INTEGRATED SENSOR ARRAYS FOR BIOLOGICAL AND CHEMICAL ANALYSIS
The invention is directed to apparatus and chips comprising a large scale chemical field effect transistor arrays that include an array of sample-retaining regions capable of retaining a chemical or biological sample from a sample fluid for analysis. In one aspect such transistor arrays have a pitch of 10 μm or less and each sample-retaining region is positioned on at least one chemical field effect transistor which is configured to generate at least one output signal related to a characteristic of a chemical or biological sample in such sample-retaining region. In one embodiment, the characteristic of said chemical or biological sample is a concentration of a charged species and wherein each of said chemical field effect transistors is an ion-sensitive field effect transistor having a floating gate with a dielectric layer on a surface thereof, the dielectric layer contacting said sample fluid and being capable of accumulating charge in proportion to a concentration of the charged species in said sample fluid. In one embodiment such charged species is a hydrogen ion such that the sensors measure changes in pH of the sample fluid in or adjacent to the sample-retaining region thereof. Apparatus and chips of the invention may be adapted for large scale pH-based DNA sequencing and other bioscience and biomedical applications.
1 .- 36 . (canceled)
37 . A device comprising:
a flow cell having an fluid inlet and an fluid outlet and a flow chamber extending between the inlet and the outlet, the flow cell including a substrate having a plurality of reaction chambers, each reaction chamber of the plurality of reaction chambers having an aperture that opens onto the flow chamber;
a reaction sensor coupled to the flow cell including an array of pixels that have a fixed position relative to the substrate of the flow cell, the pixels being assigned to select reaction chambers such that activity detected by the pixels indicates that a desired reaction has occurred within the select reaction chamber; and
an exterior surface having a plurality of pins thereon that are communicatively coupled to the pixels, the pins for delivering information to a circuitry identifying a reaction in a reaction chamber.
38 . The device of claim 37 wherein the pins interface with an array controller.
39 . The device of claim 38 wherein the array controller is associated with a processor for processing data from the device.
40 . The device of claim 39 wherein the processor determines the sequence of a nucleic acid from the data.
41 . The device of claim 39 wherein the data is displayed on a handheld device.
42 . The device of claim 37 wherein the inlet and the outlet interface with a fluidics assembly having a conduit for delivering fluid to the inlet and a conduit for removing fluid from the outlet.
43 . The device of claim 37 further including a structure for promoting substantially laminar flow across the plurality of reaction chambers.
44 . The device of claim 42 wherein the fluidics assembly includes valves for delivering fluids.
45 . The device of claim 37 wherein the reaction sensor detects voltage.
46 . The device of claim 37 wherein the reaction sensor detects current.
47 . The device of claim 37 wherein the reaction sensor further includes a nucleic acid sequence.
48 . The device of claim 47 wherein the nucleic acid sequence is attached directly to the surface of the reaction sensor.
49 . A method of performing a sequencing reaction comprising:
providing a device having:
a flow cell having an fluid inlet and an fluid outlet and a flow chamber extending between the inlet and the outlet, the flow cell including a substrate having a plurality of reaction chambers, each reaction chamber of the plurality of reaction chambers having an aperture that opens onto the flow chamber;
a reaction sensor coupled to the flow cell including an array of pixels that have a fixed position relative to the substrate of the flow cell, the pixels being assigned to select reaction chambers such that activity detected by the pixels indicates that a desired reaction has occurred within the select reaction chamber;
an exterior surface having a plurality of pins thereon that are communicatively coupled to the pixels, the pins for delivering information to a circuitry identifying a reaction in a reaction chamber;
introducing a nucleic acid sequence to the reaction chambers of the device;
amplifying the nucleic acid sequence; and
determining the sequence of the nucleic acid.
50 . The method of claim 49 wherein the amplifying includes performing emulsion PCR.
51 . The method of claim 49 wherein the amplifying includes performing bridge PCR.
52 . The method of claim 50 wherein the determining includes performing sequencing-by-synthesis.