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Patent Issued for Dispensing Nozzle for Automatic Analyzer, and Automatic Analyzer Including Same

August 26, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- Hitachi High-Technologies Corporation (Tokyo, JP) has been issued patent number 8802008, according to news reporting originating out of Alexandria, Virginia, by NewsRx editors (see also Hitachi High-Technologies Corporation).

The patent's inventors are Taniguchi, Shinichi (Tokyo, JP); Nojima, Akihiro (Yokohama, JP).

This patent was filed on November 26, 2010 and was published online on August 12, 2014.

From the background information supplied by the inventors, news correspondents obtained the following quote: "In clinical examination for medical diagnosis, protein, sugar, lipid, enzyme, hormone, inorganic ions, disease markers, and the like in biological samples, such as blood and urine, are biochemically analyzed and immunologically analyzed. In clinical examination, it is necessary to treat a plurality of examination items with high reliability at high speed, and therefore, most of them are performed by an automatic analyzer. As the automatic analyzer, for example, a biochemistry analyzer that performs biochemical analysis by using, as an object to be analyzed, a reaction solution obtained by mixing a sample, such as serum, with the desired reagent for reaction, and measuring the absorbance of the reaction solution is known. A biochemistry analyzer of this type includes containers containing samples and reagents, and reaction Cells into which the samples and the reagents are to be injected, and includes dispensing mechanisms including dispensing nozzles for automatically injecting the sample and the reagent into the reaction Cell, an automatic stirring mechanism having a stirring bar for mixing the sample and the reagent in the reaction Cell, a mechanism for measuring the absorbance of the sample during reaction or after the completion of the reaction, an automatic washing mechanism for sucking and discharging the reaction solution after the completion of the measurement and washing the reaction Cell, and the like (for example, Patent Literature 1).

"In such an automatic analyzer, generally, a large number of samples and reagents are dispensed in turn by the dispensing nozzles. For example, the sample dispensing nozzle takes a predetermined amount of a sample from a container containing the sample, such as a blood collection tube, and discharges the sample into a reaction Cell for the reaction of a reagent. The reagent dispensing nozzle discharges into the reaction Cell a predetermined amount of a reagent taken from a container containing the reagent. At this time, if the components of the dispensed liquid remaining on the dispensing nozzle surface are mixed into the next dispensed liquid, the measurement result may be affected. This is referred to as carry over.

"The problem of carry over is deeply related to a demand for trace amounts of samples and reagents in the field of automatic analyzers in recent years. With the increase of the number of analysis items, the amount of a sample that can be used for one analysis item becomes smaller. The sample itself is precious and cannot be prepared in a large amount in some cases, and there is also a demand for higher sensitivity. In addition, as the analysis content becomes more sophisticated, generally, the reagent becomes more expensive, and there is a requirement for trace amounts of reagents also in terms of cost. Due to the increase of such a demand for trace amounts of samples and reagents, the diameter of the dispensing nozzle becomes smaller, and the outer diameter of the tube is about 0.5 mm. A very small nozzle diameter increases the proportion of the surface area to the volume of a dispensed solution. Therefore, the importance of controlling the adsorption of substances on the dispensing nozzle surface to reduce carry over increases.

"In addition, when a sample for the analysis of biochemistry items, and immunity items with a wide measurement concentration range is taken from the same container and measured, it is required to reduce carry over between samples by a dispensing nozzle as much as possible.

"In order to reduce carry over, conventionally, washing with pure water or a detergent containing a surfactant has been carried out (Patent Literature 2). A method of deactivating adhering sample residues with active oxygen is also known (Patent Literature 3). A method using a disposable nozzle (disposable tip), which can be thrown away after one use, is also known as one of methods for solving carry over.

"XPS (X-ray photo electron spectroscopy) and the like are widely used for the quantification and composition analysis of chemical substances adsorbed on a surface, and, for example, analysis is performed for the composition of monomolecular films, such as self-assembled monolayers, and the quantification of chemical species (Non Patent Literatures 1 and 2). Like these, quantification can be performed by XPS also for the quantification of protein remaining on a surface (Non Patent Literature 3)."

Supplementing the background information on this patent, NewsRx reporters also obtained the inventors' summary information for this patent: "Technical Problem

"In the washing with pure water or a detergent containing a surfactant, the washing of biopolymers typified by protein may be difficult. In the method of deactivating adhering sample residues with active oxygen, the deactivated sample residues are deposited on the surface, and therefore, the dispensing nozzle cannot withstand a long period of use. In addition, in the disposable nozzle, it is difficult to form a fine structure in terms of strength and processing precision. In addition, a problem of the use of disposable nozzles is that it produces a large amount of waste to increase the environmental load.

"It is an object of the present invention to provide the sample dispensing nozzle of an automatic analyzer in which the cleanliness of the surface is increased to promote the reduction of carry over, without using a disposable nozzle, and an automatic analyzer using the same.

