Systems and methods for genetic sequencing

Abstract

A device including a transparent layer defining a surface exposed to a flow volume and to secure a target polynucleotide template and a detector structure secured to the transparent layer and including a plurality of detectors to detect a signal emitted during nucleotide incorporation along the target polynucleotide template.

What is claimed is: 
     
         1 . A device comprising:
 a transparent layer defining a surface exposed to a flow volume and to secure a target polynucleotide template; and   a detector structure in optical communication with and secured to the transparent layer and including a plurality of detectors configured to detect a fluorescent signal emitted during nucleotide incorporation during template-dependent nucleic acid synthesis, wherein the detector structure includes a plurality of pixels, each pixel of the plurality of pixels including a set of detectors of the plurality of detectors, wherein the set of detectors are defined within the semiconductor structure by a p-type substrate, a deep n-type implant, a shallow n-type implant, and a p-type implant disposed over the shallow n-type implant.   
     
     
         2 . The device of  claim 1 , wherein each pixel of the plurality of pixels includes at least two detectors of the plurality of detectors. 
     
     
         3 . The device of  claim 2 , where the at least two detectors are disposed one over the other when viewed in cross-section. 
     
     
         4 . The device of  claim 2 , wherein each pixel includes at least four detectors. 
     
     
         5 . The device of  claim 1 , wherein the transparent layer includes an energy propagation layer. 
     
     
         6 . The device of  claim 1 , further comprising an energy propagation layer disposed between the transparent layer and the detector structure. 
     
     
         7 . The device of  claim 6 , wherein the energy propagation layer includes a total internal reflection layer. 
     
     
         8 . The device of  claim 6 , further comprising an energy emitting component to provide energy to the energy propagation layer. 
     
     
         9 . The device of  claim 1 , further comprising a separator structure extending from the detector structure toward the transparent layer, the separator structure opaque to the fluorescent signal. 
     
     
         10 . The device of  claim 1 , further comprising a filter layer disposed between the device structure and the transparent layer. 
     
     
         11 . The device of  claim 10 , wherein the filter layer is configured to limit transmission of excitation energy. 
     
     
         12 . The device of  claim 1 , further comprising a well structure defining wells disposed on the transparent layer opposite the detector structure. 
     
     
         13 . The device of  claim 1 , further comprising a lid, the flow volume defined between the lid and the transparent layer. 
     
     
         14 . A method of obtaining sequence information from a polynucleotide target, the method comprising:
 applying a sequencing device to a sequencing system, the sequencing device defining a flow volume and including a transparent layer including a surface exposed to the flow volume and a detector structure disposed on an opposite side of the transparent layer from the flow volume, the detector structure including a plurality of detectors configured to detect a fluorescent signal emitted during nucleotide incorporation during template-dependent nucleic acid synthesis, wherein the detector structure includes a plurality of pixels, each pixel of the plurality of pixels including a set of detectors of the plurality of detectors, wherein the set of detectors are defined within the semiconductor structure by a p-type substrate, a deep n-type implant, a shallow n-type implant, and a p-type implant disposed over the shallow n-type implant;   applying a polynucleotide to the sequencing device;   incorporating at least one dye modified nucleotide into a nascent nucleic acid molecule using the polynucleotide as a template; and   detecting a fluorescent signal with the detector structure from a dye of the at least one dye modified nucleotide, the fluorescent signal indicative of nucleotide incorporation of the at least one dye modified nucleotide.   
     
     
         15 . The method of  claim 14 , wherein the nucleotide solution includes at least two dye modified nucleotide types. 
     
     
         16 . The method of  claim 14 , wherein the nucleotide solution includes four different dye modified nucleotide types. 
     
     
         17 . The method of  claim 14 , wherein applying the nucleotide solution includes sequentially applying at least two different nucleotide solutions. 
     
     
         18 . The method of  claim 14 , wherein the transparent layer includes an energy propagation layer, the method further comprising applying excitation energy to the energy propagation layer, the excitation energy exiting the dye of the at least one dye modified nucleotide. 
     
     
         19 . The method of  claim 18 , wherein the sequencing device further includes a filter layer disposed between the device structure and the transparent layer, wherein the filter layer is configured to limit transmission of excitation energy to the plurality of detectors. 
     
     
         20 . The method of  claim 14 , wherein the sequencing device further includes a well structure defining wells disposed on the transparent layer opposite the detector structure, wherein applying a polynucleotide to the sequencing device includes applying the polynucleotides into the wells.