Patch-type biosensor

Abstract

The present invention relates to a biosensor including a first sample inlet for providing a space into which a sample flows, an electrode unit for measuring an electrochemical signal of the flowed-in sample, a chamber for providing a space in which an electrochemical reaction of the flowed-in sample occurs, and a first sample outlet for providing a space from which the flowed-in sample is discharged, wherein a moisture-absorbing member is provided inside the chamber.

Description

[Technical Field]

[0001] The present invention relates to a patch-type biosensor. [Background technology]

[0002] A biosensor is a device or element that can confirm the presence or amount of an analyte by reacting the analyte with a bioreceptor with specificity and measuring the degree of the reaction with a signal transducer.

[0003] Biosensors are classified into electrochemical sensors, thermal sensors, optical sensors, etc. depending on the conversion method, and recently they are variously named such as glucose sensors, cell sensors, immune biosensors, DNA chips, etc. depending on the type of target substance to be analyzed.

[0004] Of these, electrochemical sensors have been widely used as a conversion method for biosensors up to now because they can convert the amount of biological sample into an electrical signal that is easy to process.

[0005] Korean Patent No. 10-0887632 also provides an electrochemical sensor that uses blood as a sample, and is capable of accurate and convenient measurement while avoiding interference with various blood types.

[0006] However, most conventional biosensors, including the biosensor of Patent No. 10-0887632, analyze the analyte by collecting a sample containing the target analyte from the subject, injecting the sample into the sensor, and measuring the electrochemical signal. However, this method has the disadvantages of requiring the sample to be collected manually from the subject, and the sample analysis is one-off, meaning that the target analyte contained in the sample cannot be measured continuously. Furthermore, as the sample flows into the biosensor, external air may flow into the biosensor along with the sample, which can result in air bubbles being contained in the biosensor in addition to the target sample, reducing the accuracy of sample detection.

[0007] Therefore, there is a need to develop a biosensor that can analyze analytes by continuously obtaining samples without artificially collecting them, while improving measurement reliability and shortening measurement time.Furthermore, there is a need to develop a biosensor that can solve problems such as reduced detection accuracy due to bubbles generated inside the biosensor. Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide a patch-type biosensor.

[0009] Another object of the present invention is to provide a biosensor that allows continuous measurement by continuously injecting and discharging a sample.

[0010] Another object of the present invention is to provide a biosensor that minimizes variations between measurement samples due to bubbles formed in a flow channel during continuous inflow and outflow of a sample. [Means for solving the problem]

[0011] The present invention relates to a biosensor including a first sample inlet for providing a space into which a sample flows, an electrode unit for measuring an electrochemical signal of the flowed-in sample, a chamber for providing a space in which an electrochemical reaction of the flowed-in sample occurs, and a first sample outlet for providing a space from which the flowed-in sample is discharged, wherein a moisture-absorbing member is provided inside the chamber.

[0012] In the first aspect of the present invention, the moisture absorbent member may have a porosity calculated by the following formula 1 of 0.5 to 0.8.

[0013] [Formula 1]

number

[0014] In a second aspect of the present invention, the chamber may have a height of 50 to 1,000 μm.

[0015] In a third aspect of the present invention, the biosensor may have a laminated structure including a first substrate portion, a second substrate portion formed on the first substrate portion, and a third substrate portion formed on the second substrate portion.

[0016] In a fourth aspect of the present invention, the first sample inlet portion may be provided in the first substrate portion.

[0017] In a fifth aspect, the present invention may be such that the width of the first sample inlet portion is 100 to 1,000 μm.

[0018] In a sixth aspect of the present invention, the chamber may be provided in the second base portion.

[0019] In a seventh aspect of the present invention, the second substrate portion may further include a second sample inlet portion formed at a position corresponding to the first sample inlet portion, and a channel for guiding the sample that has flowed into the second sample inlet portion to a chamber.

[0020] In an eighth aspect of the present invention, the width of the channel may be 100 to 1,000 μm.

[0021] In a ninth aspect of the present invention, the chamber may be directly connected to the first sample inlet portion.

[0022] In a tenth aspect of the present invention, the electrode portion may be provided between the first substrate portion and the second substrate portion.

[0023] In an eleventh aspect of the present invention, the first substrate part and the third substrate part may each independently comprise one or more materials selected from the group consisting of glass, polyethersulfone (PES), polymethyl(meth)acrylate (PMMA), polycarbonate (PC), polyethylene (PE), polyethylene naphthalate (PEN), polyphenylene sulfide (PPS), polypropylene (PP), triacetyl cellulose (TAC), cellulose acetate propionate (CAP), polyethylene terephthalate (PET), polyimide (PI), polyetherimide (PEI), polyamide (PA), cycloolefin polymer (COP), cycloolefin copolymer (COC), PMMA / PC copolymer, and PMMA / PC / PMMA copolymer.

[0024] In a twelfth aspect of the present invention, the second substrate part may be made of a pressure-sensitive adhesive (PSA) composition or an optically clear adhesive (OCA) composition.

