Methods and apparatus for measuring analytes
Methods and apparatus relating to FET arrays for monitoring chemical and/or biological reactions such as nucleic acid sequencing-by-synthesis reactions. Some methods provided herein relate to improving signal (and also signal to noise ratio) from released hydrogen ions during nucleic acid sequencing reactions.
1. A semiconductor device, comprising:
a sensor array formed in columns and rows, wherein each sensor in the sensor array comprises a two-transistor circuit that includes a chemically-sensitive field effect transistor (chemFET), and a row select transistor;
an array of microwells formed on the sensor array, wherein each microwell is capacitively coupled to at least one sensor;
circuitry for reading each chemFET in the sensor array; and
an analog-to-digital converter (ADC) for each column in the sensor array to convert an analog signal from each chemFET in each column to a digital form that is output from the semiconductor device.
2. The semiconductor device of claim 1 , wherein the circuitry for reading each chemFET in the sensor array includes a row-addressing circuit to provide a row address for each chemFET in the sensor array.
3. The semiconductor device of claim 1 , wherein the sensor array is subdivided into a plurality of sensor array sub-regions; each sensor array sub-region including:
circuitry for reading each chemFET in the sensor array sub-region; and
an ADC for each column in the sensor array sub-region to convert an analog signal from each chemFET in the sensor array sub-region to a digital form.
4. The semiconductor device of claim 3 , wherein the sensor array further comprises a first sensor array sub-region and a second sensor array sub-region.
5. The semiconductor device of claim 4 , wherein the semiconductor device further comprises a multiplexer to provide a single digital output stream.
6. The semiconductor device of claim 1 , wherein each chemFET is coupled to a reference electrode voltage circuit.
7. The semiconductor device of claim 1 , wherein the sensor array comprises at least 6.5 million sensors.
8. The semiconductor device of claim 1 , wherein each chemFET has a first terminal that is coupled to a first readout signal line common to each chemFET of a respective column.
9. The semiconductor device of claim 1 , wherein each chemFET in the sensor array further comprises a floating gate coupled to a chemically-sensitive passivation layer.
10. The semiconductor device of claim 9 , wherein the chemically-sensitive passivation layer is sensitive to ionic species.
11. The semiconductor device of claim 10 , wherein the chemically-sensitive passivation layer is sensitive to hydrogen ion.
12. The semiconductor device of claim 11 , wherein each chemFET in the sensor array has a pH range for measuring change in hydrogen ion concentration from pH 6 to pH 9.5.
13. The semiconductor device of claim 12 , wherein each chemFET in the sensor array has a pH range for measuring change in hydrogen ion concentration from pH 7 to pH 9.
14. The semiconductor device of claim 10 , wherein the chemically-sensitive passivation layer is sensitive to pyrophosphate.
15. The semiconductor device of claim 1 , wherein each microwell has a contiguous sidewall structure and a bottom surface defining each microwell.
16. The semiconductor device of claim 15 , wherein the bottom surface comprises a chemically-sensitive passivation layer coupled to a floating gate.
17. The semiconductor device of claim 16 , wherein the chemically-sensitive passivation layer is sensitive to hydrogen ion.
18. The semiconductor device of claim 16 , wherein the chemically-sensitive passivation layer is sensitive to pyrophosphate.
19. The semiconductor device of claim 15 , wherein the contiguous sidewall structure and the bottom surface defining each microwell includes a buffering inhibitor.