Biosensor including corrugated semiconductor or semi-metal material and manufacturing method thereof

WO2025048258A1PCT designated stage expired Publication Date: 2025-03-06G-MEDICS KOREA CO LTD
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Patent Information

Application Number
PCT/KR2024/010280
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-08-28
Filing Date
2024-07-17
Publication Date
2025-03-06

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Abstract

A biosensor according to the present invention comprises: a substrate extending in a first horizontal direction and a second horizontal direction intersecting the first horizontal direction; a source electrode and a drain electrode spaced apart from each other on the substrate: a corrugated semiconductor (or semi-metal) channel which is disposed between the source electrode and the drain electrode and has peak portions and valley portions having a height difference in the vertical direction on the upper surface of the substrate; a probe which is disposed on the corrugated semiconductor (or semi-metal) channel and capable of chemically bonding to a target material to be detected; a linker molecule coupling the probe and the corrugated semiconductor (or semi-metal) channel; a gate electrode for electrically controlling the corrugated semiconductor (or semi-metal) channel; and a gate dielectric film between the corrugated semiconductor (or semi-metal) channel and the gate electrode, wherein the peak portions and the valley portions are alternately arranged in a zigzag pattern along a diagonal direction between the first horizontal direction and the second horizontal direction.
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Description

Biosensor comprising a wrinkled semiconductor or semi-metal material and method for manufacturing the same

[0001] The technical field of the present invention relates to biosensors, and more particularly, to a biosensor including a wrinkled semiconductor (or semi-metal) material and a method for manufacturing the same.

[0002] The recent COVID-19 pandemic has dramatically increased the need for rapid and accurate sensors for detecting biological substances such as DNA and RNA. While a variety of optical, mechanical, and electrical sensors have been developed to detect biological substances, most sensors have required extensive preprocessing to increase the concentration of the substance of interest within the solution. In particular, for patient samples such as cancer cells, viruses, and antibodies, the number of times samples can be extracted from a patient is limited, resulting in significantly smaller sample volumes. Furthermore, detection of target substances requires lengthy and complex preprocessing.

[0003] Among sensors utilizing various methods, sensors utilizing electrical methods have been extensively studied recently due to their high sensitivity without the need for pretreatment to increase the concentration of the target substance in the solution. When detecting a target substance using electrical methods, the target substance's charge can be masked by the charge of ions other than the target substance in the solution, so stable detection is possible only when the target substance is close to the sensor surface. In other words, target substances can be detected only when they are within the sensor's Debye length. Therefore, increasing the sensor's Debye length can increase the sensor's sensitivity from Debye shielding, and is a key challenge in the industry.

[0004] A biosensor according to the technical idea of ​​the present invention comprises: a substrate extending in a first horizontal direction and a second horizontal direction intersecting the first horizontal direction; a source electrode and a drain electrode spaced apart from each other on the substrate; a corrugated semiconductor (or semi-metal) channel disposed between the source electrode and the drain electrode and having a peak portion and a valley portion having a height difference in a vertical direction with respect to an upper surface of the substrate; a probe disposed on the corrugated semiconductor (or semi-metal) channel and capable of chemically bonding to a target substance to be detected; a linker molecule connecting the probe to the corrugated semiconductor (or semi-metal) channel; a gate electrode electrically controlling the corrugated semiconductor (or semi-metal) channel; and a gate dielectric film between the corrugated semiconductor (or semi-metal) channel and the gate electrode; wherein the peak portions and the valley portions are alternately arranged in a zigzag shape along a diagonal direction between the first horizontal direction and the second horizontal direction.

[0005] In exemplary embodiments, the wrinkled semiconductor (or semi-metal) channel is characterized by being a transition metal dichalcogenide material.

[0006] In exemplary embodiments, the wrinkled semiconductor (or semimetal) channel is characterized by being molybdenum disulfide (MoS2) or tungsten disulfide (WS2).

[0007] In exemplary embodiments, the wrinkled semiconductor (or semi-metal) channel is characterized by having a wrinkled nanosheet shape.

[0008] In exemplary embodiments, the wrinkled semiconductor (or semi-metal) channel is characterized by having a structure in which the wrinkled nanosheet shapes are laminated in multiple layers.

