Signal noise reduction for imaging in biological analysis

Abstract

A system and method for characterizing contributions to signal noise associated with charge-coupled devices adapted for use in biological analysis. Dark current contribution, readout offset contribution, photo response non-uniformity, and spurious charge contribution can be determined by the methods of the present teachings and used for signal correction by systems of the present teachings.

What is claimed: 
     
         1 . A method comprising:
 providing a detector comprising a plurality of pixels that are capable of forming an optical image of fluorescent light emitted from a biological sample;   using the detector to detect a first fluorescent signal from a biological sample;   generating a first electronic signal that corresponds to said fluorescent signal;   characterizing a signal noise component of the first electronic signal as a characterized signal noise component comprising a dark current contribution;   manipulating the detector to reduce signal noise based upon the signal noise component, and to form a manipulated detector;   using the manipulated detector to detect a second fluorescent signal from the biological sample; and   using the manipulated detector to generate a second electronic signal.   
     
     
         2 . An imaging system for analysis of a biological sample, comprising:
 a detector comprising a plurality of pixels;   a readout component configured to read an output signal from each of the plurality of pixels;   a controller configured to induce a substantially uniform illumination condition to the detector and provide an exposure from each of the plurality of pixels, for a selected exposure duration; and   a processor programmed to (i) remove signal noise from the output signal of each pixel to yield a corrected signal for each pixel, (ii) identify at least one hot pixel and at least one dead pixel, (iii) determine an average value of the corrected signals from pixels that are not identified as hot pixels or dead pixels, (iv) determine a respective normalization factor for each of the plurality of pixels, and (v) save the normalization factor for each pixel.