An optical detection system for a microfluidic device and a dry-focus microfluidic device compatible with the compact optical detection system are described. The system includes an LED; means for collimating light emitted by the LED; an aspherical, fused-silica objective lens; means for directing the collimated light through the objective onto a microfluidic device; and means for detecting a fluorescent signal emitted from the microfluidic device. The working distance between the objective and the device allows light from an external LED or laser to be brought in along a diagonal path to illuminate the microfluidic device. The dry-focus microfluidic device includes multiple channels and multiple closed optical alignment marks having curved walls. At least one of the channels is positioned between at least two of the marks. The marks are illuminated for alignment and focusing purposes by light brought in on a diagonal path from an external white LED.