Detection of target analytes at picomolar concentrations

A method of determining concentration of an analyte in a solution, the method comprising:

• adding to the solution, a plurality of magnetic beads each of which includes a first binding agent that is specific to the analyte;
• adding to the solution, a plurality of dielectric nanobeads each of which has a diameter of less than 1,000 nm and includes a second binding agent that is specific to the analyte;
• forming a plurality of complexes each of which includes at least one magnetic bead of the plurality of magnetic beads bound to the analyte by the first binding agent and at least one dielectric nanobead of the plurality of dielectric nanobeads bound to the analyte by the second binding agent;
• applying a magnetic field to the plurality of complexes to retain the plurality of complexes;
• eluting the dielectric nanobeads from the plurality of retained complexes to form a plurality of surrogates;
• collecting the surrogates on a surface of a sensor;
• determining a number of the surrogates on the surface based on a property of the sensor;
• and
• comparing the number of surrogates on the surface to a standard to determine the concentration of the analyte in the solution as low as 10 aM.

An apparatus for determining concentration of an analyte in a solution, the apparatus comprising:

• a fluid circuit for receiving:
• a solution including an analyte;
• a plurality of magnetic beads each of which includes a first binding agent that is specific to the analyte;
• and
• a plurality of dielectric nanobeads and includes a second binding agent that is specific to the analyte,
• wherein the plurality of magnetic beads and the plurality of dielectric nanobeads form a plurality of complexes each of which includes at least one magnetic bead of the plurality of magnetic beads bound to the analyte by the first binding agent and at least one dielectric nanobead of the plurality of dielectric nanobeads bound to the analyte by the second binding agent;
• a magnet applying a magnetic field to a portion of the fluid circuit to retain the plurality of complexes;
• a first inlet fluidly coupled to the fluid circuit, the first inlet receiving an eluting solution for eluting the dielectric nanobeads from the plurality of retained complexes to form a plurality of surrogates;
• and
• a sensor having a nanohole array for collecting the surrogates on a surface thereof, the sensor outputting a sensor signal corresponding to a concentration of the analyte in the solution as low as 10 aM based on a number of the surrogates on the surface of the sensor.

An apparatus for determining concentration of an analyte in a solution, the apparatus comprising:

• a fluid circuit for receiving:
• a solution including an analyte;
• a plurality of magnetic beads each of which includes a first binding agent that is specific to the analyte;
• and
• a plurality of dielectric nanobeads and includes a second binding agent that is specific to the analyte,
• wherein the plurality of magnetic beads and the plurality of dielectric nanobeads form a plurality of complexes each of which includes at least one magnetic bead of the plurality of magnetic beads bound to the analyte by the first binding agent and at least one dielectric nanobead of the plurality of dielectric nanobeads bound to the analyte by the second binding agent;
• a magnet applying a magnetic field to a portion of the fluid circuit to retain the plurality of complexes;
• a first inlet fluidly coupled to the fluid circuit, the first inlet receiving an eluting solution for eluting the dielectric nanobeads from the plurality of retained complexes to form a plurality of surrogates;
• a sensor having a nanohole array for collecting the surrogates on a surface thereof;
• and
• an electrochemical cell including a first chamber and a second chamber fluidly coupled to the fluid circuit, wherein the sensor is disposed in the electrochemical cell separating the first and second chambers, and the electrochemical cell outputs a sensor signal corresponding to a concentration of the analyte in the solution as low as 10 aM based on a number of the surrogates on the surface of the sensor.