A fast method and compact device for mixing sub-microliter fluid sampl
es contained in glass capillaries is presented. The fluid is rapidly m
oved back and forth by air volume displacement driven by a piezo-ceram
ic actuator. Rapid mixing of different fluids is achieved via diffusio
n between the main fluid volume in the capillary and the thin fluid fi
lm it deposits on the capillary wall through its motion. Bubbles in th
e fluid are processed out of the capillary by use of an asymmetric vel
ocity 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 t
he fluid volume that is left in the film layer for each cycle, which i
s determined by the wetting properties and the viscosity. The mixing t
ime is therefore controlled by the dead-air volume of the system, the
fluid volume, the capillary size, and the displacement limits of the p
iezo-ceramic actuator, in addition to the intrinsic properties of the
fluid being mixed. The device described can mix two 1 mu l water solut
ions in under 3 s. The possible shear breakage of DNA in solution is i
nvestigated, and lambda-DNA is found to remain intact at aggressive mi
xing parameters. No evidence of aerosol contamination in polymerase ch
ain reaction reactions was found to date. (C) 1998 American Institute
of Physics.