[0009] In exemplary embodiments, the probe is characterized by being any one selected from among DNA having a nucleotide sequence complementary to the nucleotide sequence of the target substance, an aptamer (DNA having a specific binding ability to a specific substance), and an IL-6 antibody.

[0010] In exemplary embodiments, when the probe is the DNA, the linker molecule is characterized by comprising a PASE (Pyrenebutanoic Acid Succinimidyl Ester) molecule.

[0011] A biosensor according to the technical idea of ​​the present invention comprises the steps of: preparing a substrate; forming a corrugated semiconductor (or semi-metal) channel including peaks and valleys having a height difference in a vertical direction on the substrate; and connecting a linker molecule to the corrugated semiconductor (or semi-metal) channel and connecting a probe capable of chemically bonding to a target substance to be detected to the linker molecule; wherein the step of forming the corrugated semiconductor (or semi-metal) channel comprises the steps of: forming a preliminary semiconductor (or semi-metal) channel on the substrate; and heating the substrate to contract and deform the preliminary semiconductor (or semi-metal) channel.

[0012] In exemplary embodiments, in the step of forming the wrinkled semiconductor (or semi-metal) channel, the final length in the direction in which the wrinkled semiconductor (or semi-metal) channel extends is formed in a range of 30% to 90% of the preliminary length in the direction in which the preliminary semiconductor (or semi-metal) channel extends.

[0013] In exemplary embodiments, in the step of forming the wrinkled semiconductor (or semi-metal) channel, the final length is characterized in that it is formed to be 45% of the preliminary length.

[0014] According to the technical idea of ​​the present invention, a biosensor using a FET transistor including a wrinkled semiconductor (or semi-metal) material has a Debye length of a wrinkled semiconductor (or semi-metal) channel that is longer than a Debye length of a flat semiconductor (or semi-metal) channel, and thus ultimately has the effect of providing a biosensor with improved sensitivity to a target substance.

[0015] In addition, since the surface area of ​​the wrinkled semiconductor (or semi-metal) channel is larger than that of the flat semiconductor (or semi-metal) channel, the wrinkled semiconductor (or semi-metal) channel can bind to more probes, which has the effect of providing a biosensor with improved sensitivity to a target substance.

[0016] Furthermore, in terms of the binding force between the linker molecule connecting the semiconductor (or semimetal) channel and the probe and the semiconductor (or semimetal) channel, the binding force between the wrinkled semiconductor (or semimetal) channel and the linker molecule is greater than the binding force between the flat semiconductor (or semimetal) channel and the linker molecule, so there is an effect of providing a biosensor with improved structural stability.

[0017] FIG. 1 is a schematic cross-sectional view illustrating the structure of a biosensor according to one embodiment of the present invention.

[0018] FIGS. 2A and 2B are perspective views illustrating a wrinkled semiconductor (or semi-metal) channel included in a biosensor according to one embodiment of the present invention.

[0019] Figure 3 is an enlarged view of the R1 region of the wrinkled semiconductor (or semi-metal) channel of Figure 2a.

[0020] FIG. 4 is a drawing for explaining a method for manufacturing a wrinkled semiconductor (or semi-metal) channel included in a biosensor according to one embodiment of the present invention.

[0021] FIGS. 5A to 5C are graphs illustrating the number of linker molecules bound to a wrinkled semiconductor (or semi-metal) channel included in a biosensor according to one embodiment of the present invention.

[0022] 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 designated by the same reference numerals, and redundant descriptions thereof will be omitted.

[0023] The biosensor according to 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, development and manufacturing of new drugs, etc. by analyzing biomolecules contained in a sample.

[0024] Biosensors employ probes tailored to the target sample being analyzed. Probes that can be used in biosensors include, for example, DNA probes, enzymes, antibodies / antigens, protein probes such as bacteriorhodopsin, microbial probes, and neuronal probes.

[0025] Biosensors manufactured in chip form are also referred to as biochips. For example, depending on the type of probe employed, they can be referred to as DNA chips, protein chips, cell chips, or neuron chips.

