TWI699535B - Method for manufacturating test strips - Google Patents

Abstract

The invention discloses a method for manufacturing test strips. The method comprises the step of: providing a sheet-like object which is composed of a plurality of test strips which are connected to each other. Afterward, a predetermined depth from an interface between a slit and an upper layer to an upper surface of a reagent is provided. Then, a practical depth from the interface between the slit and the upper layer to the upper surface of the reagent is provided. According to the practical depth and the predetermined depth of each test trip, a calculation proceeds to obtain a compensation factor for the test strip. Then, a corresponding category mark is labeled on each test strip according to the compensation factor of each test strip. Finally, the sheet-like object is divided so as to cut the test strips which are connected to each other into independent units..

Description

Manufacturing method of test strip

The present invention relates to a manufacturing method of a test strip, in detail, it relates to a manufacturing method of measuring the actual optical path length and marking the classification mark on the test strip.

Diabetes is a clinical syndrome caused by factors such as absolute or relative shortage of insulin in the body, abnormal secretion time, and disorder or resistance of insulin acting body. If diabetes is not well controlled, it will cause some acute complications, such as hypoglycemia, ketoacidosis, and non-ketone hyperosmolar coma. Serious long-term complications include cardiovascular disease, chronic renal failure, retinopathy, neuropathy, and microvascular disease.

For diabetics, it is very important to monitor blood sugar from time to time. The primary goal of managing diabetes is to maintain a normal blood sugar level. If the patient can pay attention to blood sugar control, it will effectively prevent the above complications. At present, most of the blood glucose meters used at home on the market are whole-blood blood glucose tests. For example, after a blood collection needle and a test strip are used to obtain the patient's blood, the blood glucose concentration is determined by electrochemical or photochemical methods.

US Patent No. US6,858,401 discloses a test strip for detecting blood sugar, as shown in FIG. 1a as a three-dimensional view of the test strip 10. A reagent pad 11 with a hydrophilic group is fixed on a surface of a plastic carrier 12 by an adhesive 13, and the plastic carrier 12 has a hole 14 in the part where it adheres to the reagent pad 11. The blood sample is dripped from the hole 14 into the micro-hole in the reagent pad 11 to reach a test surface 15. Because there is a reagent in the reagent pad 11, a chemical reaction can occur with glucose in the blood. As shown in FIG. 1b, in the reflective optical detection method, a light emitting diode 16 projects light on the test surface 15, and a light detector 17 receives the diffusely reflected light. According to the change in reflectance or reflectance observed on the test surface 15, the glucose value in the blood can be obtained. Because the thickness and surface roughness of the adhesive 13 will vary, the diffusely reflected light received by the photodetector 17 will also vary accordingly. That is, the detected glucose value will lose accuracy due to the quality variation of the adhesive 13. In addition, the transmissive optical inspection method also has the same problems as described above, and it is impossible to control the thickness and surface roughness of the adhesive 13 to be uniform during the manufacturing process of the test strip. Therefore, it is difficult to commercialize the test strip 10 and mass-produce it.

To ensure the accuracy of blood glucose measurement, the present invention proposes a manufacturing method for measuring the actual optical path length by energy and marking the classification mark on the test strip.

This application provides a manufacturing method of a test strip, which is a manufacturing method of measuring the actual optical path length and marking the classification mark on the test strip.

Therefore, this application provides a method for manufacturing test strips. The method includes: providing a sheet, the sheet consisting of a plurality of connected test strips, wherein each test strip includes a bottom layer, a middle layer, a blood storage layer, and a top layer stacked in sequence, and A reagent, the blood storage layer includes a slit and a blood storage area connected to the slit, the reagent is disposed on the surface of the intermediate layer and exposed in the slit; providing the slit and the slit in the test strip A predetermined depth from the junction of the top layer to the upper surface of the reagent; measure the actual depth from the junction of the slit and the top layer in each test strip to the upper surface of the reagent; according to the actual depth of each test strip The depth and the predetermined depth are calculated to obtain a compensation coefficient of each test strip respectively; according to the compensation coefficient of each test strip, a corresponding classification mark of each test strip is marked; and the sheet is divided to cut The connected multiple test strips are independent units.

In another embodiment, the actual depth is measured by an optical measuring instrument, wherein the optical measuring instrument is preferably a film thickness meter. The conventional film thickness meter is an optical measurement of film thickness, and non-contact measurement of films from nanometer to micrometer.

In another embodiment, the classification mark is marked on the upper surface of the top layer or the lower surface of the bottom layer of the test strip by a laser or an inkjet printer, wherein the classification mark is in different grays. Gradation patterns or dot marks distinguish various categories.

In another embodiment, the compensation coefficient is the product of the difference between the predetermined depth and the actual depth times the reciprocal of the predetermined depth.

