Base molecule detection substrate design method based on two-dimensional transition metal sulfide

Abstract

The invention belongs to the field of biosensing, and particularly relates to a base molecule detection substrate design method based on two-dimensional transition metal sulfide. Constructing a crystal structure model of the candidate two-dimensional single-layer transition metal sulfide MS2 as a substrate model; placing the four base molecules on the substrate model in a configuration parallel to the surface of the substrate, and constructing an adsorption system model; calculating based on a first principle, respectively optimizing the structures of the substrate model and each adsorption system model, and calculating the total energy of each adsorption system; calculating the adsorption energy of the substrate model to each base molecule, and further calculating the sample standard deviation of the adsorption energy of the substrate model to the four base molecules; based on the adsorption energy, calculating the recovery time of desorption of the base molecules from the surface of the substrate model at the set temperature; the NbS2 disclosed by the invention has relatively high sensitivity and distinction degree on detection of base molecules, and is a DNA (Deoxyribonucleic Acid) sequencing and biosensing material with a prospect.

Description

Technical Field

[0001] This invention belongs to the field of biosensing, specifically a method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides. Background Technology

[0002] DNA sequencing technology is one of the core technologies in life sciences, medical diagnostics (such as early cancer screening and genetic disease detection), and pathogen detection. High sensitivity and high resolution detection of base molecules (adenine A, cytosine C, guanine G, and thymine T) are key steps in DNA sequencing.

[0003] In existing technologies, two-dimensional transition metal sulfides (such as WS2 and MoS2) have been attempted for the adsorption and detection of base molecules due to their excellent electronic properties and surface active sites, but the following core problems exist: 1. Insufficient sensitivity and discrimination: The intrinsic monolayers WS2 and MoS2 have small absolute adsorption energies for the four base molecules (WS2 adsorption energy is only -0.11 to -0.20 eV) and low standard deviation of adsorption energy (WS2 standard deviation is only 0.0477), making it impossible to effectively distinguish different bases; 2. Challenges in doping technology: Although non-metallic atomic doping can improve detection performance, precise single-atom doping is difficult to achieve in experiments, which prevents related theoretical research from being implemented. 3. Poor reusability: The adsorption of base molecules on most substrates is either too strong or too weak, making desorption difficult (affecting reuse) or desorption too fast (making stable detection impossible). 4. Low adaptability to real-time sequencing: Existing substrates cannot achieve rapid desorption and cyclic detection of base molecules while ensuring detection accuracy, making it difficult to meet the needs of real-time DNA sequencing.

[0004] Furthermore, the base adsorption characteristics of a large number of intrinsic two-dimensional transition metal sulfides (such as CrS2, NbS2, and TaS2) have not been systematically studied, and their potential high detection performance remains untapped. Therefore, there is an urgent need to develop a base molecule detection substrate that is free from complex doping, highly sensitive, has good discrimination, is reusable, and is compatible with real-time sequencing. Summary of the Invention

[0005] In order to overcome the shortcomings of the prior art, at least one technical problem raised in the background art is solved.

[0006] The technical solution adopted by this invention to solve its technical problem is: the design method for a base molecule detection substrate based on two-dimensional transition metal sulfides, as described in this invention, includes the following steps: S1. Construct a crystal structure model of the candidate two-dimensional monolayer transition metal sulfide MS2 as a substrate model, where M is a transition metal element; S2. Place four base molecules, including adenine (A), cytosine (C), guanine (G), and thymine (T), on the substrate model in a configuration parallel to the substrate surface to construct an adsorption system model; S3. Optimize the structure of the substrate model and each of the adsorption system models based on first-principles calculations, and calculate the total energy of each adsorption system; S4. Calculate the adsorption energy of the substrate model for each base molecule based on the calculation results of step S3, and further calculate the sample standard deviation of its adsorption energy for the four base molecules; S5. Calculate the recovery time of the base molecules desorbed from the surface of the substrate model at a set temperature based on the adsorption energy; S6. Select materials that meet the preset sensitivity, discrimination, and reusability requirements from the candidate MS2 materials based on the adsorption energy, adsorption energy standard deviation, and recovery time, as the design scheme for the base molecule detection substrate.

[0007] As a further technical solution of the present invention: in step S1, the transition metal element M includes at least one of niobium (Nb), chromium (Cr), tantalum (Ta) and tungsten (W); the MS2 is a 2H phase structure.

[0008] As a further technical solution of the present invention: In step S2, the base molecule is placed parallel to the center of the six-membered ring of the substrate model with its large six-membered ring composed of carbon atoms and nitrogen atoms.

