Abstract: A hand-held bioanalytic instrument is described that can perform massively parallel sample analysis including single-molecule gene sequencing. The instrument includes a pulsed optical source that produces ultrashort excitation pulses and a compact beam-steering assembly. The beam-steering assembly provides automated alignment of excitation pulses to an interchangeable bio-optoelectronic chip that contains tens of thousands of reaction chambers or more. The optical source, beam-steering assembly, bio-optoelectronic chip, and coupling optics register to an alignment structure in the instrument that can form at least one wall of an enclosure and dissipate heat.