FET for single target sensing

Abstract

A field-effect transistor sensor device comprising: a source electrode and a drain electrode separated by a channel region and defining a source-drain axis; a plurality of carbon nanotubes aligned along the source-drain axis and defining the channel region, the channel region having a width and length less than 1 micrometer; wherein the channel region is functionalized with a single capture entity per device, the capture entity being configured to bind selectively to a target entity.

Description

[0001] FET for Single Target Sensing

[0002] Field of the Invention

[0003] The present invention relates to the field of sensors, and more specifically to fieldeffect transistor sensor devices.

[0004] Background of the Invention

[0005] Advancements in sensing technologies have significantly propelled research in genomics, proteomics, and other omics fields. Single-molecule detection has become an essential aspect of these technologies, as it enables the characterization of individual biomolecules without the need for amplification or synchronization required by pooled samples. This capability is particularly important for analyzing molecules that cannot be readily copied or amplified, such as certain proteins and non-nucleic acid polymers. Despite the progress, current single-molecule sensing techniques face limitations in terms of read throughput and dynamic range. The number of molecules that can be characterized per unit of time is often insufficient to meet the demands of large-scale studies. Additionally, the ability to detect molecules across a wide concentration range— from the most abundant to the least abundant within a single sample— is constrained. These limitations hinder the comprehensive analysis required for advanced omics applications.

[0006] Silicon-based field-effect transistors (FETs), leveraging complementary metal-oxide-semiconductor (CMOS) technology, have been explored as a platform to address these challenges due to their ability to achieve high sensor densities. The potential to integrate billions of FETs on a single chip suggests a pathway toward highly parallelized sensing. However, nanoscale silicon FETs encounter several obstacles when applied to single-molecule detection.

[0007] One significant issue is the presence of a highly charged native silicon dioxide (SiO2) surface on silicon FETs. This surface charge can lead to increased ion screening in electrolyte environments, which diminishes the molecular sensitivity of the sensor. The heightened screening effect reduces the sensor's ability to detect the subtle electrical changes associated with single-molecule interactions.Another challenge involves the selective attachment of probes to the sensor's active surface. For effective sensing, it is crucial that probes bind only to the sensitive areas to prevent the loss of low-abundance analytes on non-sensitive regions. Silicon-based sensors present difficulties in achieving this selective functionalization because their surfaces are chemically similar, making it hard to distinguish and exclusively functionalize the active sensing areas.

[0008] Low-frequency noise, such as 1 / f noise, also poses a problem for silicon FET sensors. This type of noise often originates from trap states within the SiO2layer and can significantly impact the signal-to-noise ratio (SNR). A high SNR is advantageous for reliable single-molecule detection, and excessive noise can obscure the detection of individual molecular events.

[0009] Therefore, there remains a need for further advancements in the field to address at least some of these challenges and enhance the capabilities of single-molecule sensing technologies.

[0010] Summary of the Invention

[0011] It is an object of embodiments of the present invention to provide a highly sensitive sensor capable of single-molecule detection. This objective is accomplished by the aspects of the present invention.

[0012] In the first aspect, the present invention relates to a field-effect transistor sensor device comprising a source electrode and a drain electrode separated by a channel region and defining a source-drain axis, a plurality of carbon nanotubes aligned along the sourcedrain axis and defining the channel region, the channel region having a width and length less than 1 micrometer, wherein the channel region is functionalized with a single capture entity or a single coupling entity per device, the single coupling entity being capable of attaching to the capture entity, the capture entity being configured to bind selectively to a target entity.

[0013] In embodiments, the channel region may be functionalized with a single capture entity configured to bind selectively to a target entity. Alternatively, the channel region may initially be functionalized with a single coupling entity that can subsequently be attached to the capture entity. Thus, the invention covers both immediate capture-entity attachment and a two-step process where the coupling entity is introduced first and the capture entity is attached at a later stage or just prior to use.In embodiments, the capture entity may be a molecular capture entity. This allows specific detection of target entities.

[0014] In embodiments, the molecular capture entity may comprise an entity selected from the group consisting of biomolecules, synthetic molecules, polymers, nanoparticles, or combinations thereof. This provides flexibility in capture entity design.

[0015] In embodiments, the biomolecule may be selected from the list consisting of nucleic acids, peptides, proteins, lipids, and carbohydrates. These are common biological capture entities.

[0016] In embodiments, the capture entity may be selected from the group consisting of an enzyme, an antibody, an aptamer, and a DNA origami. These provide high specificity and affinity.

[0017] In embodiments, the enzyme may be selected from the list consisting of a polymerase, a nuclease, and a protease. These are useful for sequencing applications.

[0018] In embodiments, the channel region may have a width of from 4 to 500 nm, preferably less than 200 nm, more preferably less than 100 nm, yet more preferably less than 20 nm. This optimizes sensitivity.

[0019] In embodiments, the channel region may have a length of less than 500 nm, preferably from 20 to 200 nm, more preferably less than 150 nm, yet more preferably less than 100 nm, even more preferably less than 60 nm. This provides short transit times.

[0020] In embodiments, the plurality of aligned carbon nanotubes may comprise from 2 to 40 carbon nanotubes, optionally from 2 to 20 carbon nanotubes, optionally from 5 to 10 carbon nanotubes. This balances sensitivity and manufacturability.

[0021] In embodiments, neighboring carbon nanotubes may be separated by an average spacing of from 2 to 10 nm, preferably from 2 to 6 nm, yet more preferably from 3 to 5 nm. This enables capturing of the charge cloud.

[0022] In embodiments, the carbon nanotubes may have an average diameter of from 1 to 2 nm. This is the typical size range for CNTs.

[0023] In embodiments, the carbon nanotubes may be functionalized with pyrene linkers for attaching the capture entity. This allows selective attachment to CNTs.

[0024] In embodiments, the device may further comprise an insulating layer adjacent to a top or bottom side of the channel region, wherein the other side of the channel region is exposed to a cavity configured to allow a liquid electrolyte to access the channel region. This enables liquid gating.In embodiments, the insulating layer may comprise a material selected from the group consisting of SiC , Si3N4, HfC , AI2O3, and BN. These are common insulating materials.

[0025] In embodiments, the carbon nanotubes may be suspended above the channel region. This maximizes exposure to the analyte.

[0026] In embodiments, the carbon nanotubes may be of the semiconductor type. Preferably, they exhibit a purity of at least 95%, preferably at least 98%, more preferably at least 99%, even more preferably, at least 99,9999%. This reduces variability between devices.

[0027] In embodiments, the aligned carbon nanotubes may have a degree of alignment of 15 degrees or less, preferably 12 degrees or less, more preferably 10 degrees or less, as measured by polarized Raman spectroscopy. This improves device performance.

