WO2002018903A1

WO2002018903A1 - Simple implement for collecting/recovering liquid sample

Info

Publication number: WO2002018903A1
Application number: PCT/JP2000/005790
Authority: WO
Inventors: Toru Yokoyama; Naoki Shinozuka; Kenji Nakamura
Original assignee: Sapporo Immuno Diagnostic Laboratory
Priority date: 2000-08-28
Filing date: 2000-08-28
Publication date: 2002-03-07
Also published as: AU2000267325A1

Abstract

A method of collecting and recovering a sample to be examined easily and quickly, and a simple implement for collecting/recovering a sample by using this method. More specifically, a method of collecting and recovering a liquid sample, characterized by comprising the steps of collecting, in a structure comprising at least one layer of a hydrophilic absorber disposed on a water-resisting support, a liquid sample by the hydrophilic absorber and then pressing the absorber to recover the absorbed liquid sample, and a simple implement for collecting/recovering a liquid sample by using the above method.

Description

Specification

FIELD OF THE INVENTION Field of the Invention

The present invention collects and collects liquid samples, for example, urine, saliva, sputum, swabs of throat, samples derived from living organisms such as sweat, tears, and blood, food analysis samples, and environmental measurement samples. It relates to possible methods and simple appliances. Background of the Invention

In clinical tests, various body fluids are overwhelmingly used, and blood, especially serum, usually maintains homeostasis, metabolic kinetics of the whole body, and various organ information can be obtained easily. It is heavily used. Most of the collections are invasive, but urine, feces, sputum, and pharyngeal swabs are listed as non-invasive samples, and are important samples used in various tests. It has been recognized.

In particular, urinalysis includes 10 items such as protein, glucose, occult blood, etc., using the urine test paper method as a general test, and other endocrine tests such as electrolytes and minerals as biochemical tests. I have.

In recent years, urine and saliva have been shown to be useful as specimens to replace blood such as serum and plasma. Urine collection is easier and less painful to subjects and patients than blood collection. Saliva collection is not only painless, but also easy and anytime, anywhere.

Recently, simple and quick point-of-care testing (POCT) using easily collected specimens is showing signs of widespread use. Urinalysis using the test strip method has already been performed in outpatient consultation rooms and ward laboratories, and is a typical example of P TCT. Other examples of POCT include simple tests performed by healthcare professionals in clinical practice and nursing settings, and performed at home by the subject themselves.As self-tests, pregnancy tests using urine as specimens are increasing.

Tests using saliva as samples (Annals of the New York Academy of Sciences, Vol.694, p.216 (1993)) is a sample collected using a saliva collection instrument r OraSureJ (Epitope, Inc.) (e.g. US Pat.No.5,714,341 (1998)). Various screening tests such as rubella, therapeutic drugs such as theophylline and phenytoin, and drugs such as nicotine and cocaine, and drug monitoring tests are conducted (Journal of the Japan Society of Clinical Laboratory Automation, Vol. 19, p. 265 (1994)).

In addition, a saliva collection device “Omnisal (Saliva-Sampler)] (manufactured by Saliva Diagnostic Systems, Inc.) (US Patent No. 5,260,031 (1993)) and a saliva collection device r SalivetteJ (manufactured by Sarstedt) (eg, US Patent No. 4,774,962) (1988)) The same test as above is also being conducted using saliva, a non-invasive sample and a liquid sample, as described above. Excellent operability has been achieved with dedicated instruments such as a sampling instrument and a storage tube containing a preservation solution.

However, since the test is not performed on the spot, the sample stored in the storage container is transported to an inspection center or the like, where the sample is collected and the test is performed for the first time. Considering the above steps and required time, there is a problem with the speed.

In recent years, with the remarkable progress of biosensor technology, various small measuring instruments that can perform simple tests at the bench have begun to be developed, and there is a strong demand for simple instruments that can collect samples immediately after collection.

Also, since the examination is in the medical field, most of the instruments are disposable in consideration of infection and other factors, and the above-mentioned sampling instruments require dedicated instruments for sampling, storage, and collection. Another important issue is to minimize the amount of waste by reducing the number of equipment. Summary of the Invention

In order to solve the above-mentioned problems, the present invention provides a structure in which at least one layer of a hydrophilic absorber is disposed on a water-resistant support, wherein a liquid sample is collected by the hydrophilic absorber, and then the hydrophilic sample is collected. A method of collecting and collecting a liquid sample, which comprises compressing a body and collecting the absorbed liquid sample, and a simple instrument for collecting and collecting a liquid sample using the method. It is intended to realize quick collection and recovery. Description of the invention

The present invention realizes a method for collecting and collecting a specimen for simple and rapid examination. Specifically, in a structure in which at least one layer of a hydrophilic absorber is disposed on a water-resistant support, a liquid sample is collected by the hydrophilic absorber, and then the hydrophilic absorber is pressed to absorb the liquid sample. A method for collecting and collecting a liquid sample, characterized by collecting the liquid sample. Further, the present invention also provides a simple instrument for collecting and collecting a liquid sample using the above method.

