JP3541902B2 - Incubator for chemical analysis slides - Google Patents

Description

【００５０】
本発明のインキュベータを用いることによって良好な精度で血糖の測定が可能であることが確かめられた。
【００５１】
測定例４
検体の放置時間と測定値
別の検体Ｎｏ．７、８、９について測定例６と同様の処理を行った後、化学分析スライド収納用ケースに封入した状態で長時間、室温に放置した後、反射光学濃度を測定し、血糖値を求めたところ以下の結果が得られた。
【００５２】
【表２】

【００５３】
本発明のインキュベータで処理後、脱水乾燥すれば、その後長時間室温に放置しても測定値は殆ど変わらないことが確かめられた。
【００５４】
測定例５
本発明のインキュベータを下記の温度条件に設定した空気恒温槽中に設置し、測定例２と同様の試験を行って以下の結果を得た。
【００５５】
環境温度
【表３】

【００５６】
本発明のインキュベータを用いれば夏（高温）、冬（低温）の環境条件であってもほぼ一定した測定値が得られることが確かめられた。
【００５７】
【発明の効果】
本発明のインキュベータにより、在宅患者等の操作者が血液等の液体試料を化学分析スライドに点着し、これをインキュベータの凹所に設置後に一切手を触れることなくインキュベートし、密閉容器に収納して検査機関等へ送付することができる。本発明のインキュベータは構造が簡単で安価に製造でき、操作も容易であることから在宅ケア等に容易に普及させることができるという効果を奏する。
【図面の簡単な説明】
【図１】本発明の一実施例であるインキュベータの上板を取り除いた状態の斜視図である。
【図２】上記インキュベータの使用状態を示す斜視図である。
【図３】このインキュベータの蒸発防止蓋の側面図である。
【図４】化学分析スライドの一例を中央で切断した状態の斜視図である。
【図５】化学分析スライド収納用ケースの一例の斜視図である。
【図６】従来のインキュベータの一例の斜視図である。
【符号の説明】
１ インキュベータ本体
２ 凹所
３ インキュベーション室
４ 角溝
５ 角溝
６ スライド板
７ スライド板
８ 蒸発防止蓋
９ 板
１０ 閉止コマ
１１ ストップリング
１２ 設置部
１３ ヒータ
１４ サーモスタット
２０ 化学分析スライド
２１ 多層分析要素
２２ スライド枠
２３ 円孔
３０ 化学分析スライド収納用ケース
３１ ケース本体
３２ 検体
３３ 乾燥剤[0001]
[Industrial applications]
The present invention relates to a chemical analysis slide incubator used for chemical analysis for quantitatively analyzing various components present in body fluids such as blood and urine using the chemical analysis slide.
[0002]
[Prior art]
In order to quantitatively analyze various components present in a body fluid, for example, glucose, bilirubin, urea, nitrogen, etc., a liquid reagent adjusted according to the component to be analyzed is poured into a test tube into which a liquid sample such as blood is injected. There was a way to do it. However, in such a method, a large amount of valuable body fluids such as human blood, which is a liquid sample, is required, handling is troublesome, it is difficult to perform a simple and quick measurement, and a large number of test liquids are continuously measured. There is a problem that it is difficult to perform the measurement. Due to such a problem, in recent years, an analysis method by a dry method in which a clinical chemistry test is performed using a chemical analysis slide containing all the reagents necessary for analysis using a dry multi-layer film forming technique has been performed. Became.
[0003]
This chemical analysis slide has a spotting opening for spotting a liquid sample such as blood, and is therefore spotted on the chemical analysis slide in an incubating step of heating at a certain temperature for a certain time using an incubator. In some cases, the water in the liquid sample evaporates and the progress of the reaction is suppressed halfway, and the reaction is not completed. Therefore, various incubators have been proposed in which moisture is prevented from evaporating from the liquid sample during the incubate.
[0004]
By the way, in recent years, home care has been advocated as a response to rising medical costs due to the rapid transition to an aging society and the development of advanced treatment, and is expected to be one of the cores of the future medical system. Have been.