[0009] As a further technical solution of the present invention: In step S3, the PBE functional based on the generalized gradient approximation is used for structure optimization and energy calculation, and the SCAN+rVV10 functional or HSE06 hybrid functional is used to correct van der Waals interactions and improve the accuracy of band structure calculation; a vacuum layer is set in the direction perpendicular to the substrate model during the calculation.

[0010] As a further technical solution of the present invention: In step S4, the formula for calculating the adsorption energy of four base molecules adsorbed by two-dimensional monolayers CrS2, NbS2, TaS2 and WS2 is as follows: Formula (3-1) Among them, E sub+nuc E represents the total energy of base molecules adsorbed on the substrate. sub and E nuc represents the total energy of the substrate and the base molecules, respectively, and n represents the number of expanded cells in the substrate when constructing the adsorption model; θ represents the sample standard deviation of the adsorption energy of different base molecules on the same substrate, which is used to measure the material's ability to distinguish base molecules. The calculation formula is as follows: Formula (3-2) Among them, E ai Ea represents the adsorption energy of the four bases on the same substrate, where i = 1, 2, 3, 4 correspond to bases A, C, G, and T, respectively, and Ea represents the average adsorption energy of the four bases on the substrate.

[0011] As a further technical solution of the present invention: In step S5, the recovery time is introduced to evaluate the reusability of the substrate, which is calculated by the Van't-Hoff-Arrhenius formula: Formula (3-3) Where ω is the pre-factor, related to the vibrational frequency. T is the temperature, in Keltzmann constant. There is a negative correlation between recovery time and adsorption energy.

[0012] As a further technical solution of the present invention: in step S6, the screening criteria include: the absolute value of the adsorption energy of the four base molecules is greater than 0.18 eV, the standard deviation of the adsorption energy is greater than 0.26, and the recovery time at 400K temperature is less than 1 second.

[0013] As a further technical solution of the present invention: the substrate material for base molecule detection screened by the design method is a two-dimensional monolayer NbS2, CrS2 or TaS2.

[0014] As a further technical solution of the present invention, it also includes step S7: calculating the changes in electronic transport properties of the selected substrate material before and after adsorption of different base molecules; the electronic transport properties include electrical conductivity and electronic thermal conductivity; the changes include numerical changes, characteristic peak shifts or disappearances.

[0015] As a further technical solution of the present invention, it also includes step S8: calculating the changes in the ultraviolet-visible absorption spectral characteristics of the selected substrate material before and after adsorption of different base molecules; the changes include changes in the position, intensity or number of absorption peaks.

[0016] The beneficial effects of this invention are as follows: This invention discloses the microscopic interaction mechanism between two-dimensional monolayer transition metal sulfides and base molecules. CrS2, NbS2, and TaS2 exhibit stronger sensitivity and discrimination than WS2 in adsorbing base molecules. WS2 adsorbs A and G, reducing the band gap of the system. The four two-dimensional monolayer transition metal sulfides physically adsorb base molecules via van der Waals forces, maintaining the structural integrity of both the substrate material and the base molecules after adsorption. At 400 K, base molecules can desorb from the substrate surface within 1 second.

[0017] The adsorption of base molecules in this invention alters the values ​​and peak positions of the electrical conductivity and electronic thermal conductivity of the two-dimensional monolayer transition metal sulfide system. TaS2 and WS2 exhibit different electronic transport properties when adsorbing different base molecules, while CrS2 and NbS2 show similar electronic transport curves. After base molecule adsorption, the molar absorptivity, absorption peak positions, and number of absorption peaks in the UV-Vis absorption spectra of the NbS2, TaS2, and WS2 systems change, allowing for the identification and differentiation of the adsorption of different base molecules.

[0018] Based on the above analysis, the adsorption energy of the NbS2 adsorption system exhibits a large absolute value and standard deviation, and its electronic transport properties and light absorption characteristics show significant differences. Therefore, NbS2 possesses high sensitivity and discriminative power for the detection of base molecules, making it a promising material for DNA sequencing and biosensing. Attached Figure Description

[0019] The invention will now be further described with reference to the accompanying drawings.