In another embodiment, the classification mark is used to compensate for the error of a colorimetric analysis caused by the actual depth variation. The colorimetric analysis is based on a formula of Lambert-Beer law to calculate the concentration of the blood and the reaction product of the reagent.

In another embodiment, the actual depth variation causes a change in the optical path length of the formula, and the classification mark is used to compensate for errors in the calculated value of the product concentration caused by the change in the optical path length.

10: Test strip

11: Reagent pad

12: Plastic carrier

13: Adhesive

14: hole

15: Test surface

16: LED

17: Light detector

20: Test strip

21: bottom layer

22: middle layer

23: blood reservoir

24: top floor

25: Classification mark

26: Reagent

40: Flakes

51: Optical measuring instrument

52: Laser machine

212, 222, 242: through hole

211: Opening

231: slit

232: Blood Storage Area

61, 62, 63, 64, 65, 66: steps

D’: Actual depth

a, b, c, d, e: patterns

f, g, h, i, j, k: patterns

Figure 1a is a three-dimensional schematic diagram of a conventional test strip.

Figure 1b shows a schematic diagram of a conventional reflective optical inspection.

Fig. 2 is a three-dimensional exploded schematic diagram of the test strip of this application.

Fig. 3 is a three-dimensional schematic diagram of the test strip of this application.

Fig. 4 is a schematic diagram showing a plurality of connected test strips in the manufacturing process of this application.

FIG. 5 is a schematic diagram showing the actual depth measurement and classification marks of this application in the manufacturing process.

Figure 6 is a flow chart showing the manufacture of test strips in this application.

Hereinafter, various embodiments for implementing the present invention will be described. Please refer to the attached drawing and refer to its corresponding description. In addition, in this specification and drawings, substantially the same or the same configuration will be given the same reference numeral, and the repeated description will be omitted.

Fig. 2 is a three-dimensional exploded schematic diagram of the test strip of this application. A test strip 20 includes a bottom layer 21, a middle layer 22, a blood storage layer 23, and a top layer 24. The top layer 24 is a transparent film layer formed by an adhesive material. The upper surface of the top layer 24 is marked with a classification mark 25 to distinguish the characteristics and classification of the test strip 20. In this embodiment, the classification mark 25 is used to distinguish between the actual depth from the boundary between the slit 231 of the blood storage layer 23 and the top layer 24 to the upper surface of a reagent 26 (described in detail later and in Figure 4). The classification, but not limited to being marked on the upper surface of the top layer 24, can also be marked on the lower surface of the bottom layer 21, so that the penetrating optical blood glucose detection device or penetrating optical blood glucose meter can be identified for blood glucose Numerical compensation. In this embodiment, the classification mark 25 may be a mark or mark generated by a laser machine or an inkjet printer. In this embodiment, the classification mark 25 is marked by a laser machine with patterns a, b, c, d, e, f, g, h, i, j, k with different gray scales (for example, gray scales 1-11) Or dot mark or mark (as detailed in the following and table).

The bottom layer 21 of the test strip 20 can be made of opaque plastic material, such as a black polyethylene terephthalate (PET) film layer, which includes openings 211 and through holes 212. The intermediate layer 22 is a transparent film layer with light-transmitting properties, and includes a through hole 222 aligned with the through hole 212. The predetermined thickness of the blood storage layer 23 is preferably 54 μm. The blood storage layer 23 has a slit 231 extending from the outside to the inside, and the blood sampled from the finger of the subject can be introduced into a blood storage area 232 through the slit 231. The top layer 24 can be a transparent plastic material with light-transmitting properties, such as a transparent polyethylene terephthalate film layer, which includes through holes 242. especially It is noted that a reagent 26 is attached to the intermediate layer 22 and the reagent 26 is close to the surface of the blood storage layer 23. The reagent 26 is exposed in the slit 231, and is aligned with the center line of the opening 211 of the bottom layer 21, so that light can pass through the transparent top layer 24 and the intermediate layer 22 and pass through the reagent 26 to pass through the opening 211 Out. In this embodiment, the bottom layer 21, the middle layer 22, and the top layer 24 may be film layers of the same thickness, and the thickness of the blood storage layer 23 is smaller than that of the other layers. In addition, the bottom layer 21 is a plastic film layer formed by a single-sided adhesive material, and the blood storage layer 23 is a double-sided adhesive film layer formed by an adhesive material. However, precisely because the adhesive material of the blood storage layer 23 or the reagent 26 on the intermediate layer 22 is coated unevenly or contracted, it is difficult to control the uniformity of the optical path length (that is, the predetermined depth described later) in the slit 231. Therefore, the classification mark 25 needs to be used to distinguish different classification compensations formed by the actual depth variation (ie, the difference between the actual depth and the predetermined depth) from the boundary between the slit 231 and the top layer 24 to the upper surface of a reagent 26.

