High throughput biochemical detection using single molecule fingerprinting arrays

Abstract

Various embodiments provide devices, methods, and systems for high throughput biomolecule detections using transducer arrays. In one embodiment, a transducer array made up of a plurality of transducer elements may be used to detect byproducts from chemical reactions that involve redox genic tags. Each transducer element may include at least a reaction chamber and a fingerprinting region configured to flow a fluid from the reaction chamber through the fingerprinting region. The reaction chamber can have a single molecule attachment region and the fingerprinting region can include at least one set of electrodes separated by a nanogap suitable for conducting redox cycling reactions. In embodiments, by flowing chamber contents, from a reaction of a latent redox tagged probe molecule, a catalyst, and a target molecule, in the reaction chamber of the at least one transducer element through the fingerprinting region, the redox cycling reactions can be detected to identify the redox-tagged biomolecules.

What is claimed is: 
     
         1 . A device comprising:
 a transducer array comprising a plurality of transducer elements, each transducer element comprising at least a reaction chamber and a fingerprinting region, configured such that a fluid in the reaction chamber is capable of flowing through the fingerprinting region,   wherein the reaction chamber comprises a single molecule attachment region, and wherein the fingerprinting region comprises at least one electrode set comprising a first electrode and a second electrode configured having a nanogap there-between suitable for conducting a redox cycling reaction of the fluid.   
     
     
         2 . The device of  claim 1 , wherein the fingerprinting region comprises an electronic transducer comprising the first electrode and the second electrode and wherein the first electrode and the second electrode are independently electrically coupled to and individually addressable through electronics. 
     
     
         3 . The device of  claim 1 , further comprising a readout circuit coupled with the first electrode and the second electrode to read and interpret a signal from the redox cycling reaction. 
     
     
         4 . The device of  claim 1 , further comprising a readout circuit coupled with the transducer array to individually or in groups address the plurality of transducer elements in the transducer array. 
     
     
         5 . The device of  claim 1 , wherein the transducer array is disposed on an integrated circuit (IC) chip, the IC chip comprising a readout circuit coupled with the transducer array. 
     
     
         6 . The device of  claim 1 , further comprising an active drift mechanism comprising a hydrodynamic mechanism, a heating element, or a sealing component configured to flow the fluid from the reaction chamber and through the fingerprinting region. 
     
     
         7 . The device of  claim 1 , further comprising an active drift mechanism configured to simultaneously or sequentially flow the fluid from one or more reaction chambers of the transducer array. 
     
     
         8 . The device of  claim 1 , wherein the nanogap between the first and second electrodes is between of less than 500 nm. 
     
     
         9 . The device of  claim 1 , wherein the transducer array comprises about 2 to about 1,000,000,000 transducer elements. 
     
     
         10 . The device of  claim 1 , wherein the fingerprinting region comprises four or more sets of the first and the second electrodes. 
     
     
         11 . A system comprising:
 an integrated circuit chip; and   a transducer array comprising a plurality of transducer elements disposed on the integrated circuit chip, wherein the plurality of transducer elements are electrically coupled to and individually addressable through electronics in the integrated circuit chip and wherein each transducer element comprises an inlet region, a fingerprinting region, and an outlet region configured such that a fluid in the inlet region is capable of flowing through the fingerprinting region to the outlet region,   wherein the inlet region comprises a reaction chamber comprising a single molecule attachment region and wherein the fingerprinting region comprises at least one electrode set comprising a first electrode and a second electrode separated by a nanogap suitable for conducting a redox cycling reaction of the fluid.   
     
     
         12 . The system of  claim 11 , wherein the integrated circuit chip comprises a readout circuit coupled with the first electrode and the second electrode to read and interpret a signal from the redox cycling reaction. 
     
     
         13 . The system of  claim 11 , wherein the integrated circuit chip comprises a readout circuit coupled with the transducer array to individually or in groups address the plurality of transducer elements in the transducer array. 
     
     
         14 . The system of  claim 11 , wherein the integrated circuit chip comprises a readout circuit capable of implementation subtraction of the first and the second electrode currents to reinforce anticorrelated redox signal, independently acquiring both the first and the second electrode signals to reduce impact of amplifier noises by cross-correlation signal processing, using a switched capacitor implementation of a pair of transimpedance amplifiers with two separate outputs, or a combination thereof. 
     
     
         15 . The system of  claim 11 , wherein the fingerprinting region comprises four or more electrode sets. 
     
     
         16 . The system of  claim 11 , further comprising an active drift mechanism comprising a hydrodynamic mechanism, or a heating element, or a sealing component configured to flow the fluid from the reaction chamber and through the fingerprinting region. 
     
     
         17 . The system of  claim 11 , further comprising an active drift mechanism configured to simultaneously or sequentially flow a fluid from one or more inlet regions of the transducer array. 
     
     
         18 . The system of  claim 11 , wherein the nanogap between the first and second electrodes is between 10 and 500 nm suitable for conducting the redox cycling reaction. 
     
     
         19 . The system of  claim 11 , wherein the transducer array comprises about 2 to about 1,000,000,000 transducer elements. 
     
     
         20 . The system of  claim 11 , further comprising a computer operably coupled to the integrated circuit chip. 
     
     
         21 . The system of  claim 11 , further comprising a fluidic system aligned on the inlet regions of the transducer array to supply a fluid and to maintain a unidirectional flow through the fingerprinting region.