TWI737135B - Slide sets, machine and method for optical blood coagulation test - Google Patents

Abstract

The invention provides an optical blood coagulation testing specimen pairs including a detecting area, an agent area and a capillary element, wherein the agent area is separated from the detecting area, and the agent area and the detecting area are connected with a guiding path of the capillary element. By controlling the connection between the detecting area and the agent area, a blood sample is ensured to be mixed with an agent thoroughly and rapidly before being detected, thereby enhancing the accuracy of the detection.

Description

Optical coagulation test strips, optical coagulation detector and optical coagulation test Measuring method

The invention relates to a coagulation detection test strip and its application, in particular to an optical coagulation detection test strip group, a suitable optical coagulation detection machine and a coagulation detection method.

Coagulation is the process by which blood changes from liquid to gel to quickly stop bleeding and prevent the wound from contacting the outside world. After the wound is formed, coagulation occurs rapidly, triggering a series of reactions to stimulate the platelet to release prothrombin (prothrombin). Prothrombin is then activated to thrombin. Thrombin converts fibrinogen, which is dissolved in plasma, into fibrin, which is insoluble in water. The above-mentioned fibrin polymerizes into a network structure to kink other cells and platelets in the blood to form a blood clot, thereby turning the blood near the wound into a gel.

However, viral infections, genetic diseases, organ diseases, or drug use may affect blood coagulation and cause wounds to bleed continuously or form thrombus. Coagulation tests can be used to help diagnose diseases, assess the risk of surgery, or monitor the use of anticoagulant drugs. Commonly used blood coagulation tests include prothrombin time (PT), which is the time required for blood to contact a coagulation reagent to activate prothrombin and cause clotting of the blood sample.

The accuracy of the reaction detection depends on the judgment of the start and end time points of the reaction. Taking the PT measurement as an example, the reaction start time is when the blood sample reacts with the reagent, and the end time point is when the blood sample is coagulated. The accuracy of the latter judgment depends on whether the blood sample reacts quickly with the coagulation reagent. Mix thoroughly. However, for transportation and storage, most of the coagulation reagents on the market are in powder form rather than liquid that is easy to mix. Therefore, a method is needed to allow the blood sample and the coagulation reagent to be quickly and fully mixed, and the coagulation test is not unmixed. Interference of homogeneous blood samples or coagulation reagents.

In view of this, it is necessary to provide an optical coagulation test strip set to improve the accuracy of coagulation detection.

Therefore, one aspect of the present invention is to provide an optical coagulation test strip set. By controlling whether the detection area and the reagent area are connected or not, it is ensured that the blood sample flowing into the detection area is fully mixed with the coagulation reagent, thereby significantly improving Accuracy of coagulation test.

Another aspect of the present invention is to provide an optical coagulation detection machine, which is suitable for the above-mentioned optical coagulation detection test strip set.

Another aspect of the present invention is to provide an optical coagulation detection method, which can fully mix blood and coagulation reagents before performing the detection. Experiments have proved that the optical coagulation detection method can make the detection result more accurate.

According to the above aspect of the present invention, there is provided an optical coagulation detection test strip set, which may include a detection area, a reagent area, and a capillary unit, wherein the reagent area is spaced from the detection area, and the reagent area has reagents, and the capillary units can be connected The approach path between the detection zone and the reagent zone. In one embodiment, the above-mentioned approach path includes a suction end and a discharge end opposite to the above-mentioned suction end, wherein the suction end communicates with the reagent area and the outlet end communicates with the detection area. The section of the suction end may be smaller than the other section of the outlet end.

In an embodiment of the present invention, the optical coagulation detection test strip set includes a substrate, a first top sheet separated from the substrate by a first gap, and a second top sheet separated from the substrate by a second gap, wherein the substrate The material and the first top sheet cooperate to define the detection zone, the substrate and the second top sheet define the reagent zone, and the first gap is smaller than the second gap.

According to the above embodiment, the difference between the second gap and the first gap is not less than 50 microns.

In another embodiment of the present invention, the above-mentioned second gap is not greater than 1 mm.

According to the above-mentioned embodiment, the above-mentioned capillary unit includes a folded sheet that is folded to form an approach path.

In another embodiment of the present invention, the capillary unit is made of transparent hydrophilic material.

According to another aspect of the present invention, an optical coagulation detection machine is provided, which is suitable for the above optical coagulation detection test strip set, wherein the optical coagulation detection machine may include a light-emitting component, a photosensitive component, and a blocking valve. The above-mentioned light-emitting components can be arranged corresponding to the detection area, and can emit light toward the detection area. The photosensitive member can be used to receive the light emitted by the light-emitting member. The above blocking valve can be set corresponding to the capillary unit, and can move between the on position and the blocking position. When the blocking valve is in the above-mentioned conducting position, the above-mentioned approach path connects the reagent area and the detection area. When the blocking valve is in the blocking position, the blocking valve is pressed against the capillary unit, causing the detection area to be disconnected from the reagent area.

In an embodiment of the present invention, the optical coagulation detector may further include a vibration unit corresponding to the reagent area, wherein the vibration unit can cause the reagent area to vibrate with a duration of not more than 7 seconds.

According to another aspect of the present invention, there is provided an optical coagulation detection method, including preparing the optical coagulation detection test strip set and the optical coagulation detection machine, and placing the optical coagulation detection test strip set in the optical coagulation detection In the machine, move the blocking valve from the on position to the blocking position. Then, the blood sample is sent to the reagent area, and the blood sample reacts with the reagent in the reagent area to form a reaction sample. Next, move the blocking valve from the blocking position to the pilot The open position allows the reaction sample to flow from the reagent area to the detection area through the capillary unit. Next, the photosensitive member receives the light emitted from the light-emitting member toward the detection area to detect the reaction sample.

