Integrated sensor arrays for biological and chemical analysis
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:
an array of chemically-sensitive field effect transistor (chemFET) sensors; each chemFET sensor including a floating gate conductor having an upper surface, wherein the array of chemFET sensors comprises between 10{circumflex over ( )}5 to 10{circumflex over ( )}9 sensors;
an array of microwells formed over the array of chemFET sensors; each microwell in the array of microwells capacitively coupled to at least one chemFET sensor in the array of chemFET sensors and comprising an opening to a reaction region bounded by sidewalls; and
a sensing layer formed over the upper surface of the floating gate conductor, the sensing layer forming a bottom of each microwell of the array of microwells, wherein the sensing layer has a pH sensitivity of between about 40 mV/pH to about 60 mV/pH.
2. The semiconductor device of claim 1 , wherein a body connection of each chemFET sensor in the array of chemFET sensors is to a common body bias voltage.
3. The semiconductor device of claim 1 , wherein the array of chemFET sensors is an array of ion-sensitive field effect transistor (ISFET) sensors.
4. The semiconductor device of claim 3 , wherein the sensing layer is sensitive to hydrogen ions.
5. The semiconductor device of claim 4 , wherein the sensing layer is sensitive to hydrogen ions in a range of pH 6 to pH 9.5.
6. The semiconductor device of claim 3 , wherein the sensing layer is sensitive to pyrophosphate ions.
7. The semiconductor device of claim 1 , wherein the sensing layer comprises a metal, a metal oxide, a metal nitride or a metal oxynitride, and combinations thereof.
8. The semiconductor device of claim 7 , wherein the metal comprises aluminum, zirconium, titanium, tantalum, molybdenum, hafnium or tungsten.
9. The semiconductor device of claim 7 , wherein a native oxide is formed on the metal comprising the sensing layer.
10. The semiconductor device of claim 9 , wherein the native oxide is formed on a metal comprising aluminum, zirconium, titanium, tantalum, molybdenum, hafnium or tungsten, and combinations thereof.
11. The semiconductor device of claim 10 , wherein the native oxide formed on the metal oxide is formed on a metal layer formed on the sidewalls and bottom each microwell.
12. The semiconductor device of claim 7 , wherein the sensing layer comprises a mixture of at least two metals.
13. An apparatus comprising:
a semiconductor device comprising:
an array of chemically-sensitive field effect transistor (chemFET) sensors, wherein the array of chemFET sensors comprises between 10{circumflex over ( )}5 to 10{circumflex over ( )}9 sensors;
an array of microwells formed over the array of chemFET sensors; each microwell in the array of microwells capacitively coupled to at least one chemFET sensor in the array of chemFET sensors; each microwell in the array of microwells comprising an opening to a reaction region; and
a sensing layer formed over an upper surface of a floating gate conductor of each chemFET sensor in the array of chemFET sensors, wherein the sensing layer has a pH sensitivity of between about 40 mV/pH to about 60 mV/pH;
a reference electrode providing a stable reference voltage to the array of chemFET sensors; and
a field programmable gate array to acquire output signals for the array of chemFET sensors.
14. The apparatus of claim 13 , wherein the sensing layer is sensitive to hydrogen ions.
15. The apparatus of claim 14 , wherein the sensing layer is sensitive to hydrogen ions in a range of pH 6 to pH 9.5.
16. The apparatus of claim 13 , wherein the sensing layer comprises a metal, a metal oxide, a metal nitride or a metal oxynitride, and combinations thereof.
17. The apparatus of claim 16 , wherein the metal comprises aluminum, zirconium, titanium, tantalum, molybdenum, hafnium or tungsten.
18. The apparatus of claim 17 , wherein a native oxide is formed on the metal comprising the sensing layer.