Assembly and constraint technology for large arrays of capillaries

Discovering the genetic causes of common diseases may require pan-genomic mutation scanning of all genes in a million people. An increase in throughput of genetic analysis instrumentation by several orders of magnitude is essential to undertake such an ambitious task. To this end, we report on the design, manufacture, and testing of assembly and constraint technologies for arrays containing as many as 10,000 capillaries packed into 1-D rows or 2-D arrays with 1 mm spacing. Capillaries are sealed around their perimeters against pneumatic and hydrodynamic pressures useful for automated capillary array electrophoresis. We show that both ends of the arrayed capillaries are aligned axially to 11 ± 5 μm accuracy and repeatability. Radially, the capillary tips are aligned well enough for insertion into arrays of sample wells and subsequent end-of-capillary fluorescence detection. We have loaded, electrophoresed, and detected 108 to 1010 fluorescently labeled DNA molecules in a 25 capillary sub-array to validate functionality. Using our semi-automated assembly machine, we demonstrate 100 capillary array assembly in 12 min. This array assembly and constraint technology could be incorporated into commercial capillary instruments, and may enable a new generation of ultrahigh throughput instruments with 2-D arrays of 10,000 or more capillaries.