According to the above aspect of the present invention, there is provided yet another optical coagulation detection test strip set, which can include a first test strip and a second test strip, wherein the first test strip includes a light-permeable detection area, and the second test strip includes Reagent area for reagents. The second test strip can move between the reaction position and the detection position relative to the first test strip. When the second test strip is in the reaction position, the reagent area is not connected to the detection area; when the second test strip is in the detection position, the reagent area is connected to the detection area.

In an embodiment of the present invention, the above-mentioned first test piece may further include a first substrate and a first top piece separated from the first substrate by a first gap, and the first substrate and the first top piece cooperate to define the aforementioned detection area , And the second test strip further includes a second substrate, and a second upper sheet separated from the second substrate by a second gap, and the second substrate and the second upper sheet cooperate to define a reagent area, and the first gap is smaller than the second gap.

In an embodiment of the present invention, the difference between the second gap and the first gap is not less than 50 microns.

In another embodiment of the present invention, the second gap is not greater than 1 mm.

According to the above embodiment, the optical coagulation detection test strip set may further include a capillary unit forming an approach path, and when the second test strip is in the reaction position When set, one end of the approach path is connected to the detection area or the reagent area, and when the second test strip is in the detection position, the two ends of the approach path are respectively connected to the detection area and the reagent area.

In still another embodiment of the present invention, the above-mentioned approach path has an inlet end connected to the reagent zone and an outlet end opposite to the inlet end, wherein the cross section of the outlet end is larger than the cross section of the inlet end.

In another embodiment of the present invention, the above-mentioned capillary unit may include a folded sheet that is folded to form an approach path.

In another embodiment of the present invention, the first test piece and the capillary unit are made of transparent hydrophilic polymer.

According to another aspect of the present invention, there is provided an optical coagulation detection machine suitable for the above-mentioned optical coagulation detection test strip set, wherein the optical coagulation detection machine includes a light-emitting component, a photosensitive component and a vibration unit. The light-emitting component can emit light toward the detection area. The above-mentioned photosensitive member can be used to receive the light emitted by the light-emitting member. The above-mentioned vibration unit can cause the reagent area to generate vibration with a duration of not more than 7 seconds.

According to another aspect of the present invention, there is provided an optical coagulation detection method, including preparing the optical coagulation detection test strip set and the optical coagulation detection machine, and placing the optical coagulation detection test strip set in the optical coagulation detection The second test piece is located at the reaction position and relatively above the vibration unit, and the light emitted by the light-emitting component can be irradiated to the detection area. Then, send the blood sample into the reagent area, and use the vibration unit to make the reagent area vibrate with a duration of no more than 7 seconds, so that the blood sample and the reagent in the reagent area React to form a reaction sample. Then, the second test strip is moved from the reaction position to the detection position, so that the reaction sample after reacting with the reagent flows to the detection area. Next, the photosensitive member receives the light emitted from the light-emitting member toward the detection area to detect the reaction sample.

By using the optical coagulation test strip set of the present invention, the reagent area and the detection area can be distinguished so that the blood sample to be tested has been fully mixed with the coagulation reagent to form a reaction sample, thereby improving the accuracy of coagulation detection.

100,600: optical coagulation test strip group

110,610: first test piece

111,611: detection area

112,612: first substrate

113,613: the first film

115, 125, 615, 625: support

119: upper surface

120,620: second test piece

121,621: reagent area

122,622: second substrate

123,623: second film

129,629: Reagents

130,630: capillary unit

131,631: Approach

132: suction side

133‧‧‧Export

134,634‧‧‧folded sheet

135‧‧‧Part One

136‧‧‧Part Two

137‧‧‧Capillary tube

138,638‧‧‧Polyline

200,700‧‧‧Optical coagulation detector

201,701‧‧‧Carrier Platform

202,702‧‧‧Top cover

203,703‧‧‧Insertion port

210,710‧‧‧Light-emitting parts

220,720‧‧‧Photosensitive parts

230‧‧‧Block valve

231‧‧‧lower surface

240,730‧‧‧Vibration unit

632‧‧‧Entrance

633‧‧‧Exit port

705‧‧‧Fixture

707‧‧‧Displacement piece

801,803,805,807,809‧‧‧Step

1301,1303,1305,1307,1309‧‧‧Step

1410,1430,1450,1470,1510,1530,1550,1570‧‧‧Broken line

1411,1413,1431,1433,1511,1513,1531,1533‧‧‧points

H ₁ ,Y ₁ ‧‧‧First gap

H ₂ ,Y ₂ ‧‧‧Second gap

A-A’,C-C’‧‧‧axis

R ₁ ,R ₂ ‧‧‧radius

From the following detailed description in conjunction with the accompanying drawings, a better understanding of the aspect of the present disclosure can be obtained. It should be noted that, according to industry standard practice, each feature is not drawn to scale. In fact, in order to make the discussion clearer, the size of each feature can be increased or decreased arbitrarily.

[Fig. 1] is a schematic diagram showing an optical coagulation test strip group according to an embodiment of the present invention.

[Fig. 2] is an exploded view showing an optical coagulation test strip group according to an embodiment of the present invention.

[Figure 3] shows a cross-sectional view of an optical coagulation test strip group according to an embodiment of the present invention.

[FIG. 4A] to [FIG. 4B] are top views showing unfolded (FIG. 4A) and folded (FIG. 4B) capillary units according to an embodiment of the present invention.

[FIG. 5A] to [FIG. 5B] respectively show a capillary unit according to an embodiment of the present invention.

[Fig. 6] is a schematic diagram showing the optical coagulation test strip set in an optical coagulation test machine according to an embodiment of the present invention.

[FIG. 7A] and [FIG. 7B] are cross-sectional views of the blocking valve of the optical coagulation detector according to an embodiment of the present invention in the blocking position (FIG. 7A) and the conducting position (FIG. 7B), respectively.

[Figure 8] shows an optical coagulation detection method according to an embodiment of the present invention.