[0005]
As one of the home care methods, there is a method using a chemical analysis slide.In this method, a patient instills blood on a chemical analysis slide at each home, incubates the blood, and then transfers the incubated chemical analysis slide to a hospital. The hospital will perform a chemical analysis slide analysis.
[0006]
This chemical analysis slide incubator for home care also employs the above-described countermeasures for preventing the evaporation of water. For example, there is a chemical analysis slide incubator as shown in FIG. 5 (Japanese Utility Model Laid-Open No. 3-126499). ).
[0007]
In FIG. 5, reference numeral 40 denotes an incubator for a chemical analysis slide. The chemical analysis slide incubator 40 includes a case 41, a heat block 42 having an upper portion protruding from the case 41, and a cover 43 mounted on the heat block 42.
[0008]
The heat block 42 has upper and lower recesses formed in the upper surface, and the upper stage is a cover support portion 44 having a shape substantially matching the cover 43 in plan view, and the lower stage is substantially matched with the chemical analysis slide in plan view. This is a slide storage part 45 having a substantially uniform thickness and a substantially same thickness.
[0009]
Further, the heat block 42 has a built-in heater (not shown) for heating the slide housing portion 44. Reference numeral 46 is a hole for a regulator code.
[0010]
The cover 43 is configured to be detachably fitted to the cover support portion 44 to seal the slide storage portion 45. Further, when the cover 43 is fitted to the slide storage portion 45 to seal the slide storage portion 45, the volume of the slide storage portion 45 is configured to substantially match the volume of the chemical analysis slide.
Reference numeral 47 denotes an indicator lamp for indicating that the ink is being used.
[0011]
As an incubation method using this incubator, first, a chemical analysis slide 20 as shown in FIG. 4 is placed and stored in a slide storage section 45 of an incubator 40, and then blood collected from a finger or the like with a collection dropper is used. Is spotted on the multilayer analysis element 21 of the chemical analysis slide 20.
[0012]
Next, the cover 43 is attached in close contact with the cover support section 44, and the slide storage section 45 is sealed. At this time, since the volume of the slide storage section 45 and the volume of the chemical analysis slide 20 substantially match, the air in the slide storage section 45 is almost exhausted.
[0013]
Then, the slide accommodating section 45 is heated to incubate the chemical analysis slide 20 to advance the color reaction. At this time, since the water hardly evaporates from the spotted blood, the color reaction reliably proceeds to the end.
[0014]
Further, the cover 43 is opened, and in this state, the chemical analysis slide 20 is heated to remove the moisture contained in the multi-layered analysis element 21 and to dry, thereby stopping and fixing the color reaction.
[0015]
Next, the dried chemical analysis slide 20 is sealed in a bag made of plastic or the like together with a desiccant such as silica gel, and sent to a hospital or the like. Hospitals analyze chemical analysis slides with automated analyzers.
[0016]
[Problems to be solved by the invention]
The incubator described above was able to perform analysis with considerable accuracy by preventing evaporation of water during incubation.However, there was a problem with operability such as insertion and removal of chemical analysis slides, which caused variations in incubation time and operator However, there is a problem in that the surface of the multi-layered analytical element is touched by hand, and the analytical accuracy and hygiene are both problems.
[0017]
An object of the present invention is to provide a chemical analysis slide which has a simple structure, is inexpensive, is easy to operate, can secure a constant incubation condition, and can be securely put in a storage case without touching the surface of a multilayer analysis element. To provide an incubator for
[0018]
[Means for Solving the Problems]
The present inventors have conducted intensive studies to solve the above-described problems, and as a result, a recess for placing a chemical analysis slide to which a liquid sample has been supplied, an incubation chamber connected to the back of the recess, and a front of the chemical analysis slide. A pushing member for pushing the rim and pushing it into the incubation chamber, an evaporation prevention lid installed at the top of the incubation chamber to prevent the evaporation of the liquid sample supplied to the chemical analysis slide, and being connected to the incubation chamber at right angles to the recess. The temperature of the incubation chamber, the pressing member that pushes the side edge of the chemical analysis slide from the incubation chamber into the chemical analysis slide storage case, presses the side edge of the slide, and heats the incubation chamber. A temperature controller for controlling the temperature, wherein the evaporation-preventing lid is provided with a lid for closing the incubation chamber. A chemical analysis slide incubator having a lid for closing a window hole of a chemical analysis slide where an analysis element is exposed is provided, and the two lids are vertically movably connected to each other, thereby achieving the above object. The inventors have found and completed the present invention.
