Two-dimensional spectral imaging system

• US 8,139,213 B2
• Filed: 02/19/2009
• Issued: 03/20/2012
• Est. Priority Date: 06/30/2005
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Bahatt, Dar, Patel, Chirag, Tan, Roy H., Prothro, Derek
• Primary Examiner(s): Chowdhury, Tarifur
• Assistant Examiner(s): Nur, Abdullahi
• Application Number:
  US12/389,292
• Publication Number:
  US 20100039642A1
• Time in Patent Office: 1,125 Days
• Field of Search: 356402-425, 356/328
• US Class Current: 356/328
• CPC Class Codes: G01J 2003/1204 Grating and filter
• CPC Class Codes: G01J 2003/1208 Prism and grating
• CPC Class Codes: G01J 2003/1213 Filters in general, e.g. dichroic, band
• CPC Class Codes: G01J 2003/1226 Interference filters
• CPC Class Codes: G01J 3/10 Arrangements of light sources specially adapted for spectrometry or colorimetry
• CPC Class Codes: G01J 3/12 Generating the spectrum; Monochromators
• CPC Class Codes: G01J 3/18 using diffraction elements, e.g. grating gratings per se G02B
• CPC Class Codes: G01J 3/189 using at least one grating in an off-plane configuration
• CPC Class Codes: G01J 3/2803 using photoelectric array detector
• CPC Class Codes: G01J 3/2823 Imaging spectrometer
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 21/0332 with temperature control control of temperature G05D23/00; cryostats F17C3/08
• CPC Class Codes: G01N 21/253 for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• 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
• CPC Class Codes: G01N 21/6456 Spatial resolved fluorescence measurements; Imaging
• CPC Class Codes: G01N 21/76 Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2201/06113 : Coherent sources; lasers
• CPC Class Codes: G01N 2201/0621 : Supply
• CPC Class Codes: G01N 2201/0697 : Pulsed lasers

Abstract

Systems, including methods, apparatus, and algorithms, for spectrally imaging a two-dimensional array of samples.

Claims

1. A system for sample analysis, comprising:

an examination area including a two-dimensional array of examination sites;

a light detector for imaging;

an optical relay structure that spectrally disperses light received from the examination sites into a corresponding two-dimensional array of spectra directed concurrently onto the light detector in a collectively nonoverlapping relation wherein the optical relay structure includes one or more filters that truncate a portion of each spectra to substantially reduce crosstalk between the spectra of the two-dimensional array when directed concurrently onto the light detector; and

a thermal control system operatively coupled to the examination area for regulating a temperature thereof.

3. The system of claim 1 or 2, further comprising a system controller, wherein the thermal control system is operatively coupled to the system controller for automated thermal control of the examination area.

4. The system of claim 1 or 2, wherein the thermal control system is configured to repetitively follow a thermal profile in an automated manner.

5. The system of claim 1 or 2, wherein the thermal control system includes a heater and a thermally conductive member operatively coupled to the heater, further comprising a sample holder having wells and configured to be disposed in the examination area such that the wells are disposed in the examination sites and the sample holder is in contact with the conductive member.

6. The system of claim 5, wherein the conductive member and the sample holder have complementary structure that restricts lateral movement of the sample holder when the sample holder is disposed in the examination area.

7. The system of claim 6, wherein the complementary structure includes one or more projections of the conductive member that are configured to be received in one or more openings of the sample holder.

8. The system of claim 1 or 2, further comprising a sample holder having wells and configured to be disposed in the examination area such that the wells are disposed in the examination sites, wherein the wells have a staggered arrangement.

9. The system of claim 8, wherein the wells are disposed along a set of spaced parallel lines with a well-to-well spacing within each line, and wherein every other line of wells is offset along its line by about one-half the well-to-well spacing.

10. The system of claim 1 or 2, further comprising a sample holder having wells and configured to be disposed in the examination area such that the wells are disposed in the examination sites, wherein each well is at least about one millimeter in diameter.

11. The system of claim 1 or 2, further comprising a sample holder having wells and configured to be disposed in the examination area such that the wells are disposed in the examination sites, wherein each well has a capacity of at least about 100 nanoliters.

2. A system for sample analysis, comprising:

an examination area including a two-dimensional array of examination sites;

a light detector for imaging;

a controller operatively coupled to the light detector and configured to process image data collected by the light detector to correct for optical distortion in the image data;

an optical relay structure that spectrally disperses light received from the examination sites into a corresponding two-dimensional array of spectra directed concurrently onto the light detector in a collectively nonoverlapping relation wherein the optical relay structure includes one or more filters that truncate a portion of each spectra to substantially reduce crosstalk between the spectra of the two-dimensional array when directed concurrently onto the light detector; and

a thermal control system operatively coupled to the examination area for regulating a temperature thereof.

12. A method of sample analysis, comprising:

obtaining a two-dimensional array of samples for performing amplification of nucleic acids;

cycling the samples thermally through a plurality of cycles;

illuminating each sample of the array concurrently such that the samples emit light;

directing dispersed light from each sample through at least one filter to a detection area such that a corresponding two-dimensional array of spectra falls concurrently onto the detection area and a portion of each spectra is truncated at the detector, wherein each spectra of the array of the spectra is non-overlapping with the remaining spectra of the array of the spectra;

monitoring the two-dimensional array of spectra over time; and

determining an aspect of one or more of the samples based on a measurement of the corresponding two-dimensional array of spectra.