[0025] In a thirteenth aspect, the present invention may further include a fourth substrate portion formed below the first substrate portion, and the fourth substrate portion may include a third sample inlet portion.

[0026] In a fourteenth aspect of the present invention, the first sample discharge portion may be provided on the third substrate portion.

[0027] In a fifteenth aspect, the present invention may be such that the width of the first sample discharge portion is 100 to 1,000 μm. [Effects of the Invention]

[0028] The biosensor according to the present invention is provided with a moisture-absorbing material in the chamber that easily absorbs moisture, thereby suppressing the generation of bubbles that may occur inside the chamber when the sample flows in, thereby minimizing the variation between measurement samples, improving detection accuracy, and shortening the measurement time.

[0029] In addition, the biosensor according to the present invention can smoothly obtain samples without the need for a separate device by appropriately adjusting the thickness of the substrate, the number and width of the sample inlet and outlet sections, thereby eliminating the inconvenience of manually collecting samples from the subject of analysis.

[0030] Furthermore, the biosensor of the present invention allows continuous measurement of an analyte contained in a sample by continuously inflowing and outflowing the sample. [Brief explanation of the drawings]

[0031] [Figure 1] 1 is an exploded perspective view showing a biosensor according to an embodiment of the present invention. [Figure 2] FIG. 2 is a cross-sectional view of the biosensor of FIG. 1. [Figure 3A] 1 is a perspective view illustrating a first substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 3B] 1 is a perspective view illustrating a first substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 4A] FIG. 2 is a perspective view illustrating a second substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 4B] FIG. 2 is a perspective view illustrating a second substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 4C] FIG. 2 is a perspective view illustrating a second substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 5] FIG. 2 is a perspective view showing a third substrate portion included in a biosensor according to one embodiment of the present invention. [Figure 6A] FIG. 10 is a perspective view illustrating a fourth substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 6B] FIG. 10 is a perspective view illustrating a fourth substrate portion included in a biosensor according to one or more embodiments of the present invention. [Figure 7] FIG. 10 is a diagram showing the evaluation results of the stabilization index of biosensors according to Example 3 of the present invention and Comparative Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0032] The present invention relates to a patch-type biosensor that focuses on the fact that when a patch-type biosensor is fabricated, the sample is continuously inflowed and discharged due to the pressure generated by the sample, without the need for artificial collection of a sample from the subject to be analyzed, thereby enabling continuous measurement of the analyte contained in the sample.

[0033] In particular, the present invention relates to a biosensor that includes a moisture-absorbing member inside the sensor to minimize the generation of bubbles that may form in the flow path when a sample is introduced or discharged, thereby reducing the variation between measurement samples.

[0034] Specifically, the biosensor of the present invention includes a first sample inlet portion for providing a space for the sample to flow in, an electrode portion for measuring the electrochemical signal of the flowed in sample, a chamber for providing a space for the electrochemical reaction of the flowed in sample to occur, and a first sample outlet portion for providing a space for the flowed in sample to be discharged, and a moisture-absorbing member may be provided inside the chamber.

[0035] By providing a moisture-absorbing material inside a patch-type biosensor with a microfluidics structure, the fluidity of the sample is ensured, allowing the sample to flow smoothly into the biosensor, and the generation of bubbles in the flow path is suppressed, thereby improving measurement reliability even with a small amount of sample compared to conventional biosensors.

[0036] Hereinafter, the present invention will be described in more detail with reference to the drawings. However, the following drawings attached to this specification are intended to illustrate preferred embodiments of the present invention and to facilitate a better understanding of the technical concept of the present invention together with the above-described content of the invention, and therefore the present invention should not be interpreted as being limited to only the matters depicted in such drawings.

[0037] The terms used in this specification are for the purpose of describing the embodiments and are not intended to limit the present invention. In this specification, the singular form "a," "an," or "the" includes the plural form unless otherwise specified in the text.

[0038] As used in the specification, the words "comprises" and / or "comprising" do not exclude the presence or addition of one or more other components, steps, operations and / or elements other than the stated components, steps, operations and / or elements. The same reference numerals refer to the same components throughout the specification.

[0039] Spatially relative terms such as "below," "beneath," "lower," "above," and "upper" are used to easily describe the relationship of one element or component to another, as illustrated in the drawings. Spatially relative terms should be understood to include different orientations of elements in use or operation in addition to the orientation depicted in the drawings. For example, if an element depicted in the drawings were turned over, an element described as "below" or "beneath" another element would then be positioned "above" the other element. Thus, the exemplary term "below" can encompass both an orientation of below and above. Elements can be oriented in other directions, and the spatially relative terms should be interpreted accordingly.

[0040] <Biosensor> The biosensor of the present invention may be provided with a moisture-absorbing member inside to induce smooth movement of the sample and suppress the generation of bubbles in the flow path. Specifically, the biosensor may include a first sample inlet portion into which the sample flows, an electrode portion for causing an electrochemical reaction, a chamber for providing a space for the reaction, and a first sample outlet portion for guiding the discharge of the inlet sample, and the moisture-absorbing member may be provided inside the chamber.

