Systems and methods for automated reusable parallel biological reactions

Abstract

A method comprises magnetically holding a bead carrying biological material (e.g., nucleic acid, which may be in the form of DNA fragments or amplified DNA) in a specific location of a substrate, and applying an electric field local to the bead to isolate the biological material or products or byproducts of reactions of the biological material. For example, the bead isolated from other beads having associated biological material. The electric field in various embodiments concentrates reagents for an amplification or sequencing reaction, and/or concentrates and isolates detectable reaction by-products. For example, by isolating nucleic acids around individual beads, the electric field can allow for clonal amplification, as an alternative to emulsion PCR. In other embodiments, the electric field isolates a nanosensor proximate to the bead, to facilitate detection of at least one of local pH change, local conductivity change, local charge concentration change and local heat. The beads may be trapped in the form of an array of localized magnetic field regions.

1 .- 14 . (canceled) 
     
     
         15 . A device for nucleic acid sequencing, comprising:
 a surface configured to immobilize a plurality of nucleic acid molecules in solution during sequencing;   a flow cell in fluid communication with said surface, wherein said flow cell is configured to direct a plurality of nucleotides to said plurality of nucleic acid molecules during said sequencing; and   a sensor array in fluid communication with said flow cell, wherein said sensor array comprises a plurality of sensors, wherein a sensor of said plurality of sensors comprises at least two electrodes adjacent to said surface, which at least two electrodes are configured to contact said solution during said sequencing,   wherein said at least two electrodes comprise a first electrode oriented along a first plane and a second electrode oriented along a second plane that is different than said first plane,   wherein said at least two electrodes are configured to detect impedance, charge, or conductivity, or change in impedance, charge, or conductivity, of said solution adjacent to said surface during said sequencing, which impedance, charge, or conductivity, or change in impedance, charge, or conductivity, is indicative of incorporation of a nucleotide of said plurality of nucleotides into a nucleic acid molecule of said plurality of nucleic acid molecules.   
     
     
         16 . The device of  claim 15 , wherein said surface and said sensor array are part of a chip. 
     
     
         17 . The device of  claim 15 , wherein said surface is part of a planar array. 
     
     
         18 . The device of  claim 15 , wherein said surface is part of a well. 
     
     
         19 . The device of  claim 15 , wherein said surface is configured to immobilize a particle comprising said plurality of nucleic acid molecules. 
     
     
         20 . The device of  claim 19 , further comprising a magnetic array configured to immobilize said particle adjacent to said sensor. 
     
     
         21 . The device of  claim 20 , wherein said magnetic array comprises a plurality of magnets, and wherein a magnet of said plurality of magnets is disposed adjacent to said sensor. 
     
     
         22 . The device of  claim 21 , wherein said magnet comprises a permanent magnet. 
     
     
         23 . The device of  claim 21 , wherein said magnet comprises a non-permanent magnet provided by an electric field. 
     
     
         24 . The device of  claim 15 , wherein said sensor array does not comprise wells. 
     
     
         25 . The device of  claim 15 , wherein said first electrode and said second electrode are separated by a dielectric. 
     
     
         26 . The device of  claim 15 , further comprising circuitry configured to (i) receive signals from said at least two electrodes and (ii) use said signals to determine said impedance, charge, or conductivity, or change in impedance, charge, or conductivity. 
     
     
         27 . The device of  claim 26 , wherein said circuitry is configured to, based at least in part on said impedance, charge, or conductivity, or change in impedance, charge, or conductivity, identify said nucleotide of said plurality of nucleotides. 
     
     
         28 . The device of  claim 26 , wherein said circuitry comprises read-out circuitry, on-chip amplifiers, or both read-out circuitry and on-chip amplifiers. 
     
     
         29 . The device of  claim 15 , wherein said first plane is oriented above said second plane. 
     
     
         30 . The device of  claim 15 , wherein said nucleic acid molecule is part of a clonal population of nucleic acid molecules, and wherein said clonal population of nucleic acid molecules is disposed adjacent to said sensor. 
     
     
         31 . The device of  claim 15 , wherein said sensor array is configured to reduce cross-talk between said sensor and another sensor of said plurality of sensors.