阅读说明：本技术 一种多层膜干化学试剂片的制作方法 (Method for manufacturing multilayer film dry chemical reagent sheet ) 是由 徐詹程 徐艺元 赵亭亭 于 2019-11-12 设计创作，主要内容包括：本发明为一种多层膜干化学试剂片的制作方法,涉及体外诊断试剂生产领域。制作方法为：将待喷涂的透明且具有导电性的材料作为支持层,一面覆盖,置于远离喷枪一侧,以消除静电喷膜的环抱效应；支持层接地,与喷枪相距一定距离放置；试剂层涂料预先调整粘度和电阻值,按指示剂层、试剂层、扩散层的顺序依次喷涂、干燥；待所喷涂料干燥后进行下一层的喷涂作业。喷枪放电时与待涂支持层之间形成近似的匀强电场,喷出的涂料形成带电液滴,液滴之间相互排斥,延电场线运动,最终粘附于支持层。多层膜干化学试剂片静电喷膜工艺所制作的各试剂层分布均匀,试剂涂料利用率最高可达90%,试剂检测准确度高,生产成本低,同时适用于实验室和大规模生产。(The invention discloses a manufacturing method of a multilayer film dry chemical reagent tablet, and relates to the field of in-vitro diagnostic reagent production. The manufacturing method comprises the following steps: covering one side of a transparent and conductive material to be sprayed as a supporting layer, and placing the supporting layer at one side far away from a spray gun to eliminate the surrounding effect of the electrostatic spray film; the support layer is grounded and is arranged at a certain distance from the spray gun; the viscosity and the resistance value of the reagent layer coating are adjusted in advance, and the reagent layer coating, the reagent layer coating and the diffusion layer coating are sequentially sprayed and dried; and after the sprayed paint is dried, carrying out the next layer of spraying operation. When the spray gun discharges, an approximate uniform electric field is formed between the spray gun and the supporting layer to be coated, the sprayed coating forms charged liquid drops, the liquid drops repel each other, and move along electric field lines to be finally adhered to the supporting layer. The reagent layers manufactured by the electrostatic film spraying process of the multilayer film dry chemical reagent sheet are uniformly distributed, the utilization rate of the reagent coating can reach 90 percent at most, the reagent detection accuracy is high, the production cost is low, and the method is suitable for laboratories and large-scale production.)

1. A manufacturing method of a multilayer film dry chemical reagent sheet comprises a supporting layer, an indicator layer, a reagent layer and a diffusion layer, and is characterized in that the preparation process of the indicator layer, the reagent layer and the diffusion layer is an electrostatic film spraying process, and the manufacturing method comprises the following steps: covering one side of the support layer, placing the support layer at one side far away from the spray gun, grounding the support layer, placing the support layer at a certain distance from the spray gun, adjusting the viscosity and the resistance value of the coating of the reagent layer in advance, setting the direct-current voltage, the spraying distance and the spraying pressure, and spraying and drying the support layer, the reagent layer and the diffusion layer in sequence.

2. The support layer according to claim 1, which is made of a transparent conductive material or a transparent material that is electrically conductive after being electrically conductive.

3. The transparent conductive material according to claim 2, comprising ITO, AZO, and FTO films.

4. The transparent conductive material or the transparent material having conductivity according to claim 2, wherein the light transmittance is 80% or more and the thickness is 100 μm to 500 μm.

5. A transparent conductive material or a transparent material with conductivity according to claim 2, characterized by a resistivity < 1M Ω -cm, preferably < 10^-3Ω·cm。

6. The indicator layer, reagent layer and diffusion layer of claim 1 wherein each reagent layer is coated with a paint viscosity of-4 cups 15s to 40s, preferably 18s to 24 s.

7. The indicator layer, reagent layer and diffusion layer of claim 1 wherein each reagent layer has a coating resistivity of 2M Ω -cm to 50M Ω -cm, preferably 20M Ω -cm to 25M Ω -cm.

8. The indicator layer and reagent layer of claim 1, wherein the thickness is from 20 μm to 200 μm.

9. The reagent layer of claim 1, which may be a single layer or a plurality of layers.

10. The diffusion layer of claim 1 having a thickness of 100 μm to 400 μm.

11. The electrostatic film spraying process according to claim 1, wherein the direct current voltage is 6-15 ten thousand volts, preferably 10-13 ten thousand volts; the spraying distance is 15cm-45cm, preferably 20cm-35 cm; the spraying pressure is 0.1MPa to 0.5MPa, and it is preferably 0.2MPa to 0.4 MPa.

Technical Field

The invention relates to the field of in-vitro diagnostic reagent production, in particular to a manufacturing method of a multilayer film dry chemical reagent sheet.

