Chemistry: analytical and immunological testing – Including sample preparation – Volumetric liquid transfer
Reexamination Certificate
2003-05-06
2004-07-27
Ludlow, Jan M. (Department: 1743)
Chemistry: analytical and immunological testing
Including sample preparation
Volumetric liquid transfer
C422S091000, C422S105000, C101S368000, C347S110000, C400S124070, C400S124290
Reexamination Certificate
active
06767748
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a spotting pin for spotting biomolecules such as DNAs on a spotting substrate and for preparing a biochip, a spotting device and a method for spotting.
2. Background Art
With respect to gene research and others, in biochemistry, microarrays or macroarrays (hereinafter referred to collectively as “biochip” in this specification) have conventionally been used for conducting experiments such as hybridization. The microarrays are prepared by spotting dense biomolecules such as DNAs or proteins for immobilization on substrates such as glass slides, nylons, or nitrocellulose membranes. The biochips are prepared by picking up a plurality of types of biomolecules dispensed in an MTP (Micro Titer Plate) by a plurality of spotting pins installed on a spotting device and spotting the same for immobilization on a substrate such as a glass slide or a membrane in accordance with predetermined arrays.
In order to assure the reliability of the results of experiments conducted using biochips, it is necessary that uniform amounts (quantities) of biomolecules are immobilized on each position on the biochip. Spotting pins installed on the spotting device are formed of a solid material such as stainless steel, and are prepared so that identical amounts of biomolecules are always spotted. However, when the number of spotting for immobilization reaches to approximately 100,000, the tips of the pins are gradually abraded away by the repeated contact with the substrate. When the spotting is carried out with a spotting pin with worn tip, spot shapes become varied, causing spot amounts to become unstable, and thereby giving rise to problems.
In order to continue to prepare high-quality biochips with the spotting device, it is necessary to accurately assess the conditions of the spotting pins installed on the device and to replace the spotting pins with new ones at appropriate times. If a spotting pin which has exceeded its service life continues to be used, the shape of the pin tip is changed by the contact friction, and consequently there is a high possibility of causing abnormal spot shapes. However, when the timing is premature, in that the spotting pin is replaced before its service life has expired, cost increases may be incurred.
Further, different types of biochips may be produced on a lot basis using the same spotting device. When an array pattern of spotting on a biochip for one lot is different from an array pattern for a subsequent lot, some of the plurality of spotting pins installed on the spotting device may be removed or additional spotting pins may be installed thereon. In such a case, since the plurality of the spotting pins installed on the spotting device do not have the same remaining days of service life, managing the timing of replaceing spotting pins becomes complicated.
Based on the recognition of such a problem regarding spotting devices or the spotting pins, an object of the present invention is to provide a spotting device which enables spotting pins to be replaced at appropriate times and can constantly produce high quality biochips, and a spotting pin therefor.
SUMMARY OF THE INVENTION
In order to accomplish the above object, the present inventors have developed a spotting system to automatically count the number of spottings of spotting pins and to record and manage them. In the spotting system according to the present invention, each spotting pin has an information recording medium such as an IC chip, and each independently accumulates spotting information. Further, an application program controls an IC chip reader/writer, installed on the spotting device, to perform reading/writing of the accumulated spotting information of each spotting pin.
Hereinafter, an embodiment of the present invention will be described.
According to the present invention, a spotting pin for spotting a biomolecule on a substrate comprises an information recording medium, wherein information concerning the total number of spotting counts is stored in the information recording medium.
A spotting device of the present invention comprises: a pin head having a spotting pin installed thereon, the spotting pin comprising an information recording medium that stores the total number of spotting counts; a pin head driving means for moving the pin head up and down; an information reading/writing means for reading and writing information on the information recording medium; a display section; and a control section for controlling the pin head driving means, information reading/writing means and display section, wherein the control section causes the display section to display the total number of spotting counts that the information reading/writing means reads out from the information recording medium provided on the spotting pin.
When the pin head has a plurality of spotting pins installed thereon, the display section displays the total number of spotting counts for each spotting pin. Further, the control section updates the total number of spotting counts displayed on the display section on a real time basis each time spotting is performed. Furthermore, the control section writes in the information recording medium provided on the spotting pin the updated total number of spotting counts of the spotting pin via the information reading/writing means. The total number of spotting counts for each spotting pin is displayed by a graphic such as a bar graph, and a display mode of the graphic such as color of the graphic is preferably modified in accordance with the total number of spotting counts.
A method for spotting a biomolecule according to the preset invention comprises the steps of: installing, on a pin head, a spotting pin comprising an information recording medium that stores the total number of spotting counts; reading the total number of spotting counts of the spotting pin from the information recording medium; displaying the read-out total number of spotting counts on a display means; spotting the biomolecule on a substrate using the spotting pin installed on the pin head; updating the total number of spotting counts displayed on the display means; and updating the total number of spotting counts stored in the information recording medium.
When the pin head has a plurality of spotting pins installed thereon, each spotting pin is identified based on spotting pin identification information recorded in the information recording medium provided on each spotting pin and the total number of spotting counts is displayed for each spotting on the display means.
In the present invention, an IC chip may be used as the information recording medium. Further, as the information reading/writing means, an IC chip reader/writer may be used.
The term “biomolecule” used herein means a biopolymer such as DNAs, RNAs and proteins, which are immobilized on glass slides, nylon membranes or the like and used as probes to cause hybridization with target biomolecules in a sample.
The spotting system of the present invention is suitable for mass production of high quality biochips.
This specification includes part or all of the contents as disclosed in the specification and/or drawings of Japanese Patent Application No. 2002-136107, which is a priority document of the present application.
REFERENCES:
patent: 4687355 (1987-08-01), Ikehata et al.
patent: 6101946 (2000-08-01), Martinsky
patent: 2003/0035143 (2003-02-01), Glemser et al.
patent: 2002-273944 (2002-09-01), None
Kishida Hiroshi
Tachibana Mitsuhiro
Yokokawa Naoki
A. Marquez, Esq. Juan Carlos
Fisher Esq. Stanley P.
Hitachi Software Engineering Co. Ltd.
Ludlow Jan M.
Reed Smith LLP
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