Nanoliter dispensing for uHTS using pin tools.

Miniaturization of assays is an important objective in Ultra-HTS. One of the major obstacles has been to find fluid handling systems capable of reliably and accurately delivering between 2 and 200 nl of test compound to assay plates. New methods of forming pins, placing slots in the pins, and hydrophobic coatings bonded onto the pins solve many of the problems encountered by early pin tools. Unlike other low-volume liquid handlers, these new pin tools provide the ability to transfer approximately 2 nl-5 microl of compounds. These pin tools can also use low-volume source plates (2-10 microl) and achieve an accuracy of better than 5%. This, coupled with the ability to transfer small volumes directly from the compound library to assay plates without an intervening dilution plate, saves reagents, throughput time, and consumables and is, therefore, very cost effective. Pin tool compound transfers in the 2-100 nl range provide a simple method to dilute away from the toxic effect that dimethyl sulfoxide has on some assay target cells. The factors that affect liquid transfers by pin tools are discussed in detail as well as the advantages and limitations of pin tools.