A nanopore array detection method for distinguishing different substances by using weighted response mapping
By constructing nanopore arrays with differentiated response characteristics and introducing a weighted response mapping mechanism, the problem of insufficient material differentiation ability in existing technologies is solved, and efficient identification and differentiation of materials with similar structures or properties are achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- GUANGDONG UNIV OF TECH
- Filing Date
- 2026-04-22
- Publication Date
- 2026-07-14
AI Technical Summary
Existing nanopore detection technologies mainly rely on the low-dimensional signal characteristics generated by a single nanopore for discrimination, which makes it difficult to effectively distinguish substances with similar structures or properties, and nanopore arrays fail to make full use of the intrinsic relationships between channels.
A nanopore array with differentiated response characteristics was constructed, and the input of a single analyte was mapped to a multi-channel weighted response through a weighted response mapping mechanism. The differences in response patterns formed by different substances in the nanopore array were used to distinguish them.
It significantly improves the ability to distinguish substances with similar structures or properties, and achieves effective identification of substances that are difficult to distinguish in single-hole detection through multi-dimensional weighted response vectors, thereby enhancing the information expression ability and discrimination performance of the detection system.
Smart Images
Figure CN122385685A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of nanopore sensing and multi-target detection technology, and particularly relates to a nanopore array detection method that uses weighted response mapping to distinguish different substances. Background Technology
[0002] Solid-state nanopore technology, as a single-molecule detection method, detects target analytes by recording the current blocking signals generated when molecules pass through a pore under an electric field. Traditional nanopore detection methods typically rely on a single nanopore, extracting characteristic parameters such as blocking amplitude, duration, or event frequency from the current signal to identify the target analyte. To further improve detection throughput, researchers have proposed nanopore array structures, integrating multiple nanopores for parallel detection, thereby increasing signal acquisition efficiency per unit time. These methods have seen initial applications in fields such as biomolecule detection, drug screening, and environmental monitoring.
[0003] However, existing nanopore detection technologies primarily rely on the low-dimensional signal characteristics generated by a single nanopore for discrimination. When different substances are similar in size, charge, or interfacial interaction properties, their current response distributions within a single pore often overlap significantly, making effective differentiation difficult. Even when using nanopore arrays, current technologies treat each channel merely as an independent, repetitive detection unit, limiting their effectiveness to increasing data acquisition throughput while lacking a systematic utilization of the intrinsic relationships between channel responses. Specifically, existing array outputs remain at the level of simple signal superposition or independent event recording, failing to establish differentiated response weights between different channels and lacking a mechanism to uniformly map a single substance input into a multi-channel overall response pattern. Therefore, how to construct a nanopore array detection method capable of converting different substances into significantly different multi-channel response patterns has become a pressing technical problem to be solved in this field. Summary of the Invention
[0004] The purpose of this invention is to provide a nanopore array detection method that uses weighted response mapping to distinguish different substances, in order to solve the problems of existing nanopore detection technologies that mainly rely on single-pore single-signal features for discrimination, have limited distinguishing dimensions, and are insufficient in distinguishing substances with similar structures or properties.
[0005] To achieve the above objectives, this invention provides a nanopore array detection method for distinguishing different substances using weighted response mapping, comprising: Based on a pre-constructed nanopore array with differentiated response characteristics to the mass transport process, the multi-channel current response signal generated by each nanopore channel when the substance to be tested passes through the nanopore array under the drive of an electric field is obtained. Based on the multi-channel current response signal, the input of a single analyte is mapped to a multi-channel weighted response composed of responses from multiple nanopore channels. Different analytes can be distinguished based on the differences in response patterns formed by the multi-channel weighted response among different substances.
[0006] Preferably, the process of constructing the nanopore array includes: By differentially controlling the surface charge state, interface modification layer, or local interaction capability of each nanopore in the nanopore array, the same analyte can produce different basic responses in different nanopores, and different response weights can be assigned to each nanopore.
