Microlytic offers numerous products to support the crystallization of protein in the modern structural biology laboratory. Whether the method of choice is vapor diffusion or diffusive mixing-based crystallization, our consumables and devices can increase the success while improving the efficiency of any crystallization workflow.

 

Our crystallization products are:

  • made by crystallographers for crystallographers
  • unique among commercial crystallization consumables
  • developed to address specific areas of need in the structural biology market and provide ultimate flexibility
  • independently validated through collaborative efforts in industrial and academic laboratories
  • complemented by the highest commitment to customer service and support

 

 

The Ultimate First Pass Crystallization Strategy

The cost of determining protein structures at atomic resolution is high – even in the most efficient and high-throughput of pipelines.  With estimates ranging from tens of thousands to millions of dollars and some projects spanning decade of personal investment, improvements at every experimental stage can offer tremendous savings and expedite essential research.  At the heart of each project lies the crystalline protein form – obtained via diligent, but apparently stochastic sampling of libraries of chemical mixtures. Despite the development of new crystallization reagents and the automation of crystallization trials, overall success rates remain low.

 

The Microlytic approach to crystal screening is a marriage of high throughput and high output crystallization methods, maximizing coverage of crystallization space in automatable, efficient formats to minimize sample consumption and maximize crystallization returns. We accomplish this through parallel screening of each crystallization target using the Crystal Former and MCSG crystallization suite.

 

What is high output screening?

Exemplified by the Microlytic SBS High Throughput Crystal Former, high output crystallization experiments are trials in which the number of crystallization events is generally large relative to conventional experiments. Such systems explore a much greater area of crystallization space with fewer discrete crystallization conditions and low protein consumption. As offered by the Crystal Former, ideal high output crystallization platforms also feature:

  • Systematic screening for which the output is easy to interpret and highly informative, even in the absence of crystals;
  • Non-redundant exploration of crystallization space;
  •  Easy integration into all structural biology platforms, including cross-platform robotic compatibility.

 

 

How does the Crystal Former return high output crystallization data?

The Crystal Former comprises 96 U-shaped channels in which protein crystallization is driven by liquid-liquid diffusion. The protein sample is first loaded into the channel, which fills only by capillary action. The crystallization reagent is then loaded into the opposing inlet. Equilibration of these solutions occurs through diffusion within the microchannels, during which a complex gradient of all the mixture components is transiently established. Through this gradient, the behavior of the protein target is explored with infinite sampling. This continuous exploration of crystallization space for a discrete condition is virtually impossible to capture in other crystallization formats and returns a tremendous amount of information on a per-trial basis, allowing the user to observe all possible experimental outcomes in a single microchannel.  

 

How can Microlytic screens improve my current vapor diffusion pipeline?

The last two decades have seen a rapid expansion in the number of commercially available screens, each with distinguishing design rationales.  In most laboratories, multiple crystallization screens are kept on hand without a clearly defined workflow to establish the order in which screens should be used, guidance in differences of design rational or coverage of crystallization space, and without an easy reference to determine the level of redundancy between two reagent sets.  As a result, much of the crystallization screening becomes highly redundant, increasing the protein requirements without a commensurate increase in crystallization outcome. 

To support preferred vapor diffusion workflows, we introduced the MCSG Crystallization Suite, developed at the Midwest Center for Structural Genomics at Argonne National Laboratories through Phases I and II of the Protein Structure Initiative.  The MCSG Suite has been developed as a single, comprehensive set of crystallization conditions to be used in a standalone manner. The Suite features:

  • 384 non-redundant conditions, ranked in order of productivity, as scored over 10 years of crystallization screening at the MCSG Crystallization Core; 
  • Sampling from more than 15 commercially available crystallization screens
  • Crystallization success in the MCSG pipeline for ALL included crystallization conditions
  • Broader chemical diversity than other commercially-available suites
  • Data generated for targets from more than 100 distinct organisms, including both prokaryotic and eukaryotic sources

 

The end result is the best, first-pass screening suite possible, with:

  • data-driven selection of individual conditions ensuring that conditions with high productivity potential were not accidentally excluded
  • superior organization
  • the broadest coverage of crystallization space within a reasonable number of starting conditions for maximal efficiency while maintaining applicability for more unique and difficult targets.

 

Why use both the Crystal Former and the MCSG Crystallization Suite?

A well-designed first pass screening approach that covers the maximal area of crystallization space while minimizing protein consumption is an essential component of any crystallographic project, be it academic or industrial. Due to unique equilibration kinetics of each method, optimzal amount of screening in both formats in parallel will result in a more thorough coverage of crystallization space than a larger amount of screening in a single format. Covering 4 x 96 conditions of MCSG sceen by vapor diffusion and just 96 conditions in the Crystal Former by liquid-liquid diffusion is the most comprehensive yet economical screening approach.

 

Our value proposition to you is an approach that marries high throughput with high output crystallization to maximize crystallization returns.