[0019]
Chemical analysis slides consist of a multi-layer analysis element and a slide frame supporting it.
[0020]
The multilayer analytical element has at least one liquid-permeable porous layer and a water-impermeable support. The porous layer may contain all or some of the reagents that react with the component to be detected. A different portion of the reagent may be included at different depths of one porous layer. Further, another non-porous liquid-permeable layer may contain a part or all of the reagent. It may have two or more porous or nonporous liquid permeable layers.
[0021]
The water-impermeable support is preferably a light-transmissive or transparent plastic.
[0022]
The multi-layer analytical element is provided on a transparent, water-impermeable support, such as described in U.S. Pat. Nos. 3,992,158 and 4,292,272, on a liquid permeable containing at least a portion of a reagent. It is preferable that the element is an integrated multilayer analysis element in which a layer and a porous layer are sequentially provided.
[0023]
The integrated multilayer analytical element is also disclosed in U.S. Patents 3,983,005, 4,042,335, 4,066,403, 4,144,306, 4,132,528, 4,258,001, It may have a configuration as described in JP-A-4,357,363, JP-A-4,381,421 and the like.
[0024]
It may have a plurality of porous layers as described in JP-A-61-4959, JP-A-62-138756, JP-A-62-138575, and JP-A-62-138758.
[0025]
The multi-layered analysis element may be circular or square, and may have any shape as long as the analysis is not hindered.
[0026]
The slide frame supports the multi-layered analysis element at the peripheral portion to facilitate the analysis operation, and has a shape that satisfies the conditions required by a measuring instrument or the like. It is usually a rectangle close to a square. The material is arbitrary, such as plastic, paper, and metal, but preferred are water-permeable plastics, such as polystyrene, polypropylene, polyethylene, and polyvinyl chloride.
[0027]
The recess where the chemical analysis slide is placed and the incubation chamber may be flush, or the incubation chamber may be formed one step lower with a step.
[0028]
The pushing member for pushing the chemical analysis slide from the recess into the incubation chamber and the pushing member for pushing the chemical analysis slide from the incubation chamber into the storage case each comprise a pushing rod. The shape of the pushing rod is not limited, and a handle, a handle, or the like may be attached to a plate, a rod, or the like as necessary.
[0029]
The evaporation prevention lid has the function of closing the incubation chamber to eliminate the influence of external air temperature inside the chamber and the function of closing the liquid sample supply side of the multilayer analysis element of the chemical analysis slide to prevent evaporation of water during incubation. Things. For this reason, the evaporation-preventing lid has a lid that closes the incubation chamber and a lid that closes the window hole of the slide frame where the multi-layered analysis element is exposed, and is used so that the lids are vertically movable. The material is preferably a material that does not adsorb a gas that may be generated by incubation, for example, aluminum, brass, stainless steel, inexpensive and easy-to-process metal such as iron, a material whose surface is coated with plastic, or Examples include, but are not limited to, plastic plates.
[0030]
The case for storing the chemical analysis slide may be any as long as it can store and seal the chemical analysis slide, but usually a flat box shape may be used. About 1 to 5 chemical analysis slides are accommodated. The case body is preferably made of transparent plastic. The sample to be attached to the case body and sealed is preferably one having some elasticity. It is preferable to put a desiccant in the case. The desiccant may be placed in the case main body by putting it in a breathable bag or the like, or the sample may be made hollow and put therein. Known drying agents such as silica gel, zeolite and calcium chloride can be used as the drying agent.
[0031]
The installation part of the chemical analysis slide storage case needs to be able to hold this storage case. If the floor of the installation section is horizontal, it is sufficient if there is an area that can simply hold the storage case. On the other hand, the rear part of the storage case is set so as to protrude from the incubator body so that the storage case can be easily attached and detached by hand. It is also preferable to make the floor surface an outwardly inclined surface to facilitate storage of the chemical analysis slide. In this case, if necessary, measures such as sticking rubber on the floor surface, side surfaces, and the like can be taken to prevent the storage case from slipping when the storage case is mounted.
