Devices and methods for determining the length of biopolymers and distances between probes bound thereto
First Claim
1. A device for determining a length of an analyte by detecting electrical signals, the device comprising:
- a fluidic channel defined by a trench in a substrate;
a pair of electromotive electrodes disposed at a first end and a second end of the fluidic channel; and
a plurality of sensing electrodes disposed at discrete laterally offset locations along a length of the fluidic channel for detection of two or more electrical signals corresponding to two or more detector volumes disposed along the fluidic channel, each detector volume being defined by two laterally offset sensing electrodes,wherein (i) said sensing electrodes are connected to a voltmeter for capturing said electrical signals corresponding to said detector volumes, with the sensing electrodes not being connected to a voltage source, (ii) the fluidic channel is a nanochannel or a microchannel, (iii) relative positions of the sensing electrodes are known, and (iv) the captured electrical signals in conjunction with the relative positions of the sensing electrodes indicate the length of the analyte.
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Accused Products
Abstract
Devices and methods for detecting the length of analytes, and/or sequencing analytes are provided in which two or more electrical signals are obtained as an analyte traverses a fluidic channel. Detection of the relative position of probes hybridized to a biopolymer and/or the length of the analyte (e.g., a biopolymer) does not rely on the absolute time between detection events of a given electrical signal to determine a distance associated with the biopolymer. Instead, multiple signals are obtained as functions of time) corresponding to a plurality of detector volumes at known locations along a fluidic channel through which the biopolymer passes, and the distances are determined from the multiple signals.
184 Citations
35 Claims
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1. A device for determining a length of an analyte by detecting electrical signals, the device comprising:
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a fluidic channel defined by a trench in a substrate; a pair of electromotive electrodes disposed at a first end and a second end of the fluidic channel; and a plurality of sensing electrodes disposed at discrete laterally offset locations along a length of the fluidic channel for detection of two or more electrical signals corresponding to two or more detector volumes disposed along the fluidic channel, each detector volume being defined by two laterally offset sensing electrodes, wherein (i) said sensing electrodes are connected to a voltmeter for capturing said electrical signals corresponding to said detector volumes, with the sensing electrodes not being connected to a voltage source, (ii) the fluidic channel is a nanochannel or a microchannel, (iii) relative positions of the sensing electrodes are known, and (iv) the captured electrical signals in conjunction with the relative positions of the sensing electrodes indicate the length of the analyte. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 29, 30)
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20. A method for determining a length of an analyte, the method comprising the steps of:
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disposing the analyte in a fluidic channel defined by a trench in a substrate; applying a potential along the fluidic channel between a pair of electromotive electrodes disposed at a first end and a second end of the fluidic channel; translocating the analyte from a first end of the fluidic channel to a second end of the fluidic channel; detecting two or more electrical signals as the analyte moves through the fluidic channel, said two or more electrical signals corresponding to two or more detector volumes of the fluidic channel, said two or more electrical signals being detected using a plurality of sensing electrodes disposed at discrete laterally offset locations along the length of the fluidic channel, each detector volume being defined by two sensing electrodes; and determining the length of the analyte by analyzing the two or more detected electrical signals, wherein (i) said sensing electrodes are connected to a voltmeter for capturing said electrical signals corresponding to said detector volumes, with the sensing electrodes not being connected to a voltage source, (ii) the fluidic channel is a nanochannel or a microchannel, (iii) relative positions of the sensing electrodes are known, and (iv) the captured electrical signals in conjunction with the relative positions of the sensing electrodes indicate the length of the analyte. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28)
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31. A system for sequencing a biopolymer, the system comprising:
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(a) a fluidic channel defined by a trench in a substrate; (b) a pair of electromotive electrodes disposed at a first end and a second end of the fluidic channel; and (c) a plurality of sensing electrodes disposed at discrete laterally offset locations along a length of the fluidic channel for detection of two or more electrical signals corresponding to two or more detector volumes disposed along the fluidic channel, each detector volume being defined by two laterally offset sensing electrodes, wherein the fluidic channel is configured such that a biopolymer with at least a first plurality of probes attached thereto may pass therethrough, wherein said sensing electrodes are connected to a voltmeter for capturing said electrical signals corresponding to said detector volumes as said biopolymer passes through the fluidic channel, with the sensing electrodes not being connected to a voltage source, wherein the fluidic channel is a nanochannel or a microchannel, and wherein relative positions of the sensing electrodes are known; and (d) an analyzing module that determines at least a portion of the sequence of the biopolymer based at least in part on a plurality of the captured electrical signals. - View Dependent Claims (32)
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33. An apparatus for sequencing a biopolymer, the apparatus comprising:
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(a) a fluidic channel defined by a trench in a substrate; (b) a pair of electromotive electrodes disposed at a first end and a second end of the fluidic channel; and (c) a plurality of sensing electrodes disposed at discrete laterally offset locations along a length of the fluidic channel for detection of two or more electrical signals corresponding to two or more detector volumes disposed along the fluidic channel, each detector volume being defined by two laterally offset sensing electrodes, wherein the fluidic channel is configured such that a biopolymer with at least a first plurality of probes attached thereto may pass therethrough, wherein said sensing electrodes are are connected to a voltmeter for capturing said electrical signals corresponding to said detector volumes as said biopolymer passes through the fluidic channel, with the sensing electrodes not being connected to a voltage source, wherein the fluidic channel is a nanochannel or a microchannel, wherein relative positions of the sensing electrodes are known, and wherein the captured electrical signals in conjunction with the relative positions of the sensing electrodes indicate at least a portion of the sequence of the biopolymer.
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34. A device for voltage sensing of analytes, the device comprising:
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a fluidic channel defined by a trench in a substrate; a first and a second pair of sensing electrodes disposed in the channel for sensing voltage therein, the second pair of sensing electrodes being disposed distal to the first pair of sensing electrodes, and each pair of sensing electrodes comprising a first and a second electrode disposed at two discrete locations offset along a length of the channel and defining a detector volume therebetween; and a pair of electromotive electrodes disposed at a first end and a second end of the channel for applying a potential along the channel, wherein the channel comprises a nanochannel or a microchannel and said sensing electrodes are connected to a voltmeter for capturing said sensed voltage corresponding to said detector volumes as said analyte passes through the fluidic channel, with the sensing electrodes not being connected to a voltage source. - View Dependent Claims (35)
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Specification