[FIG. 9A] to [FIG. 9B] are schematic diagrams showing that the reagent area and the detection area of the optical coagulation test strip set according to an embodiment of the present invention are not connected (FIG. 9A) or connected (FIG. 9B).

[FIG. 10A] and [FIG. 10B] are cross-sectional views showing that the reagent area and the detection area of the optical coagulation test strip set according to an embodiment of the present invention are not connected (FIG. 10A) or connected (FIG. 10B).

[FIG. 11A] to [FIG. 11B] are schematic diagrams showing that the reagent area and the detection area of the optical coagulation test strip set according to different embodiments of the present invention are not connected (FIG. 11A) or connected (FIG. 11B).

[FIG. 12A] and [FIG. 12B] show that when the optical coagulation detection machine and the optical coagulation detection test strip group are set in the optical coagulation detection machine according to an embodiment of the present invention, the reagent area and the detection area are not connected (Figure 12A) ) Or connection (Figure 12B).

[Figure 13] shows an optical coagulation detection method according to an embodiment of the present invention.

[Figure 14A] and [Figure 14B] show the results of a coagulation test according to an embodiment of the present invention (Figure 14A) and perform first-order differentiation based on the results (Figure 14A). 14B).

[FIG. 15A] and [FIG. 15B] show the coagulation test results (FIG. 15A) according to an embodiment of the present invention and perform first-order differentiation based on the results (FIG. 15B).

The singular forms "a", "an" and "the" mentioned in the present invention include plural references unless the context clearly dictates otherwise. The numerical range (such as 10%~11% of A) includes the upper and lower limits (ie 10%≦A≦11%) unless otherwise specified; if the numerical range does not define the lower limit (such as less than 0.2% of B) , Or less than 0.2% of B), it means that its lower limit may be 0 (ie 0%≦B≦0.2%). The above terms are used to describe and understand the present invention, but not to limit the present invention.

The present invention provides an optical coagulation detection test strip set, an optical coagulation detection test machine and a detection method applicable thereto, which separate the reagent area for mixing reagents and blood samples and the detection area for optical detection of blood samples, and use capillary units The formed approach path connects the two areas, and then the reagent area and the detection area are connected or disconnected by controlling the approach path or the relative position of the reagent area and the detection area to ensure that the blood sample and the reagent are fully mixed in the reagent area to form a reaction sample. The test is performed, and the reaction sample does not contain unmixed reagent dry powder, which can improve the accuracy of the test.

The above blood sample contains red blood cells and plasma, such as whole blood or a blood product depleted of white blood cells. The above-mentioned reagent may be a blood coagulation reagent, which may include, but is not limited to, calcium chloride, activators (such as ellagic acid, diatomaceous earth, glass beads, or kaolin), phospholipids, and stabilizers. In one embodiment, the dosage form of the coagulation reagent is a lyophilized powder. In one embodiment, the dosage form of the coagulation reagent is liquid.

As shown in FIGS. 1 and 2, the optical coagulation detection test strip group 100 according to an embodiment of the present invention includes a first test strip 110, a second test strip 120 and a capillary unit 130. Said first test strip 110 may include a first substrate 112 and the first topsheet 113, wherein the first substrate 112 and the first interval of the first topsheet 113 and together define a gap H ₁ detection zone 111, and the first substrate 112 and the second An upper piece 113 may further include two supporting members 115 disposed on both sides of the detection area 111. The second test strip 120 may include a second substrate 122 and a second top sheet 123, wherein the second substrate 122 and the second top sheet 123 are separated by a second gap H ₂ and jointly define a reagent area 121, the reagent area 121 has a reagent 129, and Two supporting members 125 can be further arranged on both sides of the reagent area 121 between the second substrate 122 and the second upper sheet 123. Figure 2 is a concise description, so the support is omitted. In practical applications, the first substrate 112 and the second substrate 122 may be, for example, an integrally formed substrate (not shown in the figure).

It should be noted that the configuration of the support 115 (125) is not limited. In the embodiment shown in FIG. 1, there are two supporting members 115 and two supporting members 125 and they are respectively located on two sides of the detection area 111 and the reagent area 121. In another embodiment, the support 115 (125) may be cylindrical and correspondingly disposed in the detection area The four corners of 111 (reagent area 121) (not shown in the figure). In another embodiment, the support 115 (125) can be arranged around the detection area 111 (reagent area 121) but with capillary unit perforation holes (not shown in the figure). In practical applications, the support 115 (125) may be formed by curing a solidified adhesive, for example.

The capillary unit 130 can form an approach path 131, wherein the approach path 131 includes a lead-out end 133 connected to the detection area 111 and a suction end 132 connected to the reagent area 121. The cross-section of the suction end 132 is smaller than the cross-section of the lead-out end 133 (shown in Figure 2) . In an embodiment, the capillary unit 130 includes a folded sheet 134, wherein the folded sheet 134 is folded to form an approach path 131.

Please refer to FIG. 3, which is a cross-sectional view of FIG. 1 along the axis AA′, in which the chain line represents the folding line 138 formed by folding the folded sheet 134 in half. 3, a second gap larger than the first gap H ₂ H _1, in one embodiment, the second gap and the first gap difference H ₂ H ₁ is not less than 50 microns. In an embodiment, the second gap H _{2 is} not greater than 1 mm. In an embodiment, the second gap H ₂ may be, for example, 500 micrometers, and the first gap H ₁ may be, for example, 420 micrometers. Since the second gap H _{2 is} larger than the first gap H ₁ , the suction end 132 and the discharge end 133 of the guide path 131 formed by the folded sheet 134 form a height difference, so that the blood sample can be guided to flow from the suction end 132 to the discharge end 133.

