Method and apparatus for screening chemical compounds

• US 6,388,788 B1
• Filed: 06/15/1999
• Issued: 05/14/2002
• Est. Priority Date: 03/16/1998
• Status: Expired due to Fees

• Current Assignee: GE Healthcare Bio-Sciences Corporation (General Electric Company)
• Original Assignee: Praelux, Inc. (General Electric Company)
• Inventors: Harris, Timothy D., Nicklaus, Neal A., Trautman, Jay K., Karsh, William, Hansen, Richard L.
• Primary Examiner(s): Phan, James
• Application Number:
  US09/333,749
• Time in Patent Office: 1,064 Days
• Field of Search: 359/196-226, 359/368-393, 250/201.3, 250/208.1, 250/234, 250/559.07, 250/559.11, 250/235, 250/578.1
• US Class Current: 359/196.1
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/6458 Fluorescence microscopy fluorescence microscopes per se G02B21/0076 and G02B21/16
• CPC Class Codes: G02B 21/0028 specially adapted for specific applications, e.g. for endoscopes, ophthalmoscopes, attachments to conventional microscopes
• CPC Class Codes: G02B 21/006 focusing arrangements; selection of the plane to be imaged
• CPC Class Codes: G02B 21/0064 multi-spectral or wavelength-selective arrangements, e.g. wavelength fan-out, chromatic profiling G02B21/0076 takes precedence
• CPC Class Codes: G02B 21/0072 details concerning resolution or correction, including general design of CSOM objectives
• CPC Class Codes: G02B 21/0076 arrangements using fluorescence or luminescence
• CPC Class Codes: G02B 21/0084 time-scale detection, e.g. strobed, ultra-fast, heterodyne detection

Abstract

Methods and apparatus for screening large numbers of chemical compounds and performing a wide variety of fluorescent assays, including live cell assays. The methods utilize a laser linescan confocal microscope with high speed, high resolution and multi-wavelength capabilities and real time data-processing. Imaging may be done at video-rates and with use of ultraviolet illumination.

Claims

1. A confocal imaging system comprising:

a) a means for forming an elongated beam of electromagnetic radiation extending transverse to an optical axis along which the radiation propagates;

b) a means for directing and focusing the elongated beam onto a first elongated region in a first plane where an object is located and for directing electromagnetic radiation emitted from the object onto one or more second elongated regions, wherein each second elongated region is on a different second plane conjugate to the first plane;

c) in at least one of the second conjugate planes, or in a third plane conjugate to at least one of the second conjugate planes, a detection device comprising a rectangular array of detection elements on which the electromagnetic radiation emitted from the object is coincident; and

d) a means for scanning the object by moving the elongated beam relative to the object or by moving the object relative to the elongated beam such that the emitted electromagnetic radiation is delivered to the rectangular array of detection elements and is continuously converted by the detection device into a plurality of electrical signals representative of the emitted electromagnetic radiation synchronously with said scanning.

2. The confocal imaging system according to claim 1 further comprising:

a) an elongated spatial filter having a long axis which is aligned with the second elongated region; and

b) a means for forming, on the detection device, an image of the second conjugate plane.

3. The confocal imaging system according to claim 2, wherein the spatial filter has a variable width.

4. The confocal imaging system according to claim 2, wherein the elongated beam of the electromagnetic radiation directed onto the object comprises one or more wavelengths and wherein the second plane is singular.

5. The confocal imaging system according to claim 1, wherein the elongated beam of electromagnetic radiation directed onto the object comprises two or more wavelengths.

6. The confocal imaging system according to any one of claims 1, 4 or 5 wherein two or more wavelengths of electromagnetic radiation are emitted from the object in the first elongated region in the first plane, said system further comprising a means for separating the emitted wavelengths to detect at least one of the separated wavelengths by one or more detection devices.

7. The confocal imaging system according to claim 1, wherein the detection device comprises an m×

n array of detector elements wherein m is the number of detector elements in a first dimension of the array and n is the number of detector elements in a second dimension of the array and n is greater than m.

8. The confocal imaging system according to claim 7, wherein the elongated region on which the emitted electromagnetic radiation is directed has a long axis that is aligned with the array of the detection device, so that the long axis extends in the same direction as the second dimension.

9. The confocal imaging system according to claim 7, wherein at least two detector elements forming a column extending in the first dimension of the array are binned together.

10. The confocal imaging system according to claim 7, wherein a plurality of detector elements of the array are binned together.

11. The confocal imaging system according to claim 7, wherein the detection device is a CCD array.

12. The confocal imaging system according to claim 1, wherein the detection device is a rectangular format CCD array.

13. The confocal imaging system according to claim 1, wherein the radiation emitted from the object is fluorescent radiation.

14. The confocal image system according to claim 1, wherein the scanning means comprises a rotating optical element for moving the elongated beam across the object.

15. The confocal image system according to claim 1, wherein the scanning means comprises a movable stage on which the object is located.