method for micro/nanoarrays. The first possibility is to expand on the variation of heights of DNA aggregates... 

One promising sfrafegy for detecting analyte binding to nanoarrays is the use of labelled nanoparticle probes, using the striking properties of nanopar-... 

Nicolau DV, Demers LM, Ginger D (2004) Nanoarrays. In Muller U, Nicolau DV (eds) Microarray technology and applications. Chap 6. Springer, Berlin Heidelberg New York... 

Lee, M., et al. (2006) Protein nanoarray on Profinker sirrface constructed by atomic force microscopy dip-pen nanolithography for analysis of protein interaction. Proteomics. 6, 1094-103. 

However, thermoplasmonics has been limited to the use of gold nanoparticles typically dispersed in aqueous media, polymer matrices and cellular systems, but never immobilised as a nanoarray to fabricate a light-responsive substrate for bio-applications. 

Fig. 13 Comparative study of symmetric and asymmetric electroactive nanoarrays for the study of cell adhesion and polarization (a) DPN was used to pattern a SAM nanospot of hydroquinone-terminated alkanethiolates for subsequent RGD immobilization and cell adhesion, (b) Lateral force microscopy image of a symmetric nanoarmy (left) and fluorescent cell having a diffusive nucleus-centrosome-Golgi vector that indicates no preferential migratory direction (right), (c) Cell polarity vectors orient toward the direction of higher RDG density on asymmetric nanoarrays, (d) Higher magnification of the cell polarization vector (above) and its schematic (below). Reproduced from [37, 38] with permission. Copyright The American Chemical Society, 2008...

The next step in miniaturization within proteomics is the development of protein nanoarrays. In nanoarrays of proteins, the size is within an mm2 range, spot size (feature) is 3-1000 nm, and the array density (probes/mm2) is <1 x 106/mm2. There are also some initial studies on attovial arrays, in which the miniaturization of the array components is beyond our imagination (e.g., attovial arrays use 6 (0 200nm) to 4000 aL (0 5 pm) sized vials, at a density of 225 vials/mm2 (tentative densities of 90,000-225,000 vials/mm2) (Wolbers et al. 2006b). 

Wingren, C.h. and Borrebaeck, C.A.K. 2007. Progress in miniaturization of protein arrays—a step closer to high-density nanoarrays. Drug Discovery Today 12(19-20) 813-819. 

DNA templated protein arrays with predictable control at the nanometer scale could lead to single-molecule detection in proteomics studies. Individual proteins placed at unique locations on the nanoarray could be detected with single molecule imaging techniques such as recognition imaging, in which specific antibodies are attached to the scanning probe cantilever. 

Figure 6.2 Transmission electron micrograph of Mn-doped PbSe nanoarrays and In203 nanocrystals, illustrating different morphologies obtainable by controlled precipitation.

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