Journal of Crystal Growth 232 (2001) 591–595 Macromolecular crystallization in a high throughput laboratory}the search phase Joseph R. Luft a, *, Jennifer Wolfley a , Igor Jurisica b , Janice Glasgow c , Suzanne Fortier c , George T. DeTitta a a Hauptman-Woodward Medical Research Institute, 73 High Street, Buffalo, NY 14203-1196, USA b University of Toronto, Toronto, Ontario, Canada c Queen’s University, Kingston, Ontario, Canada Abstract Macromolecular crystallization efforts are frequently divided into a search phase, during which approximate conditions are sought, and an optimization phase, when the approximate conditions are optimized to yield crystals of sufficient quality for diffraction work. Faced with the possibility that, on a yearly basis, many hundreds of proteins might be generated, both in our laboratories and at the laboratories of our collaborators, we have recently designed and commissioned a high throughput robotics lab designed for the search phase. The lab is capable of setting up and photographically evaluating over 60,000 microbatch crystallization experiments per week. In the first four months of operation we have set up crystallization experiments for more than one hundred proteins. # 2001 Elsevier Science B.V. All rights reserved. Keywords: A1. High throughput; A2. Growth from solutions; A2. Microbatch; B1. Biological macromolecules 1. Introduction At the conceptual level macromolecular crystal growth efforts are often divided into two phases. In the search phase approximate conditions for crystal growth are identified. In the optimization stage these conditions are varied to identify those that reproducibly yield high quality crystals for diffraction. Faced with a promise of many hundreds of proteins, some coming from structural biology projects originating in-house and others from structural genomics projects involving out- side collaborators, we have recently focused our attention on the search phase of the process. Our strategy uses information intrinsic to the protein and information generated by microassay tech- nology to predict the basics of any recipe needed for crystallization: what crystallizing agent to use, what pH and temperature to employ, and approximately what concentrations of all solutes to test. Our work blends advances in the wet lab with advances in data storage, retrieval, mining and analysis. Here we will focus on our efforts in the wet lab; our remarks concerning the computa- tional aspects will be limited. Our approach to the search phase is to execute a large number (1536) of microbatch-under-oil *Corresponding author. Tel.: +1-716-856-9600; fax: +1-716-852-6086. E-mail address: luft@hwi.buffalo.edu (J.R. Luft). 0022-0248/01/$-see front matter # 2001 Elsevier Science B.V. All rights reserved. PII:S0022-0248(01)01206-4