[0007] Preferably, the process of obtaining the multi-channel current response signal includes: An electrical signal is applied to both sides of the nanopore array to drive the analyte to pass through each nanopore sequentially or in parallel. The current response signal generated by each nanopore channel is recorded during the process of the analyte passing through the pores. The current response signal includes the waveform of the current changing with time.
[0008] Preferably, the process of mapping the input of a single analyte to a multi-channel weighted response includes: The multi-channel weighted response is represented as a vector form composed of the response signals of each nanopore channel. The response signal of each nanopore channel is used to quantify the response intensity of the channel to the analyte, and the response intensities of different channels together constitute a multi-dimensional response vector.
[0009] Preferably, the process of obtaining the response signal of each nanopore channel includes: For each nanopore, the response weight and the basic response signal generated by the analyte in the nanopore are combined to obtain the final response signal of the nanopore channel.
[0010] Preferably, the response signal of the nanopore channel includes the current blocking amplitude, blocking duration, or a combination of both generated during the transpore process of the analyte, which are used to constitute the basic response signal of each nanopore channel; The basic response signal reflects the original transpore behavior of the analyte in a single nanopore.
[0011] Preferably, the process of determining the response weight corresponding to each nanopore includes: The response weights are set based on one or more interfacial characteristics of the nanopore, such as surface charge density, interfacial binding ability, spatial structure constraint, local hydrophilicity / hydrophobicity, or molecular recognition layer characteristics, and the response weights can be dynamically modulated as the molecular binding state or environmental conditions change.
[0012] Preferably, the distribution characteristics of the multi-channel weighted response on each nanopore channel constitute the weighted response mode corresponding to the analyte. Different analytes form different weighted response modes after weighted response mapping in the nanopore array. The weighted response mode is used to characterize the differential response fingerprint of different substances in the array.
[0013] Preferably, the process of distinguishing different substances includes: The two substances are distinguished by the differences between their multi-channel weighted response vectors. When the weighted response vectors of the two substances have different values in each dimension, the two substances are determined to be different substances.
[0014] Preferably, the process of discriminating based on the differences between weighted response vectors includes: The difference between the weighted response vectors corresponding to two different substances is calculated, and the calculated difference is compared with a pre-set discrimination threshold. When the difference is greater than the discrimination threshold, the two substances are determined to be distinguishable different substances.
[0015] Compared with the prior art, the present invention has the following advantages and technical effects: This invention constructs a nanopore array with differentiated response characteristics and introduces a weighted response mapping mechanism, expanding the low-dimensional response in traditional single-pore detection into an array-level multi-dimensional weighted response vector, thereby significantly improving information representation capabilities. Addressing the issue of overlapping responses in single-pore samples from substances with similar structures or properties, this invention modulates the responses of different channels using differentiated weights, amplifying the distribution differences of different substances in the response space, thus achieving effective identification of substances difficult to distinguish in single-pore detection. Simultaneously, this invention transforms the nanopore array from a simple parallel detection structure into a physical mapping platform with information encoding capabilities, ensuring that the array output is no longer a superposition of isolated signals but forms a stable and discriminative overall response pattern, effectively solving the problem of lacking systematic utilization of multi-channel responses in existing technologies. Attached Figure Description
[0016] The accompanying drawings, which form part of this application, are used to provide a further understanding of this application. The illustrative embodiments and descriptions of this application are used to explain this application and do not constitute an undue limitation of this application. In the drawings: Figure 1 This is a schematic diagram of the method flow according to an embodiment of the present invention; Figure 2 This is a schematic diagram illustrating the differentiation of different substances in the weighted response space according to an embodiment of the present invention. Detailed Implementation
[0017] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other. This application will now be described in detail with reference to the accompanying drawings and embodiments.
[0018] It should be noted that the steps shown in the flowchart in the accompanying drawings can be executed in a computer system such as a set of computer-executable instructions, and although a logical order is shown in the flowchart, in some cases the steps shown or described may be executed in a different order than that shown here.