"Solution to Problem

"For analysis items for which the necessity to avoid carry over is high, the analysis components are often biopolymers, such as protein. Therefore, in order to reduce carry over, a solution is to inhibit biopolymers, such as protein, from remaining on the surface of the dispensing nozzle. In the present invention, for this purpose, a molecule that inhibits nonspecific adsorption of biomolecules, such as a sample, is immobilized on the nozzle surface. In addition, in the immobilization of the above molecule, chemisorption, particularly a covalent bond, on the surface is used. At this time, the material of the nozzle is not limited as long as the molecule that inhibits nonspecific adsorption is immobilized on the outermost surface of the nozzle.

"Chemisorbing and coating a polyethylene glycol (PEG) derivative on the dispensing nozzle surface inhibits the adsorption of living body-derived polymers, such as protein, to solve the above problems. Here, chemisorption means a mode of adsorption on a solid surface with a heat of adsorption of about 20 to 100 kcal/mol, which is caused by a chemical bond, such as a covalent bond or an ionic bond. Chemisorption is distinguished from physisorption generally with a heat of adsorption of 10 kcal/mol or less, using Van der Waals force as bonding force. The polyethylene glycol derivative is hydrophilic and inhibits the adsorption of biopolymers, such as protein, by its steric repulsive force. The PEG derivative has the highest protein adsorption inhibition effect. This is because, generally, when a nonionic water-soluble polymer is coated on a material surface, the surface charge is suppressed while the hydrophilicity of the substance surface is improved. In addition to such properties, the fact that PEG has almost no toxicity is also important for clinical applications.

"From the requirements that the required number of ethylene oxide (--C.sub.2H.sub.4O--) groups is 2 or more and that the molecular interaction for molecules to be arranged is sufficient, it is desired that the molecular weight of the PEG derivative is 100 or more. On the contrary, if the steric repulsive force between molecules is too large, the amount of adsorption of the PEG derivative on the surface is reduced. Therefore, it is desired that the molecular weight of the PEG derivative is 20000 or less. The chemical structure of the coating PEG derivative need not be single and may be a mixture.

"The automatic analyzer of the present invention includes a plurality of sample containers each containing a sample; a plurality of reagent containers each containing a reagent; a plurality of reaction Cells into which the samples and the reagents are to be injected; a sample dispensing mechanism including a sample dispensing nozzle and dispensing the samples in the sample containers into the reaction Cells; and a reagent dispensing mechanism including a reagent dispensing nozzle and dispensing the reagents in the reagent containers into the reaction Cells, wherein the sample dispensing nozzle has a silicon oxide layer on a surface thereof, and a silicon derivative having polyethylene glycol, represented by the following general formula:

"Si--R.sub.1--(OCH.sub.2CH.sub.2).sub.n--O--R.sub.2 (n is a positive integer of 2 or more, R.sub.1 is a hydrocarbon group, and R.sub.2 is H or CH.sub.3)

"is chemisorbed on the silicon oxide layer.

"In addition, a method for manufacturing a dispensing nozzle for an automatic analyzer according to the present invention includes the steps of: (a) forming a silicon oxide layer on a surface of a dispensing nozzle using sputtering or drug solution application and drying; (b) washing the silicon oxide layer formed on the surface of the dispensing nozzle; immersing the washed dispensing nozzle in a solution of a polyethylene glycol derivative having a silanol group precursor, represented by the following general formula:

"R.sub.1R.sub.2R.sub.3Si--R.sub.4--(OCH.sub.2CH.sub.2).sub.n--O--R.sub.5(R- .sub.1, R.sub.2, and R.sub.3 are substituents on silicon, R.sub.4 is a hydrocarbon group, R.sub.5 is H or CH.sub.3, and n is a positive integer of 2 or more); (d) washing the treated surface of the dispensing nozzle with a solvent; and (e) drying the washed surface of the dispensing nozzle.

"Advantageous Effects of Invention

"According to the present invention, the adsorption of biopolymers, such as protein, on the dispensing nozzle can be inhibited. Therefore, carry over during dispensing operation can be reduced, and the analysis reliability of the automatic analyzer is improved, thereby contributing to trace amounts of samples and reagents and also contributing to the reduction of the running cost of the automatic analyzer."

For the URL and additional information on this patent, see: Taniguchi, Shinichi; Nojima, Akihiro. Dispensing Nozzle for Automatic Analyzer, and Automatic Analyzer Including Same. U.S. Patent Number 8802008, filed November 26, 2010, and published online on August 12, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8802008.PN.&OS=PN/8802008RS=PN/8802008

Keywords for this news article include: Alkenes, Silicon, Polyenes, Biochemistry, Hydrocarbons, Organic Chemicals, Polyethylene Glycols, Hitachi High-Technologies Corporation.

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Source: Life Science Weekly


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