[0028] In embodiments, the device may further comprise a liquid electrolyte in contact with the channel region, wherein the liquid electrolyte forms an electrolyte gate. This allows efficient gating.

[0029] Any feature of the first aspect may be as correspondingly described in any of the other aspects.

[0030] In the second aspect, the present invention relates to a method of manufacturing a field-effect transistor sensor device comprising providing a substrate having a plurality of carbon nanotubes aligned along a source-drain axis, patterning the plurality of carbon nanotubes to form a channel region between a source electrode and a drain electrode, the channel region having a width and length less than 1 micrometer, functionalizing the channel region with a single capture entity per device, the capture entity being configured to bind selectively to a target entity.

[0031] In embodiments, providing a substrate having a plurality of carbon nanotubes aligned along a source-drain axis may comprise depositing the aligned carbon nanotubes on a substrate by a process comprising providing a liquid with dispersed carbon nanotubes and the substrate therein, then raising the substrate through the liquid at a speed slow enough to achieve some alignment the carbon nanotubes on the substrate surface. This is a deposition method.

[0032] In embodiments, patterning the carbon nanotubes may comprise forming the source and drain electrodes by lift-off, then etching away carbon nanotubes outside the channel region. This isolates the active area.In embodiments, the method may further comprise forming an isolation layer over the carbon nanotubes, then patterning the isolation layer to expose the carbon nanotubes in the channel region. This protects the contacts.

[0033] In embodiments, the substrate may comprise a dielectric layer forming its top surface, wherein the method further comprises etching away the dielectric layer beneath the carbon nanotubes to suspend the carbon nanotubes. This allows electrolyte access from both sides of the channel.

[0034] In embodiments, providing a substrate having a plurality of carbon nanotubes aligned along a source-drain axis may comprise depositing the aligned carbon nanotubes on a substrate by a deposition technique selected from the group consisting of Dimension-Limited Self-Alignment (DLSA), Tangential Flow Interfacial Self-Assembly (TaFISA), and dielectrophoresis. These provide aligned CNTs. In a further step, the source and drain are provided so that the carbon nanotubes are aligned with the source-drain axis.

[0035] In embodiments, functionalizing the channel region may comprise selectively attaching the capture entity or coupling entity to the carbon nanotubes using a non-covalent (e.g. pyrene-based) [see Chen et al. doi:10.1021 / ja010172b, Choi et al. doi: 10.1126 / science.1214824] or a covalent (e.g. oxidation, diazonium-based) functionalization procedure [see Goldsmith et al. doi: 10.1126 / science.1135303, Lee et al. doi: 10.1021 / acsnano.8b03073], For the non-covalent procedure, the capture entity or coupling entity may bear an aromatic group for non-covalent attachment to the CNT. Examples of suitable aromatic groups are polycyclic aromatic groups. In embodiments, the polycyclic aromatic group may be selected from the list consisting of anthracene, porphyrins, phthalocyanines, naphthalene, phenanthrene, and pyrene. Preferred ones are pyrene, anthracene, and phenanthrene. A particular example is pyrene. For the non-covalent procedure, the concentration of the capture entity molecule or coupling entity molecule is preferably adapted to maximize the number of aligned CNT FETs with a single capture entity or coupling entity. Due to Poisson statistics a maximum number of single capture entity or coupling entity per devices of about 37% (36.8%) can be obtained in a single step. Of course, more elaborated and slower procedures can achieve higher numbers.

[0036] In embodiments, functionalizing the channel region may comprise contacting the channel region with a solution comprising a capture entity or coupling entity, the capture entity being configured to bind (e.g., non-covalently) with the CNT and bind selectively to a target entity, the coupling entity being configured to bind non-covalently with the CNTand bind with the capture entity. The solution is provided with a volume and a capture entity or coupling entity concentration such that upon application of the solution on the channel region, the probability of exactly one capture entity or coupling entity binding to the channel region per device is at least 30%. This is advantageous because this can be achieved with a rapid and simple one step procedure.

[0037] The functionalization leaves the electronic structure of the CNT unharmed. In embodiments, the functionalization may preserve the electronic structure of the carbon nanotubes through non-covalent pyrene-based chemistry maintaining sp2 hybridization.

[0038] In alternative embodiments, functionalizing the channel region may comprise a two-step process of first uniformly coating the carbon nanotubes with functional groups by contacting the channel region with a solution comprising coupling entities configured to bind non-covalently with the CNT and provide a reactive group, followed by introducing a capture entity solution comprising complementary reactive groups, wherein the solution is provided with a volume and a capture entity concentration such that upon application of the solution on the channel region, the probability of exactly one capture entity binding to the channel region per device is at least 30%.

[0039] Covalent functionalization procedures may rely on creating a single sp3defect on the CNT sidewall. The creation of the sp3defects may be performed in an oxidative [see Goldsmith et al. doi: 10.1126 / science.1135303] or diazonium salt [see Lee et al. doi: 10.1021 / acsnano.8b03073] environment by applying a bias to the gate of the CNT FET. The creation of a single sp3defect may be electrochemically controlled. Since the creation of the sp3defect typically results in the change of the conductance of the CNT FET the chemical reaction can be electrically monitored. As such the number of capture entities or coupling entities can be controlled electrically . This provides a single attachment point.

[0040] In embodiments, functionalizing the channel region may comprise creating a single sp3defect on the carbon nanotube sidewall through electrochemical control, monitoring the defect creation through carbon nanotube conductance changes, and attaching the capture entity or coupling entity at the defect site. In embodiments, the functionalization may comprise controlled sp3defect creation enabling precise attachment while maintaining device functionality.

[0041] In embodiments, the capture entity may comprise a probe molecule having a part for attachment to the CNT which is either a) an aromatic moiety (e.g., pyrene) or b) a reactive moiety capable of forming covalent bonds with sp3carbon atoms (e.g., diazonium moiety), conjugated to a part capable to bind selectively to a target entity.In embodiments, the coupling entity may comprise a linker molecule having a part for attachment to the CNT which is either a) an aromatic moiety (e.g., pyrene) or b) a reactive moiety capable of forming covalent bonds with sp3carbon atoms (e.g., diazonium moiety), conjugated to a part capable to bind to a capture entity.

[0042] Any feature of the second aspect may be as correspondingly described in any of the other aspects.

[0043] In the third aspect, the present invention relates to a method of detecting a target entity comprising providing a field-effect transistor sensor device according to any embodiments of the first aspect, exposing the functionalized channel region to a sample containing the target entity or suspected of containing the target entity, and applying a voltage between the source electrode and the drain electrode, measuring an electrical parameter indicative of binding of the target entity to the capture entity.

[0044] In embodiments, the target entity may be a nucleotide, and the capture entity comprises either a polymerase or a nuclease, or the target entity may be an amino acid and the capture entity comprises a protease. This allows the sequencing of biopolymers.

