Image reader with DC-coupled integration circuit

Radiant energy – Photocells; circuits and apparatus – Photocell controlled circuit

Reexamination Certificate

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Details

C250S2140LS, C250S586000, C356S417000

Reexamination Certificate

active

06693269

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to an image reader, and more particularly to an image reader that is usable in an autoradiographic system employing an X-ray film or storable phosphor sheet, a detection system using an electron microscope, a radiation diffraction image detection system, and a fluorescence detection system, the image reader being equipped with photoelectric conversion means having a photoelectron multiplication function, a current-voltage conversion circuit, and a logarithmic conversion circuit.
2. Description of the Related Art
In autoradiography, a radioactive labeling substance is injected into a living organism, and the living organism or part of the tissue of the living organism is sampled. This sample is stacked on a photosensitive material such as an X-ray film for a fixed time and is exposed to light. Based on the exposed part of the photosensitive material, the positional information on the radioactive labeling substance in the sample is obtained.
This autoradiography has been widely utilized in the following manner. For example, a radioactive labeling substance is injected into a medium which contains an organism-oriented high molecular substance such as the tissue of a living organism, protein, a nucleic acid, etc. The high molecular substance with the radioactive labeling substance, the derivative, or the decomposed substance, is separated on a gel support body by a separation operation such as gel electrophoresis. The gel support body is stacked on a radiation film such as a high-sensitivity X-ray film for a fixed time and is exposed to light. Based on the positional information on the radiation labeling substance obtained from the exposed part of the radiation film, the separation and identification of the high molecular substance, or the molecular weight measurement and characteristic evaluation of the high molecular substance, is performed. This autoradiography has also been utilized effectively in determining the base (nucleotide) sequence of a nucleic acid such as deoxyribonucleic acid (DNA).
In addition, as shown in Japanese Patent Publication Nos. 1(1989)-60784, 1(1989)-60782, and 4(1992)-3952 and Japanese Unexamined Patent Publication No. 10(1998)-3134, autoradiography employing a storable phosphor sheet instead of a conventional radiation film has also been put to practical use. The storable phosphor sheet is used as a photosensitive material for obtaining the positional information on a radioactive labeling substance. The storable phosphor sheet has a stimulatable phosphor layer, which contains a stimulatable phosphor. The stimulatable phosphor absorbs and stores energy of radiation when irradiated with the radiation, and emits photostimulated luminescent light, having a quantity of light corresponding to the quantity of the stored radiation energy, when excited with an electromagnetic wave such as visible light, infrared light, etc.
In autoradiography employing the storable phosphor sheet, a sample containing a radioactive labeling substance is stacked on the storable phosphor sheet for a fixed time, and the storable phosphor sheet absorbs at least part of radiation energy emitted from the radioactive labeling substance. Then, the radiation energy is emitted as photostimulated luminescent light from the storable phosphor sheet by scanning the storable phosphor sheet with an electromagnetic wave such as laser light, etc. The emitted, photostimulated luminescent light is photoelectrically detected, and the positional information on the radioactive labeling substance in the sample is obtained.
Japanese Unexamined Patent Publication Nos. 59(1984)-15843, 61(1986)-51738, and 61(1986)-93538, for example, disclose a detection system, which uses an electron microscope, for irradiating electron beams to a living organism and detecting the image of the living organism, and a radiation diffraction image detection system for irradiating radiation to a sample, detecting a radiation diffraction image, and making a structural analysis of the sample. As shown in these publications, a stimulatable phosphor is employed as a material for detecting electron beams or radiation. The stimulatable phosphor has the property of absorbing and storing the energy of electron beams or radiation when irradiated with the electron beams or radiation and also emitting photostimulated luminescent light having a quantity of light corresponding to the quantity of the stored electron-beam or radiation energy when excited with an electromagnetic wave in a specific wavelength region. Electron beams are irradiated to a metal or non-metal sample, and the diffraction image or transmitted image of the sample is detected. Based on the detected image, an element analysis, a composition analysis of the sample, a structural analysis of the sample, etc., are made.
There is also a fluorescence detection system using a fluorescent dye (labeling substance) instead of the radioactive labeling substance used in the autoradiographic system. This detection system can make an evaluation of a gene sequence and a gene expression level, an evaluation of the excretion, absorption, metabolism path, and state of an injected substance in a laboratory mouse, a separation and identification of protein, a measurement of a molecular weight, and an evaluation of characteristics, by reading a fluorescence image. For example, after a fluorescent dye is added into a solution containing a plurality of DNA fragments that are electrophoresed, the DNA fragments are electrophoresed on a gel support body. Alternatively, a plurality of DNA fragments are electrophoresed on a gel support body containing a fluorescent dye. Or, after a plurality of DNA fragments are electrophoresed on a gel support body, the gel support body is immersed into a solution containing a fluorescent dye. Next, after the thus-electrophoresed DNA fragments have been labeled, the fluorescent dye is excited with excitation light and fluorescent light is emitted. The emitted fluorescent light is detected, and an image is generated to detect DNA distribution on the gel support body. Alternatively, after a plurality of DNA fragments are electrophoresed on a gel support body, they are denatured. Next, at least some of the denatured DNA fragments are transferred onto a transfer support body such as nitrocellulose by Southern blotting, and target DNA and complementary DNA (or RNA) are labeled with a fluorescent dye to prepare a DNA or RNA probe. The DNA or RNA probe and the denatured DNA fragments are hybridized so that only the DNA or RNA probe and cDNA fragments are selectively labeled. The fluorescent light, emitted by exciting the fluorescent dye with excitation light, is detected to generate an image. A distribution of target DNAs on the transfer support body can also be detected. Furthermore, a cDNA probe, complementary to DNA containing a target gene labeled with a labeling substance, is prepared and hybridized with DNA on the transfer support body. After it is bound with the labeled cDNA, enzyme is brought into contacted with a fluorescent substrate. The fluorescent substrate is turned into a fluorescent substance which emits fluorescent light. The fluorescent light, emitted by exciting the generated fluorescent substance with excitation light, is detected and an image is generated. With this image, a distribution of target DNAs on the transfer support body can also be detected. These fluorescence detection systems have the advantage that they can easily detect a gene sequence, etc., without using a radioactive substance.
As described in the “gene expression analysis employing a microarray chip (Experimental Medical Series, Vol. 17, Jan. 1999, pp. 61 to 65)” and “gene medical science (Vol. 4, No. 1, 2000 (Medical Do)),” attention has recently been paid to application of the aforementioned fluorescence detection system to the gene expression analysis technique employing a test piece such as a microarray chip, a macroarray chip, a DNA chip, etc.
The gene expression analysis technique e

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