[0020] Figure 1 This invention relates to the structure and parameters of a two-dimensional monolayer MS2 (M = Cr, Nb, Ta, W). (a) From top to bottom, the structure is shown in a top view, a side view, and the atom types corresponding to different colors. The measured bond angles are marked in the side view. (b) The lattice parameters, bond lengths, and bond angles of the monolayer MS2; Figure 2 These are the band structures of four two-dimensional monolayer MS2 materials of this invention. (a), (b), (c), and (d) represent the band structures of CrS2, NbS2, TaS2, and WS2, respectively. (e) VBM, CBM, and band gap under the GGA-PBE and HSE06 functionals; Figure 3 This is the optimal structural diagram of the adsorption of four base molecules by four two-dimensional monolayer transition metal sulfides according to the present invention. From top to bottom, they represent the adsorption configurations of CrS2, NbS2, TaS2, and WS2. From left to right, they represent the structures of adsorbed bases A, C, G, and T. For each adsorption system, the upper half is a top view and the lower half is a side view. The pink dashed lines represent the van der Waals forces between the base molecules and the two-dimensional monolayer MS2. Figure 4 The electronic properties of four two-dimensional monolayer transition metal sulfides adsorbed with base molecules are shown in this invention. (a) Adsorption energy and standard deviation of adsorption energy and (b) Recovery time at 300 K and 400 K; Figure 5 This is a graph showing the electrical conductivity of monolayer MoS2 and WS2 as a function of chemical potential. (a) and (b) show the calculated results for monolayer MoS2 and the results reported in the literature, respectively. (c) and (d) show the calculated results for monolayer WS2, respectively. ] ; Figure 6 The present invention describes the (a) electrical conductivity and (b) electronic thermal conductivity of four two-dimensional monolayer transition metal sulfides before and after adsorption of base molecules under the same chemical potential.

[0021] Figure 7 These are the ultraviolet-visible absorption spectra of the four base molecules of this invention; Figure 8 The UV-Vis spectra of (a) CrS2, (b) NbS2, (c) TaS2, and (d) WS2 substrates and the adsorbed four base molecules are shown. The inset in (d) shows the UV-Vis spectrum of WS2 from 430 nm to 530 nm. Figure 9 This invention relates to a base adsorption differentiation strategy based on ultraviolet-visible absorption spectroscopy for NbS2 (top), TaS2 (middle), and WS2 (bottom). Detailed Implementation

[0022] To make the technical means, creative features, objectives and effects of this invention easier to understand, the invention will be further described below in conjunction with specific embodiments.

[0023] Example 1 like Figures 1 to 2 As shown in the embodiment of the present invention, the method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides includes the following steps: Based on the 2H phase WS2 crystal structure (a = b = 3.18 Å), two-dimensional monolayer CrS2, NbS2, TaS2 and WS2 models with 4×4×1 supercells were constructed as detection substrates by replacing the transition metal elements in the same group.

[0024] For two-dimensional materials, parallel-placed base molecules exhibit better adsorption performance than vertically placed base molecules. Therefore, optimized base molecules were placed parallel to each other in the middle of the substrate. A 20 Å vacuum layer was set along the c-axis direction of all structures, i.e., the direction perpendicular to the layer, to ensure the independence of the monolayer structure.

[0025] This invention utilizes VASP software to perform structural optimization and property calculations for four monolayer transition metal sulfides and their adsorbed four base molecules. Geometric optimization and self-consistent calculations are performed using PBE exchange-correlated functionals and projected annealed plane-wave pseudopotentials under GGA. The cutoff energy is set to 520 eV. For the Brillouin zone, the substrate and adsorption model are sampled using k-point Monkhorst-Pack grids of 12×12×1 and 2×2×1, respectively. The convergence criterion for self-consistent iteration is an energy below 1×10⁻⁶ eV. -5The residual force is less than 0.05 eV / Å. The HSE06 hybrid functional is used to improve the accuracy of band structure calculations. The SCAN+rVV10 functional correction is used to introduce kinetic energy density and van der Waals forces. The density of states of the two-dimensional monolayer transition metal sulfide and its adsorption system are calculated to investigate the effect of base molecule adsorption on the electronic properties of the system. Based on the carrier concentration obtained from the density of states calculation, the electronic transport properties of the adsorption system are calculated using the BoltzTrap2 code. For each input point, six irreducible k-points are interpolated, and the system temperature is set to 300 K to calculate the electrical conductivity and electronic thermal conductivity of the system. Using CP2K and Multiwfn software, the excitation energies of the excited states are calculated based on time-dependent density functional theory, and the UV-Vis spectra of the two-dimensional monolayer transition metal sulfide and its adsorbed different base molecules are simulated. The PBE functional is used, the plane wave truncation grid is set to 350 Ry, the convergence accuracy of the self-consistent calculation is 1×10⁻⁶ Hartree, and the maximum number of iterations is 128. The new charge density is mixed with the old charge density at a ratio of 40% and used as the input density for the next iteration. When calculating the excited-state properties, the convergence criterion for all excitation energies is 1 × 10⁻⁴ Hartree, and the number of excited states calculated is 400.