[0045] In embodiments, the electrical parameter may be selected from current, conductance, and charge. These are sensitive to molecular binding.

[0046] In embodiments, the method may further comprise detecting individual binding events between the target entity and the capture entity. This enables single-molecule resolution.

[0047] Any feature of the third aspect may be as correspondingly described in any of the other aspects.

[0048] In the fourth aspect, the present invention relates to a kit comprising a field-effect transistor sensor device comprising a source electrode and a drain electrode separated by a channel region and defining a source-drain axis, the channel region comprising a plurality of carbon nanotubes aligned along the source-drain axis and forming a channel region of width and length less than 1 micrometer, and

[0049] -an entity selected from:

[0050] - a capture entity configured to attach to a carbon nanotube and to bind selectively to a target entity, and

[0051] - a coupling entity configured to attach to a carbon nanotube and capable of attaching to a capture entity, and

[0052] - a solvent, wherein the entity and the solvent are provided either separately or as a solution, wherein the entity and solvent are provided in amounts such that,when combined, the concentration and volume of the solution are such that, upon application of the whole solution on the channel region, the probability of exactly one capture entity binding to the channel region per device is at least 30%.

[0053] Any feature of the fourth aspect may be as correspondingly described in any of the other aspects.

[0054] In the fifth aspect, the present invention relates to a field-effect transistor sensor array comprising a plurality of devices according to any embodiments of the first aspect arranged in an array configuration.

[0055] In embodiments, the array may comprise at least 1000 devices. This enables high-throughput sensing.

[0056] In embodiments, the array may further comprise integrated circuitry for addressing and reading out individual devices in the array. This allows multiplexed operation.

[0057] Any feature of the fifth aspect may be as correspondingly described in any of the other aspects.

[0058] It is an advantage of embodiments of the present invention that they offer highly sensitive biosensing at the single-molecule level, enabling detection of individual (bio)molecular interactions.

[0059] It is an advantage of embodiments of the present invention that they utilize aligned carbon nanotubes with low surface charge, reducing ion screening effects and enhancing molecular sensitivity compared to silicon-based sensors.

[0060] It is an advantage of embodiments of the present invention that selective functionalization can be achieved, allowing capture entities to attach only to the sensitive surface of the carbon nanotube channel, improving detection specificity and efficiency.

[0061] It is an advantage of embodiments of the present invention that the use of carbon nanotubes minimizes low-frequency noise due to the absence of charge traps in gate dielectrics, thereby improving the signal-to-noise ratio, thereby improving single-molecule detection.

[0062] It is an advantage of embodiments of the present invention that the aligned carbon nanotube devices provide manufacturability and scalability for wafer-scale fabrication, overcoming the challenges associated with placing single carbon nanotubes in device fabrication.It is an advantage of embodiments of the present invention that they enable higher sensor density and integration potential compared to optical methods, leveraging the miniaturization capabilities of CMOS technology.

[0063] It is an advantage of embodiments of the present invention that the use of aligned carbon nanotubes allows for three-dimensional integration with existing foundry technology in the back-end-of-line, as they do not require front-end-of-line integration like silicon-based sensors.

[0064] It is an advantage of embodiments of the present invention that the high mobility and potential ballistic transport properties of aligned carbon nanotubes enhance the electrical performance and sensitivity of the sensors.

[0065] It is an advantage of embodiments of the present invention that they provide natural material contrast for selective functionalization, facilitating the attachment of capture entities only to the carbon nanotube channel and not to surrounding surfaces.

[0066] It is an advantage of embodiments of the present invention that the devices can achieve aggressive scaling of the channel dimensions, with channel lengths and widths less than 1pm, or even less than 100 nanometers, leading to optimal electrostatic control and improved performance.

[0067] It is an advantage of embodiments of the present invention that the aligned carbon nanotube sensors can potentially detect biomolecules that cannot be amplified or cloned, extending the applicability beyond nucleic acids to proteins and other biomolecules.

[0068] It is an advantage of embodiments of the present invention that the devices can be operated with a liquid electrolyte gate without the need for a gate dielectric material, simplifying the device structure and reducing noise associated with dielectric materials.

[0069] It is an advantage of embodiments of the present invention that the sensors can be fabricated using existing methods for depositing aligned carbon nanotubes with high purity and uniform orientation, supporting large-scale manufacturing.

[0070] It is an advantage of embodiments of the present invention that they can achieve low device variability.

[0071] It is an advantage of embodiments of the present invention that the device can be provided (i) already functionalized with exactly one capture entity, or (ii) with a single coupling entity to which the capture entity is attached at a later time, offering flexibility in final functionalization and potentially improved storage stability.

[0072] Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may becombined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.

[0073] The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference figures quoted below refer to the attached drawings.

[0074] Brief description of the drawings

[0075] Fig. 1 is a schematic illustration of an aligned carbon nanotube FET for single-target sensing according to embodiments of the present invention.

[0076] Fig. 2 is a cross-sectional view of an aligned carbon nanotube FET for single-target sensing according to embodiments of the present invention.

[0077] Fig. 3 is a flowchart of a method of manufacturing an aligned carbon nanotube FET for single-target sensing according to embodiments of the present invention.

[0078] In the different figures, the same reference signs refer to the same or analogous elements.

[0079] Detailed description of Illustrative Embodiments

[0080] The present invention will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto but only by the claims. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes. The dimensions and the relative dimensions do not correspond to actual reductions to practice of the invention.

[0081] The following terms are provided solely to aid in the understanding of the invention.

[0082] As used herein, and unless otherwise specified, the term "channel region" refers to the portion of the field-effect transistor that lies between the source electrode and the drain electrode, through which charge carriers flow when voltage is applied, enabling current conduction within the device.

[0083] As used herein, and unless otherwise specified, the term "source-drain axis" refers to an imaginary straight line or direction that extends from the source electrode to thedrain electrode, representing the primary pathway along which charge carriers move between these electrodes within the transistor.

[0084] As used herein, and unless otherwise specified, the term "functionalized" refers to the result of the process by which the channel region is chemically modified to attach specific molecules or groups, such as capture entities, thereby imparting desired chemical or physical properties, including the ability to bind selectively to a target entity.

[0085] As used herein, and unless otherwise specified, the phrase "a single capture entity per device" means that exactly one capture entity is attached to the channel region of each individual device, ensuring that only one binding site is available for interaction with the target entity on that device.

[0086] As used herein, and unless otherwise specified, the term "capture entity" refers to an entity, such as a molecule or molecular entity, that has the specific capability to bind selectively to a target entity, facilitating the target's detection or analysis by the sensor device. For the avoidance of doubt, 'functionalized with a single capture entity' includes embodiments in which the channel region is first functionalized with a single coupling entity that, in turn, is attached to a capture entity (for example, an enzyme or antibody) prior to or during sensing. Examples of capture entities comprise biomolecules such as enzymes, antibodies, aptamers, DNA origami, nucleic acids, peptides, proteins, lipids, and carbohydrates, as well as synthetic molecules, polymers, or nanoparticles. The capture entity is typically a probe molecule used to analyze an analyte.

