Automated fluid mixing in glass capillaries

A fast method and compact device for mixing sub-microliter fluid samples contained in glass capillaries is presented. The fluid is rapidly moved back and forth by air volume displacement driven by a piezo-ceramic actuator. Rapid mixing of different fluids is achieved via diffusion between the main fluid volume in the capillary and the thin fluid film it deposits on the capillary wall through its motion. Bubbles in the fluid are processed out of the capillary by use of an asymmetric velocity profile. A simple analysis model is used to optimize the design of the device and to elucidate the mechanisms involved in mixing. The mixing time is found to be inversely proportional to the fraction of the fluid volume that is left in the film layer for each cycle, which is determined by the wetting properties and the viscosity. The mixing time is therefore controlled by the dead-air volume of the system, the fluid volume, the capillary size, and the displacement limits of the piezo-ceramic actuator, in addition to the intrinsic properties of the fluid being mixed. The device described can mix two 1 μl water solutions in under 3 s. The possible shear breakage of DNA in solution is investigated, and λ-DNA is found to remain intact at aggressive mixing parameters. No evidence of aerosol contamination in polymerase chain reaction reactions was found to date.