Manufacturing Oligonucleotide Arrays

Oligonucleotide arrays are produced in a way that is similar to the way computer chips are. We start with a matrix created over a glass substrate. Each cell in the matrix contains a ``chain'' with appropriate chemical properties, and ending with a terminator, a chemical gadget that prevents chain extension. We cover this substrate with a mask, covering some of the cells, but not others. We can then illuminate the substrate. Covered cells are unaffected. In cells that are hit by the light, the bond with the terminator is severed. If we now expose the substrate to a solution containing a nucleotide base, it will form bonds with the non-terminated chains. Thus, some of the cells will now contain this nucleotide. The process can then be repeated with different masks, and for different nucleotides. This way we can insert a specific nucleotide to each cell of the matrix. Figure 11.4 demonstrates the production process.

  

Figure 11.4: Creating DNA chips. 1 and 2: The light removes the terminator from the chains not covered by the mask, creating hydrogen bonds instead. 3: Bonds are formed with a nucleotide base. 4 through 6: The process is repeated with a different base.

It should be mentioned that in practice the process is much more complicated than that. For instance, diffraction can be a problem near the edge of the substrate, and we cannot be sure that the chain binds to the nucleotide that is present in the solution. Another problem is the manufacturing of the masks, which tends to be rather expensive (of course, these costs are amortized for standard chips, but specialized chips are still expensive).