Processive enzyme molecular electronic sensors for dna data storage

Abstract

A processive enzyme molecular sensor for use in a DNA data storage system is disclosed that can extract digital information suitably encoded into a synthetic DNA molecule. In various aspects, such sensors are provided in a high-density chip-based format that can provide the high throughput, low-cost and fast data extraction capability required for large scale DNA data storage systems. The sensor for reading the digital data stored in DNA molecules processes individual encoded DNA molecules directly, eliminating the need for complicated sample preparation such as making copies of DNA or clonal populations of such molecules.

1 - 40 . (canceled) 
     
     
         41 . A DNA information system comprising:
 a synthetic DNA molecule comprising a DNA template strand and distinguishable signaling features bonded thereon, the distinguishable signaling features encoding information in the synthetic DNA molecule;   a buffer solution in contact with the synthetic DNA molecule, the first and second electrodes, and the processive enzyme; and   a sensor capable of reading the information encoded in the synthetic DNA molecule, the sensor comprising: a first electrode; a second electrode spaced apart from the first electrode by an electrode gap; a processive enzyme conjugated to both the first and second electrodes; and a trans-impedance amplifier electrically connected to at least one of the first and second electrodes, the trans-impedance amplifier providing an output comprising a measurable electrical parameter,   wherein the measurable electrical parameter comprises distinguishable signals corresponding to the encoded information.   
     
     
         42 . The system of  claim 41 , wherein the processive enzyme comprises a native or genetically engineered polymerase, reverse transcriptase, helicase, exonuclease, or molecular motor for packaging of viral DNA. 
     
     
         43 . The system of  claim 41 , wherein the encoded information comprises binary data. 
     
     
         44 . The system of  claim 41 , wherein the distinguishable signaling features comprise one or more of a sequence of oligonucleotides or one or more chemical groups conjugated to the DNA template strand. 
     
     
         45 . The system of  claim 44 , wherein the oligonucleotides are bonded to the DNA template strand by complementary base pairing. 
     
     
         46 . The system of  claim 44 , wherein the oligonucleotides are covalently bonded to the DNA template strand and wherein each of the oligonucleotides further comprises at least one chemical group bonded thereon. 
     
     
         47 . The system of  claim 41 , further comprising a reference electrode in communication with the buffer solution. 
     
     
         48 . The system of  claim 41 , wherein the processive enzyme is positioned between the first and second electrodes to provide a conductive pathway between the first and second electrodes, through the processive enzyme. 
     
     
         49 . The system of  claim 41 , wherein the processive enzyme is conjugated to the first and second electrodes via a bridge molecule, the bridge molecule having first and second ends, the first end conjugated to the first electrode and the second end conjugated to the second electrode, wherein the processive enzyme is conjugated to the bridge molecule. 
     
     
         50 . The system of  claim 41 , wherein the processive enzyme is conjugated to the first and second electrodes via at least one intervening arm molecule, the arm molecule conjugated to at least one of the first and second electrodes and conjugated to the processive enzyme. 
     
     
         51 . The system of  claim 50 , wherein the arm molecule comprises a double stranded DNA, a protein alpha helix, a graphene nanoribbon, a carbon nanotube, an antibody, or a Fab arm of an antibody. 
     
     
         52 . The system of  claim 41 , further comprising a CMOS sensor array chip comprising an array of the sensors and supporting pixel circuitry that performs measurement of the measurable electrical parameter. 
     
     
         53 . The system of  claim 52 , comprising at least two of the CMOS sensor array chips; an electronic hardware system for controlling and managing electrical inputs and data outputs of the chips; a fluidic system for introducing the synthetic DNA molecule in the buffer solution to the chips; and a signal processing and data recording system for capturing the distinguishable signals and for converting the distinguishable signals back to the information.