JP2007132912A - Protein microarray device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a protein microarray device, having a humidity control mechanism which simultaneously controls the humidity and achieves clean environment and consumes less energy. <P>SOLUTION: Microspots of a solution containing proteins are transferred onto a substrate by spot pins to arrange a plurality of spots containing proteins as probes on the substrate at high density and produce a protein array chip in a protein microarray device. The protein microarray device uses a hollow-yarn-film type non-porous dissolved and dispersed film for controlling humidity inside the arrayer, by selectively separating the atmosphere into steam and dry air. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a protein microarrayer that integrates and immobilizes proteins and biomolecules that trap them in a high density and uniform spot shape on a chip substrate.

A method in which a so-called DNA chip is used to comprehensively perform gene analysis by spotting a large number of DNAs having biological genes called probes on a glass substrate, sprinkling the sample to be examined on the glass substrate, and examining the interaction with the probe. Has come to be used frequently.
Usually, as a method for spotting many types of DNA on a glass substrate at high density, a device called a microarrayer that attaches DNA to a plurality of spot pins and transfers it to the glass substrate is known. Therefore, the direction of medical development is comprehensive and comprehensive from gene analysis to functional analysis of proteins encoded by genes (including antibodies, peptides, lectins, etc.), as well as protein-gene interactions and protein-protein interactions Proteome analysis is rapidly shifting to analysis, and protein array chips are attracting attention as a tool. However, it has been considered difficult to apply a microarrayer similar to DNA for the production of an array of proteins and antibodies that bind to the protein (protein array).

  The reason is that proteins are modified differently depending on the environmental conditions, and they have more than 300,000 different types of proteins. Their structures and properties are diverse, and solutions for dissolving proteins are also diverse. Therefore, it was difficult to form a uniform spot on the chip substrate under the same conditions. Recently, it has been found that changing the humidity of the array environment according to the characteristics of the protein solution is effective for uniform spot formation, and an example of installing a humidifier or dehumidifier inside the arrayer has been carried out. Although all of these have been combined with humidification and dehumidification using heaters and refrigerators, etc., not only the structure of the device is complicated, but also energy such as electricity is consumed, and the amount of heat consumed is set up by the arrayer. It had the disadvantage of becoming a heat load in the clean room.

  The present invention provides a protein micro-arrayer that has a humidity control mechanism that can be humidified and dehumidified without using power, and at the same time, realizes an ultra-clean environment within the arrayer and can eliminate the need for a clean room in the room where the arrayer is installed. It is to provide. As a result, energy is not required for humidification, dehumidification, and air conditioning, and an environmentally friendly arrayer can be realized.

  The present inventor usually pays attention to a non-porous dissolution diffusion membrane (hereinafter referred to as a hollow fiber membrane) that selectively produces moisture by compressing moisture, that is, water vapor, to produce dry air. We have developed a system that can adjust both humidification and dehumidification of the atmosphere, and at the same time realizes a clean environment inside the arrayer that is more clean than a clean room.

  That is, the present invention transfers a solution containing a protein as a probe onto a chip substrate through a spot pin that moves in three dimensions by immersing the tip in the solution, and forms a plurality of spots on the substrate. (1) A hollow fiber membrane that selectively separates water vapor from air is placed outside the arrayer, and compressed air is introduced into the hollow fiber membrane. (2) Water vapor discharged from the hollow fiber membrane and drying Air is individually introduced into the microarrayer via each control valve, and (3) the control valve can automatically adjust the opening according to the setting of the humidity controller so that the humidity in the arrayer becomes the target humidity Related to microarrayer.

  In order to form a uniform spot with a spot pin in a protein array, it is necessary to adjust the humidity inside the arrayer according to the properties of the solution in which the protein is dissolved, usually within the range of 30 to 65% relative humidity. Adjusted. If the humidity is lower than the humidity suitable for the properties of the solution used, the spot shape tends to be chipped, and if it is too high, the spot shape swells and expands, and neither of them can obtain a suitable spot shape, so protein analysis Adversely affect. Finding the right humidity conditions for protein arrays and adjusting the array environment to that humidity is more important. Conventionally, in the case of humidification, water is generally evaporated and vaporized by an electric heater or ultrasonic waves, and in the case of dehumidification, a method of condensing with a refrigerator is generally required, and energy is required for both. In addition, the arrayer itself is usually installed in a clean room in order to avoid protein contamination and functional degradation due to the surrounding environment, and it requires consumption of enormous power to operate the clean room.

  According to the present invention, no energy such as power and electric heater is used for humidifying and dehumidifying operations, so there is no energy cost and there is no thermal load, so it is also a burden on the air conditioning of the clean room where the arrayer is installed. Not only does it have the feature that the interior of the arrayer can be made into an ultra-clean environment at the same time, the clean room itself can be omitted, and an environmentally friendly microarrayer can be realized. In addition, there is an incidental effect that the facility cost can be reduced by using only the membrane, the control valve, and the piping.

  A hollow fiber membrane consisting of a non-porous dissolution and diffusion membrane is used to control the humidity inside the arrayer, and the air in the room where the arrayer is installed is compressed with a compressor, etc., and passed through this hollow fiber membrane to separate into water vapor and dry air When humidifying, the separated water vapor is injected into the interior of the arrayer, and when dehumidifying and dehumidifying is performed, one dry air separated from the water vapor is injected into the interior of the arrayer to humidify and dehumidify. Is made possible by the same mechanism. If the indoor air where the arrayer is installed is used as the air passing through the hollow fiber membrane, the separated water vapor and dry air are released into the same room, so the indoor humidity does not change and there is no load on the clean room etc. In addition, since the hollow fiber membrane itself functions as an ultra-precise filter, the water vapor and dry air generated from it both are clean, and the interior of the arrayer can be made a clean environment higher than that of the clean room. Eliminates environment-friendly layering.

  It is a conceptual diagram which shows this invention. Reference numeral 1 denotes a microarray body. Reference numerals 2 and 3 denote robots that three-dimensionally move a pin holder 4 that holds a spot pin. A spot pin 5 is attached to the pin holder 4. 6 is a well plate for holding a protein solution, and is fitted in contact with the cooling plate 7. Reference numeral 8 denotes a Peltier (heating / cooling element) for cooling the cooling plate 7. 9 is a chip substrate. A hollow fiber membrane 10 serves to separate the compressed air sent from the compressor 11 into water vapor and dry air. The separated water vapor and dry air are adjusted by the control valves 14 and 15 through the water vapor pipe 12 and the dry air pipe 13, respectively, according to the set humidity of the humidity sensor 16 installed in the arrayer. Reference numeral 17 denotes a compressed air precision filter.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Microarrayer main body 2 Pin up-and-down movement robot 3 Pin back-and-forth movement robot 4 Pin holder 5 Spot pin 6 Well plate 7 Cooling plate 8 Peltier 9 Chip substrate 10 Hollow fiber membrane 11 Compressor 12 Water vapor piping 13 Dry air piping 14 Control valve 15 Control Valve 16 Humidity controller 17 Precision filter

Claims (1)

In a protein microarrayer, in which various kinds of proteins are made into solutions and the minute liquid dots are spotted at high density on the chip substrate using spot pins and fixed in an integrated array, water vapor and dry air are selectively separated from the atmosphere. Protein microarrayer characterized in that humidity can be adjusted using a porous dissolution and diffusion membrane (hollow fiber membrane)

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