[0019] This embodiment provides a nanopore array detection method for distinguishing different substances using weighted response mapping, including: Based on a pre-constructed nanopore array with differentiated response characteristics to the mass transport process, the multi-channel current response signal generated by each nanopore channel when the substance to be tested passes through the nanopore array under the drive of an electric field is obtained. Based on the multi-channel current response signal, the input of a single analyte is mapped to a multi-channel weighted response composed of multiple nanopore channel responses. Different analytes can be distinguished based on the differences in response patterns formed by multichannel weighted responses among different substances.
[0020] This embodiment discloses a nanopore array detection method for distinguishing different substances using weighted response mapping. It involves constructing a nanopore array with differential response characteristics; driving the analyte through the nanopore array under an electric field and acquiring multi-channel current response signals; utilizing the differential effect of each nanopore on substance transport, mapping a single substance input into a multi-channel weighted response; different substances forming different weighted response patterns in the nanopore array; and achieving differentiation of different substances based on these weighted response patterns. This embodiment introduces a weighted response mapping mechanism, enabling the nanopore array to form discriminative response patterns during sensing, thereby achieving efficient detection and identification of multiple target substances.
[0021] Furthermore, the process of constructing nanoporous arrays includes: By differentially controlling the surface charge state, interface modification layer, or local interaction capability of each nanopore in the nanopore array, the same analyte can produce different basic responses in different nanopores, and different response weights can be assigned to each nanopore.
[0022] Furthermore, the process of obtaining multi-channel current response signals includes: An electrical signal is applied to both sides of the nanopore array to drive the analyte to pass through each nanopore sequentially or in parallel. The current response signal generated by each nanopore channel is recorded during the process of the analyte passing through the pores. The current response signal includes the waveform of the current changing with time.
[0023] Furthermore, the response signal of the nanopore described in this embodiment includes the current blocking amplitude, duration, or a combination thereof.
[0024] Furthermore, the process of mapping the input of a single analyte to a multi-channel weighted response includes: The multi-channel weighted response is represented as a vector consisting of the response signals of each nanopore channel. The response signal of each nanopore channel is used to quantify the response intensity of the channel to the analyte, and the response intensities of different channels together constitute a multi-dimensional response vector.
[0025] Furthermore, the weighted response described in this embodiment is represented as a vector composed of response signals from multiple nanopore channels: Where x is the substance to be tested. Let be the response of the i-th nanopore.
[0026] The response of each nanopore satisfies the following relationship: in, For the actual response of the i-th nanopore, This represents the fundamental response signal generated by the substance in the i-th nanopore. The response weights correspond to the nanopores. The response weights, determined by the surface charge or interfacial interaction properties of nanopores, are modulated by changes in molecular binding state or environmental conditions. Interfacial properties include one or more of surface charge, interfacial energy, molecular interactions, or spatial confinement.
[0027] The weighted response mode is the distribution characteristic of the weighted response on multiple nanopore channels.
[0028] This is used to characterize the original transpore behavior of the analyte without considering inter-channel modulation differences. The fundamental response can consist of a single signal feature or a combination of multiple signal features. Preferably, the fundamental response can be expressed as: in, Let be the current blocking amplitude in the i-th channel. For the corresponding blocking duration, Let g be the event frequency, and g(...) be a function that combines multiple fundamental signal features into a unified response. In some implementations, the fundamental response can be further simplified to a linear combination form: in, , , These are normalization coefficients or feature weighting coefficients, used to adjust the contribution ratio of different fundamental signal features in the fundamental response. The linear form described above is merely an example; this embodiment is not limited to this and nonlinear combinations can also be used.
[0029] The response weight The physical meaning of is not an abstract mathematical coefficient, but rather the modulation intensity of the interfacial properties of the i-th nanopore regarding the transpore transport behavior of the analyte. The weights are derived from factors such as the surface charge of the nanopore, interfacial interactions, molecular recognition layers, local hydrophilicity / hydrophobicity, or spatial structural confinement. In other words, Used to describe the amplification, suppression, or offsetting effect of different nanopores on the response of the same material. Their weights can be expressed as a function of interface parameters: in, This represents the surface charge density of the i-th nanopore. This indicates parameters related to interface integration or recognition capabilities. Represents local spatial constraint parameters. Indicates other interface modulation parameters, (...) is a function of the response weights of the interface property mapping described above. Therefore, the response of the i-th channel is related not only to the analyte itself but also to the interface modulation capability of that channel. Since different nanopores have different... The responses of the same substance in different channels of the array are no longer equivalent, thus providing a basis for the subsequent formation of distinguishing patterns.