[0087] As used herein, and unless otherwise specified, the term "coupling entity" refers to any chemical group or molecule that can (1) bind or attach to the carbon nanotube channel region (e.g., via pyrene-based n-n stacking or covalent diazonium chemistry) and (2) subsequently bind or react with a capture entity (8). Examples include, without limitation, linkers such as pyrene linkers bearing reactive headgroups (NHS, maleimide, click-chemistry groups), biotin linkers, and similar anchor moieties.

[0088] As used herein, and unless otherwise specified, the term "target entity" refers to a specific molecule or substance of interest that the capture entity binds selectively. Examples of target entities comprise nucleotides, amino acids, peptides, proteins, nucleic acids, environmental pollutants, pathogens, and biomarkers associated with diseases. The target entity is typically the analyte but can also be a probe molecule (e.g., a nucleotide) used to analyze the analyte (e.g., a nucleic acid strand such as a DNA strand). For instance, a polymerase may be the capture entity, because it selectively binds its substrate (the DNA strand, plus nucleotides). The DNA and nucleotides substrates in solution are then thetarget entities. As used herein, and unless otherwise specified, the phrase "bind selectively" refers to the ability of the capture entity to interact preferentially with the target entity over other substances. This results in a specific binding event that can be distinguished from non-specific interactions. This selective binding can for instance occur through mechanisms such as complementary base pairing, antigen-antibody interactions, enzyme-substrate specificity, or receptor-ligand affinity.

[0089] As used herein, and unless otherwise specified, the term "aligned" refers to the arrangement of carbon nanotubes positioned such that the carbon nanotubes tend to have their longitudinal axes closer to be parallel to the source-drain axis rather than to be perpendicular thereto. This alignment ensures consistent electrical properties within the channel region. For example, the aligned carbon nanotubes may have a degree of alignment of 15 degrees or less from the source-drain axis, as measured by polarized Raman spectroscopy.

[0090] In embodiments, determining the degree of alignment of the carbon nanotubes may involve spectroscopic measurements. The degree of alignment may be calculated by measuring polarized Raman spectra and analyzing the intensity ratios of characteristic peaks. Specifically, the method may involve measuring the Raman G-band intensities with excitation polarized parallel and perpendicular to the nanotube alignment direction, calculating the intensity ratio [lmax(6 = 0°)] / [ lmin(6 = 90°], and correlating this ratio to the angular distribution of nanotube orientations using a Gaussian model.

[0091] Specifically, the method for determining the degree of alignment of carbon nanotubes (CNTs) may be as detailed in Liu, Lijun, et al. "Aligned, high-density semiconducting carbon nanotube arrays for high-performance electronics." Science 368.6493 (2020): 850-856.

[0092] For instance, if the ratio Imax / Imin is 45, this correlates with a Gaussian distribution with a degree of alignment of 8.3°.

[0093] As used herein, and unless otherwise specified, the terms "width (W)" and "length (L)" refer to the dimensions of the channel region measured perpendicular and parallel to the source-drain axis, respectively. Specifically, "width" is the dimension across the channel region between its lateral sides, said sides being formed by carbon nanotubes, while "length" is the distance from the source electrode to the drain electrode along the source-drain axis.

[0094] As used herein, and unless otherwise specified, the term "purity" refers to the proportion of the desired type of carbon nanotubes in a sample (here the semiconductortype), expressed as a percentage of the total carbon nanotubes present. For instance, carbon nanotubes exhibiting a purity of at least 95% contain at least 95% of the semiconducting type and less than 5% of metallic forms of nanotubes. Determining the purity of carbon nanotubes may be performed by evaluating electrical characteristics of devices incorporating the nanotubes. Determining carbon nanotube purity may involve fabricating multiple devices and measuring their current-voltage characteristics to assess electrical performance. For instance, the method for determining the purity of a population of carbon nanotubes (CNTs) may comprise:

[0095] (a) fabricating a plurality of electronic devices (e.g., at least 20, preferably at least 100, more preferably at least 1000), each device comprising a plurality of CNTs deposited on a substrate, the number of CNTs per device being determined by the deposition density and the device dimensions;

[0096] (b) measuring the current-voltage (l-V) characteristics of each device to evaluate an on-off ratio indicative of semiconducting behavior;

[0097] (c) identifying devices exhibiting metallic behavior based on the absence of a proper on-off ratio; and

[0098] (d) calculating the purity of the CNT population by correlating the number of devices exhibiting metallic behavior with the total number of CNTs per device and the total number of devices, wherein the semiconducting CNT purity is determined as a function of the observed metallic CNT contamination rate.

[0099] For example, this process can begin by fabricating a set of devices, for example, 100 devices, each containing a specific number of CNTs (for instance, 100 CNTs per device). The number of CNTs per device is determined based on the CNT deposition density and the dimensions of the devices. By analyzing the l-V curves, we can assess whether each device exhibits a proper on-off ratio, which is indicative of semiconducting behavior. If all devices demonstrate this expected behavior without any evidence of metallic shorting, it can be concluded that the CNTs used in the devices are predominantly semiconducting.

[0100] Using the data from the l-V measurements, we can estimate the purity of the CNTs. For instance, if none of the 100 devices show metallic behavior, and each device contains 100 CNTs, this implies that there are fewer than 1 metallic CNT per 10000 CNTs, corresponding to a metallic CNT contamination rate of less than one in 10000. Consequently, the semiconducting CNT purity would be greater than 99.99%. This method provides a robust and statistically sound means of assessing CNT purity, particularly in high-purity applications. Determining the purity of carbon nanotubes may more conveniently beperformed by using optical spectroscopic techniques. Assessing carbon nanotube purity may involve measuring absorbance spectra and analyzing specific peak ratios characteristic of semiconducting nanotubes. Specifically, the method may involve measuring the absorbance spectra, calculating the Szz / Mn peak ratio, and estimating the purity level based on the spectral analysis. This method allows to determine if the purity is greater than 99%.

[0101] As used herein, and unless otherwise specified, the term "insulating layer" refers to a layer of electrically insulating material positioned adjacent to the bottom side of the channel region. This layer serves to electrically isolate the channel region from the substrate or other components, preventing unwanted current flow. Examples of materials for the insulating layer include silicon dioxide (SiO2), silicon nitride (Si3N4), hafnium oxide (HfO2), aluminum oxide (AI2O3), and boron nitride (BN).

