Cartridge with lab-on-paper sensor and measurement method using same

Abstract

The invention relates to a cartridge with a lab-on-paper type sensor, characterized in that it comprises an upper cartridge housing (6) and a lower cartridge housing (10) removably connected by a hinge (8) and a chromatography paper (9) with a lab-on-paper type printed sensor structure arranged between the housings (6, 10), the upper cartridge housing (6) being divided into an outer area on which a slot (3) is arranged and on which a blister containing a solution (1) is attached with a double-sided adhesive tape (2) and an inner area including a centrally arranged slot (7) provided with a porous foil (5) and around which symmetrically arranged openings (4) are arranged, additional alignment elements are arranged at the corners of each of the components (6, 9, 10), and a spacer structure (11) is arranged inside on the lower cartridge housing (10) in a shape that envelops the area including the central slot (7) and the openings (4), the cartridge forming a measurement system when assembled. The invention also relates to a method of measurement carried out using said cartridge and to the use for the detection of explosives.

Description

[Technical field]

[0001] The present invention relates to a cartridge with a lab-on-paper type sensor and a measurement method using the same. [Background technology]

[0002] The lab-on-paper sensor cartridge is designed to test or analyze materials by determining their chemical or physical properties.

[0003] A dynamic scientific development can be discerned in this field, where all steps related to the collection of samples, preparation of the analysis, carrying out the measurements, as well as the transmission and presentation of the results, have become fully integrated.

[0004] In the scientific literature, such types of devices are called laboratories-on-chips or labs-on-chips. The main advantage of the constructed devices is the significant reduction in the sample volume of the analytical sample, expressed in microliters or nanoliters, and the reduction in the amount of reagents required during the measurement. This contributes, for example, to a reduction in the time and cost of performing a single analysis [Non-Patent Document 1].

[0005] In addition to the above mentioned technologies, the so-called lab-on-paper is a new field. In the lab-on-paper technology, it is envisaged to manufacture a flow microsystem architecture on a hydrophilic substrate (such as a blotting paper for filtration) by introducing a hydrophobic barrier. The sample to be tested is delivered by utilizing the capillary forces of the substrate. Chemical indicators, e.g. showing a colour change depending on the analyte measured, are arranged in specific areas of the lab-on-paper. A blister containing a solution for dissolving the test sample is attached to the cartridge. The blister is pierced by a needle formed in the cartridge base [Non-Patent Document 2].

[0006] Korean Patent Specification KR102447967B1 discloses a lab system solution with a lab-on-paper sensor including a heating system for isothermal amplification and a method for detecting multiple nucleic acids.

[0007] US Patent Specification US11385183B2 discloses a method for detecting heavy metals using bioactive sensors on paper inkjet printed with sol-trapping reagents, allowing a colorimetric test of enzymatic activity. The bioactive paper test allows the detection of various heavy metals individually and also as a mixture in just 10 minutes. The advantage of this test is that it detects Na + Or K + It can be used to detect heavy metals in drinking water and lake water samples without interference from metal ions such as , and provides quantitative data that is consistent with values ​​obtained by atomic absorption spectrometry. The aforementioned work describes the methods and techniques for creating sensors using chromatography paper and also shows the possibility of using lab-on-paper sensors to detect analytes in a liquid state, therefore the sample to be tested must first be prepared (dissolved) and then applied to the sensor or the sensor must be immersed in the sample. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Jaime Castillo-Leon, Winnie E. Svendsen, "Lab-on-a-Chip Devices and Micro Total Analysis Systems, A Practical Guide", Springer 2015 [Non-Patent Document 2] Jeong Hoon Lee, ed., "Paper-Based Medical Diagnostic Devices: Part 1 of 10 Bioanalytical Advanced Materials, Methods, and Devices," Springer 2021 Summary of the Invention

[0009] The technical problem solved by the present invention is to obtain a solution that provides a fully integrated measurement process using chemical sensors. The need was realized to integrate the solutions necessary for preparing liquid samples, sensors and cartridges in one measurement system. A solvent solution placed in a blister dissolves the test sample, which then diffuses through the spacer and allows it to come into contact with the chromatography paper on which the lab-on-paper type chemical sensor is manufactured.

