Devices and methods for sample analysis
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. Additonal 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. An instrument for detection of an analyte in a sample, the instrument comprising:
a control unit;
a cartridge interface for operable connection to one or more cartridges comprising one of more samples, and
a detection unit comprising an electrical detection unit for detection of an electrical signal from the one or more cartridges, the electrical detection unit comprising an electrical circuit connected to the cartridge interface, wherein the electrical circuit is operably connected to a recorder for recording the electrical signal, wherein the electrical signal is generated by:
an electrochemical species produced from action of an analyte-specific enzyme on the analyte; or
an electrochemical species produced from action of an enzyme on a substrate molecule, wherein the enzyme is conjugated to an antibody that specifically binds to the analyte;
wherein the control unit is configured for controlling a sequence of activation and deactivation of one or more electrodes to facilitate movement of a sample droplet present in one of the one or more cartridges, wherein the movement comprises:
merging the sample droplet with a reagent droplet to generate a merged droplet, and
moving the merged droplet or portion thereof to the detection unit,
wherein the detection unit detects:
i) a first analyte related signal from the merged droplet or portion thereof; and
ii) a second analyte related signal from spatially segregated single molecules.
2. The instrument of claim 1 , wherein the first analyte related signal comprises an electrical signal and the second analyte related signal comprises an optical signal.
3. The instrument of claim 1 , wherein the first analyte related signal comprises an optical signal and the second analyte related signal comprises an optical signal.
4. The instrument of claim 1 , wherein the detection unit is configured to detect both the first and second analyte related signals from one of the one or more cartridges.
5. The instrument of claim 1 , wherein the detection unit is configured to detect the first and second analyte related signals from different cartridges.
6. The instrument of claim 1 , wherein instrument further comprises a power source and wherein the control unit controls the electric power applied to the one or more electrodes.
7. The instrument of claim 1 , wherein the control unit controls duration of activation of the one or more electrodes.
8. The instrument of claim 1 , wherein the detection unit comprises an optical detection unit.
9. The instrument of claim 8 , wherein the optical detection unit is configured for detecting an optical signal from molecules spatially segregated into single wells.
10. The instrument of claim 8 , wherein the optical detection unit is configured for detecting an optical signal from single molecules spatially segregated into single wells.
11. The instrument of claim 8 , wherein the optical detection unit comprises a detector for one or more of a colorimetric signal, a turbidometric signal, or a fluorescent signal.
12. The instrument of claim 8 , wherein the optical detection unit comprises an imaging system.
13. The instrument of claim 1 , wherein the instrument comprises a processor which executes a program with instructions to the control unit to activate and de-activate the one or more electrodes and to operate the detection unit.
14. The instrument of claim 1 , wherein the instrument is configured to conduct two or more of clinical chemistry, immunoassay, spatial segregation of single molecules, imaging, agglutination assay, and hematology.
15. The instrument of claim 1 , comprising an electrical detection unit comprising an electrical circuit configured for detecting an electrical signal from a working electrode of a cartridge comprising an electrochemical detection region; and comprising an optical detection unit comprising one or more of: a camera, a microscope, a charge coupled device (CCD), a spectrometer, a complementary metal-oxide-semiconductor (CMOS) detector, a fluorimeter, a colorimeter, and a turbidometer.
16. An instrument for detection of an analyte in a sample, the instrument comprising:
a control unit;
a cartridge interface for operable connection to one or more cartridges comprising one or more samples, and
a detection unit; and
wherein the control unit is configured for controlling the sequence of activation and deactivation of one or more electrodes to facilitate movement of a sample droplet present in the one or more cartridges, wherein the movement comprises:
merging the sample droplet with a reagent droplet to generate a merged droplet, and
moving the merged droplet or portion thereof to the detection unit, wherein the detection unit detects:
i) a first analyte related signal from the merged droplet or portion thereof in a cartridge;
wherein the detection unit comprises an electrical detection unit that detects an electrical signal selected from the group consisting of current, voltage, impedance, capacitance, charge, conductivity, resistance, or a combination thereof,
wherein the cartridge interface comprises an insertion slot for accommodating the one or more cartridges, wherein the one or more cartridges comprises:
(i) an electrical detection region, the electrical detection region comprising: a working electrode and a reference electrode for detecting electrical signal from an electrochemical species generated when an analyte is present in the sample; or
(ii) an optical detection region, the optical detection region comprising an array of wells for accommodating at least one bead for detecting the analyte.
17. The instrument of claim 16 , wherein instrument further comprises a power source and wherein the control unit controls the electric power applied to the one or more electrodes.
18. The instrument of claim 16 , wherein the control unit controls duration of activation of the one or more electrodes.
19. The instrument of claim 16 , wherein the optical detection unit is configured for detecting an optical signal from single molecules spatially segregated into single wells within the array of wells.
20. The instrument of claim 16 , wherein the optical detection unit comprises a detector for one or more of a colorimetric signal, a turbidometric signal, or a fluorescent signal.
21. The instrument of claim 16 , wherein the optical detection unit comprises an imaging system.
22. The instrument of claim 16 , wherein the instrument comprises a processor which executes a program with instructions to the control unit to activate and de-activate the one or more electrodes and to operate the detection unit.
23. The instrument of claim 16 , wherein the instrument is configured to conduct two or more of clinical chemistry, immunoassay, spatial segregation of single molecules, imaging, agglutination assay, and hematology.
24. The instrument of claim 16 , comprising an electrical detection unit comprising an electrical circuit configured for detecting an electrical signal from a working electrode of a cartridge comprising an electrochemical detection region; and comprising an optical detection unit comprising one or more of: a camera, a microscope, a charge coupled device (CCD), a spectrometer, a complementary metal-oxide-semiconductor (CMOS) detector, a fluorimeter, a colorimeter, and a turbidometer.