A method for nucleic acid sequencing comprising: delivering a fluid that contains sequencing reagents to a sequencing chip, wherein the sequencing chip is an integrated analysis chip comprising: an aperture layer comprising an array of reaction cells, wherein each reaction cell in the array of reaction cells is a nanoscale aperture in the aperture layer, a waveguide layer below the aperture layer and comprising one or more waveguides, a transmission layer, and a detector array layer below the transmission layer and comprising an array of detectors, wherein the array of reaction cells are configured to receive the fluid that contains the sequencing reagents; delivering illumination light to the one or more waveguides of the sequencing chip to illuminate the sequencing reagents in the array of reaction cells, thereby generating emission light; transmitting the emission light from the array of reaction cells to the array of detectors, wherein the emission light from a respective reaction cell in the array of reaction cells is directed to a corresponding detector in the array of detectors; converting the emission light received by the array of detectors into electrical data signals; performing pre-processing of the data in the data signals using circuits on the sequencing chip wherein the pre-processing comprises data reduction through signal aggregation or combination of the electrical data signals; and transferring the pre-processed data to a processor off of the sequencing chip for downstream processing, wherein the sequencing chip is integrated such that the emission light from the array of reaction cells is transmitted to the array of detectors without passing through air or free space, wherein the pre-processing comprises refining the electrical data signals into event pulses. delivering a fluid that contains sequencing reagents to a sequencing chip, wherein the sequencing chip is an integrated analysis chip comprising: an aperture layer comprising an array of reaction cells, wherein each reaction cell in the array of reaction cells is a nanoscale aperture in the aperture layer, a waveguide layer below the aperture layer and comprising one or more waveguides, a transmission layer, and a detector array layer below the transmission layer and comprising an array of detectors, wherein the array of reaction cells are configured to receive the fluid that contains the sequencing reagents; an aperture layer comprising an array of reaction cells, wherein each reaction cell in the array of reaction cells is a nanoscale aperture in the aperture layer, a waveguide layer below the aperture layer and comprising one or more waveguides, a transmission layer, and a detector array layer below the transmission layer and comprising an array of detectors, wherein the array of reaction cells are configured to receive the fluid that contains the sequencing reagents; delivering illumination light to the one or more waveguides of the sequencing chip to illuminate the sequencing reagents in the array of reaction cells, thereby generating emission light; transmitting the emission light from the array of reaction cells to the array of detectors, wherein the emission light from a respective reaction cell in the array of reaction cells is directed to a corresponding detector in the array of detectors; converting the emission light received by the array of detectors into electrical data signals; performing pre-processing of the data in the data signals using circuits on the sequencing chip wherein the pre-processing comprises data reduction through signal aggregation or combination of the electrical data signals; and transferring the pre-processed data to a processor off of the sequencing chip for downstream processing, wherein the sequencing chip is integrated such that the emission light from the array of reaction cells is transmitted to the array of detectors without passing through air or free space, wherein the pre-processing comprises refining the electrical data signals into event pulses.