[0026] The formulas for calculating the adsorption energies of four base molecules adsorbed by two-dimensional monolayers CrS2, NbS2, TaS2, and WS2 are as follows: Formula (3-1) Among them, E sub+nuc E represents the total energy of base molecules adsorbed on the substrate. sub and E nuc θ represents the total energy of the substrate and the base molecules, respectively, where n represents the number of expanded cells in the substrate when constructing the adsorption model. θ represents the sample standard deviation of the adsorption energy of different base molecules on the same substrate, used to measure the material's ability to distinguish base molecules; the calculation formula is as follows: Formula (3-2) Among them, E ai The adsorption energies of the four bases on the same substrate are represented by i = 1, 2, 3, 4, corresponding to bases A, C, G, and T, respectively. Ea ​​represents the average adsorption energy of the four bases on the substrate. Recovery time is introduced to assess the reusability of the substrate, calculated using the Van't-Hoff-Arrhenius formula. Formula (3-3) Where ω is the pre-factor, related to the vibrational frequency. T is the temperature, in Keltzmann constant. There is a negative correlation between recovery time and adsorption energy.

[0027] like Figure 1As shown in (a), the two-dimensional monolayer MS2 (M = Cr, Nb, Ta, W) has a hexagonal structure and belongs to The space group has lattice constants a = b, α = β = 90°, and γ = 120°. Figure 1 (b) shows their lattice constants, MS bond lengths, and SMS bond angles, with specific values ​​corresponding to Table 1. The structural optimization results of this invention (lattice constants a for CrS2, NbS2, TaS2, and WS2 are 3.04 Å, 3.35 Å, 3.34 Å, and 3.19 Å, respectively) are very close to previous calculated studies (lattice constants a for 3.04 Å, 3.35 Å, 3.30 Å, and 3.18 Å, respectively) and experimental studies (lattice constants a for 3.04 Å, 3.32 Å, 3.33 Å, and 3.16 Å, respectively).

[0028] Table 1. Lattice parameters, bond lengths, and bond angles of two-dimensional monolayer MS2 materials.

[0029] The band structures of four two-dimensional monolayer transition metal sulfide materials under three functional calculations are as follows: Figure 2 As shown, the band gaps calculated by the GGA-PBE functional (CrS2, NbS2, TaS2, and WS2 are 0.93 eV, 0 eV, 0 eV, and 1.81 eV, respectively) are close to those calculated by the GGA-PBE functional (CrS2, NbS2, TaS2, and WS2 are 0.93 eV, 0 eV, 0 eV, and 1.85 eV, respectively). The band structure calculated by the Generalized Gradient Approximation (GGA) functional underestimates the band gap of the material. Therefore, the SCAN+rVV10 and HSE06 functionals are introduced. Figure 2(e) shows the calculated valence band maximum (VBM) and conduction band minimum (CBM) positions, along with their corresponding band gap values, for four materials using the GGA-PBE and HSE06 functionals. Compared to the GGA-PBE results, the SCAN+rVV10 and HSE06 calculations increase the band gap but do not alter the band structure characteristics. The bands of two-dimensional NbS2 and two-dimensional TaS2, calculated using the three functionals, cross the Fermi level, resulting in a zero band gap. Under the HSE06 functional, two-dimensional CrS2 is an indirect bandgap semiconductor with a band gap of 1.33 eV. WS2 is a direct bandgap semiconductor, with both the valence band maximum and conduction band minimum located at point K, and a band gap of 2.30 eV. The band gap values ​​calculated by the HSE06 functional (1.33 eV, 0 eV, 0 eV, and 2.30 eV for CrS2, NbS2, TaS2, and WS2, respectively) are close to the experimental values ​​(1.33 eV, 0 eV, 0 eV, and 2 eV for CrS2, NbS2, TaS2, and WS2, respectively).