[0102] As used herein, and unless otherwise specified, the term "DLSA" refers to "Dimension-Limited Self-Alignment," a deposition technique for aligning carbon nanotubes on a substrate by dipping the substrate through a liquid-air interface containing dispersed nanotubes, resulting in their orderly arrangement on the substrate surface (It is detailed in Liu, Lijun, et al. "Aligned, high-density semiconducting carbon nanotube arrays for high-performance electronics." Science 368.6493 (2020): 850-856.

[0103] As used herein, and unless otherwise specified, the term "TaFISA" refers to "Tangential Flow Interfacial Self-Assembly," a technique for depositing and aligning carbon nanotubes on a substrate by inducing a flow parallel to the substrate surface, which promotes the self-assembly of nanotubes in a controlled orientation (it is detailed in Jinkins, Katherine R., et al. "Aligned 2D carbon nanotube liquid crystals for wafer-scale electronics." Science advances 7.37 (2021): eabh0640.).

[0104] As used herein, and unless otherwise specified, the term "dielectrophoresis" refers to a method for manipulating and aligning particles, such as carbon nanotubes, within a non-uniform electric field. The induced polarization causes the particles to move and align along the field gradients, enabling precise positioning on the substrate.

[0105] As used herein, and unless otherwise specified, the term "integrated circuitry" refers to electronic circuits fabricated on a substrate that incorporate multiple electrical components (such as transistors, resistors, and capacitors) to perform specific functions. In the context of the sensor array, integrated circuitry enables the addressing, control, and readout of individual devices within the array configuration.As used herein, and unless otherwise specified, the phrase "electrical parameter indicative of binding" refers to any measurable electrical property of the sensor device that changes in response to the binding event between the capture entity and the target entity. Examples of such electrical parameters include current, conductance, and charge, where a change in these parameters signifies the occurrence of binding.

[0106] As used herein, and unless otherwise specified, the phrase "detecting individual binding events" refers to the capability of the sensor device or method to observe and measure each discrete instance of a target entity molecule binding to the capture entity on the device, allowing for single-molecule detection rather than aggregate measurements.

[0107] As used herein, and unless otherwise specified, the phrase "probability of exactly one capture entity binding per device" refers to the statistical likelihood that, when the provided solution containing capture entity is applied to the channel region of the devices under specified conditions, each individual device will have exactly one capture entity bound to its channel region. This probability is determined based on the concentration and volume of the capture entity solution and the number of available binding sites on the devices. For example, achieving a probability of at least 30% involves adjusting these parameters, in particular the volume and concentration of the capture entity solution, so that the average number of capture entities per device is controlled to favor the binding of exactly one molecule.

[0108] The invention will now be described by a detailed description of several embodiments of the invention. It is clear that other embodiments of the invention can be configured according to the knowledge of persons skilled in the art without departing from the technical teaching of the invention, the invention being limited only by the terms of the appended claims.

[0109] In the first aspect, the present invention relates to a field-effect transistor sensor device comprising a source electrode (2) and a drain electrode (3) separated by a channel region (4) and defining a source-drain axis (5). As illustrated in Figure 1, the device (1) includes a source electrode (2) and a drain electrode (3) separated by a channel region (4). The source electrode (2) and drain electrode (3) define a source-drain axis (5). A plurality of carbon nanotubes (6) are aligned along the source-drain axis (5) and define the channel region (4). The channel region (4) has a width (W) and length (L) less than 1 micrometer. The channel region (4) is functionalized with a single capture entity (8) or a single couplingentity per device (1). The single coupling entity is capable of attaching to the capture entity (8). The capture entity (8) is configured to bind selectively to a target entity.

[0110] In embodiments, the channel region may be functionalized with a single capture entity (8) configured to bind selectively to a target entity. Alternatively, the channel region may initially be functionalized with a single coupling entity that can subsequently be attached to the capture entity (8). Thus, the invention covers both immediate captureentity attachment and a two-step process where the coupling entity is introduced first and the capture entity (8) is attached at a later stage or just prior to use.

[0111] In embodiments, the capture entity (8) may be a molecular capture entity (8). This allows specific detection of target entities. The molecular capture entity may comprise an entity selected from the group consisting of biomolecules, synthetic molecules, polymers, nanoparticles, or combinations thereof, providing flexibility in capture entity design. The biomolecule may be selected from the list consisting of nucleic acids, peptides, proteins, lipids, and carbohydrates, which are common biological capture entities. The biomolecule may be selected from the group consisting of an enzyme, an antibody, an aptamer, and a DNA origami, providing high specificity and affinity. The enzyme may be selected from the list consisting of a polymerase, a nuclease, and a protease, which are useful for sequencing applications.

[0112] In certain embodiments, the channel region (4) is first functionalized with exactly one coupling entity per device (1), ensuring that, after functionalization, only one coupling entity is present in the channel region. At a later stage— e.g., immediately before measurement, or even in situ— the capture entity (8) is introduced and attaches to this single coupling entity. By controlling the number of coupling entities to exactly one per device, only one capture entity will eventually be present per channel region, in line with single-molecule detection principles.

[0113] In embodiments, the channel region (4) may have a width of from 4 to 500 nm, preferably less than 200 nm, more preferably less than 100 nm, yet more preferably less than 20 nm, optimizing sensitivity. The channel region (4) may have a length of less than 500 nm, preferably from 20 to 200 nm, more preferably less than 150 nm, yet more preferably less than 100 nm, even more preferably less than 60 nm, providing short transit times.

[0114] In embodiments, optimizing the channel dimensions, such as having a channel length of less than 500 nm and a width of less than 100 nm, may provide enhanced signal sensitivity with a gate voltage shift of approximately 10 mV upon target entity binding.In embodiments, the plurality of aligned carbon nanotubes (6) may comprise from 2 to 40 carbon nanotubes, optionally from 2 to 20 carbon nanotubes, optionally from 5 to 10 carbon nanotubes, balancing sensitivity and manufacturability. Neighboring carbon nanotubes (6) may be separated by an average spacing (s) of from 2 to 10 nm, preferably from 2 to 6 nm, yet more preferably from 3 to 5 nm, enabling capturing of the charge cloud. The carbon nanotubes (6) may have an average diameter of from 1 to 2 nm, which is the typical size range for CNTs. The carbon nanotubes may be functionalized with pyrene linkers or diazonium linkers for attaching the capture entities, allowing selective attachment to CNTs.

[0115] Utilizing aligned carbon nanotubes in the field-effect transistor sensor device may overcome limitations of silicon-based sensors. The aligned carbon nanotubes may provide a chemically inert surface with low charge, reducing ion screening and increasing analyte (e.g., biomolecule) sensitivity compared to silicon-based devices. In embodiments, the aligned carbon nanotubes may eliminate the need for a gate dielectric due to effective gating by the electrical double layer in the electrolyte, providing higher analyte sensitivity and lower low-frequency noise compared to devices with silicon dioxide gate dielectrics prone to charge traps.

