System and method for detecting molecules using an active pixel sensor

Abstract

In a molecule detection system and method, a sample containing target molecules is added to an array of test sites, with each test site containing distinct probe molecules. The probe molecules bind with the target molecules in the sample to form bound complexes. A source illuminates the array of test sites with incident electromagnetic radiation and an active pixel sensor detects the electromagnetic radiation from the array. To detect the presence of target molecules in the sample, the active pixel sensor detects changes in the optical properties of the test sites that result, either directly or indirectly, from their binding of the probe molecules with the target molecules. The target molecules may also be characterized on the basis of which probe molecules bind to them.

We claim:  
     
         1 . A system for testing a sample for the presence of target molecules, said system comprising: 
 a first test site comprising probe molecules, said probe molecules being able to bind to said target molecules to form bound complexes;    a source system for providing incident electromagnetic radiation directed at said first test site, said incident electromagnetic radiation including radiation at a first wavelength; and    an active pixel sensor having a plurality of pixels, at least one of said pixels being disposed for detecting electromagnetic radiation from said test site.    
     
     
         2 . The system of  claim 1 , further comprising a source optical system for focusing said incident electromagnetic radiation from said source system onto said first test site; and 
 a detector optical system for imaging said first test site onto said at least one pixel.    
     
     
         3 . The system of  claim 1 , wherein the absorbance at said first wavelength of said bound complexes is substantially different than the absorbance at said first wavelength of said probe molecules.  
     
     
         4 . The system of  claim 1 , wherein said bound complexes are fluorescent bound complexes, said fluorescent bound complexes absorbing said incident electromagnetic radiation at said first wavelength and emitting electromagnetic radiation at a second wavelength, said system further comprising: 
 a detector filter interposing said first test site and at least one pixel, said filter blocking electromagnetic radiation at said first wavelength and passing electromagnetic radiation at said second wavelength.    
     
     
         5 . The system of  claim 4 , wherein said detector filter is integral to said active pixel sensor.  
     
     
         6 . The system of  claim 1 , wherein said bound complexes are phosphorescent, said bound complexes emitting phosphorescence radiation at a second wavelength after absorbing said incident electromagnetic radiation at said first wavelength.  
     
     
         7 . The system of  claim 1 , wherein said plurality of pixels includes a first pixel and a second pixel, said first and second pixels being disposed for detecting electromagnetic radiation from said test site, and wherein said source system can provide incident electromagnetic radiation at said first wavelength and at a second wavelength, said source system including 
 a broadband source,    a first source filter, and    a second source filter,    said broadband source producing electromagnetic radiation at said first wavelength and at said second wavelength, said first source filter selectively passing electromagnetic radiation at said first wavelength, said second source filter selectively passing electromagnetic radiation at said second wavelength.    
     
     
         8 . The system of  claim 1 , wherein said source system includes a first source for producing electromagnetic radiation at said first wavelength and a second source for producing electromagnetic radiation at said second wavelength.  
     
     
         9 . The system of  claim 1 , wherein said bound complexes become first fluorescent bound complexes when said bound complexes bind to first reporter molecules, said first fluorescent bound complexes absorbing said incident electromagnetic radiation at said first wavelength and emitting fluorescence radiation at a third wavelength, said bound complexes become second fluorescent bound complexes when said bound complexes bind to second reporter molecules, said second fluorescent bound complexes absorbing said incident electromagnetic radiation at said second wavelength and emitting fluorescence radiation at a fourth wavelength, said system further comprising: 
 a first detector filter interposing said first test site and said first pixel and    a second detector filter interposing said test site and said second pixel,    said first detector filter blocking electromagnetic radiation at said first wavelength and passing electromagnetic radiation at said third wavelength, said second detector filter blocking electromagnetic radiation at said second wavelength and passing electromagnetic radiation at said fourth wavelength.    
     
     
         10 . The system of  claim 9 , wherein said first detector filter and said second detector filter are integral to said active pixel sensor.  
     
     
         11 . The system of  claim 1 , wherein said first test site comprises 
 a first well formed in a substrate,    a gel, at least a first portion of said gel disposed in said first well; and    first probe molecules disposed in said portion of said gel, said first probe molecules being able to bind to first target molecules.    
     
     
         12 . The system of  claim 11 , further comprising 
 a second test site, said second test site comprising 
 a second well formed in said substrate,  
 a second portion of said gel disposed in said second well, and  
 second probe molecules disposed in said second portion of said gel, said second probe molecules being able to bind second target molecules.  
   
     
     
         13 . The system of  claim 1 , wherein said first test site comprises 
 a first island of gel disposed on a substrate; and    first probe molecules disposed in said first island, said first probe molecules being able to bind first target molecules.    
     
     
         14 . The system of  claim 13 , further comprising a second test site, said second test site comprising a second island of gel disposed on said substrate; and 
 second probe molecules disposed in said second island, said second probe molecules being able to bind second target molecules    
     
     
         15 . The system of  claim 1 , wherein said first test site is defined by a first region of a gel layer, said first region containing first probe molecules, said first probe molecules being able to bind to first target molecules.  
     
     
         16 . The system of  claim 15 , further comprising a second test site defined by a second region in said gel layer, said second region containing second probe molecules, said second probe molecules being able to bind to second target molecules.