Please refer to FIGS. 4A and 4B, which are top views of the capillary unit 130 unfolded (FIG. 4A) and folded along the fold line 138 in FIG. 4A (FIG. 4B) according to an embodiment of the present invention. As shown in FIGS. 4A and 4B, the unfolded folded sheet 134 is folded in half along the fold line 138 to form a first part 135 and a second part 136 (FIG. 4A), and an approach path 131 is formed between the first part 135 and the second part 136 (Figure 4B). As shown in FIG. 4A, the unfolded folded sheet 134 extends to both sides at the lead-out end 133 to form a T-shape, and after being folded in half, it forms an L-shape as shown in FIG. 4B, so that the sectional length W _{2 of the} suction end 132 is smaller than The cross-sectional length W _{1 of the} leading-out end 133.

It should be noted that the capillary phenomenon is the result of the cohesion between liquid molecules and the adhesion between liquid and solid. Generally speaking, the larger the contact surface area between the liquid and the solid and/or the smaller the gap between the solid and the solid, the greater the adhesion force, and the easier it is to generate tension on the liquid. Taking the above embodiment as an example, since the first gap H _{1 is} smaller than the second gap H ₂ , a height difference is formed between the suction end 132 and the discharge end 133 of the approach path 131, and the cross section of the suction end 132 is smaller than the cross section of the discharge end 133, so The blood sample tends to flow from the suction end 132 to the discharge end 133. In addition, because the capillary unit 130 in some embodiments has a special shape, such as the L shape shown in FIG. 4B, it can affect the flow of the blood sample and generate tiny vortices, thereby assisting the mixing of the reagent 129 with the blood sample.

It should be noted that the configuration of the capillary unit 130 is not limited, but the cross-sectional length W _{2 of the} suction end 132 is smaller than the cross-sectional length W _{1 of the} discharge end 133. Please refer to FIG. 5A and FIG. 5B, which are respectively the capillary unit 130 according to an embodiment of the present invention. In one embodiment, the folded sheet 134 of the capillary unit 130 has a trapezoidal shape and is folded in half to form an approach path 131, as shown in FIG. 5A. In another embodiment, the folded sheet 134 is fan-shaped, and after repeated folding, a plurality of guide channels 131 are formed (not shown in the figure). In another embodiment, the capillary unit 130 includes a plurality of capillary tubes 137 in an equidirectional arrangement, wherein the guide channel 131 is formed in the capillary tube 137, as shown in FIG. 5B. _{The radius R 2 of} the capillary tube 137 at the outlet end 133 is larger than the radius R ₁ at the suction end 132.

The materials of the first test strip 110, the second test strip 120 and the capillary unit 130 are not limited. In one embodiment, the material of the capillary unit 130 is a hydrophilic material to increase adhesion to the blood sample. The hydrophilic material can be polyethylene terephthalate (PET), polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) or polyethylene glycol (poly(ethylene glycol)). oxide), PEO). In a preferred embodiment, the above-mentioned hydrophilic material is a transparent material, wherein the light transmittance is greater than 60%, or greater than 80%. In another embodiment, the first top sheet 113 and the first substrate 112 corresponding to the detection area 111 are made of the above-mentioned transparent material.

The present invention also provides an optical coagulation detector for use with the above-mentioned coagulation detector 200. Please refer to FIG. 6, which is a schematic diagram of the optical coagulation detection test strip group 100 being set in the optical coagulation detection machine 200. As shown in FIG. 6, the optical coagulation detection machine 200 may include a carrying platform 201 to carry or fix the above-mentioned optical coagulation detection test strip group 100. In addition, the optical coagulation detector 200 may further include an upper cover 202, wherein the upper cover 202 is disposed on the carrying platform 201, and the upper cover 202 has an insertion port 203 for receiving the first test. With the insertion of the sheet 110, the upper cover 202 at least covers the detection area to prevent external light from interfering with the detection. In another embodiment, the carrying platform 201 may further include a test strip slot (not shown in the figure) to further fix the coagulation test strip group 100.

FIGS. 7A to 7B show cross-sectional views of the blocking valve 230 of the optical coagulation detector 200 according to an embodiment of the present invention in the blocking position (FIG. 7A) and the conducting position (FIG. 7B ), respectively. As shown in FIG. 7A, the optical coagulation detector 200 includes a light-emitting component 210, a photosensitive component 220 and a blocking valve 230. In this embodiment, the light-emitting component 210 is located on the top of the supporting platform 201 and relatively disposed under the detection area 111, and the photosensitive component 220 is disposed at the bottom of the upper cover 202 corresponding to the light-emitting component 210. In another embodiment, the light emitting component 210 is disposed at the bottom of the upper cover 202 and the photosensitive component 220 is disposed on the top of the supporting platform 201, and the two are disposed opposite to the detection area 111 (not shown in the figure).

It is worth noting that FIGS. 7A to 7B do not limit the positions of the light emitting component 210 and the photosensitive component 220, but the light path formed by the light emitted by the light emitting component 210 needs to pass through the detection area 111 and then be received by the photosensitive component 220, where the light can be The reflection or refraction is performed by multiple mirrors or refracting mirrors to meet the above-mentioned optical path conditions (not shown in the figure).

In the above embodiment, the blocking valve 230 is provided corresponding to the capillary unit 130 to press or release the approach path 131 of the capillary unit 130. In detail, please see Figure 7A and Figure 7B. As shown in FIGS. 7A and 7B, the blocking valve 230 is located at the bottom of the upper cover 202 and can move relative to the capillary unit 130. The blocking valve 230 has a lower surface 231. When the lower surface 231 is connected to the upper surface of the first substrate 112 When the distance between 119 is not greater than the sum of the thickness of the first part 135 and the second part 136 of the folded sheet 134, the blocking valve 230 is in the blocking position. At this time, since the blocking valve 230 is pressed against the capillary unit 130, the detection zone 111 and the reagent zone 121 is not connected, as shown in Figure 7A. When the distance between the lower surface 231 and the upper surface 119 is greater than the sum of the thickness of the first portion 135 and the second portion 136 of the folded sheet 134, the blocking valve 230 is in the conducting position, and the guide channel 131 connects the reagent area 121 and the detection area 111, such as Shown in Figure 7B. In practice, the blocking valve 230 can be moved by motor control.

