Nanopipette Analysis of Polymers

Abstract

The disclosure relates to devices and instruments for detecting and individually analyzing biomolecules, biomolecular complexes and biomolecules with ligands attached thereon.

1 - 42 . (canceled) 
     
     
         43 . A method of analyzing one or more macromolecules, the method comprising:
 i. attaching one or more macromolecules to a fixed location on a solid phase surface;   ii. providing a first electrode in fluidic communication with said one or more macromolecules through an ionic aqueous buffer;   iii. providing a nanopipette containing a second electrode;   iv. applying a potential difference between the first and second electrodes to induce the flow of ions;   v. bringing the nanopipette in sufficient proximity to a macromolecule such that the macromolecule enters into the nanopipette; and   vi. measuring an ion flow,   wherein the nanopipette is one of an array of nanopipettes configured for entry of a macromolecule.   
     
     
         44 . The method according to  43  where the array of nanopipettes comprise pulled glass capillaries or monolithic, nano-fabricated or micro-fabricated structures. 
     
     
         45 . The method according to  43  where the array of nanopipettes are configured to obtain measurements of a number of macromolecules in parallel. 
     
     
         46 . The method according to  43  where the array of nanopipettes are configured to obtain measurements of a number of macromolecules in a cell in parallel. 
     
     
         47 . The method according to  43  where the array of nanopipettes are configured to obtain measurements of macromolecules in a number of cells in parallel. 
     
     
         48 . The method according to  43 , wherein each nanopipette in the array is located precisely at a location of individual wells in a microwell array 
     
     
         49 . The method according to  43 , wherein the array comprises individual reference nanopipettes with no macromolecules as a control. 
     
     
         50 . The method according to  43 , wherein the nanopipettes comprise nanopores. 
     
     
         51 . The method according to  50 , wherein the nanopores are embedded within a surface and the surface containing the nanopores is translated in the z direction with respect to the surface to which the macromolecules are attached.