Using sound pulses to solve the crystal-harvesting bottleneck

Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):986-999. doi: 10.1107/S2059798318011506. Epub 2018 Oct 2.

Abstract

Crystal harvesting has proven to be difficult to automate and remains the rate-limiting step for many structure-determination and high-throughput screening projects. This has resulted in crystals being prepared more rapidly than they can be harvested for X-ray data collection. Fourth-generation synchrotrons will support extraordinarily rapid rates of data acquisition, putting further pressure on the crystal-harvesting bottleneck. Here, a simple solution is reported in which crystals can be acoustically harvested from slightly modified MiTeGen In Situ-1 crystallization plates. This technique uses an acoustic pulse to eject each crystal out of its crystallization well, through a short air column and onto a micro-mesh (improving on previous work, which required separately grown crystals to be transferred before harvesting). Crystals can be individually harvested or can be serially combined with a chemical library such as a fragment library.

Keywords: acoustic droplet ejection; automation; crystal harvesting; crystal mounting; crystallography; drug discovery; high-throughput screening; microcrystals.

MeSH terms

  • Acoustics*
  • Crystallization / instrumentation
  • Crystallization / methods*
  • Equipment Design
  • Proteins / chemistry
  • Small Molecule Libraries
  • Specimen Handling / instrumentation
  • Specimen Handling / methods*
  • Synchrotrons
  • Time Factors

Substances

  • Proteins
  • Small Molecule Libraries