Radiant energy – Photocells; circuits and apparatus – Photocell controlled circuit
Reexamination Certificate
1999-11-16
2001-11-20
Lee, John R. (Department: 2878)
Radiant energy
Photocells; circuits and apparatus
Photocell controlled circuit
C250S216000, C359S368000
Reexamination Certificate
active
06320174
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to optical microscope technology. More particularly, the invention relates to a microscope able to scan a large area of a specimen for acquiring an image thereof in a biological diagnosis application.
BACKGROUND OF THE INVENTION
The evolution of optical microscopes has a long history, and the applications of the optical microscopes have extended beyond research and physicians's practice. In a conventional optical microscope, a single objective lens is used to focus on one location of a specimen carried by a microscopic slide and to acquire an image of the location. Dimensions of the image depend on the magnification and the numerical aperture of the objective lens. The image is viewed through an ocular lens or acquired through a camera. Then the specimen is moved and the same image-taking process is repeated at a new location. However, such process is slow for any application that requires a complete view of the specimen. Hence, there is a demand for scanning a large area of the specimen in a minimal amount of time.
One application in which high speed scanning is needed is to scan microscopical preparations for rare cells, e.g. fetal red blood cells in maternal blood during pregnancy, in prenatal diagnosis of genetic abnormalities. Given the fact that methods that can be used to increase the concentration of such cells in the maternal peripheral blood increase the risk of losing some of the cells, it is advantageous to avoid any increase of the concentration. The average frequency of finding fetal red cells in the maternal peripheral blood is one such cell per one milliliter of blood. In order to identify at least 10 cells, which are needed for an accurate prenatal diagnosis of trisomy
21
(Down syndrome), one needs to scan at least
15
milliliters of blood. A microscopical blood smear carries 50~70 micro liter of blood, and thus it needs 17~20 microscopical blood smears to carry one milliliter of blood. In that regard, about 240 microscopical blood smears are used for 15 milliliters of blood.
A similar need exists in the detection of cancer cells in the peripheral circulation of a patient. The detection of such cells at an early stage can help in a timely prognosis of the disease and increase the efficiency of treatment.
Another application where any kind of enrichment is very difficult, if not impossible, is the detection of specific microorganisms in natural waters. For example, plankton microorganisms in fresh or marine waters are mainly recognized on the basis of their morphological characteristics. Because the majority of species of such microorganisms are still unknown, recording their presence in a particular sample relies mainly on the description of their morphological features. It is often quite difficult to isolate such cells, not to mention further culture them to identify all stages of their biological cycle. It is of the utmost importance for both research and applied purposes (biological monitoring or sanitary monitoring) to have the capacity to scan microscopical preparations of such samples in order to record the presence of these microorganisms.
SUMMARY OF INVENTION
The present invention provides a solution to the existing deficiencies.
In accordance with a first embodiment of the invention, a composing microscope comprises a plurality of optical sensors, a plurality of optical projecting systems arranged adjacent to each other, and an image acquisition device connected to the optical sensors. An illuminating means such as a lamp is used to illuminate a specimen. Each of the projecting systems is connected to one optical sensor and acquires an image of one position of the specimen and projects the image on the optical sensor for digitalizing the image. The image acquisition device simultaneously receives, from the plurality of optical sensors, the digitalized images and store the same with information of their positions on the specimen to form a complete view of the specimen.
In a preferred example of the first embodiment, the optical sensor comprises a charge couple device (CCD) camera, and the optical projecting system comprises an objective lens. It is preferred that the optical projecting system comprises an objective lens and a focusing means such as a computer-controlled auto-focusing mechanism for controlling the focusing of the objective lens. The image acquisition device comprises a component in a computer. The composing microscope further comprises a motorized specimen stage for moving the specimen to be scanned by the optical projecting system and a synchronizing means such as a computer for synchronizing the movement of the specimen stage with image storage rate of the image acquisition device.
In accordance with a second embodiment of the invention, a composing microscope comprises an optical sensor, a plurality of optical projecting systems arranged adjacent to each other in rows, an optical reflector, and an image acquisition device. An illuminating means is used for illuminating a specimen. Each of the optical projecting systems has a first end proximate to the specimen for acquiring an image at one position of the specimen and a second end. The optical reflector receives the images from at least one row of the optical projecting systems at the second ends and projects on the optical sensor. The optical sensor simultaneously digitalizes these images from the optical projecting systems. The optical reflector is moveable with respect to the second ends of the optical projecting systems. The image acquisition device receives and stores the digitalized images with information of their positions on the specimen to form a complete view of the specimen.
The optical sensor, in a preferred example of the second embodiment, is a fast CCD camera or a complementary metal oxide semiconductor (CMOS) active pixel sensor. The CMOS active pixel sensor used has a resolution of no less than 500×500 pixels at an image acquisition rate of no less than 100 frames per second. It is preferred that the CMOS active pixel sensor has a resolution of 1024×1024 pixels at an image acquisition rate of 500 frames per second. The optical projecting system comprises an optical fiber, preferably having an objective lens at the first end of the optical fiber. Moreover, the objective lens may further have a focusing means therefor. The optical reflector is translated in a direction perpendicular to the direction of rows of the second ends of the optical fibers. As an alternative, the optical reflector is moved rotationally along an axis parallel to the direction of the row of said optical fibers. The optical reflector is in the form of a mirror or a prism. The composing microscope further comprises a motorized specimen stage for moving the specimen to be scanned by the optical projecting system and a synchronizing means such as a computer to synchronize the movement of the specimen stage with image acquisition rate of the optical sensor. The image acquisition device comprises a component in a computer.
In accordance with a third embodiment of the invention, a composing microscope comprises an optical sensor, a plurality of optical projecting systems arranged adjacent to each other, and an image acquisition device connected to the optical sensor. An illuminating means such as a lamp is used to illuminate a specimen. Each of the optical projecting systems has a first end and a second end, and the second end is connected to the optical sensor. The optical projecting system acquires an image of one location of a specimen at its first end and projects the image on the optical sensor through the second end. The optical sensor simultaneously receives the images of different positions of the specimen and digitalizes same. The image acquisition device stores the digitalized images with information of their positions on the specimen to form a complete view of the specimen.
The optical sensor, in a preferred example of the third embodiment, is a fast CCD camera or a CMOS active pixel sensor. The CMOS active p
Tafas Triantafyllos
Tsipouras Petros
Ikonisys Inc.
Lee John R.
Pennie & Edmonds LLP
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