Methods and apparatus for detecting molecular interactions using FET arrays

A method of determining a binding interaction between a nucleic acid sample and at least one metabolite, the method comprising:

• providing a chemical-sensitive field effect transistor (chemFET) array comprising at least 105 chemFETs formed in a substrate and a nucleic acid sample or at least one metabolite associated therewith, the chemFETs having a gate oxide, a floating gate comprising conductors formed in a plurality of conductor layers and electrically coupled to one another, and a passivation layer overlying the floating gate, the sample analyzer further comprising signal lines for the sensors within at least one of the conductor layers;
• contacting the chemFET array with the at least one metabolite when the nucleic acid sample is associated therewith or contacting the chemFET array with the nucleic acid sample when the at least one metabolite is associated with the chemFET array;
• providing suitable conditions for association or coupling between the nucleic acid sample and the at least one metabolite;
• washing the chemFET array to at least partially remove unassociated or uncoupled nucleic acid sample or metabolite;
• and
• detecting changes in the electrical properties of the chemFET array indicative of interactions between the nucleic acid sample and the at least one metabolite.

An apparatus for determining a binding interaction between a nucleic acid sample and a metabolite, the apparatus comprising:

• a chemical-sensitive field effect transistor (chemFET) array comprising at least 105 chemFETs formed in a substrate and a nucleic acid sample or a metabolite disposed thereon or associated therewith, the chemFETs having a gate oxide, a floating gate comprising conductors formed in a plurality of conductor layers and electrically coupled to one another, and a passivation layer overlying the floating gate, the sample analyzer further comprising signal lines for the sensors within at least one of the conductor layers;
• a fluidics assembly comprising:
• a reaction assembly for contacting the chemFET with the metabolite when the nucleic acid sample is disposed on or associated with the chemFET or an assembly for contacting the chemFET with the nucleic acid sample when the metabolite is disposed on or associated therewith the chemFET;
• a washing assembly for removing at least a portion of unbound metabolite or nucleic acid sample from the chemFET;
• and
• a detection system for detecting an electrical output from the chemFET,
• wherein the electrical output is indicative of a binding interaction between the nucleic acid sample and the metabolite.

A method for detecting biomolecular activity comprising:

• providing a sample analyzer comprising a plurality of chemical-sensitive field effect transistors (chemFETs), the chemFETs comprising a gate oxide, a floating gate comprising conductors formed in a plurality of conductor layers and electrically coupled to one another, and a passivation layer overlying the floating gate, the sample analyzer further comprising signal lines for the sensors within at least one of the conductor layers;
• disposing a biological sample in proximity to or in contact with at least a portion of the chemFETs;
• providing at least one chemical compound in proximity to or in contact with at least a portion of the chemFETs wherein interactions or reactions with the biological sample effectuate changes in at least one electrical property of at least a portion of the chemFETs;
• and
• identifying interactions or reactions between the at least one chemical compound and the biological sample by detecting the changes in electrical properties of at least a portion of the chemFETs.