[0041] Furthermore, the present invention may be formed into a laminated structure from the viewpoint of ease of fabrication, process economy, etc. Specifically, the present invention may include a first substrate part, a second substrate part formed on the first substrate part, and a third substrate part formed on the second substrate part.

[0042] Fig. 1 is an exploded perspective view showing a biosensor according to one embodiment of the present invention, and Fig. 2 is a cross-sectional view of the biosensor shown in Fig. 1.

[0043] 1 and 2, the biosensor may have a laminated structure including a first substrate 10, a second substrate 20 formed on the first substrate 10, and a third substrate 30 formed on the second substrate 20. The biosensor may also include a first sample inlet 11 for providing a space into which a sample flows, electrodes 12 and 13 for measuring an electrochemical signal of the flowed-in sample, a chamber 22 for providing a space for an electrochemical reaction between the flowed-in sample and the electrodes 12 and 13, and a first sample outlet 31 for providing a space from which the flowed-in sample flows out, and may also include a moisture absorbent member 25 provided inside the chamber 22.

[0044] FIG. 3 is a perspective view showing a first substrate member 10 included in a biosensor according to an exemplary embodiment.

[0045] In one or more embodiments, the thickness of the first base member 10 may be 100 to 1,000 μm.

[0046] Referring to FIG. 3, the first substrate unit 10 may include a first sample inlet unit 11 formed on the lower surface of the first substrate unit 10 and penetrating the first substrate unit 10 .

[0047] The number of first sample inlet sections 11 is not particularly limited as long as it allows the sample to flow in smoothly, and in one embodiment, there may be only one, as shown in Figure 3A. In some embodiments, there may be multiple first sample inlet sections 11, for example, three first sample inlet sections 11 as shown in Figure 3B. In this case, bubbles are not generated when the sample flows into and moves inside the biosensor, and the sample can flow quickly into the chamber 22.

[0048] In one or more embodiments, the width of first sample inlet 11 may be 100 to 1,000 μm, preferably 150 to 600 μm, and more preferably 200 to 400 μm. When the width of first sample inlet 11 satisfies this range, the pressure of the sample secreted from the subject to be analyzed allows the sample to smoothly flow into and move within the biosensor without the need for a separate device, and no air bubbles are generated within the biosensor.

[0049] FIG. 4 is a perspective view showing a second substrate portion 20 included in a biosensor according to an exemplary embodiment.

[0050] In one embodiment, the second substrate part 20 is located between the first substrate part 10 and the third substrate part 30 and serves as an adhesive surface, and may be, for example, an adhesive, preferably made of a pressure sensitive adhesive (PSA) composition or an optical clear adhesive (OCA) composition.

[0051] In one embodiment, the second substrate portion 20 is provided as a substrate layer in which a chamber 22 is formed.

[0052] The chamber 22 may be provided to provide a space in which the sample that has flowed in can undergo an electrochemical reaction with the electrode portions 12 and 13 .

[0053] In one embodiment, the height of chamber 22 may be 50 to 1,000 μm, preferably 50 to 500 μm, and more preferably 100 to 300 μm. When the height of chamber 22 satisfies this range, a decrease in the rate at which the sample is filled into chamber 22 can be prevented, the minimum amount of sample required for measurement can be reduced, and the generation of bubbles during the sample filling process can be suppressed.

[0054] In one embodiment, the chamber 22 may have a second sample inlet 21 and a second sample outlet 24, as shown in FIG. 4A, and may be connected to the second sample inlet 21 and the second sample outlet 24 by a channel 23.

[0055] In one or more embodiments, the width of second sample inlet section 21 may be 100 to 1,000 μm, preferably 150 to 600 μm, and more preferably 200 to 400 μm. When the width of second sample inlet section 21 satisfies the above range, the inflow and movement of the sample is smooth, and no air bubbles are generated when the sample flows into or moves within the biosensor.

[0056] The second sample inlet portion 21 is preferably formed at a position corresponding to the first sample inlet portion 11, and is provided as a space into which the sample supplied from the first sample inlet portion 11 flows.

[0057] In one embodiment, as shown in FIG. 4A, a single second sample inlet portion 21 corresponding to a single first sample inlet portion 11 may be included.

[0058] In some embodiments, the second sample inlet section 21 may be multiple, and for example, as shown in Figure 4B, the first substrate section 10 may include three second sample inlet sections 21 corresponding to the three first sample inlet sections 11 formed in the first substrate section 10. In this case, the sample is supplied from the multiple first sample inlet sections 11, so that the sample can be supplied to the chamber 22 quickly, and no air bubbles are generated when the sample flows in and moves in the chamber 22.

[0059] The channel 23 serves as a guide for guiding the sample supplied from the second sample inlet 21 to the chamber 22 and for guiding the sample discharged from the chamber 22 to the second sample outlet 24.