[0010] The present invention relates to a cartridge with a lab-on-paper type sensor, comprising an upper cartridge housing and a lower cartridge housing removably connected by a hinge located at the edge of the cartridge housing, and a chromatography paper (9) with a lab-on-paper type printed sensor structure arranged between the housings, the upper cartridge housing being divided into an outer region, on which a slot is disposed and on which a solution-containing blister is attached with double-sided adhesive tape, and an inner region including a centrally disposed slot, the inner region being provided with a porous foil and having symmetrically disposed openings disposed around its periphery; a shape of an interior region of the upper cartridge housing corresponds to a shape of the chromatography paper and the lower cartridge housing; Additional alignment elements are located at the corners of each of the components, and a spacer structure (11) is located on the inside of the lower cartridge housing shaped to encompass the area including the central slot and the opening, such that when assembled the cartridge forms a measurement system.

[0011] In one embodiment of the solution according to the invention, the cartridge is characterized in that in the inner area of ​​the upper cartridge housing there are four openings arranged symmetrically with respect to a central slot, forming a cloverleaf shape corresponding to the spacer structures arranged on the lower cartridge housing.

[0012] The cartridge according to the invention is equipped with a tapered needle on the inner edge of the slot, which pierces the blister with solvent when the cartridge is assembled.

[0013] In the cartridge according to the present invention, the chromatography paper with the lab-on-paper type printed sensor structure is further secured by four cartridge alignment elements, which at the same time include latches compatible with corresponding ones implemented in the lower cartridge housing.

[0014] Preferably, the cartridge is manufactured by micromilling of polyvinyl chloride.

[0015] Another subject of the invention is a measurement method carried out using a cartridge according to the invention, characterized in that a sample made up of a solid material is placed in the slot, then the symmetrical position of the upper housing, the lower housing and the blotting paper is set by the alignment opening, then the cartridge is closed, and while the cartridge is closed a conical needle pierces the blister with a solvent, dissolving the sample and the resulting solution is carried by the generated capillary forces to a sensor placed on the paper, the sensor changes color under the influence of the sample and the result reading is realized through the opening.

[0016] Preferably, the solvent placed within the blister is a 50:50% mixture of acetone and distilled water.

[0017] A cartridge according to the invention can be used for the detection of explosives.

[0018] The advantage of the solution according to the invention is that it realizes a fully integrated measurement process using chemical sensors: the solution integrates in one instrument the solvent solutions necessary to prepare the liquid sample, the sensor with the indicator fixed on the chromatography paper with the paper-printed sensor mechanism lab where the dissolved sample diffuses, and the place where the result is read out in the form of a color change or fluorescence of the sample.

[0019] An advantage of the solution according to the invention is that a fully integrated measurement process can be realized using chemical sensors. [Brief description of the drawings]

[0020] The subject matter of the invention is illustrated in the drawings. [Figure 1] 1-2 show schematic diagrams of the structure of the cartridge according to the present invention. The subject matter of the present invention is presented in more detail in preferred embodiments, which do not limit the scope of the present invention. [Diagram 2] 1-2 show schematic diagrams of the structure of the cartridge according to the present invention. The subject matter of the present invention is presented in more detail in preferred embodiments, which do not limit the scope of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS EXAMPLES

[0021] Cartridge design and sample testing method The cartridge with the lab-on-paper sensor consists of a blister with a solvent 1 placed in a slot 3 by means of a double-sided adhesive tape 2, a lower cartridge housing 10 made of polyvinyl chloride, an upper cartridge housing 6 made of polyvinyl chloride, a chromatography paper 9 with a printed sensor structure of the lab-on-paper type, a hinge 8, an opening 4 for reading the result of the color change of the used lab-on-paper sensor 9, a porous foil 5 in which the dissolution of the test sample takes place, a slot 7 for placing the test sample and a spacer structure 11 that separates the chromatography paper from the surface of the lower cartridge housing 10. Furthermore, at its inner edge, there is a conical needle 13 in the slot 3, which is used to pierce the blister 1 when closing the cartridge.

