Devices and methods for sample analysis

Abstract

Integrated devices that include a sample preparation component integrated with a detection component are disclosed. The sample preparation component may be a digital microfluidics module or a surface acoustic wave module which modules are used for combing a sample droplet with a reagent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or absence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells. Additional analyte detection devices configured to operate an analyte detection chip to prepare a test sample and to detect an analyte related signal from the prepared test sample in the analyte detection chip are disclosed. The analyte detection chip may include a digital microfluidics (DMF) region and an analyte detection region which may overlap or may be spatially separated. The analyte detection device may be configured for detection of analyte by an optical or electrochemical means operably connected with an analyte detection chip inserted into the device.

1 .- 60 . (canceled) 
     
     
         61 . A method for electrochemical detection of an analyte in a sample, the method comprising:
 (a) introducing the sample into a cartridge, the cartridge comprising:   a first substrate; a second substrate; a gap separating the first substrate from the second substrate; a plurality of electrodes to generate electrical actuation forces on a liquid droplet; and an electrochemical species sensing region comprising a working electrode and a reference electrode;   (b) actuating the plurality of electrodes to provide a first liquid droplet comprising the analyte;   (c) actuating the plurality of electrodes to provide a second liquid droplet comprising an enzyme selective for the analyte;   (d) actuating the plurality of electrodes to merge the first and second droplets to create a mixture;   (e) actuating the plurality of electrodes to move all or a portion of the mixture to the electrochemical sensing region;   (f) detecting, via the working and reference electrodes, an electrical signal of an electrochemical species generated by action of the enzyme on the analyte.   
     
     
         62 . The method of  claim 61 , wherein the second liquid droplet comprises a redox mediator. 
     
     
         63 . The method of  claim 61 , further comprising determining a concentration of the analyte based on the electrical signal. 
     
     
         64 . The method of  claim 61 , wherein the electrochemical sensing region is located in a capillary region. 
     
     
         65 . A method for electrochemical detection of an analyte in a sample, the method comprising:
 (a) introducing the sample into a cartridge, the cartridge comprising:   a first substrate; a second substrate; a gap separating the first substrate from the second substrate, a plurality of electrodes to generate electrical actuation forces on a liquid droplet; and an electrochemical species sensing region comprising a working electrode and a reference electrode;   (b) actuating the plurality of electrodes to provide a first liquid droplet comprising the analyte;   (c) actuating the plurality of electrodes to provide a second liquid droplet comprising a solid substrate comprising a first binding member that specifically binds to the analyte;   (d) actuating the plurality of electrodes to merge the first and second droplets to create a mixture;   (e) actuating the plurality of electrodes to merge all or a portion of the mixture with a third liquid droplet comprising a second binding member that specifically binds to the analyte;   (f) holding the solid substrate in place while actuating the plurality of electrodes to remove any unbound analyte and/or second binding member;   (g) actuating the plurality of electrodes to contact the solid substrate with a substrate molecule for the enzyme conjugated to the second binding member; and   (h) detecting, via the working and reference electrodes, an electrical signal of an electrochemical species generated by action of the enzyme on the substrate molecule.   
     
     
         66 . The method of  claim 65 , wherein the method comprises moving a liquid droplet comprising the solid second substrate from step (f) to the electrochemical sensing region prior to steps (g) and (h). 
     
     
         67 . The method of  claim 65 , wherein the method comprises moving a liquid droplet comprising the solid second substrate and enzyme substrate from step (g) to the electrochemical sensing region. 
     
     
         68 . The method of  claim 65 , further comprising determining a concentration of the analyte based on the electrical signal. 
     
     
         69 . The method of  claim 65 , further comprising conducting an immunoassay on a sample, using a single cartridge or a different cartridge. 
     
     
         70 . The method of  claim 69 , comprising spatially segregating single molecules and optically detecting the segregated single molecules to detect presence of an analyte in the sample. 
     
     
         71 .- 86 . (canceled)