[0032]
The incubator can be provided with a timer in addition to a heating member such as a heater and a temperature controller such as a thermostat.
[0033]
The supply amount of the liquid sample is usually about 2 to 30 μl, particularly about 5 to 10 μl, and the incubation is performed at 10 to 60 ° C., preferably 20 to 40 ° C. for 1 to 15 minutes, preferably about 2 to 6 minutes. It is necessary that the fluctuation range of the temperature is controlled with an accuracy of ± 5 ° C., preferably about ± 2 ° C. around the set value.
[0034]
[Action]
The chemical analysis slide to which the liquid sample has been supplied is pushed from the recess into the incubation chamber by the pushing member. Then, after incubation is performed at a constant temperature for a predetermined time, it is pushed out of the incubation chamber by the next push-in member, and is housed in a chemical analysis slide housing case main body that has been installed in an installation section in advance. Therefore, the operator holds the lower part of the case body, pulls it out, attaches the specimen, seals the specimen, and sends the specimen to an inspection organization or the like. Therefore, the operator does not touch the chemical analysis slide after setting in the recess.
[0035]
【Example】
FIG. 1 shows an incubator according to an embodiment of the present invention, and FIG. 2 shows a use state thereof.
[0036]
FIG. 1 is a perspective view showing a state in which an upper plate (not shown) of an incubator has been removed. And an incubation chamber 3 is connected to the storage section. The width and depth of the recess 2 are slightly larger than the overall length and thickness of the chemical analysis slide, respectively. The width and depth of the incubation chamber 3 correspond to the recess. The bottom surface of the recess 2 and the bottom surface of the incubation chamber 3 are flush with each other, and the overall planar shape of the two is a rectangle whose overall length is longer than twice the overall width of the chemical analysis slide. At the approximate center of the front edge of the recess 2 of the incubator body 1 and the approximate center of the left edge of the incubation chamber 3, shallow angular grooves 4 and 5 communicating with the outside are formed. The plates 6 and 7 are slidably loosely fitted. The outer edges of the slide plates 6 and 7 are bent upward to facilitate the push-pull operation. The evaporation prevention lid 8 is made of stainless steel, and comprises a rectangular plate 9 slightly larger than the incubation chamber 2 and a closing piece 10. As can be understood from FIGS. 1 and 3, the closing piece 10 is composed of a disk portion and a shaft portion projecting upward from the upper surface thereof, and the outer periphery of the bottom surface of the disk portion is cut into a shallow and wide shape to form a tapered surface. The bottom is coated with Teflon. A circular hole is provided at the center of the plate 9, and the shaft of the closing piece penetrates the circular hole with play and protrudes upward. A circumferential groove is provided in the upper part of the shaft portion, and the stop ring 11 is fitted therein. On the right side of the incubation chamber 3, a square groove-shaped recess that is slightly larger and deeper than the incubation chamber 3 is formed so as to communicate with the outside, and this recess serves as the installation portion 12 of the chemical analysis slide storage case. The upper plate of the incubator (not shown) has a rectangular shape corresponding to the size of the incubator main body 1, and has a window hole formed by combining two rectangles at the center. The position and size of the rectangle at the front of this window hole coincide with the recess 2. On the other hand, the position of the rear rectangle coincides with the incubation chamber 3, but its size substantially coincides with the plate 9 of the evaporation prevention lid 8, and is therefore slightly larger than the incubation chamber 3. As a result, a step is formed between the upper plate and the incubator main body 1, and the evaporation preventing lid 8 is fitted and positioned at the rear of the window hole and is supported by the step. A heater 13 for heating the incubation chamber 3 and a thermostat 14 for keeping the temperature of the incubation chamber 3 constant are mounted in the incubator body 1.
[0037]
As shown in FIG. 4, the chemical analysis slide 20 includes a disk-shaped multilayer analysis element 21 and a slide frame 22 supporting the same. The multilayer analytical element 21 has a reagent layer, a reflective layer, and a spreading layer laminated in this order on a support that is a transparent film. The slide frame 22 has a substantially rectangular shape as a whole, and a circular hole 23 slightly smaller than the multilayer analysis element 21 is provided at the center. On the upper side of the multi-layer analysis element is located a developing layer on which the liquid sample is spotted, while on the lower side a transparent support is located so that the color developed on the reagent layer can be measured from below. It has become.
