Droplet ejecting apparatus

Fluid sprinkling – spraying – and diffusing – With means to vibrate or jiggle discharge – By electric transducer

Reexamination Certificate

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Details

C347S014000

Reexamination Certificate

active

06719211

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a droplet ejecting apparatus for stably and accurately ejecting micro droplets. More specifically, the present invention relates to a droplet ejecting apparatus, which can be promptly operated at an arbitrary moment when said droplet ejecting apparatus is operated, in which case the amount of droplets actually ejected is quantitatively measured, and control is performed, based on the information obtained by the quantitative measurement.
2. Description of the Related Art
Micro droplet ejecting means play an essential role in the fields of biotechnology as well as in the fields of manufacturing chemicals, foods, etc, since the stability regarding the amount of ejected droplets and the accuracy regarding the position thereof directly relates to the quality and the producibility of the products manufactured using the droplet ejecting apparatus.
Generally, the amount of droplets is normally determined only by the droplet ejecting means itself. However, there is no means for determining the final positions at which the ejected droplets arrive. At present, the products produced from ejected droplets are inspected in an initial test in terms of the quality and/or byproducts produced from the ejected droplets by using certain detection means. On the basis of the results obtained in these investigations, the droplet ejecting means is controlled. As a result, a relatively long inspection period is necessary in periodical inspections of the ejected goods or articles, and therefore there is a problem in that the productivity is reduced. If the amount of a droplet can be evaluated in real time without delay for each ejection, the inspection can be frequently carried out without any reduction in the productivity, so that in an early stage either a bad condition can be ascertained or variations in quality can be suppressed, thereby allowing a high quality to be maintained. Such requirements have been previously described.
For instance, a method for uniformly mixing materials and a mixing apparatus have been proposed in Japanese Unexamined Patent Application Publication No. 11-262644. In the specification, it is pointed out that a treatment of mixing micro materials and reacting them with each other is required for research in the field of biotechnology, and in order to satisfy these requirements, two or more piezoelectric control type droplet ejecting means are employed. By colliding micro droplets ejected from different droplet ejecting means with each other, these droplets can be uniformly mixed, thereby enabling different materials to be uniformly reacted with each other, thus allowing uniform reaction products to be obtained.
In such a method for uniformly mixing materials as well as in such a mixing apparatus, the rate of non-collision is determined by collecting uncollided droplets, thereby allowing the collision rate to be increased by correcting the ejection direction of the materials on the basis of the thus determined rate of non-collision via a feedback system.
Moreover, the origin of the instability in the ejection, for instance, the deflection of a droplet flight direction, the variation in both the purity and the reaction of the droplets, the variation in the reaction speed due to variations in temperature and/or variations in both the viscosity and specific gravity of the liquid in a fluid channel, must be investigated in advance, and such instability should preferably be suppressed, based on the results obtained from the investigation.
In these methods, the state of an apparatus was controlled by determining the conditions of operation indirectly relating to the ejection of droplets.
Furthermore, for instance, in Japanese Unexamined Patent Application Publication No. 8-201265, a viscosity measuring apparatus and a method for determining fluid characteristics have been proposed. In this specification, it is emphasized that it is important to measure the viscosity of a fluid in order to ensure the quality of products and/or to control the process for manufacturing the products, where the products are in the form of a fluid, e.g., a chemical, food, lubricant, car wax or the like, and for this reason the viscosity of the fluid is determined, based on the change in the specific electrical constant of an oscillating element made of a piezoelectric material, where the oscillating element is oscillated in the fluid and is subjected to a mechanical resistance resulting from the viscosity of the fluid.
When an anomaly is found in the specific electrical constant of the piezoelectric element, the ejection of droplets is set to cease and then a recovery treatment is performed.
In this method, there is an advantage in that the piezoelectric element can be used not only as an actuator but also as a sensor. However, the piezoelectric element is used exclusively to monitor the characteristics, such as the viscosity, of the fluid stored in a cavity or the like before the ejection, and not to monitor the characteristics of the droplets after ejection.
Moreover, in order to determine the amount of liquid ejected, an electronic force balance is conventionally used to measure the accumulated mass of ejected droplets within the measurement range of the balance, and the mass of one droplet is determined by dividing the accumulated mass by the number of droplets. This method is also unsuitable for controlling the stability in the amount of ejection for a droplet.
Moreover, the present applicant has proposed a micropipette and a separate injecting apparatus in Japanese Patent Application No. 11-301626. In the specification, it is emphasized that, in the production of a DNA chip for analyzing gene structure, it is important to suppress variations in the volume and the shape of individual micro droplets and to preserve the distance between the micro spots at a fixed value. It is described that the micropipette comprises both a main body including a sample supplying opening, a cavity for storing the sample and a sample discharging opening, and a piezoelectric element mounted on the outer surface of the main body at the position corresponding to the cavity, and it is also described that a certain amount of the sample in the cavity can be ejected from the sample ejecting opening with the aid of a change in volume of the cavity by activating the piezoelectric element, thereby enabling micro spots such as DNA chips to be formed very accurately and rapidly.
In this proposal, the cavity is filled in advance with a substitution solution, such as buffer solution or physiological saline solution, and then a sample is supplied into the cavity from the sample supplying opening, by substituting the substitution solution therewith in a laminar flow. After that, the piezoelectric element is activated. In this case, the completion of the substitution in the cavity using the laminar flow is preferably determined not by the volume and moving speed of the sample, but by the change in fluid characteristics in the cavity, in which case the piezoelectric element is activated by applying a voltage thereto and the change in the specific electrical constant in the oscillation of the piezoelectric element is sensed.
In order to more accurately determine the completion of the laminar flow substitution, it is desirable that the change in the characteristics, not of the liquid in the cavity, but of the droplets actually ejected therefrom be measured, if possible. From this viewpoint, the present applicant tried to further modify the droplet ejecting apparatus, and made certain discoveries to reach the present invention, after many investigations.
As described above, it is necessary to maintain the stability in the amount of droplets ejected from a micro droplet ejecting means and the accuracy in sensing the arrival position of the droplets, e.g., in the formation of DNA chips which are necessary for the treatment of mixing and reaction and for analyzing gene structure in biotechnology, or in the formation of micro spots which are necessary for p

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