Method and system for molecular array scanner calibration

Abstract

A method and system for calibrating molecular arrays to a reference molecular array, and for subsequently calibrating the molecular arrays to maintain a constant signal-intensity-to-label-concentration ratio. In the first step of the two-step calibration method, a reference array coated with the fluorophore or chromophore used to label probe molecules is employed, while in the second step of the two-step method, a reference array coated with a stable dye is employed.

1 - 10 . (canceled)  
   
   
       11 . A method for calibrating a first molecular array scanner with a second, reference molecular array scanner, the method comprising: 
 calibrating said first molecular array scanner with said second, reference molecular array scanner by using a same-dye reference array that comprises a first dye; and    maintaining calibration of said first molecular array scanner with said second, reference molecular array scanner by using a stable-dye reference array that comprises a second dye.    
   
   
       12 . The method according to  claim 11 , wherein said first molecular array scanner is calibrated using said stable-dye reference array to maintain a constant signal-intensity-to-dye-concentration-ratio.  
   
   
       13 . The method according to  claim 11 , wherein said second dye is more stable than said first dye.  
   
   
       14 . The method according to  claim 11 , wherein said first dye is a fluorophore or chromophore.  
   
   
       15 . The method according to  claim 11 , wherein said same-dye reference array comprises said first dye coated on a surface of a substrate.  
   
   
       16 . The method according to  claim 11 , wherein said second dye is a fluorophore or chromophore.  
   
   
       17 . The method according to  claim 11 , wherein said stable-dye reference array comprises said first dye coated on a surface of a substrate.  
   
   
       18 . The method of  claim 11  wherein said same-dye reference array is used to initially calibrate the first molecular array scanner with the second, reference molecular army scanner by: 
 scanning the same-dye reference array in the second, reference molecular array scanner to determine a measured signal intensity for the same-dye reference array in the reference molecular array scanner;    calculating an expected intensity for scanning the same-dye reference array in the second, reference molecular array scanner a second time; and    scanning the same-dye reference array in the first scanner, and adjusting parameters in the first molecular array scanner to produce the expected intensity.    
   
   
       19 . The method of  claim 18  wherein calculating an expected intensity for scanning the same-dye reference array in the second, reference molecular array scanner a second time further comprises: 
 determining a function of expected intensity per scan of the same-dye reference array; and    selecting the expected intensity corresponding to one more than a number of times that the same-dye reference array has been scanned.    
   
   
       20 . The method of  claim 11  wherein maintaining the initial calibration using one or more stable-dye reference arrays further includes: 
 following initial calibration, scanning a stable-dye reference array with the first molecular array scanner in order to determine a signal-intensity-to-stable-dye-concentration ratio; and    periodically rescanning the stable-dye reference array with the first molecular array scanner, adjusting the first molecular array scanner to provide the determined signal-intensity-to-stable-dye-concentration ratio.    
   
   
       21 . A computer readable medium having recorded thereon signal intensity data, scanned from the surface of a molecular array by a molecular array scanner calibrated to a reference molecular array by the method of  claim 11 .  
   
   
       22 . A system for calibrating a number of molecular array scanners to provide a fixed signal-intensity-to-label-concentration ratio, the system comprising: 
 a reference molecular array scanner;    a same-dye reference array comprising a first dye; and    a stable-dye reference array comprising a second dye that is different from said first dye.    
   
   
       23 . The system according to  claim 22 , wherein said second dye is more stable than said first dye.  
   
   
       24 . The method according to  claim 22 , wherein said first dye is a fluorophore or chromophore.  
   
   
       25 . The method according to  claim 22 , wherein said same-dye reference array comprises said first dye coated on a surface of a substrate.  
   
   
       26 . The method according to  claim 22 , wherein said second dye is a fluorophore or chromophore.  
   
   
       27 . The method according to  claim 22 , wherein said stable-dye reference array comprises said first dye coated on a surface of a substrate.  
   
   
       28 . The system of  claim 22  configured so that the same-dye reference array is used to establish an initial calibration of a first molecular array scanner to the reference molecular array scanner by: 
 scanning the same-dye reference array in the reference molecular array scanner to determine a measured signal intensity for the same-dye reference array in the reference molecular array scanner;    calculating an expected intensity for scanning the same-dye reference array in the reference molecular array scanner a second time; and    adjusting the first molecular array scanner to produce the respective calculated expected intensity.    
   
   
       29 . The system of  claim 28  wherein calculating the expected intensity for subsequently scanning the same-dye reference array in the first molecular array scanner further comprises: 
 determining a function of expected intensity per scan of the same-dye reference array; and    selecting the expected intensity for the first molecular array scanner corresponding to one more than a number of times that the same-dye reference array has been scanned.    
   
   
       30 . The system of  claim 22  configured so that one or more stable-dye reference arrays are used to maintain the initial calibration of the first molecular array scanner by: 
 scanning a stable-dye reference array with the molecular array scanner in order to determine a signal-intensity-to-stable-dye-concentration ratio; and    periodically rescanning the stable-dye reference array with the molecular array scanner, adjusting the molecular array scanner to provide the determined signal-intensity-to-stable-dye-concentration ratio.    
   
   
       31 . A computer readable medium having recorded thereon signal intensity data, scanned from the surface of a molecular array by a molecular array scanner calibrated to a reference molecular array by the system of  claim 22.