[0116] As depicted in Figure 2, the device (1) may further comprise an insulating layer (21) adjacent to a bottom side of the channel region (4). The other side of the channel region (4) is exposed to a cavity (22) configured to allow a liquid electrolyte (23) to access the channel region (4). The liquid electrolyte (23) is in contact with the channel region (4) and forms an electrolyte gate (25), enabling liquid gating. The insulating layer (21) may comprise a material selected from the group consisting of SiO2, Si3N4, HfO2, AI2O3, and BN, which are common insulating materials.

[0117] In embodiments, the carbon nanotube channel may be exposed to the analyte from multiple directions. The carbon nanotube channel may be suspended, allowing electrolyte access to both the top and bottom surfaces of the nanotubes. In embodiments, the field-effect transistor sensor device may comprise a suspended aligned carbon nanotube channel not supported by the substrate, with structural features permitting liquid electrolyte to contact the nanotubes from all sides. This maximizes exposure to target entities and reduces noise.

[0118] In embodiments, the carbon nanotubes may be of the same type (typically a semiconductor type) and exhibit a purity of at least 99%, reducing variability between devices. The aligned carbon nanotubes may have a degree of alignment of 15 degrees orless, preferably 12 degrees or less, more preferably 10 degrees or less, as measured by polarized Raman spectroscopy. This improves device performance.

[0119] The device may further comprise a liquid electrolyte in contact with the channel region, wherein the liquid electrolyte forms an electrolyte gate, allowing efficient gating.

[0120] In the second aspect, the present invention relates to a method of manufacturing a field-effect transistor sensor device. As illustrated in Figure 3, the method involves providing a substrate (26) having a plurality of carbon nanotubes (6) aligned along a source-drain axis (5). The plurality of carbon nanotubes (6) is patterned to form a channel region (4) between a source electrode (2) and a drain electrode (3), the channel region (4) having a width (W) and length (L) less than 1 micrometer. The channel region (4) is functionalized with a single capture entity (8) per device (1), the capture entity (8) being configured to bind selectively to a target entity.

[0121] In embodiments, providing a substrate having a plurality of carbon nanotubes aligned along a source-drain axis may comprise depositing the aligned carbon nanotubes on a substrate by a process comprising providing a liquid with dispersed carbon nanotubes and the substrate therein, then raising the substrate through the liquid at a speed slow enough to achieve some alignment the carbon nanotubes on the substrate surface. This is a simple deposition method.

[0122] The step of depositing the carbon nanotubes on the substrate may comprise using a deposition technique selected from the group consisting of DNA-assisted alignment, Langmuir-Blodgett assembly, Dimension-Limited Self-Alignment (DLSA), Tangential Flow Interfacial Self-Assembly (TaFISA), and dielectrophoresis, which provide aligned carbon nanotubes.

[0123] The substrate on which the deposition is carried may comprise a silicon wafer with a deposited or grown insulator material on top, a glass or quartz wafer, a silicon wafer with a layer stack containing interconnects, or a fully processed ASIC wafer which already contains integrated circuits.

[0124] In embodiments, patterning the carbon nanotubes may comprise defining the active channel region using lithographic and etching techniques. Patterning may involve defining the active channel region using electron beam lithography and plasma etching. Specifically, the method may comprise defining the active carbon nanotube channel region using electron beam lithography and inductively coupled plasma (ICP) etching.

[0125] In embodiments, forming the source and drain contacts may comprise depositing and patterning a conductive material. The conductive material may be a transition metal.Specifically, forming the source and drain contacts may comprise depositing and patterning palladium.

[0126] In embodiments, the patterning steps may utilize lithographic resists. Electron beam lithography and photolithography may be used with appropriate resists. Specifically, electron beam lithography may utilize polymethyl methacrylate (PMMA) as a resist and photolithography may utilize SU-8 as a photoresist.

[0127] In embodiments, the method may further comprise passivating exposed surfaces except for the active channel region. This may involve passivating the metal contacts and patterning an isolation layer to expose only the active carbon nanotube channel region. Specifically, the method may comprise passivating the metal contacts and opening only the carbon nanotube active region window to expose the active channel.

[0128] In embodiments, the method further comprises forming an isolation layer over the carbon nanotubes and patterning the isolation layer to expose the carbon nanotubes in the channel region, protecting the contacts. The substrate may comprise a dielectric layer forming its top surface, wherein the method further comprises etching away the dielectric layer beneath the carbon nanotubes to suspend the carbon nanotubes, allowing electrolyte access from all sides around the nanotubes transversal cross-section.

[0129] In embodiments, the method of manufacturing may allow for integration of carbon nanotube-based sensor devices with existing semiconductor fabrication technologies. The carbon nanotube sensors may be integrated into the back-end-of-line (BEOL) processes of semiconductor fabrication, allowing for additional layers without interfering with front-end-of-line (FEOL) processes. Specifically, the method may involve fabricating aligned carbon nanotube sensor devices atop existing circuitry using BEOL processing techniques, enabling three-dimensional integration without affecting underlying silicon-based components.

[0130] In embodiments, functionalizing the channel region may comprise selectively attaching the capture entity to the carbon nanotubes using a capture entity functionalized with a group capable of attaching to the carbon nanotubes. For instance, a pyrene-based or diazonium-based reaction can be used, providing specific attachment. For this purpose, a diazonium-functionalized capture entity or a pyrene-functionalized capture entity is contacted with the carbon nanotubes. The method of functionalizing the carbon nanotube channel may achieve selective capture entity attachment. This may involve reactions that preferentially attach capture entities to the nanotubes rather than surrounding materials. Specifically, functionalizing may involve employing pyrene-based or diazonium-basedreactions to selectively attach a single capture entity to the carbon nanotubes, ensuring that capture entities bind only to the nanotubes and not to adjacent oxide surfaces.

[0131] In the third aspect, the present invention relates to a method of detecting a target entity. The method comprises providing a field-effect transistor sensor device (1) according to any embodiments of the first aspect, exposing the functionalized channel region (4) to a sample suspected of containing the target entity, applying a voltage between the source electrode (2) and the drain electrode (3), and measuring an electrical parameter indicative of binding of the target entity to the capture entity (8).

[0132] In embodiments, the target entity may be a polynucleotide and the capture entity may be either a polymerase or a nuclease, or the target entity may be a peptide and the capture entity may be a modified peptidase, or vice versa the target entity may be a modified peptidase and the capture entity may be a peptide, allowing sequencing of biopolymers. The electrical parameter may be selected from current, conductance, and charge, which are sensitive to molecular binding. The method may further comprise detecting individual binding events between the target entity and the capture entity, enabling single-molecule resolution.