As shown in FIGS. 7A and 7B, the optical coagulation detector 200 may further include a vibration unit 240 corresponding to the reagent area 121 and disposed on the top of the carrier platform 201, wherein the vibration unit 240 can cause the reagent area 121 to vibrate continuously. Less than or equal to 7 seconds.

Please refer to FIG. 8 together with FIG. 2, FIG. 7A and FIG. 7B, which is an optical coagulation detection method according to an embodiment of the present invention. As shown in step 801, the above-mentioned optical coagulation detection test strip group 100 is placed in the above-mentioned optical coagulation detection machine 200. Next, as shown in step 803, move the blocking valve 230 from the conducting position shown in FIG. 7B to the blocking position shown in FIG. The reagent 129 reacts to form a reaction sample. Subsequently, as shown in step 807, the blocking valve 230 is moved from the blocking position shown in FIG. 7A to the conducting position shown in FIG. It flows to the detection area 111 through the capillary unit 130. Then, follow the steps As shown in step 809, the light transmittance of the reaction sample is optically detected, and the clotting time is calculated. In addition, the step 805 to step 807 may further include using the vibration unit 240 to cause the reagent area 121 to vibrate continuously but not more than 7 seconds to further mix the reagent 129 and the blood sample. In this embodiment, since the detection area 111 and the reagent area 121 are not directly connected, but indirectly connected by the approach path 131, the blocking valve 230 can be used to control the connection or disconnection of the detection area 111 and the reagent area 121, Make sure that the blood sample and the reagent 129 are fully mixed before being introduced into the detection area 111 from the approach path, thereby improving the accuracy of detection.

In addition to pressing the capillary unit 130 by the blocking valve 230, the connection or disconnection between the detection area 111 and the reagent area 121 can also determine the relative position of the detection area 111 and the reagent area 121. Please refer to FIGS. 9A and 9B, which are schematic diagrams showing that the reagent area 621 and the detection area 611 of the optical coagulation test strip set 600 according to an embodiment of the present invention are not connected (FIG. 9A) or connected (FIG. 9B ). As shown in FIGS. 9A and 9B, the optical coagulation detection test strip group 600 includes a first test strip 610 and a second test strip 620, wherein the first test strip 610 includes a light-permeable detection area 611, and the second test strip 620 It includes a reagent area 621 with a reagent 629, and the detection area 611 and the reagent area 621 can communicate with the passage 631 of the capillary unit 630. In an embodiment, the capillary unit 630 includes a folded sheet 634, and the approach path 631 may be formed by folding the folded sheet 634, for example. Specifically, the first test strip 610 further includes a first substrate 612 and the first substrate 612 and the first gap interval of the first topsheet 613 Y _1, by the first substrate 612 and the first topsheet 613 cooperate to defining a detection zone 611, 620 further comprises second test strip 622 and the second substrate and the second substrate 622 spaced a second gap of the second topsheet 623 Y _2, and by a second substrate 622 and the second topsheet 623 Cooperate to define a reagent area 621. In one embodiment, between the first substrate 612 and the first top sheet 613 and between the second substrate 622 and the second top sheet 623, a plurality of supporting members 615 and supporting members 625 may be included, but not limited to, to make the first _{A first gap Y 1} and a second gap Y ₂ are spaced between the upper sheet 613 and the first substrate 612 and between the second upper sheet 623 and the second substrate 622, respectively. In this embodiment, the second test strip 620 can move relative to the first test strip 610 between the reaction position (FIG. 9A) and the detection position (FIG. 9B ). When the second test strip 620 is in the reaction position, the reagent area 621 is not connected to the detection area 611, and when the second test strip 620 is in the detection position, the reagent area 621 is connected to the detection area 611.

In the above embodiment, the first gap Y _{1 is} smaller than the second gap Y ₂ . In an embodiment, _{the difference between the second gap Y 2} and the first gap Y ₁ is not less than 50 microns. In an embodiment, the second gap Y _{2 is} not greater than 1 mm. In one embodiment, the second gap Y ₂ is 800 microns, and the first gap Y1 is 200 microns.

In detail, please refer to FIGS. 10A and 10B, which are cross-sectional views of FIGS. 9A and 9B along the axis C-C', respectively. The chain line represents the folding line 638 formed by folding the folded sheet 634 in half. The approach path 631 has an inlet end 632 and an outlet end 633 opposite to the inlet end 632. The inlet end 632 can be inserted into the reagent area 621 and the outlet end 633 can be inserted into the detection area 611. When the second test strip 620 is at the reaction position, the approach path 631 is only connected to the reagent area 621 or the detection area 611 Either one is connected. In one embodiment, the approach path 631 communicates with the detection area 611 only through the outlet end 633 but does not communicate with the reagent area 621 (FIG. 10A ). In another embodiment, the approach path 631 only communicates with the reagent area 621 and does not communicate with the detection area 611 (not shown in the figure). When the second test strip 620 is located at the detection position, the approach path 631 communicates with the reagent area 621 and the detection area 611 at the same time, as shown in FIG. 10B.

In particular, the configuration of the first test strip 610 and the second test strip 620 is not limited. In addition to those shown in FIGS. 9A and 9B, they can also be shown in FIGS. A schematic diagram of the optical coagulation test strip set 600 of the embodiment in which the reagent area 621 and the detection area 611 are not connected (FIG. 11A) or connected (FIG. 11B ). In this embodiment, the first substrate 612 of the first test strip 610, the first top sheet 613, and the support 615 are integrally formed so as to cooperate to define the detection area 611, and the second substrate 622 of the second test strip 620 , The second top piece 623 and the supporting member 625 are integrally formed so as to cooperate to define the reagent area 621. As shown in FIG. 11A, the outlet end 633 of the capillary unit 630 is not connected to the detection area 611, so the blood sample in the reagent area 621 cannot flow into the detection area 611. As shown in FIG. 11B, the detection area 611 and the reagent area 621 are connected by the capillary unit 630, so the blood sample in the reagent area 621 can be introduced into the detection area 611.