[0038]
As shown in FIG. 5, the chemical analysis slide storage case 30 includes a flat box-shaped case main body 31 and a specimen 32 that seals the case main body. It contains a desiccant 33 along with the chemical analysis slide 20. Zeolite was used as a desiccant.
[0039]
How to use this incubator will be described with reference to FIG. First, the power is turned on, the incubation chamber 3 is heated to a constant temperature, and the evaporation prevention cover 8 is attached to close the incubation chamber 3. The chemical analysis slide storage case main body 31 is inserted into the installation portion 12 in advance. The chemical analysis slide 20 on which the liquid sample has been spotted and which has been developed and infiltrated in the multi-layer analysis element is put into the recess 2 through the opening at the front of the window hole of the upper plate, and the slide plate 6 is used to put it into the incubation chamber. Press into 3. Then, the rear edge of the chemical analysis slide 20, which becomes the front end in the advancing direction, contacts the tapered surface of the top 10 of the evaporation preventing lid 8 and further advances while pushing up the same, and this rear edge abuts the rear surface of the incubation chamber 3. And stop. The top 10 is located above the circular hole 23 of the chemical analysis slide and descends by its own weight, and the tapered surface comes into contact with the peripheral portion of the circular hole 23 to close it. Then, the operator measures the time with a clock or the like and performs incubation for a certain period of time, and then pushes the slide plate 7 to take out the chemical analysis slide 20 from the incubation chamber 3 and put it in the case main body 31. The case main body 31 is pulled out from the installation section 12, a desiccant 33 is put therein, a sample 32 is attached, and the case is sealed. In this state, it is mailed to a hospital or a laboratory.
[0040]
Measurement example 1
1) Preparation of Sample 20 ml of venous blood of a healthy person was collected with a vacuum blood collection tube (manufactured by Terumo) containing a predetermined amount of a glycolytic inhibitor (NaF).
[0041]
A part of this blood was collected and the test no. It was set to 1. In addition, aliquots of 5 ml each were taken into two sample tubes, and 35 μl and 70 μl of a 15% glucose aqueous solution were added thereto to obtain a whole blood sample No. having a different sugar concentration. 2 and No. 3 was prepared.
[0042]
2) Measurement of blood glucose level in plasma Plasma was obtained by centrifuging 0.5 ml of 1, 2, and 3. Using this plasma as a sample, the blood glucose level was measured using a Hitachi 7150 automatic analyzer. 1:87 mg / dl; 2: 184 mg / dl, no. 3: 268 mg / dl.
[0043]
3) Spotting, incubation, dehydration and drying of the sample Fuji Drychem GLU-W slide was set in the incubator of the embodiment of the present invention. 1 μl of whole blood was spotted, immediately moved to a heating stage, and placed at 37 ° C. for 6 minutes at 37 ° C. in a chemical analysis slide storage case made of plastic together with a 2 g plate-shaped (30 mm × 55 mm × 2 mm) zeolite. The slides were mounted and left at room temperature to dehydrate and dry the slides. Similar operation No. Each of 1, 2, and 3 was repeated three times.
[0044]
4) Preparation of Calibration Curve After approximately one hour, the slide was taken out of the chemical analysis slide storage case, and the reflection optical density at a wavelength of 505 nm was measured with a Fuji Dry Chem Analyzer 5500 measuring instrument. Each No. Measurement results were averaged for three slides on which each sample was spotted, and the following values were obtained. No. 1: 0.3941, no. 2: 0.4628, no. 3: 0.5395. The reflection optical density thus obtained and the blood glucose level measured by the automatic analyzer measured earlier were plotted on a graph, and a correlation regression equation (calibration curve) between the optical density and the blood glucose level was set.
[0045]
Measurement example 2
A venous blood sample was collected from another healthy subject in the same manner as in Measurement Example 1-1), and an aqueous glucose solution was added to adjust the blood glucose level. 4, 5, and 6 were obtained.
