Integrated analytical system and method
An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed.
1. A method for nucleic acid sequencing comprising:
delivering sequencing reagents onto a sequencing chip having at least 10,000 analytical devices, each analytical device having a reaction cell, optical elements, one or more detection elements that detect light emitted from the reaction cell and convert the detected light into electrical data signals, and waveguides that deliver illumination light to the reaction cells, wherein the reaction cell, waveguides, optical elements, and detection elements, are pre-aligned and locked in during manufacturing of the sequencing chip and there is no substantial open or free space between the reaction cell, waveguides, optical elements, and detection elements;
delivering illumination light to the waveguides of the sequencing chip;
detecting the emitted light from the reaction cells using the detection elements while sequencing reactions are occurring within the reaction cells;
converting the detected light into electrical data signals using the detection elements; and
transferring the electrical data signals through electrical connections on the sequencing chip to a processor to process the electrical data signals.
2. The method of claim 1 , wherein the reaction cell comprises a zero mode waveguide.
3. The method of claim 1 , wherein the sequencing chip further comprises circuitry for refining the electrical data signals from the analytical devices into event pulses.
4. The method of claim 3 , wherein the event pulses comprise information including temporal onset and offset times and signal strengths.
5. The method of claim 3 , further comprising:
processing, using the processor, the electrical data signals, wherein the processing comprises data reduction, digitization, buffer storage, or bus arbitration.
6. The method of claim 1 , wherein the sequencing reactions occurring in the reaction cells are asynchronous, and circuits on the sequencing chip align these random events to a system clock whereby the data that is transmitted off of the chip is read off in a synchronous manner.
7. The instrument of claim 1 , wherein the sequencing chip has at least a million analytical devices.
8. The method of claim 1 , wherein the electrical data signals from the sequencing chip comprise data from single molecule real time sequencing.
9. The method of claim 1 , wherein the sequencing chip comprises a silicon chip.
10. The method of claim 1 , wherein the sequencing chip is produced by forming stacks on top of a silicon chip that comprises the detection elements.
11. The method of claim 1 , wherein each reaction cell is associated with a single detection element.
12. The method of claim 1 , wherein each reaction cell is associated with two detection elements, each associated with a different color filter to allocate spectrally different signals to each element.
13. The method of claim 1 , wherein each reaction cell is associated with four detection elements, each associated with a different color filter to allocate spectrally different signals to each element.
14. The method of claim 1 , wherein the detection elements are CMOS sensors.