[0026] In some embodiments, the biosensor may include an oligomeric probe as a probe. The term "oligomeric probe" implies that the number of monomers employed in the probe is at the oligomeric level. Here, the term "oligomer" may be used to refer to a polymer composed of two or more covalently bonded monomers, having a molecular weight of about 1000 or less.

[0027] The monomers that make up the oligomeric probe can be modified depending on the type of biological sample to be analyzed, and can be, for example, nucleosides, nucleotides, amino acids, peptides, etc. Nucleosides and nucleotides can include not only the known purine and pyrimidine bases, but also methylated purines or pyrimidines, acylated purines or pyrimidines, etc. Furthermore, nucleosides and nucleotides can include not only the known ribose and deoxyribose sugars, but also modified sugars in which one or more hydroxyl groups are substituted with a halogen atom or an aliphatic group, or functional groups such as ethers or amines are bonded. Amino acids can be L-, D-, and achiral amino acids found in nature, as well as modified amino acids, amino acid analogs, etc. Peptides refer to compounds formed by an amide bond between the carboxyl group of an amino acid and the amino group of another amino acid.

[0028] In the embodiments of the present invention, the probe exemplarily assumed is a DNA probe, 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 goes without saying that various probes described above can be applied.

[0029] FIG. 1 is a schematic cross-sectional view illustrating the structure of a biosensor according to one embodiment of the present invention.

[0030] Referring to FIG. 1, the biosensor (100) may include a substrate (110), a gate electrode (112), a wiring structure (114), a gate dielectric film (116), a source electrode (120), a drain electrode (122), and a corrugated semiconductor (or semi-metal) channel (124).

[0031] The substrate (110) may have an upper surface extending 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 be orthogonal to each other. The direction perpendicular to the upper surface of the substrate (110) may be defined as a vertical direction (Z direction).

[0032] The substrate (110) may include a material capable of causing shrinkage deformation so that the wrinkled semiconductor (or semi-metal) channels (124) disposed on the upper surface of the substrate (110) have a wrinkled shape. The substrate (110) may include a material that causes shrinkage deformation, particularly at high temperatures. For example, the substrate (110) may include a thermoplastic polymer that causes shrinkage deformation at about 100°C to 200°C.

[0033] Suitable polymers for use in the present invention include, for example, one or a combination of polystyrene (PS), polyetherimide (PEI), polyethersulfone (PES), polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), and liquid crystal polymers.

[0034] For example, when a substrate (110) including polystyrene is annealed at about 110° C. to 115° C. for about 10 to 120 minutes, wrinkles may be formed in the wrinkled semiconductor (or semi-metal) channel (124) in a range of several micrometers to several hundred nanometers.

[0035] The substrate (110) may exhibit a degree of shrinkage deformation that varies depending on the annealing temperature. For example, the substrate (110) may exhibit a greater degree of shrinkage deformation as the annealing temperature increases. In addition, the substrate (110) may exhibit a degree of shrinkage deformation that varies depending on the annealing time. For example, the substrate (110) may exhibit a greater degree of shrinkage deformation as the annealing time increases.

[0036] A source electrode (120) and a drain electrode (122) may be disposed on a substrate (110). The source electrode (120) and the drain electrode (122) may be disposed to be spaced apart from each other in a first horizontal direction (X direction). The source electrode (120) and the drain electrode (122) may be formed of various materials. For example, each of 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 an alloy thereof. However, in terms of ease of contact with the material forming the wrinkled semiconductor (or semi-metal) channel (124) and etching, it is preferable that each of the source electrode (120) and the drain electrode (122) be made of gold (Au) or a chromium / gold (Cr / Au) alloy.

[0037] Between the source electrode (120) and the drain electrode (122), a wrinkled semiconductor (or semimetal) channel (124) including a transition metal dichalcogenide material may be interposed. The wrinkled semiconductor (or semimetal) channel (124) may extend in a first horizontal direction (X direction) on the substrate (110). However, the wrinkled semiconductor (or semimetal) channel (124) 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 the vertical direction (Z direction) on the upper surface of the substrate (110).

[0038] In this specification, a specific description of the structure of the wrinkled semiconductor (or semimetal) channel (124) is provided later in the description of FIGS. 2A and 2B. The degree to which the wrinkled semiconductor (or semimetal) channel (124) is wrinkled may vary depending on the temperature and time of the annealing process described above.

