Biomarker sensors and method for multi-color imaging and processing of single-molecule life signatures

Abstract

A device comprising an array of active regions for use in reacting one or more species in at least two of the active regions in a sequential process, e.g., sequential reactions. The device has a transparent substrate member, which has a surface region. The device has a silane material overlying the surface region. The device has a first active region formed overlying a first portion of the silane material. In a specific embodiment, the first active region has a first dimension of less than 1 micron in size and has one or more first molecules capable of binding to the first portion of the silane material. In a specific embodiment, the device has a second active region formed overlying a second portion of the silane material. The second active region has a second dimension of less than 1 micron in size and has one or more second molecules capable of binding to the second portion of the active region. In a specific embodiment, the device has a spatial distance separating the first active region and the second active region. In a preferred embodiment, the spatial distance is characterized by a dimension of 1 micron and less. The device has a fluid material in contact with the first active region, the second active region, and the spatial distance according to a specific embodiment. The device also has a reactant species within the fluid material. The reactant species is capable of spatially moving from the first active region to the second active region over the spatial distance of 1 micron and less within a time of less than 10 microseconds.

1 . A device comprising an array of active regions for use in reacting one or more species in at least two of the active regions in a sequential process, the device comprising: 
 a transparent substrate member, the transparent substrate member having a surface region;    a silane material overlying the surface region;    a first active region formed overlying a first portion of the silane material, the first active region having a first dimension of less than 1 micron in size, the first active region comprising one or more first molecules capable of binding to the first portion of the silane material;    a second active region formed overlying a second portion of the silane material, the second active region having a second dimension of less than  1  micron in size, the second active region comprising one or more second molecules capable of binding to the second portion of the active region;    a spatial distance separating the first active region and the second active region, the spatial distance being characterized by 1 micron and less;    a fluid material in contact with the first active region, the second active region, and the spatial distance;    a reactant species within the fluid material, the reactant species being ;capable of spatially moving from the first active region to the second active region over the spatial distance of 1 micron and less within a time of less than 10 microseconds.    
     
     
         2 . The device of  claim 1  wherein the silane material is a blanket layer or a patterned layer.  
     
     
         3 . The device of  claim 1  wherein the transparent substrate member is selected from glass, quartz, or ceramic.  
     
     
         4 . The device of claim 1 wherein the first active region comprises one or more first biological molecules and the second active region comprises one or more second biological molecules.  
     
     
         5 . The device of  claim 1  wherein the first active region comprises one or more first chemical species and the second active region comprises one or more second chemical species.  
     
     
         6 . The device of  claim 1  wherein the first active region is provided by a first dip pen process.  
     
     
         7 . The device of  claim 1  wherein the second active region is provided by a first dip pen process.  
     
     
         8 . The device of  claim 1  wherein the spatial movement is provided by a diffusion process of the reactant species from the first active region to the second active region.  
     
     
         9 . The device of  claim 1  wherein the spatial movement is provided by a convection process of the reactant species from the first active region to the second active region.  
     
     
         10 . The device of  claim 1  wherein the first region and the second region are two of a plurality of active regions in an array configuration.  
     
     
         11 . A method for processing an array of active regions for use in reacting one or more species in at least two of the active regions in a sequential process, the method comprising: 
 providing a substrate member, the substrate member having a surface region, the surface region having a first active region formed overlying a first portion of the surface region and a second active region formed overlying a second portion of the surface region, a spatial distance separating the first active region and the second active region, the spatial distance being characterized by 1 micron and less;    subjecting the first active region, the second active region, and the spatial distance with a fluid material; and    dispensing a reactant species within the fluid material; and    causing movement of the reactant species from the first active region to the second active region over the spatial distance of  1  micron and less within a time of less than 10 microseconds.    
     
     
         12  A method for processing one or more materials using a probe device, the method comprising: 
 suspending a probe device coupled to a tip region, the tip region having a determined spatial size;    moving the probe device including the tip region toward a surface of a substrate member having one or more species thereon, while maintaining the tip region immersed in a fluid overlying the one or more species thereon;    applying an electrical bias on the probe device relative to a reference potential to cause the tip region to change in electrical characteristic; and    selectively processing the one or more species.    
     