[0060] In one or more embodiments, the width of channel 23 may be 100 to 1,000 μm, preferably 150 to 600 μm, and more preferably 200 to 400 μm. When the width of channel 23 satisfies the above range, the sample moves smoothly and no air bubbles are generated during the movement of the sample inside the biosensor.

[0061] The second sample discharge section 24 is provided as a space where the sample discharged from the chamber 22 is guided by the channel 23 and discharged.

[0062] 4A and 4B, the second sample discharge section 24 may include a single second sample discharge section 24. However, the number of second sample discharge sections 24 is not particularly limited, and a user may select a plurality of second sample discharge sections 24 as appropriate to adjust the appropriate inflow and outflow of the sample.

[0063] In one or more embodiments, the width of second sample discharge section 24 may be 100 to 1,000 μm, preferably 150 to 600 μm, and more preferably 200 to 400 μm. When the width of second sample discharge section 24 satisfies this range, the sample flows smoothly in and out of chamber 22, and air bubbles are not generated when the sample moves inside the biosensor.

[0064] 4C , the chamber 22 may be integrally formed without including the second sample inlet portion 21, the second sample outlet portion 24, and the channel 23. In this case, the first sample inlet portion 11 is directly connected to the chamber 22 and is configured to supply the sample to the chamber 22.

[0065] Furthermore, referring to FIGS. 4A to 4C, the chamber 22 may include a moisture absorbing member 25 for guiding smooth movement of the sample.

[0066] The moisture absorbent member 25 is not particularly limited as long as it can guide the smooth movement of the sample and suppress the generation of bubbles that may occur in the flow path. In one or more embodiments, it may be filter paper containing α-cellulose or the like that can filter particles on the micrometer (μm) level, and in some cases, it may contain 0.005 to 0.1% ash. Commercially available products that can be used include Whatman® Grade 1 Qualitative Filter Paper, Whatman® Grade 2 Qualitative Filter Paper, Whatman® Grade 4 Qualitative Filter Paper, and Whatman® Grade 6 Qualitative Filter Paper, all of which are available from Whatman.

[0067] In order to suppress the generation of bubbles in the flow channel and to guide the smooth movement of the sample, it is preferable that the moisture absorbent member 25 is selected in consideration of the porosity of the moisture absorbent member 25. Specifically, the porosity of the moisture absorbent member 25, calculated by the following formula 1, is preferably 0.5 to 0.8, and more preferably 0.6 to 0.75.

[0068] [Formula 1]

number

[0069] In another embodiment, the moisture absorbent member 25 may have a product of the porosity calculated by the above formula 1 and the thickness of the moisture absorbent member 25 of 95 μm to 160 μm, and more preferably 95 μm to 150 μm.

[0070] When the porosity and / or the product of the porosity and the thickness of the moisture-absorbing member 25 satisfy the above range, the fluidity of the sample is further improved, and the generation of bubbles in the flow path can be more efficiently suppressed, thereby reducing the dispersion of data from the measurement sample and shortening the time required for measurement.

[0071] Meanwhile, it will be apparent to those skilled in the art that the porosity is calculated by taking into account various parameters, including pore size and pore density, and that the value cannot be predicted by a single parameter alone, but must be calculated by comprehensively considering various parameters. For example, the porosity may decrease even if the pore size increases, and may increase even if the pore density decreases. In one or more embodiments, the pore size of the moisture absorbent member 25 is preferably 1 to 15 μm in order to facilitate smooth sample movement and prevent bubble formation. However, if the pore size falls within the above range but does not satisfy the porosity range calculated by Equation 1, the effect of improving sample movement and preventing bubble formation may be reduced.

[0072] The area of ​​the moisture-absorbing member 25 is not particularly limited as long as it can guide the smooth movement of the sample and suppress the generation of bubbles in the flow path, but it is preferable that it includes at least the electrode parts 12 and 13 in order to reduce the dispersion of data from the measurement sample and shorten the measurement time.

[0073] In one or more embodiments, the thickness of the moisture absorbent member 25 may be 100 to 1,000 μm, preferably 100 to 500 μm, and more preferably 150 to 350 μm. When the thickness of the moisture absorbent member 25 satisfies the above range, the porosity can be maintained at an appropriate level, which is advantageous in terms of improving the fluidity of the sample and suppressing the generation of bubbles.

[0074] The biosensor of the present invention can include a first electrode part 12 and a second electrode part 13 that constitute electrode parts 12, 13 for measuring an electrical signal resulting from a reaction of a sample.

[0075] In one embodiment, the first electrode portion 12 and the second electrode portion 13 may be formed on the upper surface of the first substrate portion 10, or preferably, may be formed on the upper surface of the first substrate portion 10 in an area corresponding to an area in which a chamber 22 is formed in the second substrate portion 20.

[0076] In one embodiment, the first electrode portion 12 may be a working electrode and the second electrode portion 13 may be a reference electrode.

[0077] The first electrode part 12 constituting the working electrode is an electrode where a reaction with the sample occurs, and is provided as an electrode that allows a current to flow during the electrode reaction.

