Chemical apparatus and process disinfecting – deodorizing – preser – Control element responsive to a sensed operating condition
Reexamination Certificate
2000-10-23
2004-11-09
Soderquist, Arlen (Department: 1743)
Chemical apparatus and process disinfecting, deodorizing, preser
Control element responsive to a sensed operating condition
C347S008000, C347S020000, C347S086000, C073S863320, C073S864010
Reexamination Certificate
active
06814937
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a dispenser to be used for the production of a DNA chip (DNA microarray) in which several thousands to not less than ten thousands kinds of different types of DNA fragments are aligned and fixed as minute spots at a high density on a base plate such as a microscopic glass slide, and a method for producing a DNA chip by using the dispenser.
2. Description of the Related Art
The method for analyzing the genetic structure has been remarkably progressed in recent years. A large number of genetic structures represented by those of the human genome have been clarified. The analysis of the genetic structure as described above uses a DNA chip (DNA microarray) in which several thousands to not less than ten thousands kinds of different types of DNA fragments are aligned and fixed as spots on a base plate such as a microscopic glass slide.
Those widely used as a method for forming the spots for the production of the DNA chip are based on a system such as the QUILL system, the pin & ring system, and the spring pin system in which a sample solution containing DNA fragments is supplied (stamped) onto the base plate by using a so-called pin. Even when any one of the foregoing methods is adopted, it is necessary to suppress the dispersion of the volume and the shape of each of the spots to be low so that the distance between the respective spots is maintained to be constant.
On the other hand, in order to realize a higher density, it is also greatly expected to develop a new method which is excellent in productivity and in which the shape control performance for the spot is satisfactory.
The QUILL system lies in a method in which a sample is stored in a recess formed at a pin tip, and the pin tip is allowed to make contact with the base plate so that the sample in the recess is transferred onto the base plate to form a minute spot. However, this system involves, for example, a problem of durability such that the pin tip is deformed or it is damaged by the contact with the base plate. Further, this system also involves, for example, a problem such that the sample stored in the recess is incompletely washed to facilitate the occurrence of cross-contamination.
The pin & ring system lies in a method in which a sample solution in a microplate is reserved with a ring, and then the sample in the ring is trapped by a pin tip so that the pin tip penetrates through the inside of the ring reserved with the solution to form a spot on the base plate. However, the sample, which can be reserved once, depends on the number of rings. Conventionally, the number of rings can not be increased. For this reason, in order to form several thousands to several tens of thousands of minute sample spots, it is also necessary to perform washing and drying steps several hundreds to several thousands of times. Therefore, it is difficult to say that the productivity is necessarily high.
The spring pin system lies in a method in which a sample adhered to a pin tip is transferred onto the base plate by pressing the pin tip against the base plate. A double pin structure containing a spring is used to mitigate the damage of the pin and the base plate while the sample is ejected. However, basically, only one time of spotting can be performed with one time of reserve. This system is inferior in productivity.
In all of the conventional methods for forming the minute spots, the sample solution is transported onto the base plate in a state of being exposed to the atmospheric air. Therefore, an inconvenience arises such that the sample is dried during the transport, and it is impossible to perform the spotting. A problem arises such that the extremely expensive sample solution is used with bad efficiency.
On the other hand, a method is also investigated by using the so-called ink-jet system which is practically used for printers. However, many tasks arise concerning the size and the cost when several thousands to several tens of thousands of individual flow passages corresponding to every sample are formed. Further, in the case of the ink-jet system, it is necessary to previously charge the sample in a pump before the spotting so that no bubble is formed. For this reason, a large amount of sample is required to effect the purge. Therefore, the efficiency of the use of the sample is extremely inferior. In general, in order to remove the bubble, it is preferable to move the liquid at a high speed in the flow passage including a pump chamber. As a result, the sample is agitated in the flow passage. When a delicate DNA solution is used as a sample, for example, DNA is damaged in some cases.
SUMMARY OF THE INVENTION
The present invention has been made taking the foregoing problems into consideration, an object of which is to provide a dispenser which comprises a large number of micropipettes arranged to makes it possible to form minute spots accurately at a high speed, which makes it possible to supply a solution to the respective micropipettes quickly and reliably, and which makes it possible to smoothly perform the steps from the supply of the solution to the supply onto a base plate.
Another object of the present invention is to provide a method for producing a DNA chip, which makes it possible to smoothly perform the steps from the supply of a solution to the supply onto a base plate and which makes it possible to improve the quality of the DNA chip and improve the yield.
According to the present invention, there is provided a dispenser comprising a plurality of arranged micropipettes each including a pouring port for pouring a sample solution from the outside, a cavity for pouring and charging the sample solution thereinto, and a discharge port for discharging the sample solution, formed on at least one or more substrates. The micropipette further includes a piezoelectric/electrostrictive element disposed on at least one wall surface of the substrate which forms the cavity so that the sample solution is movable in the cavity, and the sample solution is discharged from the discharge port of each of the micropipettes; wherein a pin, which protrudes upwardly, is provided at the pouring port of each of the micropipettes.
According to another aspect of the present invention, there is provided a method for producing a DNA chip, comprising the steps of using a dispenser comprising a plurality of arranged micropipettes each including a pouring port for pouring a sample solution from the outside, a cavity for pouring and charging the sample solution thereinto, and a discharge port for discharging the sample solution, formed on at least one or more substrates. The micropipette further includes a piezoelectric/electrostrictive element disposed on at least one wall surface of the substrate which forms the cavity so that the sample solution is movable in the cavity; and discharging the sample solution onto a base plate from the discharge port of each of the micropipettes to produce the DNA chip; wherein the dispenser to be used is provided with a pin protruding upwardly at the pouring port of each of the micropipettes.
Accordingly, a hole can be bored with the pin through a solution storage section of a cartridge positioned over the pouring port so that the solution stored in the solution storage section may be introduced into the pouring port.
That is, a cartridge, which is arranged with a large number of solution storage sections, is positioned over the dispenser, and the cartridge is moved toward the dispenser. At this time, a hole is bored with the pin through each of the solution storage sections. Accordingly, the solution stored in the solution storage section is introduced into the pouring port along the pin. By doing so, it is unnecessary to use any special apparatus when the sample solution is poured into the dispenser from the solution storage section of the cartridge. Thus, no sample solution remains in the special apparatus, and the efficiency of the use of the sample solution is not lowered.
In this process, it is also preferable that when the so
Hirota Toshikazu
Ohnishi Takao
Takeuchi Yukihisa
NGK Insulators Ltd.
Quan Elizabeth
Soderquist Arlen
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