[0030] Example 2 The adsorption configurations of four two-dimensional monolayer transition metal sulfides for the adsorption of base molecules A, C, G, and T are as follows: Figure 3 As shown, the pink dashed lines depict the van der Waals forces between the base molecules and the monolayer disulfide. All four base molecules are adsorbed parallel to each other on the two-dimensional monolayer MS2 surface. The large six-membered rings of the base molecules, composed of carbon and nitrogen atoms, are close to the six-membered rings of the MS2 substrate, composed of M and S atoms. After adsorption by TaS2 and WS2, the changes in the positions of atoms and the molecular structure in the system are relatively small, indicating weak adsorption. When CrS2 adsorbs cytosine (C) and guanine (G), the structure of the base molecules changes significantly. The O atom of cytosine shifts downwards by 0.01 Å, perpendicular to the Cr atom on the substrate. This may be because Cr has low electronegativity and readily attracts the more electronegative O atom. The H atom at the guanine end shifts downwards by 0.22 Å, adsorbing perpendicularly above the S atom. After NbS2 adsorbs G, the H atom at the guanine end shifts downwards by 0.14 Å, approaching the more electronegative Nb atom. Furthermore, the van der Waals forces between the four monolayer disulfides and A and G are strong, while their adsorption of T is weak. In most adsorption systems, the atom that is perpendicular to the substrate plane and closest to the base molecule is the H atom. This is because the S atom has a higher electronegativity and attracts the H atom, which is more prone to losing electrons, causing the H atom to move towards the substrate. In other cases, the atom that is perpendicular to the substrate plane and closest to the base molecule is the O, N, or C atom, in which case these atoms are perpendicular to the M atom of the substrate. The M atom exhibits a positive charge and easily attracts the more electronegative O, N, and C atoms, thus reducing the distance between them. For example, as... Figure 3As shown in the first row and second column, when cytosine is adsorbed on the CrS2 substrate, the O atom is closest to the CrS2 plane, and at this time the O atom is adsorbed vertically above the Cr atom.

[0031] The adsorption energies and recovery times of four base molecules adsorbed by two-dimensional monolayer transition metal sulfides are shown in Table 2. E a (eV) and θ These represent the adsorption energy and standard deviation of the base molecules adsorbed on the substrate, respectively. Based on transition state theory, we set... The recovery time of adsorbed base molecules on each substrate at 300 K and 400 K was obtained using formula (3-3). . Figure 4 The differences in adsorption energy and recovery time of base molecules adsorbed by two-dimensional monolayer transition metal sulfides were demonstrated.

[0032] Table 2 Adsorption energies and standard deviations of base molecules adsorbed in two-dimensional monolayer MS2, and recovery times at 300 K and 400 K.

[0033] From Table 2 and Figure 4 (a) It can be seen that the adsorption energies of WS2 for bases A, C, G, and T are only -0.20 eV, -0.20 eV, -0.14 eV, and -0.11 eV, respectively, with a standard deviation of only 0.0477, indicating that WS2 has poor sensitivity and discrimination for base molecules. The other three substrate materials have lower adsorption energies and higher standard deviations for base molecules, and their adsorption performance is better than WS2. Among them, CrS2 and NbS2 have adsorption energy standard deviations of 0.28 and 0.31, respectively, and have the highest adsorption sensitivity and discrimination for base molecules. The absolute values ​​of the adsorption energies of WS2 are in the order of C>A>G>T, while the absolute values ​​of the adsorption energies of CrS2, NbS2, and TaS2 are in the order of G>A>C>T. In addition, the recovery time reflects the time required for base molecules to desorb from the substrate surface. At 300 K, the recovery time of the substrate is relatively long, especially for CrS2 and NbS2 when adsorbing base G, which require 2.46 × 10⁻⁶ eV, respectively. 2 s and 7.11×10 6 Desorption was completed in s. Increasing the temperature to 400 K reduced the desorption time to 3.50 × 10⁻⁶. -2 s and 7.74×10 -1 The data shows that increasing the temperature can significantly accelerate the desorption process. At 400 K, all base molecules can desorb from the surfaces of four two-dimensional monolayer transition metal sulfides within 1 second, which makes real-time DNA sequencing possible.

[0034] The partial density of states (PDOS) before and after the adsorption of four base molecules on four two-dimensional substrates were presented. The PDOS of all adsorption systems was primarily contributed by the two-dimensional monolayer transition metal sulfides, with the conduction band mainly contributed by the d orbitals of the transition metal atoms, and the p orbitals of the S atoms also contributing. The contributions of the H, C, N, and O atoms of the base molecules to the conduction band were negligible. For NbS2 and TaS2, the d orbitals of Nb / Ta atoms and the p orbitals of S atoms crossed the Fermi level. The p orbitals of N and O atoms of the base molecules contributed to the [-1, 0] eV range, and the p orbitals of C atoms contributed slightly near 0 eV. Therefore, the band gap of NbS2 and TaS2 was 0. After the adsorption of base molecules, the PDOS of the d orbitals of Nb / Ta atoms and the p orbitals of S atoms changed very little on NbS2 and TaS2. In the semiconductor systems CrS2 and WS2, the valence band near the Fermi level is occupied by the d orbitals of Cr / W atoms and the p orbitals of S atoms. Base molecules contribute to the band gap in the range [-2, -1] eV, primarily provided by the p orbitals of N and O atoms. After CrS2 adsorbs base molecules, the density of states (DSO) of the Cr atom near the CBM increases. After the adsorption of C, G, and T base molecules, the d orbitals of the Cr atom split into two DSO peaks in the range [1, 1.5] eV. The p orbitals of the S atom show a new DSO peak near 2 eV, while the DSO peak near -2 eV weakens. Within the range [2.3, 3] eV, a new DSO peak appears in the adsorption system, composed of both the d orbitals of Cr and the p orbitals of S. When WS2 adsorbs base molecules A and G, the CBM shifts to lower energies, and the band gap of the system decreases by 0.25 eV and 0.57 eV, respectively. In the WS2 adsorption system, the p orbitals of C and N atoms hybridize with the d orbitals of W and the p orbitals of S atoms at a distance of [3.5, 4.0] eV. Except for the WS2-A and WS2-G systems, the adsorption of base molecules does not affect the positions of the VBM and CBM.