[0133] In the fourth aspect, the present invention relates to a kit comprising a field-effect transistor sensor device (1) comprising a source electrode (2) and a drain electrode (3) separated by a channel region (4) and defining a source-drain axis (5). The channel region (4) comprises a plurality of carbon nanotubes (6) aligned along the source-drain axis (5) and forming a channel region (4) of width (W) and length (L) less than 1 micrometer. The kit includes an entity selected from:

[0134] a capture entity (8) configured to, on one hand attach (e.g., non-covalently) to a carbon nanotube, and on another hand bind selectively to a target entity, and a coupling entity configured to attach (e.g., non-covalently) to a carbon nanotube and capable of attaching to a capture entity (8).

[0135] The kit also comprises a solvent, provided either separately from the entity or as a solution in which the capture or coupling entity is dissolved. The capture entity (8) and solvent are provided in amounts such that, when combined, the concentration and volume of the solution are such that, upon application of the whole solution on the channel region, the probability of exactly one capture entity (8) or coupling entity binding to the channel region (4) per device (1) is at least 30%. This optimizes single-molecule occupancy.

[0136] In the fifth aspect, the present invention relates to a field-effect transistor sensor array comprising a plurality of devices (1) according to any embodiments of the first aspectarranged in an array configuration. In embodiments, the array may comprise at least 1,000 devices, enabling high-throughput sensing. The array may further comprise integrated circuitry for addressing and reading out individual devices in the array, allowing multiplexed operation.

[0137] Example 1: Fabrication and Characterization of an Aligned Carbon Nanotube bioFET for Single-molecule Biosensing

[0138] This experiment aims to fabricate and characterize an aligned carbon nanotube (ACNT) bioFET device for single-molecule biosensing applications. The significance of this experiment lies in the potential of ACNT bioFETs to overcome challenges faced by silicon-based sensors and to enable highly parallelized, label-free detection of analytes (e.g., biomolecules) at the single-molecule level.

[0139] The materials used in this experiment include a silicon substrate, carbon nanotubes, palladium for source and drain electrodes, PMMA as an e-beam resist, and SU-8 as a photoresist. The equipment utilized consists of a DLSA system for depositing aligned CNTs, an e-beam lithography system for patterning the active channel region, and an ICP for etching.

[0140] The experimental procedure begins with the deposition of a spatially uniform film of aligned parallel CNTs on a silicon wafer using the DLSA method. The wafer is then diced into smaller pieces, and the CNTs are cleaned using a plasma treatment. E-beam lithography is employed to define an active CNT channel region with a length less than 500 nm and a width less than 100 nm. Palladium is deposited and patterned to form the source and drain contacts. The metal contacts are passivated, leaving only the CNT active region exposed. Selective functionalization of the CNT channel with a single capture entity is achieved using pyrene or diazonium reaction-based methods.

[0141] The fabricated ACNT bioFET devices are characterized using polarized Raman spectroscopy to assess the degree of alignment of the CNTs. The results show that the CNTs exhibit a high degree of alignment of less than 10°, as evidenced by an observed Imax / lmin ratio of 45. The purity of the semiconducting CNTs is evaluated using electrical measurements, revealing a purity greater than 99.99% based on the on-off ratios of 1000 fabricated devices.

[0142] The ACNT bioFET device offers several advantages over silicon-based sensors. The absence of a native oxide on the CNT surface results in lower surface charge and reduced ion screening, leading to higher biomolecular sensitivity. The selective functionalization of CNTs enables the attachment of a single capture entity to the channel, minimizing the lossof low-abundance analytes. Furthermore, the use of a liquid electrolyte gate eliminates the need for a gate dielectric, potentially reducing low-frequency noise associated with traps in the dielectric.

[0143] The experiment also highlights the benefits of using aligned CNTs over single CNTs in bioFET devices. The ACNT approach enables wafer-scale manufacturability and reduces device variability. Additionally, the multiple CNTs in the ACNT device capture more of the charge cloud in certain configurations, potentially leading to better signal-to-noise ratios.

[0144] Example 2: DNA Sequencing by Synthesis. An ACNT bioFET device is fabricated with a channel length of 50 nm and width of 15 nm, comprising 4 aligned carbon nanotubes with an average spacing of 5 nm. The channel is first functionalized with pyrene-based linker molecules, followed by the attachment of a DNA polymerase enzyme (the capture entity), and a template DNA strand (a target entity). The device is exposed to a solution containing charge-labeled nucleotides. As the polymerase incorporates individual nucleotides (further target entities) into the growing complementary DNA strand, distinct electrical signals are detected for each incorporated base (A, T, C, G), enabling real-time, single-molecule DNA sequencing. The detection focuses on the incorporation events rather than the initial attachment of the capture entity.

[0145] Example 3: Protein-Protein Interaction Detection

[0146] An ACNT bioFET array is created with 10,000 individual devices, each having a channel length of 100 nm and width of 30 nm. The channels contain 6 aligned carbon nanotubes with 5 nm spacing. Each device is functionalized with a single protein specific to a different protein of interest. The array is exposed to a complex biological sample. Binding events between target proteins and their corresponding binding partners are detected as discrete changes in conductance, allowing for multiplexed, single-molecule protein interaction studies.

[0147] Example 4: microRNA Detection

[0148] An ACNT bioFET is fabricated with a suspended channel region 80 nm in length and 25 nm in width, comprising 5 aligned carbon nanotubes. The channel is functionalized with a single PNA or DNA capture entity complementary to a specific microRNA sequence. When the target microRNA binds to the capture entity, it causes a measurable change in the device's electrical properties, enabling ultra-sensitive, single-molecule detection of microRNAs in biological samples.

[0149] Example 5: Enzyme Kinetics StudyAn ACNT bioFET device is created with a channel length of 60 nm and width of 20 nm, containing 3 aligned carbon nanotubes. The channel is functionalized with a single enzyme molecule. By monitoring real-time changes in the electrical signal as individual substrate molecules interact with the enzyme, the device enables single-molecule studies of enzyme kinetics and mechanisms.

[0150] Example 6: Aptamer-based Small Molecule Detection

[0151] An ACNT bioFET is fabricated with a channel length of 70 nm and width of 23 nm, comprising 4 aligned carbon nanotubes. The channel is functionalized with a single aptamer molecule designed to bind a specific small molecule target. The device is used to detect the presence of individual small molecule analytes in complex mixtures, demonstrating its potential for applications in drug discovery and metabolomics.

[0152] Example 7: DNA Fragment Binding Detection

[0153] An ACNT bioFET device is constructed with a channel length of 60 nm and width of 20 nm, containing 5 aligned carbon nanotubes. The functionalization proceeds in multiple steps: first, attachment of pyrene linkers to the carbon nanotubes, followed by binding of template DNA strands. The device detects the binding of charged complementary PNA or DNA fragments to the template strand, similar to XGenomes assay methodology. Unlike traditional sequencing, this approach does not involve strand synthesis but rather monitors temporary binding events between the template and charged fragments, providing sequence information through the detected electrical signals.

