Biosensor comprising pedot:PSS electrode and method for manufacturing same

Abstract

The technical concept of the present invention provides a biosensor and a method for manufacturing same, the biosensor comprising: a substrate extending in a first horizontal direction and a second horizontal direction intersecting each other; a source electrode and a drain electrode disposed on the substrate spaced apart from each other; a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) electrode electrically connected to the source electrode and the drain electrode and including PEDOT:PSS; a probe which is disposed on the PEDOT:PSS electrode and can bind to a target substance to be detected; and a linker for coupling the probe and the PEDOT:PSS electrode, wherein the PEDOT:PSS electrode comprises peaks and valleys having a height difference in the vertical direction on the upper surface of the substrate.

Description

Biosensor including PEDOT:PSS electrode and method for manufacturing the same

[0001] The technical concept of the present invention relates to a biosensor comprising a PEDOT:PSS electrode and a method for manufacturing the same.

[0002] The recent COVID-19 pandemic has led to a surge in the need for the development of rapid and accurate sensors to detect biological substances such as DNA and RNA. While sensors utilizing various optical, mechanical, and electrical methods for detecting biological substances have been developed in the past, most of these sensors presented a problem requiring significant pretreatment to increase the concentration of the target substance within a solution. In particular, for samples extracted from patients—such as cancer cells, viruses, and antibodies—the number of extractions must be limited, resulting in significantly small sample volumes; consequently, target substances could only be detected after undergoing complex, long-term pretreatment. Among these, sensors utilizing electrical methods possess high sensitivity without the need for pretreatment to increase the concentration of target substances within a solution, leading to significant recent research in this field. Electrochemical biosensors are well-known in the industry and have been used to determine the concentrations of various analytes from biological samples, particularly blood.

[0003] The above-described biosensor forms an electrode system comprising multiple electrodes on an insulating substrate using methods such as screen printing. Here, the presence or concentration of a target substance contained in the sample can be determined by measuring the current generated after a certain voltage is applied following the introduction of a sample. One of the most critical factors in the development of such a biosensor is the development of electrodes with high sensing sensitivity. Accordingly, PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)) has emerged as a representative type of conductive polymer that can be included in the electrode.

[0004] The problem that the technical concept of the present invention aims to solve is to provide a biosensor comprising a PEDOT:PSS electrode having a rough surface and a method for manufacturing the same.

[0005] To solve the aforementioned problem, according to exemplary embodiments based on the technical concept of the present invention, a biosensor is provided comprising: a substrate extending in a first horizontal direction and a second horizontal direction; a source electrode and a drain electrode spaced apart from each other and disposed on the substrate; a PEDOT:PSS electrode electrically connected to the source electrode and the drain electrode and comprising PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)); a probe disposed on the PEDOT:PSS electrode and capable of binding to a target substance to be detected; a linker that combines the probe and the PEDOT:PSS electrode; and the PEDOT:PSS electrode comprising a peak portion and a valley portion having a height difference in the vertical direction on the upper surface of the substrate.

[0006] To solve the aforementioned problem, according to exemplary embodiments in accordance with the technical concept of the present invention, a method for manufacturing a biosensor is provided, comprising the step of forming a PEDOT:PSS electrode having a rough surface on a substrate, and a source electrode and a drain electrode electrically connected to the PEDOT:PSS electrode, wherein the step of forming the PEDOT:PSS electrode comprises: the step of applying a PEDOT:PSS solution on the surface of the plasma-treated substrate; and the step of drying the PEDOT:PSS solution to form the PEDOT:PSS electrode on the substrate.

[0007] According to exemplary embodiments of the present invention, a biosensor with enhanced sensitivity to a target substance can be provided by including a PEDOT:PSS electrode having a rough surface.

[0008] Figure 1 is a diagram illustrating the structure of PEDOT:PSS.

[0009] FIG. 2 is a diagram illustrating a biosensor in some embodiments of the present invention.

[0010] Figure 3a is a diagram illustrating the PEDOT:PSS electrode of Figure 2.

[0011] Figure 3b is an enlarged view of the area marked "EX" in Figure 3a.

[0012] FIG. 3c is a drawing showing the area corresponding to the area marked "EX" in FIG. 3a.

[0013] FIG. 4 is a diagram illustrating a PEDOT:PSS electrode in some other embodiments of the present invention.

[0014] FIGS. 5a to 5c are drawings illustrating PEDOT:PSS electrodes in other embodiments of the present invention.

[0015] FIG. 6a is a diagram illustrating a method for manufacturing a PEDOT:PSS electrode in some embodiments of the present invention.

[0016] FIG. 6b is a diagram illustrating a method for manufacturing a PEDOT:PSS electrode in some other embodiments of the present invention.

[0017] FIGS. 7 to 11 are each AFM images of a PEDOT:PSS electrode in some embodiments of the present invention.

[0018] Figures 12a and 12b are the results of sensing samples having different pH concentrations using the biosensor of the present invention.

[0019] Figures 13a and 13b are the results of sensing samples having different concentrations using the biosensor of the present invention.

[0020] Hereinafter, embodiments of the technical concept of the present invention will be described in detail with reference to the attached drawings. Identical components in the drawings are denoted by the same reference numerals, and redundant descriptions thereof are omitted.

[0021] The biosensor according to the embodiments of the present invention is used for gene expression profiling, genotyping, detection of mutations and polymorphisms such as SNPs (Single Nucleotide Polymorphisms), protein and peptide analysis, screening of potential drugs, and new drug development and manufacturing by analyzing biomolecules contained in a biosample.