[0035] In summary, the two-dimensional monolayer transition metal sulfides physically adsorb base molecules via van der Waals forces, without disrupting the structure of the substrate or base molecules. The adsorption of base molecules A and G by WS2 reduced the band gap of the system by 0.25 eV and 0.57 eV, respectively. The adsorption of base molecules did not alter the positions of the CBM and VBM in the other adsorption systems. Furthermore, the adsorption system exhibits a short recovery time; base molecules can desorb within 1 second at 400 K, enabling real-time sequencing. The adsorption energies of CrS2, NbS2, and TaS2 are superior to those of WS2, which has been previously reported, with CrS2 and NbS2 showing particularly significant improvements in adsorption sensitivity and discriminability for base molecules.

[0036] Example 3 First, the conductivity of monolayer MoS2 and monolayer WS2 at 300 K was calculated. Figure 5 As shown, (a) and (c) are the conductivity results of MoS2 and WS2 calculated in this paper, respectively, and (b) and (d) are the conductivity calculation results of MoS2 and WS2.

[0037] At room temperature (300 K), the electrical and electronic thermal conductivity of four monolayer transition metal sulfide substrates and their adsorption systems varied with chemical potential. After CrS2 adsorbed base molecules, the electrical and electronic thermal conductivity values ​​of the system decreased significantly, while the peak positions remained unchanged. The electrical and thermal conductivity curves of the four base molecule adsorption systems were similar. NbS2 adsorbed base molecules slightly reduced the electrical and electronic thermal conductivity of the system, with the portion below 1 eV shifting to lower energy directions by approximately 0.25 eV. The shift distance was greatest when G was adsorbed, indicating that G adsorption had the greatest impact on the system, consistent with the adsorption energy analysis. The electrical and thermal conductivity peaks near 2 eV and 2.7 eV disappeared with the adsorption of base molecules. When TaS2 adsorbed T, the electrical and electronic thermal conductivity of the system increased, while the corresponding values ​​decreased when A, C, and G were adsorbed. After NbS2 and TaS2 adsorbed base molecules, the electrical and electronic thermal conductivity peaks near 0.8 eV of the substrate disappeared. The adsorption of base molecules by WS2 causes the conductivity and conductivity peaks of the system to shift to lower energy directions, with the shift distance from largest to smallest being G>A>C ≈ T.

[0038] The chemical potentials corresponding to the conductivity peaks and electronic thermal conductivity peaks closest to the Fermi level in the valence band of the substrate were selected. The conductivity and electronic thermal conductivity values ​​of the substrate and the adsorbed four base molecules were compared at the selected chemical potentials. The results are as follows: Figure 6 As shown, differences exist in the electronic transport properties of the substrates and the four base molecule adsorption systems, reflecting the influence of base molecule adsorption on the values ​​or positions of the conductivity and thermal conductivity peaks. Base molecule adsorption significantly reduces the conductivity and electronic thermal conductivity of the CrS2 system, resulting in significantly higher values ​​for the CrS2 substrate at the same chemical potential compared to the adsorbed systems. Base molecule adsorption causes the disappearance of the conductivity and electronic thermal conductivity peaks near 0.8 eV, thus the values ​​for the NbS2 and TaS2 substrates are significantly higher than those for the adsorbed systems. The difference in conductivity and thermal conductivity values ​​in the WS2 system is due to the shift of the curves towards lower chemical potentials. Among these, at the same chemical potential, the value of G adsorption in WS2 is significantly lower than in the other systems, indicating that G adsorption causes the greatest shift in the electronic transport curve.

[0039] In summary, the adsorption of base molecules alters the electronic transport properties of the two-dimensional monolayer transition metal sulfide system, including changes in electrical conductivity and electronic thermal conductivity values, curve shifts, and the disappearance of peak values.

