Sensor and method for detection of a target substance

Abstract

A sensor, in one configuration, includes a plurality of beads located in a channel. The beads are attached to a surface of the channel by a biological binding mechanism that can be selectively unbound in the presence of a target substance. A measurement system is configured and arranged to determine the population of beads in the channel after the introduction of an analyte solution into the channel.

1 . A sensor to determine if a target substance is present in an analyte comprising: 
 molecular tethers attached to a sensor surface such that at least some of a plurality of beads, as a result of a biological interaction between a target substance and the tethers, can at least one of be attached to the sensor surface by the tethers or released from the surface by cleaving the tethers; and    a measurement system configured and arranged to determine the population of beads at the sensor surface after the introduction of the analyte into the sensor.    
     
     
         2 . The sensor of  claim 1  wherein a tether includes a hybrid double-stranded DNA molecule, an antibody, a modified antibody, a modified antigen or a peptide.  
     
     
         3 . A sensor to determine if a target substance is present in an analyte comprising: 
 a plurality of beads located in a channel and attached to a surface of the channel by a molecular tether that can be selectively cleaved in the presence of a target substance to release at least some of the beads from the surface of the channel; and    a measurement system configured and arranged to determine the population of beads in the channel after the introduction of the analyte into the channel.    
     
     
         4 . The sensor of  claim 3  wherein the target substance is a target antigen and a molecular tether includes a modified antigen and an antibody with the modified antigen having a lower binding constant than the target antigen.  
     
     
         5 . The sensor of  claim 4  wherein the modified antigen has an approximately 2 orders of magnitude lower binding constant than the target antigen.  
     
     
         6 . The sensor of  claim 3  wherein the target substance is a target DNA and a molecular tether is a hybridized double-stranded DNA tether with one of the single-stranded DNA fragments of the double-stranded DNA tether being complementary to the target DNA.  
     
     
         7 . The sensor of  claim 6  wherein the hybridized double-stranded DNA tether includes first and second single-strand DNA fragments, the first single-strand DNA fragment being attached to a surface of the channel, the sequence of the first single-strand DNA fragment being complementary to the target DNA, and the second single-strand DNA fragment being attached to a surface of a bead.  
     
     
         8 . The sensor of  claim 3  wherein the measurement system is a signal transduction system, a conductivity measurement system, a coulometric measurement system, a spectrometric measurement system, an optical measurement system, or an electrochemical counting system.  
     
     
         9 . A sensor to detect a target antigen comprising: a plurality of beads attached to a sensor surface by a modified antigen and an antibody wherein the modified antigen has a lower binding constant than the target antigen.  
     
     
         10 . A sensor to detect a target antibody comprising: a plurality of beads attached to a sensor surface by a modified antibody and an antigen wherein the modified antibody has a lower binding constant than the target antibody.  
     
     
         11 . A sensor to detect a target substance in an analyte comprising: 
 a channel;    a plurality of beads located in the channel and attached to a surface of the channel by a molecular tether that can be selectively cleaved in the presence of a target substance to release at least some of the beads from the surface of the channel;    measurement means for determining the population of beads in the channel after the introduction of the analyte into the channel.    
     
     
         12 . A method of detecting a target substance comprising: 
 providing a number of molecular tethers at a channel surface of a sensor such that at least some of a plurality of beads, as a result of a biological interaction between a target substance and the tethers, can at least one of be attached to the channel surface by the tethers or released from the channel surface by cleaving the tethers;    introducing an analyte into the channel; and    thereafter, determining the population of beads at the channel surface to indicate a presence of the target substrate in the analyte.    
     
     
         13 . The method of  claim 12  wherein the tethers include a hybrid double-stranded DNA molecule, an antibody, a modified antibody, a modified antigen or a peptide.  
     
     
         14 . The method of  claim 12  wherein the target substance is a target DNA and a molecular tether is a hybridized double-stranded DNA tether with one of the single-stranded DNA fragments of the double-stranded DNA tether being complementary to the target DNA.  
     
     
         15 . The method of  claim 14  wherein the hybridized double-stranded DNA tether includes first and second single-strand DNA fragments, the first single-strand DNA fragment being attached to a surface of the channel, the sequence of the first single-strand DNA fragment being complementary to the target DNA, and the second single-strand DNA fragment being attached to a surface of a bead.  
     
     
         16 . The method of  claim 12  wherein the target substance is a target antigen and a molecular tether includes a modified antigen and an antibody with the modified antigen having a lower binding constant than the target antigen.  
     
     
         17 . The method of  claim 12  wherein the target substance is a target antibody and a molecular tether includes a modified antibody and an antigen with the modified antibody having a lower binding constant than the target antibody.