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.
1. A digital microfluidic and analyte detection device, comprising:
a first substrate and a second substrate aligned to define a gap therebetween, the first substrate comprising a plurality of electrodes to generate electrical actuation forces on a liquid droplet disposed in the gap;
at least one reagent disposed in a printed or dried form on at least one of the first substrate and the second substrate and configured to be carried by the liquid droplet upon contact with the liquid droplet, wherein the liquid droplet with the at least one reagent further comprises at least one solid support and an analyte of interest; and
an array of elements, each element dimensioned to hold a single one of the at least one solid support or the at least one analyte of interest, wherein each element of the array of elements comprises a first sidewall and a bottom surface, and wherein at least a top portion of the first sidewall is oriented at an obtuse angle with reference to the bottom surface.
2. The device of claim 1 , wherein each element comprises a well.
3. The device of claim 2 , wherein the first substrate comprises a first portion at which the liquid droplet is introduced and a second portion toward which a liquid droplet is moved, wherein the array is disposed proximate the second portion.
4. The device of claim 2 , wherein at least one of the first and second substrates is substantially transparent to facilitate optical interrogation of the wells.
5. The device of claim 1 , wherein the reagent is selected from the group consisting of a detectable label, a binding member, a dye, a surfactant, and a combination thereof.
6. The device of claim 5 , wherein the detectable label comprises at least one binding member that specifically binds to the analyte of interest.
7. The device of claim 5 , wherein the detectable label comprises a chromagen, a fluorescent compound, an enzyme, a chemiluminescent compound, or a radioactive compound.
8. The device of claim 5 , wherein the binding member comprises a receptor or an antibody.
9. The device of claim 2 , further comprising a first layer disposed on the surface of the first substrate and extending over the plurality of electrodes and a second layer disposed on a surface of the first layer, wherein the first layer is a dielectric layer and the second layer is a hydrophobic layer.
10. The device of claim 9 , wherein each well is positioned in the second layer.
11. The device of claim 1 , wherein a bottom portion of the first sidewall is oriented at the obtuse angle with reference to the bottom surface.
12. The device of claim 1 , wherein each element of the array of elements comprises a second sidewall that is perpendicular to the bottom surface.
13. The device of claim 1 , wherein each element of the array of elements comprises a second sidewall that is oriented at an acute angle with reference to the bottom portion.
14. A method of detecting an analyte of interest in a liquid droplet, comprising:
introducing a liquid droplet containing an analyte of interest into a device comprising:
a first substrate and a second substrate aligned to define a gap therebetween, the first substrate comprising a plurality of electrodes to generate electrical actuation forces on the liquid droplet when disposed in the gap;
at least one reagent disposed in a printed or dried form on at least one of the first substrate and the second substrate and configured to be carried by the liquid droplet upon contact with the liquid droplet, wherein the liquid droplet with the at least one reagent further comprises at least one solid support; and
an array of elements, each element dimensioned to hold at least a portion of the liquid droplet in a discrete region, wherein each element of the array of elements comprises a first sidewall and a bottom surface, and wherein at least a top portion of the first sidewall is oriented at an obtuse angle with reference to the bottom surface;
using an electrical actuation force to move the liquid droplet towards the array;
labeling the analyte of interest with a detectable label; and
detecting the analyte of interest in the array.
15. The method of claim 14 , wherein the liquid droplet is a mixture comprising a first liquid including the analyte of interest and a second liquid including the at least one solid support,
the method further comprising mixing the mixture by moving the mixture back and forth, moving the mixture in a circular pattern, splitting the mixture into two or more submixtures and merging the submixtures.
16. The method of claim 14 , wherein the electric actuation force is droplet actuation, electrophoresis, electrowetting, dielectrophoresis, electrostatic actuation, electric field mediated, or electrode mediated.
17. The method of claim 14 , wherein the elements comprise wells, and the method further comprises sealing at least one of the wells within the array with a hydrophobic liquid.
18. The method of claim 14 , further comprising measuring the analyte of interest, wherein the measuring comprises:
identifying solid supports in the array that contain the detectable label; and
calculating a ratio of the solid supports containing the detectable label to solid supports without the detectable label.
19. The device of claim 2 , wherein the plurality of electrodes generates electrical actuation forces on a wash droplet disposed in the gap to wash the solid supports to remove molecules not bound to the solid supports.
20. The device of claim 19 , wherein the plurality of electrodes generates electrical actuation forces on the wash droplet to move the wash droplet across the array of wells.