Automated fluid mixing in glass capillaries

Abstract

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.

Experimental study and nonlinear dynamic analysis of time-periodic micro chaotic mixers

“…One way to achieve this linking is to mix a DNA solution with DNA probes and examine their reaction. Mixing in conventional laboratories is usually performed by either manually shaking, tapping the test tube followed by centrifuging, or mixing using a stirrer (Evensen et al, 1998). However, these conventional mixing methods are difficult, if not impossible, to implement in miniaturized systems.…”

“…Miyake et al (1993) designed a double-layered micro mixer, in which 400-micron-diameter nozzles were fabricated to provide micro-plumes, which could increase the surface contact area for faster mixing. Evensen et al (1998) designed a mixer driven by a piezo-ceramic actuator such that fluids, e.g., λ-DNA, were perturbed periodically in a glass capillary. They reported no apparent shear breakage of the DNA after mixing by testing with agarose gel electrophoresis.…”

Electromagnetophoretic Micro-convection around a Droplet in a Capillary

“…4 To develop electromagnetophoretic applications more extensively to various microscale systems, it will be crucially important to investigate in detail the phenomena of the electromagnetophoretic convection of the medium. Any study of the convection of a liquid in micro-systems will have a more important meaning as a novel technique of micro-mixing, since it has been widely studied as a bottle-neck technique in μTAS, 11 lab-on-a-chip, 12,13 capillary systems, [14][15][16] and many microchannel methods. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Some reviews have also been reported concerning effective mixing in microchannels 34,35 and in small-scale production.…”

Automated microfluidics for genomics

“…Mixing of reagents can take from 3 to 15 seconds depending on the volumes and viscosities of the fluids being mixed [7]. Thus, in the ACAPELLA-5K system, mixing has been parallelized; mixing can occur while a capillary is held in an aspirator/mixer chuck and moved through three stations or up to 17.28 seconds (see Figure 3).…”

“…The fluid is aspirated or moved back and forth by air volume displacement driven by the piezoelectric actuator. (see [7] for a model of a version of this device).…”