[0022] Biosensors employ probes suitable for the target biosample to be analyzed. Examples of probes that can be employed in biosensors include DNA probes, protein probes such as enzymes, antibodies / antigens, and bacteriorhodopsin, microbial probes, and neuronal probes. Biosensors manufactured in the form of chips are also referred to as biochips. For example, depending on the type of probe employed, they may be referred to as DNA chips, protein chips, cell chips, neuron chips, etc. Biosensors according to some embodiments of the present invention may include oligomer probes as probes. The term "oligomer probe" implies that the number of monomers in the employed probe is at the oligomer level. Here, "oligomer" may be used to refer to a polymer composed of two or more covalently bonded monomers with a molecular weight of about 1,000 or less. Specifically, it may include 2 to 500 monomers, preferably 5 to 30 monomers. However, the meaning of "oligomer probe" is not limited to the above numerical values. The monomers constituting the oligomer probe can be modified depending on the type of biosample to be analyzed and may be, for example, nucleosides, nucleotides, amino acids, peptides, etc. Nucleosides and nucleotides may include known purine and pyrimidine bases, as well as methylated purines or pyrimidines, acylated purines or pyrimidines, etc. Furthermore, nucleosides and nucleotides may include conventional ribose and deoxyribose sugars, as well as modified sugars in which one or more hydroxyl groups are substituted with halogen atoms or aliphatic atoms, or functional groups such as ethers or amines are attached. Amino acids may be L-, D-, and nonchiral types of amino acids found in nature, as well as modified amino acids or amino acid analogs, etc.A peptide refers to a compound formed by an amide bond between the carboxyl group of an amino acid and the amino group of another amino acid. Unless otherwise specifically stated, the probe exemplarily conceived in the following examples is a DNA probe, which is an oligomeric probe in which monomers of about 5 to 30 nucleotides are covalently bonded. However, the present invention is not limited thereto, and it is understood that various probes described above may be applied.

[0023] In this specification, the term "probe" refers to a substance connected to a PEDOT:PSS electrode that can chemically bind with a target substance within a sample, and the term "linker" refers to a substance responsible for connecting the probe and the PEDOT:PSS electrode.

[0024] Figure 1 is a diagram illustrating the structure of PEDOT:PSS.

[0025] Referring to Fig. 1, PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)) is shown. PEDOT:PSS is one of the most widely used conductive plastic materials because it has high conductivity, good transmittance in the visible light region, is soluble in water allowing for environmentally friendly solution processing, and has excellent stability.

[0026] FIG. 2 is a drawing for illustrating a biosensor (100) in some embodiments of the present invention.

[0027] Referring to FIG. 2, the biosensor (100) may include a substrate (110), a source electrode (120), a drain electrode (122), and a PEDOT:PSS electrode (PS). The substrate (110) may extend in a first horizontal direction (X direction) and a second horizontal direction (Y direction). The first horizontal direction (X direction) and the second horizontal direction (Y direction) may intersect each other. A direction perpendicular to the upper surface of the substrate (110) may be defined as a vertical direction (Z direction).

[0028] It will be obvious to a person skilled in the art that, within this specification, any description made with respect to the first horizontal direction (X direction) may be understood in the same or similar way with respect to the second horizontal direction (Y direction).

[0029] In exemplary embodiments, the substrate (110) may comprise a material selected from the group consisting of glass, quartz, SiC, MgO, Si, SiO2, Ge, GaN, AlN, GaP, InP, GaAs, SiC, Al2O3, LiAlO3, MgO, graphite, graphene, plastic, ceramic, rubber, and combinations thereof. However, this is exemplary, and the substrate (110) of the present invention is not limited to the material exemplified. Examples of the above plastics may include, but are not limited to, materials selected from polystyrene (PS), polydimethylsiloxane (PDMS), polyimide (PI), polyethersulfone (PES), polyacrylate (PAR), polyetherimide (PEI), polyethylene naphthalate (PEN), polyethylene terephthalate (PET), polyphenylene sulfide (PPS), polyarylate, polycarbonate (PC), cellulose triacetate (CTA), and cellulose acetate propionate (CAP).

[0030] The source electrode (120) and the drain electrode (122) may be disposed on the substrate (110). The drain electrode (122) may be disposed spaced apart from the source electrode (120) in a first horizontal direction (X direction). The source electrode (120) and the drain electrode (122) may be formed of various materials and may include metals or metal alloys. For example, the source electrode (120) and the drain electrode (122) may include gold (Au), copper (Cu), ruthenium (Ru), aluminum (Al), cobalt (Co), tungsten (W), molybdenum (Mo), titanium (Ti), tantalum (Ta), nickel (Ni), platinum (Pt), chromium (Cr), or alloys thereof.

[0031] A PEDOT:PSS electrode (PS) may be interposed between the source electrode (120) and the drain electrode (122). However, the PEDOT:PSS electrode (PS) may not have a flat structure extending along the upper surface of the substrate (110), but may include peaks and valleys having a height difference in a direction perpendicular to the upper surface of the substrate (110) (e.g., the vertical direction (Z direction)). A detailed description of the structure of the PEDOT:PSS electrode (PS) will be provided later in the description regarding FIGS. 3a, 3b, and 3c. The shape of the uneven surface and the degree of unevenness of the PEDOT:PSS electrode (PS) may vary depending on the manufacturing process. Although not illustrated, a gate electrode for supplying voltage to the PEDOT:PSS electrode (PS) may be electrically connected to the PEDOT:PSS electrode (PS).

