In recent years techniques for performing analysis with smaller systems have been developed in chemical and biochemical fields. A typical example is a μ-TAS system using a microchannel. Separation/mixing, reaction and so on have been performed with channels smaller than conventional ones. Moreover, a detecting element called DNA chip for reading biological and genetic information has been developed with the development of biotechnology and bioindustry.
Further, as three-dimensional micromachining develops in recent years, attention has been given to systems in which a small channel, a liquid device such as a pump and valve, and a sensor are integrated on a substrate made of a material selected from the group consisting of glass and silicon, and chemical analysis is performed on the substrate. These systems are called a miniaturizing analysis system, a μ-TAS (Micro Total Analysis System) or Lab on a Chip. By reducing the size of a chemical analysis system, a reactive volume can be reduced and an amount of a sample can be largely reduced. Besides, analysis time can be shortened and the power consumption of the whole system can be reduced. Furthermore, a smaller system raises expectations for the lower cost thereof. Since the μ-TAS can miniaturize the system, reduce the cost, and remarkably shorten analysis time, it is expected that μ-TAS will be applied to a medical field including home care and bedside monitoring and a biotechnological field including DNA analysis and proteome analysis.
For example, a microreactor is disclosed in which a series of biochemical experiments can be performed by a combination of several cells (Japanese Patent Application Laid-Open No. 10-337173). In the series of experiments, after a solution is mixed and reaction is performed, quantitative analysis is performed and then separation is performed. FIG. 11 schematically shows the concept of a microreactor 11. The microreactor 11 has a separate reaction chamber which is covered tightly with a flat plane on a silicon substrate. A reservoir cell 12, a mixture cell 13, a reaction cell 14, a detection cell 15, and a separation cell 16 are combined in the reactor. By forming a number of reactors on the substrate, a number of biochemical reactions can be performed in parallel. Not only simple analysis but also substance synthesis such as protein synthesis can be performed on cells.
Such a μ-TAS system and a biochip finally require a detecting step after operations including reaction are performed. Detection with light has been used as a method less affecting an analyte with higher accuracy due to its non-contact property and nonresponsiveness. For example, measuring methods have been used which include a measuring method of adding a fluorescence label to an analyte and emitting light from an exciting light source to detect fluorescence, a measuring method of irradiating an analyte with light from a light source to measure the intensity of transmitted light, and a method of bringing a prism close to an analyte, emitting light from a light source, and measuring loss of total reflected light.
However, the method using a fluorescence label raises a problem of congeniality between an analyte and a label, so that a desired label, that is a label with a high sensitivity may not be used. Further, excitation light and fluorescence have different wavelengths in this method. Although degradation is less caused by intensive excitation light serving as noise components, efficiency of generating fluorescence serving as signal components is hard to increase. Therefore, it is difficult to increase an overall S/N ratio.
According to the method of measuring a transmittance and an absorbance by using transmitted light, when an analyte has a low transmittance, that is when a measured substance which is included in a detected fluid has a high concentration, a signal is reduced due to a small quantity of transmitted light, resulting in a low S/N ratio. When the concentration of a measured substance is reduced to improve the S/N ratio, the original signal is reduced and thus the S/N ratio is degraded. Further, although measurements are less affected by light, light directly crosses a detected fluid. Thus, measurements are prone to being affected by heat generation or photoreaction, thereby limiting a quantity of usable light.
According to the method of measuring a loss of total reflected light, it is possible to use a larger quantity of light as compared with transmitted light. However, light having a change (loss) to be detected and irradiated light are equal in wavelength, so that a detector requires quite a large dynamic range. Namely, it is not possible to precisely measure a small loss caused by slight reaction or the like in a microchannel.
The present invention is devised to solve the above problem of the conventional technique and provides a sensor and a measuring apparatus whereby in microchemistry and biochemical analysis of a μ-TAS system, a bioanalysis chip, and so on using a microchannel, detection can be performed with a high sensitivity by using devices integrated into a compact configuration, and detection can be freely performed on a desired position of a channel. Moreover, according to the present invention, microcavity laser is applied to provide a portable tester.
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