In this embodiment, the shape of the capillary unit 630 is not limited, but the cross section of the outlet end 633 is larger than the other cross section of the inlet end 632. The capillary unit 630 can be, for example, the capillary unit 130 shown in FIG. 4B, FIG. 5A or FIG. 5B.

In one embodiment, the material of the second test piece 620 is not limited, but the first substrate 612, the portion of the first top piece 613 corresponding to the detection area 611, and the capillary unit 630 are made of the above-mentioned transparent hydrophilic polymer.

Please refer to Figures 12A and 12B, which show that when the optical coagulation test strip set 600 according to different embodiments of the present invention is set in the optical coagulation detector 700, the reagent area 621 and the detection area 611 are not connected (Figure 12A) or Schematic diagram of connectivity (Figure 12B). As shown in FIG. 12A, the optical coagulation detector 700 may include a carrying platform 701, an upper cover 702, a light-emitting component 710, a photosensitive component 720, and a vibration unit 730, wherein the upper cover 702 is disposed on the carrying platform 701 so as to cover at least the detection area 611, The upper cover 702 includes an insertion port 703 to accommodate the first test strip 610 of the optical coagulation test strip group 600 described above. The position of the light-emitting component 710 and the photosensitive component 720 is not limited, but the light path of the light emitted by the light-emitting component 710 needs to pass through the detection area 611 to be received by the photosensitive component 720. For example, as shown in FIGS. 12A and 12B, the light-emitting component 710 detects correspondingly. The area 611 is disposed on the top of the supporting platform 701, and the photosensitive component 720 is disposed on the bottom of the upper cover 702 corresponding to the light emitting component 710. In one embodiment, the light-emitting component 710 is disposed on the upper cover 702 and the photosensitive component 720 is disposed on the supporting platform 701 (not shown in the figure). In addition, on the supporting platform 701, the second test strip 620 is provided with the above-mentioned vibration unit 730 below the reagent area 621 of the reaction position, so that the reagent area 621 generates vibration with a duration of not more than 7 seconds.

In the above embodiment, the second test strip 620 can move relative to the first test strip 610 between the reaction position (FIG. 12A) and the detection position (FIG. 12B), so that the detection area 611 and the reagent area 621 are not connected (FIG. 12A) ) Or connected (Figure 12B). In detail, the movement of the second test strip 620 relative to the first test strip 610 is not limited, and it can be the movement of the second test strip 620 relative to the carrier platform 701, or the second test strip 620 is fixed on the carrier platform 701 and The movement of the carrier platform 701 drives the movement of the second test piece 620. For the former, a sliding rail and a sliding table (not shown in the figure) movable on the sliding rail can be provided on the carrying platform 701, wherein the sliding table can be used to fix the second test piece 620 and make the second test piece 620 in the reaction position and Movement between detection positions. The latter is shown in FIG. 12A, the carrying platform 701 may include a fixing part 705 and a displacement part 707, wherein the fixing part 705 carries the first test piece 610 and the displacement part 707 carries the second test piece 620. When the second test strip 620 moves from the reaction position to the detection position, the displacement member 707 moves to the fixing member 705 until the second test strip 620 is located at the detection position connecting the detection area 611 and the reagent area 621 (FIG. 12B ). The manner in which the displacement member 707 moves to the fixed member 705 is not limited. For example, a slide rail is used to connect the displacement member 707 and slide the displacement member 707 on the slide rail, or a telescopic rod is connected to the displacement member 707 and the displacement member is driven by the extension of the telescopic rod. Movement of 707 (not shown in the figure).

Please refer to FIG. 13 together with FIG. 9A, FIG. 9B, FIG. 12A, and FIG. 12B, which is an optical coagulation detection method according to an embodiment of the present invention. As shown in step 1301, the optical coagulation detection test strip group 600 is placed in the optical coagulation detection machine 700, wherein the first test strip 610 is accommodated in the insertion port 703, so that the light emitted by the light-emitting component 710 can irradiate the detection area 611. Then, as shown in step 1303, the second test strip 620 is positioned at the reaction position and the reagent area 621 is positioned on the vibration unit 730. Then, as shown in step 1305, the blood sample is sent into the reagent area 621, and the vibration unit 730 is used to make the reagent area 621 vibrate with a duration of not more than 7 seconds, so that the blood sample reacts with the reagent 629 in the reagent area 621 to form For the reaction sample, as shown in step 1307, the second test strip 620 is moved from the reaction position to the detection position, so that the reaction sample flows to the detection area 611. Next, as shown in step 1309, the light transmittance of the reaction sample is optically detected, and the clotting time is calculated.

Several embodiments are used below to illustrate the application of the present invention, but they are not used to limit the present invention. Those with ordinary knowledge in the technical field of the present invention can make various modifications and changes without departing from the spirit and scope of the present invention. Retouch.

Prothrombin time (PT) refers to the time required for the conversion of prothrombin to thrombin and clotting of the blood sample after the blood sample comes into contact with the coagulation reagent. Because the light transmittance of the blood sample during the clotting process of the blood sample will change The change occurs, so the PT can be estimated from the change in the light transmittance of the blood sample. In this embodiment, the change in signal voltage is used to characterize the light transmittance of the blood sample. Please refer to FIGS. 14A and 14B. In FIG. 14A, the horizontal axis represents time, and the vertical axis represents signal voltage. Broken line 1410 and broken line 1430 respectively represent the coagulation results of the optical coagulation test strip provided by the present invention or not used. The point 1411 and the point 1413 are respectively the broken line 1410 in the 0th The relatively small value and the relatively large value between the second to the 20th second interval, points 1431 and 1433 are respectively the relatively small value and the relatively large value of the broken line 1430 between the 10th second to the 30th second interval; In FIG. 14B, the horizontal axis represents time, and the vertical axis represents the result of first-order differentiation of the signal voltage with respect to time (dV/dt). The broken line 1450 and the broken line 1470 are the rate of change of the broken line 1410 and the broken line 1430 in FIG. 4A, respectively. It should be noted that in this embodiment, no matter whether the optical coagulation test strip provided by the present invention is used or not, the blood sample is not subjected to vibration processing before being added to the reagent area until the test is performed. In addition, the signal voltage greater than 0.145V in FIG. 14A represents the light transmittance before detection, so it is omitted and not shown.