Further, in a structure in which at least one permeable hole is provided in the water-resistant support, and at least one layer of the hydrophilic absorber is disposed on the permeable hole, a liquid sample is collected by the hydrophilic absorber. Thereafter, the present invention also provides a method of recovering the absorbed liquid sample by pressing the hydrophilic absorber through the perforation hole.

The hydrophilic absorber is also characterized in that it has a separation function capable of removing the contaminant at the time of recovery by selecting a material having a property of adsorbing the contaminant in the liquid sample.

The separation function is provided by selecting a material having a positive or negative charge or a material having an ionic binding ability and a covalent binding ability for the adsorption layer.

Further, by forming the hydrophilic absorber into a multilayer structure comprising at least an absorption layer and filtration layers of various pore sizes, at the time of collection through the permeation hole, the liquid sample having a pore size equal to or smaller than the pore size selected for the filtration layer is obtained. Another major feature is that it has a filtration function that allows fractionation.

For example, when collecting bacteria in a liquid sample, filtration can be performed by setting the pore size to 0.22 m. In addition, in order to obtain blood plasma or serum components by filtering blood cell components from whole blood, the pore size can be reduced to 10 x m or 5 m or less. Various whole blood filtration methods have been reported for separating plasma or serum using a porous component (eg, WO96 / 03194 (1996)).

Although there are many reports on whole blood filtration, the present invention also provides a simple collection and recovery method having both separation and filtration functions, which combines the above-mentioned contaminant removal method and fractionation method. Further, as the liquid sample, a sample derived from a living body such as blood, urine, and saliva, a sample for food analysis, a sample for environmental measurement, and a sample that can be liquefied can be used. When handling, for example, in the case of a sample that may be infected, use a compression plate with a perforated hole at the time of collection to avoid adherence to the practitioner.

As described above, by providing a simple instrument for collecting and collecting a liquid sample, extremely simple operability was realized, and the instrument was configured with inexpensive members, and was formed into a shape that could be mass-produced. In addition, the process from collection to collection can be performed with at most two instruments, collection and collection equipment, and compression plates. As a result, waste was reduced, and environmental issues were taken into account by minimizing the use of non-combustible materials such as plastics. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a top view and a side view of a simple device for collecting and collecting a liquid sample in Example 1 of the present invention;

FIG. 2 is a schematic diagram of a method of collecting a liquid sample using a compression plate in Example 1; FIG. 3 is a schematic diagram of a method of collecting and collecting a liquid sample having a separation function in Example 2;

FIG. 4 is a schematic diagram of a method for collecting and collecting a liquid sample having a filtration function according to the third embodiment.

The symbols in the above figures are explained as follows:

1 is a water-resistant support; 2 is a hydrophilic absorber; 3 is a liquid sample; 4 is a permeation hole; 5 is a compression plate; 6 is an absorption layer; 7 is an adsorption layer; 8 is a filtration layer; 0 is a seal; 11 is a sample supply hole. Description of preferred embodiments

The water-resistant support and the compression plate used in the present invention are machines that do not adsorb to the collected liquid sample or contaminate the liquid sample, are water-resistant, have good workability and are not damaged during use. There is no particular limitation as long as the target strength is provided. For example, plastic films such as polyester, polyethylene, polyethylene terephthalate (PET), polystyrene, and polypropylene, and thick paper treated with water resistance are inexpensive. From the viewpoint of good adhesion to a hydrophilic absorber and good workability, it was found that water-treated paper was preferred here.

Depending on the sample to be collected, the use of water-resistant paper may ease the disposal conditions of the used simple instrument after collection and collection.

The hydrophilic absorber, which collectively refers to the absorption layer, adsorption layer, filtration layer, and spreading layer, is free from unspecific unintended adsorption with the collected liquid sample and contamination of the liquid sample, and is a material that absorbs the liquid sample And there is no particular limitation as long as it is hydrophilic. For example, fibers such as glass fiber, silica fiber, and cell mouth fiber, and carboxymethyl cellulose, methylaminoethyl cellulose, cell mouth varnish acetate, cellulose mixed ester, nylon, nitrocellulose, polyether sulfone, polyester, and polyester Len, polyvinyl chloride, polycarboxylic acid, polytetrafluoroethylene, polyvinylidene fluoride, polyvinylidene difluoride, polypropylene and the like can be used.