[0039] A sample (126) in contact with a wrinkled semiconductor (or semi-metal) channel (124) may contain a target material. The target material may include a protein, DNA, RNA, or any base sequence, and the sample (126) may include fragments containing the target material, a biological solution such as blood, saliva, etc.

[0040] The sample (126) may be placed in a sample storage container (130). The sample storage container (130) may be a container for containing the sample (126) and may be made of a polymeric or non-polymeric material. In some embodiments, rubber may be used as the sample storage container (130). The shape and size of the sample storage container (130) are not limited to those shown in the drawing.

[0041] The corrugated semiconductor (or semi-metal) channel (124) can be electrically controlled by a gate electrode (112). The gate electrode (112) can include a conductive metal material. The gate electrode (112) can be connected to a power source through a wiring structure (114) and can receive a gate voltage. A gate dielectric film (116) can be positioned between the corrugated semiconductor (or semi-metal) channel (124) and the gate electrode (112).

[0042] By observing the electrical parameters of the wrinkled semiconductor (or semi-metal) channel (124), the presence or absence of a target material within the sample (126) can be determined. At this time, changes in the electrical parameters may correspond to the presence of the target material. For example, the electrical parameters may be expressed as capacitance, voltage, average current, etc.

[0043] The biosensor (100) may further include a probe (128) capable of chemically binding to a target substance molecule. The probe (128) may be placed on a corrugated semiconductor (or semi-metal) channel (124). For example, the probe (128) may be any one of DNA, peptide nucleic acid (PNA), aptamer, protein, antibody, and capture agent. For example, when 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.

[0044] The biosensor (100) may further include a linker molecule (129) to facilitate chemical bonding between the probe (128) and the corrugated semiconductor (or semimetal) channel (124). The linker molecule (129) may be disposed on the corrugated semiconductor (or semimetal) channel (124). Specifically, the corrugated semiconductor (or semimetal) channel (124) binds to the linker molecule (129), and the probe (128) may be bound to the corrugated semiconductor (or semimetal) channel (124) via the linker molecule (129). In some embodiments, when the target substance is DNA, a PASE (Pyrenebutanoic acid succinimidyl ester) molecule of the following [Chemical Formula 1] may be selected as the linker molecule (129).

[0045] [Chemical Formula 1]

[0046]

[0047] The pyrene group in the PASE molecule can bind to a folded semiconductor (or semimetal) channel (124), and the succinimidyl ester group in the PASE molecule can bind to a 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. The binding of the pyrene group in the PASE molecule to the folded semiconductor (or semimetal) channel (124) may be a π-π bond among van der Waals bonds.

[0048] FIGS. 2A and 2B are perspective views illustrating a wrinkled semiconductor (or semi-metal) channel included in a biosensor according to one embodiment of the present invention.

[0049] Referring to FIGS. 2A and 2B together, the wrinkled semiconductor (or semi-metal) channel (124) may include a peak portion (P) and a valley portion (V) having a height difference in the vertical direction (Z direction).

[0050] The wrinkled semiconductor (or semi-metal) channel (124) may have various wrinkled shapes. In some embodiments, as shown in FIG. 2a, the peaks (P) and valleys (V) of the wrinkled semiconductor (or semi-metal) channel (124) may be alternately arranged in a zigzag pattern along the first horizontal direction (X direction). In other embodiments, as shown in FIG. 2b, the peaks (P) and valleys (V) of the wrinkled semiconductor (or semi-metal) channel (124) may be alternately arranged in a zigzag pattern in a diagonal direction between the first horizontal direction (X direction) and the second horizontal direction (Y direction). However, the wrinkled shape of the wrinkled semiconductor (or semi-metal) channel (124) is not limited to that illustrated.

[0051] The interval between the peaks (P) and the valleys (V) of the wrinkled semiconductor (or semi-metal) channel (124) may vary. In some embodiments, the peaks (P) may be arranged to be spaced apart at a first constant interval (W1) in a range of about 1 nanometer to 10 nanometers along the first horizontal direction (X direction). The valleys (V) may be arranged to be spaced apart at a second constant interval (W2) in a range of about 1 nanometer to 10 nanometers along the first horizontal direction (X direction). In other embodiments, the peaks (P) and the valleys (V) may be arranged to be spaced apart at non-constant intervals along the first horizontal direction (X direction). As the degree of wrinkles in the wrinkled semiconductor (or semi-metal) channel (124) increases, the interval between the peaks (P) and the valleys (V) along the first horizontal direction (X direction) may decrease.