[0032] A sample (SP) in contact with a PEDOT:PSS electrode (PS) may contain a target substance. The target substance may contain a protein, DNA, RNA, or any base sequence, and the sample (SP) may contain biological solutions such as fragments, blood, or saliva containing said target substance. The sample (SP) may be placed within a sample storage container (130). The sample storage container (130) may be a container for holding the sample (SP) and may be composed of a polymer or non-polymer material. As one embodiment, silicon rubber may be used. The shape and size of the sample storage container (130) are not limited to those illustrated, and any sample storage container (130) that can store the sample (SP) and allow said sample (SP) to come into contact with the PEDOT:PSS electrode (PS) may be used as the sample storage container (130) of the present invention.

[0033] The biosensor (100) may further include a probe (128) capable of chemically binding to a target substance on a PEDOT:PSS electrode (PS). For example, the probe (128) may be one of a polynucleotide, a peptide nucleic acid probe, an aptamer (DNA having the ability to specifically bind to a specific substance), a protein, an antibody, or a capture agent. For example, if the target substance is DNA, the probe (128) may have a nucleotide sequence complementary to the nucleotide sequence of the target substance DNA for chemical binding with the target substance.

[0034] The biosensor (100) may further include a linker (129) between the probe (128) and the PEDOT:PSS electrode (PS) to facilitate chemical bonding between the probe (128) and the PEDOT:PSS electrode (PS). In one embodiment, when the target substance is DNA, nano-sized gold (Au) particles may be selected as the linker (129).

[0035] In another embodiment, when the target substance is DNA, PASE (pyrenebutanoic acid succinimidyl ester) of the following chemical formula 1 may be selected as the linker (129).

[0036]

[0037] The pyrene group in the PASE can bind to the PEDOT:PSS electrode (PS), and the succinimidyl ester group in the PASE can bind to the probe (128). In this case, the probe (128) to which the succinimidyl ester group binds may be DNA having a nucleotide sequence complementary to the nucleotide sequence of the target substance DNA.

[0038] It is possible to determine whether a target substance is present in a sample (SP) by observing electrical parameters measured by supplying voltage to the PEDOT:PSS electrode (PS). For example, electrical parameters may include capacitance, voltage, average current, etc. Specifically, regarding a first sample in which no target substance is present and a second sample for which observation regarding the presence of a target substance is required, the presence of a target substance in the second sample can be confirmed by comparing the electrical parameters measured by supplying voltage to the PEDOT:PSS electrode (PS) when the first sample is introduced with the electrical parameters measured by supplying voltage to the PEDOT:PSS electrode (PS) when the second sample is introduced. A difference in the electrical parameters of the second sample compared to the first sample may indicate the presence of the target substance.

[0039] Figure 3a is a diagram illustrating the PEDOT:PSS electrode (PS) of Figure 2.

[0040] Figure 3b is an enlarged view of the area marked "EX" in Figure 3a.

[0041]

[0042] * FIG. 3c is a drawing showing the area corresponding to the area marked "EX" in FIG. 3a.

[0043] Referring to FIGS. 3a, 3b, and 3c, the surface of the PEDOT:PSS electrode (PS) may have a rough shape. For example, the PEDOT:PSS electrode (PS) may include a peak (P) and a valley (V) having a height difference in the vertical direction (Z direction). In some embodiments, the peak (P) and the valley (V) of the PEDOT:PSS electrode (PS) may be alternately arranged along one direction (e.g., a first horizontal direction (X direction), a second horizontal direction (Y direction), or a diagonal direction between the first horizontal direction (X direction) and the second horizontal direction (Y direction). In some embodiments, the peak (P) and the valley (V) of the PEDOT:PSS electrode (PS) may extend in another direction perpendicular to the one direction in which the peak (P) and the valley (V) are alternately arranged. For example, the peak portion (P) and the valley portion (V) can be formed in a line shape extending in the other direction.

[0044] As illustrated in FIG. 3a, regarding the first valley portion (V1) disposed on one side of the peak portion (P) of the PEDOT:PSS electrode (PS) and the second valley portion (V2) disposed on the other side of the peak portion (P), the first valley portion (V1) and the second valley portion (V2) are spaced apart from each other in the first horizontal direction (X direction) with the peak portion (P) in between, and the peak portion (P), the first valley portion (V1), and the second valley portion (V2) can be extended in the second horizontal direction (Y direction).

[0045] In exemplary embodiments, as illustrated in FIG. 3b, a first inclined surface (SL1) extending from a peak (P) to a first valley (V1) and a second inclined surface (SL2) extending from a peak (P) to a second valley (V2) may face each other in a second horizontal direction (Y direction) with the peak (P) in between.

[0046] In exemplary embodiments, the peak portion (P) and the valley portion (V) are shown to have a curved shape, but are not limited thereto and may have a pointed shape.

[0047] In exemplary embodiments, the peak portion (P) may be arranged at a first interval (W1) in a range of about several nanometers to several tens of micrometers along the first horizontal direction (X direction). The valley portion (V) may be arranged at a second interval (W2) in a range of about several nanometers to several tens of micrometers along the first horizontal direction (X direction). For example, the first interval (W1) and the second interval (W2) may be within about 0.01 nanometers to 10 micrometers. In one embodiment, the peak portion (P) and the valley portion (V) may each be arranged at a constant interval along the first horizontal direction (X direction). In another embodiment, the peak portion (P) and the valley portion (V) may each be arranged at an inconsistent interval along the first horizontal direction (X direction).