The absorption layer is not particularly limited as long as quick absorption of the liquid sample is realized.

The adsorbent layer should be made of a material that has positive or negative charge or a material that has ionic and covalent bonding capabilities, so long as it can realize a separation function that can remove contaminants by adsorption. There is no limitation.

The filtration layer is not particularly limited as long as it realizes a filtration function capable of preparatively determining the molecular size of the recovered sample by selecting various pore sizes.

The spreading layer is not particularly limited as long as it has a function of sequentially spreading the sample after filtration when the filtering layer is provided and improving the filtering efficiency.

The seal is water-resistant and does not adsorb to the collected liquid sample or contaminate the liquid sample. Furthermore, when collecting through the perforated hole, it shields around the perforated hole to prevent contamination. There is no particular limitation as long as it can hold a water-resistant support. The adhesion between the water-resistant support and the hydrophilic absorber is not particularly limited as long as it is a substance that does not adsorb to the liquid sample or contaminate the liquid sample. Example

Hereinafter, examples of the present invention will be specifically described, but the present invention is not limited to these. It is not something to be done. Example 1 Preparation of simple instrument for collecting and collecting liquid sample

FIG. 1 is a top view and a side view showing an example of manufacturing a simple instrument for collecting and collecting a liquid sample in the present embodiment. FIG. 2 is a schematic diagram showing a method of recovering a liquid sample using a compression plate in the present embodiment.

A hydrophilic absorber 2 made of cellulose (made by Nippon Pall Co., Ltd.) is placed on a water-resistant support 1 made of thick paper (made by Oji Yuka Kagaku Synthetic Paper Co., Ltd.) that has been subjected to a water-resistant treatment with an adhesive. 'T. The liquid sample 3 is brought into contact with the hydrophilic absorber 2;

In the case of non-infectious liquid sample 3, it is possible to compress the hydrophilic absorber 2 by bending the water-resistant support 1 and collect the collected liquid sample 3 from the end surface of the water-resistant support 1. It became.

Next, in the case of the liquid sample 3 which may be infected, the liquid sample 3 is already collected by the compression plate 5 having the transmission hole 4 in the insulating support 1 having the transmission hole 4. By sandwiching the instrument and pressing it, it becomes possible to collect it from the end face of the water-resistant support 1 or through the perforation holes 4 of both the water-resistant support 1 and the compression plate 5, thereby preventing the sample from adhering to the operator. Could be prevented.

In addition, when saliva was actually collected as liquid sample 3 using this simple device, it showed good absorbability and quick collection was possible. In addition, the simple shape of the simple device makes it easy to place it at the target site. Was easily carried out. In particular, in the sample collected after collection, a viscous substance considered to be mucin was trapped by the hydrophilic absorber 2 and became serous. It was also confirmed that food residues and the like were captured to some extent by the hydrophilic absorber 2. Example 2 Addition of separation function

FIG. 3 is a schematic diagram of a collection method in which a separation function is added to a simple device for collecting and collecting a liquid sample in the present embodiment. A two-layer hydrophilic absorber 2 composed of an absorbent layer 6 made of cellulose (manufactured by Nippon Pall Co., Ltd.) and an adsorption layer 7 made of nylon (manufactured by Nippon Pall Co., Ltd.) was disposed on the water-resistant support 1. . Further, the transmission hole 4 on the lower surface side in the sample supply direction was shielded by a seal 10 in which an adhesive was applied to one surface of the PET film. The selected adsorption layer 7 has the ability to adsorb proteins by covalent bonds.

Using this simple device, urine with various protein concentrations was spotted on the absorbent layer 6 as actual samples. Sixty seconds later, the seal 10 on the lower surface was peeled off, and the absorbing layer 6 and the absorbing layer 7 were pressed by the compression plate 5 to collect the gas from the permeation hole 4.

Here, 'spotting' showed good absorption, and quick sampling was possible. Thereafter, the collected sample had a lower protein concentration than before the collection, and protein binding by the adsorbent layer 7 was recognized, thus realizing the separation function.

In this example, the proteins in the sample were separated by the two-layer structure of the absorption layer 6 and the adsorption layer 7, but the same separation effect can be obtained by using only one layer of the adsorption layer 7. At that time, after removing the excess sample attached to the portion other than the adsorption layer 7, the sample can be recovered from the end surface of the water-resistant support 1 without using the permeation hole 4. Example 3 Addition of filtration function

FIG. 4 is a schematic view of a collection method in which a filtering function is added to a simple device for collecting and collecting a liquid sample in the present embodiment.

