1. Field of the Invention
The present invention relates to a spotter that, in a substrate or a solid phase carrier having plural probes capable of specifically binding to a target substance, such as a micro array or a DNA chip, is used for work for immobilizing the plural probes, a detection device for an immobilization substrate on which the plural probes are immobilized, and a dispensing device that dispenses the plural probes to be used by a spotter.
2. Related Background Art
As an example of a probe immobilization substrate that is formed by immobilizing plural probes, which are capable of specifically binding to a target substance, on a surface of a solid phase carrier or a substrate, there is a DNA chip. The DNA chip is a DNA probe array obtained by aligning a large number of DNA fragments or oligonucleotides, which have different base sequences, on a solid phase surface to be immobilized at high density as probes for hybridization reaction. As regards DNA probes to be immobilized on such a DNA chip, combinations of base sequences, which are effective in analyzing expression, mutation, polymorphism, and the like of genes simultaneously, are selected.
As a method of immobilizing nucleic acid molecules on a solid phase surface in array, for example, U.S. Pat. No. 5,688,642 discloses a solid phase oligonucleotide array formed by preparing oligonucleotides in a desired base sequence using photolithography according to solid phase synthesis. On the other hand, WO 95/25116 and U.S. Pat. No. 5,688,642 disclose a preparation method for a solid phase DNA probe array, in which DNA molecules prepared in advance are spotted on a solid phase surface using an ink-jet method.
In addition in a detecting process for a target substance on the basis of probe hybridization reaction, in general, a so-called hybridization reaction is performed in which a target substance labeled by a fluorescent substance or the like is brought into contact with probes of a solid phase probe array to form a specific hybrid between the target substance and the probes. This hybridization reaction is usually a reaction with which the solid phase DNA probe array is brought into contact with or immersed in a solution, in which the target substance is solved, and the target substance forms a specific hybrid with respect to the probes while the target substance and the probes are heated. In this case, conditions for reaction such as concentration and temperature vary depending upon a combination of the probes and the target substance. Moreover, presence or absence of a hybrid formed by allowing the probes and the target substance to bind together, an amount of generation of the hybrid, and the like are observed by detecting fluorescence, which is derived from the fluorescent substance previously used for labeling the target substance, using a detection device such as a fluorescent detector.
As proposed in JP 2002-101878 A, this DNA chip is also used for the gene diagnosis.
A DNA chip for gene diagnosis used actually for diagnosis includes results (information) of observation of presence or absence of a hybrid corresponding to gene information peculiar to each patient, an amount of generation of the hybrid, and the like. For example, in a DNA chip using a fluorescent label, there is no depletion with time of a labeling capability as in a radio element label. Therefore, the DNA chip has an advantage that the results (information) can be read repeatedly. On the other hand, since the results (information) can be read repeatedly, if a name of the patient is leaked together with the DNA chip for gene diagnosis used for diagnosis, even a third party is likely to know a diagnosis result of the patient.
It is needless to mention that, in medical institution, for example, hospitals, measures for confidentiality are taken carefully such that information on individual patients is never leaked to a third party. On the other hand, hospitals and the like often treat instruments and test kits used for diagnosis as medical wastes and entrust disposal thereof to waste disposers having appropriate disposal facilities.
Note that, in a stage of waste disposal entrusted to the waste disposers, naturally, the hospitals are fully equipped with a physical management system meeting standards stipulated for each medical waste, for preventing the outflow and spread of “pathogenic substances”, which are likely to adhere to medical wastes. However, in a process of this disposal, although management for “physical leakage” is attained sufficiently, for example, there is a tendency that attention is not sufficiently paid to “information” remaining on a DNA chip used for diagnosis. For example, if a third party can read the “information” remaining on the DNA chip used for diagnosis again under the management for “physical leakage”, it is likely that the “information” is leaked to the outside even if the DNA chip itself is not carried out to the outside. Thus, in light of higher confidentiality and management therefor, there is a need for a technique that, even if “information” remaining on a DNA is leaked to the outside, prevents the “information” from being easily linked to diagnostic results of patients.
For example, analysis of base sequences of respective DNA probes constituting a DNA chip is difficult only with an amount of DNAs existing on one DNA chip. However, if respective DNA probes are separated and collected from plural unused DNA chips, and a relatively large quantity of DNAs are obtained, it is possible to analyze base sequences of the DNA probes. That is, when the base sequences of the respective DNA probes constituting the DNA chips are decoded, it is also interpreted what kind of diagnostic result “information” remaining on the DNA chip used for diagnosis is equivalent to. If it is found diagnosis of which patient the DNA chip was used for, as a result, it is possible that a diagnostic result of the patient is leaked to the outside.
Therefore, in light of higher confidentiality and management therefor, there is a need for a technique that, even if plural unused DNA chips could be prepared, can prevent base sequences of respective DNA probes arranged in array on respective DNA chips from being easily analyzed for the DNA chips.
Usually, in a DNA chip for diagnosis used in a medical field, information is disclosed to a user concerning what kind of gene information can be detected by DNA probes constituting the DNA chip. However, since a social position of a source of provision of base sequences of the DNA probes is taken into consideration, the base sequences themselves may be excluded from the information to be disclosed. In addition, when base sequences of DNA probes used in diagnosis are decoded, a problem of maintenance of confidential information also arises, for example, the base sequences are copied by a third party that is not permitted to use the base sequences. From these viewpoints, there is a need for a technique that serves for prevention of decoding such that a third party cannot easily decode base sequences of DNA probes constituting a DNA chip.