[0048] In one embodiment, the height difference in the vertical direction (Z direction) between adjacent peaks (P) and valleys (V) of the PEDOT:PSS electrode (PS) may be within a range of about 0.1 nanometers to 10 micrometers. In one embodiment, the height difference in the vertical direction (Z direction) between adjacent peaks (P) and valleys (V) of the PEDOT:PSS electrode (PS) may be constant. In another embodiment, the height difference in the vertical direction (Z direction) between adjacent peaks (P) and valleys (V) of the PEDOT:PSS electrode (PS) may not be constant and may vary.

[0049] As one embodiment, as shown in FIG. 3b, for a first valley portion (V1) disposed on one side of the peak portion (P) of a PEDOT:PSS electrode (PS) and a second valley portion (V2) disposed on the other side of the peak portion (P), the slope of the first inclined surface (SL1) from the first valley portion (V1) to the peak portion (P) and the slope of the second inclined surface (SL2) from the second valley portion (V2) to the peak portion (P) may be the same. The first inclined surface (SL1) from the first valley portion (V1) to the peak portion (P) and the second inclined surface (SL2) from the second valley portion (V2) to the peak portion (P) may be symmetrical to each other with respect to the peak portion (P). As another embodiment, as shown in FIG. 3c, for the first valley (V1) and the second valley (V2) which are valleys (V) adjacent to the peak (P) of the PEDOT:PSS electrode (PS), the slope of the first sloped surface (SL1) from the first valley (V1) to the peak (P) and the slope of the second sloped surface (SL2) from the second valley (V2) to the peak (P) may be different from each other.

[0050] In exemplary embodiments, the PEDOT:PSS electrode (PS) may have a thickness of about tens of nanometers to hundreds of nanometers, and preferably may have a thickness of about 10 nanometers to 100 nanometers.

[0051] In FIG. 3a, only the front surface (FS) of the PEDOT:PSS electrode (PS) is shown, but the rear surface (BS) of the PEDOT:PSS electrode (PS) may also have a rough surface similar to the front surface (FS). In this specification, the description of the front surface (FS) of the PEDOT:PSS electrode (PS) may be applied in the same or similarly to the rear surface (BS) of the PEDOT:PSS electrode (PS).

[0052] In some embodiments, the rough shape of the front surface (FS) of the PEDOT:PSS electrode (PS) and the rough shape of the rear surface (BS) of the PEDOT:PSS electrode (PS) may correspond to each other. For example, for the location where the peak portion (P) and the valley portion (V) are formed respectively on the front surface (FS) of the PEDOT:PSS electrode (PS), the peak portion (P) and the valley portion (V) may be formed respectively on the rear surface (BS) of the PEDOT:PSS electrode (PS) at a corresponding location. However, the present invention is not limited thereto, and the rough shape of the front surface (FS) of the PEDOT:PSS electrode (PS) and the rough shape of the rear surface (BS) of the PEDOT:PSS electrode (PS) may not correspond to each other.

[0053] The number of PEDOT:PSS layers forming the PEDOT:PSS electrode (PS) is not limited to one as illustrated, but can be composed of multiple layers. For example, the biosensor may include a first PEDOT:PSS layer and a second PEDOT:PSS layer disposed on the first PEDOT:PSS layer. The first PEDOT:PSS layer and the second PEDOT:PSS layer may have the same or different shapes from each other.

[0054] When detecting a target substance using an electrical method, the charge of the target substance may be obscured by the charge of ions other than the target substance present in the solution, so the target substance can be detected reliably only when it is close to the sensor surface. In other words, since the target substance can be detected only when it is within the Debye length of the sensor, increasing the Debye length of the sensor can increase the sensitivity of the sensor from Debye shielding, which is an important challenge in the industry. When detecting a target substance using a biosensor (100) that utilizes a PEDOT:PSS electrode having a rough surface according to the technical concept of the present invention, compared to using a PEDOT:PSS electrode having a flat surface, the Debye length for the target substance increases, thereby improving sensitivity. Therefore, a biosensor (100) with improved sensing sensitivity for the target substance can be provided.

[0055] FIG. 4 is a diagram illustrating a PEDOT:PSS electrode (PSa) in some other embodiments of the present invention. Since it is configured generally similarly to the PEDOT:PSS electrode (PS) described in FIG. 3a, 3b, and 3c, the differences from the PEDOT:PSS electrode (PS) described in FIG. 3a, 3b, and 3c will be explained in detail below.

[0056] As illustrated in FIG. 4, the peak (P) and valley (V) of the PEDOT:PSS electrode (PSa) may be arranged alternately in both directions (e.g., a first horizontal direction (X direction) and a second horizontal direction (Y direction)). In exemplary embodiments, regarding a first valley (V1) positioned on one side of the peak (P) of the PEDOT:PSS electrode (PS) and a second valley (V2) positioned on the other side of the peak (P), the first valley (V1) and the second valley (V2) may be spaced apart from each other in the first horizontal direction (X direction) with the peak (P) in between, and the peak (P), the first valley (V1), and the second valley (V2) may be extended relatively briefly in the second horizontal direction (Y direction).

[0057] In exemplary embodiments, a first inclined surface (SL1) extending from a peak portion (P) to a first valley portion (V1) and a second inclined surface (SL2) extending from a peak portion (P) to a second valley portion (V2) may face each other in a second horizontal direction (Y direction) with the peak portion (P) in between.

[0058] In FIG. 4, a plurality of peak portions (P) and a plurality of valley portions (V) having different vertical heights in the second horizontal direction (Y direction) are shown, but this is for convenience of illustration and the present invention is not limited to what is shown, and a plurality of peak portions and a plurality of valley portions having the same vertical height may be arranged.