An absorption layer 6 made of cellulose (manufactured by Nippon Pall Co., Ltd.), a filtration layer 8 made of polyether sulfone (manufactured by Nippon Pall Co., Ltd.), and a spreading layer 9 made of polyester (manufactured by Nippon Pall Co., Ltd.) The hydrophilic absorber 2 having a layer structure was disposed on the water-resistant support 1, and the hydrophilic absorber 2 was covered with a seal 10 in which an adhesive was applied to one surface of a PET film. The transmission hole 4 on the lower surface side in the sample supply direction was also shielded by the seal 10. Whole blood as an actual sample was spotted from the sample supply hole 11 of the seal on the upper surface. Sixty seconds later, the seal 10 on the upper surface was partially peeled off, and separated from the other two layers so as to enclose the absorbent layer 6 containing the blood cell component in whole blood. Thereafter, the seal 10 on the lower surface was peeled off, and the filtration layer 8 and the developing layer 9 were pressed by the compression plate 5, whereby the liquid component in the whole blood could be collected from the permeation hole 4. In this embodiment, the filtration function of separating blood cells was provided by setting the pore size of the filtration layer 8 to 5 m, which is smaller than the size of blood cells in whole blood.

In the above embodiment, the specific shape of the simple instrument for collecting and collecting the liquid sample is illustrated, but the shape and arrangement of other components are not limited.

Claims

The scope of the claims

1. In a structure in which at least one layer of a hydrophilic absorber is disposed on a water-resistant support, a liquid sample is sampled by the hydrophilic absorber, and then the hydrophilic sample is pressed to absorb the liquid sample. Collecting the liquid sample and collecting the liquid sample.

2. The structure in which the water-resistant support has at least one permeation hole, and at least one layer of the hydrophilic absorber is disposed on the permeation hole, the liquid sample is subjected to the hydrophilic absorption. 2. The method for collecting and collecting a liquid sample according to claim 1, wherein the liquid sample is collected by a body, and thereafter, the hydrophilic sample is compressed to recover the absorbed liquid sample through the transmission hole.

3. The hydrophilic absorber has a separation function capable of removing the contaminants at the time of collection by selecting a material having a property of adsorbing the contaminants in a liquid sample. Or the method for collecting and collecting a liquid sample according to 2.

4. By forming the hydrophilic absorber into a multilayer structure comprising at least an absorption layer and filtration layers of various pore sizes, the liquid sample having a pore size equal to or smaller than the pore size selected for the filtration layer at the time of collection through the permeation hole is obtained. The method for collecting and collecting a liquid sample according to any one of claims 1 to 3, wherein the method has a filtration function capable of fractionation.

5. The liquid sample according to any one of claims 1 to 4, wherein a sample derived from a living body such as blood, urine, and saliva, a sample for food analysis, a sample for environmental measurement, and a sample that can be liquefied can be used. The method for collecting and collecting a liquid sample according to any one of the above.

6. In a structure in which at least one layer of the hydrophilic absorber is disposed on the water-resistant support, a liquid sample is collected by the hydrophilic absorber, and then the hydrophilic absorber is pressed to absorb the liquid sample. The method according to claim 1, wherein the liquid sample is collected. An instrument for collecting and collecting used liquid samples.

7. In the structure in which the water-resistant support has at least one permeation hole and at least one layer of the hydrophilic absorber is disposed on the permeation hole, a liquid sample is collected by the hydrophilic absorber. 7. The device for collecting and collecting a liquid sample according to claim 6, wherein the device absorbs the liquid sample through the perforation hole by pressing the hydrophilic absorber.

8. The hydrophilic 'absorber is provided with a separation function capable of removing the contaminants at the time of collection by selecting a material having an affinity for adsorbing contaminants in a liquid sample. Item 6. A device for collecting and collecting a liquid sample according to Item 6 or 7.

9. By forming the hydrophilic absorber into a multilayer structure including at least an absorption layer and filtration layers of various pore sizes, the liquid sample having a pore size equal to or smaller than the pore size selected for the filtration layer at the time of collection through the permeation hole is obtained. 9. The device for collecting and collecting a liquid sample according to claim 6, wherein the device has a filtering function capable of fractionation.

10. The liquid sample according to any one of claims 6 to 9, wherein a sample derived from a living body such as blood, urine, saliva, etc., a sample for food analysis, a sample for environmental measurement, and a sample that can be liquefied can also be used. A device for collecting and collecting a liquid sample according to any one of the above.