[0030] Further optimize the scheme, weight The setting of this variable is not arbitrary, but rather a core variable that determines the distinguishing ability. For any given set of test substances... Different weight distributions will correspond to different pattern separation effects.
[0031] In one preferred embodiment, the overall distinguishing performance can be expressed as: Where J(W) represents the evaluation function of the overall distinguishability between different substances under the weight matrix W. The larger the value of this function, the higher the degree of separation between different substances in the weighted response space.
[0032] Therefore, this embodiment constructs a nanopore array with an appropriate channel weight distribution to maximize J(W), thereby improving the ability to distinguish different substances. Furthermore, the above description clearly demonstrates that the weights are not secondary parameters, but rather core design variables that determine whether the array has high discriminative power.
[0033] Furthermore, in dynamic weighting scenarios, weights can be represented as functions of time or environmental variables: Where t is time, pH is the ambient acidity / alkalinity, V is the applied bias voltage, and c is the ion concentration. The array response at this time can be expressed as: Dynamic weights allow the same array to form different mapping relationships under different conditions, thereby enhancing its adaptability to complex samples and multi-target scenarios.
[0034] This embodiment introduces response weights by constructing a nanopore array with differential interface properties. A physical mapping relationship is established from the substance to be tested x to the weighted response vector R(x), and the differences in the distribution of different substances in this response space are used to distinguish them.
[0035] Furthermore, the process of obtaining the response signal for each nanopore channel includes: By combining the response weights corresponding to each nanopore and the basic response signal generated by the analyte in the nanopore, the final response signal of the nanopore channel is obtained.
[0036] Furthermore, the response signal of the nanopore channel includes the current blocking amplitude, blocking duration, or a combination of both generated during the transpore process of the analyte, which are used to constitute the basic response signal of each nanopore channel. The basic response signal reflects the original transpore behavior of the analyte in a single nanopore.
[0037] Furthermore, the process of determining the response weight corresponding to each nanopore includes: The response weights are set based on one or more interfacial characteristics of the nanopore, such as surface charge density, interfacial binding ability, spatial structure constraint, local hydrophilicity / hydrophobicity, or molecular recognition layer characteristics, and the response weights can be dynamically modulated as the molecular binding state or environmental conditions change.
[0038] Furthermore, the distribution characteristics of the multi-channel weighted response on each nanopore channel constitute the weighted response mode corresponding to the analyte. Different analytes form different weighted response modes after weighted response mapping in the nanopore array. The weighted response mode is used to characterize the differential response fingerprint of different substances in the array.
[0039] Furthermore, Figure 1 This represents the source of the interfacial properties and response weights of different channels in a nanopore array. For example... Figure 1As shown, different nanopores (2a, 2b, 2c) in the nanopore array possess different interfacial properties, including but not limited to different surface charge states, interfacial modification layers, or local interaction capabilities. Due to the differences in interfacial properties, the transpore transport behavior of the same analyte in different nanopores is modulated differently, resulting in different fundamental responses in each channel and corresponding to different response weights. The response weights are used to characterize the modulation intensity of the transpore transport process of the analyte in each nanopore, and are the physical basis for forming the weighted response map.
[0040] Furthermore, the process of distinguishing different substances includes: The two substances are distinguished by the differences between their multi-channel weighted response vectors. When the weighted response vectors of the two substances have different values in each dimension, the two substances are determined to be different substances.
[0041] Furthermore, in this embodiment, the distinction between different substances is based on the differences between their corresponding weighted responses, satisfying the following: Where R(x) is the weighted response vector of the test substance x.