[0059] FIGS. 5a to 5c are drawings illustrating a PEDOT:PSS electrode in some other embodiments of the present invention. Since it is configured generally similarly to the PEDOT:PSS electrode (PS) described in FIGS. 3a, 3b, and 3c, the differences from the PEDOT:PSS electrode (PS) described in FIGS. 3a, 3b, and 3c will be explained in detail below.

[0060] As illustrated in FIG. 5a, the peak portion (P) and the valley portion (V) of the PEDOT:PSS electrode (PS1) may be arranged alternately in both directions (e.g., a first horizontal direction (X direction) and a second horizontal direction (Y direction)). For example, the PEDOT:PSS electrode (PS1) may include a plurality of rows and a plurality of columns consisting of alternately arranged peak portions (P) and valley portions (V), and the peak portions (P) included in each of the plurality of rows may be arranged in a line, and the same applies to the valley portions (V) included in each of the plurality of rows.

[0061] In exemplary embodiments, regarding the inclined surface (SL) extending from the peak portion (P) to the valley portion (V), the inclined surface (SL) may be arranged in a shape that surrounds the peak portion (P) in a first horizontal direction (X direction) and a second horizontal direction (Y direction).

[0062] As illustrated in FIG. 5b, the peak portions (P) and valley portions (V) of the PEDOT:PSS electrode (PS2) may be arranged alternately in both directions (e.g., a first horizontal direction (X direction) and a second horizontal direction (Y direction)). For example, the PEDOT:PSS electrode (PS2) may include a plurality of rows and a plurality of columns consisting of alternately arranged peak portions (P) and valley portions (V). The peak portions (P) included in each of the plurality of rows may be arranged in a zigzag pattern relative to each other, and the same applies to the valley portions (V) included in each of the plurality of rows.

[0063] As illustrated in FIG. 5c, the peak portion (P) and valley portion (V) of the PEDOT:PSS electrode (PS3) may be arranged alternately in all directions. The peak portion (P) and valley portion (V) of the PEDOT:PSS electrode (PS3) may be arranged alternately irregularly without regularity regarding a specific direction. For example, the distance between adjacent peak portions (P) and the distance between adjacent valley portions (V) may not be constant, and the height difference in the vertical direction (Z direction) between the peak portion (P) and the valley portion (V) may not be constant. Although the peak portion (P) and valley portion (V) of the PEDOT:PSS electrode (PS3) are illustrated as having a pointed shape, they are not limited thereto and may have a curved shape as illustrated in FIG. 3a.

[0064] FIG. 6a is a drawing illustrating a method for manufacturing a PEDOT:PSS electrode in some embodiments of the present invention. FIG. 6b is a drawing illustrating a method for manufacturing a PEDOT:PSS electrode in other embodiments of the present invention. FIG. 6c is a drawing illustrating a method for manufacturing a PEDOT:PSS electrode in other embodiments of the present invention.

[0065] With reference to FIG. 3a, the method for manufacturing a biosensor of the present invention includes the step of forming a PEDOT:PSS electrode (PS) having a rough surface on a substrate (110), and a source electrode (120) and a drain electrode (122) electrically connected to the PEDOT:PSS electrode (PS). Hereinafter, with reference to FIG. 6a and FIG. 6b, the manufacturing process for forming the PEDOT:PSS electrode (PS) during the manufacturing process of the biosensor of the present invention will be described in detail. However, the manufacturing process for forming the PEDOT:PSS electrode (PS) may vary and is not limited to the manufacturing process described below.

[0066] Referring to FIG. 6a, a preliminary substrate is first prepared, and a step (S10) of etching or deforming the preliminary substrate so that the preliminary substrate has a rough surface in order to form a rough surface of the PEDOT:PSS electrode may be performed. The process of deforming the preliminary substrate may include a process of heating the preliminary substrate or deforming the preliminary substrate by applying force to the preliminary substrate. However, this is exemplary, and the formation of a preliminary substrate having a rough surface may vary depending on the constituent material of the preliminary substrate, and any process capable of forming the PEDOT:PSS electrode (PS) into a rough surface may be employed.

[0067] As one embodiment, a pre-substrate having a flat upper surface may be prepared, and the upper surface of the pre-substrate may be etched to form a rough surface. The etching process may be performed using dry etching, wet etching, or a combination thereof. For example, the pre-substrate may comprise silicon or silicon oxide.

[0068] As another embodiment, a pre-substrate comprising a thermoplastic polymer may be prepared, and the pre-substrate may be baked in an oven to deform the pre-substrate and form a rough surface. For example, the pre-substrate may include polyethylene (PE), polypropylene (PP), polystyrene, or acrylonitrile butadiene styrene (ABS).

[0069] Alternatively, as another embodiment, a preliminary substrate comprising a polymer that can be easily deformed by stress may be prepared, and stress may be applied to the preliminary substrate to deform the preliminary substrate and form a rough surface. For example, the preliminary substrate may comprise polystyrene or polydimethylsiloxane.

[0070] In some embodiments, UV-ozone (O3) treatment or oxygen (O2) plasma treatment may be further performed on the surface of the etched or modified substrate to increase the adhesion between the substrate and the PEDOT:PSS electrode.