In addition, the center lines of the through holes 212, 222, and 242 of the other group are also aligned with each other, and their center lines pass through the blood storage area 232, that is, communicate with each other. Similarly, the red blood cells in the blood are obtained by optical measurement. The percentage of the volume occupied (ie, hemolysis ratio, HCT) can better understand the blood glucose measurement value. Because the blood glucose measurement value is often affected by the hemolysis ratio, the measured hemolysis ratio can be used to correct the blood glucose measurement value. The measurement of the blood cell volume ratio is not the focus of the present invention, so it will not be repeated.

Diabetes patients can use a blood sampling needle (not shown) to take a blood sample from a finger, and the blood will be introduced into the internal blood storage area 232 through the slit 231, and react with the reagent 26, and the concentration of the reaction product and the blood glucose value will become Proportional or a proportional relationship, and change the color of blood, the blood glucose level can be obtained by a colorimetric analysis. It is specifically stated here that the result of colorimetric analysis is directly proportional to the blood glucose value.

Colorimetry (colorimetry) is a very commonly used method in biochemical testing. It uses the Beer-Lambert Law as the basis for calculating the concentration of reaction products. Its formula is expressed as: A=αLC (Formula 1 ) Where A is the absorbance of light; α is the optical path length or the thickness of the absorption layer; L is the optical path length; C is the concentration of the light-absorbing substance.

FIG. 4 is a schematic diagram showing a plurality of test strips connected in the manufacturing process of this application. In the production process of mass-produced test strips, a large area of the bottom layer 21, the middle layer 22, the blood storage layer 23, and the top layer 24 are sequentially stacked or coated to form a plurality of test strips 20 with subsequent cutting processes. The sheet 40. After the stacking of the sheets 40 is completed, the actual depth from the boundary between the slit 231 and the top layer 24 in each test strip 20 to the upper surface of a reagent 26 is measured, and then a compensation coefficient is calculated according to the predetermined depth , And then mark each test strip 20 with a corresponding classification mark 25 in sequence according to the compensation coefficient. In this embodiment, the compensation coefficient calculation formula is the difference between the predetermined depth and the actual depth multiplied by the reciprocal of the predetermined depth.

A cross-section with the slit 231 and the reagent 26 is taken along the A-A section line in FIG. 4 to draw FIG. 5, and FIG. 5 is a schematic diagram showing the actual depth measurement and classification marks in the manufacturing process of the embodiment of the present invention. In this embodiment, an optical measuring instrument 51, such as a film thickness meter, is used to quickly measure the boundary between the slit 231 and the top layer 23 in each test strip 20 and the upper surface of the reagent 26 in an S-shaped back and forth measurement. Actual depth D'. The optical measuring instrument 51 can emit light of a specific wavelength, and then analyze the actual depth D'based on the light reflected by the reagent 26 and/or the junction of the slit 231 and the top layer 23. This embodiment only exemplifies that the optical measuring instrument for measuring the actual depth D'is a film thickness meter, but the invention is not limited to this. Substituting the actual depth D'in each test strip 20 into the aforementioned compensation coefficient calculation formula, so that a corresponding compensation coefficient for each test strip 20 can be obtained. Use the compensation coefficient and the classification mark to have a corresponding relationship or correspondence table (as detailed in the table below), and then use a laser machine 52 or an inkjet printer to generate the mark of the classification mark 25 or mark it on the top layer 24 The upper surface or the lower surface of the bottom layer 21.

Theoretically, the thickness of the blood storage area 232 minus the thickness of the reagent 26 is the optical path length of the aforementioned formula 1. If the design of the test strip 20, the predetermined thickness of the blood storage area 232 is 54 μm, and The predetermined thickness of the reagent 26 is 4μm. In order to make the colorimetric analysis result acceptable or allowable error range, it needs to be controlled so that the optical path length (that is, the predetermined depth in the slit 231) is equal to 50μm (ideal design value), Otherwise, a concentration value exceeding the allowable error will be obtained. However, in the actual manufacturing process, the blood storage layer 23 is connected with the top layer 24 and the middle layer 22 by an adhesive material, which is difficult to control due to the uneven coating of the reagent 26 on the test strip manufacturing process or the shrinkage/squeezing of the upper and lower layers The actual depth D′ in the slit 231 is uniform and equal to a predetermined depth (D, not shown in the figure), which affects the optical path length L in the aforementioned formula 1 is very large.