[0042] When the analyte x enters an array composed of n nanopores, its overall output is no longer determined by a single channel, but by all channels together. This overall response is defined as a weighted response vector: Substituting the single-hole response formula into the equation, we get: Further written as a matrix: in, This is the weight matrix. Let x be the fundamental response vector of the substance to be tested.
[0043] The above formula shows that the "weighted response mapping" in this embodiment is essentially a physical mapping process in which the weight matrix W acts on the basic response vector F(x). This mapping is not assigned by software later, but is naturally formed by the interface structure and channel differences of the nanopore array itself during the transpore transport of molecules. In other words, the array itself assumes the function of an "information encoder".
[0044] Furthermore, a normalized response vector can be defined: Normalization reduces the impact of absolute signal intensity fluctuations, background drift, and concentration changes on the discrimination results, making the discrimination more dependent on the relative response patterns between different channels.
[0045] like Figure 2 The schematic diagram showing the differentiation of different substances in the weighted response space illustrates the technical effect of this embodiment in converting different substances into different response modes through weighted response mapping, thereby achieving differentiation.
[0046] Furthermore, the process of discriminating based on the differences between weighted response vectors includes: The difference between the weighted response vectors corresponding to two different substances is calculated, and the calculated difference is compared with a pre-set discrimination threshold. When the difference is greater than the discrimination threshold, the two substances are determined to be distinguishable different substances.
[0047] Furthermore, for two different substances Because their molecular size, shape, charge distribution, dipole moment, interfacial bonding tendency, transport resistance, and solvation state differ, their fundamental response vectors are generally different, i.e.: Under the influence of the weight matrix W, we can obtain: Typically, there are: This means that different substances will form different weighted response modes in the same nanopore array.
[0048] To quantify the distinguishability between different substances, this embodiment defines a difference degree between response vectors. This embodiment achieves distinction by calculating the difference degree between the weighted response modes corresponding to different substances, whereby the difference degree is defined as: Preferably, the difference is expressed using Euclidean distance. Alternatively, a normalized response difference can be used. when At that time, the judgment Different substances, among which This is a preset threshold.
[0049] or At that time, determine the substance Distinguished, among which and This is a preset threshold.
[0050] To reflect the improvement in discrimination capability brought about by array mapping, the discrimination enhancement factor can be defined as: when A value greater than 1 indicates that the differences between different substances are amplified in the response space after weighted response mapping. This formula explains the advantage of this embodiment over traditional single-hole or unweighted array detection from a mechanistic perspective: this embodiment does not simply collect more signals, but actively enhances the pattern separation between different substances through differentiated weights.
[0051] In this embodiment, the nanopore array is constructed as a physical mapping system with differential modulation capability, so that a single material input is converted into a multi-channel weighted response vector after passing through the array, and the different distributions of the vector in the response space are used to distinguish different materials.
[0052] Example 1 As an optional implementation, this embodiment is used to illustrate the application of the weighted response mapping method described in this embodiment in distinguishing substances with similar properties.
[0053] This embodiment constructs a nanopore array comprising three nanopore channels (denoted as channel 1, channel 2, and channel 3). The geometric dimensions of each nanopore are essentially identical to avoid the dominant influence of pore size differences on the response. By differentially modulating the interfaces of each nanopore, different channels acquire different interfacial properties, thus corresponding to different response weights. Specifically, channel 1 has a higher surface charge density, channel 2 has a lower surface charge density, and channel 3 has an interface modification layer to enhance molecular interactions, thereby forming a nanopore array with differential modulation capabilities.
[0054] During the detection process, an electrical signal is applied to both sides of the nanopore array, causing the analyte to pass through each nanopore channel under the drive of the electric field. The current response signal generated during the passage through the pores is then collected. For each channel, the current blocking amplitude is extracted as the basic response feature, and the basic response of the i-th channel is defined as: in, This represents the current blocking amplitude generated by the substance under test in the i-th nanopore.