[0052] In some embodiments, the height difference in the vertical direction (Z direction) between adjacent peaks (P) and valleys (V) of the corrugated semiconductor (or semi-metal) channel (124) may be constant within a range of about 0.2 nanometers to 20 nanometers. In other embodiments, the height difference in the vertical direction (Z direction) between adjacent peaks (P) and valleys (V) of the corrugated semiconductor (or semi-metal) channel (124) may not be constant.

[0053] A valley portion (V) may be arranged between adjacent peak portions (P) of a wrinkled semiconductor (or semi-metal) channel (124), and a peak portion (P) may be arranged between adjacent valley portions (V). The shapes of the peak portions (P) and valley portions (V) of the wrinkled semiconductor (or semi-metal) channel (124) are not limited to those illustrated.

[0054] In some embodiments, for the first valley portion (V1) and the second valley portion (V2), which are valley portions (V) adjacent to the peak portion (P) of the wrinkled semiconductor (or semi-metal) channel (124), the slope of the first intermediate region (COL1) from the first valley portion (V1) to the peak portion (P) and the slope of the second intermediate region (COL2) from the second valley portion (V2) to the peak portion (P) may be different from each other.

[0055] In other embodiments, for the first valley portion (V1) and the second valley portion (V2), which are valley portions (V) adjacent to the peak portion (P) of the corrugated semiconductor (or semi-metal) channel (124), the slope of the first intermediate region (COL1) from the first valley portion (V1) to the peak portion (P) and the slope of the second intermediate region (COL2) from the second valley portion (V2) to the peak portion (P) may be the same. In this case, the first intermediate region (COL1) from the first valley portion (V1) to the peak portion (P) and the second intermediate region (COL2) from the second valley portion (V2) to the peak portion (P) may be symmetrical with respect to the peak portion (P). However, the structure of the corrugated semiconductor (or semi-metal) channel (124) is not limited thereto.

[0056] The wrinkled semiconductor (or semi-metal) channel (124) may have a thickness in the range of about 1 nanometer to 2 nanometers and a surface area in the range of about 1 square millimeter to 100 square millimeters.

[0057] In addition, the number of material layers constituting the wrinkled semiconductor (or semimetal) channel (124) is not limited to that illustrated. The wrinkled semiconductor (or semimetal) channel (124) may be composed of a plurality of nanosheets. The wrinkled semiconductor (or semimetal) channel (124) may be composed of a first nanosheet and a second nanosheet disposed on the first nanosheet. The first nanosheet and the second nanosheet may have the same or different shapes. For example, the first nanosheet may have a smaller separation distance between adjacent peak portions (P) than the second nanosheet.

[0058] Additionally, atoms included in the plurality of nanosheets constituting the wrinkled semiconductor (or semi-metal) channel (124) may be arranged in a vertical direction (Z direction) in a straight line or in an offset direction. In some embodiments, atoms constituting the first nanosheet and atoms constituting the second nanosheet may be arranged in a vertical direction (Z direction). In other embodiments, atoms constituting the first nanosheet and atoms constituting the second nanosheet may be arranged in an offset direction in the vertical direction (Z direction).

[0059] A target material can be directly or indirectly attached to the wrinkled semiconductor (or semi-metal) channel (124), and the presence or absence of the target material in the sample (126) can be determined by changing the electrical parameters when the target material is attached to the wrinkled semiconductor (or semi-metal) channel (124).

[0060] When detecting a target substance using a corrugated semiconductor (or semi-metal) channel (124) according to the present invention, the Debye length between the target substance and the corrugated semiconductor (or semi-metal) channel (124) may be longer than when using a typical flat semiconductor (or semi-metal) channel. Therefore, when using the corrugated semiconductor (or semi-metal) channel (124) according to the present invention, sensitivity to the target substance may be improved despite the Debye shielding effect compared to when using a flat semiconductor (or semi-metal) channel. Accordingly, a biosensor (100) with improved sensitivity to the target substance may be provided.

