A novel approach to design and optimize linear multicapillary arrays (LMCAs) for high-throughput DNA sequencing is proposed. A significant increase in the number of capillary lanes is obtained due to the use of composite insertions alternately placed between working capillaries of the array and a specific combination of refractive indices of the DNA separation matrix, capillary glass, the insertions and a medium which surrounds the capillary array. Theoretical and experimental studies showed that in conjunction with a dual-side laser illumination scheme, the proposed LMCA design allows a simultaneous uniform irradiation of as many as 550 working capillaries.