Diagnostic device and system

Abstract

A portable diagnostic device has a lysate stage ( 167 ) with a port for receiving a sample and containing magnetic beads with a probe, and an outlet port. A series of assay stages ( 161 - 164 ) are linked with the lysate vessel, each with a reservoir linked by channels. The final stage ( 164 ) has a sensor ( 169 ) for detecting beads attached to analyte molecules which have been conveyed according to attachment to probes on beads. Larger transport beads cause reporter beads which are tethered by target NA and probes to be transported to the final sensor stage, where they are released and detected when the transport beads have been removed.

1 - 94 . (canceled) 
     
     
         95 . A portable device comprising:
 a cartridge;   a sensor chip comprising an integrated circuit mounted to the cartridge;   electrodes connected to the circuit at or beneath a sensing surface of the chip;   a capacitance-to-digital converter connected via the circuit to the electrodes; and   terminals of the integrated circuit mounted on a connector on the cartridge for mating with a connector in a reader unit.   
     
     
         96 . The device of  claim 95 , wherein the cartridge comprises reporter beads linked to reporter probes that attach to a target nucleic acid, the beads comprising a material with a dielectric constant higher than dry air. 
     
     
         97 . The device of  claim 96 , further comprising bead capture probes immobilized on the sensing surface. 
     
     
         98 . The device of  claim 97 , wherein the beads are further linked to surface capture probes that anneal to the bead capture probes. 
     
     
         99 . The device of  claim 96 , further comprising magnetically-susceptible transport beads linked to transport probes that anneal to target nucleic acid. 
     
     
         100 . The device of  claim 96 , wherein the reporter probes comprises peptide nucleic acid. 
     
     
         101 . The device of  claim 99 , wherein the reporter probes, bead capture probes, surface capture probes, and transport probes comprise peptide nucleic acid. 
     
     
         102 . The device of  claim 95 , wherein the sensor chip comprises a complex metal oxide semiconductor (CMOS) integrated circuit. 
     
     
         103 . The device of  claim 95 , wherein the integrated circuit includes a temperature sensor operable to determine the temperature of the cartridge, wherein when the cartridge is inserted into the reader unit, a heater in the reader brings the cartridge to a start temperature and the temperature sensor provides feedback from the sensor chip to the reader. 
     
     
         104 . The device of  claim 95 , further comprising calibration data stored on the chip in non-volatile memory, wherein the calibration data is used in self-testing by the device when the cartridge is inserted into the reader unit. 
     
     
         105 . The device of  claim 95 , wherein the cartridge includes
 assay stages, each with a reservoir linked by channels, at least one of the assay stages including the sensor chip;   an inlet for receiving a sample;   a lysing agent in, or in fluid communication with, the inlet;   a wax plug between the inlet and the assay stages; and   magnetic transport beads linked to probes embedded in the wax plug.   
     
     
         106 . A detection method comprising:
 binding a nucleic acid target to a solid substrate and a reporter in a reservoir, wherein the reporter has a dielectric constant higher than air;   washing the bound target to remove non-attached reporter;   placing the reporter-bound target on a sensor; and   measuring capacitance of the reporter on the sensor to detect a quantity of the target.   
     
     
         107 . The method of  claim 106 , wherein the solid substrate comprises magnetic beads. 
     
     
         108 . The method of  claim 106 , further comprising using a magnet to move the reporter-bound target into a wash stage for the washing step. 
     
     
         109 . The method of  claim 106 , wherein there is a 1:1 ratio of reporter to target in the reporter-bound target placed on the sensor. 
     
     
         110 . The method of  claim 106 , wherein the sensor comprises a capacitance sensor on a chip, wherein a capacitance measured by the sensor correlates to a quantity of the nucleic acid target. 
     
     
         111 . The method of  claim 110 , wherein the circuitry further comprises terminals for a connection of the ship to an external device. 
     
     
         112 . The method of  claim 110 , wherein the chip is housed within an encapsulated fluidic structure, wherein the fluidic structure includes an inlet in fluidic communication with: the reservoir, a wash station, and a surface of the sensor. 
     
     
         113 . The method of  claim 106 , wherein the reporter comprises reporter beads linked to probes that anneal to the target, wherein each reporter bead has a capacitance greater than dry air 
     
     
         114 . The method of  claim 113 , wherein the probes comprise peptide nucleic acid complementary to the target.