[0061] In addition, the wrinkled semiconductor (or semi-metal) channel (124) according to the present invention has a larger surface area than a flat semiconductor (or semi-metal) channel, so it can bind to more probes, which may be advantageous for detecting a target substance.

[0062] In addition, since the equilibrium state energy (unit: eV) of the wrinkled semiconductor (or semimetal) channel (124) according to the present invention is relatively lower than the equilibrium state energy of a flat semiconductor (or semimetal) channel, the stability of the atoms constituting it can be further increased. Accordingly, the biosensor (100) including the wrinkled semiconductor (or semimetal) channel (124) according to the present invention can have improved structural stability due to an increased binding force between the wrinkled semiconductor (or semimetal) channel (124) and the linker molecule (129).

[0063] The wrinkled semiconductor (or semimetal) channel (124) according to the present invention may be a transition metal dichalcogenide material, for example, may be composed of molybdenum disulfide (MoS2) or tungsten disulfide (WS2).

[0064] Specifically, transition metal dichalcogenide materials have the structural formula MX2 (where M is a transition metal and X is a chalcogen element). The transition metal disulfide exhibits diamagnetic properties, insolubility in solvents, and semiconductor (or semimetal) properties. In addition, research results have been published that show that molybdenum disulfide (MoS2) and tungsten disulfide (WS2) can be used in transistors as semiconductors (or semimetals).

[0065] In addition, the structure of the above transition metal dichalcogenide material is a layered structure similar to graphene, and the interlayer spacing is several angstroms, for example, in the range of about 5 Å to 9 Å, and is composed of strong covalent bonds and weak van der Waals forces. In this way, the above transition metal dichalcogenide having the properties of a semiconductor (or a semimetal) has the characteristic that the properties of a semiconductor (or a semimetal) can vary depending on the number of layers due to the quantum confinement effect.

[0066] Figure 3 is an enlarged view of the R1 region of the wrinkled semiconductor (or semi-metal) channel of Figure 2a.

[0067] Referring to FIG. 3, an intermediate region (COL) is defined between the peak portion (P) and the valley portion (V) of the wrinkled semiconductor (or semi-metal) channel (124).

[0068] A first distance (d1) in the vertical direction (Z direction) from a center line (A-A') crossing the middle region (COL) of the corrugated semiconductor (or semi-metal) channel (124) to the peak portion (P) may be several nanometers. A second distance (d2) in the vertical direction (Z direction) from a center line (A-A') crossing the middle region (COL) of the corrugated semiconductor (or semi-metal) channel (124) to the valley portion (V) may be equal to the first distance (d1).

[0069] FIG. 4 is a drawing for explaining a method for manufacturing a wrinkled semiconductor (or semi-metal) channel included in a biosensor according to one embodiment of the present invention.

[0070] Referring to FIG. 4, first, a preliminary semiconductor (or semi-metal) channel (P124) can be formed on a base substrate (B110).

[0071] The preliminary semiconductor (or semi-metal) channel (P124) can be formed by depositing the atoms that constitute it on a base substrate (B110) using a chemical vapor deposition (CVD) process.

[0072] Next, a protective film (134) may be formed on the preliminary semiconductor (or semi-metal) channel (P124). In some embodiments, the protective film (134) may include a polymer such as an acrylic resin. In some embodiments, the protective film (134) may be formed by spin coating. Specifically, a small amount of liquid for forming the protective film (134) may be dropped on the preliminary semiconductor (or semi-metal) channel (P124), and then the base substrate (B110) may be rotated. Due to the rotation of the base substrate (B110), the small amount of liquid may spread to the edge of the preliminary semiconductor (or semi-metal) channel (P124), thereby forming a protective film (134) that coats the preliminary semiconductor (or semi-metal) channel (P124).

[0073] Next, the base substrate (B110) can be removed from the preliminary semiconductor (or semi-metal) channel (P124). In some embodiments, the base substrate (B110) can be removed using a chemical etching method.