[0078] In one or more embodiments, the first electrode portion 12 constituting the working electrode may be made of one or more materials selected from the group consisting of gold (Au), silver (Ag), copper (Cu), platinum (Pt), titanium (Ti), nickel (Ni), tin (Sn), molybdenum (Mo), palladium (Pd), cobalt (Co), and alloys thereof; pyrolytic graphite; glassy carbon; carbon paste; perfluorocarbon (PFC); and carbon nanotubes (CNT). Considering ease of fabrication, excellent reproducibility, and a wide potential window in the oxidation / reduction direction, carbon paste is preferred. The above materials may be used alone, but are not limited thereto, and may also be used as a multilayer film of two or more materials.

[0079] The second electrode section 13, which constitutes a reference electrode, has a constant potential and is provided as an electrode that serves as a reference for obtaining the potential generated by the working electrode.

[0080] In one or more embodiments, the second electrode unit 13 constituting the reference electrode may be one or more selected from the group consisting of a silver-silver chloride (Ag / AgCl) electrode, a calomel electrode, a mercury-mercury sulfate electrode, and a mercury-mercury oxide electrode. In consideration of reduced potential hysteresis with respect to temperature cycles and stable potential up to high temperatures, a silver-silver chloride (Ag / AgCl) electrode is preferred.

[0081] In some embodiments, in addition to the first electrode portion 12 and the second electrode portion 13, a third electrode portion (not shown) or an electrode protection layer may further be included.

[0082] The third electrode portion may be a counter electrode or may serve as an electrode for sending or receiving current so that a reaction occurs at the surface of the working electrode.

[0083] In one or more embodiments, the third electrode portion constituting the opposing electrode can be made of any of the materials described for the first electrode portion 12 and the second electrode portion 13, and it is preferable to use the same material as the first electrode portion 12 and / or the second electrode portion 13 in order to simplify the process and improve manufacturing costs.

[0084] The working electrode constituting the first electrode unit 12, the reference electrode constituting the second electrode unit 13, and the counter electrode constituting the third electrode unit may be manufactured by a conventional manufacturing method. In one or more embodiments, the manufacturing method may include one or more steps selected from the group consisting of screen printing, letterpress printing, intaglio printing, lithography, and photolithography. In one example, it is preferable to form the electrodes integrally with the wiring unit by a photolithography step, and each electrode may be manufactured by any one method selected from the group consisting of screen printing, letterpress printing, intaglio printing, and lithography, preferably by screen printing.

[0085] FIG. 5 is a perspective view showing a third substrate portion 30 included in a biosensor according to an exemplary embodiment.

[0086] In one embodiment, the third substrate part 30 serves as a cover for the biosensor while isolating the second sample inlet part 21, the chamber 22, the channel 23, the second sample outlet part 24, etc. formed in the second substrate part 20 from the outside.

[0087] In one or more embodiments, the thickness of the third base member 30 may be 100 to 1,000 μm.

[0088] Referring to FIG. 5, the third substrate part 30 may include a first sample discharge part 31 formed on the lower surface of the third substrate part 30 and penetrating the third substrate part 30 .

[0089] In one embodiment, the first sample discharge portion 31 is formed at a position corresponding to the second sample discharge portion 24 formed in the second substrate portion 20, and serves as a passage through which the sample discharged from the second sample discharge portion 24 is discharged to the outside.

[0090] In one or more embodiments, the width of first sample discharge section 31 may be 100 to 1,000 μm, preferably 150 to 600 μm, and more preferably 200 to 400 μm. When the width of first sample discharge section 31 satisfies the above range, the movement and discharge of the sample inside the biosensor is smooth, and no air bubbles are generated.

[0091] 5, the first sample discharge portion 31 may include a single first sample discharge portion 31 corresponding to a single second sample discharge portion 24. However, the number of first sample discharge portions 31 is not particularly limited, and can be selected appropriately by the user to adjust the appropriate inflow and outflow of the sample. The first sample discharge portion 31 may include a plurality of first sample discharge portions 31 corresponding to a plurality of second sample discharge portions 24 provided on the second substrate portion 20.

[0092] In one or more embodiments, the first substrate member 10 and the third substrate member 30 are not particularly limited, and may, for example, each independently comprise one or more materials selected from the group consisting of glass, polyethersulfone (PES), polymethyl(meth)acrylate (PMMA), polycarbonate (PC), polyethylene (PE), polyethylene naphthalate (PEN), polyphenylene sulfide (PPS), polypropylene (PP), triacetyl cellulose (TAC), cellulose acetate propionate (CAP), polyethylene terephthalate (PET), polyimide (PI), polyetherimide (PEI), polyamide (PA), cycloolefin polymer (COP), cycloolefin copolymer (COC), PMMA / PC copolymer, and PMMA / PC / PMMA copolymer.

[0093] In one embodiment, the first substrate portion 10 and the third substrate portion 30 may be manufactured using the same material, in which case the process can be simplified and manufacturing costs can be improved.

