Nanopump devices and methods
First Claim
1. A nanopump comprising a supply reservoir for holding a supply electrolyte solution, disposed against a wall region of the reservoir, a membrane having a plurality of flow-through channels extending between an inner membrane surface adapted for contact with said supply electrolyte solution, and an outer side adapted for contact with a recipient electrolyte solution contained outside of the supply reservoir, where said channels have a minimum cross-sectional dimension between 2 and 100 nm and a net surface charge when the pH of the supply solution is within a given pH range, electrodes disposed on either side of membrane for contact with said supply and recipient solutions, and a controller including a power source operatively connected to said electrodes for applying a selected voltage potential across said channel, to pump solution in the supply reservoir through said channel.
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Abstract
Disclosed is a nanopump for pumping small volumes of electrolyte solution under the control of a voltage source. The device includes a chamber and a nanopore membrane which partitions the chamber into upstream and downstream regions. When a voltage potential is applied across the membrane, electroosmotic flow through the membrane channels produces a precise-volume flow between the two chamber regions. Also disclosed is a method for precis-volume pumping employing the nanopump. Also disclosed is device for determining the lengths of nucleic acid fragments in an electrolyte solution of different-length fragments is disclosed. The device includes a chamber having disposed therein, a nanopore channel extending between upstream and downstream chamber regions. By applying a voltage potential across upstream and downstream electrodes in the chamber regions, individual nucleic acid fragments contained in the solution are moved through the channel. A current detector detects time-dependent current flow across said membrane, and from the measured flow times, fragments lengths can be estimated. Also disclosed is a device for separating macromolecules in a solution of macromolecules having different molecular sizes. The device includes a separation chamber having upstream and downstream ends, and one or more nanopore membranes disposed in the chamber between said upstream and downstream ends, partitioning the chamber into two or more chamber regions, respectively. Upstream and downstream electrodes are disposed at the upstream and downstream ends of the chamber, respectively. A controller in the device has a power source operatively connected to the electrodes for applying a selected voltage potential across said channel, to pump solution through each of said membranes, in an upstream-to-downstream direction, wherein macromolecules contained in the solution are filtered at each successive membrane, to concentrate successively smaller macromolecules in successively more downstream chamber regions.
54 Citations
28 Claims
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1. A nanopump comprising
a supply reservoir for holding a supply electrolyte solution, disposed against a wall region of the reservoir, a membrane having a plurality of flow-through channels extending between an inner membrane surface adapted for contact with said supply electrolyte solution, and an outer side adapted for contact with a recipient electrolyte solution contained outside of the supply reservoir, where said channels have a minimum cross-sectional dimension between 2 and 100 nm and a net surface charge when the pH of the supply solution is within a given pH range, electrodes disposed on either side of membrane for contact with said supply and recipient solutions, and a controller including a power source operatively connected to said electrodes for applying a selected voltage potential across said channel, to pump solution in the supply reservoir through said channel.
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9. A method of pumping controlled and reproducible nanoliter quantities of an electrolyte solution from a supply reservoir into a recipient electrolyte solution comprising
placing the electrolyte solution in a supply reservoir, in contact with a membrane having a plurality of flow-through channels extending between an inner membrane surface adapted for contact with said supply electrolyte solution, and an outer membrane surface, said channels having a minimum cross-sectional dimension between 2 and 100 nm and a net surface charge at the pH of the supply solution, placing the outer membrane surface in contact with a recipient electrolyte solution, and with a pair of electrodes placed across said membrane, in contact with solution in said supply reservoir and with said recipient electrolyte, applying across said electrodes, a voltage potential effective to pump supply solution across said membrane from the supply reservoir into the recipient solution.
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13. A separation device for separating macromolecules in a solution of macromolecules having different molecular sizes, comprising
a separation chamber having upstream and downstream ends, one or more membranes disposed in said chamber between said upstream and downstream ends, partitioning said chamber into two or more chamber regions, respectively, where (i) each membrane has a plurality of flow-through channels extending between adjacent chamber regions, (ii) said channels have a selected minimum cross-sectional dimension in the range between 2 and 100 nm and a net surface charge when exposed to a solution within a given pH range, and (iii) if the device contains two or more such membranes, the selected minimum cross-section of the channels in any membrane is greater than that in membrane immediately adjacent in the downstream direction, upstream and downstream electrodes disposed in said chamber, for contacting solution placed in the chamber and contained in the in the upstream-most and downstream-most of the chamber regions, respectively, and a controller including a power source operatively connected to said electrodes for applying a selected voltage potential across said channel, to pump solution through each of said membranes, in an upstream-to-downstream direction, wherein macromolecules contained in said solution are filtered at each successive membrane, to concentrate successively smaller macromolecules in successively more downstream chamber regions.
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18. A method of separating macromolecules in a solution of macromolecules having different molecular sizes, comprising:
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(a) placing the electrolyte solution in an upstream chamber region of a chamber having upstream and downstream chamber regions separated by a membrane having a plurality of flow-through channels extending between an inner membrane surface adapted for contact with said solution, and an outer membrane surface in contact with electrolyte solution contained in a downstream reservoir, where (i) said channels have a minimum selected cross-sectional dimension between 2 and 100 nm which is effective to block passage through the membrane of at least one of the different-sized macromolecules, and (ii) a net surface charge at the pH of said solution, (b) with a pair of electrodes placed across said membrane, in contact with solution in said upstream and downstream reservoirs, applying across said electrodes, a voltage potential effective to pump supply solution across said membrane from the upstream into the downstream reservoir, wherein macromolecules in said solution are separated on the basis of their ability to pass through the channels in said membrane.
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21. A device for determining the lengths of nucleic acid fragments in an electrolyte solution of different-length fragments and having a selected pH, comprising
a chamber, a membrane disposed in said chamber and having a channel extending between an upstream chamber region adapted to hold the electrolyte solution of such different-length fragments, and a downstream chamber region adapted to hold an electrolyte solution, where (i) said channel has a selected minimum cross-sectional dimension in the range between 2 and 15 nm and a net surface charge within a given pH range that includes the selected solution pH, upstream and downstream electrodes disposed in said upstream and downstream chamber regions, respectively, for contacting solution placed in the corresponding chamber regions, a controller including (i) a power source operatively connected to said electrodes for applying a selected voltage potential across said channel, to move individual nucleic acid fragments contained in the solution through said channel, and (ii) a current detector for detecting time-dependent current flow across said membrane.
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26. A method for determining the lengths of nucleic acid fragments in an electrolyte solution of different-length fragments and having a selected pH, comprising
(a) placing the solution in an upstream chamber region of a chamber having upstream and downstream chamber regions separated by a membrane having a channel extending between the two chamber regions, where (i) said channel has a selected minimum cross-sectional dimension in the range between 2 and 15 nm and a net surface charge within a given pH range that includes the selected solution pH, (b) with a pair of electrodes placed across said membrane, in contact with solution in said upstream and downstream chamber regions, applying across said electrodes, a voltage potential effective to pump solution across said channel, wherein individual nucleic acid fragments move through said channel, and (c) detecting time-dependent changes in current flow through said channel, as a measure of the length of individual nucleic acid fragments moving through said channel.
Specification