Capacitive sensor and method of use
AssigneeAltratech Limited
InventorsTimothy Cummins, Brian O'Farrell
Life of this patent
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Abstract
An analyte in a liquid sample is detected using a capacitive sensor having electrodes and a sensor surface, and a signal processor. The sample is dried to reduce its liquid content, and capacitive measurements are made after the drying and preferably also before the drying. The sample may include particles, and the analyte is part of or attached to the particles, and the particles provide a major part of the capacitance change compared to absence of particles. In another example the particles are degenerative and form an integral mass upon application of heat, enhancing the extent of capacitance change.
Claims53
A method of detecting an analyte in a liquid sample using a capacitive sensor (1) having electrodes (3) and a sensor surface (5), and a processor (10) linked with the electrodes, the method comprising the steps of:
- bringing the sample (20, 31) into contact with said sensor surface, measuring capacitance of the sample, and using said measurement to provide data concerning the analyte.
A method as claimed in any preceding claim, wherein the sensor has a CMOS architecture in which CMOS layers provide the electrodes and signal processing circuitry (10).
A method as claimed in any preceding claim, wherein the sensor has a planar top surface without features such as bond wires.
A method as claimed in any preceding claim, wherein the sensor comprises a sensing capacitor (Cs) and a reference metal-insulator-metal (MIM) capacitor (Cr) and said capacitors form the front-end (11) of a second-order sigma-delta switched-capacitor modulator A-to-D converter (12) providing a one-bit digital output bit stream representing the charge balancing between sensing and reference capacitors, and a filter (13) for averaging the bit-stream to provide a digital output word.
A method as claimed in any preceding claim, wherein the sample is dried by a heater incorporated within the layers of a CMOS structure which includes the electrodes at a top level.
A method as claimed in any preceding claim, wherein the signal processor (10) monitors the rate of evaporation of sample liquid to provide a characteristic signature for the analyte.
A method as claimed in any preceding claim, wherein the sample is milk, and the method determines protein and/or casein concentration.
A method as claimed in any preceding claim, comprising the step of providing a PNA probe for binding to the analyte.
A method as claimed in any preceding claim, comprising the steps of:
- providing PNA probes n the sensor surface and attracting DNA molecules to the sensor surface by temporarily stopping the signal processor (10) and placing a positive voltage on a plurality of the electrodes of the sensor and,
- once the target DNA molecules are bound to the PNA probes, a negative voltage is then applied to said electrodes to repel any non-specifically bound DNA molecules, whereas the specifically-bound target DNA molecules stay tethered at the surface due to the Watson-Crick complementary binding energies, and
- resume operation of the signal processor to measure capacitance.
A method as claimed in any preceding claim, wherein the signal processor modulates electrode drive frequency and enable spectral analysis of the analyte at the surface, to assist distinguishing between big and small particles, or between bound and un-bound molecules.
A method as claimed in any preceding claim, wherein the electrodes are arranged to provide analyte, negative and reference sensors, and are calibrated with a positive fluid or buffer solution containing a known amount of beads to be measured;
- an analyte channel containing the same fluid or buffer solution, with an unknown amount of beads to be determined;
- and a negative channel containing the same fluid or buffer solution with none of the target beads present.
A method as claimed in any of claims 5 to 33, comprising the step of attracting target Nucleic Acid molecules to the sensor surface so that they act as a ligand tethering a magnetic bead to the surface due to Watson-Crick pairing of the NA to a first complementary probe on the bead, and to a second complementary probe immobilised on the sensor surface, and then applying a magnetic field at a level so that the beads stay bound initially due to the NA-PNA Watson-Crick binding energies, applying heat to the sample until the temperature reaches the characteristic NA-probe melting temperature at which some bonds break and some beads (202) are pulled away under magnetic attraction, and monitoring real time capacitance change.
A method as claimed in any preceding claim, wherein the sensor surface has a plurality of different sensor regions, each with a different immobilized probe, and differential sensing is performed.
A sensing apparatus comprising a sensor (1) comprising capacitive electrodes (3, 4) beneath a sensor surface, and a processor (10) linked with the electrodes, wherein the apparatus comprises means for:
- bringing the sample into contact with said sensor surface,
- measuring capacitance of the sample, and
- using said measurement to derive data concerning the analyte.
Dependencies are inferred from the claim text.