Although this is an auxiliary tool in forensics, thin layer chromatography can be used to compare inks used in pens. We don’t know for certain whether Zodiac used the same blue felt pen throughout, used each until they ran out or had several pens, but using thin layer chromatography (TLC) comparisons can be made between individual pens and batches of pens.

Samples of the ink are placed on an absorbent paper near its base and the papers edge and dipped in a solvent. The capillary action separates the ink into its constituent colors, in a banding not unlike DNA and denotes a particular type of ink or pen.
Unfortunately with this method the ink would have to be dissolved back into solution to test, in part destroying the part being tested.

If the aim was to determine whether writing was made by a specific pen, both samples should be run on the same plate and then they can be compared directly. However, caution must be taken when making conclusions about the results. While if the two samples do not produce matching bands that means that the note was not written using that pen, if the bands do match this means that the note could have been written using that pen. Due to the number of pens produced that will contain the same ink it is not possible to say conclusively from this single test that one specific pen was used to write a note. However, if this result is combined with others suggesting the same thing, it will lend weight to the argument that it is likely that the pen was used to write the note. http://the-gist.org/2011/07/tlc-the-forensic-way/

If the Zodiac used a limited number of pens, a direct comparison of pen ink could be made between verified Zodiac letters and dubious letters. Certain researchers have questioned letters beyond the Debut of Zodiac letter. If a direct comparison can be made claims such as these could finally be put to rest. I believe there are 9,500 ink types on the database.