[0022] The sample to be tested is placed in the slot 7, the cartridge is closed with a flexible hinge 8, the blister 1 is pierced, the solvent solution from the blister dissolves the sample and is transported through the porous foil 5 to the chromatography paper 9 with the lab-on-paper sensor. The solution thus prepared reaches, by capillary forces, the location where the chemical indicator is located, whose optical properties change (it changes colour or becomes fluorescent) depending on the concentration of the analyte to be tested. The state of the lab-on-paper sensor is observed through the opening 4. EXAMPLES

[0023] Cartridge Creation Process The cartridge housing, designed for mounting the lab-on-paper sensor, consists of two parts, an upper 6 and a lower 10, both made by micromilling in PVC using a Datron Neo+ Series 2 milling device. All milling operations were performed at a spindle speed of 19,000 rpm. To minimize the risk of tool overheating, milling was performed inside an ethanol mist cooling shield. The upper cartridge housing 6 has a maximum thickness of 2.8 mm and is composed of two regions:

[0024] The structure of the upper cartridge housing 6 is produced by milling on both sides. First, the inner structure of the upper cartridge housing 6 is produced. The main area, which is square (38x38mm), has four 5mm diameter openings 4 for reading the analytical results and a central slot 7 for introducing and dissolving the solid sample. The inner structure of the upper cartridge housing 6 fixes and presses the chromatography paper 9 with the lab-on-paper type printed sensor mechanism. The chromatography paper 9 with the lab-on-paper type printed sensor mechanism is further fixed by four alignment elements 12 that align the lab-on-paper cartridge, which also act as latches compatible with the corresponding elements formed in the lower cartridge housing 10.

[0025] On the outside of the upper cartridge housing 6, slots 7 are made with four conical needles that can pierce the blisters. These needles were made using a milling cutter with a diameter of 0.5 mm with the following parameters: feed rate of the XY axis of 1500 mm / min, plunge speed of 300 mm / min, plunge step of 0.05 mm, overlap of 0.5. On the outer surface of the upper cartridge housing 6, two openings are also arranged, the position of these openings corresponds to the position of two stubs of the second area of ​​the upper cartridge housing. The second area also contains a slot 3 for the blister with the solvent 1, which is fixed there by a double-sided adhesive tape 2 that fixes the blister to the housing. Both areas are separated by a hinge 8, which, when bent, snaps the stubs into the openings, the upper cartridge housing 6 is assembled and finally functional.

[0026] The surface of the main area of ​​the upper cartridge housing 6 was first machined with a double flute end milling cutter with a diameter of 2 mm. The milling machine was set with an XY feed rate of 2000 mm / min, a plunge speed of 250 mm / min, a plunge step of 0.5 mm, and a tool diameter overlap of 50%. The final machining was performed with a double flute end milling cutter with a diameter of 1 mm. The machine was set with an XY feed rate of 2000 mm / min, a plunge speed of 250 mm / min, a plunge step of 0.2 mm, and a tool diameter overlap of 75%. The machining of the surface where the slot 3 of the solvent 1 blister was located was performed with a double flute end milling cutter with a diameter of 2 mm. The machine was set with an XY feed rate of 2000 mm / min, a plunge speed of 250 mm / min, a plunge step of 0.5 mm, and a tool diameter overlap of 50%. In the final stage, the plunge step was reduced to 0.2 mm and the tool diameter overlap was increased to 75% to achieve the highest quality surface at the optimal time throughout the process. The opening in the upper cartridge housing 6 was created in multiple steps using a 1 mm diameter double flute end milling cutter with a 0.2 mm plunge step.