[0094] In some embodiments, the biosensor may further include a fourth substrate portion 40 on the underside of the first substrate portion 10 .

[0095] FIG. 6 is a perspective view showing a fourth substrate portion 40 included in a biosensor according to an exemplary embodiment.

[0096] In one or more embodiments, the fourth base member 40 may have a thickness of 50 to 1,000 μm.

[0097] In one embodiment, the fourth substrate portion 40 is positioned between a patch-type biosensor and an analyte and serves as an adhesive surface, which may be, for example, an adhesive, and preferably may be made of a pressure-sensitive adhesive (PSA) composition or an optically clear adhesive (OCA) composition.

[0098] In one embodiment, the fourth substrate portion 40 has a third sample inlet portion 41 formed at a position corresponding to the first sample inlet portion 11 formed on the underside of the first substrate portion 10, and serves as a guide for guiding the sample generated from the analysis target through the third sample inlet portion 41 to the first sample inlet portion 11.

[0099] In one embodiment, as shown in FIG. 6A, a single third sample inlet portion 41 corresponding to a single first sample inlet portion 11 may be included.

[0100] In some embodiments, there may be multiple third sample inlet sections 41, for example, as shown in Figure 6B, three third sample inlet sections 41 may be included corresponding to the three first sample inlet sections 11 formed in the first substrate section 10. In this case, by guiding the sample to the multiple first sample inlet sections 11, air bubbles are not generated when the sample flows into and moves inside the biosensor, and the sample can be quickly flown into the chamber 22.

[0101] In one or more embodiments, the width of the third sample inlet section 41 may be 100 to 3,000 μm.

[0102] In one or more embodiments, the sample containing the analyte to be analyzed may be a liquid sample, such as, but not limited to, a biological sample, such as blood, bodily fluids, urine, saliva, tears, sweat, etc.

[0103] In one or more embodiments, the analyte to be analyzed may be, for example, but not limited to, glucose, lactate, cholesterol, ascorbic acid, alcohol, various cations, and various anions.

[0104] <Electrochemical signal measurement method> The present invention also includes a method for measuring an electrochemical signal of an analyte contained in a sample using the biosensor. The method for measuring an electrochemical signal of the present invention allows for the acquisition of a sample without artificially collecting a sample from the subject to be analyzed, and allows for the continuous measurement of the analyte contained in the sample by continuously inflowing and outflowing the sample.

[0105] This is due to a microfluidics structure that utilizes the pressure generated when a sample is secreted from the analyte, and unlike capillary action that occurs even in capillaries without specific constraints, it can be achieved by appropriately adjusting the number, width, thickness, etc. of each substrate part, sample inlet part, and sample outlet part described in the <Biosensor> section above.

[0106] As used herein, "electrochemically measuring" refers to measuring by applying an electrochemical measurement technique. In one or more embodiments, examples include amperometry, potentiometry, coulometry, and the like, and preferably amperometry.

[0107] The method for measuring an electrochemical signal of an analyte according to the present invention will now be described in more detail with reference to the drawings, although as mentioned above, the present invention should not be construed as being limited to the details shown in the drawings.

[0108] 1 and 2, the fourth substrate portion 40, which constitutes the bottom layer of the patch-type biosensor, may be attached to the analyte, preferably at the site where the sample is secreted. In one embodiment, the biosensor of the present invention is for measuring glucose contained in sweat and may be attached to the upper arm.

[0109] Due to the pressure of the sample secreted from the subject to be analyzed, a portion of the secreted sample is guided through the third sample inlet 41 provided on the underside of the fourth substrate part 40 to the first sample inlet 11 provided on the first substrate part 10.

[0110] The sample guided to the first sample inlet section 11 is guided to the second sample inlet section 21 formed in the second substrate section 20, and is guided by a channel 23 to move to a chamber 22.

[0111] The sample that has moved to the chamber 22 fills the chamber 22 through the moisture absorbing member 25 provided in the chamber 22 and moves toward the second sample outlet 24. At this time, the analyte contained in the sample reacts with the receptor formed on the first electrode unit 12, which constitutes the working electrode, to generate an electrical change.

[0112] A voltage is applied to the electrode section including the first electrode section 12 and the second electrode section 13, the response current value emitted in response to the electrical change is measured, and the electrochemical signal of the target substance (analyte) in the sample is calculated based on the response current value.

[0113] The applied voltage is not particularly limited, but in one or more embodiments, it may be −500 to +500 mV, or preferably −200 to +200 mV, relative to a silver-silver chloride electrode (Ag / AgCl electrode).

[0114] In other embodiments of the electrochemical signal measurement method for a substance to be detected disclosed herein, after contact with the reagent, a voltage may be applied to the electrode portion after maintaining the electrode portion in a non-voltage state for a predetermined period of time, or a voltage may be applied to the electrode portion simultaneously with contact with the reagent.

[0115] Thereafter, the sample that has completed the reaction with the first electrode unit 12 is guided to the second sample discharge unit 24 by the channel 23 and discharged through the first sample discharge unit 31 formed in the third substrate unit 30.