As shown in Figure 14A, the change in signal voltage can be divided into three stages. In the first stage, the signal voltage drops sharply, as shown by the time point corresponding to the broken line 1410 from the 0th second to the point 1411, or as shown by the time point corresponding to the broken line 1430 from the 10th second to the point 1413. In the first stage, as the blood sample mixed with the reagent enters the detection area, cells such as red blood cells in the blood sample block the passage of light, causing a sharp drop in the light transmittance of the detection area, resulting in a sharp drop in signal voltage. It should be noted that in the second stage, the signal voltage rises until the blood starts to coagulate (as shown from the point 1411 to the point 1413 of the broken line 1410, or as shown from the point 1431 to the point 1433 of the broken line 1430). This is because the original spread The red blood cells in the blood are affected by fibrinogen or the ions in the reagent and condense into rouleaux, so that light can pass between the red blood cells in the rouleaux, resulting in an increase in light transmittance.

In the third stage, the signal voltage drops. In the third stage, under the action of the blood sample and the coagulation reagent, the prothrombin in the blood sample starts to act, causing fibrinogen to form fibrin with a network structure, resulting in agglomeration The money string-shaped red blood cells are dispersed on the mesh structure again, causing the light transmittance of the blood sample to decrease again until the blood sample is completely coagulated.

As mentioned earlier, the PT measurement begins with the contact of the blood sample with the coagulation reagent, and finally the formation of agglomerates in the blood sample, which is the time point when prothrombin starts to act. When prothrombin starts to work, the signal voltage drop rate has a relatively large absolute value. As shown in FIG. 14B, the broken line 1470 has a relatively small value (relatively large absolute value) at about the 27th second, and this time point is the time point when the PT measurement ends.

In addition, for accurate calculation of PT, the voltage signal needs to be able to clearly characterize the process of blood coagulation. As shown in Figure 14A, if the optical coagulation test strip set of the present invention is not used for the coagulation test, after the time point when the blood begins to coagulate (as indicated by point 1413), the broken line 1410 slowly drops, and the rate of change is not significant However, if the optical coagulation test strip set of the present invention is used for coagulation test, after the time point when the blood starts to coagulate (as indicated by point 1433), the broken line 1430 drops drastically and has a significant slope change. As shown in FIG. 14B, after the first-order differentiation of the broken line 1430 (the broken line 1470), there is a relatively small value that is clearer and easier to distinguish at about the 27th second. Accordingly, the application of the optical coagulation detection test strip set of the present invention can obtain a clearer coagulation detection signal, thereby increasing the accuracy of PT measurement.

In order to make the blood sample and the reagent mix more uniformly, when the optical coagulation test strip set of the present invention is used for coagulation detection, after the blood sample is placed, a motor is further used to provide a vibration source to cause the reagent area to vibrate, thereby reducing the blood The sample and reagent are mixed evenly, and the results are shown in Figure 15A and Figure 15B.

Please refer to Figures 15A and 15B. In Figure 15A, the horizontal axis represents time and the vertical axis represents signal voltage. The broken line 1510 and the broken line 1530 respectively represent no or no vibration processing. Points 1511 and 1513 are broken lines 1510 in the 10th. The relatively small value and the relatively large value between the second to the 30th second interval, points 1531 and 1533 are respectively the relatively small value and the relatively large value of the broken line 1530 between the 10th second to the 30th second interval; In FIG. 15B, the horizontal axis represents time, and the vertical axis represents the result (dV/dt) of the first-order differentiation of the signal voltage with respect to time. The broken line 1550 and the broken line 1570 are the rate of change of the broken line 1510 and the broken line 1530 in FIG. 5A, respectively.

As shown in Figure 15A, after the blood coagulation starts (as shown at points 1513 and 1533), compared to the signal after the shock treatment (as shown by the broken line 1530) before the vibration treatment (as shown by the broken line 1510) The voltage drop is relatively large. It can be seen from FIG. 15B that, compared with the broken line 1550, the broken line 1570 has a clearer and easily distinguishable minimum value. Therefore, by applying the optical coagulation test strip set of the present invention and mixing the reagent and the blood sample with vibration, a more obvious and clear signal can be obtained, so that the result of the coagulation test is more accurate.

It can be seen from FIGS. 15A and 15B that when the optical coagulation test strip set of the present invention is used, vibration processing can be supplemented to improve the signal quality. However, because the optical coagulation test strip set of the present invention is connected with the reagent area and the detection area by a capillary unit, the vibration processing time cannot exceed the PT of a normal person (about 11 to 13.5 seconds), so as to prevent the blood sample from sticking in the approach channel It cannot be imported into the detection area smoothly. In order to find a better vibration time, the blood samples were shaken at different times. The results are shown in Table 1. The figure number ○ represents the smooth flow of blood into the detection area, and the figure number X represents that the blood does not flow into the detection area smoothly. . When the vibration time is 1 second, 3 seconds, 5 seconds, and 7 seconds, the blood sample can smoothly flow into the detection area and improve the signal quality (not shown in the figure), but if the vibration time is 9 seconds, the blood cannot flow into the detection smoothly Area. Therefore, the vibration time is not more than 7 seconds.

Table 1

In summary, although the present invention takes a specific structure and a specific detection method as an example to illustrate the optical coagulation test strip set of the present invention, the equipment containing the test strip, and the detection method thereof, any technical field of the present invention has common Those skilled in the art know that the present invention is not limited to this, and the present invention can also be carried out using other structures or other detection methods without departing from the spirit and scope of the present invention.