[0154] Example 8: Peptide Sequencing via Charge Tags

[0155] An ACNT bioFET is fabricated with a suspended channel region 80 nm in length and 25 nm in width, comprising 5 aligned carbon nanotubes. The channel is functionalized through a two-step process: initial attachment of linker molecules followed by binding of protease enzymes. The device detects the binding of charge-tagged molecules to specific amino acid residues in a target peptide. These charge tags may for instance comprise modified amine groups, carboxylic acid groups, thiol groups, hydroxyl groups, aromatic groups, imidazole groups, guanidino groups, amide groups, sulfate groups, or phosphate groups. The electrical signals generated by these binding events enable determination of the peptide sequence.

[0156] Example 9: Protein Detection with Charge-Tagged Antibodies

[0157] An ACNT bioFET device is created with a channel length of 40 nm and width of 18 nm, containing 3 aligned carbon nanotubes. The functionalization involves first attaching linker molecules to the carbon nanotubes, followed by immobilization of specific proteins.The device detects binding events between these immobilized proteins and charge-tagged antibodies, enabling sensitive protein detection and analysis of protein-protein interactions. The electrical signals arise from the charge tags rather than the proteinprotein binding event itself.

[0158] It is to be understood that although preferred embodiments, specific constructions and configurations, as well as materials, have been discussed herein for devices according to the present invention, various changes or modifications in form and detail may be made without departing from the scope of this invention. For example, any formulas given above are merely representative of procedures that may be used. Functionality may be added or deleted from the block diagrams and operations may be interchanged among functional blocks. Steps may be added or deleted to methods described within the scope of the present invention.

Claims

Claims1. A field-effect transistor sensor device (1) comprising:o a source electrode (2) and a drain electrode (3) separated by a channel region (4) and defining a source-drain axis (5);o a plurality of carbon nanotubes (6) aligned along the source-drain axis (5) and defining the channel region (4), the channel region (4) having a width (W) and length (L) less than 1 micrometer;o wherein the channel region (4) is functionalized with a single capture entity (8) or a single coupling entity per device (1), the single coupling entity being capable of attaching to the capture entity (8), the capture entity (8) being configured to bind selectively to a target entity.

2. The field-effect transistor sensor device according to claim 1, wherein the capture entity is a molecular capture entity.

3. The field-effect transistor sensor device according to claim 1, wherein the molecular capture entity comprises an entity selected from the group consisting of biomolecules, synthetic molecules, polymers, nanoparticles, or combinations thereof.

4. The device (1) according to claim 1, wherein the channel region (4) has a width (W) of from 4 to 500 nm, preferably less than 200 nm, more preferably less than 100 nm, yet more preferably less than 20 nm.

5. The device (1) according to claim 1 or 4, wherein the channel region (4) has a length (L) of less than 500 nm, preferably from 20 to 200 nm, more preferably less than 150 nm, yet more preferably less than 100 nm, even more preferably less than 60 nm.

6. The device (1) according to any one of the preceding claims, wherein the plurality of aligned carbon nanotubes (6) comprises from 2 to 40 carbon nanotubes (6), optionally from 2 to 20 carbon nanotubes (6), optionally from 5 to 10 carbon nanotubes(6).

7. The device (1) according to any one of the preceding claims, wherein neighboring carbon nanotubes (6) are separated by an average spacing (S) of from 2 to 10 nm, preferably from 2 to 6 nm, yet more preferably from 3 to 5 nm.

8. The device (1) according to any one of the preceding claims, wherein the carbon nanotubes (6) have an average diameter of from 1 to 2 nm.

9. The device (1) according to any one of the preceding claims, further comprising an insulating layer (21) adjacent to a top or bottom side of the channel region (4), wherein the other side of the channel region (4) is exposed to a cavity (22) configured to allow a liquid electrolyte (23) to access the channel region (4).

10. The device (1) according to any one of claims 1 to 8, wherein the carbon nanotubes (6) are suspended above the channel region (4).

11. The device (1) according to any one of the preceding claims, wherein the aligned carbon nanotubes (6) have a degree of alignment of 15 degrees or less, preferably 12 degrees or less, more preferably 10 degrees or less, as measured by polarized Raman spectroscopy.

12. A method of manufacturing a field-effect transistor sensor device (1) comprising:o providing a substrate (26) having a plurality of carbon nanotubes (6) aligned along a source-drain axis (5);o patterning the plurality of carbon nanotubes (6) to form a channel region (4) between a source electrode (2) and a drain electrode (3), the channel region (4) having a width (W) and length (L) less than 1 micrometer;o functionalizing the channel region (4) with either a single capture entity (8) or a single coupling entity per device (1), the single coupling entity being capable ofattaching to the capture entity (8), the capture entity (8) being configured to bind selectively to a target entity.

13. A method of detecting a target entity comprising:o providing a field-effect transistor sensor device (1) according to any one of claims 1 to 11;o exposing the functionalized channel region (4) to a sample containing or suspected of containing the target entity, wherein the sample further comprises the capture entity if the channel region (4) is functionalized with a single coupling entity per device not yet attached to the capture entity;o applying a voltage between the source electrode (2) and the drain electrode (3);o measuring an electrical parameter indicative of binding of the target entity to the capture entity (8).

14. A kit comprising:a) a field-effect transistor sensor device (1) comprising:o a source electrode (2) and a drain electrode (3) separated by a channel region (4) and defining a source-drain axis (5);o the channel region (4) comprising a plurality of carbon nanotubes (6) aligned along the source-drain axis (5) and forming a channel region (4) of width (W) and length (L) less than 1 micrometer; andb) - an entity selected from:- a capture entity (8) configured to attach to a carbon nanotube and to bind selectively to a target entity, and- a coupling entity configured to attach to a carbon nanotube and capable of attaching to a capture entity (8), and- a solvent, wherein the entity and the solvent are provided either separately or as a solution, wherein the entity and solvent are provided in amounts such that, when combined, the concentration and volume of the solution are such that, upon application of the whole solution on the channel region, the probability of exactly one capture entity (8) binding to the channel region (4) per device (1) is at least 30%.

15. A field-effect transistor sensor array comprising:o a plurality of field-effect transistor sensor devices (1) arranged in an array configuration, each field-effect transistor sensor device (1) comprising:a source electrode (2) and a drain electrode (3) separated by a channel region (4) and defining a source-drain axis (5);a plurality of carbon nanotubes (6) aligned along the source-drain axis (5) and defining the channel region (4), the channel region (4) having a width (W) and length (L) less than 1 micrometer;wherein the channel region (4) is functionalized with a single capture entity (8) per device (1), the capture entity (8) being configured to bind selectively to a target entity.

Images