[0074] Next, a substrate (110) can be attached to the lower portion of the preliminary semiconductor (or semi-metal) channel (P124). Plasma treatment can be performed on the upper portion of the substrate (110) to bond the substrate (110) and the preliminary semiconductor (or semi-metal) channel (P124) on which the protective film (134) is formed.

[0075] Next, after bonding the preliminary semiconductor (or semi-metal) channel (P124) to the substrate (110), the protective film (134) on the preliminary semiconductor (or semi-metal) channel (P124) can be removed. In some embodiments, when the protective film (134) includes an acrylic resin, the protective film (134) can be removed using acetic acid (CH3COOH) and ultrapure water.

[0076] Next, the substrate (110) having the preliminary semiconductor (or semi-metal) channel (P124) bonded thereto may be annealed. For example, the annealing process may be performed at a temperature ranging from about 110°C to 120°C, and for a period ranging from about 10 minutes to 120 minutes. Depending on the shrinkage deformation of the substrate (110) due to the annealing process, the preliminary semiconductor (or semi-metal) channel (P124) may be transformed into a wrinkled semiconductor (or semi-metal) channel (124). At this time, the final length in the direction in which the wrinkled semiconductor (or semi-metal) channel (124) extends may be formed to be 30% to 90% of the preliminary length in the direction in which the preliminary semiconductor (or semi-metal) channel (P124) extends.

[0077] Depending on the time and / or temperature of the annealing process, the degree to which the wrinkled semiconductor (or semi-metal) channel (124) is wrinkled may vary. In some embodiments, when the substrate (110) to which the preliminary semiconductor (or semi-metal) channel (P124) is bonded is annealed at about 120° C. for about 60 minutes, the final length may be about 1 / 4 of the preliminary length. However, the change in length is not limited thereto.

[0078] As the degree of wrinkles in the wrinkled semiconductor (or semimetal) channel (124) increases, the time consumed in the process for bonding the wrinkled semiconductor (or semimetal) channel (124) and the linker molecule (129) increases. Therefore, it is preferable that the degree of wrinkles in the wrinkled semiconductor (or semimetal) channel (124) is about 55% of the preliminary semiconductor (or semimetal) channel (P124). In other words, it is preferable that the final length is formed to be 45% of the preliminary length, but is not limited thereto.

[0079] Figures 5a to 5c are graphs illustrating the number of linker molecules bound to a wrinkled semiconductor (or semi-metal) channel included in a biosensor according to one embodiment of the present invention. Specifically, Figures 5a to 5c are CV graphs observing current density using the biosensor of the present invention. In addition, Figure 5c is a graph recording the anodic current peak of Figures 5a and 5b.

[0080] Referring to FIGS. 5A to 5C together, line (a) of FIG. 5A represents when voltage is applied to a flat semiconductor (or semimetal) channel, and line (b) of FIG. 5A represents a change in current density when voltage is applied to a flat semiconductor (or semimetal) channel that has undergone PASE processing. In addition, line (a) of FIG. 5B represents when voltage is applied to a wrinkled semiconductor (or semimetal) channel, and line (b) of FIG. 5B represents a change in current density when voltage is applied to a wrinkled semiconductor (or semimetal) channel that has undergone PASE processing.

[0081] Referring to Fig. 5c, the cathode current peak is -0.907 Acm when voltage is applied to the wrinkled semiconductor (or semimetal) channel. -2 In , when a voltage was applied to the wrinkled semiconductor (or semi-metal) channel after PASE processing was completed, -8.185 Acm- 2, while when voltage was applied to a flat semiconductor (or semi-metal) channel, it was -2.671 Acm -2 In , when a voltage was applied to a flat semiconductor (or semi-metal) channel after PASE processing was completed, -5.503 Acm -2 It increased by 29.89%.

[0082] That is, since the increase in the cathode current peak can be attributed to the PASE electron-mediated transport reaction, it can be confirmed that the PASE electron-mediated transport reaction occurs more actively on the wrinkled semiconductor (or semimetal) channel.

