1. Field of the Invention
The present invention relates to a biological technique for analyzing, for example, cell, microorganism, chromosome, nucleic acid and the like in a sample by utilizing a biochemical reaction, such as an antigen-antibody reaction or a nucleic acid hybridization reaction.
2. Description of the Related Art
Most of analyzers for analyzing samples such as blood use an immunological procedure utilizing an antigen-antibody reaction or a procedure utilizing nuclei acid hybridization. For example, protein such as an antibody or antigen, or a single-stranded nucleic acid, which specifically connects with a target substance, is used as a probe and is fixed on a surface of a solid material, such as fine particles, beads or a glass plate, and an antigen-antibody reaction or nucleic acid hybridization is then performed with the target substance, Subsequently, an antigen-antibody compound or double-stranded nucleic acid is detected using a labeled substance supporting a labeling material, so that determination of the presence or absence of the target substance or quantitative determination thereof is performed, the target substance having a specific interaction with the probe. As the labeled substance, for example, there may be mentioned a labeled antigen, a labeled antibody, or a labeled nucleic acid. The labeling material has a high detection sensitivity, and for example, there may be mentioned an enzyme, a fluorescent material or a luminescent material.
As an extension of these techniques, for example, U.S. Pat. No. 5,445,934 has disclosed a so-called DNA (deoxyribonucleic acid) array in which a great number of DNA probes having mutually different base sequences are arranged on a substrate in array form.
In addition, Anal. Biochem., 270(1), pp. 103-111 (1999) has disclosed a process for preparing a protein array, like the DNA array, such that many types of proteins are arranged on a membrane filter. By using the DNA array, the protein array and the like, it has become possible to carry out a test including a considerably great number of items at the same time.
Furthermore, in various methods of sample analysis, in order to realize reduction of contamination by sample, promotion of reaction efficiency, reduction in apparatus size, simplification of operation and the like, there have also been proposed a disposable biochemical reaction cartridge in which a necessary reaction is performed therein. In addition, a system in which flow paths, reaction chambers, detectors, and the like are integrated by a micro-fabrication technique so that analysis, synthesis and/or the like is performed for a substance introduced therein is called μ-TAS (micro total analysis system), and research thereof has been aggressively performed. For example, PCT Japanese Translation Patent Publication No 11-509094 has disclosed a biochemical reaction cartridge, which is a μ-TAS including a DNA array, in which a plurality of chambers is disposed and a solution is moved by a differential pressure so as to allow reaction, such as extraction, amplification or hybridization of DNA in a sample, to proceed within the cartridge.
In addition, in U.S. Pat. No. 6,100,541, a μ-TAS in which an optical detection member is embedded adjacent to one of flow paths has been disclosed: In addition, although the following are not μ-TASs, a liquid measurement device has been disclosed in Japanese Patent Laid-Open No. 4-131763 which outputs an alarm in the case in which when a sample is recovered, the pressure does not reach a predetermined level after a predetermined time passes, and in Japanese Patent Laid-Open No. 11-304817, a dispenser device has been disclosed in which a suction amount and the number of suction and ejection during agitation are calculated based on a remaining amount of a sample which is determined from the liquid level thereof using a probe.
As a method for detecting the abnormality of movement of a liquid, a method for detecting a liquid in a flow path is generally performed; however, this method is not sufficient to detect leakage and clogging, and in addition, in the case of a μ-TAS, since the flow path thereof is very narrow, the structure becomes complicated and expensive. In addition, various methods for detecting the volume of liquid remaining in chambers or the like have also been proposed; however, in all the methods, the detection results obtained from individual chambers are independently used, and the normality of a process is not determined using a plurality of measurement results. Furthermore, there has been a method in which the abnormality is determined when the pressure is abnormal; however, since a fluid is not directly detected in this method, the detection result is not so much reliable.
USPTO Backgrounds
USPTO Backgrounds