Monitoring enzymatic process

Abstract

Techniques, apparatus and systems are described for performing label-free monitoring of processes. In one aspect, a label-free monitoring system includes an array of label-free optical sensors to detect an optical signal in response to synthesis of one or more target genetic structures. Each label-free optical sensor is functionalized with a respective target genetic structure. The system also includes a fluid flow control module that includes fluid receiving units to provide paths for different fluids to flow into the fluid flow control module and at least one switch connected to the fluid receiving units to selectively switch among the fluid receiving units to receive a select sequence of the fluids through the fluid receiving units. The select sequence of the fluids includes at least a dNTP or base. A fluid channel is connected between the fluid flow control module and the array of sensors to allow the select sequence of the fluids to flow from the fluid flow control module to the array of label-free optical sensors.

1 - 22 . (canceled) 
     
     
         23 . A method comprising:
 causing a known sequence of nucleotides to continuously flow by a label-free optical sensor having a surface functionalized with an unknown species of nucleic acid;   measuring changes in an output signal of the optical sensor to detect synthesis reactions between the unknown species of nucleic acid and the known sequence of nucleotides; and   identifying a sequence of nucleotides in the unknown species of nucleic acid based on the measured changes in the output signal and the known sequence of nucleotides.   
     
     
         24 . The method of  claim 23 , further comprising discouraging comingling of different nucleotides in the known sequence of nucleotides. 
     
     
         25 . The method of  claim 24 , wherein discouraging comingling of different nucleotides in the known sequence of nucleotides comprises providing buffer solutions in between the different nucleotides. 
     
     
         26 . The method of  claim 24 , wherein discouraging comingling of different nucleotides in the known sequence of nucleotides comprises providing air bubbles in between the different nucleotides. 
     
     
         27 . The method of  claim 23 , further comprising detecting repeated incorporation of a nucleotide, from the known sequence of nucleotides, in the unknown species of nucleic acid based on magnitude of change in the output signal of the optical sensor. 
     
     
         28 . The method of  claim 27 , further comprising detecting a double incorporation of a nucleotide, from the known sequence of nucleotides, in the unknown species of nucleic acid based on a doubled change in the output signal of the optical sensor. 
     
     
         29 . A device comprising:
 a fluid flow control module configured to cause a known sequence of nucleotides to continuously flow by a label-free optical sensor having a surface functionalized with an unknown species of nucleic acid;   wherein the device is configured to measure changes in an output signal of the optical sensor to detect synthesis reactions between the unknown species of nucleic acid and the known sequence of nucleotides; and   wherein the device is configured to identify a sequence of nucleotides in the unknown species of nucleic acid based on the measured changes in the output signal and the known sequence of nucleotides.   
     
     
         30 . The device of  claim 29 , wherein the fluid flow control module is configured to discourage comingling of different nucleotides in the known sequence of nucleotides. 
     
     
         31 . The device of  claim 30 , wherein the fluid flow control module is configured to provide buffer solutions in between the different nucleotides in the known sequence of nucleotides. 
     
     
         32 . The device of  claim 30 , wherein the fluid flow control module is configured to provide air bubbles in between the different nucleotides in the known sequence of nucleotides. 
     
     
         33 . The device of  claim 29 , wherein the device is configured to detect repeated incorporation of a nucleotide, from the known sequence of nucleotides, in the unknown species of nucleic acid based on magnitude of change in the output signal of the optical sensor. 
     
     
         34 . The device of  claim 33 , wherein the device is configured to detect a double incorporation of a nucleotide, from the known sequence of nucleotides, in the unknown species of nucleic acid based on a doubled change in the output signal of the optical sensor.