[0083] The reason why the change in the cathode current peak from the wrinkled semiconductor (or semimetal) channel to the PASE-treated wrinkled semiconductor (or semimetal) channel is greater than the change in the cathode current peak from the flat semiconductor (or semimetal) channel to the PASE-treated flat semiconductor (or semimetal) channel is that the wrinkled semiconductor (or semimetal) channel has a larger surface area than the flat semiconductor (or semimetal) channel, allowing more PASE molecules to be adsorbed on the nanosheets. Since more PASE molecules are adsorbed on the wrinkled semiconductor (or semimetal) channel, more electron transfer is induced, which can lead to a larger change in the cathode current peak than that of the flat semiconductor (or semimetal) channel.

[0084] Ultimately, when utilizing the wrinkled semiconductor (or semi-metal) channel according to the present invention, a biosensor with improved sensitivity to a target substance can be provided by combining the wrinkled semiconductor (or semi-metal) channel with a large number of linker molecules.

[0085] While the technical concepts of the present invention have been described with reference to the attached drawings, those skilled in the art will appreciate that the present invention can be implemented in other specific forms without altering the technical concepts or essential features thereof. Therefore, the embodiments described above should be understood to be illustrative in all respects and not restrictive.

Claims

1. A substrate extending in a first horizontal direction and a second horizontal direction intersecting the first horizontal direction; A source electrode and a drain electrode spaced apart from each other on the substrate; A wrinkled semiconductor (or semi-metal) channel disposed between the source electrode and the drain electrode and having a peak portion and a valley portion having a height difference in a direction perpendicular to the upper surface of the substrate; A probe disposed on the above-mentioned wrinkled semiconductor (or semi-metal) channel and capable of chemically bonding with a target material to be detected; A linker molecule that connects the probe and the wrinkled semiconductor (or semi-metal) channel; A gate electrode electrically controlling the above-mentioned wrinkled semiconductor (or semi-metal) channel; and a gate dielectric film between the above-mentioned wrinkled semiconductor (or semi-metal) channel and the gate electrode; The peak portion and the valley portion are alternately arranged in a zigzag shape along the diagonal direction between the first horizontal direction and the second horizontal direction. Biosensor.

2. In paragraph 1, A biosensor characterized in that the above-mentioned wrinkled semiconductor (or semi-metal) channel is a transition metal dichalcogenide material.

3. In paragraph 2, A biosensor characterized in that the above-mentioned wrinkled semiconductor (or semi-metal) channel is molybdenum disulfide (MoS2) or tungsten disulfide (WS2).

4. In paragraph 1, A biosensor characterized in that the above-mentioned wrinkled semiconductor (or semi-metal) channel has a wrinkled nanosheet shape.

5. In paragraph 4, A biosensor characterized in that the above wrinkled semiconductor (or semi-metal) channel has a structure in which the above wrinkled nanosheet shape is laminated in multiple layers.

6. In paragraph 1, A biosensor characterized in that the probe is any one selected from among DNA, aptamer, and IL-6 antibody having a nucleotide sequence complementary to the nucleotide sequence of the target substance.

7. In paragraph 6, A biosensor characterized in that when the probe is the DNA, the linker molecule comprises a PASE (Pyrenebutanoic Acid Succinimidyl Ester) molecule.

8. Step for preparing the substrate; A step of forming a wrinkled semiconductor (or semi-metal) channel including a peak portion and a valley portion having a height difference in the vertical direction on the substrate; and A step of connecting a linker molecule to the above-mentioned wrinkled semiconductor (or semi-metal) channel, and connecting a probe capable of chemically bonding to a target substance to be detected to the linker molecule; The step of forming the above wrinkled semiconductor (or semi-metal) channel is: A step of forming a preliminary semiconductor (or semi-metal) channel on the substrate; and a step of heating the substrate to shrink and deform the preliminary semiconductor (or semi-metal) channel; Method for manufacturing a biosensor.

9. In paragraph 8, In the step of forming the above wrinkled semiconductor (or semi-metal) channel, A method for manufacturing a biosensor, characterized in that the final length in the direction in which the above-mentioned wrinkled semiconductor (or semi-metal) channel extends is formed in a range of 30% to 90% of the preliminary length in the direction in which the above-mentioned preliminary semiconductor (or semi-metal) channel extends.

10. In paragraph 9, In the step of forming the above wrinkled semiconductor (or semi-metal) channel, A method for manufacturing a biosensor, characterized in that the final length is formed to be 45% of the preliminary length.

Citation Information

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