[0116] According to the biosensor of the present invention, the above series of processes do not occur singly, but the sample is continuously inflowed and outflowed due to the pressure of the sample secreted from the analyte, thereby enabling continuous measurement of the target substance (analyte) contained in the sample. Furthermore, since the sample moves through the moisture-absorbing member, the generation of bubbles in the flow path, particularly in the chamber where the electrochemical reaction with the electrode occurs, is suppressed, thereby improving the reliability of measurement even with a small amount of sample.

[0117] <Electrochemical signal measurement system> The present invention also includes an electrochemical signal measurement system for measuring the electrochemical signal of an analyte in a sample, comprising the biosensor, a means for applying a voltage to the electrode portion of the biosensor, and a means for measuring the current at the electrode portion. The electrochemical signal measurement method of the present invention makes it possible to obtain a sample without artificially collecting a sample from the subject to be analyzed, and enables continuous measurement of the analyte contained in the sample by continuous inflow and outflow of the sample.

[0118] The application means is not particularly limited as long as it is electrically connected to the electrode portion of the biosensor and can apply a voltage, and any known application means can be used. In one or more embodiments, the application means can include a contactor that can come into contact with the electrode portion of the biosensor, and a power source such as a DC power source.

[0119] The measuring means is for measuring multiple currents generated in the electrode portion when a voltage is applied, and in one or more embodiments, it is sufficient that it is capable of measuring a response current value related to the amount of electrons released from the electrode portion of the biosensor, and any measuring means used in conventional or later developed biosensors can be used. [Example]

[0120] Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments disclosed below, and may be realized in various different forms. These embodiments are provided solely for the purpose of complete disclosure of the present invention and to fully convey the scope of the invention to those skilled in the art. The present invention is defined solely by the scope of the claims.

[0121] <Examples and Comparative Examples> With reference to the contents of Tables 1 and 2 below, biosensors according to examples and comparative examples were fabricated.

[0122] Example A first sample inlet for guiding the sample was formed on the PET film constituting the first substrate using a laser cutting machine. Then, a working electrode and a reference electrode were printed by screen printing using carbon paste and silver paste, respectively, to correspond to the positions of the chambers provided on the second substrate.

[0123] A second sample inlet, a chamber, and a second sample outlet were formed in the OCA film constituting the second substrate portion by the same method as described above, and then moisture absorbent members were aligned to correspond to the chambers.

[0124] A first sample discharge part was formed on the PET film constituting the third base part by the same method as above.

[0125] A third sample inlet was formed in the OCA film constituting the fourth base material portion by the same method as above.

[0126] The biosensors of Examples 1 to 4 were fabricated by laminating the first to fourth substrate parts such that the sample inlet and sample outlet portions formed on each part corresponded to each other.

[0127] Comparative Example A first sample inlet for guiding the sample was formed on the PET film constituting the first substrate using a laser cutting machine. Then, a working electrode and a reference electrode were printed by screen printing using carbon paste and silver paste, respectively, to correspond to the positions of the chambers provided on the second substrate.

[0128] A second sample inlet, a chamber, and a second sample outlet were formed in the OCA film constituting the second substrate portion by the same method as above.

[0129] A first sample discharge part was formed on the PET film constituting the third base part by the same method as above.

[0130] A third sample inlet was formed in the OCA film constituting the fourth base material portion by the same method as above.

[0131] The biosensors of Comparative Examples 1 and 2 were fabricated by laminating and attaching the first to fourth substrate parts so that the sample inlet and sample outlet portions formed on each part corresponded to each other.

[0132] [Table 1]

[0133] [Table 2]

[0134] <Experimental Example> Evaluation 1: Biosensor evaluation using moisture-absorbing material A sample with a glucose concentration of 0.1 mM was injected into the biosensors of the examples and comparative examples, and the presence or absence of sample injection, the sample injection rate, the rate of bubble generation in the flow path at the completion of injection, and the stabilization index were evaluated, and the results are shown in Table 3 below.

[0135] The stabilization index is the current value (I t ) to the current value (I s ) is subtracted from the current measured in a stable state (I s ) and multiplying by 100.

[0136] The smaller the stabilization index, the higher the precision of the biosensor. Therefore, among different biosensors measured at the same time, a biosensor with a smaller stabilization index value will have a shorter measurement time and higher precision. Stabilization index={(I t -Is ) / I s}*100

[0137] [Table 3]

[0138] Referring to the contents of Table 3, it can be seen that the stabilization indices at 30 seconds and 60 seconds measured by the biosensors of Examples 1 to 4 are smaller than the stabilization indices at the same times measured by the biosensors of Comparative Examples 1 and 2.

[0139] Furthermore, in the case of the biosensors of Examples 1 to 4, no bubbles were generated in the flow path when the sample flowed in, but in the case of the biosensors of Comparative Examples 1 and 2, it was confirmed that bubbles were generated as the sample flowed in.