[0071] Subsequently, a step (S20) of applying a PEDOT:PSS solution onto the etched or modified preliminary substrate may be performed. The PEDOT:PSS solution may be a solution containing PEDOT:PSS as described above in FIG. 1. For example, a commercially available PEDOT:PSS aqueous solution, such as Baytron, Clevios, and Orgacon, may be used as the PEDOT:PSS solution, or the commercially available PEDOT:PSS aqueous solution may be used after being appropriately diluted to a required concentration. For example, the commercially available PEDOT:PSS aqueous solution may be used as is, or the commercially available PEDOT:PSS aqueous solution may be used after being diluted in water at a 1:1 ratio to water, or the commercially available PEDOT:PSS aqueous solution may be used after being diluted in water at a 1:3 ratio to water.

[0072] In some embodiments, the PEDOT:PSS solution may further include dimethyl sulfoxide (DMSO) or ethyleneglycol as an additive to improve the bonding strength and electrical conductivity of the PEDOT:PSS electrode (PS). In some embodiments, the PEDOT:PSS solution may further include the linker described above in FIG. 2. For example, the PEDOT:PSS solution may further include PASE.

[0073] In one embodiment, if the PEDOT:PSS solution does not contain a linker, after performing the subsequent process (S14) for forming a PEDOT:PSS electrode, an additional manufacturing process for bonding a linker onto the PEDOT:PSS electrode may be performed. In another embodiment, if the PEDOT:PSS solution further contains a linker, after performing the subsequent process (S14) for forming a PEDOT:PSS electrode, an additional manufacturing process for bonding a linker onto the PEDOT:PSS electrode may not be performed.

[0074] In some embodiments, the PEDOT:PSS solution may be applied by spin coating. The spin coating process may be performed at a speed of about 1,000 rpm to 4,000 rpm for about 30 seconds to 1 minute 30 seconds, but this is exemplary and may be appropriately modified to suit the area of ​​the PEDOT:PSS electrode to be formed. The method of applying the PEDOT:PSS solution is not limited to spin coating and may use, for example, drop coating or slot-die coating.

[0075] Subsequently, a step (S14) of forming a PEDOT:PSS electrode on the above-mentioned pre-substrate may be performed. The coated PEDOT:PSS solution may be dried to form the PEDOT:PSS electrode. For example, the drying process may be performed by heating the pre-substrate coated with the PEDOT:PSS solution in a hot plate or oven at a temperature of about 50 to 120 degrees Celsius. In some embodiments, an annealing process may be further performed on the pre-substrate coated with the PEDOT:PSS solution at a temperature of about 120 to 200 degrees Celsius to densify the structure of the PEDOT:PSS electrode.

[0076] In one embodiment, the preliminary substrate may be a substrate employed in the biosensor of the present invention. In another embodiment, the preliminary substrate may not be a substrate employed in the biosensor of the present invention, but is a substrate provided simply for the purpose of forming a PEDOT:PSS electrode having a rough surface, and may be separated from and removed from the PEDOT:PSS electrode after the PEDOT:PSS electrode is formed.

[0077] Referring to FIG. 6b, a step (S20) of first preparing a preliminary substrate and applying a PEDOT:PSS solution onto the preliminary substrate may be performed. Similar to that described in FIG. 6a, methods such as spin coating, drop coating, or slot die coating may be used to apply the PEDOT:PSS solution onto the preliminary substrate.

[0078] Subsequently, a step (S22) of forming a PEDOT:PSS electrode on a pre-substrate may be performed. Similar to that described in FIG. 6a, the coated PEDOT:PSS solution may be dried to form a PEDOT:PSS electrode. In some embodiments, the heat treatment process described above may be further performed to densify the structure of the PEDOT:PSS electrode.

[0079] Subsequently, a step (S24) of etching the PEDOT:PSS electrode so that the PEDOT:PSS electrode has a rough surface or deforming the pre-substrate on which the PEDOT:PSS electrode is formed may be performed. Similar to what is described in FIG. 6a, the pre-substrate on which the PEDOT:PSS electrode is formed may be deformed by heating or applying stress according to the physical properties of the constituent material of the pre-substrate to form a PEDOT:PSS electrode having a rough surface.

[0080] Referring to FIG. 6c, a step (S30) of first preparing a preliminary substrate and placing a plurality of nanoparticles on the preliminary substrate may be performed. The nanoparticles are a general term for nano-sized polymer particles, and the polymer particles may include, but are not limited to, polystyrene (PS). The plurality of nanoparticles may be placed by spin coating and may be placed spaced apart from each other.

[0081] Subsequently, a step (S32) of applying a PEDOT:PSS solution onto a pre-substrate on which the plurality of nanoparticles are disposed may be performed. Similar to the description in FIG. 6a, methods such as spin coating, drop coating, or slot die coating may be used to apply the PEDOT:PSS solution onto the pre-substrate.

[0082] Subsequently, a step (S34) of forming a PEDOT:PSS electrode on a pre-substrate on which the plurality of nanoparticles are disposed may be performed. Similar to what is described in FIG. 6a, the coated PEDOT:PSS solution may be dried to form the PEDOT:PSS electrode. In some embodiments, the heat treatment process described above may be further performed to densify the structure of the PEDOT:PSS electrode. Since the PEDOT:PSS electrode is formed on a pre-substrate on which the plurality of spaced-apart nanoparticles are disposed, rather than directly on the pre-substrate, the PEDOT:PSS electrode may have a rough surface.

[0083] FIGS. 7 to 11 are AFM images of PEDOT:PSS electrodes in some embodiments of the present invention.

