Biochip manufacturing method and biochip manufacturing device

Abstract

Provided is a method of manufacturing a biochip using a droplet discharging device including a droplet discharging head having a cavity and a nozzle hole provided in communication with the cavity, and a liquid housing unit connected to the cavity via a passage, having the steps of filling a retention liquid which separates without getting mixed with the sample liquid into the liquid housing unit, the passage, and the cavity; injecting the sample liquid into the liquid housing unit; moving the sample liquid from the liquid housing unit to the cavity by discharging the retention liquid from the nozzle hole; stopping the discharge of the retention liquid at the moving step upon detecting with a sensor that the sample liquid reached a position adjacent to the nozzle hole; and delivering the sample liquid as droplets onto the object by discharging the sample liquid from the nozzle hole.

Description

CROSS-REFERENCES[0001]This application is a divisional of U.S. patent application Ser. No. 11 / 497,736 filed on Aug. 2, 2006. This application claims the benefit of Japanese Patent Application No. 2005-248756 filed on Aug. 30, 2005. The disclosures of the above applications are incorporated herein by reference.BACKGROUND[0002]1. Technical Field[0003]The present invention pertains to improved technology in the case of using a droplet discharging device for the manufacture of a so-called biochip in which a biological material is immobilized on an object such as a substrate.[0004]2. Related Art[0005]In recent years, so-called biochips (microarrays) formed by immobilizing a biological material such as DNA (nucleic acid), protein or antibody as the probe onto a substrate (chip) is attracting keen attention. Conventionally, biochips were manufactured by attaching a sample liquid containing DNA to the tip of a pin with a solid pin spotter, and transcribing this onto a chip. Nevertheless, th...

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Benefits of technology

[0008]Accordingly, an advantage of some aspects of the invention is to provide manufacturing technology enabling the manufacture of biochips by avoiding as much as possible the waste of the sample liquid.

[0011]According to the manufacturing method of the foregoing aspects, it is possible to replace the waste liquid, which is discharged until the sample liquid is sufficiently filled in the cavity, with a retention liquid by suitably selecting an inexpensive retention liquid. Therefore, it is possible to manufacture biochips by avoiding as much as possible the waste of the expensive and scarce sample liquid.

[0014]According to the above, it is possible to easily realize the combination of a sample liquid and a retention solution that get separated without getting mixed together.

[0016]When a fluorescent material is contained in the sample liquid to be used for manufacturing biochips, it is possible to easily detect the switching from the retention liquid to the sample liquid by using such fluorescent material.

[0020]According to the foregoing configuration, it is possible to replace the waste liquid, which is discharged until the sample liquid is sufficiently filled in the cavity, with a retention liquid by suitably selecting an inexpensive retention liquid. Therefore, it is possible to manufacture biochips by avoiding as much as possible the waste of the expensive and scarce sample liquid.

[0022]Since a fluorescent material is often contained in the sample liquid used for manufacturing biochips, it is possible to easily detect the switching from the retention liquid to the sample liquid by using such fluorescent material.

Problems solved by technology

Nevertheless, this method had inconveniences such as contamination due to the contact with the spotter, low productivity and so on.

Generally, biological materials such as nucleic acid used as the probe are often extremely expensive, and the obtained amount (absolute amount) for use in medical diagnosis and so on is usually small.

Nevertheless, in the case of a droplet discharging head, when filling the sample liquid from the cartridge to the head through minute flow channels, there are inherent problems in that small amounts of waste fluid will arise due to the discharge of air bubbles, and residual liquid that could not be discharged will remain in the head even after the discharge.

Thus, the foregoing problems could not be completely resolved even with the miniaturization of the cartridge as described above, and there is still room for improvement.

Here, even assuming that it is possible to stop the suction operation at the instant the sample liquid reaches the nozzle hole, since it is difficult to instantaneously eliminate the inertia of the sample liquid or the negative pressure of the suction pump, the sample liquid will continue to be discharged from the nozzle hole for a while after the suction operation is stopped.

More realistically, air bubbles are engulfed in the sample liquid due to the sudden aspect change between the minute flow channels and the cavity (liquid housing chamber) in the droplet discharging head connected to such minute flow channels, and these air bubbles cause a defective discharge.

Therefore, the current status is that large amounts of sample liquid are wasted as waste liquid.

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