[0046]
The treatment was performed according to the procedures of Measurement Examples 1-3) and 4), and the reflection optical density of the dehydrated and dried slide was measured. The blood sugar level was calculated from this value and the calibration curve to be 83 mg / dl, 198 mg / dl, and 249 mg / dl. On the other hand, for the same sample, sample No. Plasma was separated for 4, 5, and 6 and measured with a Hitachi 7150 automatic analyzer. The results were 85 mg / dl, 198 mg / dl, and 254 mg / dl.
[0047]
Since the measured values obtained by the two methods were almost the same, it was confirmed that the blood glucose level of whole blood could be correctly measured by using the incubator of the present invention.
[0048]
Measurement example 3
Simultaneous reproducibility When the simultaneous reproducibility was examined by repeating measurement 10 times for each of the samples 4, 5, and 6, the following results were obtained.
[0049]
[Table 1]

[0050]
It was confirmed that blood glucose can be measured with good accuracy by using the incubator of the present invention.
[0051]
Measurement example 4
The sample no. After the same treatment as in Measurement Example 6 was performed for 7, 8, and 9, the sample was left at room temperature for a long time in a state of being enclosed in a chemical analysis slide storage case, and then the reflection optical density was measured to determine the blood glucose level. However, the following results were obtained.
[0052]
[Table 2]

[0053]
It was confirmed that if the sample was treated in the incubator of the present invention and then dehydrated and dried, the measured value hardly changed even after being left at room temperature for a long time.
[0054]
Measurement example 5
The incubator of the present invention was installed in an air thermostat set under the following temperature conditions, and the same test as in Measurement Example 2 was performed to obtain the following results.
[0055]
Environmental temperature [Table 3]

[0056]
It has been confirmed that the use of the incubator of the present invention can provide a substantially constant measurement value even in summer (high temperature) and winter (low temperature) environmental conditions.
[0057]
【The invention's effect】
With the incubator of the present invention, an operator such as a home patient spots a liquid sample such as blood on a chemical analysis slide, incubates it without any touch after setting it in a recess of the incubator, and stores it in a closed container. Can be sent to inspection organizations. The incubator of the present invention has a simple structure, can be manufactured at low cost, and is easy to operate, so that it can be easily spread to home care and the like.
[Brief description of the drawings]
FIG. 1 is a perspective view showing a state where an upper plate of an incubator according to an embodiment of the present invention is removed.
FIG. 2 is a perspective view showing a use state of the incubator.
FIG. 3 is a side view of an evaporation preventing lid of the incubator.
FIG. 4 is a perspective view of an example of a chemical analysis slide cut at the center.
FIG. 5 is a perspective view of an example of a chemical analysis slide storage case.
FIG. 6 is a perspective view of an example of a conventional incubator.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 1 Incubator main body 2 Recess 3 Incubation chamber 4 Square groove 5 Square groove 6 Slide plate 7 Slide plate 8 Evaporation prevention lid 9 Plate 10 Closing piece 11 Stop ring 12 Installation part 13 Heater 14 Thermostat 20 Chemical analysis slide 21 Multi-layer analysis element 22 Slide Frame 23 Round hole 30 Case for storing chemical analysis slide 31 Case body 32 Sample 33 Desiccant

Claims (1)

A recess for placing a chemical analysis slide to which a liquid sample has been supplied, an incubation chamber connected to the back of the recess, a pushing member for pushing a front edge of the chemical analysis slide and pushing it into the incubation chamber, and an upper part of the incubation chamber An evaporation-preventing lid that prevents the liquid sample supplied to the chemical analysis slide from evaporating, a chemical analysis slide storage case installed in the incubation chamber at right angles to the recess, A push member for pushing the side edge of the analysis slide into the chemical analysis slide storage case, a heating member for heating the incubation chamber, and a temperature controller for adjusting the temperature of the incubation chamber, wherein the evaporation prevention lid covers the incubation chamber. Close the window on the chemical analysis slide with the lid and the multilayer analysis element exposed. Has a lid for sealing, incubator for chemical analysis slides between hunting case is connected vertically movably

Images