Precise automated control of fluid volumes inside glass capillaries

A precise automated apparatus for controlling the position of small fluid sample volumes inside glass capillaries has been developed as part of an automated system for handling submicroliter reaction volumes for genomic analysis. The apparatus uses a linear charge-coupled device (CCD) array, dc motor, pneumatic pump, feedback controller, and a digital signal processor (DSP) to detect the menisci and control in real-time the position of fluid in a clear glass capillary with a resolution of 50 /spl mu/m. This information is used to infer fluid volumes and control aspiration and dispensing to within 15 nanoliters depending on the inner diameter of the capillary. A computer simulation was developed to determine the effect of thick- and thin-walled capillaries on the detected signals. This simulation showed that, with a geometry appropriate for the overall automated system, a capillary with an inner diameter greater than 0.6 times the outer diameter is optimal to detect the presence of fluid inside the capillary. Thicker walled glass capillaries may be employed if a focusing lens is placed between the light source and the capillary. This result was verified experimentally.