Chamber free nanoreactor system

Abstract

Aspects of the invention include methods for improving the accuracy and read length of sequencing reactions by utilizing unlabeled unincorporable nucleotides, or by rephasing colony based sequencing reactions. Other aspects include systems and devices for improved measurement of biological reactions associated with bead which may be removed, utilizing current measurement methods through the counter ions associated with said beads due to the presence of reactants bound or associated with said bead, wherein electrodes for generating and measuring said current may be within the Debye length of said bead. Other aspects of the invention include methods for determining concentrations of input samples, means for reuse of an array, methods and apparatus for separating beads with different charge levels from each other.

1 .- 2 . (canceled) 
     
     
         3 . A system for sensing or sequencing a biological molecule during a sequencing reaction, comprising:
 a support that immobilizes said biological molecule in solution during said sequencing reaction;   at least two electrodes in contact with said solution and positioned such that, during sensing by said at least two electrodes, said at least two electrodes sense signals indicative of a change in conductivity or charge adjacent to said support during said sequencing reaction; and   a device that (i) receives said signals from said at least two electrodes during said sequencing reaction, which signals are indicative of said change in conductivity or charge adjacent to said support, and (ii) uses said signals to sense or sequence said biological molecule.   
     
     
         4 . The system of  claim 3 , wherein an electrode of said at least two electrodes is adjacent to a substrate, a dielectric layer is on said device electrode, and another electrode of said at least two electrodes is adjacent said dielectric layer. 
     
     
         5 . The system of  claim 3 , further comprising an array of electrodes comprising said at least two electrodes. 
     
     
         6 . The system of  claim 5 , wherein said array is a planar array. 
     
     
         7 . The system of  claim 3 , wherein said solution is an aqueous solution. 
     
     
         8 . The system of  claim 7 , wherein said aqueous solution has an ionic concentration of less than 10 −8  molar. 
     
     
         9 . The system of  claim 3 , wherein said solution is a miscible mixture of an aqueous solution and an organic solution. 
     
     
         10 . The system of  claim 9 , wherein said miscible solution has an ionic concentration less than 10 −7  molar. 
     
     
         11 . The system of  claim 3 , wherein at least one of said at least two electrodes is within a Debye length of said support. 
     
     
         12 . The system of  claim 3 , wherein at least one of said at least two electrodes is within at least 0.1 Debye lengths of said support. 
     
     
         13 . The system of  claim 3 , wherein said at least two electrodes comprises a first electrode and a second electrode separated by a dielectric layer, and wherein said device further comprises a substrate adjacent to said first electrode. 
     
     
         14 . The system of  claim 13 , wherein said first electrode is below a center line of said support, and said second electrode is above a center line of said support. 
     
     
         15 . The system of  claim 3 , wherein said electrodes are planar. 
     
     
         16 . The system of  claim 3 , wherein an individual electrode of said at least two electrodes has a Debye layer during said sequencing reaction. 
     
     
         17 . The system of  claim 3 , wherein said signals are steady-state signals. 
     
     
         18 . The system of  claim 3 , wherein said signals are indicative of a change in impedance adjacent to said support. 
     
     
         19 . The system of  claim 3 , wherein said at least two electrodes comprise a first electrode and a second electrode, wherein said first electrode is above said second electrode. 
     
     
         20 . The system of  claim 3 , wherein said support is a particle in said solution. 
     
     
         21 . The system of  claim 3 , wherein said biological molecule is a protein. 
     
     
         22 . The system of  claim 3 , wherein said biological molecule is a nucleic acid molecule.