Signal offset for prevention of data clipping in a molecular array scanner

• US 6,914,229 B2
• Filed: 02/28/2002
• Issued: 07/05/2005
• Est. Priority Date: 02/28/2002
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Staton, Kenneth L., Ghosh, Jayati, Corson, John F., Sillman, Debra A.
• Primary Examiner(s): Luu, Thanh X.
• Application Number:
  US10/086,658
• Publication Number:
  US 20030168579A1
• Time in Patent Office: 1,223 Days
• Field of Search: 250/214.DC, 250/214.A, 250/214.R, 250/234, 382/133
• US Class Current: 250/214.00R
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/6452 Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Abstract

A method and system for preventing signal clipping in a molecular array scanner by adding an offset signal to the signal generated by the photodetectors and initial stages of signal processing within a molecular array scanner in order to promote the signal above the level where signal information is lost during analog-to-digital signal conversion and/or digital signal integration. A portion of the offset is then subtracted from the digital signal or integrated digital signals, leaving a smaller, constant offset that is reported to the user, stored in a data file, or otherwise made available for further correction during later molecular array data processing.

Claims

1. A method for reliably acquiring emitted-light intensity from the surface of a molecular array, the method comprising:

providing a probe-molecule excitation system;

providing an emitted-light photodetection system;

producing an analog signal by detecting light emitted from the surface of the molecular array;

adding a signal offset to the analog signal;

digitizing the analog signal to produce a digital signal;

subtracting a portion of the signal offset from the digital signal; and

integrating the digital signal to produce integrated digital signals that are each associated with a pixel in an image of the molecular array.

2. The method of claim 1 wherein the photodetection system outputs an analog current signal that is converted to an analog voltage signal.

3. The method of claim 1 further including:

prior to detecting light emitted from the surface of the molecular array, carrying out a dark scan with no molecular array in order to determine a mean intensity and standard deviation for background generated by the photodetection system.

4. The method of claim 3 wherein the portion of the signal offset subtracted from the digital signal is the signal offset minus four times the standard deviation of the background.

5. Integrated digital signals produced by the method of claim 1 encoded by:

storing representations of the signal intensity data in a machine readable medium;

transmitting representations of the signal intensity data over an electronic communications medium;

displaying the signal intensity data on display device; and

printing representations of the signal intensity data in a human readable medium.

6. A set of computer instructions for carrying out the method of claim 1 encoded by one of:

storing the computer instructions in a machine readable medium;

transmitting the computer instructions over an electronic communications medium; and

printing the computer instructions in a human readable medium.

7. A molecular array scanner comprising:

a probe-molecule excitation system;

an emitted-light photodetection system that produces an analog signal representative of the emitted-light intensity;

a signal-offset adder that adds an offset to the analog signal;

an analog-to-digital converter that digitizes the analog signal to produce a digital signal;

signal-offset-subtractor logic that subtracts a portion of the signal offset from the digital signal; and

a digital-signal integrator that integrates portions of the digital signal to produce integrated digital signals that are each associated with a pixel in a scanned image of the molecular array.

8. The molecular array scanner of claim 7 further including:

a memory component that stores a value that allows for calculation of the portion of the signal offset subtracted by the signal-offset-subtractor logic.

9. The molecular array scanner of claim 8 further including:

dark scan logic that controls the molecular array scanner to carry out a dark scan with no molecular array in order to determine a mean intensity and standard deviation for background generated by components within the photodetection and the signal processing systems of the molecular array scanner prior to scanning a molecular array to acquire data.

10. The molecular array scanner of claim 9 wherein the dark scan logic wherein the portion of the signal offset subtracted by the signal-offset-subtractor logic is the signal offset minus four times the standard deviation for the background.

11. Integrated digital signals produced by the molecular array scanner of claim 7 encoded by:

storing representations of the signal intensity data in a machine readable medium;

transmitting representations of the signal intensity data over an electronic communications medium;

displaying the signal intensity data on display device, and

printing representations of the signal intensity data in a human readable medium.