Protein crystallization screening and optimization droplet actuators, systems and methods

A droplet actuator system comprising:

• a computer processor electronically coupled to a screening droplet actuator;
• one or more input devices electronically coupled to the computer processor;
• one or more output devices electronically coupled to the computer processor;
• and
• a screening droplet actuator comprising:
• (a) a port for introduction of one or more crystallization reagents and/or one or more protein solutions;
• (b) a substrate in fluid communication with the port, the substrate comprising:
• (i) an array of two or more mixing wells;
• and
• (ii) electric field mediated microfluidics for moving droplets by electrowetting comprising the crystallization reagents and protein solutions into the mixing wells;
• (c) one or more dispensing wells comprising protein sample loaded therein;
• and
• (d) one or more dispensing wells comprising crystallization reagents loaded therein;
• and
• wherein the system is programmed to execute steps mediated by the electric field microfluidics comprising conducting droplet operations on the substrate to:
• (a) produce sample droplets and crystallization reagent droplets;
• and
• (b) combine sample droplets and crystallization reagent droplets into two or more of the mixing wells to produce a unique crystallization condition in each of the two or more mixing wells.

A droplet actuator system comprising:

• a computer processor electronically coupled to a screening droplet actuator;
• one or more input devices electronically coupled to the computer processor;
• one or more output devices electronically coupled to the computer processor;
• and
• a screening droplet actuator comprising:
• (a) a port for introduction of one or more crystallization reagents and/or one or more protein solutions;
• (b) a substrate in fluid communication with the port, the substrate comprising:
• (i) an array of two or more mixing wells;
• and
• (ii) electric field mediated microfluidics for moving droplets by electrowetting comprising the crystallization reagents and protein solutions into the mixing wells;
• (c) one or more dispensing wells comprising protein solution loaded therein;
• and
• (d) one or more mixing wells comprising crystallization reagents loaded therein, said crystallization reagents representing multiple crystallization conditions;
• and
• wherein the system is programmed to execute steps by electrowetting on the substrate, the steps comprising:
• (a) dispensing one or more sample droplets from the protein solution from the one or more dispensing wells;
• and
• (b) transporting at least a portion of the dispensed sample droplets to the mixing wells, wherein at least a portion of the mixing wells each receives one or more of the sample droplets, thereby yielding an array of crystallization droplets comprising protein sample and having the capacity to yield one or more protein crystals.

A droplet actuator system comprising:

• a computer processor electronically coupled to a screening droplet actuator;
• one or more input devices electronically coupled to the computer processor;
• one or more output devices electronically coupled to the computer processor;
• and
• a screening droplet actuator comprising:
• (a) a port for introduction of one or more crystallization reagents and/or one or more protein solutions;
• (b) a substrate in fluid communication with the port, the substrate comprising:
• (i) an array of two or more mixing wells;
• and
• (ii) electric field mediated microfluidics for moving droplets comprising the crystallization reagents and protein solutions into the mixing wells;
• wherein the system is programmed to separate by electrowetting on the substrate a protein solution sample into multiple protein solution sample droplets and move, using droplet operations, each of the protein solution sample droplets to a mixing well where it is combined with a pre-loaded crystallization reagent to yield a sample potentially comprising one or more crystals.