[0040] Example 4 The UV-Vis absorption spectra of four base molecules were calculated to verify the reliability of the calculations. The results are as follows: Figure 3-7 As shown. The absorption peaks of the base molecules are concentrated in the deep ultraviolet region of 150 nm - 250 nm. It should be noted that the experimentally measured absorption peaks of the base molecules in the gas phase are concentrated in the near ultraviolet region of 250 nm - 300 nm. The difference between the calculated results and the experimental results may be due to residual intermolecular interactions in the experimental samples. Purines are composed of pentagonal and hexagonal heterocycles, while pyrimidines are composed of a single hexagonal heterocycle. Hexagonal heterocycles are formed by alternating single and double bonds, forming a conjugated system. π electrons move in the conjugated system, resulting in the existence of π electrons in the base molecules. Leap forward. The transition requires relatively little energy, the absorption wavelength is in the near-ultraviolet region, and the molar absorptivity is generally greater than 100%. This is consistent with the UV-Vis absorption spectrum of the base molecules that we calculated.

[0041] The UV-Vis absorption spectra of four two-dimensional monolayer transition metal sulfide substrates and their base adsorption systems were calculated, as follows: Figure 8 As shown. Figure 8 Images (a), (b), (c), and (d) show the UV-Vis absorption spectra of CrS2, NbS2, TaS2, and WS2, respectively. Figure 8 The illustration in (d) shows the weak absorption peaks of A, C, G, and T adsorbed by WS2 in the wavelength range of 430 nm to 530 nm. All four materials exhibit absorption peaks in the visible light range (390 nm to 800 nm). The absorption peaks of the CrS2 substrate are located at 557 nm, 576 nm, 644 nm, and 739 nm. The positions of the absorption peaks did not change after the adsorption of base molecules. The adsorption of A, C, and G caused the molar absorptivity of the absorption peak at 557 nm to decrease from [previous value]. Reduced to approximately However, the absorption peak positions and intensities of the A, C, and G adsorption systems are similar, making them difficult to distinguish. After NbS2 adsorbs base molecules A and G, the wavelengths of the absorption peaks at 626 nm and 686 nm on the substrate decrease to 616 nm and 681 nm, and 613 nm and 673 nm, respectively. After adsorbing C and T, the wavelengths of the absorption peak at 626 nm on the substrate increase to 635 nm and 634 nm, respectively, and the intensity of the absorption peak at 689 nm for adsorbed C increases significantly, forming an absorption band from 635 nm to 689 nm. Furthermore, the adsorption of base molecules A, G, and T significantly increases the molar absorptivity of the system, with the order G > A ≈ C. TaS2 and its adsorption system exhibit multiple absorption peaks in the visible light range, and the molar absorptivity of the adsorption system increases significantly. The TaS2 substrate exhibits the strongest absorption peak at 656 nm. When adsorbing base molecule C, TaS2 exhibits two absorption peaks of similar intensity at 584 nm and 616 nm. When adsorbing base molecules A, G, and T, the strongest absorption peaks in the system are located at 570 nm, 556 nm, and 604 nm, respectively. According to the verification procedure of JJG 178—2007 "Ultraviolet, Visible, and Near-Infrared Spectrophotometers", the maximum allowable wavelength error for spectrophotometers in the 340 nm to 2600 nm range is 6 nm. Therefore, the adsorption behavior of TaS2 on the four base molecules can be identified and distinguished by the number and position of the strongest absorption peaks. The absorption peak of WS2 is located at 400 nm, which is an optical transition between the valence band and the conduction band density of states peaks, slightly lower than the experimental results (~450 nm). This difference may be due to residual intermolecular interactions in the experimental samples. The absorption peaks of WS2 adsorbing the four base molecules are strongest below 420 nm, but the intensity and position are similar. Above 420 nm, WS2 adsorbs A, C, and T with absorption peaks at 518 nm, 492 nm, and 442 nm, respectively. The WS2 adsorbed G exhibits two absorption peaks of similar intensity at 440 nm and 504 nm.

[0042] Based on the above analysis, the adsorption behavior of base molecules on NbS2 and TaS2 surfaces can be identified by the increase in molar absorptivity, while the adsorption behavior on WS2 surfaces can be identified by the appearance of weak absorption peaks above 420 nm. Combining the number, position, and molar absorptivity of the absorption peaks, the adsorption behavior of different base molecules can be distinguished. Figure 9 The strategies for distinguishing the adsorption of different base molecules by UV-Vis spectroscopy for NbS2, TaS2, and WS2 are summarized.