Although the present invention has been disclosed in several embodiments as above, it is not intended to limit the present invention. Anyone with ordinary knowledge in the technical field to which the present invention belongs can make various modifications without departing from the spirit and scope of the present invention. Modifications and modifications, therefore, the scope of protection of the present invention shall be subject to those defined by the attached patent application scope.

100: Optical coagulation test strip group

110: The first test piece

111: detection area

112: first substrate

113: The first film

115, 125: support

120: second test piece

121: Reagent area

122: second substrate

123: Second Top

130: capillary unit

131: Approach

134: Folded sheet

H1: The first gap

H2: second gap

A-A’: axis

Claims (17)

An optical coagulation detection test strip group, comprising: a detection area; a reagent area spaced from the detection area and the reagent area has a reagent; a capillary unit forming an approach path connecting the detection area and the reagent area , Wherein the approach path includes a suction end connected to the reagent zone and a discharge end connected to the detection zone opposite to the suction end, a cross section of the suction end is smaller than another cross section of the discharge end; a substrate; The substrate is separated by a first upper sheet with a first gap, and a second upper sheet is separated from the substrate by a second gap, wherein the substrate and the first upper sheet cooperate to define the detection area, the substrate The reagent area is defined by the material and the second top sheet, and the first gap is smaller than the second gap. The optical coagulation test strip set according to claim 1, wherein a difference between the second gap and the first gap is not less than 50 microns. The optical coagulation test strip set according to claim 1, wherein the second gap is not greater than 1 mm. The optical coagulation test strip set according to any one of claims 1 to 3, wherein the capillary unit includes a folded sheet folded to form the approach path. The optical coagulation test strip set according to claim 4, wherein the capillary unit is made of transparent hydrophilic material. An optical coagulation detection machine, suitable for such as claim 1 In the optical coagulation detection test strip set, the optical coagulation detection machine includes: a light-emitting component arranged corresponding to the detection area and capable of emitting a light toward the detection area; and a photosensitive component for receiving the light-emitting component The emitted light; and a blocking valve, which is set corresponding to the capillary unit and can be moved between a conducting position and a blocking position. When the blocking valve is in the conducting position, the guide channel communicates with the reagent area And the detection zone, when the blocking valve is in the blocking position, the blocking valve is pressed against the capillary unit, so the detection zone is not connected with the reagent zone. The optical coagulation detector according to claim 6, wherein the optical coagulation detector further comprises a vibration unit corresponding to the reagent area, and the vibration unit can cause the reagent area to generate a vibration with a duration of not more than 7 seconds . An optical coagulation detection method, comprising: preparing the optical coagulation detection test strip set according to claim 1 and the optical coagulation detection machine according to claim 6; placing the optical coagulation detection test strip set The optical coagulation detection machine; the blocking valve is moved from the conducting position to the blocking position; a blood sample is sent into the reagent zone, so that the blood sample reacts with the reagent in the reagent zone to form a reaction sample The blocking valve moves from the blocking position to the conducting position, and the reaction sample flows from the reagent area to the detection area through the capillary unit; and The light-sensitive component receives the light emitted from the light-emitting component toward the detection area to detect the reaction sample. An optical coagulation detection test strip group, comprising: a first test strip, comprising a first substrate and a first top sheet separated from the first substrate by a first gap, the first substrate and the first top sheet Cooperate to define a detection area that can transmit light; and a second test piece, including a second substrate, and a second upper piece separated from the second substrate by a second gap, the second substrate and the first The two upper plates cooperate to define a reagent area with a reagent, and the first gap is smaller than the second gap, wherein the second test strip can move between a reaction position and a detection position relative to the first test strip, When the second test strip is in the reaction position, the reagent area is not connected to the detection area, and when the second test strip is in the detection position, the reagent area is connected to the detection area. The optical coagulation test strip set according to claim 9, wherein a difference between the second gap and the first gap is not less than 50 microns. The optical coagulation test strip set according to claim 9, wherein the second gap is not greater than 1 mm. The optical coagulation test strip set according to any one of claims 9 to 11 further includes a capillary unit forming an approach path. When the second test strip is at the reaction position, one end of the approach path The detection area or the reagent area is connected, and when the second test strip is at the detection position, the two ends of the approach path are respectively connected to the detection area and the reagent area. The optical coagulation test strip set of claim 12, wherein the approach path has an entrance end connected to the reagent area and opposite to the entrance An outlet end of the end, a cross section of the outlet end is larger than another cross section of the inlet end. The optical coagulation test strip set according to claim 12, wherein the capillary unit includes a folded sheet that is folded to form the approach path. The optical coagulation test strip set according to claim 14, wherein the first test strip and the capillary unit are made of transparent hydrophilic polymer. An optical coagulation detection machine suitable for the optical coagulation detection test strip set according to claim 9, wherein the optical coagulation detection machine includes: a light-emitting component capable of emitting a light toward the detection area; a photosensitive component, Used to receive the light emitted by the light-emitting component; and a vibration unit to cause the reagent area to generate a vibration with a duration of not more than 7 seconds. An optical coagulation detection method, comprising: preparing the optical coagulation detection test strip set according to any one of claims 9 to 15 and the optical coagulation detection machine according to claim 16; the optical coagulation The detection test strip group is placed in the optical coagulation detection machine, so that the second test strip is located at the reaction position and on the vibration unit, and the light emitted by the light-emitting component can irradiate the detection area; a blood sample Send into the reagent area, and use the vibration unit to make the reagent area vibrate with a duration of no more than 7 seconds, so that the blood sample reacts with the reagent in the reagent area to form a reaction sample; Moving the second test strip from the reaction position to the detection position so that the reaction sample after reacting with the reagent flows to the detection area; and the photosensitive member receives the light emitted from the light-emitting member toward the detection area to Test the reaction sample.

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