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.

1 . An analyte detection device, comprising:
 a first substrate and a second substrate aligned to define a gap therebetween;   an array of wells disposed in the second substrate, wherein:
 each well is of the array of wells is dimensioned to hold a single solid support of a plurality of solid supports, the plurality of solid supports being configured to bind to an analyte of interest; 
 each well of the array of wells comprises a first sidewall and a bottom surface; and 
 at least a top portion of the first sidewall is oriented at an obtuse angle with reference to the bottom surface; and 
   an actuation component configured to facilitate movement of the plurality of solid supports to the array of wells.   
     
     
         2 . The analyte detection device of  claim 1 , wherein a bottom portion of the first sidewall is oriented at the obtuse angle with reference to the bottom surface. 
     
     
         3 . The analyte detection device of  claim 1 , wherein each well comprises a second sidewall that is perpendicular to the bottom surface. 
     
     
         4 . The analyte detection device of  claim 1 , wherein each well comprises a second sidewall that is oriented at an acute angle with reference to the bottom portion. 
     
     
         5 . The analyte detection device of  claim 1 , wherein each well has a frustoconical shape. 
     
     
         6 . The analyte detection device of  claim 1 , wherein each well has an inverted frustoconical shape. 
     
     
         7 . The analyte detection device of  claim 1 , wherein the first substrate comprises a first portion at which a liquid containing the analyte of interest is introduced and a second portion toward which the liquid is moved, wherein the array of wells is disposed proximate the second portion. 
     
     
         8 . The analyte detection device of  claim 1 , wherein at least one of the first and second substrates is substantially transparent to facilitate optical interrogation of the wells. 
     
     
         9 . The analyte detection device of  claim 8 , further comprising an optical imaging component configured to determine a number of the solid supports disposed in a well and bound to the analyte of interest. 
     
     
         10 . The analyte detection device of  claim 1 , wherein a plurality of the plurality of solid supports are magnetic solid supports. 
     
     
         11 . The analyte detection device of  claim 10 , wherein a magnetic field is used to facilitate loading the magnetic solid supports into respective wells. 
     
     
         12 . The analyte detection device of  claim 1 , further comprising a reagent reservoir disposed on the first substrate. 
     
     
         13 . The analyte detection device of  claim 12 , wherein at least one reagent disposed in the reagent reservoir comprises a detectable label, a binding member, a dye, or a surfactant. 
     
     
         14 . The analyte detection device of  claim 12 , wherein at least one reagent is disposed in the reagent reservoir in a printed or dried form. 
     
     
         15 . The analyte detection device of  claim 1 , wherein each solid support comprises a passivating layer configured to minimize non-specific attachment of non-capture components to the solid support. 
     
     
         16 . A method of detecting an analyte of interest, comprising:
 introducing a liquid comprising an analyte of interest into an analyte detection device comprising:
 a first substrate and a second substrate aligned to define a gap therebetween; 
 an array of wells disposed in the second substrate, wherein:
 each well is of the array of wells is dimensioned to hold a single solid support of a plurality of solid supports, the plurality of solid supports being configured to bind to an analyte of interest; 
 each well of the array of wells comprises a first sidewall and a bottom surface; 
 at least a top portion of the first sidewall is oriented at an obtuse angle with reference to the bottom surface; 
 the first substrate comprises a first portion at which the liquid comprising the analyte of interest is introduced and a second portion toward which the liquid is moved, wherein the array of wells is disposed proximate the second portion; and 
 
 an actuation component configured to facilitate movement of the plurality of solid supports to the array of wells; 
   introducing the solid supports to the liquid comprising the analyte of interest;   moving the plurality of solid supports bound to the analyte of interest towards the array of wells;   loading the plurality of solid supports into respective wells of the array of wells; and   imaging the array of wells to determine a number of the solid supports disposed in the array of wells and bound to the analyte of interest.   
     
     
         17 . The method of  claim 16 , wherein at least one of the first and second substrates is substantially transparent to facilitate optical interrogation of the wells. 
     
     
         18 . The method of  claim 16 , wherein a plurality of the plurality of solid supports are magnetic solid supports, the method further comprising:
 actuating a magnetic field to facilitate loading the magnetic solid supports into respective wells.   
     
     
         19 . The method of  claim 16 , further comprising:
 calculating a ratio of the solid supports bound to the analyte of interest to solid supports not bound to the analyte of interest.   
     
     
         20 . The method of  claim 19 , wherein at least one of the first substrate and the second substrate is substantially transparent to facilitate optical interrogation of the wells.