[0084] Specifically, FIG. 7 is an image of a PEDOT:PSS electrode observed with an atomic force microscope (AFM) after applying stress in the longitudinal direction to a substrate containing polydimethylsiloxane so that it is stretched by about 15% to 20% of its existing horizontal length in one direction (i.e., the strain is about 0.15 to 0.20), then removing the stress to cause shrinkage deformation in the substrate, and then applying a PEDOT:PSS solution onto the substrate by spin coating at 2000 rpm for 60 seconds to form a PEDOT:PSS electrode.

[0085] Referring to FIG. 7, it can be seen that the peak and valley portions of the PEDOT:PSS electrode are arranged alternately in one horizontal direction, and that the peak and valley portions extend in another horizontal direction intersecting the one horizontal direction. Additionally, it can be seen that the vertical height difference between the peak and valley portions is generally constant within approximately 550 nanometers to 750 nanometers, and that the spacing between multiple adjacent peak portions is generally constant within approximately 2 micrometers to 10 micrometers.

[0086] Specifically, FIG. 8 is an image of a PEDOT:PSS electrode observed with an atomic force microscope (AFM) after fixing one side of a substrate containing polystyrene and the other side opposite to said one side, heating the substrate at 130 degrees Celsius for 40 minutes to cause shrinkage deformation, and then applying a PEDOT:PSS solution onto the substrate by spin coating to form a PEDOT:PSS electrode.

[0087] Referring to FIG. 8, it can be seen that the peaks and valleys of the PEDOT:PSS electrode are arranged alternately in both directions. Additionally, it can be seen that the vertical height difference between the peaks and valleys is generally constant within about 100 nanometers to 200 nanometers, and the spacing between multiple adjacent peaks is generally constant within about 4 micrometers to 6 micrometers in one direction and generally constant within about 0.01 micrometers to 1 micrometer in the other direction.

[0088] Specifically, FIG. 9 is an image of a PEDOT:PSS electrode observed with an atomic force microscope (AFM) after a substrate containing polystyrene was heated at 130 degrees Celsius for 40 minutes without fixing either side to cause shrinkage deformation, and then a PEDOT:PSS solution was applied to the substrate by spin coating to form a PEDOT:PSS electrode.

[0089] Referring to Fig. 9, it can be seen that the PEDOT:PSS electrode has a surface that is uneven in all directions, and that peaks and valleys are arranged alternately spaced apart in all directions. It can be seen that the vertical height difference between the peaks and valleys is generally constant within approximately 4 to 20 nanometers. Additionally, it can be seen that the spacing between multiple adjacent peaks is within approximately 1 to 5 micrometers, but that the spacing between multiple adjacent peaks is generally not constant.

[0090] Specifically, FIG. 10 is an image of a substrate containing a wet-oxidized silicon oxide film, which was etched by performing a reactive ion etching (RIE) process with 4 sccm of oxygen (O2) gas and 26 sccm of fluorocarbon (CF4) gas at 100W for 15 minutes, and then a PEDOT:PSS solution was applied by spin coating at 3000 rpm for 60 seconds to form a PEDOT:PSS electrode, and the PEDOT:PSS electrode was observed using an atomic force microscope (AFM).

[0091] Referring to FIG. 10, it can be seen that the PEDOT:PSS electrode has a rough surface and that peaks and valleys are arranged alternately in all directions. It can be seen that the vertical height difference between the peaks and valleys is within approximately 4 to 20 nanometers, but that the vertical height difference between the peaks and valleys is generally not constant. Additionally, it can be seen that the spacing between multiple adjacent peaks is within approximately 0.01 micrometers to 1 micrometer, but that the spacing between multiple adjacent peaks is generally not constant. Furthermore, it can be seen that the area of ​​the peaks and the area of ​​the valleys are relatively small, within 0.01 micrometers to 1 micrometer.

[0092] Specifically, FIG. 11 is an image of a substrate containing a dry-oxidized silicon oxide film, etched by performing an RIE process with 4 sccm of oxygen (O2) gas and 26 sccm of fluorocarbon (CF4) gas at 100W for 9 minutes, and then forming a PEDOT:PSS electrode by spin coating a PEDOT:PSS solution at 3000 rpm for 60 seconds on the etched surface of the substrate, and then observing the PEDOT:PSS electrode with an atomic force microscope (AFM).

[0093] Referring to Fig. 11, it can be seen that the PEDOT:PSS electrode has a rough surface and that peaks and valleys are arranged alternately in all directions. It can be seen that the vertical height difference between the peaks and valleys is within approximately 4 to 20 nanometers, but that the vertical height difference between the peaks and valleys is generally not constant. Additionally, it can be seen that the spacing between adjacent multiple peaks is within approximately 0.01 micrometers to 1 micrometer, but that the spacing between adjacent multiple peaks is generally not constant. Furthermore, it can be seen that the area of ​​the peaks and the area of ​​the valleys are relatively small, within approximately 0.01 micrometers to 1 micrometer.

[0094] When comparing the PEDOT:PSS electrodes of FIGS. 10 and 11 with the PEDOT:PSS electrodes formed in FIGS. 7 to 9, it can be seen that the PEDOT:PSS electrodes of FIGS. 10 and 11 include peaks and valleys with relatively sharp shapes.

[0095] Figures 12a and 12b are the results of sensing samples having different pH concentrations using the biosensor of the present invention.

[0096] Specifically, FIG. 12a is a graph showing the gate voltage of a PEDOT:PSS electrode when formed on a substrate having a flat surface (wherein the substrate contains polystyrene), and FIG. 12b is a graph showing the gate voltage of a PEDOT:PSS electrode when formed on a substrate having a rough surface (wherein the substrate contains polystyrene). The experiments were conducted at room temperature, with Vsd (source-drain voltage) at 0.4V, and the gate voltage was gradually varied from 0V to 0.5V.