However, the embodiment of the present invention only illustrates that the optical path length L is controlled to a fixed predetermined depth, that is, 50 μm. In this embodiment, the predetermined depth may preferably be between 40 μm and 50 μm. The aforementioned classification mark 25 can distinguish the different classifications formed by the actual depth variation in the slit 231 of the blood storage layer 23, so that the error caused by the variation of the optical path length in formula 1 can be compensated, and the measurement can be directly compensated. The blood glucose value obtained. For example: the actual depth D'obtained by the measurement is 54μm, the value obtained in formula 1 needs to be compensated by about (50-54)×2%, which is minus 8%, that is, 0.92 times the blood glucose value obtained after the measurement is the final The displayed blood glucose value. On the contrary, if the actual thickness D is 47μm, the value obtained in formula 1 needs to be compensated by about (50-47)×2%, that is, because the actual depth (actual optical path length) is less than the predetermined depth, the measured value The blood glucose value is compensated by positive 6%, that is, 1.06 times the blood glucose value obtained after the measurement is the last displayed blood glucose value.

Figure 6 is a flow chart showing the manufacture of test strips in this application. In step 61, a sheet is provided, and the sheet is composed of a plurality of connected test strips, that is, the sheet 40 shown in FIG. 4. Then, a predetermined depth from the boundary between the slit and the top layer in the test strip to the upper surface of the reagent is provided, as shown in step 62. Then step 63 is performed to measure the actual depth from the boundary between the slit and the top layer in each test strip to the upper surface of the reagent. Then, calculation is performed according to the actual depth and the predetermined depth of each test strip to obtain a compensation coefficient of each test strip, as shown in step 64. Step 65 is then executed to mark a classification mark corresponding to each test strip according to the compensation coefficient of each test strip. Finally, the sheet 40 is divided and connected by cutting The plurality of detection strips are each independent unit, that is, the sheet 40 is divided into a plurality of independent detection strips 20 (as shown in FIG. 3), as shown in step 66. In other embodiments, steps 64 and 65 can be omitted/replaced. After step 63, the compensation coefficient of each test strip corresponding to the compensation coefficient table shown in Table 1 is obtained by the actual depth of each test strip Coefficient, and then implement the marking pattern. For example, if the actual depth of a test strip of the sheet 40 is 54 μm, the compensation coefficient table shows that the compensation coefficient is minus 8%, and the pattern b can be marked on the test strip.

The technical content and technical features of the present invention have been disclosed above, but those familiar with the technology may still make various substitutions and modifications based on the teaching and disclosure of the present invention without departing from the spirit of the present invention. Therefore, the protection scope of the present invention should not be limited to those disclosed in the embodiments, but should include various substitutions and modifications that do not deviate from the present invention, and are covered by the following patent applications.

61‧‧‧Step

62‧‧‧Step

63‧‧‧Step

64‧‧‧Step

65‧‧‧Step

66‧‧‧Step

Claims (10)

A method for manufacturing a test strip, comprising: providing a sheet, the sheet consisting of a plurality of connected test strips, wherein each test strip includes a bottom layer, a middle layer, and a blood storage layer stacked in sequence Layer, a top layer, and a reagent. The blood storage layer includes a slit and a blood storage area connected to the slit. The reagent is disposed on the surface of the middle layer and exposed in the slit; and the test strip is provided A predetermined depth from the boundary between the slit and the top layer to the upper surface of the reagent; measure the actual depth from the boundary between the slit and the top layer in each test strip to the upper surface of the reagent; The actual depth and the predetermined depth of the test strip are calculated to obtain a compensation coefficient of each test strip; based on the compensation coefficient of each test strip, a corresponding classification mark of each test strip is marked; and the slice is divided For objects, the plurality of test strips connected by cutting are independent units. The method for manufacturing a test strip according to claim 1, wherein the actual depth is measured by an optical measuring instrument. The method for manufacturing a test strip according to claim 2, wherein the optical measuring instrument is a film thickness meter. The method for manufacturing a test strip according to claim 1, wherein the classification mark is marked on the upper surface of the top layer of the test strip by a laser or an inkjet printer. The method of manufacturing a test strip according to claim 1, wherein the classification mark is marked on the bottom surface of the test strip by a laser or an inkjet printer. The method for manufacturing a test strip according to claim 1, wherein the classification mark distinguishes various classifications with patterns or dot marks of different gray levels. The method for manufacturing a test strip according to claim 1, wherein the compensation coefficient is the product of the difference between the predetermined depth and the actual depth times the reciprocal of the predetermined depth. The method for manufacturing a test strip according to claim 1, wherein the classification mark is used to compensate for the error of a colorimetric analysis caused by the difference between the actual depth and the predetermined depth. The method for manufacturing a test strip according to claim 8, wherein the colorimetric analysis is based on a formula of Lambert-Beer law to calculate the concentration of the product reacted by the blood and the reagent. The method for manufacturing a test strip according to claim 9, wherein the difference between the actual depth and the predetermined depth causes the optical path length of the formula to change, and the classification mark is used to compensate for the change in the optical path length. The error caused by the calculated value of the concentration of the product.

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