[0055] Choose two test substances with similar properties. The two are similar in size or charge characteristics, and the current blocking amplitude distribution generated in a single nanopore overlaps significantly, making them difficult to distinguish using a single-channel signal. A distinction threshold is set at... Through experimental statistics, the average baseline response values (expressed using normalization) of the two substances in each channel were obtained as follows: For matter ,have: For matter ,have: 0.95 Furthermore, the response weights of each channel are set according to the characteristics of the nanopore interface as follows: Based on the weighted response model in this embodiment, the response of the i-th channel satisfies: The weighted responses of the two substances in each channel can then be calculated: For matter ,have Substituting into the difference calculation, we get: because Identifiable substances and They are different substances.
[0056] From a mechanistic perspective, within a single nanopore, the fundamental responses of two substances are similar, resulting in overlapping signal distributions that make them difficult to distinguish. However, in this embodiment, different response weights are introduced through a nanopore array, allowing different channels to modulate the signal differentially. This maps the originally similar fundamental responses into a multi-channel weighted response vector. The distribution of this vector in the response space exhibits significant differences, corresponding to different response modes, thereby enabling the differentiation of substances with similar properties.
[0057] This embodiment demonstrates that by constructing a nanopore array with differentiated response weights and utilizing a weighted response mapping mechanism, substances that are difficult to distinguish in a single channel can be transformed into response modes that are distinguishable in a multi-channel response space, thereby improving the discrimination capability of the detection system.
[0058] Example 2 Based on Example 1, this embodiment further illustrates the weighted response mapping and discrimination capability under multi-feature response conditions.
[0059] This embodiment constructs a nanopore array comprising three nanopore channels, each channel forming a different response weight through interface modulation. The detection method is the same as in Embodiment 1: an electrical signal is applied to both sides of the nanopore array to drive the analyte through each nanopore channel, and the current signal during the transpore process is collected.
[0060] Unlike Example 1, which uses only a single current blocking amplitude as the basic response, this example introduces a multi-feature description method, defining the basic response as a combination of multiple signal features. The basic response of the i-th channel is defined as follows: In this implementation case, =1.0, =0.5, =0.2, set the discrimination threshold as .
[0061] Choose two analytes with similar properties. and Their individual characteristic distributions within a single nanopore overlap significantly, making them difficult to distinguish. Weights are set for each channel: The basic signal characteristics (normalized representation) of each channel were obtained through experimental statistics as follows: for As shown in Table 1: Table 1 for As shown in Table 2: Table 2 The degree of difference is: because Identifiable substances and They are different substances.
[0062] Under single-feature conditions, the responses of different substances in a single pore are prone to overlap, making it difficult to distinguish them. This embodiment introduces a combination of multiple features to extend the basic response into a multi-dimensional information expression, thereby improving the ability to characterize molecular behavior.
[0063] Based on this, the response weights of different channels are further modulated to amplify or suppress multi-feature information in different channels, thereby forming a weighted response vector with higher resolution.
[0064] Therefore, this embodiment not only utilizes the channel differences of the nanopore array, but also utilizes the fusion of multiple feature information to achieve an improvement from "single feature detection" to "multi-feature + multi-channel mapping", thereby further enhancing the ability to distinguish substances with similar properties.
[0065] Example 3 Based on Examples 1 and 2, this embodiment further illustrates the weighted response mapping and material discrimination capability under dynamic weighting conditions.
[0066] This embodiment constructs a nanopore array comprising three nanopore channels, each channel exhibiting different initial response characteristics through interface modulation. Unlike previous embodiments, the response weights of each channel in this embodiment are not fixed constants but can be modulated according to changes in external conditions, thereby forming a dynamic weighted response mapping mechanism. A discrimination threshold is set as... .
[0067] In this embodiment, by adjusting the bias voltage, electrolyte environment parameters, or interface state applied to both sides of the nanopore, the interface characteristics of the nanopore are changed, thereby altering the modulation intensity of the transpore behavior of the analyte in each channel.
[0068] In dynamic weighting scenarios, weights can be represented as functions of time or environmental variables: During the testing process, the basic response definition remains consistent with that of Example 1.