[0140] Therefore, according to the present invention, it is possible to manufacture a biosensor with improved accuracy, which has a better sample inflow rate and a shorter measurement time than conventional biosensors.

[0141] Evaluation 2: Biosensor evaluation based on sample concentration Samples with glucose concentrations of 0.1 mM, 0.2 mM, and 0.3 mM were injected into the biosensors according to Example 3 and Comparative Example 1, respectively, to evaluate the stabilization index, and the results are shown in Table 4 below and FIG.

[0142] [Table 4]

[0143] Referring to Table 4 and FIG. 7, it can be seen that the stabilization indices at 30 seconds and 60 seconds measured by the biosensor of Example 3 for glucose concentrations of 0.1 to 0.3 mM are smaller than the stabilization indices at the same times measured by the biosensor of Comparative Example 1.

[0144] Therefore, according to the present invention, it is possible to manufacture a biosensor with improved accuracy and shorter measurement time compared to conventional biosensors, even for various concentration ranges within the measurement range. [Industrial Applicability]

[0145] The biosensor according to the present invention is provided with a moisture-absorbing material in the chamber that easily absorbs moisture, thereby suppressing the generation of bubbles that may occur inside the chamber when the sample flows in, thereby minimizing the variation between measurement samples, improving detection accuracy, and shortening the measurement time.

[0146] In addition, the biosensor according to the present invention can smoothly obtain samples without the need for a separate device by appropriately adjusting the thickness of the substrate, the number and width of the sample inlet and outlet sections, thereby eliminating the inconvenience of manually collecting samples from the subject of analysis.

[0147] Furthermore, the biosensor of the present invention allows continuous measurement of an analyte contained in a sample by continuously inflowing and outflowing the sample. [Explanation of symbols]

[0148] 10:First base material part 11: First sample inlet 12: Working electrode 13:Reference electrode 20:Second base material part 21: Second sample inlet 22: Chamber 23: Channel 24: Second sample discharge section 25: Moisture absorbing material 30: Third base material part 31: First sample discharge section 40: 4th base material part 41: Third sample inlet

Claims

1. a first sample inlet portion for providing a space into which the sample flows; an electrode portion for measuring an electrochemical signal of the sample that has flowed in; a chamber for providing a space in which an electrochemical reaction of the introduced sample occurs; a first sample discharge section for providing a space for discharging the inflowing sample; A moisture absorbing member is provided inside the chamber, a laminated structure including a first substrate part, a second substrate part formed on the first substrate part, and a third substrate part formed on the second substrate part, The chamber is provided in the second substrate portion, The second substrate portion is a second sample inlet formed at a position corresponding to the first sample inlet; The biosensor further includes a channel for guiding the sample that has flowed into the second sample inlet to a chamber.

2. The biosensor according to claim 1, wherein the moisture-absorbing member has a porosity of 0.5 to 0.8 as calculated by the following formula 1: [Formula 1] [Equation 1] In the above formula 1, ε is the porosity of the moisture-absorbing material, bw ０ is the basis weight of the moisture-absorbing material (kg / m ２ ), ρ ｃｅｌ is the cellulose density of the moisture-absorbing member (kg / m ３ ), and τ ｐ indicates the thickness (m) of the moisture-absorbing member.

3. 2. The biosensor according to claim 1, wherein the chamber has a height of 50 to 1,000 μm.

4. The biosensor according to claim 1 , wherein the first sample inlet portion is provided in the first substrate portion.

5. 5. The biosensor according to claim 4, wherein the first sample inlet has a width of 100 to 1,000 μm.

6. 2. The biosensor according to claim 1, wherein the channel has a width of 100 to 1,000 μm.

7. The biosensor of claim 1 , wherein the chamber is directly connected to a first sample inlet.

8. The biosensor according to claim 1 , wherein the electrode portion is provided between the first substrate portion and the second substrate portion.

9. 2. The biosensor of claim 1, wherein the first substrate portion and the third substrate portion each independently comprise one or more materials selected from the group consisting of glass, polyethersulfone (PES), polymethyl(meth)acrylate (PMMA), polycarbonate (PC), polyethylene (PE), polyethylene naphthalate (PEN), polyphenylene sulfide (PPS), polypropylene (PP), triacetyl cellulose (TAC), cellulose acetate propionate (CAP), polyethylene terephthalate (PET), polyimide (PI), polyetherimide (PEI), polyamide (PA), cycloolefin polymer (COP), cycloolefin copolymer (COC), PMMA / PC copolymer, and PMMA / PC / PMMA copolymer.

10. The biosensor according to claim 1 , wherein the second substrate portion is made of a pressure sensitive adhesive (PSA) composition or an optical clear adhesive (OCA) composition.

11. further comprising a fourth substrate portion formed below the first substrate portion; The biosensor of claim 1 , wherein the fourth substrate portion comprises a third sample inlet portion.

12. The biosensor according to claim 1 , wherein the first sample discharge portion is provided in the third substrate portion.

13. 13. The biosensor according to claim 12, wherein the width of the first sample discharge portion is 100 to 1,000 μm.

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