Background

So-called "dry chemistry" is in contrast to traditional "wet chemistry". The method is a mode that liquid in a sample to be detected is used as a medium, and an object to be detected directly reacts with a dry powder reagent solidified on a carrier. Compared with wet biochemical detection, dry biochemical detection is simple and convenient to operate, does not need professional personnel, consumes short time, and is suitable for emergency detection, point-of-care testing (POCT) and home detection. With the progress of enzyme separation and purification technology, the development of photoelectric detection technology and computer application technology, the dry chemical detection technology has great progress, and the detection accuracy is almost comparable to that of wet chemical detection.

The dry chemical reagent tablets can be classified into three categories according to their production modes:

the first type is a dry chemical production mode of multilayer film dry sheets represented by Qiangsheng corporation, reagent materials such as a diffusion layer, a reflection layer, an interference removal layer, a reagent layer and the like are coated on a transparent support layer by utilizing a coating technology of a photosensitive film, and the change of light is detected from one side of the transparent support layer, so that the method has high production cost, complex process and high requirement on equipment;

the second type is a dry chemical reagent sheet represented by kyoto corporation of japan, the reagent layer on the transparent support layer is a reagent carrier made of a certain fiber product, and the reagent sheet is formed by fixing a plurality of reagent layers and transparent support layers which are arranged in sequence, the production method is relatively simple, but bubbles are easily generated in the reagent layer, which affects the detection result;

the third type is a dry chemical product represented by Roche, the reagent is placed on a certain fiber product, and the body fluid to be detected is transversely filtered by the glass fiber and then contacts with the fiber product layer containing the reagent for reaction, and the method is mainly used for qualitative detection.

The multilayer film dry sheet technology is a dry chemical technology with the highest detection accuracy at present, the key points of the technology are the formula of different reagent layers and the preparation of uniform reagent layers, and the formula of the reagent layers is matched with the production process while the detection requirements are met. The production process of the photosensitive film applied by Qiangsheng company is complex, the coating process used by Qiangsheng company needs to strictly control the extrusion speed of the coating and the running speed of the object to be coated, continuous operation is needed, the equipment requirement and the technical requirement have high thresholds, and the popularization of multilayer film dry chemistry is restricted. Through a large number of experiments, the method for manufacturing the multilayer film dry chemical reagent sheet electrostatic spray film is simple and convenient to operate, simple in equipment, even in prepared reagent layer and suitable for laboratories and large-scale production.

The electrostatic spraying technology is applied to the technical process of producing the multilayer film dry chemical reagent tablet, and according to the principle of electrophoresis, a coated object is generally used as an anode and is grounded (the coated object can also be used as a cathode); the reagent coating atomizing mechanism is used as a cathode and is connected with a negative high voltage of a power supply, so that a high-voltage electrostatic field is formed at the two poles. Because corona discharge is generated at the cathode, the sprayed material medium can be negatively charged and further atomized. According to the principle of 'like charges repel and opposite charges' the charged reagent coating medium is acted by electric field force and flows to the positively charged surface of the coated object along the electric line, so that a layer of film which is uniformly distributed and firmly attached can be deposited on the surface of the coated object. The electrostatic spray film has excellent spray uniformity and is suitable for the production of multilayer film dry chemical reagent sheets.

The supporting layer used by the common multilayer film dry chemical reagent sheet is mostly a transparent plastic product or a glass product, the transmittance is more than 80%, and the requirement of a photoelectric detector can be met but the requirement of an electrostatic spray film cannot be met. The electrostatic film spraying process requires that a support layer to be sprayed has certain conductivity, and the photoelectric detection requires that the support layer has high transparency, so that the support layer used in the electrostatic film spraying process of the multilayer film dry chemical reagent sheet is required to be a transparent material with conductivity.

The other reagent layers except the supporting layer are uniformly sprayed on the supporting layer by using an electrostatic film spraying process in sequence according to the overlapping sequence, and the next layer is sprayed after the sprayed reagent coating is dried. The reagent coatings used in different reagent layers need to meet the requirements of electrostatic spray films in addition to the service functions. Therefore, the conductivity of the reagent coating formula is also a key parameter of the electrostatic film spraying technology of the multilayer film dry chemical reagent sheet. The resistance value of the reagent paint is too high, the conductive effect is not obvious, the spraying uniformity is poor, and the reagent paint is wasted; if the resistance value is too low, electrostatic breakdown is easy to occur, danger is easy to occur during construction, and high requirements are made on the insulation property and the fire resistance of equipment.

Some reagent layer paint contains enzyme with biological activity, and the change of the enzyme activity directly affects the accuracy of the final reagent test result. Experiments show that the enzyme activity changes approximately in a parabolic form to the electric field intensity, when the electric field intensity is increased, the enzyme activity is increased, but when the electric field intensity reaches a certain value (most enzymes are about 3000-5000V/cm), the enzyme activity is reduced along with the increase of the electric field intensity. The sensitivity of different enzymes to the electric field intensity is different, and the high-voltage electrostatic field used by the electrostatic spray film is strictly controlled according to the characteristics of different enzymes, so that the adverse effect of high-voltage static on the enzyme activity can be reduced or even eliminated.