[0069] Two control states were set: state A was the initial state, and state B was the control state. The results obtained by adjusting the environmental variables are shown in Table 3. Table 3 Choose two analytes with similar properties. and Its basic response is similar to that of Example 1 (normalized representation), and the specific results are shown in Table 4: Table 4 In state A, the degree of difference is: because Unable to determine the substance and They are different substances.
[0070] In state B, the degree of difference is: 212 because Determine the substance and They are different substances.
[0071] Under dynamic control, by adjusting the response weights of each channel, the distribution of different substances in the weighted response space is further separated, thereby increasing the degree of difference from below the threshold to above the threshold, and realizing the transformation from indistinguishable to distinguishable.
[0072] The above are merely preferred embodiments of this application, but the scope of protection of this application is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in this application should be included within the scope of protection of this application. Therefore, the scope of protection of this application should be determined by the scope of the claims.
Claims
1. A method for detecting nanopore arrays that distinguishes different substances using weighted response mapping, characterized in that, include: Based on a pre-constructed nanopore array with differentiated response characteristics to the mass transport process, the multi-channel current response signal generated by each nanopore channel when the substance to be tested passes through the nanopore array under the drive of an electric field is obtained. Based on the multi-channel current response signal, the input of a single analyte is mapped to a multi-channel weighted response composed of responses from multiple nanopore channels. Different analytes can be distinguished based on the differences in response patterns formed by the multi-channel weighted response among different substances.
2. The method according to claim 1, characterized in that, The process of constructing the nanopore array includes: By differentially controlling the surface charge state, interface modification layer, or local interaction capability of each nanopore in the nanopore array, the same analyte can produce different basic responses in different nanopores, and different response weights can be assigned to each nanopore.
3. The method according to claim 1, characterized in that, The process of obtaining the multi-channel current response signal includes: An electrical signal is applied to both sides of the nanopore array to drive the analyte to pass through each nanopore sequentially or in parallel. The current response signal generated by each nanopore channel is recorded during the process of the analyte passing through the pores. The current response signal includes the waveform of the current changing with time.
4. The method according to claim 1, characterized in that, The process of mapping the input of a single analyte to a multi-channel weighted response includes: The multi-channel weighted response is represented as a vector form composed of the response signals of each nanopore channel. The response signal of each nanopore channel is used to quantify the response intensity of the channel to the analyte, and the response intensities of different channels together constitute a multi-dimensional response vector.
5. The method according to claim 4, characterized in that, The process of obtaining the response signal for each nanopore channel includes: For each nanopore, the response weight and the basic response signal generated by the analyte in the nanopore are combined to obtain the final response signal of the nanopore channel.
6. The method according to claim 4, characterized in that, The response signal of the nanopore channel includes the current blocking amplitude, blocking duration, or a combination of both generated during the transpore process of the analyte, which are used to constitute the basic response signal of each nanopore channel. The basic response signal reflects the original transpore behavior of the analyte in a single nanopore.
7. The method according to claim 5, characterized in that, The process of determining the response weight corresponding to each nanopore includes: The response weights are set based on one or more interfacial characteristics of the nanopore, such as surface charge density, interfacial binding ability, spatial structure constraint, local hydrophilicity / hydrophobicity, or molecular recognition layer characteristics, and the response weights can be dynamically modulated as the molecular binding state or environmental conditions change.
8. The method according to claim 1, characterized in that, The distribution characteristics of the multi-channel weighted response on each nanopore channel constitute the weighted response mode corresponding to the analyte. Different analytes form different weighted response modes after weighted response mapping in the nanopore array. The weighted response mode is used to characterize the differential response fingerprint of different substances in the array.
9. The method according to claim 1, characterized in that, The process of distinguishing different substances includes: The two substances are distinguished by the differences between their multi-channel weighted response vectors. When the weighted response vectors of the two substances have different values in each dimension, the two substances are determined to be different substances.
10. The method according to claim 9, characterized in that, The process of determining the differences between weighted response vectors includes: The difference between the weighted response vectors corresponding to two different substances is calculated, and the calculated difference is compared with a pre-set discrimination threshold. When the difference is greater than the discrimination threshold, the two substances are determined to be distinguishable different substances.