Libraries of pharmaceutical compounds are typically stored in solvents and frozen in microplates, which consist of 96 or more wells of about 1 ml, each well capable of retaining a distinct compound. In current practice, when the microplates are removed from the storage freezer, the entire microplate with all wells is allowed to thaw in ambient air or water bath, thus permitting extraction of liquid solution from the wells. This results in the thawing of all compounds, even if only one or several were selected for retrieval from that microplate. This process is inefficient as well as damaging to the nonselected compounds that are refrozen. For the present work we consider thawing in an individual well, independent of all other wells in the microplate, which is surrounded by a metallic sleeve; this effects time-dependent, radial heat transfer from the sleeve to the frozen compound. Partial differential equations are formulated to describe the phase-change thawing process. Regimes of the process are identified as solid-sensible, latent, and liquid-sensible. Semi-analytical solutions are obtained which indicate rapid thawing for a specified, safe sleeve temperature. The thermal system is investigated experimentally for a well containing frozen DMSO. A typical sleeve in thermal contact with the well is fitted with a heater and thermal sensor, and digital feedback control is achieved using a PID algorithm in conjunction with a P/C computer and A/D conversion. Experimental results are found to agree with theory for the conditions tested. It is concluded that the use of thermal sleeves greatly enhances the rate of thawing of compounds in microplates, and that individual wells can be safely and gently thawed independent of other wells in the plate.

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