     
         13 . The method of  claim 12  wherein the electrical bias is a positive bias or a negative bias.  
     
     
         14 . The method of  claim 12  wherein the one or more species comprises a linker layer of molecules.  
     
     
         15 . The method of  claim 12  wherein the tip region comprises a conductive characteristic.  
     
     
         16 . The method of  claim 12  wherein the tip region comprises a coating thereon.  
     
     
         17 . The method of  claim 12  wherein the fluid is characterized by a pH of 7.  
     
     
         18 . The method of  claim 12  wherein the fluid is characterized by a pH of less than  7  or greater than 7.  
     
     
         19 . The method of  claim 12  wherein the selectively processing occurs by causing an acidic characteristic within a vicinity of the one or more species.  
     
     
         20 . The method of  claim 12  wherein the selectively processing occurs by causing a basic characteristic within a vicinity of the one or more species.  
     
     
         21 . The method of  claim 12  wherein the selectively processing occurs by causing a pH=7 characteristic within a vicinity of the one or more species.  
     
     
         22 . The method of  claim 12  wherein the tip is on and in contact with at least one of the one or more species.  
     
     
         23 . The method of  claim 12  wherein the substrate is made of a material selected from glass, quartz, ceramic, plastic, or semiconductor.  
     
     
         24 . The method of  claim 12  wherein the change in electrical characteristic forms one or more proton species within a vicinity of the tip region within the fluid.  
     
     
         25 . The method of  claim 12  wherein the change in electrical characteristic forms one or more hydroxide species within a vicinity of the tip region within the fluid.  
     
     
         26 . A system for processing one or more local regions on substrate members, the system comprising: 
 a suspension member;    a probe device coupled to the suspension member, the probe device coupled to a tip region, the tip region having a determined spatial size, the probe device including the tip region being adapted to move toward a surface of a substrate member having one or more species thereon; and    an electrical drive device coupled to the probe device, the electrical drive device being adapted to apply an electrical bias to the probe device relative to a reference potential to cause the tip region to change in electrical characteristic to cause a localized change within a vicinity of the one or more species; and    a fluid immersing the tip region as the tip region moves toward the surface, the fluid including a local region, the local region being subject to the localized change, the localized change being a change in a pH characteristic of the local region of the fluid upon at least application of the electrical bias to the probe device from the electrical drive device.    
     
     
         27 . The system of  claim 26  wherein the fluid immerses the tip region while the tip region moves toward and in contact with one or more of the species overlying the surface of the substrate.  
     
     
         28 . The system of  claim 26  wherein the localized change is a reaction rate change associated with the one or more species.  
     
     
         29 . The system of  claim 26  wherein the localized change is a change in the local region associated with the one or more species.  
     
     
         30 . The system of  claim 26  wherein the electrical characteristic is either an electron donation process or an electron acceptance process.  
     
     
         31 . The system of  claim 26  wherein the electrical change induces an electric field polarity change of the tip region.  
     
     
         32 . The system of  claim 26  wherein the localized change is the change in the pH characteristic in the vicinity of the one or more species in the fluid.  
     
     
         33 . The system of  claim 26  wherein the localized change comprises an increase in either protons or hydroxide ions.  
     
     
         34 . The system of  claim 33  wherein the increase in the protons or hydroxide ions cause an increase in a reaction rate of one or more of the species.  
     
     
         35 . The system of  claim 26  wherein the tip region comprises a portion of a single walled nanotube.  
     
     
         36 . The system of  claim 26  wherein the fluid comprises a salt, water, acid, base, or organic material.  
     
     
         37 . The system of  claim 26  wherein the substrate is a solid or gelled material.  
     
     
         38 . The system of  claim 26  further comprising a detection device coupled to the substrate member, the detection device being operably configured to capture information associated with the one or more species.  
     
     
         39 . The system of  claim 26  wherein the one or more species are provided on an array configuration.  
     
     
         40 . The system of  claim 26  wherein the one or more species is provided on an active region, the active region having a size of less than 10 nanometers.