[0043] By comprehensively applying density functional theory, Boltzmann transport theory, and time-dependent density functional theory, this study investigated the adsorption configurations, electronic properties, electronic transport properties, and UV-Vis absorption spectra of four two-dimensional monolayer transition metal sulfides (CrS2, NbS2, TaS2, and WS2) for the adsorption of four base molecules (A, C, G, and T). The potential of CrS2, NbS2, TaS2, and WS2 for base molecule detection and real-time DNA sequencing was explored.

[0044] Technical principle: This invention uses specific two-dimensional transition metal sulfides (NbS2, CrS2, TaS2) as detection substrates and combines them with electrical or optical detection methods to achieve highly sensitive, highly distinguishable, and reversible detection of DNA base molecules. It has broad application prospects in the field of next-generation DNA sequencing technology and biosensors.

[0045] The foregoing has shown and described the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the invention. Various changes and modifications can be made to the invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed. The scope of protection of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides, characterized in that: Includes the following steps: S1. Construct a crystal structure model of the candidate two-dimensional monolayer transition metal sulfide MS2 as a substrate model, where M is a transition metal element; S2. Place four base molecules, including adenine (A), cytosine (C), guanine (G), and thymine (T), on the substrate model in configurations parallel to the substrate surface to construct adsorption system models; S3. Optimize the structure of the substrate model and each adsorption system model based on first-principles calculations, and calculate the total energy of each adsorption system; S4. Calculate the adsorption energy of the substrate model for each base molecule based on the calculation results of step S3, and further calculate the sample standard deviation of its adsorption energy for the four base molecules; S5. Calculate the recovery time of base molecules desorbing from the substrate model surface at a set temperature based on the adsorption energy; S6. Select materials from the candidate MS2 materials that meet the preset sensitivity, discrimination, and reusability requirements as the design scheme for the base molecule detection substrate based on the adsorption energy, adsorption energy standard deviation, and recovery time.

2. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 1, characterized in that: In step S1, the transition metal element M includes at least one of niobium (Nb), chromium (Cr), tantalum (Ta), and tungsten (W); MS2 has a 2H phase structure.

3. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 2, characterized in that: In step S2, the base molecules are placed parallel to the center of the six-membered ring of the substrate model, with the large six-membered ring composed of carbon and nitrogen atoms close to it.

4. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 3, characterized in that: In step S3, the PBE functional based on the generalized gradient approximation is used for structure optimization and energy calculation, and the SCAN+rVV10 functional or HSE06 hybrid functional is used to correct van der Waals interactions and improve the accuracy of band structure calculation. A vacuum layer is set in a direction perpendicular to the substrate model during the calculation.

5. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 4, characterized in that: In step S4, the adsorption energies for the four base molecules adsorbed by the two-dimensional monolayers CrS2, NbS2, TaS2, and WS2 are calculated using the following formulas: Official (3-1) Among them, E sub+nuc E represents the total energy of base molecules adsorbed on the substrate. sub and E nuc represents the total energy of the substrate and the base molecules, respectively, and n represents the number of expanded cells in the substrate when constructing the adsorption model; θ represents the sample standard deviation of the adsorption energy of different base molecules on the same substrate, which is used to measure the material's ability to distinguish base molecules. The calculation formula is as follows: Official (3-2) Among them, E ai Ea represents the adsorption energy of the four bases on the same substrate, where i = 1, 2, 3, 4 correspond to bases A, C, G, and T, respectively, and Ea represents the average adsorption energy of the four bases on the substrate.

6. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 5, characterized in that: In step S5, the recovery time is introduced to evaluate the reusability of the substrate, calculated using the Van't-Hoff-Arrhenius formula: Official (3-3) Where ω is the pre-factor, related to the vibrational frequency. T is the temperature, in Keltzmann constant. There is a negative correlation between recovery time and adsorption energy.

7. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 6, characterized in that: In step S6, the screening criteria include: the absolute value of the adsorption energy for all four base molecules is greater than 0.18 eV, the standard deviation of the adsorption energy is greater than 0.26, and the recovery time at 400K is less than 1 second.

8. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 7, characterized in that: The substrate materials selected by the design method for base molecule detection are two-dimensional monolayer NbS2, CrS2, or TaS2.

9. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 1, characterized in that: It also includes step S7: calculating the changes in electronic transport properties of the selected substrate material before and after adsorption of different base molecules; electronic transport properties include electrical conductivity and electronic thermal conductivity; changes include numerical changes, shifts in characteristic peaks, or disappearances.

10. The method for designing a base molecule detection substrate based on two-dimensional transition metal sulfides according to claim 9, characterized in that: It also includes step S8: calculating the changes in the UV-Vis absorption spectral characteristics of the selected substrate material before and after adsorption of different base molecules; the changes include changes in the position, intensity or number of absorption peaks.

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