Cellular microarray

Fernandes T.G. Diogo M.M. Clark D.S. Dordick J.S. Cabral J. High-throughput cellular microarray platforms Applications in drug discovery, toxicology and stem cell research. Trends in Biotechnology, 2009, 27, 342-349. 

Lee MY, Kumar RA, Sukumaran SM, Hogg MG, Clark DS, Dordick IS. Three-dimensional cellular microarray for high-throughput toxicology assays. Proc. Natl. Acad. Sci. U.S.A. 2008 105 59-63. 

Keywords Microarray DNA microarray Carbohydrate microarray Protein microarray Antibody microarray G protein-coupled receptor microarray Cellular microarray Optical biosensor Resonant waveguide grating biosensor Surface plasmon resonance Dynamic mass redistribution... 

Fig. 2 Common types of microarrays DNA microarray (a), carbohydrate microarray (b), antibody microarray (c), functional protein microarray (d), biomembrane and membrane protein microarray (e), and cellular microarray (f)...

Examples of biomarker assays operating at different levels are given in Table 4.2. The recent development of omics technology should provide strong support to this approach (Box 4.3). Microarray analysis, for instance, can give a time-related sequence of gene responses that relate to the cellular changes of toxicity. 

The ultimate goal of microarray-based expression analysis is to acquire a comprehension of the entire cellular process, in order to exploit and to standardize the multidi-menisional relations between genotype and phenotype. However, an increasingly important parameter, which has not yet been substantially taken into account, is the role of cellular translation. This means that mRNA expression data need to be correlated with the assortment of proteins actually present in the cell. One approach is based on the use of microarrays containing double-stranded DNA probes for the analysis of DNA-protein interaction and, thus, the detection and identification of DNA-binding proteins by means of fluorescence [130] or mass spectrometry analysis [131]. Moreover, substantial efforts are currently under way to develop protein, antibody, or even cell arrays, applicable to the cor-... 

Amundson SA et al. Fluorescent cDNA microarray hybridisation reveals complexity and heterogeneity of cellular geno-toxic stress responses. Oncogene 1999 18 3666-3672. 

Flaim CJ, Chien S, Bhatia SN (2005) An extracellular matrix microarray for probing cellular differentiation. Nat Methods 2 119-125... 

Gusterson BA, Ross DT, Ffeath VJ, Stein T (2005) Basal cytokeratins and their relationship to the cellular origin and functional classification of breast cancer. Breast Cancer Res 7(4) 143 148 Ffsu FD, Nielsen TO, Alkushi A, Dupuis B, Huntsman D, Liu CL, van de Rijn M, Gilks CB (2002) Tissue microarrays are an effective quality assurance tool for diagnostic immunohistochem istry. Mod Pathol 15 1374 1380... 

Expression analysis using DNA microarrays analyzes only the transcriptome it should be mentioned that mRNA abundance in a cell often correlates poorly with the amount of protein synthesized (27). Important regulation takes place at the levels of translation and enzymatic activities. The only effect of a signal transduction pathway that is observed in a gene expression experiment is that at the endpoint of a given pathway. DNA microarrays currently have little value in determining post-translational modifications, which influence the diversity, affinity, function, cellular abundance, and transport of proteins. 

The basal immunological mechanisms are complex but can now be analyzed with refined and more powerful laboratory methods, such as the microarray technique. With the help of this technique, additional information besides that concerning IgE and cytokine levels about the association between adaptive and innate immune response as well as other cellular responses can be gathered (6-8). 

A number of commercial antibody-based microarrays for multiplexed cytokines analysis are now available (Beckman Coulter BD Biosciences Panom-ics Pierce S S Zyomyx and others). Cytokines are essentially biomarkers of cell injury, inflammation, and apoptosis. They are released by cells in culture in response to drug action (Turtinen et al., 2004) or are elevated in serum in various disease states. Moreover, numerous cytokines are involved in cellular response and many serve as dual effectors (Asao and Fu, 2000). As a result, anticytokine microarrays are being evaluated in drug discovery for off-target toxicity testing to replace standard ELISA plate formats. 

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