[0027] The lower cartridge housing 11, with dimensions of 38x38mm and height at its highest point of 2.8mm, was also made by milling PVC. In the central part, a trefoil-shaped structure was placed to separate the chromatography paper 9 with the lab-on-paper type printed sensor mechanism from the underside of the lower cartridge housing 11. A double-flute end milling cutter with a diameter of 1mm was used to create the internal structure. The XY feed rate of the device was set to 2000mm / min, the plunge speed to 250mm / min, the plunge step to 0.35mm, and the tool diameter overlap to 65%.

[0028] After all elements were milled, the plates were washed with detergent and rinsed thoroughly with deionized water. EXAMPLES

[0029] How to detect explosives A cartridge with a lab-on-paper sensor was used to detect explosives such as trotyl. For this purpose, a solid sample was placed in the central slot 7 of the cartridge. The blister with solvent 1 contained a 50:50% mixture of acetone and distilled water. After closing the cartridge with a flexible hinge 8, the blister with solvent 1 was punctured, so that the solvent reached the test sample of explosives. The solution resulting from dissolving the explosives is transferred by capillary forces to an indicator fixed on a chromatography paper 9 equipped with a lab-on-paper type printed sensor mechanism. An example of such an indicator is 3-aminopropyltriethoxysilane (APTES). APTES is a compound that contains a functional primary amino group. As a result of the Meisenheimer reaction, trotyl forms a colored complex with the amino group of APTES, which changes the natural color of the lab-on-paper sensor to red, indicating the detection of an explosive. [Explanation of symbols]

[0030] 1...Blister containing solvent 2...Adhesive tape 3...Slots 4...Opening 5...Porous foil 6...Upper cartridge housing 7...Slots 8... Hinge 9. Lab-on-paper sensor 10...Lower cartridge housing 11...Spacer structure 12...Alignment elements 13...Tapered needle

Claims

1. A cartridge with a lab-on-paper type sensor, comprising an upper cartridge housing (6) and a lower cartridge housing (10) removably connected by a hinge (8) located at the edge of the cartridge housing (6), and a chromatography paper (9) with a lab-on-paper type printed sensor structure disposed between the housings (6, 10); The upper cartridge housing (6) is divided into an outer region, on which a slot (3) is arranged and on which a blister containing a solution (1) is attached with a double-sided adhesive tape (2), and an inner region including a centrally arranged slot (7) provided with a porous foil (5) and around which symmetrically arranged openings (4) are arranged, the shape of the inner area of ​​the upper cartridge housing (6) corresponds to the shape of the chromatography paper (9) and of the lower cartridge housing (10); A cartridge characterized in that additional alignment elements are arranged at the corners of each of the components (6, 9, 10) and a spacer structure (11) shaped to enclose an area including the central slot (7) and the opening (4) is arranged on the inside of the lower cartridge housing (10), such that when assembled, the cartridge forms a measurement system.

2. 2. The cartridge according to claim 1, characterized in that the inner area of ​​the upper cartridge housing (6) is provided with four openings (4) arranged symmetrically with respect to the central slot (7) and forming a cloverleaf shape corresponding to the spacer structures (11) arranged on the lower cartridge housing (10).

3. A cartridge according to any one of claims 1 to 2, characterized in that at the inner edge of the slot (3) there is a tapered needle (13) having a conical needle (13) which pierces the blister with the solvent (1) when the cartridge is assembled.

4. A cartridge according to any one of claims 1 to 3, characterized in that the chromatography paper (9) having the lab-on-paper type printed sensor structure is further fixed by four alignment elements (12) of the cartridge (6), which at the same time constitute latches compatible with the counterparts implemented in the lower cartridge housing (10).

5. A measuring method carried out with the cartridge according to claim 1, characterized in that a sample consisting of a solid material is placed in the slot (7), then the symmetrical position of the upper housing (6), the lower housing (10) and the chromatography paper (9) is set by means of an alignment opening, then the cartridge is closed, and while the cartridge is closed, the conical needle (13) pierces the blister containing the solvent (1) and dissolves the sample, the solution obtained is transported by the generated capillary forces to a sensor located on the chromatography paper (9) which changes color under the influence of the sample, and the resulting reading is realized through the opening (4).

6. 2. Use of the cartridge according to claim 1 for explosives detection.

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