The reagent paint to be sprayed is sprayed in an atomized form at the nozzle of the spray gun under the action of spraying pressure, and is further atomized and electrified at the pole needle of the spray gun generating high-voltage direct current under the action of an uneven electric field, and the atomized small droplets move along the electric field lines in the electric field, so that the spraying uniformity is improved. The smaller the droplet, the less the gravitational and air resistance it experiences over short distances, and the droplet can therefore move in the approximate direction of the electric field lines. The spraying pressure is a key factor for determining the size of the liquid drop, and the larger the spraying pressure is, the smaller the liquid drop is, and the smaller the gravity and air resistance is. However, too large a spraying pressure will cause the atomized droplets to have a certain initial velocity, which is generally different from the direction of the electric field lines, so that the droplets cannot move along the electric field lines, and finally the spraying is not uniform. Therefore, the spraying pressure needs to be reasonably controlled to ensure the spraying uniformity.

Disclosure of Invention

The invention provides a manufacturing method of a multilayer film dry chemical reagent sheet, which can be used for preparing the multilayer film dry chemical reagent sheet with uniform reagent layers, reducing the production difficulty of the multilayer film dry chemical reagent sheet, improving the detection accuracy of the multilayer film dry chemical reagent sheet and being beneficial to popularization and use of multilayer film dry chemistry.

The technical scheme of the invention is as follows:

the invention relates to a method for manufacturing a multilayer film dry chemical reagent sheet, the reagent sheet comprises a support layer, an indicator layer, a reagent layer and a diffusion layer, and the method is characterized in that the preparation process of the indicator layer, the reagent layer and the diffusion layer is an electrostatic film spraying process, and the manufacturing method comprises the following steps: covering one side of the support layer, placing the support layer at one side far away from the spray gun, grounding the support layer, placing the support layer at a certain distance from the spray gun, adjusting the viscosity and the resistance value of the coating of the reagent layer in advance, setting the direct-current voltage, the spraying distance and the spraying pressure, and spraying and drying the support layer, the reagent layer and the diffusion layer in sequence.

The supporting layer is made of transparent conductive materials or transparent materials which are conductive after conductive treatment.

The transparent conductive material comprises an Indium Tin Oxide (ITO) film, a zinc oxide aluminum film (AZO) and a fluorine-doped tin oxide Film (FTO).

The transparent conductive material or the transparent material with conductivity has light transmittance of more than 80% and thickness of 100-500 μm.

The transparent conductive material or the transparent material with conductivity has resistivity less than 1M omega cm, preferably less than or equal to 10^-3Ω·cm。

The indicator layer, the reagent layer and the diffusion layer are prepared by spraying corresponding liquid coatings on the support layer in sequence by using an electrostatic film spraying process, and spraying the next layer after drying each layer.

The coating viscosity of the indicator, reagent and diffusion layers is from-4 cups 15s to 40s, which is preferably from 18s to 24 s.

The coating resistivity of the indicator layer, reagent layer and diffusion layer is 2M Ω -cm to 50M Ω -cm, which is preferably 20M Ω -cm to 25M Ω -cm.

The thickness of the indicator layer and the reagent layer is 20-200 μm.

The reagent layer may be one or more layers.

The thickness of the diffusion layer is 100-400 μm.

The direct current voltage used in the electrostatic film spraying process is 6-15 ten thousand volts, preferably 10-13 ten thousand volts; the spraying distance is 15cm-45cm, preferably 20cm-35 cm; the spraying pressure is 0.1MPa to 0.5MPa, and it is preferably 0.2MPa to 0.4 MPa.

The DC voltage, the spraying distance and the spraying pressure are selected according to the characteristics of different enzymes and reagent coatings so as to achieve the optimal spraying effect.

The specific manufacturing method of the multilayer film dry chemical reagent sheet comprises the following steps: covering one surface of a transparent material with conductivity to be sprayed as a supporting layer, and placing the supporting layer at one side far away from a spray gun to eliminate the surrounding effect of the electrostatic spray film and prevent the coating from being sprayed on the surface; the support layer is grounded and is arranged at a certain distance from the spray gun; the viscosity and the resistance value of the reagent layer coating are adjusted in advance, and the reagent layer coating, the reagent layer coating and the diffusion layer coating are sequentially sprayed and dried; and after the sprayed paint is dried, carrying out the next layer of spraying operation. When the spray gun discharges, an approximate uniform electric field is formed between the spray gun and the support layer to be coated, the sprayed coating forms charged small droplets, the droplets repel each other, and the droplets move along electric field lines and finally adhere to the surface of the support layer.

The reagent layers manufactured by the electrostatic film spraying process of the multilayer film dry chemical reagent sheet are uniformly distributed, the utilization rate of the reagent coating can reach 90 percent at most, the reagent detection accuracy is high, the production cost is low, and the method is suitable for laboratories and large-scale production.

Detailed Description

The following examples are intended to enhance an understanding of the present invention and do not represent a whole content of the present invention. The present invention includes, but is not limited to, the following examples.