Translocation of a polymer through a nanopore

Abstract

Embodiments of the present disclosure are directed to methods, systems and devices, for analyzing the molecules. For example, in some embodiments, a system is provided which includes a first volume of conducting fluid, a second volume of conducting fluid, an orifice in communication with the first and second volumes of fluid, and means for applying an electric potential difference between the first and second volumes of fluid. In some such embodiments, a conjugate product is provided which comprises charged polymers each having attached thereto at least one first molecule for analysis, where the product carries a predetermined charge greater than the charge on the first molecule, and upon dissolving the product in the first volume of fluid, the product is directed into the orifice.

1 . A molecule directing device for directing an oligosaccharide for analysis into an orifice, the device comprising:
 a first chamber and a second chamber, wherein each chamber includes an electrolytic solution, wherein:
 the electrolytic solution in the first chamber includes a dissolved product comprising a plurality of oligosaccharides, and 
 each oligosaccharide is coupled to a polymeric ion via a cross linker; 
   a membrane separating the second chamber from the first chamber;   an orifice in the membrane and configured to receive and pass each oligosaccharide between the first and the second chambers;   a first electrode in the first chamber; and   a second electrode in the second chamber, wherein each oligosaccharide is directed into the orifice by applying an electrical potential between the first and second electrodes;   a third electrode located within the orifice; and   a fourth electrode located with the orifice, wherein the third and fourth electrodes are positioned to make contact with the oligosaccharide as it passed through the orificepair of orifice.   
     
     
         2 . The device of  claim 1 , wherein the presence of the oligosaccharide in the orifice is detected by means of non-linear processing of an AC current signal. 
     
     
         3 . The device of  claim 1 , further comprising an electronic circuit for controlling values of bias applied between the first electrode and the orifice electrodes and the second electrode and the orifice electrodes, wherein the circuit receives input from a signal generated by the orifice electrodes. 
     
     
         4 . The device of  claim 1 , wherein the voltage applied between the orifice electrodes comprises an AC and a DC component. 
     
     
         5 - 14 . (canceled) 
     
     
         15 . The device of  claim 1 , wherein the polymeric ion comprises repeated negative charges such that when the first electrode is biased negative and the second electrode is biased positive, the polymeric ion is pulled into the orifice. 
     
     
         16 . The device of  claim 1 , wherein:
 a first electric field of a first predetermined amount is established on a first side of the orifice facing the first chamber and extends a distance λ from the orifice;   a second electric field of a second predetermined amount is established on a second side of the orifice facing the second chamber and extends the distance λ; and   the first electric field pulls the product into the orifice from the first chamber, and the second electric field pulls the product out of the orifice into the second chamber.   
     
     
         17 . The device of  claim 1 , wherein the electrical potential is configured such that the product does not fold when it is directed through the orifice. 
     
     
         18 . The device of  claim 1 , wherein the electrolytic solution in the first chamber comprises a salt solution of less than about 1M concentration. 
     
     
         19 . The device of  claim 1 , wherein the electrolytic solution in the second chamber comprises a salt solution.