[0097] Referring to Figures 12a and 12b together, it can be seen that the difference between the gate voltages of the pH 4 solution, PBS (Phosphate-Buffered Saline, pH 7.4), and pH 8 solution is relatively large compared to Figure 12a in Figure 12b at the same current value. In other words, it can be seen that the biosensor using the PEDOT:PSS electrode with a rough surface has relatively high sensing sensitivity.

[0098] Figures 13a and 13b are the results of sensing samples having different concentrations using the biosensor of the present invention.

[0099] Specifically, FIG. 13a is a graph showing the gate voltage of a PEDOT:PSS electrode when formed on a substrate having a flat surface (wherein the substrate includes silicon), and FIG. 13b is a graph showing the gate voltage of a PEDOT:PSS electrode when formed on a substrate having a rough surface (wherein the substrate includes silicon). The experiments were conducted at room temperature, and Vsd (source-drain voltage) was 0.2V in the experiment where the PEDOT:PSS electrode was formed on a substrate having a flat surface and 0.4V in the experiment where the PEDOT:PSS electrode was formed on a substrate having a rough surface, and the gate voltage was gradually changed from 0V to 1V.

[0100] Referring to Figures 13a and 13b together, it can be seen that compared to Figure 13a, the difference between the gate voltages of a solution diluted 1 / 10 times the standard PBS concentration (e.g., 100 mM) (0.1XPBS), a PBS solution of the standard PBS concentration (1XPBS), and a solution concentrated 10 times more than the standard PBS concentration (10XPBS) at the same current value in Figure 13b is relatively large. In other words, it can be seen that the biosensor using a PEDOT:PSS electrode with a rough surface has relatively high sensing sensitivity.

[0101] As described above, exemplary embodiments have been disclosed in the drawings and specification. Although specific terms have been used to describe the embodiments in this specification, they are used only for the purpose of explaining the technical concept of this disclosure and are not intended to limit the meaning or the scope of this disclosure as defined in the claims. Therefore, those skilled in the art will understand that various modifications and equivalent alternative embodiments are possible therefrom. Accordingly, the true technical scope of protection of this disclosure should be determined by the technical concept of the appended claims.

Claims

1. A substrate extending in a first horizontal direction and a second horizontal direction intersecting each other; Source electrode and drain electrode spaced apart from each other on the substrate; A PEDOT:PSS layer electrically connected to the source electrode and the drain electrode and comprising PEDOT:PSS(poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)); A probe disposed on the above PEDOT:PSS layer and capable of binding to a target substance to be detected; and It includes a linker that combines the above probe and the above PEDOT:PSS layer, The above PEDOT:PSS layer is a biosensor comprising a peak portion and a valley portion having a height difference in the vertical direction on the upper surface of the substrate.

2. In Paragraph 1, The above peak portion and the above valley portion are alternately arranged along the first horizontal direction in a biosensor.

3. In Paragraph 1, The above peak portion and the above valley portion are alternately arranged along the first horizontal direction and the second horizontal direction in a biosensor.

4. In Paragraph 1, The above-mentioned valley portion includes a first valley portion disposed on one side of the peak portion and a second valley portion disposed on the other side of the peak portion, and The first valley portion and the second valley portion are spaced apart from each other in the first horizontal direction with the peak portion in between, The above peak portion, the above first valley portion, and the above second valley portion are biosensors extending in the above second horizontal direction.

5. In Paragraph 4, The above PEDOT:PSS layer has a first inclined surface extending from the peak portion to the first valley portion and a second inclined surface extending from the peak portion to the second valley portion, The first inclined surface and the second inclined surface are biosensors facing each other in the second horizontal direction with the peak portion in between.

6. In Paragraph 1, The above PEDOT:PSS layer has an inclined surface extending from the peak portion to the valley portion, and The above inclined surface is a biosensor that surrounds the peak portion in the first horizontal direction and the second horizontal direction.

7. In Paragraph 1, A biosensor in which the height difference between the peak portion and the valley portion is in the range of 0.1 nanometers to 10 micrometers.

8. In Paragraph 1, The probe is DNA comprising a second nucleotide sequence capable of binding complementarily to a first nucleotide sequence of the target substance, and The above linker is a biosensor containing a PASE (pyrenebutanoic acid succinimidyl ester) molecule.

9. In Paragraph 1, The above substrate is a biosensor comprising any one of polydimethylsiloxane (PDMS), polystyrene (PS), silicon, and silicon oxide.

10. A step of forming a PEDOT:PSS layer having a rough surface on a substrate, and a step of forming a source electrode and a drain electrode electrically connected to the PEDOT:PSS layer, comprising The step of forming the above PEDOT:PSS layer is, A step of applying a PEDOT:PSS solution onto the surface of the plasma-treated substrate; and A method for manufacturing a biosensor comprising the step of drying the above PEDOT:PSS solution.

11. In Paragraph 10, The above PEDOT:PSS solution is a method for manufacturing a biosensor containing PASE (pyrenebutanoic acid succinimidyl ester).

12. In Paragraph 10, Prior to the step of applying the above PEDOT:PSS solution, A method for manufacturing a biosensor, further comprising the step of etching, heating, or deforming the substrate to have a rough surface.

13. In Paragraph 10, After the step of drying the above PEDOT:PSS solution, A method for manufacturing a biosensor, further comprising the step of etching the PEDOT:PSS layer so that the PEDOT:PSS layer has a rough surface, or heating or applying force to deform the substrate on which the PEDOT:PSS layer is formed.

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